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pmc-6115556-1 | We report a case of 38 year old lady, diagnosed case of Rheumatoid arthritis (RA) for two years. Apart from the symptoms of joint pains, there was history of Raynaud’s phenomenon as well. There were no systemic complaints and she remained well on treatment for RA, i.e. Hydroxychloroquin, Leflonamide and NSAID as per need. She presented to us, for the first time in June 2016, with complaints of blackish discoloration of right big toe and left 4th toe for 1.5 years. She initially developed a small ulcerated lesion over one of her toes 1.5 year back, that was attributed to RA associated vasculitis and her treatment was modified in accordance with the suspected diagnosis, which included Aspirin, Nefidipine, and Prednisolone. There was no complaint of pain, itching or temperature change at that time and she remained static until a week prior to her presentation to us. This time she had moderate intensity pain in her toes, specifically right big toe and left 4th toe which turned blackish in color. () She was admitted in ward on this occasion. Examination showed a young lady, BMI 21 Kg/m2, Pulse- 90bpm, BP - 150/80 mmHg, temperature – 99°F, RR- 18bpm. There was mild pallor, but no jaundice, rash or joint deformity. There was blackish discoloration of her big toe with partially healed necrotic ulcer on top of it, while the toe of left foot showed blackish discoloration but no ulceration. Both were tender to touch. Peripheral pulses were palpable in both upper limbs and lower limbs, although the posterior tibial and dorsalis pedis arteries had low volume. There was no temperature change and sensations were intact. Her systemic examination was entirely unremarkable. DAS-28 was calculated which was 1.8, i.e. remission. Initial labs are shown in . Doppler ultrasound of legs showed reduced blood flow in left posterior tibial and dorsalis pedis arteries with reduced peak systolic velocities. Due to her persistently increased platelets further work-up was done to evaluate the cause of thrombocytosis. JAK2 V617 mutation analysis was done, which turned out to be positive. Furthermore her bone marrow trephine biopsy was done which showed clusters of mature megakaryocytes with multi-lobulated staghorn nucleoli, suggestive of Essential thrombocytosis. Hence, this patient was diagnosed as a case of RA with associated ET. Treatment was modified in accordance with the revised diagnosis, which included Aspirin 75mg and Hydroxyurea 1g per day, in addition to her RA treatment. Patient responded well to the treatment with regard to clinical as well as laboratory parameters and is on regular follow-up visits, however, she developed gangrene of toe, for which amputation of distal phalanx of toe and nail excision was done, later in the disease course. Anagleride was started with the given treatment due to a surge in her platelet counts. Her follow-up platelet counts are shown in . |
pmc-6115580-1 | A 32 years old male presented with painless and gradually enlarging right testicular swelling of 3 months duration. Right inguinal orchiectomy was performed and 3 weeks post Op B-hCG was 2900IU, AFP was 890 ng/ml while LDH was 560mg/ml. Histopathology showed yolk sac tumor (65%), immature teratoma (20%) and seminoma (15%). Baseline CT scan showed a 1.8cm right para-aortic lymph node with no other metastatic disease. Patient was staged as Stage IIA-S1, Good risk Mixed Germ Cell Tumor (MGCT) depending upon the markers & CT findings. Chemotherapy was planned within 3 weeks of surgery; however patient presented after 2nd week of orchiectomy to ER with severe chest pain. At presentation, cardiac enzymes were elevated and his Trop-I was 6.2 (normal < 0.4), while EKG showed 1.8mm ST segment elevation in leads V1-V3. Cardiology team was consulted immediately & echocardiogram was performed which showed apical hypokinesis with EF of 49%. His cardiac catheterization was reported to be normal with normal coronaries and without any flow restriction (). Depending upon the presentation, EKG changes, elevated Trop-I with absence of any flow restriction and normal coronary angiogram, TCM diagnosis was established, based upon Mayo clinic diagnostic criteria (). Patient was started on angiotensin converting enzyme inhibitors and beta-blockers, and his chemotherapy was delayed by 3 weeks.
Later his chemotherapy regimen was modified to EC x 4 (Etoposide 100 mg/m2IV Day 1-5 / Carboplatin AUC-5 IV Day 1 only) instead of EP (Etoposide / Cisplatin). Though there is scarce data regarding the use of Carboplatin in MGCT and Cisplatin has been shown to be superior to Carboplatin, however due to a risk of Cisplatin induced vasculitis or acute thrombosis, the treatment regimen was modified with informed consent. Patient was treated with 4 cycles of EC and after 2nd cycle his markers normalized. At this time decision was reviewed to cut down his chemotherapy to only 3 cycles of EC but it was considered that he is already getting sub-optimal regimen, so he was continued with complete 4 cycles. He tolerated his treatment well, achieved complete biochemical and radiological response and placed on surveillance. Patient has completed 4.6 years of follow-up according to National Comprehensive Cancer Network guidelines and remains well without any evidence of relapse. After 6 months of his treatment with ACEi and BBs, both were also stopped as he had normal EF (62%) on echocardiogram. |
pmc-6116288-1 | A 28-year-old Thai male with past medical history of E-beta-thalassemia and splenectomy presented to emergency department with a 3-month progressive tightness in bilateral flank region, weakness, and difficulty walking requiring crutches. Review of system was also significant for unintentional 10-pound weight loss due to poor appetite. Further review of history revealed that he was diagnosed with E-beta-thalassemia at the age of 13 months old. The condition was managed with intermittent transfusion, deferoxamine for iron overload, and hydroxyurea until he turned 21 years old when he stopped following up with his hematologist. He reported that, since then, his baseline hemoglobin was 6 g/dL. Vital signs at admission were within normal limits. Physical exam was significant for frontal bossing with depression of nasal bridge, bilateral costovertebral angle tenderness, slow broad-based gait with ambulation, decreased light touch sensation of the thorax at the level T7-T10, at left medial thigh, and in bilateral lower extremities below the knees. Further neurological exam revealed knee and Achilles hyperreflexia in addition to positive bilateral Babinski, clonus, and Romberg.
Laboratory studies were significant for leukocytosis of 72.5 × 109/L, hemoglobin 6.8 g/dL, platelet 732 × 109/L, and reticulocyte count 44.59%. Hemoglobin electrophoresis showed fetal hemoglobin of 49% and hemoglobin E of 59%. Total bilirubin was elevated at 5.3 mg/dL; the rest of the comprehensive metabolic panel was otherwise unremarkable. Further investigations showed that zinc, copper, folate, and vitamin B12 levels were within normal limits. Two-view chest, kidney/ureter/bladder, thoracic, lumbar, and pelvic spine X-rays showed prominence of ribs anteriorly, hepatomegaly, right paraspinal soft tissue prominence surrounding mid-thoracic spines, degenerative joint disease with osteopenia. Magnetic resonance imaging (MRI) of the brain with/without contrast did not show any acute findings but did demonstrate diffuse enhancement involving the clivus and medial occipital bone with mass extension into the bilateral maxillary/sphenoid sinuses, posterior aspect of ethmoid cells, bilateral maxillary bones, inferolateral orbits, and parietal calvarium. MRI of the thoracic spine with/without contrast showed extension of enhancing masses into the spinal canal at the levels of T2-T12 (). MRI of the lumbar spine with/without contrast showed prominent medullary expansion of the visualized bony pelvis with associated extension of enhancing mass into the lumbar spinal canal at L5 level causing severe central spinal stenosis and neural foramen narrowing at levels of L5-S1 (). These masses were associated with intermediate increased T1 and T2 signal mass-like abnormality suggestive of EMH.
Given the history of untreated chronic severe anemia in the past 8 years, the current physical exam, abnormal laboratory findings, and imaging evidence of paraspinal masses, it was concluded that the masses were extramedullary hematopoietic elements without the need of biopsy risking excessive bleeding. Given the extent and the chronicity of cord compression and severe anemia, the neurosurgical team agreed with hematology to initiate medical management rather than surgical intervention or radiation. Therefore, packed red blood cell (PRBC) transfusion was initiated to gradually increase baseline hemoglobin to above 10 g/dL along with hydroxyurea 15 mg/kg/day. Hydroxyurea dose then gradually was increased to 2000 mg daily to achieve maximum possible hematopoiesis suppression. Surprisingly, 2 days later, the patient regained gross sensation in his lower extremities. After 1 week of hospitalization, gait was noted to be increasingly sturdy, clonus and Romberg improved, and gross sensation of the thoracic area returned. The patient subsequently graduated from physical therapy. By hospitalization day-14 when he was discharged, the patient received a total of 6 units of PRBC. Hydroxyurea was maintained at 2000 mg daily without causing neutropenia or thrombocytopenia. MRI of the thoracic/lumbar spine repeated 2 weeks after the initial imaging showed significant reduction in mass effect on spinal cord and decreased spinal canal stenosis ( and ). After discharge, he was maintained on hydroxyurea 2000 mg daily with blood transfusion to maintain hemoglobin above 10 g/dL. Seven weeks after discharge, neurological symptoms were completely resolved except for patellar hyperreflexia. At this point, hydroxyurea was discontinued due to recurrent pancytopenia. Nine weeks after discharge, repeat MRI of the thoracic/lumbar spines showed no cord compression or spinal stenosis ( and ). |
pmc-6116300-1 | Fifty-seven-year-old Caucasian female with a past medical history significant for hypertension and recently diagnosed stage IV moderately differentiated distal rectal adenocarcinoma with liver and lung metastasis status post second cycle of FOLFOX palliative chemotherapy 1 week ago was admitted with the primary complaint of hypertensive urgency with a severe headache, intractable nausea and vomiting, and diarrhea. At presentation, her blood pressure was 191/68. Examination did not show any focal neurological deficits. She was alert, awake, and oriented to time, place, and person; cranial nerves II–XII were intact; muscle power was five out of five bilaterally in upper and lower extremities; coordination was intact bilaterally; reflexes were 2+ bilaterally in upper and lower extremities; sensation was intact; and gait was normal. The case was discussed with oncologists who were of the view that symptoms may be due to hypertensive urgency versus BM (which are quite rare for CRC) or possible opiate withdrawal as the patient has been on high-dose opiates for her cancer-related pain. Computed tomography (CT) scan of the abdomen-pelvis did not show any evidence of bowel obstruction. Imaging of the brain would be considered if the patient did not improve with medical therapy. The patient was started initially on IV hydralazine but over the next 8 h patient blood pressure remained uncontrolled despite successive antihypertensives (IV labetalol, PO amlodipine, PO clonidine, IV enalaprilat, transdermal clonidine, IV metoprolol, and eventually IV nicardipine drip), ranging from 185/98 to 230/111. Brain imaging was ordered due to continuous severe headache and refractory hypertension. CT scan of the brain without contrast showed 3.3 × 2.3 × 2.8 cm hyperdense rounded mass in the region of the left cerebellum with surrounding vasogenic edema and a 5–6-mm shift of the posterior midline toward the right. Brain magnetic resonance imaging (MRI) with and without contrast showed left cerebellar lesion measuring 3.6 × 3.2 × 2.9 cm with high T1 signal intensity, low T2 signal intensity, and low gradient echo sequence signal intensity with peripheral and mild internal enhancement, and a significant amount of surrounding vasogenic edema, ipsilateral transtentorial herniation, and obliteration of the fourth ventricle (). After discussion with the patient, the decision was made for urgent neurosurgical resection of the mass and subsequent whole-brain radiation therapy (WBRT). This decision was made as this was a solitary lesion which was symptomatic with a high degree of mass effect and edema in a patient with a good baseline functional status. The patient was started on IV dexamethasone 6 mg every 6 h, and transferred for an urgent neurosurgical intervention at a tertiary care center. The tumor was resected using an operative microscope, and a combination of suction and cautery. Postoperatively patient recovered well from the surgery and was discharged. Patient followed up outpatient and had WBRT in 4 weeks post discharge. On her 1-year follow-up, patient reported no new neurological deficits, and her repeat MRI brain () did not show any recurrence of her metastatic lesion or new metastasis. |
pmc-6116378-1 | A 13-year-old girl of African ancestry was referred to our breast clinic for evaluation of a left breast mass. She had been complaining of the left breast lump for 2 years. The lump was gradually increasing in size and it was tender. There was no history of skin changes, nipple discharge, fever, or trauma. Furthermore, there was no family history of similar conditions, no history of traveling abroad, and no contact with a person with tuberculosis. Her medical history revealed history of rheumatic heart disease. She underwent mitral and tricuspid valve repair more than 2 years prior to presentation at our breast clinic. She was a student in primary school living with her parents and siblings.
On examination she was hemodynamically stable. She had a normal body build for her age. She was not pale or jaundiced. A breast examination revealed an irregular left breast mass that was palpable at six o’clock position. The mass was approximately 4 cm in maximal diameter; it was hard, tender, and fixed on the posteromedial side. There were no inflammatory skin changes or any nipple changes. Her right breast was unremarkable. There were no palpable bilateral axillary lymph nodes. Abdomen, chest, and neurological examinations were unremarkable. Her blood work, including complete blood count, liver function test, urea and electrolytes, and coagulation profile, was within normal ranges. Ultrasound of her left breast (Fig. ) showed a large, irregular, complex, heterogeneous mass measuring 4.3 × 2.7 × 3.5 cm at 6 o’clock position. There were central cystic changes but no significant intrinsic vascular flow. There was significant associated skin and subcutaneous edema and thickening with fluid seen tracking within subcutaneous tissue. The surrounding fat appeared more echogenic, consistent with the inflammatory and infectious changes seen in breast abscesses. Given the echogenicity of the mass, an infectious cause was suspected and malignancy was less likely but could not be excluded. An ultrasound-guided biopsy was recommended. A left axillary lymph node appeared prominent with a cortical thickness of 5 mm.
An ultrasound-guided aspiration of the cystic portion was attempted with an 18-gauge needle. Minimal yellowish fluid was retrieved and sent for aerobic bacteria, anaerobic bacteria, and fungi culture and sensitivity analysis. A biopsy of the mass was performed. The culture showed moderate growth of Staphylococcus aureus. An acid-fast bacilli stain was negative. Microscopic tuberculosis bacilli were not detected. Histopathology sections revealed cores of breast tissue heavily infiltrated with mixed acute and chronic inflammatory cells. The diagnosis was consistent with chronic abscess. She received one gram of amoxicillin and clavulanate potassium every 12 hours for 10 days. However, she remained symptomatic, and the mass did not decrease in size. Therefore, we proceeded to surgical excision.
Excision of the breast lump through a peri-areolar incision was performed. During the operation, we found a circumscribed semi-cystic lesion that was not typical of fibroadenoma; the mass was fixed to the underlying rib. The cystic part was opened, and the turbid fluid that emerged was sent for culture. A long, thin, metallic wire was found inside the cavity; it emerged from a small opening above the rib and moved synchronously with her heartbeat (Fig. ).
A cardiothoracic surgeon was consulted intraoperatively. The wire was removed; it was a retained TEPW that was inserted during the tricuspid and mitral valve repair procedure and had migrated to the breast. The mass was excised and sent for histopathology, which revealed mammary tissue with acute and chronic inflammatory cells.
She was discharged to home on the same day and was followed up at our out-patient clinic 2 weeks later. Her wound site was clean and dry. There were no palpable masses and no signs of inflammation. She was later seen at our out-patient clinic for a 1-year post-surgery follow-up. She had no complaints, and a breast examination revealed no palpable masses. |
pmc-6116383-1 | A 30-year-old female presented with complaints of epigastric burning and indigestion for 1 year, which was occasionally associated with pain and vomiting. On a previous oesophago-gastroduodenoscopy, multiple oesophageal ulcers were noted, located from 30 to 35 cm and the mucosa was seen to be circumferentially hyperaemic. Upon investigation, chest and abdominal X-ray showed abnormal air-fluid level at right hemithorax as shown in Fig. . Computed Tomography (CT) scan demonstrated organo-axial gastric volvulus accompanied with right hemi-diaphragm elevation and a slight mediastinal shift to the left, with gastric bubble above the diaphragm (Fig. ), and sections through the lower chest showed mild bilateral pleural effusion with basal atelectasis of the right lower lobe. The small and large bowel loops were unremarkable and there was no evidence of bowel obstruction.
An elective laparotomy was performed through a midline incision. Stomach was not seen in the abdominal cavity, but pull on the gastrocolic ligament revealed the greater curvature of the stomach through foramen of Morgagni in the right hemi-diaphragm, with the defect measuring 4 × 5 cm (Fig. ). The hernia was reduced, with excision of the hernial sac and the defect was repaired using a size zero non-absorbable polypropylene suture—no mesh was placed. Since there was a high jejunal repair, a gastrostomy was created which served to secure the stomach in place. Following the reduction of hernia, on further exploration, multiple diverticuli were observed in the small and large intestine (Fig. ). Interestingly, these were unremarkable on CT scan. Only the largest and most proximal jejunal diverticulum (Fig. ), which was about 6 cm in size, was resected using a linear stapler as it had a narrow neck. A pelvic drain was placed and the wound was closed in layers using absorbable polyglactin suture. Figure exhibits the normal anatomy and a schematic diagram of this case depicting the presence of gastric volvulus through MH on the right side. The postoperative period was uneventful and the patient was discharged on the 10th post-operative day. The patient was stable and asymptomatic on follow up after one month, and she is doing well as of writing of this report. ‘Timeline for Case Report’ in Additional file represents the events of this case in a chronologic order. |
pmc-6116405-1 | An 18-year-old female with an allergy to penicillin and a past medical history of migraines presented to the emergency department with pleuritic chest pain and dyspnea on exertion. Three months prior she had an upper respiratory infection. Her initial workup was unrevealing, including negative troponin and normal complete blood count. Her electrocardiogram (ECG) revealed normal sinus rhythm. A computed tomography angiogram (CTA) chest had no significant findings. She was diagnosed with atypical chest pain and discharged home.
She returned three days later with worsening chest pain. ECG () was significant for sinus tachycardia, PR depressions, and diffuse ST elevations, consistent with pericarditis. Significant findings at that time included a Troponin-I of 0.28 ng/ml and white blood cell count (WBC) of 16.2 (16,200). Shortly after admission, she was transferred to the intensive care unit (ICU) for hypotension and tachycardia in the 150 s. Echocardiography demonstrated a moderate pericardial effusion with evidence of tamponade. Pericardiocentesis yielded 300 ml of serous fluid and established hemodynamic stability. She was initiated on empiric antibiotic therapy with vancomycin and meropenem. Later that same day, she underwent emergent intubation and vasopressor support after two separate episodes of ventricular fibrillation and pulseless electrical activity, requiring multiple rounds of advanced cardiac life support. After stabilization, fluid aspiration from the pericardial drain revealed 130 ml of purulent fluid. Her final pericardial fluid cultures and blood cultures grew Streptococcus pyogenes. Antibiotic coverage was weaned to intravenous cefazolin monotherapy. She continued to drain 240–360 milliliters of purulent pericardial fluid daily and was on norepinephrine for pressure support. Post resuscitation, she developed acute renal failure that required intermittent renal replacement therapy secondary to acute tubular necrosis. Antibiotic coverage was broadened to vancomycin and cefepime after the development of acute respiratory distress syndrome (ARDS) secondary to multifocal pneumonia. She was gradually weaned from the ventilator and subsequently extubated. The remaining hospital course was uneventful, and she was discharged home on oral levofloxacin for completion of her antibiotic course.
The patient returned to the ED several days later with shortness of breath and worsening back pain that radiated to her chest. The ECG () at that time was significant for sinus tachycardia and an S1Q3T3 phenomenon. She was admitted for severe sepsis and started on ceftriaxone for concern of recurrent bacteremia. Repeat transthoracic echocardiography demonstrated right ventricular strain and what appeared to be a near to total occlusion of her pulmonary trunk (). Computed tomography (CT) angiography was significant for a 4.8 cm small-necked pseudoaneurysm arising off the anterolateral aspect of the aorta and was found to be compressing the pulmonary trunk and right pulmonary artery ().
Our patient was again transferred to the ICU. A subsequent CT chest with contrast demonstrated pseudoaneurysm expansion to 5.3 cm. Emergent cardiothoracic surgery with circulatory arrest was performed. The operation revealed a 2 cm × 1 cm wall defect in the distal ascending aorta, extending into the arch of the aorta. Intraoperative transesophageal echocardiography revealed right ventricular remodeling resulting in a severely strained D-shaped ventricle and severely dilated RVOT of 4 cm (). Additionally, there was significant clot burden in the anterior mediastinum encasing the ascending aorta and the pulmonary artery. A CorMatrix patch was used to close the defect, and a specimen of the anterior mediastinal mass was sent for pathological analysis, confirming our diagnosis of a mycotic pseudoaneurysm. The patient tolerated the surgical procedure well and did not require additional operations during her inpatient hospital recovery. |
pmc-6116406-1 | A 17-year-old girl with a recurrent cardiac tumor presented for the heart transplant evaluation. Initially, at the age of 10, she first presented with dyspnea and holosystolic murmur at apex. She did not have any significant medical history, other than a first-degree relative family history of CM. Echocardiography revealed a 3.5 × 4.8-cm LA mass. The mass was mobile, heterogeneous, and protruded from atrial septum into LA, suspected for CM and causing mitral regurgitation (). The patient underwent tumor removal surgery via midline sternotomy. The pathology showed myxoid stroma with clusters of spindle cells and small blood vessels confirming the diagnosis of CM.
A year after the surgery, at the age of 12, she presented to the emergency department with sudden abdominal and right leg pain. The abdominal examination showed left upper abdominal tenderness and guarding. There were also signs of arterial occlusion in her right leg. Echocardiogram showed multiple cardiac masses in LA (2.5 × 1.9 cm) and left ventricular (LV) (1.8 × 1.0 cm) (). A computed tomography of the abdomen and lower extremities confirmed the diagnosis of splenic infarction and femoral arterial embolism. She underwent splenectomy and embolectomy. An open heart operation revealed 5 cardiac masses (3 in LA, and 2 in LV) which all were removed. All specimens including the tissue from embolectomy were reported as a CM. The surgery was uneventful and echocardiography afterward did not show tumor residual. The repeat physical examination did not reveal signs of Carney complex.
Unfortunately, at the age of 13, a right ventricular (RV) mass sized 1.7 × 1.6 cm was detected on the echocardiography. She was asymptomatic but with the follow-up echocardiogram showing increasing in size of the mass to 2.8 × 4.7 cm extended into RV outflow tract causing obstruction (peak RV outflow velocity of 3.8 m/s) (). After discussion, she underwent a third sternotomy for tumor resection and specimens were reported as CM. The surveillance echocardiography was performed every 6 months and at the age of 15. There were recurrent of cardiac masses in LA, LV, and RV, sized 2.4 cm, 2.1 cm, and 2.4 cm, respectively ().
Even though CM is considered benign, due to the infrequent recurrence, fast growing, and the complications from the neoplasm including valve regurgitation and obstruction, and embolic event, the heart transplant was proposed with the fourth recurrence of CM. Other than elevated panel reactive antibody with multiple significant anti-human leukocyte antibodies, there were no other contraindications. She was on the waiting list for 11 months. She was treated with warfarin while on the waitlist without new events. Of note, at the time of heart transplant operation, she was 17 years old. The heart transplant was performed with a bicaval anastomosis. Attention was given to maximally excise the recipient cardiac tissue. The gross examination of the excision heart showed 4, 1, and 1 masses in RV, LA, and LV (). These masses showed homogenous tan white, gelatinous, rubbery cut surface. The masses were reported as CM.
The clinical course was uneventful. Regarding immunosuppression, she was given standard regimen of our institution for high risk patient including perioperative plasmapheresis and induction therapy with basiliximab, then maintenance regimen with a combination of cyclosporine, mycophenolate, and prednisone. Now, 6 months after the surgery, the patient is doing well with New York Heart Association functional class I. The steroid was weaned off. There was no episode of treated rejection. The physical examination and echocardiogram did not reveal signs of recurrent masses. The echo was planned in a 6-month interval.
The details of each episode of tumor presentation and operations are summarized in . |
pmc-6116445-1 | A 71-year old female, gravida 2, para 2 presented with abdominal distention which had worsened over the previous year. Her past medical history was appendicitis, and an appendectomy was performed in her thirties. Her past family history was unremarkable. A pelvic examination identified a very large mass in both hypochondrium which was hardly movable. Pelvic and abdominal ultrasonography showed a huge cystic mass with a solid component. Serum tumor marker levels were carcinoembryonic antigen (CEA): 2.0 ng/mL (normal < 37.0), CA19–9: 459.2 U/mL (normal < 37.0), SCC: 18.9 ng/mL (normal < 1.5), and CA125: 329.9 U/mL (normal < 35.0). Other blood examination results were unremarkable. A pelvic MRI showed a huge cystic mass with a nodular component which was enhanced and under diffused in diffusion weighted image (Fig. ). Computed tomography (CT) showed a 3 cm mass in the liver, and fluorodeoxyglucose-positron emission tomography (FDG-PET) showed FDG uptake not only in the pelvic tumor (SUVmax = 22.9) but also in the hepatic nodule (SUVmax = 13.7), thus suggesting metastases (Fig. ).
Ovarian cancer and liver metastasis was suspected on these data, and a subsequent percutaneous liver biopsy was performed. The pathology showed metastatic cells in normal hepatocytes, and a diagnosis of poorly differentiated carcinoma was made (Fig. ). Immunohistochemical staining showed that p40, p63, and hepatocytes were all negative, thus denying primary hepatocellular carcinoma. Therefore, a clinical diagnosis of ovarian cancer stage IVB with malignant transformation of the MCT was made.
A total abdominal hysterectomy, bilateral salpingo-oophorectomy and partial omentectomy was performed. The left ovary was enlarged (about 300 mm) and filled with 13,000 ml of yellowish fluid. Adhesion was not particular, and the uterus and right ovary appeared to have no remarkable changes (Fig. ). The cytology of ascites was negative. The patient’s postoperative course was uneventful.
The pathological findings revealed that most of the ovary consisted of an MCT with squamous cell epithelium, cutaneous appendage and cartilaginous tissue (Fig. ); however, some parts consisted of papillary or glandular lesion with hobnail-like atypical cells (Fig. ). We made a diagnosis of left ovarian clear cell carcinoma and malignant transformation of MCT based upon the proof of transition from simple squamous epithelium via simple glandular epithelium to papillary change with atypia (Fig. ). Histopathology showed no endometriosis in either ovary and, therefore, endometriosis-associated malignancy was denied. However, the uterus and omentum showed no signs of malignancy. The left fimbria of the fallopian tube had a lymphovascular space of invasion with calcifying carcinoma cells (Fig. ). However, the uterus and omentum showed no signs of malignancy. Immunohistochemical analysis of the left ovary indicated that AE1/AE3, CK7, PAX-8 and Napsin A were all positive, and that 34βE12 and P53 were slightly positive (Fig. ). Although CK20 and vimentin were negative, Ki-67 (MIB-1) index was 25% positive in the carcinomatous part. Moreover, PAS was positive in the stromal part, and PAS and ALB were both positive in some glandular lesions. This was classified as stage IVB (pT2aNXM1) according to the International Federation of Gynecology and Obstetrics (FIGO) 2014 classifications.
The patient subsequently underwent chemotherapy with 3 courses of paclitaxel and carboplatin. Afterward, CT scanning revealed a vanished hepatic metastasis and emerged swelling of the para-aorta lymph node. Although 3 courses of doxorubicin were administered, the para-aorta lymph node continued to enlarge. As chemotherapy was not effective due to her progressive disease, the patient began to receive the best possible supportive care. After 17 months from the operation, she passed away. |
pmc-6116566-1 | A 65-year-old man from the Indian subcontinent presented to our hospital with complaints of a mild, dull, aching left-sided abdominal pain for the past year, loss of weight and appetite for 6 months. There was a history of per rectum bleeding and recent history of altered bowel habits. He had no history of malignancy in the family. There was no other clinically significant history.
A general examination of our patient was within normal limits. There was no significant lymphadenopathy.
On abdominal examination, a 7 cm × 6 cm size lump was palpable in the epigastric region extending up to the left hypochondrium; it was nodular, nontender, firm in consistency, with a well-defined border, and not moving with respiration. The rest of his abdomen was unremarkable. A rectal examination was normal.
Routine laboratory investigations including a complete blood count, an international normalized ratio, liver function tests, and renal function tests were within normal limits. Ultrasonography of his abdomen and pelvis was performed, and a multicystic lesion in the distal body and tail of the pancreas measuring about 7 × 7 cms was seen; no lymph nodes were seen. The rest of his pancreas was normal, and the proximal pancreatic duct was dilated, his liver was normal, and no free fluid was seen. Abdominal and pelvic contrast-enhanced computed tomography (CECT) was performed and revealed a multicystic lobulated mass arising from the distal body and tail of the pancreas with proximal pancreatic duct dilatation, a normal liver, no free fluid, an irregular mass in the sigmoid colon with mild narrowing of the lumen, with no proximal dilatation of the colon. Tumor marker tests showed carcinoembryonic antigen (CEA) test results of 10.48 ng/ml (normal value. < or = 3.0 ng/mL, in smokers: < or = 5.0 ng/mL), and a CA19–9 test result of 7.19 U/mL (< 37 U/mL). A colonoscopy revealed ulceroproliferative, nonobstructing growth in the distal sigmoid colon with small polyps nearby. Colonoscopic biopsy result showed well-differentiated adenocarcinoma. A positron emission tomography/computed tomography (PET-CT) scan was performed and showed metabolically active circumferential thickening in the distal sigmoid colon with a maximum standard uptake value (SUV max) 7.0. and a multicystic lobulated mass with low metabolic activity arising from the distal body and tail of pancreas.
Endoscopic ultrasound confirmed the picture of microcystic serous cystadenoma with no vessel involvement or lymph nodes. An endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS- FNA) was done, his fluid amylase levels were within normal limits, and his fluid CEA levels were not elevated. Cytology showed only benign cells (Figs. and ).
Distal pancreaticosplenectomy and radical sigmoidectomy with end-to-end colorectal anastomosis was performed.
His postoperative course was uneventful. The histopathology report showed microcystic (benign) serous cystadenoma of the pancreas, and moderately differentiated adenocarcinoma of the sigmoid colon with lymph node metastasis 0/37. Angiolymphatic invasion was positive, and perineural invasion was absent.
Our patient was followed up every third month for 1 year and was evaluated. Blood reports and imaging studies were unremarkable and did not detect any recurrence (Figs. , and ). |
pmc-6117226-1 | A 14-year-old male was admitted to our hospital with right lower abdominal pain and vomiting. He had no history of abdominal surgery or trauma. Physical examination revealed deep tenderness at McBurney’s point without abdominal distension. A blood test on admission revealed slight leukocytosis (9840/μl) without elevation of the C-reactive protein level (0.01 mg/dl). Enhanced computed tomography scan showed a slightly enhanced, thickened appendiceal wall (Fig. ). Although a slightly dilated ileum and ascites at the recto-vesical pouch were also observed (Fig. ), intestinal obstruction was not diagnosed by these imaging studies. These abnormalities were thought to be inflammatory changes due to appendicitis. The initial diagnosis was mild acute appendicitis based on the physical examination findings and blood test and imaging results, and appendectomy with small laparotomy was therefore planned. However, the patient’s abdominal pain was so severe that analgesics were completely ineffective; continuous vomiting was also observed. Additionally, the ascites at the recto-vesical pouch was unusual considering the mild appendicitis. We performed laparoscopic surgery to explore the abdominal cavity and obtain a definitive diagnosis.
Laparoscopic surgery with three trocars was performed (12-mm camera trocar in the infra-umbilical position and two 5-mm trocars in the left lower quadrant and lower median abdomen). Strangulated small bowel obstruction caused by trapping of ileal bowel loops by a band was observed (Fig. ). After reduction, the band was found to be connecting the right medial umbilical fold to the ileal mesentery (Fig. ,) and was resected using laparoscopic coagulation shears. The band was connected to the ileal mesentery, 30 cm proximal to the ileocecal valve, and neither Meckel’s diverticulum nor ischemic change of the trapped ileum was detected (Fig. ). The appendix showed slight inflammatory change (Fig. ), and appendectomy was also performed. Serous ascites was found at the recto-vesical pouch (Fig. ) and was thought to be caused by strangulated small bowel obstruction. The patient was discharged without complications on postoperative day 4.
Pathological examination revealed that the band consisted of blood vessels, and it was diagnosed as a vitelline vascular remnant (Fig. , ). The macroscopic view of the resected appendix is shown in Fig. . Fecal stones were found on the proximal side of the appendix, and the wall was slightly thickened. Pathological examination revealed diffuse infiltration of lymphocytes and eosinophils throughout the muscularis propria, and the patient was diagnosed with mild chronic appendicitis (Fig. ). |
pmc-6117228-1 | An 81-year-old man presented with abdominal discomfort. Computed tomography imaging revealed a large tumor with intermediate signal intensity, showing heterogeneous contrast enhancement in the subphrenic area (Fig. a) and the feeding artery originated from the diaphragm (Fig. b). Within several days, he suddenly experienced loss of consciousness. Serum examination indicated hypoglycemia (glucose levels, 18 mg/dL). Insulin (1.05 μIU/mL), C-peptide (0.71 ng/ml), and IGF1 (39 ng/mL) levels were all relatively low but still within the physiological range. Western blot analysis of the patient’s serum revealed overexpression of high-molecular-weight IGF-2 designated “big IGF-2” (Fig. ). Along with glucose compensation, the patient underwent surgery for total tumor resection. In the operative view, the large tumor appeared to compress the right lobe of the liver without invasion. The feeding artery originating from the diaphragm was ligated and divided. A part of the diaphragm was resected with autosuture owing to firm adherence of the diaphragm to the artery. The tumor was then dissected along the liver surface without simultaneous resection of any other organs, and a tumor-free margin was achieved macroscopically. The tumor measured 34 cm at the major axis and weighed 1350 g and was well demarcated by a fibrous membrane. The resected surface was elastic, firm, had an ivory-like appearance, and was multilobulated with trabeculation. The solid component was predominant, and a small myxoid component was also noted (Fig. ). Microscopically, spindle cells generally constituted the tumor without specific cellular arrangement in the solid component (Fig. a). A few areas in this component demonstrated keloid-like collagenous stroma (Fig. b) and stag horn-like vessels. However, some areas with myxoid appearance upon gross examination revealed a multi-cystic formation by cavernous hemangioma-like septa. Karyokinesis was detected in more than 0/10 high-power fields in the hypercellular area. Necrosis was obscure. Immunohistochemically, the tumor cells expressed STAT6 (Fig. c) and CD34. The highest Ki-67 labeling index was 15%. These results confirmed that the tumor was a malignant SFT. In addition, the tumor cells exhibited cytoplasmic IGF2 expression (Fig. d), specifically with paranuclear dot-like reactivity. The tumor cells were positive for IGF2R (Fig. e) but negative for IGF1R. Since surgery, the patient has been free from tumor recurrence and hypoglycemia for more than 24 months. |
pmc-6117531-1 | The third patient (P3), an 18 year old female, presented with frequent simple and complex motor as well as vocal tics (age at onset: 14 years). She was also suffering from OCD symptoms. Motor tics included hitting own thorax and pelvis with her fists, flipping, grimacing, jerking of the head, shoulders and hands, gesturing (Russian roulette), saluting and locking her feet while walking. Vocal tics included harrumphing, whistling, caterwauling, uttering syllables, words, limited sentences and echolalia. Tic-free sequences were short (max. 1 min), urges to perform tics were rated very high by the patient. OCD symptoms included compulsive counting, repeating, checking and arranging/collocating. Current treatment consisted of risperidone 6 mg/day and biperiden 4 mg/day in a stable dose for 3 weeks. Previous treatment included antidepressants and atypical antipsychotics (fluoxetine 30 mg/day, aripiprazole 10 mg/day, tiapride 600 mg/day, and quetiapine in unknown dosage) and was discontinued more than 1 year before due to symptom-alleviation (fluoxetine) or lack in positive therapeutic outcome or inacceptable side effects (aripiprazole, tiapride, quetiapine). |
pmc-6117874-1 | Our patient was a 45-year-old white man. He was a farmer, former alcoholic, and former smoker. He had had high blood pressure for the past 3 years, which was treated with losartan. He had been followed at Barretos Cancer Hospital (BCH) since November 2015 because he had a diagnosis of Binet stage B CLL. Three months after receiving the diagnosis, he developed stage B symptoms and a significant increase of lymph nodes. Because rituximab is not available in our public health system, the patient was treated with fludarabine and cyclophosphamide. He received six cycles of chemotherapy, achieving a partial response. He was followed up, and after 8 months, his disease relapsed, which led to the indication of ibrutinib. However, before the new treatment could be started, he returned to BCH in April 2017, reporting fever and lesions in the oropharynx and skin that had begun 2 weeks prior to this consultation. He reported that he had used penicillin 3 weeks before because of an unrelated condition.
He also said that, in the beginning, the skin lesions were formed by bullae that burst and caused erosions, crusts, and hemorrhagic surface with bloody exudation. He also had oral mucosa and lips lesions. The patient complained of pain in the affected areas and difficulty eating because of the oral lesions. He also reported episodes of a small amount of anal bleeding.
The patient’s physical examination showed lesions in ocular, oral, and urogenital mucosae; chest; scalp; back; and hand palms. The lesions in the oral mucosa were painful erosions, and hematic crusts were present in the lips. The cutaneous lesions were polymorphic, with bullous erosions, ulcerations, and hemorrhagic crusts involving many areas of the body (Fig. and ). The patient’s Nikolsky sign was positive.
Initially, the main diagnostic hypothesis was Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis based on the previous report of penicillin use []. The patient was directed to the intensive care unit for supportive treatment. Intravenous immunoglobulin was administered for SJS treatment, the lesions were dressed daily, and meropenem and fluconazole were prescribed for a possible secondary skin infection. Although these measures had been taken, the skin and mucosal lesions worsened progressively. The patient’s clinical status deteriorated significantly, which led to the need for oxygen supplementation.
Given the unsatisfactory evolution, biopsies of the skin lesions were performed. The histological analysis showed keratinocyte apoptosis and acantholysis suggestive of PNP (Fig. ). Direct immunofluorescence was not performed, owing to unavailability, but based on the clinical-pathological correlation, the diagnosis of PNP was established.
Pulse therapy with methylprednisolone was prescribed for 5 days. There was a discreet initial improvement, but new bubbles appeared in the patient’s face, chest, and limbs, accompanied by intense pain. Four days after the diagnostic confirmation, the patient died of respiratory failure. |
pmc-6117877-1 | A 77-year-old woman was referred to our division for a mixed ground-glass opacity lesion in the right upper lung. The patient was symptom-free and in good performance status. There were no remarkable findings on physical examination. Chest computed tomography revealed a 34 mm × 20 mm partial solid nodule with spicule formation and pleural indentation at the right S3 (Fig. ). The consolidation tumor ratio was 30%. Preoperative positron emission tomography-computed tomography (PET-CT) revealed that the standard uptake value (SUV) of the lesion was 1.9, and there was no suspicious metastasis. Kommerell diverticulum at the origin of the left subclavian artery and a right-sided aortic arch were detected through preoperative three-dimensional computed tomography (3D CT) reconstruction (Fig. , ). Echocardiography revealed no cardiac abnormalities.
A right upper lobectomy was performed because the lesion was considered to be malignant. A three-port VATS approach with no rib spreading (no soft tissue retractor or direct visualization) was used. A 3-cm incision in the fourth intercostal space (ICS) at the anterior axillary line was made as the main manipulation port, and a 1-cm incision in the seventh ICS at the scapular line was made as an assisted manipulation port. A 1-cm thoracoscopic port was made in the seventh ICS at the middle axillary line. After dividing the interlobar fissure with a linear stapler, we detached and divided the ascending A2, right superior pulmonary vein (RSPV), A1 + A3, and right upper lobe bronchus sequentially. There were no anatomic variations of pulmonary vessels or bronchi (Fig. ). After histologically confirming the invasive carcinoma, radical mediastinal lymph node dissection was performed. After the routine dissection of the pulmonary ligament lymph node (#9) and the paraesophageal lymph node (#8), we dissected the subcarinal lymph node (#7). It was difficult to expose the left main bronchus, as the esophagus could not be suspended easily due to the obstruction of the right descending aorta (Fig. ). When dissecting the paratracheal lymph node, we identified the right vagus nerve above the azygos vein by blunt separation, and we then proceeded with the dissection in the cranial direction (Fig. ). The right recurrent laryngeal nerve (RLN) was observed to branch from the right vagus nerve and hook around the right-sided aortic arch (Fig. ). No upper paratracheal lymph node was dissected because of the obstruction of the right-sided aortic arch. The total operative time was 170 min with an estimated blood loss of 100 cc.
The postoperative histological diagnosis was moderately differentiated adenocarcinoma (80% lepidic and 20% acinar). There were five lower paratracheal lymph nodes, five subcarinal lymph nodes, two paraesophageal lymph nodes, two pulmonary ligament lymph nodes, one #10 lymph node, and two #11 lymph nodes retrieved. No lymph node metastasis was detected. The patient was discharged on postoperative day 7 without any complications such as hoarseness. |
pmc-6117928-1 | A 67-year-old man had the first episode of left leg weakness at the age of 65 years and subsequently experienced numbness of the bilateral fourth and fifth fingers (Additional file ). At the age of 66, he developed right leg weakness and difficulty in walking and was admitted to our hospital. Neurological examination revealed no abnormalities in orientation, memory, or cranial nerves. Mild weakness was noted in the distal muscle of the upper limbs, and pronator drift test was positive in the left upper limb. Lower limb muscle weakness was moderate and particularly noticeable in the left anterior tibialis muscle. Deep tendon reflexes were decreased at the triceps and brachioradialis and absent at the knees and ankles. Babinski sign was positive. Pes cavus and toe clawing were absent. There were no finger tremors. A sensory examination showed bilateral hypoesthesia in the lower leg region, below the knees and bilateral numbness of the fourth and fifth fingers. No abnormalities in the urinary tract were found. The ankle-brachial index of blood pressure was normal. The results of a blood study revealed a mild inflammatory reaction and elevated serum proteinase-3-anti-neutrophil cytoplasmic antibody (PR3-ANCA; 4.0 U/mL; normal range, < 3.5 U/mL). Complete blood count and CRP level were normal. His liver and renal function were normal. Blood sugar was 97 mg/dl and HbA1c was 6.5%. A nerve conduction study was performed at a skin temperature of approximately 30 °C (Table ). Distal motor and sensory nerve palm latency (DL) were prolonged in the left median nerve, and a slight decrease in sensory conduction velocity (SCV) was noted. Compound muscle action potentials (CMAP) at stimulation points above the elbow and sensory nerve action potentials (SNAP) were undetectable in the left ulnar nerve. These electrophysiological abnormalities were consistent with multiple mononeuropathy. Brain magnetic resonance imaging showed asymptomatic multiple cerebral infarctions and multiple micro-bleeding lesions in the white matter (Fig. ). His symptoms did not improve after methylprednisolone pulse therapy and oral prednisolone (30 mg/day) and azathioprine (50 mg/day) therapies.
The pathological findings of a right sural nerve showed neither inflammatory cells around vessels nor any rupture of the inner elastic plate. The loss of smaller fibers and thickening of the blood vessel wall were not observed. Electron microscopy showed granular osmiophilic material (GOM) in the wall of endoneurial small vessels, which indicated peripheral neuropathy resulting from CADASIL (Fig. ). The heterozygous missense mutation p.Arg75Pro was detected in exon 3 of the NOTCH3 gene in the leukocyte DNA of the patient. No family history displayed cerebrovascular diseases or peripheral neuropathies. His father was diagnosed as heart failure of unknown etiology.
There was no history of smoking or drinking. |
pmc-6117941-1 | A 19-year-old Chinese woman was admitted to our institution for the treatment of monostotic FD of her femoral neck. She presented in June 2015 with non-traumatic, nonspecific left hip pain that occurred during university basketball training. She first noticed the pain a month before and visited an out-patient clinic in another hospital when the pain did not improve. She denied any injury to the area or loss of range of motion (ROM), and her condition was not improved by analgesia. X-rays of the region demonstrated a fairly extensive ground glass lesion (Fig. ) in her left femoral neck, which is a classic sign of FD. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed the lesion to be 10 cm in length (Fig. ). She was managed conservatively for 6 months; however, because the pain did not improve she was referred to Keio University Hospital for management. She opted for surgical treatment of the lesion for pain relief and to prevent future fractures and to return to her active lifestyle. She has no other significant past medical history.
In July 2016, she underwent surgery to augment her left femoral neck with an autologous cortical, free fibula bone graft. A minimal curettage and lavage of the femoral neck was done to remove fibrous dysplastic tissue to make room for the graft. The free fibula graft was then harvested from her left fibula. The graft was 10 cm long and hammered into the femoral defect to act as an intramedullary pin. No screws or plates were used and the defect in the fibula was filled with β-tricalcium phosphate (Superpore®; HOYA Technosurgical Inc., Japan) (Fig. and Table ). Samples of the tissue were sent to our pathology department for histological analysis, which confirmed the diagnosis of FD. There were no intraoperative complications and her postoperative course was uncomplicated; a short course of prophylactic cefazolin and adequate analgesia were prescribed. She discharged with non-weight bearing (NWB) on crutches on postoperative day 7.
As no dynamic hip screw was used, she was NWB for 6 weeks to allow for adequate healing and integration of the bone graft. With physiotherapy, she returned to partial weight bearing (PWB) at 4 weeks postoperation, full weight bearing (FWB) at 8 weeks, and returned to her sporting activity at 3 months. The operative site and the donor site have healed well and her postoperative course has been unremarkable. Follow-up X-rays demonstrated healing and integration of the femoral graft without reabsorption and with no recurrence of FD (Fig. ). She was followed up regularly for a year to monitor for reabsorption of the fibula graft, which is a common complication of autologous bone grafting. At 1-year follow-up, she had completely returned to competitive basketball, recently taken up tai-chi, and had no limitation of activities and no residual hip pain. |
pmc-6117974-1 | A 66-year-old Caucasian man presented with recurrent, metastatic MCC that involved several sites in liver, bones and disseminated lymphadenopathy. Primary MCC diagnosed 3 years before was located on the forearm without lymph node involvement and was treated with surgery and adjuvant radiation therapy. Serologic testing for antibodies to the Merkel cell polyomavirus T-antigen oncoprotein was negative []. The patient’s past medical history included hypertension, hyperlipidemia, coronary artery disease treated with stenting, gastroesophageal reflux, and mild cerebral palsy that had been stable. His activities of daily living were not limited by his comorbidities. Medications included lisinopril, simvastatin, aspirin, omeprazole, and zolpidem. His ECOG performance status was 0 and his physical exam revealed a stable speech impediment. After a discussion of various systemic therapeutic options for his metastatic MCC, the patient decided to participate in a clinical trial investigating ICIs in virus-associated cancers including MCC (; NCT02488759). The patient provided informed consent for treatment and for information sharing as part of a research protocol approved by the University of Washington/Fred Hutchinson Cancer Research Center IRB. He received dual immune checkpoint blockade with one dose of ipilimumab (1 mg/kg) plus nivolumab (3 mg/kg) administered on day 1.
At the time of treatment on day 1, he had no concerning neurologic, GI or other symptoms. Seven days after the administration of first dose of combination immunotherapy, the patient reported diffuse muscle aches, urinary retention, abdominal distention and a sensation of ‘gagging’ with swallowing attempts. He began taking low doses of oxycodone 5 mg every 4-6 h with partial relief. Four days later (day 11 post-immunotherapy), he was hospitalized due to worsening symptoms and a need for supportive care. A CT scan showed air-filled loops of small and large bowel and an increased stool burden within the right colon consistent with pseudo-obstruction without clear signs of mechanical obstruction. Diverticulosis was present without pericolonic fat stranding suggestive of diverticulitis. Despite methylnaltrexone (given for treatment of possible opioid induced constipation) and escalating doses of laxatives, no bowel movement was produced. Abdominal distention and constipation persisted, together with recurrent bouts of emesis. On day 13 post-immunotherapy, the patient developed hypoxic respiratory failure, attributed to an episode of aspiration, and required mechanical ventilation. A CT scan showed mildly distended fluid filled small bowel loops, moderate to large stool burden in the right colon and fecalization of the terminal ileum contents. Microbiological blood and urine cultures were sterile. The patient was treated with supportive care for 5 days after which extubation was successful. Video laryngoscopy showed a widely patent airway, with severe aspiration due to swallow delay/discoordination, weakness of base of tongue, hyolaryngeal excursion, moderate to severely weak pharyngeal constrictors and cricopharyngeal dysfunction. The patient was also noted to have nasal regurgitation due to uncoordinated velar elevation. A fluoroscopic study of oral contrast (gastrografin) showed absence of contrast progression to colon 48 h following administration.
On day 22 post-immunotherapy, the patient’s respiratory status decompensated again and repeat intubation was required. A second CT scan of the abdomen showed partial regression of the MCC metastases in the liver and resolution of retroperitoneal lymphadenopathy. A fluid-filled esophagus and dilated loops of proximal small bowel, again without a transition point, was essentially unchanged from the prior scan. Placement of a nasogastric tube returned nearly 2 L of bilious and later feculent material. This clinical presentation of diffuse intestinal paresis and pharyngeal dysfunction following administration of immune checkpoint blockade suggested the possibility of immune-mediated neuropathy of the enteric nervous system or a similar irAE (based on our prior experience with a similar case published by our group) []. Due to this concern, treatment with methylprednisolone 2 mg/kg daily was initiated on day 22 post-immunotherapy.
Evaluating whether this patient was suffering from an immune adverse effect of checkpoint immunotherapy on myenteric ganglia was challenging because the myenteric plexus, which lies within the muscularis propria, is evaluable only by a full-thickness biopsy. The feasibility of this endoscopic procedure was discussed extensively with the multidisciplinary team involved in the patient’s care, but was considered to pose a prohibitively high risk for perforation and poor wound healing. There was also concern that use of endoscopic cautery after biopsy could ignite bowel gases in the setting of obstipation. The patient’s three prior episodes of pulmonary decompensation resulted in increased risk for prolonged intubation following anesthesia. These considerations also placed the patient at prohibitively high risk for surgery. Thus, invasive diagnostic testing was not attempted. Serologic testing for antibodies to the acetylcholine receptor was negative. Additional serologic tests for anti-Hu antibodies as well as antibodies to P/Q type and N type calcium channels, neuronal (V-G) potassium channels, striated muscle, antineuronal nuclear antibodies, anti-glial nuclear antibodies, Purkinje cell cytoplasmic antibodies, amphiphysin antibodies and CRMP 5 were negative. The patient did not exhibit any arrhythmia during periods of cardiac monitoring.
Following 1 week of treatment with high dose steroids, there was no apparent improvement in gut motility and the patient continued to have no bowel movement or passage of flatus. On day 30, the patient was started on tacrolimus with a target trough of 5–15 ng/mL. Enemas were attempted to induce defecation, but were unsuccessful. Plasmapheresis to remove potential pathogenic autoantibodies was initiated on day 45 post-treatment and repeated every other day for a total of 5 treatments. A venting gastrostomy tube was placed on day 49 due to worsening abdominal distention. On day 51 post-treatment, a CT scan showed focal inflammatory stranding and air involving the transverse colon compatible with diverticulitis with contained perforation. The known MCC tumors had regressed further (see Fig. ). The percutaneous gastrostomy tube was noted in the appropriate position. Surgical consultants suggested that repairing the perforation was very high risk and would not correct the underlying suspected pathology. Therefore, best supportive care was continued for a further 5 days. Following absence of improvement, the patient and family decided to transition to comfort care. On day 58 post-treatment, the patient died from progressive sepsis complicated by multi-organ failure.
After obtaining permission from the family, an autopsy was performed. Findings upon gross examination included peritoneal fluid contaminated by stool and diverticulosis with two associated perforations. The spleen was enlarged with diffluent parenchyma, and the liver histology showed cholestasis and biliary pools, findings associated with sepsis. Extensive sampling of the gastrointestinal tract was performed to include esophagus, stomach, small and large bowel, with microscopic evaluation revealing severe hypoganglionosis along its entire length, with absence of ganglion cells within the myenteric plexus and only rare submucosal ganglion cells (see Fig. -). Within the myenteric plexus residual glial cells remained, however no conspicuous lymphocytic infiltrate was identified. Immunohistochemistry with appropriate controls was performed. Within the myenteric plexus, no immunoreactivity for neuron-specific anti-Hu antibodies was seen, consistent with complete absence of ganglion cells. Furthermore, while staining with antibody PFP9.5 demonstrated scattered residual neuronal processes, likely the projections from extra-enteric autonomic or sensory ganglia, no staining of myenteric ganglion cell bodies or intramuscular nerves was seen, again supporting extensive loss of ganglion cells within the myenteric plexus. Rare submucosal ganglion cells were identified with each neuronal marker (Fig. and , inset), but were far fewer than normal. Immunostaining for SOX10 highlighted condensation of residual glial cells consistent with the death of nearby nerve cells []. A trichrome stain demonstrated some fibrosis in the areas of residual glial cells, consistent with a chronic injury response (not shown). A search for other sites of injury revealed reduced numbers of nerves and ganglia in the urinary bladder and epicardium as well (not shown).
The area of radiologic abnormality associated with clinical suspicion for residual MCC within the right lobe of the liver was grossly identified as a pale-yellow discolored nodule within the hepatic parenchyma. Microscopic examination demonstrated fibrosis and necrosis without identifiable residual carcinoma. Representative lymph nodes in the areas of previous radiologic enlargement were similarly free of carcinoma by gross inspection as well as histologic examination (not shown).
To investigate the possible pathogenetic involvement of the humoral immune system, we stained histologic sections of colon tissue for C4d. C4d is a serine protease in the classical complement cascade that can be generated and deposited during complement activation by the antibody complexes, resulting in formation of multi-molecular complexes with immune effector and cytolytic activity []. We found intense C4d immunoreactivity around and occasionally within the aneuronal ganglia of our patient (Fig. ), as well as in vessel walls and along probable intramuscular nerves in the muscularis propria. The perineuroglial pattern was observed around the patient’s myenteric plexus, but not around his residual submucosal nerves. No immunoreactivity was observed in sections for which the primary antibody was omitted. In contrast, sections from the colons of 4 controls (cadaveric samples with similar autolysis, but no history or intestinal dysmotility) showed only very weak immunolabelling of some vascular endothelial surfaces and no perineural C4d immunoreactivity (Fig. ). These results demonstrate local complement activation at the site of organ dysfunction (the myenteric plexus) and support a possible contributing role of antibodies in the pathogenesis of this patient’s myenteric plexopathy. |
pmc-6117978-1 | A 39-year-old Caucasian female was diagnosed with nodular melanoma of the right upper back following a biopsy. Wide local excision (WLE) and right axillary sentinel lymph node (SLN) biopsy were performed; although WLE was negative, SLN was positive for multiple foci of residual melanoma in two LN. Completion lymph node dissection (CLND) was negative for any involvement of 19 LN. She was staged with IIIA (T3aN2aMx) disease and offered adjuvant therapy with ipilimumab based on the EORTC 18071 data []. Between January 4, 2017 and February 24, 2017, she received 3 doses of ipilimumab 10 mg/kg IV. Prior to fourth induction dose of ipilimumab, she developed flu-like symptoms and persistent headaches although no neurologic deficits were noted. Magnetic resonance imaging (MRI) of the brain and spine showed mild pituitary enlargement and leptomeningeal enhancement with a nodular focus of enhancement in the right internal auditory canal (Fig. and ). On lumbar puncture, opening pressures were elevated (> 30 mm water) while cerebrospinal fluid (CSF) examination was negative for any malignant cells but showed lymphocytic pleocytosis. Extensive testing excluded infectious and autoimmune etiologies; and other laboratory tests were consistent with central hypothyroidism and adrenal insufficiency. She was diagnosed with ipilimumab-related meningoencephalomyelitis, and treated with methylprednisolone 1.0 mg/kg daily with rapid improvement and discharged on an oral prednisone taper. As an outpatient, prednisone was gradually tapered over an eight-week period till she was on physiologic doses of hydrocortisone. She was also treated with levothyroxine 100 mcg daily for ipilimumab-related hypothyroidism. Ipilimumab adjuvant therapy was permanently discontinued.
Approximately 3 months following initial admission, she developed lower extremity weakness and fecal and urinary incontinence. MRI imaging of the brain and spine showed recurrent leptomeningeal and cranial nerve enhancement; diffuse lack of FLAIR suppression of CSF signal; and expansion of the cervical cord and T2 hyper-intense cord signal alteration with abnormal patchy intramedullary enhancement (Fig. and ). CSF studies documented recurrent lymphocytic pleocytosis while serological studies were negative for autoimmune etiologies including paraneoplastic syndromes. Her CSF protein was elevated to 120 mg/dL (range 15–45 mg/dL). Imaging was negative for any evidence of recurrent malignancy. Per American Society of Clinical Oncology (ASCO) clinical practice guidelines, IVIG 1 g/kg and methylprednisolone 1.0 mg/kg IV daily were administered for 5 days albeit with scant improvement. In the setting of IVIG/steroid refractory ipilimumab-related meningoencephalomyelitis, a trial of infliximab was offered. Infliximab 5 mg/kg IV was administered while prednisone 1 mg/kg daily was continued with improvement in neurologic function []. Two days after first dose of infliximab, she was able to ambulate with support although she continued to have urinary retention. Subsequently, she was discharged for spinal cord rehabilitation. Infliximab 5 mg/kg was continued for a further two doses at two and 4 weeks following initial administration. Prednisone was continued at 60 mg daily for 2 months then tapered gradually by 10 mg every 2 weeks over a 3-month period after which she was transitioned to physiologic replacement doses of hydrocortisone on which she remains indefinitely. Her headaches and neurologic symptoms have improved substantially with near complete neurologic recovery including continence except mild spasticity in lower extremities. Repeat MRI imaging of the brain and spine documented progressively decreased leptomeningeal enhancement and eventual normalization of T2 signal (Fig. and ). Restaging scans remain negative for recurrent melanoma. |
pmc-6117978-2 | A 55 year-old male was diagnosed with stage IIIB (T4bN1aMx) superficial spreading melanoma of the right distal thigh after initial surgery, right inguinal SLN biopsy and right inguinal CLND. He was treated with ipilimumab 10 mg/kg IV every 3 weeks and received 2 doses. Following second dose, he developed parasthesias in distal lower extremities bilaterally that subsequently ascended to involve proximal lower extremities, then upper extremities along with weakness and loss of deep tendon reflexes. No bladder or bowel incontinence and/or difficulties with speech were observed. MRI brain and whole spine revealed abnormal enhancement involving the bilateral 5th, 7th and 8th cranial nerves, cauda equina nerve roots as well as the conus surface and peripheral nerves at the thoracolumbar junction (Fig. and ). CSF studies were negative for malignant cells but showed lymphocytic pleocytosis. CSF protein was elevated to 175 mg/dL (range 15–45 mg/dL). An extensive evaluation for autoimmune and paraneoplastic etiologies was negative although laboratory studies revealed concomitant adrenal insufficiency. Electromyography showed electrophysiologic evidence consistent with a generalized, sensory and motor, length-dependent, predominantly axonal, peripheral polyneuropathy without definite electrophysiologic evidence of a presynaptic neuromuscular junction transmission disorder or proximal myopathy. He was diagnosed with ipilimumab-related acute inflammatory demyelinating polyneuropathy (AIDP).
Methylprednisolone 1.5 mg/kg twice daily was initiated with rapid improvement in motor symptoms in hands and lower extremities after 2 days. Steroids were tapered slowly from prednisone 1 mg/kg by decreasing by 10 mg weekly over a 12-week period with gradual recovery. Towards the end of the taper, prednisone was transitioned to physiologic doses of hydrocortisone to treat ipilimumab-related adrenal insufficiency. Although weakness resolved completely, he continued to have minimal parasthesias in upper extremities and lower extremities in a glove-and-stocking distribution. Approximately 4 months after initial ipilimumab therapy, he developed hypothyroidism for which he was treated with levothyroxine 125mcg daily. Systemic imaging studies remain negative for recurrent disease. |
pmc-6118036-1 | A 34-year-old gentleman was first referred to orthopaedic services with a history of persistent knee pain, located over the right femoral condyle near the origin of the lateral collateral ligament. Eleven years prior to presentation, the patient was involved in a road traffic accident where he sustained a fracture of the right femoral neck and ipsilateral shaft. Initial management consisted of open reduction, fixation of the femoral neck fracture with cannulated screws and the ipsilateral shaft fracture with plating. The patient later had a revision of the plate to a femoral nail. Union was subsequently achieved with the femoral shaft fracture; however, a significant external rotation deformity was noted, and discomfort to the knee.
The patient was referred on to our tertiary referral orthopaedic centre for femoral de-rotation surgery. An initial CT scan performed revealed an external rotation deformity of 45 degrees. The patient procedure included removal of femoral nail, osteotomy with de-rotation surgery, and subsequent exchange nail. The femoral nail was fixed proximally and locked into place distally, following the corrective 45 degrees of internal rotation achieved to the distal femur during osteotomy, performed under intraoperative radiographic guidance. The post-operative rehabilitation regime consisted of initial touch weight bearing only, with gradual increments in weight bearing status. At six months follow-up, the patient complained of distal lateral femur pain. A repeat CT scan was performed, revealing a delayed femoral union. This was initially thought to be the cause of the patient’s symptoms. The patient was admitted for dynamization of the femoral nail with an injection of bone graft substitute, and iliac crest graft. Despite eventual union, the patient continued to complain of pain at the distal lateral femur, with a cracking sensation on movement now noted.
Repeat clinical examination revealed a palpable crepitus over the distal iliotibial band with a snapping sensation, as it appeared to catch. A palpable small, solid swelling was noted at the posterolateral right knee. Ultrasound and CT revealed intra-articular loose bodies lying within the lateral para-patellar gutter. The patient subsequently underwent arthroscopy with removal of loose bodies. Despite this, at six-months follow-up to arthroscopy, the patient continued to complain of posterolateral knee pain. MRI showed no evidence of abnormality to the popliteus tendon or muscle, but highlighted the fabella embedded within the lateral head of gastrocnemius at the posterolateral corner of the knee. (Image ). The fabella was also notable on radiographs (Image ) and CT (Image ). Ultrasound scan confirmed the fabella as mobile on movement and associated with tenderness. The diagnosis of Fabella Syndrome was made, and the patient planned for a Fabellectomy procedure.
An initial arthroscopy was performed to review the knee joint, and to potentially assist in surgical excision of the fabella. A complete diagnostic arthroscopy was performed, with the fabella unable to be identified through the posterior capsule. After arthroscopy, open fabellectomy was performed. In view of the patient’s extensive scarring from prior orthopaedic procedures, a short 2cm incision was made directly over the palpable fabella (Image ). The common peroneal nerve was identified and spared. Subsequent incision left a cuff of biceps femoris to protect the nerve. Gastrocnemius was split and incised directly over the fabella, which was removed in entirety (Image ). Histopathology confirmed the diagnosis.
The patient was followed-up at two and ten months postoperatively. At both follow-ups, he described the complete resolution of his posterolateral knee pain. |
pmc-6118291-1 | A 68-year-old man presented to our outpatient clinic for good health maintenance. He had a past medical history of vitamin B12 deficiency for which he was getting monthly parenteral therapy. A detailed history is taken and he reported that he had no fever, chills, diarrhea, cough, anorexia, weight loss, or rash. On physical examination, the heart rate was 85 beats/min and the blood pressure was 130/70 mmHg. The abdomen was soft, with normal bowel sounds and with no organomegaly. No peripheral edema was seen. No rash, petechiae, ecchymoses, oral lesions, or lymphadenopathy was found. The arms revealed no abnormalities and the legs were normal. Neurological examination was normal.
The levels of glucose, urea nitrogen, creatinine, calcium, phosphorus, and magnesium were normal; also the levels of total bilirubin, aminotransferase, and alkaline phosphatase were normal. Lipid panel showed total cholesterol (TC) 144 mg/dl, triglycerides (TG) 79 mg /dl, HDL-C 5 mg/dl, and low density lipoprotein (LDL) 123 mg/dl. Lipid panel done three years ago showed a HDL-C of 41 mg/dl. Further workup revealed serum apolipoprotein A1 (APO A1) 97 mg/dl (94-176), apolipoprotein B (APO B) 35 mg/dl (52-109), the ratio of APO B/ APO A 1 0.36 , lipoprotein A 19.0 nmol/l (<75), and direct LDL 28 mg/dl ( <130). Important laboratory investigations are given in Table .
The patient was treated with an incremental dose of extended-release nicotinic acid but his HDL remained low. The secondary causes of low HDL-C levels such as the use of androgens, progestins, cigarette smoking, obesity, low-fat diet, and drugs like beta-blockers were ruled out. This leads us to consider the less well-known but well-documented fact that monoclonal gammopathies have unusual specificity for apolipoprotein, and paraproteins may interfere with the measurement of HDL-C in some automated analyzers. To confirm our hypothesis we performed serum protein electrophoresis with immunofixation, which showed IgG 720 mg/dl (576-1782), IgA 116 mg/dl ( 59-484) and an abnormally high IgM at 3510 mg/dl (57-266). Bone marrow biopsy showed a paratrabecular and intertrabecular infiltrates of small noncleaved lymphocytes. Immunohistochemical studies showed B cell phenotype (CD 45, CD20 positive, and negative CD 3 and CD 10) consistent with Waldenstrom macroglobulinemia. He is being followed conservatively by hematology as has been stable thus far. |
pmc-6118292-1 | A 63-year-old woman, nursing home resident, with uncontrolled type-2 diabetes and chronic schizophrenia presented to the hospital with complaints of altered mentation, fever, and profound diarrhea for two days. At the time of admission, she was febrile (temperature 101.5° F) but hemodynamically stable. Pertinent physical exam findings included hyperactive bowel sounds and an abdomen which was tympanitic to percussion. There were no peritoneal signs or rebound tenderness.
Initial work-up revealed the following: white blood cell (WBC) count 15,400 cells/mL with 89% neutrophils; serum glucose 195 mg/dL; urea 13 mg/dL; creatinine 1.5 mg/dL; and lactic acid 3 mmol/L. Blood cultures were negative. A urine culture revealed > 100,000 CFU/ml Klebsiella pneumoniae. An abdominal computed tomography (CT) scan demonstrated significant (1.6 cm) mucosal wall thickening of the walls of the urinary bladder with perivesical inflammatory stranding. Intraluminal/intramural gas was identified within the walls of the urinary bladder that was consistent with EC with possible perforation (Figure ). The CT scan further showed pneumoperitoneum predominantly in the anterior pelvis as well as diffuse colitis and proctitis with mesenteric fat stranding. Stool cultures were negative for Salmonella, Campylobacter or Yersinia species. However, the stool polymerase chain reaction tested positive for C. difficile.
The patient was intubated due to her low Glasgow Coma Scale (GCS) score and poor airway reflexes. Since the patient did not have signs of acute abdomen or findings requiring emergency laparotomy, she was treated non-operatively. Antibiotics including ceftriaxone were initiated along with oral vancomycin and intravenous metronidazole.
Urology was consulted and ordered a cystogram to further evaluate for suspected perforation which revealed no radiographic evidence of a bladder perforation and hence recommended conservative management (Figure ). In consultation with General Surgery for pneumoperitoneum in the setting of diffuse C. difficile colitis, it was suspected that the free intraperitoneal air was unlikely secondary to colonic perforation but instead related to EC with tracking of air into the pre-peritoneal space. Conservative management was pursued through the placement of an indwelling catheter for one week. Strict glycemic control was maintained to optimize the patient's uncontrolled diabetes. The patient's fever, diarrhea, and mentation, as well as leukocytosis and renal function, improved and she was subsequently extubated and transferred to the general medical floor on day 4 and discharged to a nursing home on day 12 of hospitalization. A follow-up CT scan three days after discharge showed radiological improvement (Figure ). |
pmc-6118296-1 | A 56-year-old female presented to our department with chest discomfort. Contrast-enhanced chest computed tomography (CT) revealed a 35-mm well-circumscribed cyst and an adjacent 10-mm nodule in the anterior mediastinum (Fig. A). Positron emission tomography–CT demonstrated an increased uptake only in the small nodule (maximum standardized uptake value: 3.8; Fig. B). The patient took pitavastatin for hyperlipidaemia (triglyceride 271 mg/dL, LDL-cholesterol 180 mg/dL) and had no evidence of cholesterol deposition in tissue or organ at the time. She had no history of trauma and was not on any anticoagulant drugs. The laboratory findings, including the tumour marker levels, were all within the normal range. Therefore, based on the diagnosis of cystic thymoma, total thymectomy was performed for a definitive diagnosis and treatment plan creation.
Macroscopically, a 20 × 20 × 10-mm cyst containing yellowish-brown jellied effusion and a 13 × 13 × 12-mm, light-brown, solid nodule were observed separately in the thymus. Microscopically, different-sized cysts with foam cell infiltration were noted to be scattered in the thymus. Almost all cysts were filled with several cholesterol clefts and showed three different phase characters. Inflammatory granulation was noted inside the ruptured cystic wall (Fig. A). Granuloma involving cholesterol clefts was formed in the lining of the cystic wall (Fig. B), and this replaced the whole lumen (Fig. C). Conversely, the 10-mm nodule, not bordering the thymic cysts, was composed of several granuloma-containing cholesterol clefts without any cystic component. Cholesterol clefts in the granuloma were arranged in an alveolar-like growth pattern (Fig. D), which was different from that in the lumen (Fig. C). Based on the above-mentioned findings, the pathological diagnosis of multifocal thymic cysts with cholesterol granuloma was made. The patient was discharged without any post-operative complication and was followed up for two years post-operatively without any recurrence. |
pmc-6118646-1 | In October 2016, A 54-year-old male presented with bilateral crippling hip pain in the groin on both sides radiating to the front of the thigh with reduced mobility for almost 3 years and progressive worsening of symptoms. He had developed a significant limp preventing him from walking and performing routine activities independently with disturbed sleep.
On examination, he had a bilateral stiff hip, antalgic gait with a BMI of 34.1. Both hips had very limited range of motion (). He had a poor Harris Hip Score of 34.2 in the left hip and 34.3 in the right hip. Anteroposterior X-ray of the pelvis with both hip joints showed severe bone-on-bone arthritis () in both the hip joints. He elected to undergo simultaneous bilateral soft tissue sparing bikini anterior hip replacements described previously by the senior surgeon []. The left hip was operated first followed by right with a surgical time of 135 minutes total.
Post-operatively, mechanical thromboprohpylaxis was used for 24 h followed by oral aspirin 300 mg with nexium for 6 weeks. He was mobilized within few hours after surgery as part of our enhanced recovery programme. He started walking with the aid of a walking frame and even managed a dozen steps unaided the same day. He was discharged on the 2nd post-operative day. He started on his exercise bike Day 5 post op and resumed driving on the sixth day onwards as he was very mobile with a single crutch mainly for safety and not on any narcotic analgesia. He felt very confident and comfortable and had no issues driving.
On day 9 post-op, he was back at work doing light duties and clerical activities by which time he was mobile with pain free hip movements and without any mechanical dysfunction. At the 6 week mark he had a well healed surgical scar with no swelling and walked in without a limp. He was followed up regularly at 3 months and 12 months post-operatively. His last follow up was 16 months post-surgery by which time he was having no issues in either hip joints and was able to do all his day to day activities, with a highly improved quality of life. His X-rays () were showing well aligned acetabular and femoral prosthesis insitu on both sides. His post-operative Harris Hip score was excellent, for both hips being 100. |
pmc-6118646-2 | In October 2017, a 59-year-old female presented with severe pain in both her hips over the preceding 3 years. Most of her pain was localized to her groin, right worse than the left. Over the preceding few months her pain increased to a level where she couldn't perform her normal daily activities with disturbed sleep at night. Along with this pain, she started developing a noticeable limp over 12 months. She used two crutches to support herself with a walking distance of only 30–50 m. Her quality of life was severely compromised and taking strong analgesics including opiods.
On examination, she walked with a bilateral stiff hip antalgic gait with a BMI of 24.1. Both her hips had very limited range of motion (). She had a poor Harris Hip Score of 19.5 for the left hip and 19.4 for the right hip. Her X-rays revealed, severe bone on bone osteoarthritic changes bilaterally (). She underwent one stage bilateral anterior hip replacement.
The same post-operative recovery protocol was followed as in the first case. She went to rehab on day 3 as she lived alone. At her 2-week post-operative visit, she was doing excellent and hardly experienced any pain. She had a well healed scar with hip flexion beyond 90° in both hips (). She commenced driving within 2 weeks. On her 6-week post-operative visit, her Harris Hip Score was 100 for both hips.
The prosthesis used for both the cases was polar stem (uncemented − Smith and Nephew AG, Baar, Switzerland), Oxinium femoral head (Smith and Nephew Memphis Tennessee) R3 three hole HA acetabular shell (Smith and Nephew Memphis Tennessee) and acetabular liner R3 XLPE (Smith and Nephew). |
pmc-6119177-1 | This case report describes an adult male patient with class II subdivision malocclusion, dental crossbite, and crowding treated successfully with aligners.
An 18-year-old hyperdivergent male patient presented for treatment. Extraoral photos (Fig. ) and frontal examination revealed good incisor exposure; however, buccal corridors and upper midline deviation towards the left with respect to the facial midline were present. The profile had a convex aspect characterized by mandibular retrusion and increased lower facial height.
Clinical examination revealed class II subdivision with lower midline deviation towards the right of the upper midline, dental crossbite, slight crowding in both arches, and small alteration of the upper right lateral incisor morphology.
Periodontal biotype and oral hygiene were good (Fig. ).
Panoramic radiography revealed full dentition, a lack of bone defects, no infection and no temporomandibular joint abnormalities (Fig. ).
Latero-lateral teleradiograpy (Fig. ) showed skeletal class II from mandibular retrusion, and a hyperdivergent facial type; maxillary incisor were proclined and mandibular incisors had a correct inclination. Overbite and overjet were increased as reported in Table .
Clinical examination showed no sign of bad habits.
The primary objective was to achieve a molar and canine class I and centering the upper midline with the lower and facial midlines. Additional objectives were to correct the crowding and dental crossbite, obtain ideal overjet and overbite (Fig. ), improve facial esthetics, and reduce black buccal corridors during smile.
As there were no major skeletal discrepancies, a combined orthodontic/surgical approach was ruled out. Fixed multibracket treatment with extraction of four premolars was considered, but also excluded due to potential worsening of the profile. The patient was therefore offered a treatment plan involving unilateral distalization by fixed multibracket appliances in order to center the upper midline with the lower and facial midlines. However, the patient refused this option due to the unsightliness of the device, and we therefore agreed upon a non-extractive treatment with F22 aligners (Sweden & Martina, Due Carrare, Italy) for unilateral distalization and mesialisation of the lower arch in order to correct the class II relationship.
The virtual set-up dictated 20 treatment steps for each arch. To achieve upper midline correction, the plan involved distorotation of teeth 1.6 (22°) and 1.7 (13°) in association with distalization. The use of class II elastics had a double function: the anchorage, used to obtain simultaneous distalization of the elements of the quadrant I and support the correction of the lower midline.
In the lower arch, the plan involved mesorotation of teeth 4.6 and 4.7 associated with mesial tipping. The plan also involved alignment of the arches and retroclination of the upper incisors.
In order to achieve correct alignment and valid intercuspidation, vestibular grip points on teeth 1.6, 1.7, 4.5, 4.4, and 4.3 were planned, alongside 0.2 mm of stripping at each interproximal point in the lower right sector, from the mesial surface of tooth 4.6 to the distal surface of 4.2.
In order to promote achievement of class I, 6 oz. intermaxillary elastics were to be hooked directly on the apposite notches in the aligners at the upper canines and lower first molars from step 1 onwards (Fig. ). The patient was instructed to wear each aligner for 22 h per day and to move on to the next one in the series after 14 days.
After 10 months of treatment, the treatment objectives had been successfully fulfilled, although it was necessary to plan another three steps per arch for detailed finishing of the case and complete class correction. Specifically, the derotation of teeth 4.5, 1.6, and 1.5 was improved.
Post-treatment records demonstrate satisfactory final results with all objectives achieved. Extraoral photos show a good profile, correct incisor exposure during smile and the absence of buccal corridors (Fig. ). Intraoral examination reveals the achievement of all planned objectives, namely class I, centered midlines, and crowding correction (Fig. ). Post-treatment panoramic radiography (Fig. ) showed good root parallelism, no sign of crestal bone height reduction, and no evidence of apical root resorption. Cephalometric indices and post-treatment latero-lateral teleradiograpy show good vertical control and proclination of the lower incisors (Table ). Superimposition of pre- and post-treatment cephalometric tracings (Figs. , , , , and ), carried out according to the methodology described in the images captions as developed by Professor Arne Björk [, ], highlight the distal tipping movement of the right upper sector, the retroclination achieved at the upper incisors, and the proclination of the upper incisors with respect to the basal bone—an acceptable outcome due to the morphology and conformation of the patient’s symphysis.
Check-up at 1 year demonstrates the excellent stability of results (Figs. and ).
The last pair of aligners was used for retention due to the elastic propriety of the thermoplastic material [].
Restoration of the 1.2 was performed in order to improve its morphology. |
pmc-6119261-1 | On July 2017, a 52 year old Caucasian woman was admitted to our Emergency Department with acute respiratory failure. She had complained in the previous days of drowsiness, apathy and headache. Arterial blood gas determination showed the following values: pH 7.48, pCO2 92.0 mmHg, pO2 58.5 mmHg, B.E. (B) 16 mmol /L, HCO3 42.6 mmol/L, SO2 91.3%. Significant data at clinical history were a former smoking habit and quadrantectomy for breast carcinoma in 2012. In the latest two years she had been followed by a nutritionist for unintentional weight loss. For a long-term history of headache, 3 months before she had undergone to a brain Nuclear Magnetic Resonance (NMR) found to be normal. Due to depressive symptoms in the latest 12 months, she had been prescribed by a psychiatrist citalopram and then duloxetine without benefits.
At hospital admission chest X-ray did not show significant alterations. An electromyographic study was performed, including nerve conduction evaluation, repetitive nerve stimulation, and concentric needle examination (this latter of limited reliability for the effect of sedation on patient’s cooperation). Commonly tested nerves and muscles were explored with normal findings.
The whole clinical scenario was interpreted as an exacerbation of chronic ventilatory failure not related to a neurological cause. Actually, the presence of long-standing symptoms such as headache, tremor, drowsiness, psychic alterations were attributed to chronic hypercarbia caused by a broncho-pulmonary disorder.
In the following days, a transient clinical improvement allowed to extubate the patient. Distress of accessory muscles with rapid recurrence of respiratory failure required a prompt re-intubation. A percutaneous tracheotomy was performed with the placement of a cuffed non-fenestrated cannula (Tracoe 301–06, internal diameter 6.0 mm). The patient was ventilated in Pressure Support Ventilation (PSV) mode. A chest CT showed parenchymal consolidation areas in the right upper lobe and bilateral pleural effusion, with no evidence of diaphragm elevation. A bronchoscopy with bronchoalveolar lavage (BAL) ruled out significant alterations in the tracheobronchial tree, after removal of dense mucous exudate. Blood tests showed anemia (Haemoglobin 8.2 g/dL), absence of leukocytosis and normal values of creatine kinase (CK) (43 U/L).
The following week, a second electromyographic study confirmed normal data at limb examination. A diaphragm nerve conduction study revealed pathological low amplitude of both right and left responses as the only isolated neurophysiological alteration. The interpretation of the latter data was uncertain but a diagnostic work-up searching for primary neurological causes was scheduled. Blood CK, brain and cervical spine MRI, contrast-enhanced brachial plexus CT scan and cerebrospinal fluid examination were all found to be normal.
Following 10 days in the Intensive Care Unit, the patient was admitted to the Respiratory Intensive Care Unit (RICU) of our Pneumological ward. After a long period on continuous mechanical ventilation the patient showed a progressive clinical improvement allowing a gradual weaning. Unfortunately, a sharp increase in CO2 values (> 100 mmHg) was associated with the appearance of nonconvulsive status epilepticus. The patient was treated with intravenous phenytoin, with improvement in symptoms and regression of electroencephalography abnormalities (EEG). A switch to volumetric mode ventilation accelerated a good compensation of respiratory exchanges, with a progressive decrease of CO2 values and regression of epileptiform abnormalities on EEG. Recurrent respiratory infections sustained by various bacteria (Stenotrophomonas Maltophilia, Morganella Morganii, Enterobacter cloacae), required repeated cycles of targeted antibiotic therapy with piperacillin/tazobactam, cotrimoxazole, ceftriaxone, levofloxacin, meropenem.
In the following weeks the patient reached a complete recovery of awareness and collaboration, permitting to perform a quantitative electromyography testing (QEMG), which showed myopathic changes in few proximal and axial muscles. A diffused myopathy with prevalent clinical involvement of the axial and respiratory muscles was therefore hypothesized as the origin of a condition leading to respiratory muscle exhaustion. The autoantibody research was also performed to rule out neuromuscular junction diseases and autoimmune neuropathies.
A muscle biopsy was performed by incision on the left brachial biceps. The analysis confirmed myopathic changes with glycogen storage vacuoles and atrophy of type 1 and 2 fibers; enzimatic testing disclosed markedly reduced acid α-glucosidase activity in muscle tissue. A molecular analysis of the Glucosidase Alpha Acid (GAA) gene was also performed by examining DNA from peripheral blood leukocytes using new generation sequencing with Illumina MiSeq and Agilent Haloplex HS kit. The regions analyzed were the coding region and intron-exon junctions. The pathogenetic mutations were identified in heterozygous c.-32-13 T > G and c.1551 + 1G > C. Therefore, the final diagnostic outcome was “Glycogen Storage Dysease type 2” also known as LOPD.
At the end of August, enzyme replacement therapy (ERT) was started with infusion of recombinant human alglucosidase alpha (rh-GAA, Myozyme®; Genzyme Corporation, Cambridge, MA, USA), 20 mg/kg of body weight (900 mg), administered every 2 weeks.
The patient was then transferred to the Unit of Respiratory Rehabilitation and in the following months there was a progressive clinical improvement with gradual reduction of ventilatory support to night hours only, and recovery of autonomous walking. Evaluation of the diaphragmatic function was not performed since at that point it would have not contributed to modify the clinical management. A monitoring at follow up did not show any development of anti-rhGAA antibodies, without any variation of the response to the replacement treatment. |
pmc-6119272-1 | A 21-year-old female patient without any known adverse medical background presented with a 1 month history of headache, nausea, fatigue and blurred vision. Physical examination and computer tomographic (CT) scan showed pericardial inflammation and splenomegaly (2 cm). Ophthalmoscopy of the right eye revealed papillary edema, retinal hemorrhages (Roth’s spots) and arteriovenous nickings (for further details see Fig. and Table ). Initial laboratory evaluation of peripheral blood (PB) revealed a white blood cells (WBC) of 113.2 × 109/l (72% were blasts), red blood cells (RBC) count was 2.53 × 106/mm3, with a hemoglobin level of 9 g/dl and a platelet count (Plt) of 61 × 109/l. Prothrombine time was 15.1 s (normal value 10.0–13.0 s) while partial thromboplastin time (PTT) was 25.8 s (normal value 29 ± 3.5 s). Creatinine value showed 38.7 μmol/l (normal 45–120) and uric acid value 498.2 μmol/l (normal 150–450). Bone marrow (BM) aspiration revealed 70% of blasts (Fig. ).
At this point the first cytogenetic and immunophenotypic data were determined. Flow cytometric (FCM) analysis classified this case as AML-M1. The patient was given standard treatment for AML including (3 + 7) induction chemotherapy (Daunorubicin 60 mg/m2 for 3 days and Cytarabine 200 mg/m2 for 7 days). On day + 28 of treatment with (3 + 7) protocol, the patient had not responded as expected to the treatment, i.e. her PB revealed pancytopenia/cytopenia (WBC 0.4 × 109/l), anemia (hemoglobin level = Hgb: 9.5 g/dl); thrombocytopenia (Plt 12 × 109/l) and less than 7% blasts in BM aspiration. The patient was given re-induction chemotherapy (ICE protocol: Cytrabin 200 mg/day: day 1 ➔ day 7, Etobside 100 mg/day: day 1 ➔ day 5, and Idarubicin 20 mg/day: day 1 ➔ day 3) and she achieved complete remission on day 30 of ICE protocol treatment (WBC 7.4 × 109/l; Hgb 11.6 g/dl; Plt 183 × 109/l), with less than 4% blasts in BM aspiration. Still the patient suffered from blurred vision in the right eye (retinal detachment sensory serous) during ICE protocol treatment but her karyotype was normal. The patient was given consolidation I chemotherapy (High dose Ara-C = HIDAC: Cytarabine 3 g/m2/day; day 1 ➔ day 3; and Methoxantron 20 mg/day; day 1 ➔day 2). Afterwards the patient did not return to the hospital to continue the treatment for 6 weeks. Then she was referred to the hospital again for blurred vision in the right eye and a mass under the vascular arch with splint edema of optical nerve of the right eye was diagnosed, being the cause of her severe decrease in vision. While cerebrospinal fluid (CSF) test was negative, BM aspiration revealed 20–30% of blasts. In PB WBC was 5.6 × 109/l (98.5% of neutrophils), Hgb was 11.6 g/dl, Plt of 70 × 109/l indicated for thrombocytopenia while CT scan of brain was normal. Now she treated with consolidation II chemotherapy (HIDAC), 2 weeks later her PB had WBC 0.1 × 109/l, Hgb 8.4 g/dl and Plt still 20 × 109/l; the mass behind the retina of the right eye was still present.
About 2 months later the patient relapsed and the following values were found: in PB WBC was 7.5 × 109/l with 77.7% of neutrophils, Hgb 12 was g/dl and Plt was 178 × 109/l; BM aspiration revealed 15% of blasts. The MD’s suggested to apply now the Flag-Ida protocol; however, due to the political situation in her home country only available treatment at this point was treatment with Cytrabin 100 mg/day. Again 2 weeks later the patient suffered from blurred vision of the right eye due to serious central retinal detachment; her PB revealed a WBC of 60 × 109/l (70% of them were blasts), Hgb of 13.3 g/dl; thrombocytopenia with Plt of 13 × 109/l was present with a normal brain MRI. Now the patient treated with Cytrabin 1 g/day: day 1 ➔ day 3, Etoposide 100 mg/day: day 1 ➔ day 3, and Methoxantron 20 mg/day: day 1 ➔day 2).
Ten days later, the patient relapsed; her PB shows cytopenia [WBC 1.5 × 109/l with 44% blasts)], anemia (Hgb 9.6 g/dl) and thrombocytopenia (Plt 17 × 109/l). Now the patient stopped the treatment on her own request for 1 month. Afterwards she suffered from fever (more than 40 °C for more than 3 days), menorrhagia and blurred vision in the right eye. Approximately 8.5 months after initial diagnosis she died in her house and no autopsy was performed. Her husband agreed with scientific evaluation of her case and the study was approved by the ethical committee of the Atomic Energy Commission, Damascus, Syria.
Conventional cytogenetics analysis on unstimulated BM sample according to standard procedures was performed [] prior and post chemotherapy treatments. Karyotypes according to the International System for Human Cytogenetic Nomenclature were classified [].
Prior to chemotherapy treatment: GTG-banding cytogenetics revealed the following karyotype:48–50,X,- X,der(1)t(1;2)(?;?),der(1)t(1;3)(?;?),+ 4,+ 4,+ 4,+ 6,t(8;11)(?;?),t(10;12)(?;?),dic(12;17)(?;?)× 2 [] (Fig. ), which was further specified by molecular cytogenetic studies (Figs. and ). Fluorescence in situ hybridization (FISH) using (WCP) probes for chromosomes 1, 2, 3, 4, 5, 6, 9, 12, 17 and X (MetaSystems, Altlussheim, Germany), a specific probe for ETV6 break apart probe and a specific probe for 17p13 (TP53) (Q-Biogene, USA) were applied according to manufacturer’s instructions. Array-proven multicolor banding (aMCB) probes sets for chromosomes 1, 2, 3, 8, 10, 11, 12 and 17 were used []. Thus, the following final karyotype prior to chemotherapeutic treatment was determined using a fluorescence microscope []. 48–50,X,-X,der(1)t(1;2)(p35;p22),der(1)t(1;3)(p36.21;p26.2),der(2)(:1p36.21- > 1p35::2p22- > 2qter),+ 4,+ 4,+ 4,+ 6,der(8)t(8;11)(q24.3;q13.4),der(10)t(10;12)(p15.3;q24.11),del(10)(q21q21),dic(12;17)(p11.2;p11.2),del(15)(q14q14),del(15)(q21.1q21.1),del(15)(q22.32q24)del(17)(q12q12) [].
Genomic DNA was extracted from BM cells prior to chemotherapy treatment as previously reported []. aCGH was performed using the Agilent Sure Print G3 Human Genome Microarray 180 K as previously described []. The aCGH analysis revealed different genomic imbalances (Fig. ). Thus, copy number alterations (CNAs) could be grouped according to their sizes as follows:
Focal CNAs (e.g. deletion on 14q14.3); CNAs involving variable numbers of genes (e.g. deletion on 17q21.3); CNAs involving large parts of chromosomal p or q arms (e.g. duplication of 3q26.1q29) and CNAs of whole chromosomes (e.g. trisomy # 6 -Table ).
Immunophenotyping was performed on BM specimen prior and after chemotherapy treatment using a general panel of fluorescent antibodies against antigens typical for different cell lineages and cell types []: CD1a, CD2, CD3, CD4, CD5, CD8, CD10, CD11b, CD11c, CD13, CD14, CD15, CD16, CD19, CD20, CD22, CD23, CD32, CD33, CD34, CD36, CD38, CD41a, CD45, CD56, CD57, CD64, CD79a, CD103, CD117, CD123, CD138, CD209, CD235a and CD243; In addition to antibodies to Kappa and Lambda light Chains, IgD, sIgM, and HLADr. All antibodies were from BD Biosciences. Flow cytometric data acquisition and analysis were conducted []. FCM analysis of BM specimen prior to chemotherapy treatment characterized this case as AML-M1 according to WHO classifications. The abnormal cell population (60% of tested cells) was positive for CD45dim, CD34, HLADr, CD33, CD117, and CD13. Blast cell population was negative for CD3, CD79a, CD14, CD64, CD32, CD7, CD19, CD10 and CD5.
After chemotherapy and relapse GTG-banding revealed a mosaic of tetraploidy and HH as 92,XXXX []/62,XX,+ 1,+ 4,+ 5,+ 5,+ 6,+ 6,+ 11,+ 15,+ 16,+ 17,+ 19,+ 19,+ 20,+ 20,+ 21,+ 22 []/46,XX [] (Figs and ).
FCM analysis of BM specimen post to chemotherapy treatment characterized this case as AML-M6 according to WHO classifications. The abnormal cell population (15%) was positive for CD45dim, CD36, HLADr, CD33, CD34, CD117, CD13, CD235a and MPO. Those blasts were negative for: CD10, CD19, CD20, CD22, CD5, CD7, CD2, CD3, CD16, CD56, CD1a, CD14, CD64, CD32, TdT, cyCD3 and cyCD79a. |
pmc-6119281-1 | A Norwegian 19-year old male with healthy, non-consanguineous parents attended a reference center for rare connective tissue disorders with a diagnosis of Larsen syndrome. The diagnosis was based on clinical findings in the neonatal period. He was born with dislocated, hyperextended knees up to 90 degrees, which was treated with serial casting without success. This treatment was followed by surgery with Ilizarov’s frame and braces at 9 months of age. Adductovarus of the feet responded well to non-surgical treatment. His neck was kyphotic with a subluxation of C3-C4 and dislocations of C4-C5 and C5-C6. A fixation from C1 to C5 was performed bilaterally using a bone graft from his rib when he was 16 months old. A small mandible and occult cleft palate were observed. Cerebral ultrasound showed some dilatation of the ventricular system. Hypotonia and joint hypermobility of the knees, ankles, and wrists were also observed. In addition, he had an umbilical hernia and a large, left medial inguinal hernia.
As a toddler, he had recurrent serous otitis media and was examined by an ENT consultant. A combined conductive and sensorineural hearing loss was detected and necessitated a hearing aid. The patient was followed by an ophthalmologist because of hyperopia, astigmatism, and exotropia. His hyperopia was corrected with glasses, and the exotropia was treated with patching and strabismus surgery. Further, he has asthma and atopic eczema.
At 10 years of age, the patient was admitted to the hospital with acute chest pain. Echocardiography and CT showed a dilated and dissected aortic root to 7 cm, aortic valve regurgitation, and hemopericardium but normal dimensions in the aortic arch. Emergency surgery to replace the aortic root with a mechanical valve was performed. Following surgery, the patient was treated with beta-blockers and warfarin. At this point a PubMed search was carried out. According to his medical records, one not named case article about a child with Larsen syndrome and arterial tortuosity and dilatation was found. No clinical diagnostic screening was performed.
At age 19, MR angiography revealed a dilatation of 44 mm of the ascending aorta and arch distal to the graft. There was also severe tortuosity of the vertebral, carotid, and subclavian arteries (Fig. ) and a moderate dilatation of the left iliac artery. According to guidelines [], surgery is recommended at ascending aortic diameter of 42 mm in LDS. The patient has now undergone aortic arch surgery.
He had a radius fracture when he was 15 years old. DEXA scan revealed osteopenia with an age-matched score of − 2. At age 20, he was 167 cm tall (2 cm below the 3rd percentile for his age and gender), and a whole body skeletal survey revealed scaphocephaly (Fig. ), generally slender long bones and slender ribs. He had slight platyspondyly with biconcave endplates. There was slight scalloping of the posterior vertebral wall of some of the lumbar vertebras []. Reminescents of coronal clefts could not be excluded []. There were small olistheses in the coronal and sagittal planes, especially in the lumbar region, and wire fixation in the cervical spine. He had a flattened thoracic kyphosis (Figs. , and ). No significant scoliosis was noted. There were no signs of extra ossification centers in the calcaneus. CT of the aorta at age 19 also demonstrating the spine and hips showed dural ectasia and slight protrusion of acetabuli bilaterally [].
The widespread arterial affection in addition to other clinical and radiological observations gave rise to the suspicion of another genetic connective tissue disorder rather than Larsen syndrome. One of the physicians at the resource center suspected that his diagnosis could be LDS based on his medical history. However, his hearing loss and extensive skeletal affection caused a somewhat unusual and more pronounced phenotype than what is typically seen in LDS, at least in the experience of this physician. He was then referred for a second opinion by a clinical geneticist, who confirmed the findings of arachnodactyly, mild short stature, pectus carinatum, bifid uvula, micrognathia, hypertelorism, down-slanting palpebral fissures, and wide, atrophic scars. High throughput sequencing (HTS) analysis of 34 genes associated with hereditary connective tissue disorders identified two sequence variants: a novel unclassified missense mutation, c.1361 T > C (p.Leu454Pro) in the gene for LDS type 2, TGFBR2 (NM_003242.5), as well as a likely pathogenic nonsense mutation, c.115C > T (p.Gln39*) in COL2A1 (NM_001844.4), a gene that encodes collagen type 2. Parental testing indicated that the variant in TGFBR2 was de novo, while the variant in COL2A1 was inherited from the father. No pathogenic or unclassified variant was identified in the gene for autosomal dominant Larsen syndrome, FLNB.
An ophthalmological reexamination revealed no new findings. The lens and the vitreous were clear, and there was no sign of retinal degeneration or other pathology in the posterior segment of the eyes. The axial length was in the normal range, indicating an eye globe of normal size. |
pmc-6119284-1 | An 11-year-old girl noticed a small subcutaneous nodule in her iliac region. As the nodule was asymptomatic, she did not consult a doctor for 1 year. After the nodule began to gradually increase in size, she visited a nearby hospital where T1-weighted magnetic resonance imaging (MRI) revealed a 4.3- × 4.1-cm tumor in the subcutaneous iliac region (Fig. A). A T2-weighted image showed the tumor with high intensity in the inner cystic region (Fig. B). A non-specialized surgeon undertook an unplanned marginal resection, after which MRI showed no evidence of tumor residue (Fig. C). An approximately 4-cm scar from surgery was observed in her iliac region (Fig. D). As the resected specimen displayed sarcoma-like features on histological examination, she was referred to our hospital. She displayed no symptoms, and her blood test results were normal (Hb = 12.7 g/dl, CRP = 0.019 mg/dl). In our hospital, the histological specimen was investigated again using hematoxylin–eosin (H–E) and immunohistochemical staining. H–E staining showed proliferation of spindle-shaped cells with enlarged nuclei, with stroma composed of fibrous tissue (Fig. A, B). Furthermore, we noted the presence of pseudoangiomatous spaces filled with blood and surrounded by tumor cells (Fig. C), in addition to lymph nodes surrounding the tumor (Fig. D). Immunohistochemical findings revealed positive staining for CD68, CD99, CD56 (focally), and epithelial membrane antigen (EMA) (Fig. A–D). Staining for CD34 was positive only in the blood vessels, whilst staining for Bcl-2 was only focally positive within the lymph nodes (Fig. E, F). Staining for S-100 was negative (data not shown). On the basis of the aforementioned histological features, we diagnosed AFH. Based on this diagnosis, we undertook an additional extended resection. Skin and one layer of the underlying iliac muscle was resected (Fig. A). Because the tumor involved the lateral femoral cutaneous nerve, we had no choice but to excise the nerve clumping with the tumor. We performed closure of the membrane of the iliac muscle (Fig. B). There was no evidence of tumor on macroscopic examination of the resected specimen (Fig. C, D), which was confirmed by histological examination (data not shown). It has been 3 years since treatment, and the patient has remained disease-free. However, perceptual disorders of the femoral front have remained. |
pmc-6119299-1 | A 70-year-old Asian man with ventricular fibrillation, who collapsed suddenly at a public bath, was brought to our hospital via ambulance. He had been prescribed allopurinol to treat gout for 15 years. No other relevant past history was found, including no history of diabetes or heart disease. He was an ex-tobacco smoker and drank one can (350 mL) of beer daily. ECMO was initiated 20 minutes after unsuccessful conventional resuscitation with five attempts of electrical cardioversion. On the sixth cardioversion attempt, sinus rhythm was achieved. His initial blood investigations showed the following: white blood cells, 70,510 cells/μL; hemoglobin, 14.3 mg/dL; platelets, 433,000 cells/μL; random blood sugar, 174 mg/dL; serum creatinine, 4.90 mg/dL; blood urea nitrogen, 82 mg/dL; serum glutamic-pyruvic transaminase, 76 IU/L; serum glutamic oxaloacetic transaminase, 58 IU/L; creatinine kinase 194 U/L; and serum C-reactive protein, 40.7 mg/dL (Table ). Transthoracic echocardiography demonstrated diffuse hypokinesis, and anteroseptal and apical akinesis with impaired left ventricular function and an ejection fraction of 25%. Emergency coronary angiography revealed normal coronary arteries. On physical examination, a large abscess in his right gluteal region was detected; computed tomography showed a large low-density area in the right gluteus maximus muscle (Fig. ).
Thus, we diagnosed our patient as having septic shock due to a gluteal abscess and conducted surgical drainage (Fig. ). Concurrently, a rapid antigen GAS test (Quick Chaser Dip Strep A®; Mizuho Medy Co., Japan) was performed using a sample obtained from the right gluteal abscess. Positive results were observed within a minute; therefore, antibiotic therapy comprising benzylpenicillin (1200 U/day) and clindamycin (1200 mg/day) was initiated immediately. Five days after admission, the culture of the purulent matter yielded Streptococcus pyogenes; thus, we diagnosed our patient as having STSS based on the criteria []. Subsequently, his general condition improved; he was successfully weaned from ECMO and continuous hemodiafiltration on day 4 and successfully weaned from ventilation on day 9. The intravenous administration of antibiotics was continued until day 37 since the initiation of therapy. He was discharged after receiving a skin graft on day 83 (Fig. ). He had no clinical problem at 6 months after hospital discharge. |
pmc-6119301-1 | A 76-year-old male was referred to the hospital because of acute heart failure, AECOPD and ulcers on the right leg. The ulcers were scattered as multifocal lesions with the size of 2–4 cm, with purulent discharge (Fig. ). The ulcers developed in two months and the patient denied histories of trauma and plant cultivation. There was 1-year history of COPD, 11-year history of hypertension, and no history of diabetes mellitus (Additional file ).
On admission, the patient was dyspneic with a respiratory rate of 30 breaths per minute. Physical examination revealed wheezing and moist rale in both lungs. Slight pitting edema and cyanosis were observed at cold extremities. Results of routine laboratory tests were as follows: WBC 18 × 109/mL; N% 92; CRP 15 mg/L; PCT 0.74 ng/mL; and GFR (glomerular filtration rate) 32 mL/min. Arterial blood gas analysis showed an acute decompensated metabolic acidosis. Several Gram stains from the ulcers showed moderate amount of Gram-negative bacteria and large amount of leukocytes. Chest X-ray showed pulmonary infection (Additional file : Figure S1A). The patient received treatment for heart failure, and incision and drainage of purulent spots. Anti-infection therapy was initiated with cefoperazone/sulbactam (2:1).
Three days after the treatment, the dyspnea was apparently remitted and wheezing and moist rale in the lung disappeared. The microbiological culture of the pus obtained on the day of admission revealed colonies of Klebsiella pneumonia and Proteus vulgaris. Laboratory reexamination showed elevated PCT (3.86 ng/mL), N% (90%) and CRP (66 mg/L). BDG (1, 3-β-D-glucan) was 554 pg/mL. Echocardiography displayed no vegetation. Pulmonary infection was improved according to the chest X-ray (Additional file : Figure S1B). Antibiotic treatment was terminated and adequate dressing change was assured.
On the seventh day of hospitalization, the patient did not show dyspnea, but the body temperature rose to 38.5 °C. The surface of ulcers on the right leg was dry and granulation was observed but with no evidence for further wound healing. Laboratory reexamination showed abnormal PCT (1.02 ng/mL), N% (85%) and CRP (68 mg/L). GFR increased to 51 mL/min. Pus obtained from deep part of the ulcer was tested and fungal hyphae were found in smear examination. MRI of the right leg indicated the skin damage as inflammatory changes. Voriconazole and piperacillin/tazobactam were administrated intravenously for suspected infection. The patient did not show fever again. Three days after intravenous administration of voriconazole, GFR dropped to 40 mL/min. Intravenous voriconazole treatment was then terminated and replaced by oral voriconazole. The lesions were obviously attenuated with anti-infection treatment and adequate dressing change (Fig. ). The fungal culture of the pus obtained after admission revealed filamentous fungi for several times. The isolated fungi were further identified as Corynespora cassiicola by morphological characteristics and gene analysis (Fig. ). Laboratory tests showed improvement in PCT (0.9 ng/mL), N% (67%) and CRP (40 mg/L).
Two weeks after voriconazole treatment, the patient was discharged but oral voriconazole treatment continued at the out-patient clinic. A month after the discharge, most of the lesions crusted and showed signs of healing (Fig. ). The voriconazole treatment lasted for 6 weeks was terminated and the lesions were washed with potassium permanganate (1:5000) once every day. At the 2-month follow-up, all lesions healed completely. |
pmc-6119327-1 | A 59-year-old Sri Lankan woman, recipient of an ABO matched, living donor kidney transplant performed in 1997, presented with a 3-day history of fever, a fall, mild headache, arthralgia, myalgia, abdominal pain, and progressive drowsiness. She was on tenofovir, azathioprine 75 mg daily, and prednisolone 5 mg daily. She denied respiratory, bowel, or urinary symptoms. We did not find a contact history of fever. She did not have any seizures during the illness. Her primary renal disease was membranous glomerulopathy diagnosed in 1989. She had diabetes and developed end-stage disease in 1996 and was commenced on hemodialysis. She received a transplant in 1997 and enjoyed an uncomplicated post-transplant period with creatinine values between 84 and 104 umol/L (50–110), and an excellent quality of life.
In 2013, she presented with progressive abdominal distension due to ascites and with stigmata of liver disease and was diagnosed as having cirrhosis. She was diagnosed as having hepatitis B infection, where the viral load was in the order of log 9, and renal function was within normal range. Serology for hepatitis C and human immunodeficiency virus (HIV) was negative. Therapy was initiated with lamivudine, but an inadequate response led to replacement with tenofovir 330 mg daily, which brought down the viral loads to order of log 2. She was very compliant in all her medications and did not have major adverse effects to any of her medications.
On examination she was drowsy, with Glasgow Coma Scale (GCS) of 12/15, and had flapping tremors. She was pale, anicteric, and was well hydrated. No skin rashes, cutaneous bleeding, or neck stiffness was noted. Her abdomen was soft on examination and tenderness noted in right iliac fossa overlying the graft. Her respiratory system and cardiovascular system examinations were clinically normal. Optic fundi were normal except for background diabetic retinopathy. Capillary blood sugar on admission was 7.7 mmol/L. Her initial investigations revealed pancytopenia on day 3 of the illness with hemoglobin (Hb) of 78 g/L (120–160), white cell count of 3.7 × 109/L (3.5–12), and platelet count of 52 × 109 /L (150–400). Blood picture showed normochromic normocytic red cells with reduced count, mild to moderate rouleaux formation, normal white cell count with hypersegmented and toxic-looking neutrophils. Severe thrombocytopenia was confirmed on the blood picture. We did not find any evidence of microangiopathic hemolytic anemia. Her C-reactive protein (CRP) level on admission was 108 mg/dL (< 6). Urine analysis showed 4–6 pus cells and 2–4 red cells, but no proteinuria. Serum creatinine was raised to 630 umol/L, from a background of 96 umol/L, checked 2 weeks ago on her routine clinic visit. Her serum creatinine phosphokinase level was normal. Urine and blood cultures were negative on day 3 of the illness. Non-contrast computed tomography (CT) of her brain was normal and a hip X-ray did not show evidence of any fracture. An ultrasound scan of her abdomen showed swollen kidney, with preserved corticomedullary demarcation, raising suspicions of acute renal parenchymal disease. She had no splenomegaly ultrasonically and portal vein diameter was 1.7 cm. She did not have oligo-anuria at that time. She developed metabolic acidosis, and with rising potassium levels, we decided to start renal replacement. Dengue non-structural protein 1 (NS1) antigen (day 2) was positive, but other viral studies such as cytomegalovirus and Epstein–Barr virus were negative. Subsequent blood counts revealed progressive decline in platelet and white cell counts. She developed an upper gastrointestinal (GI) bleed on day 6 (Hb, 52 g/L) and was supported with blood. From day 3 onward, of the illness, we empirically treated her with intravenously administered ceftriaxone for a suspected bacterial infection owing to her high CRP. Azathioprine and tenofovir were temporarily withheld due to possible marrow suppression and orally administered steroids doses were increased from 7.5 mg to 30 mg daily. Dengue IgM and IgG on day 6 were positive. Blood and urine cultures were sterile. Free fluid in the hepatorenal pouch was demonstrated on day 6 of the illness where she entered the critical phase. The lowest platelet count recorded was 5 × 109/L. Her conscious level gradually improved and she was fully alert by day 5. She was never oligo-anuric during the period of illness. Upper GI endoscopy revealed portal gastropathy, antral gastritis, and non-bleeding small esophageal varices. We reintroduced tenofovir from day 5 onward. We had already taken her off azathioprine, but pancytopenia persisted. Intravenously administered ceftriaxone 1 g twice daily was continued up to 14 days, until CRP returned to normal. Her fluid management was monitored clinically, rather than according to the National Dengue guidelines, due to acute kidney injury (AKI). She was discharged on day 16 with creatinine normalized, but her liver enzymes and thrombocytopenia took 6 weeks to correct themselves. A review of this patient 12 weeks later revealed normal serum creatinine level and return of her blood counts to baseline. Figure shows the case presentation in a timeline, while Fig. describes the changes in the biochemical parameters. Table describes pre-morbid, the most abnormal and convalescent values of important biochemical tests. |
pmc-6119557-1 | A 32-yr-old man with a 10-yr history of scalp seborrhea referred to Skin and Stem Cell Research Center, Tehran, Iran, in 2015. He voluntarily participated in this study. He first was examined by a physician, who took a complete medical history and administered a dermatological examination. The patient had not used any topical or oral agents to reduce the oiliness of his skin for the previous 10 weeks. He had no symptoms of seborrheic dermatitis or any other dermatological disorder with the exception of acne lesions on his face and upper parts of the chest and back.
Informed consent was obtained directly and in writing from the patient before publication of this manuscript.
The patient also had been experiencing functional dyspepsia for the previous last three months as based on the Rome III criteria. He experienced postprandial fullness, excessive belching and upper abdominal bloating. His endoscopic and biopsy evaluations were normal. Omeprazole had been prescribed by a gastroenterologist for eight weeks but no improvement in gastrointestinal symptoms was observed.
The scalp seborrhea was evaluated using a Sebumeter SM815. Sebumetry is a well-accepted method of measuring the casual levels of sebum. Sebumetry was performed on the patient’s vertex region 24 h after shampooing with his usual shampoo without a topical agent. The patient was also asked to record any changes in his GI symptoms in his self-report diary. The severity and frequency of the symptoms were assessed before and at the end of treatment using a Likert scale. During the 8-wk therapeutic period, the patient consumed capsules containing 500 mg of Triphala twice daily (after breakfast and dinner). No restrictions were placed on the frequency of shampooing. He was asked to inform his physician of any adverse effects. He also was visited two times during this period to examine for possible complications. No adverse effects or drug intolerance were detected during treatment. The treatment outcome showed a significant improving in his scalp seborrhea index, changing from 211 (μg cm−2) at the beginning of treatment to 67 (μg cm−2) at the end of 8 weeks of treatment. His gastrointestinal complications also improved dramatically noted in . |
pmc-6119586-1 | A Japanese 11-month-old baby boy presented at our institution with symptoms including fever, weight loss, and gallop rhythm. His fever persisted for 3 days before presentation but no treatment was provided. He was born by vaginal delivery at 37 weeks of gestation with a weight of 2612 g (36th percentile) and a head circumference of 33.7 cm. There was no family history of aortic disease and sudden death. When he was 7-months old, he had a fever of unknown origin that persisted for 2 weeks. He was poor in weight gain and was 7.55 kg (6th percentile) at the age of 10 months; his body weight decreased by 0.57 kg in the 3 weeks before presentation.
On examination at the presentation, his height was 70.8 cm, his weight was 6.98 kg, and his head circumference was 43 cm. He was ill-appearing and febrile to 38.4 °C. His blood pressure was 124/62 mmHg and pulse 146/minute. There was a notable S3 gallop and systolic murmur at the apex (Levine scale grade III/VI); however, there were no signs of rales or peripheral edema. Other physical and neurological examinations were normal. A chest X-ray revealed cardiomegaly, with 58% cardiothoracic rate (Fig. ). Echocardiography indicated left ventricular (LV) enlargement and dysfunction with LV diastolic dimension of 32 mm (130% of normal), LV ejection fraction 48% (Fig. , ), moderate mitral regurgitation, and slight aortic regurgitation. Blood tests indicated the following: white blood cell count, 11.07 × 103/μl; hemoglobin, 10.6 g/dl; C-reactive protein, 5.59 mg/dl; creatine phosphokinase, 294 U/l; creatine phosphokinase-MB isozyme, 27 U/l; fibrin degradation products D-dimer, 2.1 μg/ml; brain natriuretic peptide, 2841 pg/ml; human atrial natriuretic peptide, 1360 pg/ml; and serum troponin T, 0.26 ng/ml. His blood culture at admission was negative.
As dilated cardiomyopathy was diagnosed, we initiated diuretics. However, his fever and high blood pressure (systolic blood pressure, 130–140 mmHg), which rarely present with dilated cardiomyopathy, persisted. To investigate the causes of high blood pressure, computed tomography was performed and revealed thoracic and abdominal aortic aneurysms on hospital day 3 (Fig. ). It also revealed severe celiac artery stenosis and bilateral renal artery stenosis. From these findings, TA was diagnosed and 1 mg/kg per day prednisolone was consequently initiated as first-line therapy. His fever had resolved on day 5; his C-reactive protein levels returned to normal on day 10.
Although his general condition improved, deterioration of vascular lesions was evident, as shown by echocardiography, on day 15. Celiac artery occlusion, severe right renal artery stenosis, and new superior mesenteric artery stenosis were also observed on day 15. We increased the dose of prednisolone to 2 mg/kg per day for 1 week due to the possibility of active inflammation around vascular lesions. In addition, we attempted continuous intravenous infusion of lipo-PGE1 at 10 ng/kg per minute to suppress the progression of angiostenosis. We performed vascular echocardiography twice a week and confirmed that there was no progression of angiostenosis following initiation of lipo-PGE1. We terminated infusion of lipo-PGE1 on day 36 (Fig. ) and performed cardiac catheterization on day 45. His right renal artery was not visualized by angiography, and his right kidney was fed by collateral arteries, while vascular echocardiography revealed patency of his right renal artery with severe stenosis. We also confirmed celiac artery occlusion and superior mesenteric artery stenosis to be the same as those observed in previous echocardiography findings (Fig. ). His cardiac function gradually improved (Fig. ). After his C-reactive protein levels returned to normal, 1 mg/kg per day of prednisolone was administered for 1 month, after which the dose was tapered every other 2 weeks. We observed him for 13 months after the termination of lipo-PGE1. The inflammatory findings remained negative and the diameters of abdominal aortic vessels were stable. |
pmc-6119591-1 | A 10-year-old white girl presented to our emergency room in January 2015 with a 1-month history of headache and morning vomiting. On examination, she appeared slightly pale, with body temperature of 36.5 °C, heart rate of 90 beats per minute, blood pressure of 106/62 mmHg, respiratory rate of 18 breaths per minute, and oxygen saturation of 100% in ambient air. Her neurological status was normal. Laboratory test results are shown in Table . A chest X-ray was within limits. An urgent non-enhanced brain computed tomography (CT) scan showed a focal lesion in the left frontal subcortical region with prominent surrounding edema and mass effect (Fig. ). She was therefore admitted to our hospital. Magnetic resonance imaging (MRI) demonstrated ring enhancement on post-contrast T1-weighted (T1W) sequences; fluid-attenuated inversion recovery (FLAIR) sequences confirmed extensive vasogenic edema (Fig. ). She lived with her parents and siblings in Southern Italy. Before the onset of the current illness, at 5 years of age she had undergone surgical excision of a pleomorphic adenoma of the parotid gland. No evidence of a pre-existing congenital airway malformation was referred. She was not sexually active, and she did not smoke cigarettes, drink alcohol, or use illicit drugs. Her father, a heavy tobacco smoker, was a merchant. Her mother, a housewife, reported three miscarriages. Her maternal grandfather had died from colon cancer at 40 years. Her paternal aunt was affected by , and a second-degree cousin presented ovarian immature teratoma. After multidisciplinary discussion, neuronavigation and left frontal craniotomy with tumor resection with direct cortical and subcortical stimulation was done under general anesthesia. She received preoperative steroid medication which was tapered post-surgery. MRI scanning within 72 hours after surgery documented total resection (Fig. ).
Microscopy on tissue sections showed malignant neoplasms with extensive necrosis, composed of atypical columnar and cuboidal cells, which had vesicular nucleolated nuclei and eosinophilic cytoplasm. Tumor cells covered papillary structures with fibrovascular cores or formed small glands and micropapillae lacking stroma. The surrounding brain parenchyma showed evidence of reactive gliosis and lymphohistiocytic infiltrate (Fig. ). On immunohistochemical examination, neoplastic cells were positive for cytokeratin 7, thyroid transcription factor 1 (TTF-1) (Fig. ), cytokeratin AE1/AE3, and epithelial membrane antigen (EMA), whereas all other markers tested were negative: cytokeratin 20, carcinoembryonic antigen (CEA), thyroglobulin, vimentin, cluster of differentiation (CD) 10, WT1, calretinin, inhibin, CD117, CD30, S100 protein, melan-A, actin, chromogranin, synaptophysin, and glial fibrillary acidic protein (GFAP). INI1 expression was retained. Thus, a diagnosis of metastatic lung adenocarcinoma was proposed. A chest CT scan showed a parenchymal nodular lesion in the lower lateral basal segment of the right lobe, measuring 32 mm × 18 mm × 17 mm, thought to be the primary lung cancer (Fig. ) with mediastinal nodal metastasis. Tumor spread was confirmed by positron emission tomography (PET)/CT showing a primary lung tumor and with high fluorodeoxyglucose (FDG) uptake: maximum standardized uptake value (SUVmax) of 8.5 and 8, respectively (Fig. ).
At fluorescence in situ hybridization (FISH) analysis, no rearrangements of anaplastic lymphoma kinase (ALK), c-ros oncogene 1, receptor tyrosine kinase (ROS1), and rearranged during transfection (RET) genes were found. ROS1 gene was found deleted in 57% of neoplastic cells. Next generation sequencing (NGS) analysis was applied to genomic deoxyribonucleic acid (DNA) extracted from formalin-fixed paraffin-embedded tissue. Both the “Cancer Hotspot Panel” (50 genes) and the “Comprehensive Cancer Panel” (444 genes) through the Personal Genome Machine with Ion Torrent™ technology (Life Technologies, Applied Biosystems) were applied. NGS analyses with Comprehensive Cancer Panel highlighted the presence of multiple non-targetable mutations in fms-related tyrosine kinase 4 (FLT4), ubiquitin-protein ligase E3 component N-recognin 5 (UBR5), ataxia telangiectasia mutated (ATM), and TATA-box binding protein associated factor 1 (TAF1). Epidermal growth factor receptor (EGFR) mutation status was negative.
One month after admission our patient started chemotherapy treatment for NSCLC with cisplatin and vinorelbine for six cycles over a 5-month period. Two months later, an MRI 3 months after diagnosis revealed cerebral recurrence; therefore, she underwent a second surgical resection, followed by radiosurgery (CyberKnife). A brain MRI and PET/CT scan after completion of her last dose of chemotherapy showed absence of cerebral metastasis and partial regression of the lesion of the lower lobe of her right lung (RLL); thus, between 7 and 8 months after admission she received adjuvant thoracic radiation therapy. Unfortunately, 1 month later surveillance imaging revealed lung tumor progression and multiple brain metastases. She subsequently started whole brain radiotherapy (WBRT) and three cycles of docetaxel. One year after admission a rapid lung tumor progression was documented. One month later she developed headache and vomiting due to increased cerebral edema and growth of brain metastases. Therefore, she started corticotherapy and third-line pemetrexed treatment (five cycles), but 5 months later a PET/CT scan revealed further worsening of intracranial lesions and skeletal metastases. She underwent radiosurgery by CyberKnife technique on brain metastases and the following month she received nivolumab at 3 mg/kg intravenously every 2 weeks compassionately. Due to worsening of clinical conditions, a month later PET/CT was performed, revealing disseminated (skeletal, pulmonary, cerebral, lymphonodal) disease. She continued nivolumab, receiving a total of five cycles without adverse events. Given the ongoing clinical and imaging deterioration, palliative treatment was initiated and she died of respiratory failure 23 months after diagnosis of metastatic lung adenocarcinoma (Fig. ). Autopsy was declined by parents. |
pmc-6119709-1 | A 51-year-old woman was found comatose and hypotonic in her home. The patient was resuscitated and intubated on site and admitted to an external hospital. An opiate antagonization, because of suspected opiate intoxication (she was on a treatment of for chronic pain syndrome with fentanyl patches), did not show any effect on the patient's consciousness. She had a past medical history of arterial hypertension, obesity, sleep apnea syndrome, and depression.
A blood sample-laboratory analysis revealed rhabdomyolysis. Subsequently, the patient developed acute kidney- and liver failure, which led to immediate transfer to the intensive care unit of our hospital.
On neurological examination, the patient presented with coma, but did not show any focal neurologic impairment. An unenhanced computed tomography (CT) of the head showed almost symmetrical bilateral hypointensities of the globus pallidus (Figure ). These changes were interpreted as of primarily hypoxic origin, possibly caused by carbon monoxide (CO) poisoning, although there were no anamnestic indications supporting this assumption. A spinal tap showed no pathological findings of the cerebrospinal fluid (CFS). Four days after the initial event, the patient clinically improved and was cleared for extubation. The neurological examination thereafter was discreet with no focal neurological deficits and her mental status returned to normal.
MRI of the brain 3 weeks after hospitalization confirmed the bilateral lesions of the globus pallidus seen on CT, characterized by restricted diffusion and FLAIR-hyperintense signal changes (Figure ). At this time no leukoencephalopathy could be detected. These findings were again interpreted as of post hypoxic origin.
Approximately 3 weeks after the initial event, the patient developed progressive neuropsychiatric symptoms. First, she attracted attention with odd behavior (e.g., urinating into the rubbish bin or other patients' beds) and phases of agitation. Within a few days, the disturbance in behavior turned into a clinical picture dominated by reduced psychomotor activity and apathy, finally progressing into mutism. In addition, a novel increase in muscle tone with generalized rigidity and spontaneous myoclonus was observed.
A follow-up MRI-scan of the brain 5 weeks after the initial event showed, in addition to the known changes of the basal ganglia, a symmetrical, extensive increased FLAIR-signal with correlating marked diffusion restrictions of the white matter, primarily in the fronto-parietal regions of both hemispheres (Figure ). The cortex remained spared from these changes. Neither the brain stem nor the cerebellum showed any pathological changes on MRI. In conjunction with the clinical course the changes were diagnosed as DPHL.
A supportive therapy followed. During the course of the inpatient stay, the patient's impairment remained unchanged and she was released into early neurological rehabilitation about 6 weeks after the initial event. A follow up MRI nine months later showed a marked regression of the leukoencephalopathy with a remaining faint hyperintensity predominantly in the parietal white matter of both hemispheres and a complete regression of the diffusion restriction. A slight symmetrical enlargement of the ventricles could be seen indicating a mild atrophy (Figure ). |
pmc-6119735-1 | A 62 years old male presented with recurrent SCC of the left nasal bulbar conjunctiva. The patient's previous medical history detailed multiple interventions at this site. Initially, the diagnosis of a left nasal pterygium (a wing-shaped growth that starts on the conjunctiva and can spread across the limbus to the cornea affecting visual function) was made 3 years prior to the reported presentation, and was surgically removed with local excision. The lesion recurred 1-year post-surgery, and was subsequently managed surgically with a wide local excision. At this time, pathology revealed positive margins for SCC. A further recurrence 6 months later was treated with Plaque Therapy to a dose of 50 Gy in 5 fractions. Subsequently, the lesion was re-excised with adjuvant cryotherapy 7 months later.
On presentation 3 months post-cryotherapy, a recurrent lesion (10 × 5 × 2 mm) was detected on the nasal bulbar conjunctiva (Fig. ). The patient declined enucleation following this SCC recurrence. Subsequently, multidisciplinary consultation offered SXRT as an alternative treatment option (Fig. ).
The patient also presented with a history of Crohns Colitis (treated with immunotherapy) and a previous excision of a non-melanoma skin cancer from the right temple, and a subsequent skin graft of the area. The patient was on no other medications and had no allergies.
The patient was prescribed a dose of 48.4 Gy in 22 fractions, to a depth of 3 mm. This resulted in a skin surface dose of 54.4 Gy. A 2.0 cm diameter direct applicator was used with a 3 mm margin on the treatment region (Fig. ). To allow for an acceptable treatment margin that encompases the target volume and accounts for set up variability, the left inner canthus and tear duct were included in the treatment field. A single en-face beam of 2.0 mm Aluminium energy (2 mm Al) was used to meet the previously articulated dose prescription. The risk of ulceration, scleral perforation, ischemia and nasolacrimal duct obstruction was explained to the patient. This risk was further exacerbated in this case due to re-irradiation of the previously treated area, and a particularly sensitive region post-cryotherapy, surgery and plaque therapy. Topical anaesthesia (Tetracaine eyedrops) was administered to the left eye prior to retractor positioning, to ensure eyelids remained open throughout SXRT delivery. After positioning of the retractors the patient was instructed to maintain gaze on a target positioned to the left side of the room, and the eye was monitored throughout treatment delivery by video surveillance. Lubricating eye drops were prescribed for use prior to treatment administration to prevent drying of the ocular surface, and for the patients self-use between fractions to relieve dry eye symptoms. Total set up and treatment time for this patient was approximately 20 min, with the retractors in place on average less than 10 min. The anaesthetic drops and ocular surface lubricants induced limited sensation and the patient found it mildly uncomfortable. As a precaution, the patient was informed to avoid contact with the anaesthetised eye and wear a protective patch for 60 min post-treatment delivery daily. |
pmc-6120049-1 | A 37-year-old man with a VNS presented for further evaluation. The patient had focal seizures with dyscognitive symptoms and occasionally evolution to bilateral convulsive seizures since he was 18 years old. Several events were captured during an epilepsy monitoring unit (EMU) admission, all of which localized to the right temporal region. An MRI of his brain did not reveal any structural abnormalities. SPECT (F) and PET imaging (G) suggested a right temporal seizure focus. A MEG recording analyzed by SAM(g2) revealed a right mesial temporal focus centered on the hippocampus (B) and amygdala (C), with some occasional right ventral frontal, right posterior, and lateral temporal spread from this zone, and some additional spread to right insula. While the raw MEG sensor data exhibited artifacts due the VNS, the virtual electrode data from hippocampus and amygdala (A) displayed no evidence of VNS artifact. While clear spikes existed in the virtual electrode data, the EEG data only occasionally exhibited simultaneous interictal spikes. Invasive monitoring was planned on the basis of the concordant findings between MEG, SPECT, and PET. Subdural grids were placed over the lateral and mesial aspects of the right temporal lobe, and depth electrodes were inserted into the right amygdala and right anterior and posterior hippocampus. Frequent interictal spikes were seen on the hippocampal and amygdalar electrode contacts (D), and several seizures arose from the anterior hippocampal and amygdalar electrodes, an example of which can be seen in E. Following the invasive monitoring the patient received a right anterior temporal lobectomy with amygdalohippocampectomy. Prior to his surgery, the patient experienced ~2 seizures per month. Following surgery, the patient was seizure-free for several months, but experienced a breakthrough of two seizures following a dose reduction in antiseizure medication, and another breakthrough of four seizures coincident with the onset of an illness. |
pmc-6120049-2 | A 24-year-old man whose focal seizures began at age 7 presented for further evaluation. During his episodes, the patient was reported as having a surprised look on his face, covering his mouth with his hands, and laughing. These episodes happened several times per day and were followed by marching movements of the legs and grunting noises. The patient had no alteration of consciousness during his seizures. He also experienced hypermotor seizures arising out of sleep at least nightly and often had several per night. The patient sustained bilateral frontal lobe damage, intraparenchymal hemorrhages, and extra axial hemorrhages following a severe fall in 2006. He was seen by several neurologists before coming to WFBH.
The patient’s epilepsy was refractory to multiple antiseizure medications. His initial EMU admission in 2001 was unable to localize the seizure onset zone. The interictal EEG showed very frequent epileptiform discharges arising from the right frontal region, but PET showed mild decreased activity in the left medial temporal lobe which was consistent with an epileptogenic focus. Both ictal and interictal SPECT indicated slightly asymmetric activity within the temporal lobes with the right side greater than the left, also suggestive of an epileptogenic focus within the left temporal lobe. Because of the discordant findings, the patient proceeded to invasive monitoring. ICEEG pointed towards a right frontal lobe origin, but the pattern of spiking occurred almost simultaneously with patient’s clinical semiology. At that time, it was felt that the seizure focus was not clearly localized to warrant right frontal lobectomy. The patient then received a VNS in addition to medication, and this combination was effective for several years.
The patient began to experience more problems around 2012 and was recommended for a MEG scan. The patient’s MEG data were very noisy owing to metal hardware in his skull that covered the burr holes from his previous invasive monitoring, but SAM(g2) sufficiently removed these artifacts and revealed a single focus in the right middle frontal gyrus (A) with numerous, MEG-only spikes (B). (Because the head is magnetically transparent, MEG is not susceptible to breach effects from craniotomies or other defects.) The MRI obtained for the MEG scan also revealed a small focus of cortical thinning and irregularity with subtle T2 hypointensity in the right frontal lobe. Based on the MEG results, the patient underwent invasive monitoring with a stereo-EEG array placed over the MEG focus (C). The patient’s epileptiform activity (green arrowhead, D) was subsequently localized to the three ICEEG contacts (green arrows) nearest to the peak of the SAM focus (red sphere, C). The patient then received a right frontal lobe resection of the seizure focus and has been seizure free since. |
pmc-6120049-3 | A 21-year-old man with an onset of seizures in 2004 presented for further evaluation. He had one febrile seizure in infancy and has a history of headaches. His events consisted of staring off for a few minutes, being unaware of surroundings, and exhibiting abnormal behavior and incomprehensible speech. He felt tired afterwards and typically had an aura of a right frontal headache. The patient’s seizure frequency was 1–2 per week, and his longest seizure-free interval was two years. The patient had tried multiple antiseizure medications but his seizures were insufficiently controlled under them. During a subsequent EMU admission, scalp EEG recorded several seizures originating in the left temporal region, and his interictal EEG was notable for occasional left temporal slowing and left temporal epileptiform activity. Ictal SPECT exhibited left occipital and left temporal hyperperfusion during one of these seizures, and a later interictal SPECT uncovered two possible anterior and posterior left temporal foci that were considered worrisome for seizure foci. The PET scan was negative. Structural MRI indicated a possible subtle form of hippocampal malrotation as well as two small foci of T2 hyperintensity in the bilateral frontal white matter that were nonspecific, but were thought to be the sequelae of prior ischemia, inflammation/infection, trauma or demyelination. In contrast, the patient’s MEG scan revealed a left occipital focus (A) with hundreds of MEG-only spikes visible on the virtual electrode (B). Based on the collective results, the patient received invasive monitoring with inter-hemispheric and left lateral occipital grids and left temporal depth electrodes. ICEEG confirmed the left occipital MEG focus as the seizure generator. The patient had a left occipital resection and had a few seizures shortly after surgery in the setting of medication nonadherence. Following this, he has been seizure-free for over a year. |
pmc-6120049-4 | A 31-year-old woman with a VNS implantation three years prior to her MEG recording presented for further evaluation. Since age 5, the patient had focal seizures that began with a “funny feeling,” flushing, and head turning to the right. Some seizures terminated at this point, while at other times her seizures progressed to impair awareness and/or evolved into a bilateral convulsive seizure. Treatment with several antiseizure medicines failed to improve the woman’s seizure frequency. An MRI did not demonstrate any structural brain abnormalities. An EMU evaluation captured seizures with a broad, right hemispheric onset. An initial MEG recording prior to VNS implantation captured epileptiform activity, which was originally and unsuccessfully analyzed using equivalent current dipole modeling (A). The interpretation at the time was that the MEG study did not provide localizing information. As the patient’s seizure focus was not localized with any modality, she received a VNS.
However, the patient continued to have seizures after the VNS implantation. Because we had subsequently implemented SAM(g2) as an alternative to dipole analyses, the patient returned for a second MEG scan. SAM(g2) was used to analyze this second MEG recording, as well as the previous recording performed prior to VNS implantation. Even though the second recording was separated from the first by six years and the raw MEG sensor data were strongly contaminated by artifact from the VNS during the second recording, an equivalent right frontal focus was identified on both recordings (A), a focus not revealed by dipole analysis previously. This indicates that SAM can reproducibly localize interictal epileptiform activity despite the presence of large artifacts due to the VNS implant. (The dipole localization in the presence of VNS artifact is shown in B for comparison. The dipole tails have been omitted for clarity.) Examination of the virtual electrodes reconstructed from the SAM(g2) focus demonstrated MEG epileptiform discharges that correlated with the simultaneously recorded scalp EEG during the second recording (C), and, importantly, that lacked the high-amplitude fluctuations present in the raw MEG data that were induced by the VNS (B). (For comparison, the raw MEG sensor data prior to VNS implantation are depicted in the top part of B.) Furthermore, during the patient’s second MEG recording an electrographic seizure was recorded on EEG, with a preceding MEG-recorded discharge detected in the virtual electrode (D). Given the new localizing information provided by the MEG recordings, the patient was determined to be a candidate for ICEEG and possible resection. A subdural grid was placed over the right frontal lobe, covering the focus identified on MEG (F). Seizures captured during the invasive monitoring demonstrated electrographic onset (E) very close to the focus of peak kurtosis identified by SAM(g2) on the MEG recordings (F). Following resection, which included the focus identified by SAM(g2), the patient experienced a significant improvement in her seizures, improving from four to six focal seizures with loss of awareness and sometimes evolution to bilateral convulsive seizures monthly to two to four focal seizures with retained awareness monthly. Her scalp EEG recordings demonstrated a greatly reduced frequency of interictal epileptiform activity. |
pmc-6120049-5 | A 31-year-old woman with spells preceded by visual symptoms of macropsia and micropsia and olfactory auras presented for further evaluation. Following the auras, the patient often exhibited right eye deviation and tonic flexion of the right upper extremities followed by a loss of awareness and generalized tonic-clonic events of 2–3 min in length. Afterwards, the patient experienced mild confusion and was tired for tens of minutes. She also had jerking of her arms and legs during sleep and the patient’s husband was unable to arouse her. The patient’s auras occurred every few days. She had 1–2 daytime spells a month, and she estimated that she had several more nighttime spells. These spells had been captured on routine EEG and during two EMU admissions and no electrographic change suggestive of seizure was noted. Neither a CT nor an MRI demonstrated any structural brain abnormalities. Treatment with several antiseizure medicines failed to provide adequate relief, and the patient had allergic reactions to some of the medicines. Despite the significant concern that her spells were nonepileptic in nature, given the severity of her events the patient received a diagnostic MEG scan.
SAM(g2) identified three foci of epileptiform activity during her MEG scan: one focus in the left posterior temporal/lateral occipital cortex (A), and bilateral mesial temporal foci (not shown). The left posterior temporal/lateral occipital cortical focus was likely responsible for her visual symptoms, and the bilateral mesial temporal foci were likely responsible for her olfactory auras as the irritable zones encompassed entorhinal cortex. The irritability of the mesial temporal cortices was initially supported by bilateral sphenoidal electrodes, which detected interictal epileptiform activity. Importantly, MEG captured two seizures during the recording which originated within the posterior temporal/lateral occipital cortex, and neither of these seizures was discernable on EEG (B). Based on the MEG localizing information, ICEEG was performed as part of a presurgical evaluation. During a recorded seizure, ICEEG demonstrated early epileptiform activity (red channel, D) at electrodes (green) near the SAM(g2) peaks (red crosses, C). While ICEEG confirmed the localization of the three SAM(g2) foci, it also corroborated the MEG finding that the posterior temporal/lateral occipital focus was indeed the seizure initiator. Interestingly, the morphology of the ICEEG seizure was very similar to the morphology of the MEG seizure; both started with an initial spike, then exhibited a period of fast activity, and then evolved into a rhythmic discharge. Because the patient’s primary focus encompassed part of visual cortex, she decided against surgery to avoid a potential visual field defect. However, the MEG findings were still useful as they definitively identified the patient as having epilepsy. The patient is currently being considered for responsive neurostimulation device (RNS) placement. |
pmc-6120064-1 | A 67-year-old female patient came to our observation with a history of adverse contrast reaction: 10 years previous, after administration of unspecified CM for abdominal CT, the patient had presented skin rash and swelling of the limb, the injection site of the CM, with maintenance of vital parameters.
A month previous, during angio-CT, 15 min after injection of the CM, iopromide, despite having been premedicated as in case 5, the patient presented erythema and mild edema of the limb in the injection site of the CM and dry cough which lasted for some days. Immediately upon the appearance of the adverse reaction the patient was treated with chlorpheniramine 10 mg intramuscular therapy. In addition to the aforementioned therapy, salbutamol was administered by aerosol. Blood pressure, oxygen saturation and thoracic objectivity were normal.
The patient had a negative history for latex allergy, respiratory allergies, and food allergy. Given the need to repeat angio-CT due to the presence of cerebral aneurysms, SPTs and IDTs were therefore performed with iopromide according to the following scheme of administration: SPT 1:10 diluted, SPT undiluted, IDT 1:1000 diluted, IDT 1:100 diluted, IDT 1:10 diluted. The test results were negative. Subsequently, the CM used was well tolerated during the execution of the radiological examination. |
pmc-6120066-1 | A 41-year-old Asian man was transferred to the Center of Trauma Surgery in our hospital 6 hours after injury for the closure of an open infected wound with a large skin defect in his right lower limb caused by an accidental explosion of 100 pieces of a blasting cap. Hemostasis of the wound was achieved by applying pressure and a total of 2500 ml Ringer's solution, which is a kind of balanced salt solution, was given intravenously during the emergency. He was mildly obese, described himself as quite heathy, and had never been admitted to a hospital previously. He reported no chronic medical history, such as primary hypertension, heart disease, diabetes mellitus, an impaired immune system, malignancies, liver cirrhosis, renal failure, or hemodialysis. He also reported no history of infectious disease, such as tuberculosis, any types of hepatitis, or acquired immunodeficiency syndrome (AIDS). His medical history revealed no trauma, blood transfusion, other surgical procedures, or other serious event. He had not lived in an epidemic area and had no contact history of radioactive exposure. He denied any family history of inherited diseases. He usually did not smoke tobacco or consume alcohol and had no other unhealthy behaviors. He was a business executive and he often traveled for business.
His blood pressure at admission was 99/50 mmHg, pulse rate was 102 beats per minutes, and his respiratory rate was 21 breaths per minute. On examination, his mucous membrane was dry and his conjunctivae were pale. No positive signs were found during neurological, cardiopulmonary, and abdominal examinations. There was no pain around the kidney area with percussion or tenderness along the bilateral ureteral approach.
A specialized examination revealed that the wounds were located on his right gluteal and were approximately 40 cm × 35 cm in size with a darkened appearance. The margins of the wounds were 2 cm above the bottom of iliac crest, inferior to the superior segment of back side of his thigh, 3 cm interior of the anal cleft, and external to the lateral thigh (as shown in Fig. ). The wound had hemorrhaged and contained scattered metallic foreign bodies. Most of his gluteus maximus muscle was injured and the motion of his right hip joint was limited.
In addition, related laboratory examinations were conducted. His complete blood count values were as follows: white blood cell count of 10,940 cells/uL, red blood cell count of 3,250,000 cells/uL, hemoglobin of 9.8 g/dL, and platelet count of 153,000 cells/uL. D-Dimer was 5678μg/L. His total protein was 45.7 g/L, among which the albumin and globulin content were 21 g/L and 24.7 g/L, respectively. The results of serology for renal function were normal. Blood and aerobic and anaerobic bacterial cultures were performed. Microorganisms were not found in the blood cultures. The secretions from injured tissue revealed that a little of the Gram-positive bacteria, Bacillus subtilis, was detected. A diagnosis of explosion injury in left gluteal region and hemorrhagic shock was made.
He underwent aggressive fluid administration, hemodynamic support, and intravenously administered antibiotic therapy. Debridement of his right gluteal was carried out 6 hours after the explosion under general anesthesia. Then, the wound was sutured with VSD and adhesive membrane, which finally was connected to negative pressure drainage equipment. During the operation, 800 ml erythrocytes and 400 ml plasma were infused into our patient. Three days after the first operation, he underwent a second operation. The necrotic muscles were excised and then the wound was closed with interrupted suture to shorten the defect to 12 cm × 40 cm (as shown in Fig. ). The VSD was also connected to the wound as described above.
Nine days after the second treatment, although a few scattered necrotic muscles were located in the wound, the granulation tissues were growing well. The skin around the wound was healthy, with only mild edema and migrated to the wound margins. The pinch test demonstrated that the skin had some mobility, which indicated that it could be sufficiently stretched. Under general anesthesia, the skin margins were minimally free to facilitate the insertion of intradermal needles on both sides of the wound. The wound itself was left undisturbed. Three SSDs (Life Medical Sciences, Inc., Princeton, NJ) were inspected every few hours. The healthy skin was stretched for 4 minutes, followed by 1 minute of relaxation. After stress relaxation had occurred, the tension was adjusted to 3 kg, as indicated by the tension gauge (as shown in Fig. ).
This procedure was repeated five times during the operation until the skin reached approximation to the wound margins. Then, the devices and the intradermal needles were removed from our patient. During this process, the granulation tissues looked good, the wound was thoroughly irrigated, and the stretched skin margins were closed with interrupted suturing to reduce the size of the defect to 5 cm × 38 cm (as shown in Fig. ). After stretching treatment, the VSD was applied again to close the wound as before.
After 9 days, the size of the wound had decreased to 4.5 cm × 35 cm (as shown in Fig. ). The SSD was then applied again as before. During the last operation, the wound was thoroughly irrigated, and the stretched skin margins were closed with interrupted suturing (as shown in Fig. ). Eighteen days after this operation, there were only two small wounds that were approximately 1.0 cm × 0.8 cm without edema or inflammation. The local granulation was healthy (as shown in Fig. ). At that time, our patient was ambulatory. Although he had been in hospital for over 1 month, there was no evidence of damage to the skin margins. The timeline of the patient’s treatment is shown in Table .
At 3 months postoperatively the wound was healing perfectly and our patient could walk freely and do some suitable exercise. At 6 months postoperatively, he returned to business work as usual. |
pmc-6120074-1 | A 53-years-old Japanese woman with ascites and a pelvic tumor was transferred to the Maruyama Memorial General Hospital on the suspicion of ovarian malignancy. A trans-vaginal ultrasound examination confirmed a large ascites volume and approximately 10-cm single ovarian cystic tumor with a mural nodule. The serum level of CA19–9 was 37 IU/L and that of CA125 was increased markedly at 333 IU/L. Magnetic resonance imaging (MRI) revealed ascites and an approximately 10-cm single cystic tumor with a 4-cm mural nodule. T1- and T2-weighted MRI revealed a high-intensity cystic area. In addition, the T1-weighted and fat-suppressed MRI showed the high-intensity cystic area. Therefore, we expected the cyst to contain blood. Moreover, gadorinium-enhanced T1-weighted MRI revealed an enhanced mural nodule (Fig. ). Interestingly, the mural nodule crossed the cyst wall into the cavity and onto the surface, which is an extremely rare finding and may be the characteristic of this tumor type. Computed tomography (CT) imaging showed a large ascites volume and tumor dissemination throughout the pelvis (Fig. ). On the basis of these examinations, we suspected a malignant tumor. The patient underwent bilateral salpingo-oophorectomy with hysterectomy, omentectomy, resection of disseminated lesions and optimal debulking of the tumor. Lymph node biopsy was omitted because of the suggestion of enhanced CT image findings and palpation during surgery. The content of the left ovarian cyst was chocolate-like. We identified a mural nodule of approximately 4-cm size on the cyst wall (Fig. , ). The histopathological examination revealed columnar tumor cells on the cyst wall. Eosinophilic epithelial cells suggestive of papillary hyperplasia and squamous metaplasia were identified on the endometriosis tissues. The cells showing dysplasia were categorized as borderline malignant. The cyst showed positivity for estrogen receptor and vimentin antibodies, and it was negative for WT-1; therefore, the immunohistochemical staining led to the diagnosis of ovarian seromucinous borderline malignancy (Fig. –). The mural nodule contained dense hyperplastic polymorphic and eosinophilic undifferentiated cells. The mural nodule was positive for CAM5.2, AE1/AE3, and vimentin and was identified as an anaplastic carcinoma by immunohistochemistry (Fig. –). A nodule present in the omentum showed the same pathological findings as the mural nodule and was thus diagnosed as a metastasis from the anaplastic carcinoma. The disseminated lesion was < 2 cm in size. We classified the ascites as class I by cytodiagonosis and diagnosed the patient as having an anaplastic carcinoma in the left ovarian seromucinous cystic tumor of borderline malignancy, with a FIGO stage IIIB. She underwent 6 courses of pacritaxel and carboplatin. After 3 years, the patient is still alive without any clinical findings of tumor recurrence. |
pmc-6120083-1 | A 56-year-old man of Asian origin was in his usual state of health until 4 days prior to presentation in our emergency room (ER); he had complaints of a rapidly progressing weakness of bilateral upper and lower limbs immediately prior to which he had a gastrointestinal upset. The weakness started from his lower limbs and gradually involved bilateral upper limbs in a similar glove and stocking fashion. He, however, did not have any sensory deficits and at the initial presentation in our hospital he had no respiratory and ocular muscle involvement. Consciousness and orientation were intact and he did not have significant hemodynamic instability. There was no significant medical or surgical condition requiring long-term hospitalization or medication use in the past. A government officer by profession, our patient had an active lifestyle and had no history suggestive of substance abuse or accidental or intentional poisoning. He lived with his wife and had two sons; one of his sons was living with him to support him and the elder son lived abroad but had been on good terms with the family. Our patient did not take any regular medications apart from the hypoglycemic agent metformin 500 mg administered orally twice daily. He did not smoke tobacco or consume alcohol regularly. During his initial presentation in our intensive care unit (ICU), he was conscious yet unable to speak properly. His vital signs were blood pressure (BP) 120/65 mmHg with no inotropic support, heart rate (HR) 102/minute regular, respiratory rate (RR) 26/minute regular, and he had no fever on admission.
Our initial assessment led to a provisional diagnosis of GBS and immediate supportive tests were performed. A nerve conduction velocity test showed findings of motor axonal and demyelination neuropathy. A lumbar puncture done on the sixth day of the development of symptoms showed evidence of albuminocytologic dissociation with total counts (TC) of five cells/cc, which were all lymphocytes and CSF protein of 81 mg/dl (Table ). On the sixth day of the development of symptoms and third day of admission in ICU, he had complaints of difficulty in breathing with gradual decline in saturation with pulse oximeter reading of oxygen saturation (SpO2) to < 85% at fraction of inspired oxygen concentration (FiO2) of > 80%, and hypercapnia with partial pressure of carbon dioxide in arterial blood (PaCO2) of 86 mmHg. He was immediately intubated and kept on mechanical ventilator support.
Discussion was held with his relatives regarding available treatment options. A plan to initiate IVIG was made and started at 0.4 mg/kg per day for 5 days. The administration of IVIG was not associated with any significant complications. He did not, however, show major signs of recovery from respiratory weakness and was continuously kept on assist-control mode of ventilation with intermittent spontaneous breathing trials. At this time, he had occasional blood-tinged secretion in the subglottic suction and during intermittent endotracheal suctioning. A detailed coagulation profile did not show significant abnormalities. On the ninth day of admission in ICU, a plan for tracheostomy was made anticipating prolonged need for mechanical ventilation and as a part of routine pre-anesthetic preparation, a unit of group-specific (A +ve) blood was asked to be arranged. However, we were then notified by the blood bank that they had problems with cross-matching of the blood. A repeated blood sample of our patient was sent which also had a similar problem of inability to cross-match the blood. A literature search for the possible causes of such an occurrence was made but we only had a few reports of such problems. With a provisional diagnosis of significant hemolysis leading to cross-matching difficulties, further tests were sent (Table ). An arrangement of O negative blood was made as a reserve and a tracheostomy was performed with no major problems.
His stay in ICU was then complicated with hospital-acquired chest infections for which he received antibiotics based on organisms’ susceptibility. Liver function tests (LFTs) which were initially deranged subsequently normalized after gradual stabilization of his condition and de-escalation of drugs. Serological tests which included quantitative HIV, hepatitis B surface antigen (HBsAg), and anti- hepatitis C virus (HCV) antibody were negative. He was subsequently moved out of ICU on the 19th day with tracheostomy in situ and on portable bilevel positive airway pressure (BIPAP) support. Three days after being moved to a ward, he was brought back to ICU for sudden-onset dyspnea and tachypnea. He had coarse crepitations more on the anterior aspect of bilateral chest and slight decrease in breath sounds on bilateral basal regions. He did not, however, have fever or changes in vital signs and his consciousness was intact. He was managed conservatively with chest physiotherapy, deep breathing exercises, regular tracheostomy care, and suctioning of secretions from lungs. He recuperated in 2 days and was moved back to a ward where he slowly recovered from his weakness. No other untoward events occurred during this period of approximately 4 months. He is being planned for discharge to the care of a nursing home and the prognosis of the disease has been well explained to his relatives. |
pmc-6120096-1 | A 60-year-old Thai woman presented with a 4-month history of episodic, painful, horizontal binocular diplopia. She denied any oscillopsia. She was previously treated for nasopharyngeal carcinoma with several courses of chemotherapy and external beam radiotherapy (total dose of 7000 cGy). The tumor was well controlled; her most recent radiotherapy was administered 13 years previously. General neurological examination findings were unremarkable. Neuro-ophthalmic examination revealed normal visual acuity, visual fields, pupils, and fundi. Ocular alignment showed orthotropia and orthophoria by alternate cover test. Her ocular motility was normal in all gazes, including adduction. Myasthenic eyelid signs, including orbicularis oculi weakness, fatigable ptosis, and Cogan’s lid twitch, were absent. However, following a 30-s right eccentric gaze, she developed involuntary contraction of the left medial rectus, which resulted in left esotropia while returning both eyes to the primary position. The left esotropia lasted approximately 2 min, then spontaneously resolved (Fig. and Additional file : Video S1). Likewise, these spells occurred following a 30-s gaze in the opposite direction (left eccentric gaze), which resulted in right esotropia in the primary position (Fig. and Additional file : Video S1). During these spells, esotropia was steady (until it waned) and not variable. Both the pupils and the eyelid positions remained normal throughout the examination. No anisocoria was detected during the episodes of esotropia. Prolonged vertical eccentric gaze did not induce any ocular misalignment. Magnetic resonance imaging revealed neither brain parenchyma/brain stem lesions nor tumor recurrence. Her symptoms were successfully treated with carbamazepine at 200 mg daily. |
pmc-6120170-1 | A 24-year-old Hispanic male who previously worked as a nurse in Mexico presented to
our facility 4 months prior as a self-referral. He had been suffering from recurrent
bilateral pleural effusion and thickening for the past 2 years without any diagnosis
().
During our initial workup, he was found to have a positive QuantiFERON-TB test but
had negative sputum acid-fast bacilli (AFB) smear and culture and was discharged to
follow-up in our pulmonary clinic. He was lost to follow-up and presented again,
this time with new-onset headaches and seizures. Physical examination was
significant for bitemporal visual deficits. A brain computed tomography (CT) and
magnetic resonance imaging (MRI) revealed numerous infratentorial and supratentorial
ring-enhancing brain lesions with vasogenic edema ( and ). At this point, our differentials were the
following: neurocysticercosis versus tuberculomas versus toxoplasmosis versus
lymphoma versus metastatic brain cancer. After the brain CT and MRI, and due to the
patient not having any focal neurological deficits, reduced Glasgow Coma Scale, and
abnormal respirations or papilledema, the decision was made to perform a lumbar
puncture (LP) to rule in what we believed to be an infectious etiology. LP showed an
opening pressure of 370 mm H2O, cerebrospinal fluid (CSF) white blood
cell count of 8 × 103/µL, and CSF glucose and protein were 50 mg/dL and
89 mm/dL, respectively, with a 55% lymphocyte predominance. The patient was also
screened for HIV with an Ab/Ag (antibody/antigen) screen, which was nonreactive.
Due to a high index of suspicion for TB, he was empirically placed on 4 anti-TB
medications and a steroid. A pleural biopsy was performed, which showed caseating
granulomata pleural with negative AFB stain (). Throughout hospitalization, he had
2 additional LPs to alleviate elevated intracranial pressure. Airborne isolation was
cleared after 3 negative sputum AFBs, and he was discharged home with the same
4-drug regimen and a steroid taper dose. His biopsy grew M
tuberculosis complex after 6 weeks in the laboratory and a report by
the Public Health Services Department showed pansensitivity without any resistance.
The patient’s drug regime consisted of isoniazid, rifampin, pyrazinamide,
ethambutol, pyridoxine, and dexamethasone. All 4 anti-TB medications were given for
2 months with maintenance therapy consisting of isoniazid and rifampin for an
additional 9 months. Dexamethasone was administered and tapered over a total of 8
weeks at 0.3 to 0.4 mg/kg/day for 2 weeks, 0.2 mg/kg/day for week 3, 0.1 mg/kg/day
for week 4, and then 4 mg per day and tapered 1 mg off the daily dose each week. The
patient’s symptoms rapidly improved with this drug regime, and repeat brain imaging
a few weeks after initiation of medications revealed that some of the tuberculomas
had already resolved. |
pmc-6120172-1 | An overweight 9-year-old Hispanic male with no significant past medical history presented to the emergency room with 2 days of mild, persistent RLQ abdominal pain and tactile fevers for 1 day. The pain was initially intermittent, nonradiating, and mild on the pain scale, and was relieved by Pepto-Bismol. On the day of admission, the pain became constant, moderate, and was aggravated by walking, causing the patient to limp. Over the prior 2 days, he continued to attend school despite his abdominal discomfort. However, his mother noted that, while normally an avid eater, he had been avoiding food and had a reduced appetite. He complained of some nausea on the day of admission, but denied any prior nausea, emesis, or change in bowel habits.
On physical examination, the patient had stable vital signs and was in no acute distress. His abdomen was soft and nondistended. There was mild tenderness, localized to the RLQ, without peritoneal signs. He had no tenderness at McBurney’s point and negative psoas and Rovsing signs. An obturator’s test did elicit mild pain. Laboratory workup showed a leukocytosis 14 400 cells/µL with elevated CRP 109.6.
In the absence of classic signs of appendicitis with high inflammatory markers, the patient underwent computed tomography (CT) imaging to look for other intraabdominal pathology and to rule out appendicitis. Abdominal CT revealed a normal appendix and moderate inflammation of fatty structure surrounding the anterior ascending colon with mesenteric edema and pelvic ascites. These findings and a benign appendix suggested omental infarction versus epiploic appendagitis. However, CT findings of the latter would more likely show fatty inflammation of an oval-shaped paracolic mass, although definitive differentiation based on imaging may be difficult.
The patient was hospitalized and placed on intravenous fluids. Pediatric surgery was consulted, who supported a diagnosis of omental infarction. No surgical intervention was recommended. The patient was placed on complete bowel rest with serial abdominal examinations to rule out progression to overt appendicitis, given the location of the pain in the context of leukocytosis with elevated CRP. Serial abdominal examinations showed slow improvement in his discomfort over the next 24 hours with no need for pain medication. After 24 hours of inpatient stay, our patient was able to walk and even jump without significant pain. Abdominal examination showed decreased tenderness of the RLQ compared with admission and no peritoneal signs. The patient was started on a clear liquid diet and advanced to regular diet, which he tolerated without any nausea or vomiting. He was discharged home with the recommendation to take over-the-counter ibuprofen for pain control and to return if symptoms worsened. |
pmc-6120174-1 | A 48-year-old male presented to the psychiatric emergency room with dysmorphic mood.
He was subsequently referred to medical service for the management of hyponatremia.
His past medical history was notable for lumbar spondylosis managed with
intermittent nonsteroidal anti-inflammatory drug use. The patient reported
occasional alcohol consumption, with no intake during the past 4 weeks. He denied
any history of diabetes or prediabetes, obesity, binge drinking, abdominal trauma,
any offending drugs, and any procedures including endoscopic retrograde
cholangiopancreatography. Family history was not significant for coronary artery
disease, cerebrovascular accident, diabetes, dyslipidemia, pancreatitis, or
gallstones.
On the first day of admission, the patient experienced abdominal discomfort that
worsened alongside a fever of 101.3°F. His clinical picture began to deteriorate on
day 2, with a pulse of 124 beats per minute, and blood pressure of 98/67 mm Hg.
Physical examination was notable for mild tenderness in the epigastrium to palpation
without distension, organomegaly, or rigidity. Laboratory evaluation showed a
hematocrit of 39%, leukocyte 14 200 (4500-11 000 mm3) with neutrophil
predominance of 85%, platelets 113 000 (130 000-400 000 mm3), sodium 122
mEq/L (136-144), creatinine 0.6 (0.4-1.3), C-reactive protein 47 mg/L (0-3 mg/L),
amylase 140 U/L (28-100 U/L), and lipase 560 U/L (22-51). The most alarming
laboratory finding was a severe elevation of TGs of 10 612 mg/dL (0-149 mg/dL).
Liver chemistry was notable for a bilirubin of 2.8 mg/dL, aspartate aminotransferase
90 IU/L (8-46 IU/L), alanine aminotransferase 60 IU/L (7-55 IU/L), alkaline
phosphatase 160 IU/L (45-115 IU/L), protein 6.9 (6.1-7.9 g/dL), and prothrombin time
11.6 (9.8-13.4 seconds). Serum immunoglobulin G4 level was 75 mg/dL (8-140 mg/dL).
Urinalysis and chest X-ray were unremarkable. Abdominal ultrasound showed a normal
gallbladder and liver with normal intrahepatic and extrahepatic bile ducts. CT scan
of the abdomen and pelvis showed a hypodense lesion in the pancreas surrounded by a
moderate amount of peripancreatic fluid ( and ). Ranson’s score was calculated at 2,
indicating mild AP.
Initial management included aggressive intravenous rehydration therapy, antiemetics,
and opioids for pain control while awaiting urgent transfer to the intensive care
unit for the supportive measure and close monitoring. The patient had a persistent
low-grade fever, tachycardia of 112 beats per minute, and elevated lactic acid of
2.7 (0.5-1). Blood cultures were drawn, and meropenem was initiated empirically due
to a high clinical suspicion of pancreatic infection pending culture sensitivity.
Insulin was initiated in an attempt to reduce TG levels rapidly. Infusion of insulin
was initiated at a rate of 1 to 2 U/kg/day with 5% dextrose in 100-mL infusion to
prevent hypoglycemia. His blood glucose level was ranging between 180 mg/dL and 210
mg/dL (random = 140-200 mg/dL). He never developed hypoglycemia during the duration
of insulin infusion. The decision was made to initiate apheresis, but the patient
improved significantly with insulin infusion alone along with supportive measures.
There was a fall in TG level to 6120 mg/dL on day 2 after insulin infusion, with a
further drop to 3510 mg/dL by day 4, and finally levels decreased to 500 mg/dL by
day 7. Insulin was used for the total duration of 8 days until TG level decreased
below 300 mg/dL, and unlike diabetic ketoacidosis, the patient was not bridged with
subcutaneous insulin therapy. The patient was nil per os (nothing by mouth)
initially, and from day 4 of hospitalization, he began tolerating oral feeds in
addition to fenofibrate, which was initiated at a dose of 90 mg/day. Empiric
antibiotic therapy was stopped due to negative blood cultures. Based on a temporal
association as well as ruling out other competing etiologies, a final diagnosis of
HTG-induced AP was made. His last TG level recorded was 325 mg/dL during the
hospital stay, and the patient was discharged after recovery from AP on long-term
fenofibrate therapy. The patient was followed-up after 3 months from the time of
discharge with the TG level of 230 mg/dL without any further complications. The
patient was counseled to continue fenofibrate indefinitely in order to prevent
further attacks of AP. |
pmc-6120274-1 | We present a case of a 28-year-old African American female without any comorbid conditions who presented to the emergency department with right-sided pleuritic chest pain, dyspnea, and menorrhagia. She had been having intermittent pleuritic pain since 5 years and had been to the hospital many times in the past but without any diagnosis and resolution of her symptoms.
On examination, patient had stable vitals and her chest exam revealed absent breath sounds on right basal region.
Initial laboratory studies revealed a severe microcytic anemia with normal coagulation profile. Her initial chest X-ray showed right pleural effusion and airspace disease while computed tomography (CT) of chest identified large right pleural effusion.
She underwent ultrasound of the pelvis that revealed approximately 6 cm fibroid in uterine fundus.
Interventional Radiology was consulted for thoracentesis and 500 ml of serosanguinous fluid consisting of blood elements was drained. There was suspicion of thoracic endometriosis due to the temporal relationship between commencement of symptoms and menstrual cycle each month. The patient underwent video-assisted thoracoscopy surgery (VATS) that identified implants on diaphragm () and abnormal lung with remnants of hemorrhage in pleura. The specimens were studied histologically, and diagnosis of thoracic endometriosis was confirmed (Figures and ).
Patient was started on Leuprolide; however, after a few months, she stopped the treatment, as she was not able to tolerate it. She did have a relapse of her symptoms and again presented to emergency department where she was managed conservatively. |
pmc-6120276-1 | A 45-year-old male, smoker, who presented a 10-day history of painful, cyanosis, and progressive digital necrosis in both hands. In the four previous months, he noticed painless mass in the right axillary gap, drenching night sweats, and 5 kg weight loss. No clinical features of connective tissue disease were acknowledged such as systemic lupus erythematosus or systemic sclerosis (e.g., photosensitivity, arthralgias, arthritis, skin hardening, and sicca syndrome). Physical examination at admission highlighted necrotic lesions on the distal phalanges of both hands (except the thumbs) (), enlarged lymph nodes in right axillary (3 cm), and right supraclavicular gaps (4 cm). All pulses were palpable. A computed tomographic scan evidenced right axillary adenopathic conglomerate (6 cm), right supraclavicular gap (5 cm), and multiple retroperitoneal adenopathies (<10 cm). Initial investigation showed hemoglobin 113 g/L, hematocrit 42%, total white cell 18.3 × 109/L, lymphocyte count 4.8 × 109/L, platelets 280,000/mm3, and albumin 2.4 g/dl. Electrolytes, liver function, lipidic profile, and serum protein electrophoresis (SPEP) were normal. Results of coagulation test were also normal. Serum complement levels and serologic test for rheumatoid factor, antinuclear, antineutrophil-cytoplasmatic, lupus anticoagulant, anticardiolipin, anti-B2 glycoprotein 1, cryoglobulins, and cryoaglutinins were negative. Hereditary thrombophilia was not evaluated. Human immunodeficiency virus and hepatitis B and C viruses were negative. Arteriography of upper limbs demonstrated a distal stop in all bilateral digital arteries. Transthoracic echocardiogram was normal. He was initially treated for 10 days with anticoagulation with low-molecular-weight heparin, antiplatelet agents such as acetylsalicylic acid at 100 mg once daily and nifedipine, without improvement of ischemia.
As other common etiologies had been ruled out with investigations, digital ischemia was interpreted as a paraneoplastic phenomenon. Corticosteroids (hydrocortisone 200 mg every 8 hours) and a bolus of 1 g intravenous cyclophosphamide were indicated. A significant decline of pain, cyanosis, and progression of ischemic lesions was noticed after 6 days of treatment. However, amputation of three phalanges was required due to necrosis. After surgery, a delay for healing due to acrosyndrome was not observed (). The use of iloprost was not discussed due to the evolution. Biopsy of axillary nodes demonstrated nodular sclerosis classical Hodgkin's lymphoma (HL) ().
Bone marrow was not infiltrated. Classical HL stage IIIb was confirmed. The patient then started conventional ABVD protocol (doxorubicin, bleomycin, vinblastine, and dacarbazine), which was well tolerated. After 6 cycles, he remained asymptomatic, and symptoms of digital ischemia were completely resolved. At the end of treatment, positron emission tomography/computed tomography was negative, confirming complete remission of HL. Follow-up was performed monthly during 6 months and then every 3 months. After 18 months, the patient remains in remission of HL, with no evidence of digital ischemia recurrence. |
pmc-6120283-1 | A 6-year-old male child was admitted to our hospital with his parents for adenotonsillectomy with the history of recurrent tonsillitis and obstructive sleep apnea. Examination revealed grade five enlarged tonsils that were almost meeting at the midline. His adenoids were found to be blocking 90% of his airway in a lateral nasopharyngeal X-ray. Preoperative workup including chest radiography and electrocardiography was normal.
Adenotonsillectomy was performed under general anesthesia with endotracheal intubation. Standard surgical technique was used, and dissection of palatine tonsil was performed meticulously on the subcapsular plane to avoid excessive trauma. Adenoids were removed gently by curettage. Hemostasis was performed by means of careful bipolar electrocoagulation. The surgical procedure proceeded uneventfully with no intraoperative or early postoperative complications. The patient recovered from anesthesia well within 15 minutes.
During the first postoperative hours, there were no episodes of coughing, but the patient had an episode of emesis, one severe vomitting attack. Dyspnea and generalised swelling of his face, neck, and chest wall developed immediately after vomitting at the three-hour postoperative period.
He was conscious and in sitting position because of dyspnea. He did not state an obvious chest pain. But he was uncomfortable and moderately anxious. His vital signs were blood pressure, 110/70 mmHg; pulse rate, 135 beats/minute; respiratory rate, 35 breaths/minute with shallow breathing; temperature, 36.7°C; and oxygen saturation, 98% at room air. A physical examination revealed painless swelling of the face, neck, and chest area with marked crepitus on palpation consistent with cervicofacial subcutaneous emphysema. Emphysema was palpated on anterior chest wall from sternum to axillary regions. Inspection of the oropharynx and nasopharynx did not evidence any bleeding from the operation sides or the presence of any mucosal tear and muscle dehiscence. He had a normal neurologic examination including intact cranial nerves, sensation, and muscle strength.
Because of suspicion of subcutaneous emphysema and pneumomediastinum on chest X-ray, a computed tomography (CT) of the thorax was obtained simultaneously. The CT showed the subcutaneous emphysema of the neck and the chest wall along with a large volume of air (Figures and ). The emphysema extended to both axillae, even the perihumeral region and along the precervical and anterolateral cervical soft tissues (). The CT also showed extensive pneumomediastinum, the presence of pneumopericardium, large epidural pneumatosis, retropharyngeal-prevertebral pneumatosis, and air in paraesophageal spaces without pneumothorax (). No masses, bullae, and blebs were seen.
Since the patient did not present with additional cardiorespiratory compromise and was hemodynamically stable, conservative management was decided. He was transferred to pediatric intensive care unit for close monitorization and conservative treatment. The patient also was instructed to refrain from coughing. The patient was administered analgesics, oxygen, cold-vapor, and broad-spectrum prophylactic antibiotics, and food intake was forbidden. He was followed up by chest radiographs. He was relieved from signs and symptoms around the sixth day, and his thorax CT revealed absence of air at seventh day after adenotonsillectomy. Then he was discharged at the seventh day, and follow-up examinations did not reveal any abnormal findings. |
pmc-6120288-1 | A 49-year-old male with history of alcohol-induced pancreatitis presented with 1 month of worsening left pleuritic chest pain and shortness of breath. Initial physical exam was unremarkable, and laboratory tests were only remarkable for increased lactate dehydrogenase and borderline-low albumin. Initial chest radiograph showed moderate left and small right pleural effusions with left retrocardiac opacity (). Computed tomography (CT) pulmonary angiogram was performed and was negative for pulmonary embolism and showed only small bilateral pleural effusions.
On admission, patient underwent thoracentesis and approximately 1L of brown fluid from the left pleural space was removed. Pleural fluid evaluation demonstrated an exudative effusion with lipase of 2912 IU/L and amylase of 2783 IU/L. CT abdomen and pelvis demonstrated a fluid density tract arising from the pancreatic tail, extending caudally through the diaphragm from the esophageal hiatus, communicating with the left pleural space (). The patient was started on medical therapy with octreotide. Magnetic resonance cholangiopancreatography (MRCP) confirmed a PPF tract with irregular, dilated, main pancreatic and common bile ducts (). The patient underwent ERCP two days after admission which redemonstrated mild diffuse dilatation of ventral pancreatic duct involving the head, body, and tail of the pancreas with evidence of pancreatic duct leak in the most upstream tail of the pancreas that extended caudally to the left pleural cavity, consistent with PPF. A 5 FR x 10 cm plastic stent was placed in the pancreatic duct and a biliary and pancreatic sphincterotomy was performed to divert the fluid leak.
The hospital course was complicated by post-ERCP acute pancreatitis, which was treated with bowel rest and empiric antibiotics. Postprocedure chest radiograph showed worsening pleural effusions and surgical management including distal pancreatectomy was considered. However, surgery was deferred after the patient improved clinically with medical management, and a repeat chest radiograph revealed improvement of the pleural effusions. The patient improved clinically and was discharged with pain medications.
The patient returned to the emergency department within the first week after discharge with complaints of worsening abdominal and chest pain. Another thoracentesis was performed with removal of 400 mL fluid. The study of pleural fluid specimen demonstrated amylase level > 1000 IU/L which was positive for Klebsiella and enterococcus faecalis. The patient was treated with intravenous antibiotics and the pancreatic stent was upsized to 7Fr.
Approximately 9 weeks following the initial ERCP, repeat ERCP demonstrated no extravasation of contrast from the pancreatic tail, and the stent was downsized to 5Fr. Repeat ERCP 15 weeks after the index procedure showed mild diffuse dilatation of the main pancreatic duct with no extravasation of contrast or stenosis (). Therefore, the pancreatic duct stent was removed. Chest radiograph and CT abdomen pelvis showed complete resolution of pleural effusions bilateral as well as the PPF tract (Figures and ). |
pmc-6120290-1 | A 47-year-old male with a past history of nephrolithiasis, irritable bowel syndrome, and mild depression presented to the emergency center with two weeks of flank pain and four days of cola-colored urine. He described a throbbing, stabbing pain in his left flank that persisted and progressively worsened, which was associated with dark urine, nausea, unmeasured fever, chills, and a 10-lb weight loss. He denied dysuria or urinary hesitancy.
On physical exam, vital signs showed a temperature of 37.2°C, blood pressure of 121/55 mmHg, pulse of 95 bpm, and respirations at 20 breaths per minute while saturating at 94% on room air. He was alert and oriented x 3, but in moderate distress from his left-sided flank pain. There was no cervical, axillary, or femoral lymphadenopathy present. On auscultation, he was noted to have bilateral, basilar crackles without rhonchi or wheezing. Cardiac exam showed a regular rate and rhythm, with a 2/6 systolic, crescendo-decrescendo murmur heard best over the left sternal border. There was severe, left CVA tenderness on exam, but his abdomen was soft, nondistended, and nontender. Extremities showed no edema, and skin exam showed no evidence of petechiae or rashes.
Initial laboratory data showed a WBC of 3.8 bil/L, Hgb of 7.7 g/dL, platelet count of 89 bil/L, sodium of 138 mmol/L, potassium of 4.4 mmol/L, chloride of 114 mmol/L, CO2 21 of mmol/L, calcium of 7.4 mg/dL, phosphorus of 3.0 mg/dL, BUN of 19 mg/dL, creatinine of 2.36 mg/dL, and glucose of 97 mg/DL. Urinalysis showed 3+ blood, 1+ protein, > 50 RBC/HPF, 0-5 WBC/HPF, and RBC casts.
Abdominal ultrasound showed a 12.6 cm right kidney, 12.4 cm left kidney with no hydronephrosis, and a spleen with wedge-shaped areas suggestive of infarct. An MRI showed splenomegaly of 17.9 cm and a wedge-shaped infarct ()
Further blood test results showed a haptoglobin of 159 mg/DL, LDH of 272 U/L, fibrinogen of 248 mg/dL, an elevated CRP of 4.9 mg/dL, ESR of 25 mm/hr, C3 of 94 mg/dL, C4 of 23 mg/dL, negative antibodies to hepatitis A, B, and C, and negative ANA, ASO, and anticardiolipin antibodies. ANCA testing was negative using an indirect immune-fluorescent assay (IIF) with a positive lab test considered for results greater than 1:20. Myeloperoxidase antibody (MPO-ANCA) was negative, but proteinase-3 (PR3-ANCA) antibody titer was elevated at 160 units, using an enzyme-linked immunosorbent assay (ELISA) with a positive result greater than 21 units. Blood cultures were negative and remained so after 5 days.
A renal biopsy was performed. Light microscopy (, left) showed focal proliferative injury with two nonnecrotic crescents. Immunofluorescence was positive for IgM, IgA, C3, and C1q located predominantly along the glomerular capillary loops and rarely in the mesangial areas. Electron microscopy (, right) showed segmental foot process fusion with mesangial and subendothelial immune deposits with no subepithelial deposits, consistent with an immune complex GN.
Concerned with the heart murmur and renal biopsy results, a transthoracic echocardiogram was performed and was negative for valvular vegetations. A subsequent transesophageal echocardiogram showed a bicuspid aortic valve with a vegetation. Culture-negative endocarditis was diagnosed and valve replacement performed with pathology showing necrosis, neutrophils, and B. henselae on tissue culture and specialized stains.
The patient received 6 weeks of antibiotic therapy with doxycycline and rifampin and clinically improved with decrease in flank pain. Urinalysis also improved showing 4-10 RBC/HPF, 0-5 WBC/HPF, and no visible casts. Creatinine decreased to 1.4 mg/dL, and ESR and CRP normalized within 2 months to 3 mm/hr and <0.4 mg/dL respectively. Repeat proteinase-3 antibodies remained elevated at 121-163 units despite antibiotic therapy. |
pmc-6120294-1 | A four-year-old Japanese girl with no remarkable medical history was referred to our orthopedic clinic for treatment of 2 cm of LLD. She had a two-year history of progressive LM in a wide range of the posteromedial aspect of the right thigh and the medial aspect of the right lower leg. At the first presentation, skin lesions exhibited hyperpigmentation, induration, and xerosis. The range of motion of the right knee was full extension to 80° of flexion. Radiographs of the right lower extremity revealed dysplastic/atrophic femur and tibia. LLD increased with time and reached nearly 10 cm at seven years of age (). As she and her parents refused to undergo epiphysiodesis of the unaffected side of the lower extremity, we performed simultaneous lengthening of the right femur and tibia using a unilateral external fixator (EBI/Zimmer Biomet Carbon Rail Deformity System; Warsaw, Indiana, USA). She had taken low-dose prednisolone every day or every second day prior to the first lengthening procedure. The dosage regimen had been dependent on the disease activity based on clinical and thermographic assessment. Tibial osteotomy was performed with the Gigli saw, whereas femoral osteotomy was done with a multiple drilling technique. No postoperative immobilization was used, and full-weight bearing was encouraged from the second postoperative day. After 14 days of the waiting period, distraction of the femur and tibia was commenced at a rate of 1 mm and 0.5 mm per day, respectively. Femur was lengthened at the same rate throughout the distraction period, whereas the distraction speed of the tibia was gradually decreased after the lengthening callus showed thin and sparse on radiographs. Distraction of the tibia was occasionally interrupted until the callus width and continuity were reestablished. As a result, the lengthening period/amount of lengthening of the femur and tibia were 90 days/83 mm and 163 days/37 mm, respectively, and an overall leg length was 7 mm longer in the affected limb at the end of the lengthening period (). During the neutralizing period, an accordion technique and daily low-intensity pulsed ultrasound (LIPUS) exposure were applied to the tibia to stimulate callus maturation. She received LIPUS treatment using a sonic accelerated fracture healing system (SAFHS; Teijin Pharma Ltd., Tokyo, Japan) once a day for 20 minutes without interruption. After 84 days and 194 days of the neutralizing period in the femur and tibia, respectively, the device was loosened to allow dynamization of the lengthened callus so that it could fully mature. The dynamization period reached 49 days in the femur and 58 days in the tibia to obtain matured callus exhibiting fusiform/cylindrical shape and similar density to that of the adjacent cortical bone on radiographs. Before pin removal, we dislodged the fixator frame with the fixation pins leaving in situ for a while to monitor the development of regenerate bone fracture or bending. The monitoring period was 47 days for the tibia and only one day for the femur, because the femoral pins had already been loosened. A healing index (HI) was 29 days/cm and 129 days/cm in the femur and tibia, respectively. Regenerate fracture of the femur, however, occurred due to minor trauma three days after the pin removal (). Since parental consent for open reduction and internal fixation was not obtained, she was treated conservatively with skin traction, resulting in malunion associated with a marked anterolateral bowing.
After the first lengthening procedure, LLD gradually increased again and reached 11 cm at eleven years of age (), when the flexion angle of the right knee decreased to 30 degrees. The second simultaneous lengthening of the femur and tibia was performed through percutaneous osteotomy using a multiple drilling technique. In the femur, acute correction of the bowing was done at the osteotomy site with the use of a fixator. The angulation was corrected up to 25 degrees using a proximal rotational clamp, followed by mechanical realignment of the bone axis using a distal translational clamp. After correction of the angular deformity, the osteotomy site was compressed (). Distraction by 1 mm and 0.5 mm per day was initiated at 14 days postoperatively in the femur and tibia, respectively. During the lengthening period, the rate of distraction was adjusted appropriately in order not to deteriorate the continuity of the callus on radiographs. Since the callus was poorly consolidated in the femur (), a modified “chipping and lengthening technique” was performed to enhance bone regeneration at nine months postoperatively () []. Briefly, both ends of the osteotomy site and the callus were drilled with a 3.0 mm Kirschner wire in advance and then broken into smaller pieces with an osteotome. Subsequently, the comminuted bones were compressed until a radiolucent area was no longer recognized. Hard callus that obliterated the medullary cavity at the ends of the osteotomy site was removed with a sharp spoon. Two weeks after the chipping surgery, the distraction was resumed at a rate of 0.5 mm per day. The lengthening period/amount of the femur and tibia were 435 days/55 mm and 209 days/29 mm, respectively, and an overall leg length was 31 mm shorter in the affected limb at the end of the lengthening period. Symptomatic pin tract infection occasionally occurred during the treatment period and was resolved with oral antibiotics without any sequelae. The HI of the femur and tibia was 182 days/cm and 222 days/cm, respectively. Currently, two or three years have passed since the final removal of the femoral or tibial pins, respectively, and 38 mm of LLD is left with acceptable lower limb alignment (). The range of motion of the right knee is 20° of flexion and 0° of extension, but she can walk independently without a brace or a crutch. She and her parents are satisfied with the outcome despite the long treatment period. |
pmc-6120333-1 | We present the case of a 73-year-old woman with a history of asymptomatic sinus bradycardia that presented to our facility with a chief complaint of acute chest pain. She was found to have elevated troponin I of 0.3 ng/ml (normal < 0.057). Chest X-ray was normal. Laboratory workup revealed normal complete blood count, bleeding profile, basic metabolic panel, thyroid-stimulating hormone, and random blood glucose. The 12-lead electrocardiogram (ECG) was suggestive of junctional escape rhythm with a heart rate (HR) of 37 beats/minute (). Transthoracic echocardiography (TTE) showed reduced left ventricular function (ejection fraction (EF) of 30%), with apical ballooning suggestive of takotsubo cardiomyopathy versus acute coronary syndrome (). Left ventriculogram also showed ventricular ballooning suggestive of takotsubo cardiomyopathy (). Cardiac catheterization revealed normal coronary arteries. Thus, she was diagnosed with classical TC. Due to her symptomatic bradycardia, a temporary pacing wire was placed. Her diagnosis was suggestive of sick sinus syndrome as she had occasional P waves that were fine (). Overnight, she went into an atrial flutter with a variable block (). Although, no rate control agent was started, the HR was 83 beats/minute (). Her atrial flutter continued over the next 24 hours. A dual-chamber pacemaker was recommended and placed without complications by the electrophysiology team. Her rhythm on discharge was rate-controlled atrial flutter. She was discharged home on a beta-blocker, angiotensin-converting enzyme inhibitor, and anticoagulation. Her TTE findings were resolved on a follow-up visit two weeks later. However, pacemaker interrogation revealed frequent episodes of paroxysmal rate-controlled atrial fibrillation alternating with bradycardia requiring cardiac pacing. The patient is still under regular follow-up in the cardiology clinic. |
pmc-6120334-1 | A 31-year-old man with a history of epilepsy presented twice to the Emergency Room (ER) in the span of 10 days after experiencing GTC seizures. On initial presentation, the patient had a witnessed seizure while at work and was postictal on arrival. While in the ER he again had a witnessed GTC seizure which broke 1 minute after receiving 2 mg of lorazepam intravenously. Almost immediately after the seizure, he became dyspneic and hypoxic despite a Nonrebreather (NRB) mask. He was subsequently intubated for hypoxic respiratory failure. Chest radiograph postintubation showed diffuse bilateral infiltrates (), and pink frothy sputum was seen collecting in the endotracheal tube (ETT). The ER team believed that this was blood related to a tongue laceration and suspected aspiration pneumonitis given the radiographic findings consistent with Acute Respiratory Distress Syndrome (ARDS). The patient was loaded with 1 gram of intravenous levetiracetam, per neurology, and then restarted on his home regimen of 1 gram twice daily. He was admitted to the Medical Intensive Care Unit (MICU), started on a course of ampicillin/sulbactam for possible aspiration pneumonia, and, due to a PaO2:FiO2 of 128 mm Hg, was started on inhaled epoprostenol and placed on lung protective ventilation. Brain computed tomography (CT) showed no acute intracranial abnormality, and continuous electroencephalogram (EEG) showed diffuse background slowing and occasional bifrontal spike and wave discharges that were thought to suggest frontal lobe epilepsy. ENT performed a bedside nasopharyngolaryngoscopy and found no upper airway source of bleeding. Repeat chest radiograph the following day showed rapid resolution of the initial bilateral infiltrates () with PaO2:FiO2 recovered to >200 mm Hg. His blood, urine, and sputum cultures were unremarkable, and influenza and respiratory syncytial virus polymerase chain reaction were negative. Antibiotics and inhaled epoprostenol were discontinued, and the patient was successfully extubated 48 hours after intubation. MRI brain showed mesial temporal sclerosis primarily affecting the left posterior hippocampus. He was discharged in a stable condition with instructions to take 1.5 grams of levetiracetam twice daily with scheduled neurology follow-up. Upon further history, it was discovered that the patient had been diagnosed with epilepsy one year prior and had a history of nonadherence to his antiepileptic medications.
The patient returned eight days later to the ER after again experiencing two GTC seizures at home. He was similarly postictal and suffered yet another GTC seizure in the ER which lasted for approximately 1 minute and broke after receiving 2 mg of lorazepam intravenously. The patient was subsequently dyspneic and hypoxic. Bilateral diffuse crackles were auscultated, and he was once more intubated for hypoxic respiratory failure. Postintubation chest radiograph showed increased bilateral airspace opacities (), similar in appearance to his prior admission. Frothy pink sputum was also seen in the ETT. Due to a difficult intubation, ER staff believed there was again possible oropharyngeal trauma or tongue biting. He was started on antibiotics for a possible pneumonia and admitted to the MICU, and given imaging suspicious for ARDS with a PaO2:FiO2 of 75 mmHg he was placed on lung protective ventilation. The patient was reloaded on intravenous levetiracetam. Brain CT again showed no acute intracranial abnormalities, and continuous EEG showed diffuse encephalopathy likely secondary to medication effect with no epileptiform activity. Repeat chest radiograph the day after admission showed rapid resolution of bilateral opacities (). His cardiac brain natriuretic peptide was within normal limits, there was no growth from blood, urine, and sputum cultures, and a transient postictal leukocytosis resolved. Antibiotics were stopped, and patient was successfully extubated within 72 hours of mechanical ventilation. A transthoracic echocardiogram was performed during this admission that showed a normal ejection fraction, normal diastolic function, no significant valvular disease, and no evidence of pulmonary hypertension. |
pmc-6120336-1 | A woman with TOF underwent left classic BTS operation by the late cardiac surgeon Professor Shigeru Sakakibara at the Tokyo Women's Medical College, Tokyo, Japan, in the 1950s when she was 10 years old. She stopped visiting the hospital a few years postoperatively because she did not have difficulty performing daily activities. Subsequently, she got married at 25 years of age and gave birth to two children at 29 years of age without special gynecological care at a local hospital. She kept working on a production line while raising her children without experiencing symptoms of heart failure.
At 70 years of age, she was found to have a low oxygen saturation during a health examination program, but she did not seek hospital care. She developed dyspnea and leg edema when she was 72 years old, and then diuretic was started for a diagnosis of heart failure at a local clinic. When she was referred to our hospital for further evaluation, her symptoms of heart failure were comparable with the New York Heart Association (NYHA) functional class III. Her oxygen saturation was 88% on room air at rest. Her heart examination revealed a continuous murmur (Levine III/VI) and systolic ejection murmur (IV/VI) in the second right sternal border. Laboratory data showed the following values (reference ranges): hemoglobin level 15.7 g/dl, hematocrit 44.5%, platelet count 19.7 × 104/μl, prothrombin time 11.4 seconds, 98.5%, D-dimer level 1.2 μg/dl (<1.0 μg/dl), creatinine level 1.35 mg/dl (0.4–0.8 mg/dl), and serum brain-type natriuretic peptide level 210 pg/ml (<18.4 pg/ml). A chest radiograph revealed a cardiothoracic ratio of 66%, right-sided aortic arch, and prominently dilated PA without pulmonary congestion (). The electrocardiogram showed sinus rhythm with a prolonged PR interval and ST-T segment abnormalities (). The echocardiogram showed a large ventricular septal defect with a bidirectional, mainly left-to-right shunt, overriding the aorta, right ventricular (RV) hypertrophy, and a stenotic RV outflow tract with a peak velocity of 4.9 m/s (). Left ventricular (LV) diastolic indices of echocardiogram were as follows: peak E velocity 80 cm/s, E/A 0.72, septal E′ velocity 4.1 cm/s, lateral E′ velocity 3.5 cm/s, and average E/E′ 21. Abnormal relaxation pattern of transmitral flow, low E′ velocity, and high E/E′ suggested the existence of LV diastolic dysfunction. The cardiac magnetic resonance imaging scan showed reduced RV ejection fraction (EF) of 28% and preserved LVEF of 60% with a LV end-diastolic volume index of 103 ml/m2 (Figures and ). There was no abnormality in the pulmonary valve (PV), and the diameter of the PV annulus was 24 mm. The catheter angiogram revealed a patent BTS and severe stenosis at the ostium of the left PA (). Right heart catheterization showed a normal PA wedge pressure (systolic/diastolic/mean pressure: 15/9/8 mmHg), mildly elevated PA pressure (systolic/diastolic/mean pressure: 35/20/30 mmHg), elevated RV systolic and end-diastolic pressure (135/20 mmHg), mean right atrial pressure (11 mmHg), and systolic and end-diastolic LV pressure (149/23 mmHg). The pressure gradient between the PA and right ventricle was 117 mmHg. Cardiac output calculated by the Fick principle was 2.9 l/min, and pulmonary vascular resistance index was 5.95 Wood units·m2. The brain's magnetic resonance imaging scan showed no significant abnormalities. She started to take diuretics and home oxygen inspiration therapies; her heart failure symptom improved to NYHA II. Based on the clinical and hemodynamic assessments and her age, we decided not to perform radical operation. |
pmc-6120337-1 | A two-year-old boy was brought to the emergency department with respiratory distress without fever. He did not have a pathological perinatal history, nor a personal or family atopy. There was no history of choking episodes or ingestion of a foreign body witnessed by the parents, and he had never experienced dysphagia.
During the last month before admission, he had repeated attacks of cough and wheezing without history of dysphagia or drooling. He was given antibiotics and steroids for a month in response to suspected asthma. However, cough got progressively worse. The appearance of dyspnea had motivated an emergency consultation.
On examination, the patient was conscious, without cyanosis. He had a temperature of 37.5°C, a heart rate of 130 beats per minute, a respiratory rate of 40 breaths per minute, an oxygen saturation of 93%, and no sign of dehydration or malnutrition. Pulmonary examination revealed suprasternal recession, scattered snoring, and diffuse wheeze. The cardiovascular examination was normal; the rest of the physical examination was unremarkable. Blood tests showed a normal complete blood count and a C-reactive protein of 14 mg/l; nevertheless, an anteroposterior chest X-ray showed a foreign body in the upper region of the mediastinum ().
The foreign body was extracted by hypopharyngoscopy under sedation. A clothing button was removed from the upper thoracic esophagus. The mucosa around the button was irregular. There was no obvious stricture or perforation.
Thereafter, the infant was maintained on intravenous fluids, with corticosteroids, to decrease the periesophageal inflammation and was discharged at 24 hours. There were no clinical signs indicative of a perforation, and the following day, he was started on a clear liquid diet. Over the ensuing 1 year, the child has been well and gaining weight satisfactorily. There were no reports of subsequent hospital attendances related to this episode. |
pmc-6120339-1 | A 6-year-old girl presented to the Department of Pediatric and Preventive Dentistry with the history of trauma in her right upper front region of the jaw. She had a fall on the school ground while playing 1 hr before the presentation, had no symptoms of nausea, and did not have any discharge or bleeding from her nose. The medical history was unremarkable and did not have any history of daily medication. No gross facial asymmetry was evident. She had no abrasions on the lower or upper lip. Her temporomandibular joints were functioning within limits and with no clicking, pain, or any abnormal mandibular deviation. On intraoral examination, the patient had a complete set of primary dentition and had moderate oral hygiene, with mild plaque deposits at the gingival margins. There was a fracture in the right maxillary canine (tooth number 53) with the oblique fracture line extending subgingivally (). Radiograph (IOPA) taken in the right anterior region of the jaw (tooth number 53) revealed evidence of fracture line running 2 mm below the cementoenamel junction and involving the pulp ().
The treatment options and prognosis for tooth 53 were discussed with the patient's mother. Preoperative photographs were taken, and local anaesthesia was administered (2% xylocaine with 1 : 80,000 adrenaline) on the buccal and palatal aspects of tooth 53. The mobile tooth fragment was extracted, and the remaining tooth structure was surgically extruded using a maxillary anterior forceps (). Occlusion was checked to ensure that there are no occlusal interferences. Acid etching of tooth numbers 51, 52, 53, and 54 was done. The bonding agent was applied, and a semirigid splint was placed and stabilised using a flowable composite (). The patient was advised to consume a soft diet and to be meticulous with her oral hygiene. A 0.2% chlorhexidine gluconate mouthwash was also prescribed twice daily for the next two weeks. The patient was reviewed a day following her initial presentation, and pulpectomy was carried out on the next day and obturated using Metapex. Composite splinting was removed at the end of the third week, and polishing was done. Mobility was checked, and radiographs were taken. On eight weeks following trauma, a periapical radiograph and photograph were updated. The patient was followed up periodically at the 3rd month, 6th month, and 12th month (Figures and ). |
pmc-6120858-1 | A 73-year-old woman presented with shortness of breath; however, the symptom was not serious. A computed tomography scan was performed at an outpatient clinic in her neighborhood, which revealed a giant mediastinal tumor (Fig. ) and enlarged left supraclavicular lymph node (Fig. ). At first, not an esophageal tumor but malignant lymphoma was suspected, and she was referred to another hospital specializing in blood cancers. At the second hospital, an upper gastrointestinal endoscopy was performed showing a giant submucosal lesion without mucosal changes located 18–23 cm from the incisor teeth. Endoscopic ultrasonography (EUS) revealed a homogeneous and hypoechoic solid lesion with a clear margin appearing to originate from the esophageal submucosa. Magnetic resonance imaging clearly showed a solid mass 6 cm in diameter that was compressing her trachea and esophagus (Fig. ). 18F-fluorodeoxyglucose (FDG)-positron emission tomography imaging revealed an upper mediastinal homogenous mass and left supraclavicular lymph node with increased FDG accumulation (Fig. , ). The standardized uptake value of the upper mediastinal lesion was 9.4, suggesting high glycolytic activity in the mass. Laboratory data were unremarkable with normal levels of serum tumor markers such as CEA, AFP, and CA 19-9. The level of interleukin-2 receptor was within normal limits, and CRP remained negative. There were no pigmented patches, and von Recklinghausen disease (VRD) was not diagnosed.
EUS-guided fine-needle aspiration (FNA) biopsy was conducted in order to provide a definitive diagnosis. Three EUS-FNA specimens revealed spindle cell tumors; however, a definitive diagnosis was not determined with immunohistochemical staining. Immunohistochemical staining was negative for c-KIT, CD34, cytokeratin AE1/AE3, p53, and desmin, but a partial positive for S-100. The patient was required to undergo surgery with general anesthesia for further investigation or treatment; however, tracheal intubation was considered to be a very high risk at the second hospital due to the severe tracheal stenosis. Hence, she was referred to our hospital for further treatment after 5 months of visiting the second hospital.
At our hospital, we reviewed previous findings, and the differential diagnoses were leiomyoma, gastrointestinal stromal tumor (GIST), and neurogenic tumor. Although EUS-FNA specimens revealed spindle cell tumors, malignant lymphoma was not excluded completely because of left supraclavicular lymph node with increased FDG accumulation. A definite diagnosis could be reached by performing left supraclavicular lymph node dissection under general anesthesia if the giant tumor was malignant lymphoma. However, tracheal intubation could be impossible because of severe tracheal stenosis, and extracorporeal membrane oxygenation (ECMO) is considered to be life-saving when tracheal intubation fails. The catheters were inserted into internal jugular vein and femoral vein before inducing anesthesia. Under the preparation of VV-ECMO when tracheal intubation fails, single-lumen tracheal tube was inserted over the tracheal stenosis, and the ventilation was performed via intubation alone. Under general anesthesia, left supraclavicular lymph node was dissected; however, the dissected lymph node revealed only inflammation and malignant lymphoma was excluded completely. Her symptom of shortness of breath was not so serious although severe tracheal stenosis was observed; hence, there was no urgency of treatment. However, her shortness of breath suddenly worsened after a few days of lymph node dissection and she suffered from wheezing. We decided to perform quasi-urgent lifesaving surgery. Preoperative diagnosis was GIST because of spindle cell and increased FDG accumulation, and differential diagnoses were leiomyoma and neurogenic tumor. Because the tumor was too large to perform enucleation, esophagectomy was first considered.
Again, under the preparation of VV-ECMO when tracheal intubation fails, bronchial blocker was inserted over the tracheal stenosis and the left-lung ventilation was performed via intubation alone. Under general anesthesia, the patient was placed in the left lateral position, and right thoracotomy through the fourth intercostal space was performed. Tumor exploration showed the giant tumor occupying the upper mediastinum and heavily compressing her trachea (Fig. ). First, arch of the azygos vein was cut to expose the tumor and adjacent esophagus. The tumor strongly adhered to the trachea; however, the trachea or recurrent laryngeal nerves were not damaged in the surgery (Fig. ). The esophagus was encircled above and below the tumor (Fig. ). At that time, the tumor enucleation was considered to pose a high risk of mucosal injury or poor mucosal blood flow; thus, we decided to perform esophagectomy with tumor removal as planned. We reconstructed the esophagus using the gastric conduit through the posterior mediastinum and performed hand-sewn anastomosis at the left neck. The operation time was 565 min and blood loss was 582 ml.
The resected tumor was soft in elasticity, measuring 90 × 50 × 50 mm (Fig. ). Histologic examination revealed a large spherical nodular tumor and comprised mixed fibrillary collagen sheets and cords of spindle cells with nodular growth (Fig. ). No signs of atypia or significant mitotic activity were observed. Immunohistochemical staining was positive for S-100 but negative for c-KIT, CD34, α-SMA, and desmin (Fig. ), and these morphologic and immunohistochemical characteristics were consistent with a diagnosis of neurofibroma. Postoperatively, the patient experienced anastomotic leakage, but she was discharged on the 57th postoperative day with sufficient oral intake.
Benign esophageal submucosal tumors (SMT) are relatively rare, and leiomyoma is the most common, accounting for > 80% of these tumors []. Neurofibromas associated with esophageal SMTs are very rare, as Plachta reported neurofibromas in four cases of 432 SMTs (0.9%) [] and Enterkine et al. reported five cases of 571 SMTs (0.9%) []. Neurofibromas can be associated with genetic disorders and are usually a manifestation of VRD []. They are typically benign tumors comprising neural and connective tissue components, such as Schwann and perineural cells as well as myofibroblasts []. One fourth of patients with VRD report gastrointestinal involvement []. There are three types of neurofibromas: localized, diffuse, and plexiform []. Localized neurofibromas of the gastrointestinal (GI) tract, unlike VRD, are benign nerve sheath tumors in the peripheral nervous system originating from Auerbach plexus and Meissner submucosal plexus [, ]. Our patient had localized neurofibromas without VRD. Localized neurofibroma is far more common in the GI tract, and to date, there has been only one report of plexiform esophageal neurofibroma associated with VRD [].
A few reports have described localized esophageal neurofibromas, and Nishikawa et al. summarized 16 cases [, , –]. In addition, Yang et al. recently reported a giant esophageal neurofibroma []; thus, including our case, we summarized 18 cases of localized esophageal neurofibromas (Table ). The mean age of the patients was 53.6 years (range, 26–75 years), and there was no difference in sex distribution (male:female, 8:10). Dysphasia symptoms were observed in approximately one third of patients. Tumors were located primarily in the mid to upper section of the thoracic esophagus (83%), and the mean tumor size was 6.2 cm (range, 0.5–22.5), whereas leiomyomas were located in the middle or distal regions [].
In summary, dysphagia most commonly manifests in patients with esophageal neurofibromas. Our case is the first report of a patient suffering from wheezing with severe tracheal stenosis and requiring quasi-urgent surgery. The utility of ECMO in patients with severe airway obstruction was reported in the systematic review []. From the systematic review, all cases reported a favorable outcome with all patients surviving to hospital discharge without significant complications []. In our case, under the preparation of VV-ECMO when tracheal intubation fails, we were able to perform tracheal intubation safely and radical surgery thereafter.
It is often difficult to diagnose localized esophageal neurofibroma using diagnostic imaging; thus, histopathologic diagnosis of neurofibroma is necessary in most cases. We hesitated to perform radical surgery without a definite diagnosis as tumor resection and separation from the trachea seemed to be difficult. If the giant tumor was malignant lymphoma, chemotherapy would be effective, and the patient would be saved without radical surgery. It is well known that malignant tumor or malignant lymphoma had increased FDG accumulation; however, Watanabe et al. reported benign esophageal SMT such as esophageal schwannoma had also increased FDG accumulation []. The histopathologic characteristic appearance of neurofibroma consists of spindle-shaped cells associated with collagen fibrils. Additionally, immunohistochemical staining aids in distinguishing neurogenic from myogenic and other submucosal tumors. In our case, the tumor comprised fibrillary collagen and spindle cells organized in whorls, and it was positive for S-100 but negative for c-KIT, CD34, α-SMA, and desmin.
Surgery is the primary treatment for esophageal neurofibroma if clinical symptoms are present. Enucleation of esophageal neurofibromas is sufficient treatment if the tumor is small, and the thoracoscopic approach could be adapted for such small tumors [, –]. However, in our case, a definitive diagnosis could not be determined for giant esophageal SMT; malignancy was suspected due to increased FDG accumulation, and performing right thoracic esophagectomy was necessary. |
pmc-6121109-1 | A 57-year-old male was initially diagnosed with locally advanced rectal cancer (T3N1M0) and treated with neoadjuvant chemoradiation followed by surgical resection (Figure ). He subsequently received adjuvant modified (m) FOLFOX6 followed by colostomy reversal.
Two years later, CT imaging demonstrated new retroperitoneal lymphadenopathy suspicious for metastatic disease, and retroperitoneal lymph node (LN) biopsy revealed metastatic adenocarcinoma consistent with CRC primary. He received first-line treatment with FOLFIRI plus bevacizumab, but eventually experienced disease progression. He then progressed on a clinical trial combining capecitabine with an investigational therapy, followed by progression on regorafenib.
As his tumor was KRAS and NRAS wild-type, he was then treated with anti-EGFR antibody therapy (panitumumab). After 7 months of disease control, imaging revealed a new hypermetabolic LN at the right common iliac chain, and irinotecan was added to panitumumab. This treatment was eventually discontinued due to disease progression. A new biopsy of a mediastinal LN was performed and next generation sequencing (NGS) revealed that the tumor was still KRAS, NRAS, and BRAF wild-type, and there was no evidence of MET amplification (see Table ). After progression on another phase I clinical trial with an investigational therapy, he was then enrolled in a phase Ib clinical trial combining cabozantinib and panitumumab (NCT02008383). At the time that he started treatment, he was increasingly symptomatic due to extensive pulmonary metastases, with worsening cough and shortness of breath. After ~6 weeks of treatment, CT demonstrated dramatic improvement in his pulmonary tumor burden (see Figure ), as well as resolution of dyspnea and cough. As part of the trial protocol, plasma-EDTA was collected before the start of treatment to explore potential drivers of treatment response and/or resistance. CfDNA profiling utilizing a 54-gene targeted NGS panel (Guardant 360™) was performed on this sample. Blood-based profiling revealed subclonal EGFR, KRAS and BRAF resistance mutations. Additionally, EGFR amplification and MET amplification were observed in cfDNA, but not in tissue obtained 3 months prior (Table ). Unfortunately his treatment course was complicated by anastomotic dehiscence and leak with abscess evolution. Because the dehiscence was apparently related to marked treatment response and tumor involution, treatment was discontinued. CfDNA profiling performed after 28 days of treatment revealed loss of MET and EGFR amplification (Figure ), while the mutant allele frequency (MAF) of KRAS G13D increased from 0.3 to 0.6%. There was also a nearly 10-fold decrease in the MAF of TP53 R213* post treatment, likely correlating with the dramatic reduction of tumor burden (Figure ).
After 2 months off therapy, his CEA increased and his dyspnea and cough returned. Capecitabine was initiated and panitumumab was added 2 months later for additional control. He experienced brief stabilization of disease on capecitabine and panitumumab, with subjective improvement of his pulmonary symptoms. He then experienced disease progression and was transitioned to hospice. He died ~10 months after discontinuing cabozantinib and panitumumab. |
pmc-6121195-1 | A 29-year-old man, without a past medical history, was admitted in September 2015 at Réunion University Hospital for sepsis with eosinophilic pneumonia (Figures and ). His blood cell count revealed severe thrombocytopenia (31 × 109/L) with hypereosinophilia (8 × 109/L). Amoxicillin/clavulanic acid had been prescribed 1 week earlier for an inflammatory axillary tumefaction that occurred after shaving. The initial diagnostic workup revealed only pulmonary disorders: bronchoalveolar lavage showing marked eosinophilia (97%), alveolar hemorrhage, with quantitative culture of 104 CFU/mL Streptococcus oralis. A bone marrow aspirate revealed rich marrow proliferation. Screens for autoimmune disease (including anti-phospholipids and ANCA vasculitis test) were negative; no allergies were reported. In the context of sepsis and a probable diagnosis of secondary ITP, the patient received a first course of IVIg, combined with antibiotics, and antiparasitics.
Six days after admission, the patient was transferred to the neurointensive care unit for both spontaneous intracerebral and abdominal hemorrhage. He presented with drowsiness, predominantly brachiofacial hemiplegia associated with lower back pain, and a PC of 60 × 109/L. A CT scan showed a large hemorrhage in the right frontal lobe (40 mL) with mass effect (Figure A) and a large (6 cm) left adrenal gland hematoma. CT angiography revealed a spot sign within the brain hematoma without any suggestion of arteriovenous malformation or cerebral venous thrombosis. A 24-h follow-up CT scan revealed a slight expansion of the frontal hematoma (45 vs. 40 mL) (Figure B). Therefore, ITP therapy was intensified with iterative platelet transfusions to achieve a PC ≥ 100 × 109/L.
At day 12, the patient was found to be in convulsive status epilepticus, and clinical seizure control was achieved with antiepileptic medication (benzodiazepine, then phenytoin). A sustainable decrease in Glasgow Coma Score to 8 required general anesthesia with IV midazolam and mechanical ventilation. An EEG revealed a non-convulsive status epilepticus controlled with propofol infusion. A brain CT venography showed a left lateral sinus thrombosis complicated by small temporal hemorrhage (Figure C). An intraparenchymal pressure monitor (Codman® MicroSensor) was placed in the left frontal lobe; revealing an initial intracranial pressure (ICP) of 40 mmHg. ICP decreased only transiently despite deeper level of standard sedation (propofol, midazolam, and sufentanil), prevention of secondary systemic brain insults, pharmacological neuromuscular paralysis, and controlled mild hypothermia (35°C). Finally, a barbiturate coma was required to control intracranial hypertension but ICP increased again above 40 mmHg at day 14. A new CT scan showed no expansion of the right frontal hematoma but substantial worsening of edema with increased mass effect (Figure D). Because of refractory intracranial hypertension (ICHT), a mini-craniotomy was performed to evacuate the hematoma, although iterative platelet transfusions failed to secure the procedure and avoid perioperative bleeding. Thus, romiplostim was initiated, at the advice of the hematologist, with a first injection the day after surgery and a second course 1 week later. A sustainable complete response was achieved 8 days after first administering romiplostim. No further hemorrhage expansion or new bleeding into the craniotomy site was noted on follow-up brain imaging (Figure E). Note that immunosuppressive agents could not be used because of a concomitant septic shock related to a pyothorax.
Heparin could then be initiated for cerebral sinus thrombosis and further invasive procedures performed to complete the diagnostic workup (lung biopsy, transesophageal echocardiography, and cerebral angiogram), which remained non-contributory. Thereafter, the patient was discharged from hospital 2 months after being admitted with predominantly brachiofacial paresis. |
pmc-6121195-2 | A 14-year-old female teenager, with a previous medical history of chronic ITP (diagnosed in 2012), was admitted to Mayotte’s Hospital (French overseas department) in October 2015 for gingival bleeding, intense headaches, and drowsiness (Figures and ). A blood cell count revealed severe thrombocytopenia at 13 × 109/L and hemoglobin of 80 g/L. A CT scan showed a 36 mL right parieto-occipital hematoma with significant perilesional edema and mass effect (Figure A). She received first-line therapy including corticosteroids, IVIg, and platelet transfusion. Subsequently, she had a generalized tonic–clonic seizure. On the third day, she was transferred to the Pediatric Intensive Care Unit of Saint Pierre (Reunion Island, France), which is equipped with a neurosurgical department.
After admission, the neurological status of the patient deteriorated, with coma and anisocoria related to cerebral hematoma growth (50 mL) (Figure B). A barbiturate-induced coma was required to control ICHT, and corticotherapy was intensified because of persistent severe thrombocytopenia. The day after, ICHT remained uncontrolled. Salvage surgery was performed (craniotomy with hematoma evacuation). Despite massive platelet transfusion in the perioperative period, the PC remained below 15 × 109/L before the procedure, which was complicated by significant subcutaneous bleeding (Figure C). Consequently, romiplostim was initiated at the advice of the hematologist, with a first administration the day after surgery and a second course 1 week later. At this point, a PC of 81 × 109/L was achieved, largely due to a massive platelet transfusion. A sustainable “complete response” was achieved only 6 days after romiplostim administration. We noted a PC peak of 1,554 × 109/L 2 weeks after the second romiplostim injection, without clinical consequences. No further hemorrhage expansion or new bleeding into the craniotomy site was noted on follow-up brain imaging (Figure D). No hemorrhagic complication was observed related to the intraparenchymal ICP monitor (Figure E) placed at the end of the surgical procedure. ICP was initially measured at 27 mmHg and then decreased gradually by continuing sedation for a few more days.
Eighteen days after her hospitalization the patient was discharged from intensive care with left residual hemiparesis. She full recovered a few months later. |
pmc-6121308-1 | A 4-year-old boy presented with bilateral periorbital oedema dating back a month and was admitted to our hospital. He had a good general condition and normal pressure values. The results of laboratory tests revealed normal creatinine, hypoprotidaemia (3.8 g/day), hypoalbuminaemia (1.8 g/dL), hypercholesterolaemia (283 mg/dL), hypertriglyceridaemia (242 mg/dL) and nephrotic proteinuria (2.7 g/day < 40 mg/mq/h). Immunological studies showed normal C3 and C4, increased antinuclear antibody titre with mild positivity at IFA Hep-2 (titre of 1:160, speckled pattern), anti-dsDNA antibody negativity, phospholipase A2 receptor (PLA2R) antibodies negativity, IgG 450 mg/dL (less than 2 standard deviations below the normal age-adjusted mean), IgA 3 mg/dL (less than 2 standard deviations below the normal age-adjusted mean) and IgM 94 mg/dL (normal). HBsAg and hepatitis B and C virus serology results were negative, while Epstein-Barr virus, cytomegalovirus and varicella-zoster virus serology results were positive for IgG. Renal ultrasound was normal.
Without performing renal needle biopsy due to ethical issues, a diagnosis of idiopathic nephrotic syndrome associated with IgAD was made, and steroid treatment (prednisone 60 mg/mq/day) was started. Proteinuria became negative after 12 days of treatment; after 4 weeks, the prednisone dose was tapered to 40 mg/mq/day given every other day for 4 weeks, and then this alternate-day dose was slowly tapered over the next 2 months. The subsequent measurement of serum immunoglobulins showed normal IgG and IgM values, but IgA remained very low.
Three months after diagnosis of nephrotic syndrome, during steroid tapering, the child experienced a relapse that was treated with high dose of prednisone (60 mg/mq/day) until remission, then changed to an alternate-day dose for 4 weeks that gradually tapered over three months. During decalage of steroid therapy for the first relapse, the child experienced a second relapse that required a high dose of steroid treatment as before. Subsequently, the child had two additional relapses, becoming frequent and steroid dependent. Therefore, he required rituximab (a chimeric monoclonal anti-CD20 antibody) infusion. Currently, after 2 years his nephrotic syndrome is in remission. His IgA is always very low, with normal values of other immunoglobulins and IgG subclasses. |
pmc-6121308-2 | A 2-year-old boy was admitted to our hospital for bilateral periorbital oedema, scrotal oedema and weight gain. He had a good general condition and normal pressure values. Investigations showed normal creatinine, hypoprotidaemia (3.9 g/day), hypoalbuminemia (2 g/dL), hypercholesterolaemia (417 mg/dL), hypertriglyceridemia (444 mg/dL), nephrotic proteinuria (spot proteinuria/creatininuria 15.5; nephrotic range > 2) and transient microscopic haematuria (5–10 erythrocytes per high-power field). Immunological studies revealed normal C3 and C4, increased antinuclear antibody titre (30.2 U/mL) with mild positivity at IFA Hep-2 (titre of 1:80, speckled pattern), anti-dsDNA antibody negativity, PLA2R antibodies negativity, IgG 42 mg/dL (less than 2 standard deviations below the normal age-adjusted mean), IgA 5 mg/dL (less than 2 standard deviations below the normal age-adjusted mean) and IgM 87 mg/dL (normal). Virus serology was negative, and renal ultrasound was normal.
Without performing renal needle biopsy due to ethical issues, a diagnosis of idiopathic nephrotic syndrome associated with IgAD and partial deficiency of IgG was made, and steroid treatment (prednisone 60 mg/mq/day) was started. The proteinuria decreased, but after 6 weeks of steroid therapy, it did not become negative. Therefore, he was treated with 3 high-pulse doses of methylprednisolone followed by steroid therapy, which achieved remission. As late responder, he started cyclosporin, and then steroid was gradually tapered over one month. While he was on cyclosporin therapy, he relapsed six months later and was treated with steroid therapy, with transitory remission. Therefore, cyclosporin was shifted to tacrolimus after one year. In the next three years, while he was on tacrolimus therapy, he had three relapses that required steroid treatment, and then he was treated with ofatumumab (a fully human monoclonal anti-CD20 antibody) infusion. As he had a relapse nine months later, a second ofatumumab infusion was made.
After 2 years, he is still in remission. During follow-up, the measurement of serum immunoglobulins showed IgAD associated with partial deficiency of IgG and normal values of IgM; coeliac disease antibody tests were negative, but he is HLA-DQ2 positive. |
pmc-6121338-1 | A 68-year-old man was referred to our oncology clinic with the pathologic diagnosis of duodenal malignant melanoma. This patient had a history of controlled diabetes mellitus, controlled hypertension and myocardial infraction before admission. He had suffered from fatigue, weakness, lethargy and weight lost (more than 10%) since one month prior to admission. Physical examination revealed no additional clinical data.
A complete blood count (CBC) test showed an iron deficiency anemia. Thyroid function tests were normal. Moreover, he underwent an upper gastrointestinal endoscopy (GIE) and a colonoscopy that revealed some erosion around pylorus of stomach and a prominent papilla of duodenum along with an ulcerative lesion adjacent to D2. Several biopsies were taken from the antrum and D2 lesions.
Histopathologic evaluation showed a high-grade malignant neoplasm involving the bowel wall. Tumor was composed of sheets of loosely cohesive pleomorphic cells with prominent nucleoli and eosinophilic cytoplasm. There was no visible melanin pigment in tumoral cells. Necrosis was also noted. The tumor cells labeled for S100 protein and markers of melanocytic differentiation; Melan-A. As staining for CK, LCA, CD117, and CD34 were negative, the diagnoses of carcinoma, lymphoma and gastrointestinal stromal tumor were ruled out. Morphologic and immunohistochemical findings were consistent with malignant melanoma ( and ).
Subsequently, after confirming the diagnosis of malignant melanoma of duodenal mucosa, the patient underwent secondary full medical evaluation including detailed inspection of the eyes, skin and mucosal surface. These examinations did not show any clinically significant lesion. Moreover, he underwent anoscopy for any visible lesion that was negative. Abdominopelvic computed tomography (CT) scan with intravenous contrast revealed multiple abnormalities. CT scan exhibited an ovaloid mass in the gallbladder with washout in delayed phase that was suggestive of a tumoral lesion. There were two small nodules in the right adrenal and a heterogeneous hypodense mass (diameter: 3.2 cm) in the left adrenal. In the proximal (and to a lesser extent in distal) loops of the small intestine, a heterogeneous increase in thickness was also observed. Moreover, there were several mesenteric lymphadenopathies along the superior mesenteric artery ().
Considering the pathologic diagnosis of the duodenal lesion and its metastatic nature, we commenced treatment of patient with oral temozolomide (every 28 days) and scheduled further diagnostic interventions including CT guided fine needle aspiration biopsy of the abdominal mass and re-upper GIE, unfortunately he expired due to active disease. |
pmc-6121350-1 | A 66-year old male patient was admitted to the emergency service with a six-week history of complaints of hiccup and fever. Hiccups mostly correlated with lead stimulation. The patient had a diagnosis of dilated cardiomyopathy and underwent dual chamber pacemaker and implantable cardioverter defibrillator implantation (ICD) due to atrioventricular complete block three months ago in another hospital. A coronary angiography was performed before the procedure showed normal coronary arteries. Six weeks after the implantation, the patient had fever and was given antibiotic therapy in another hospital. The medical history revealed diabetes and hypertension for 10 years.
On admission, the patient had a fever of 39.5°C, blood pressure of 100/50 mmHg and heart rate of 100/min. Pulmonary sounds were rough and there was no crepitation. A 2/6 pansystolic murmur was audible at all cardiac foci. There was mild edema in both legs. There were splinter hemorrhages in the nails ().
An electrocardiogram showed pacemaker rhythms. A bigeminy ventricular extrasystole was noted. A chest x-ray revealed a bilateral reticulonodular pattern. There were bilateral pleural effusions. The cardiothoracic index was increased. The pacemaker generator implanted in the left pectoral region was present along with two (atrial and ventricular) leads, which appeared to extend into the heart ().
Laboratory tests revealed a WBC of 12.300/m3, sedimentation of 62mm, and CRP of 235 mg/L. HbA1C level was 6.2%. The patient with these clinical manifestations was hospitalized with the diagnosis of unknown fever and hiccups in the department of infectious diseases and was initiated on drug therapy with sulbactam+ampicillin+ciprofloxacin. His blood culture yielded positive result for methicillin-sensitive staphylococcus aureus. His body temperature tended to decrease for a while but increased again to 39°C on day nine, upon which the patient was designated to undergo transthoracic echocardiography. The hiccups continued with intervals. A transthoracic echocardiography showed global hypokinesia of the left ventricle with a low ejection fraction (EF= %35). Besides mild mitral insufficiency, the patient had moderate tricuspid insufficiency. There was an amorphous and mobile mass measuring 2x2.1 cm that was consistent with vegetation, both floating freely on the atrial surface of the tricuspid valve and attached to the pacemaker lead and was continuous inside the ventricle. The mass appeared to be obstructing the tricuspid orifice intermittently ().
These findings confirmed the diagnosis of lead-related infective endocarditis. Given the presence of resistant fever and the size of the mass, lead extraction was planned. The patient was initiated on antibiotic therapy with sulbactam+ampicillin+rifampicin. Upon his request, the patient was transferred to the center where the pacemaker had been implanted. In the mentioned center, the pacemaker lead was extracted and implanted as a temporary transvenous pacemaker. Antibiotic therapy was given for two weeks. After the signs of infection disappeared, a dual chamber pacemaker and ICD were implanted in the patient. After implantation, antibiotic treatment was continued for two weeks. The patient who was followed-up 3 months later was in pacemaker rhythm. He did not complain hiccups, was in good condition and had no signs of infection. There was no echocardiography vegetation. |
pmc-6121486-1 | A 33-year-old Italian man of Indo-European descent, in military service since 2001, was admitted to the Policlinico of an Italian city because of sudden hearing loss NDD, within 24 h of receiving two vaccines: intramuscular tetanus and diphtheria vaccines (Ditanrix 0.5 mL) and subcutaneous meningococcal polysaccharide vaccine (Mencevax 0.5 mL). After informed consent, the subject had underwent two vaccinations: on the right arm meningococcal vaccine and on the left arm tetanus-diphtheria vaccines. Nothing relevant was observed in his family and remote pathological history. He also completed a questionnaire to exclude conditions that could be the reasons for temporary or permanent contraindication to the aforementioned vaccinations. The following conditions were excluded:Concomitant intake of other drugs, homeopathic, nutritional supplements, products based on medicinal plants. A history of adverse reactions to previous vaccination. Suspected or documented allergies to eggs, feathers, chicken meat, duck meat, beef/gelatine, formaldehyde, antibiotics (neomycin, streptomycin, kanamycin, polymyxin B, mercurial compounds). Recent positive history of fever conditions > 38°, airway disorders, diarrhea, intake of any treatments in the last 72 h (antibiotics, NSAIDs, cortisones, aspirin, antimalarial drugs), blood transfusion in the last 6 months, and administration of immunoglobulins.
Twenty four hours after the vaccinations, the subject complained of dizziness, nausea and right hearing loss due to NDD, and in emergency department he underwent audiometric examination, tympanogram with a diagnosis of “severe right perceptual deficit”. Following the persistence of the symptoms despite the pharmacological medical was admitted to the otorhinolaryngology department. During the few days of hospitalization, many investigations were performed such as brain NMR to exclude a vascular origin of the hearing loss or other causes, as well as other audiometric and otorhinolaryngology examinations. Since the second day of admission until discharge, the patient underwent the following therapy: Bentelan (betamethasone 21-sodium phosphate) 4 mg 1 fl e.v. twice daily, vitamin B12 1 fl i.m. once a day, omeprazole and Trental (pentoxifylline) 1 fl i.m. 1 once a day, carbogen for 30 min every two hours. After 11 days he was discharged with a diagnosis of “improvement of sudden hearing loss” and the following home treatment: Bentelan 1 cpr/day for 30 days, Deflan (deflazacort) 25 mg 1cpr/day × 2 for 3 days, then ½ cpr × 2 for 3 days and ½ cpr × 1 for 4 days, Lucen (esomeprazole) 20 mg 1 cpr for 10 days.
We report the results of the audiometric tests at the time +1 (24 h after vaccination), +2 (during hospitalization, 48 h after vaccination), at discharge (+9) and after about 6 months (+159) ().
The last audiometry performed approximately 6 months after the morbid event shows a functional recovery on low and medium frequencies. The subject enjoys good health at present. He expressed his consent to the therapy and to the elaboration of this study.
The subject chose to make personal information available after learning that its personal data would be classified as critical data. They also accepted the processing of anonymous and collective data, analyzed using scientific methods and for scientific purposes based on the declarations of the Helsinki Declaration. |
pmc-6122461-1 | We report a 75-year old man with stage IV BRAF V600E mutated malignant melanoma. On his initial 18fluoro-deoxy-glucose (FDG) positron emission tomography computed tomography (PET-CT) scan, he presented with multiple bilateral pulmonary nodules, bone and cutaneous lesions, peritoneal metastases and a lesion at the head of the pancreas (Fig. and ). A palliative combination therapy with a BRAF- (dabrafenib 2x 150 mg) and MEK inhibitor (trametinib 2 mg) was started. Six weeks later a CT-scan revealed a partial remission of the lung, bone and cutaneous lesions but a progression of the lesion in the pancreas. A fine needle aspiration of the pancreatic lesion confirmed metastasis of the melanoma. This metastasis was irradiated and the combination targeted therapy continued. Eight months later, a progression with several new pulmonary lesions and peritoneal metastasis (Fig. ) was observed and a second line therapy with the CTLA4 inhibitor ipilimumab (3 mg/kg) started. After 2 cycles, a disease progression (Fig. ) prompted a third line therapy with the PD-1 inhibitor pembrolizumab and radiotherapy of a myocardial metastasis. After the start of pembrolizumab, the condition of the patient rapidly improved and the patient achieved a good partial remission (Fig. ). At 24 months under pembrolizumab a routine CT-scan showed multiple bilateral part solid lung lesions in the upper parts of the lung. At that stage, the patient reported NYHA II dyspnea. Endoscopically the tracheobronchial system was unremarkable. Bronchoalveolar lavage (BAL) demonstrated only a slight lymphocytosis of 13% lymphocytes without signs of pulmonary infection (negative microbiological cultures and PCR for viral pathogens). A transbronchial lung biopsy showed only normal lung morphology. Since it was unclear if the new lesions were metastases, we decided to surgically obtain a histological specimen. Wedge resection of several nodular lesions of the lung was therefore performed. Surprisingly, only one pulmonary lesion represented a melanoma metastasis with almost complete regressive necrosis as a sign of excellent response to treatment. The other lesions distant to the metastasis represented circumscribed areas of OP (Fig. ). We found a strong CD3+ cell infiltration of the inflammatory lesion with predominantly CD4+ cells over CD8+ cells (Fig. ). Also, a several FOXP3+ cells were found (Fig. ). Interestingly, clusters of PD-L1 positive macrophages were seen (Fig. , SP-263 clone). A therapy with corticosteroids according to current guidelines for grade I-II pulmonary irAE was initiated with prednisone of 1 mg/kg and stopping of pembrolizumab. After a rapid regression of pulmonary lesions, the corticosteroid dose was tapered to 10 mg daily during a time period of 7 weeks. At this point, the patient presented with dyspnoea NYHA II and mainly thoracic pain. A CT revealed no lung embolism, but a progression of the bilateral part solid lung lesions corresponding to OP (Fig. and ). With the OP relapse, a course of antibiotics and corticosteroids 50 mg daily was initiated with a rapid clinical and radiological improvement. A reduction of the corticosteroids by 10 mg every 4 weeks was recommended as performed for OP in routine pneumological practice. However, as soon as the doses of prednisone were lower than 20 mg daily a clinical and radiological worsening was observed. For dose reduction/ steroid sparing we decided to establish a combined immunosuppressive therapy consisting of mycophenolate mofetil (Cellcept) twice daily when the dose of prednisone 20 mg daily was reached again. After 4 weeks, the patients relapsed again with dyspnoea and new pulmonary lesions on the CT-scan (Fig. ). Because of the insufficient response to mycophenolate the TNFα-blocking agent infliximab was started. Initial dosing with 5 mg/kg was given for 3 doses and then a maintenance therapy was installed (100 mg). This led to a significant improvement after 4 months of therapy and corticosteroids could be completely stopped. The patient developed again dyspnoea at exertion, but a CT-scan showed no lung lesions or any direct cause for the dyspnoea (Fig. ). A cardiac stress test demonstrated some myocardial perfusion deficit and a coronary angiogram a high-grade stenosis of the left anterior descending (LAD) artery, which could be dilated and stented with a drug-eluting stent. After 6 months, infliximab was stopped and the patient is currently in an enduring very good partial remission for his melanoma (Fig. ). |
pmc-6122623-1 | Patient 1 was a healthy 25-year-old primigravida woman without any familial medical history. She experienced an uneventful pregnancy until 23 + 5 weeks gestation (WG), when the anatomical scan demonstrated a potential cleft lip associated with dilatation of the left cerebral ventricle and a short corpus callosum. The patient did not recall any particular illness previously in her pregnancy (see the Timeline presented in Fig. ). The scan performed at 24 + 5 WG in our unit identified intra-uterine growth restriction (IUGR; <5th percentile) concurrent with multiple fetal anomalies including a bilateral cleft palate, colpocephaly (both atriums measuring 10 mm), dysgenesis of the corpus callosum and enlargement of the cisterna magna (14 mm) associated with a posterior fossa cyst (Fig. and ). A diagnostic amniocentesis and fetal blood sampling were performed at 25 + 5 WG for congenital infections and genetic analysis. Toxoplasmosis, rubella and syphilis were previously excluded by negative maternal serology. Due to the ongoing ZIKV epidemic, ZIKV screening (RT-PCR RealStar® ZIKV RT-PCR Kit 1.0, Altona Diagnostics, Hamburg, Germany) was added to the routine testing despite the absence of suggestive symptoms in the mother. The amniotic fluid and fetal blood were positive for ZIKV RNA confirming a congenital ZIKV infection. Fetal biological parameters (Table ) also suggested fetal infection with elevated total IgM (120 [<20 mg/l]); β2-Microglobulin 4.8 [<5 mg/ml]) and a cholestasis-like pattern (GGT 589 [<100 UI/l], AST 17 [<20 UI/l]), associated with moderate anemia and thrombocytopenia (Hb 13.4 [>15 g/100 ml], platelets 128 [>150 G/L]). However, maternal blood and urine were negative for ZIKV RNA. We therefore performed retrospective serum analysis, which confirmed a maternal ZIKV infection that occurred between 5 + 3 and 14 + 3 WG (see Fig. ). Fetal serological analyses were negative for ZIKV IgM and equivocal for IgG, which may have resulted from materno-fetal passage. Meanwhile, an initial FISH analysis revealed mosaic trisomy 18 with 36% of cells affected.
Due to the poor prognosis, the patient opted for termination of pregnancy as permitted by French legislation. At 29 + 5 WG, a stillborn male infant was delivered with a weight of 870 g (<3rd percentile), head circumference (HC) of 220 mm (<3rd percentile) and length of 36 cm, presenting with dysmorphic features: a large bilateral cleft lip, peaked palate, exophthalmia and hyperthelorism. At the time of delivery, fetal blood was negative for ZIKV RNA, however it was amplified from the cerebro-spinal fluid confirming ZIKV persistence in the central nervous system despite systemic clearance. Ultimately, cell culture and complete cytogenetic analysis confirmed the diagnostic of mosaic trisomy 18, while CGH array did not reveal any additional genetic anomalies. Autopsy was declined. |
pmc-6122623-2 | Patient 2 was a 25-year-old healthy, gravida 4 para 2, woman with a past history of stillbirth at 7 months gestation of unknown etiology. Screening test for aneuploidy was at low risk (1/10,000). At 19 + 5 WG, the patient experienced a maculo-papular pruritic rash associated with mild fever, arthralgia and headaches, compatible with a viral infection. The anatomical scan at 22 + 5 WG showed hydrops fetalis with skin edema, ascites, a large pericardial effusion and prefrontal edema (5.9 mm), associated with symmetric IUGR (estimated fetal weight 427 g; <3rd percentile, biparietal diameter (BPD) of 44 mm (<3rd percentile), HC of 165 mm (<3rd percentile), abdominal circumference of 193 mm (measurement unreliable secondary to presence of ascites), and femur length of 29.7 mm (<3rd percentile). No morphological anomalies were detected (Fig. and ). Non-alloimmune fetal anemia was highly suspected. Amniocentesis and fetal blood sampling were performed, which confirmed severe fetal anemia and thrombocytopenia (Table ) (Hb 3.6 [>15 g/100 ml]; platelets 68 [>150 G/L]). Fetal blood transfusion was performed. The amniotic fluid was positive for PVB-19 DNA, while negative for ZIKV RNA and CMV DNA. However, ZIKV RNA was detected in fetal blood and placenta confirming a combined PVB-19 and ZIKV fetal infection. Congruently, ZIKV RNA was detected in both maternal blood and urine. As persistent viremia has been described in pregnant women [], timing of maternal infection was confirmed based on retrospective serum analysis. The identification of PVB-19 specific IgM at 13 + 5 WG, while both ZIKV specific IgG and IgM were negative confirmed a primary PVB-19 infection in the first trimester (see Timeline presented in Fig. ). Maternal ZIKV infection occurred later and probably correlated with maternal symptoms at 19 + 5 WG. These unspecific symptoms could have corresponded to either a primary ZIKV or PVB-19 infection. Fetal blood analysis revealed an elevation of general inflammatory markers (β2-Microglobulin 7.8 [mg/ml] (<5), total IgM 49 [mg/l] (<20)). Unlike case 1, the GGT remained low, while hepatic cytolysis was observed (GGT 12 [UI/l] (<100), AST 96 [UI/l] (<20)). Due to worsening fetal clinical status after transfusion (absent end diastolic flow on umbilical artery Doppler, increasing ascites, pericardial effusion and skin edema), the patient requested medical termination of pregnancy, which was performed at 25 WG. A stillborn male infant weighing 530 g (<3rd percentile) presenting with significant edema was delivered. No other macroscopic anomalies were noted. Autopsy was declined. |
pmc-6122635-1 | A 52-year-old male without a history of hypertension and diabetes, from Huizhou, Guangdong, was referred to Huizhou Central People’s Hospital in June 2016 with symptoms of fever for 1 week. He worked on a farm with poor hygiene management and was responsible for breeding. Before admission, he was treated with flu in the local community clinic, but respiratory infection, CNS infection, septicemia, and hepatic dysfunction were suspected when he was admitted to the Central People’s Hospital.
During physical examination, he had fever (38.1°C) and headache with normal blood pressure (100/80 mmHg). All respiratory, cardiovascular and neurological examinations were normal. There was no evident sign of neck stiffness, initial unilateral limb weakness or flaccid paraparesis. Hepatosplenomegaly and peripheral edema were also not observed.
The initial laboratory investigation displayed high white blood cell (WBC) count of 10.2 × 10^9/L with predominant 88.4% neutrophil, normal hemoglobin and platelet count. The liver profile showed elevated total bilirubin (TBIL) 39.7umol/L, direct bilirubin(DBIL)19.9umol/L, alanine aminotransferase (ALT)75 U/L, and aspartate transaminase(AST)46 U/L; renal function was normal. The chest computed tomography showed slight bilateral fiber tissue hyperplasia. These examinations strongly suggested typical infection by bacteria with a variety of clinical manifestations.
A lumbar puncture was conducted, and a CSF biochemical test was subsequently performed. The WBC count was 72.0 × 10^6/L, showing predominantly mononuclear cells, and the cerebrospinal fluid pressure (CSFP) was 220 mmH2O. The C-reactive protein was 139.87 mg/L. The level of protein in CSF was elevated, while that of glucose was normal. To confirm the pathogen leading to infection, both the blood and CSF were cultured for further characterization, as described below. Moreover, bilateral brain parenchymal enhancement of lesions with an obvious enhancement of left lateral pterygoid and temporalis were observed in the following brain Magnetic Resonance Imaging (MRI). The Magnetic Resonance Angiography (MRA) of the cerebral arteries was normal. Furthermore, testing was all negative for tuberculosis, autoimmune disease, acid-fast bacilli, Cryptococcus, and Hepatitis B virus. Combined with the above results, the patient was diagnosed with neurological melioidosis (Table ). It took a week to diagnose this patient in the hospital.
Despite the patient being treated with intravenous injection of ceftazidime at a dose of 2 g 12-hourly, The patient became agitated, and an intermittently persistent fever was observed during treatment of this patient. Samples of the patient’s blood and CSF were sent to the Guangdong provincial CDC (No.160 Qunxian Road, Panyu District, Guangzhou, Guangdong province, China) for further identification of CNS infection. The culture results coincided with those in hospital, excluding other bacterial and fungal infections. Both sample were cultured on blood plate. After incubating the blood and CSF specimens at 35°C on blood agar for 48 h, a single grey wheel-shaped isolates morphology was observed (Fig. ). This culture was tested with biochemical and molecular diagnostic method to identify the pathogen. The isolates were tested utilizing the Automatic microbiological analysis system(VITEK 2 Systems, Biomerieux, France), the biochemical results details listing in the Fig. , and B. pseudomallei was identified with 99% probability. The DNA of the isolates, CFS and blood were extracted (QiAamp DNA kit) and real-time PCR (B. pseudomallei real-time PCR kit, shanghai ZJ bio-tech, China) results were positive for B. pseudomallei, confirming the original clinical diagnosis of neurological melioidosis. The presence of IgM antibodies specific to JEV were detected using ELISA(JE Detect IgM ELISA, InBios, America) and were confirmed as positive, revealing the B. pseudomallei and JEV co-infection in this patient. Considering the possibility of cross-reacting with DENV, the serum sample was detected for specific antibodies against DENV and result showed negative(DENGUE DUO CASSETTE, Panbio, Australia). Furthermore, the detection was negative for screening viruses including enterovirus, influenza virus, adenovirus, and poliovirus by ELISA. The patient received symptomatic management with ceftazidime (2 g 12-hourly), oxiracetam (6 g per day) and dipyridamole (150 mg per day). After 22 days of treatment, he was discharged on eradication therapy with oral 960 mg trimethoprim-sulfamethoxazole (160 mg trimethoprim and 800 mg sulfamethoxazole) per 12 h for 2 months. At follow-up 3 months after initial admission, the patient had recovered well without fever or headache. There was no growth of B. pseudomallei on CSF culture in physical review from Aug. |
pmc-6122642-1 | A 28-year-old-man presented to our outpatient department with lower back pain lasting two years and getting progressively worse. The patient stated the pain started when he tried to pick up heavy luggage. He began taking over-the-counter pain medication supplemented with applying a hot water bottle to the painful region, which provided symptomatic relief. He reported using the hot water bottle for the past few months, and he used to sleep with the hot water bottle underneath his body.
The area of erythema ab igne developed a mild itch, and over next few months, the area developed hyperpigmentation (Figure ).
He presented to our clinic with back pain. We investigated using x-rays and magnetic resonance imaging (MRI), which revealed L4-L5 and L5-S1 disc bulges (Figure ). He was treated with a transforaminal nerve block (TFNB) injection which provided him with reasonable relief. He was told, however, that the lumbar spine pathology may require surgery later in his life.
He was advised to stop using the hot water bottle, and he was referred to a dermatologist for further evaluation and treatment. |
pmc-6122645-1 | A 42-year-old nonpregnant, housewife with no known comorbidities, presented to the emergency room (ER) with chest pain for 15 minutes where electrocardiography (ECG) was done and it showed acute onset anterior wall ST-segment elevation MI. She was kept in coronary care unit (CCU) under observation for two days; no thrombolysis was done because the patient had a history of bleeding peptic ulcer and, therefore, was started on aspirin, clopidogrel, and simvastatin where her ST-segment elevation settled but again started to rise. Hence, angiography was done that showed dissection in left anterior descending (LAD) artery (Figure ).
The patient had no family history of sudden cardiac death, coronary heart disease, or coronary artery dissection; past medical, surgical, and psychosocial histories were unremarkable. Physical examination was unremarkable. Chest radiography was normal. Cardiac enzymes were normal. The echocardiogram was normal. Due to recurrent chest pain, emergent off-pump CABG was performed, and the left internal mammary artery was anastomosed to the LAD distally. She had an uneventful recovery and during 18 months follow-up period, the patient was free of chest pain and her ECG became normal. |
pmc-6122655-1 | A 31-year-old man with no known medical history presented after being found down outside his home. On arrival at the emergency department (ED), he was lethargic but following commands without extremity weakness. Mild dysarthria was noted. His blood pressure in the ED was 121/57 mmHg. He was not taking any medications and the toxicology screen was negative. Computed tomography (CT) showed SAH with a large clot burden in the basal cistern and a left Sylvian fissure (Figure ). There was a trace intraventricular hemorrhage (Fisher Grade 4). A CT angiography of the head and neck was obtained and was negative for a vascular abnormality/aneurysm. Serum sodium was 143 mEq/L (normal 135-145 mEq/L). Six hours after admission, he became stuporous and required intubation. Repeat CT imaging showed increased SAH and new, left frontoparietal intracerebral hemorrhage (ICH; Figure ). His left pupil became dilated and nonreactive. He was resuscitated with hyperventilation, hyperosmolar therapy, including mannitol and hypertonic saline, as well as sedation. An external ventricular device (EVD) was placed, which revealed an elevated opening pressure. He was hemodynamically unstable with fluctuations in blood pressure and heart rate. He was eventually stabilized with vasopressors and was taken to the operating room for emergent decompressive hemicraniectomy and clot evacuation. The distal middle cerebral arteries were subsequently clipped. The post-procedure cerebral angiography was negative for a vascular abnormality/aneurysm. CT head showed the right frontal EVD, clips in the left middle cerebral artery distribution, and decompressive hemicraniectomy (Figure ).
Post-evacuation, he developed refractory intracranial hypertension. He continued to receive osmolar therapy and eventually required prolonged neuromuscular blockade. His serum sodium increased to 156 mEq/L. Despite the elevated ICP, his cerebral perfusion pressure was maintained. His oxygenation requirements continued to increase, requiring increasing positive end-expiratory pressure (PEEP). Chest x-ray showed increasing bilateral pulmonary opacities. He developed a refractory fever that was controlled with an advanced cooling device (Arctic Sun, Bard Medical Division, Covington, GA, US). He received broad-spectrum antibiotics for aspiration pneumonia. TTE showed a normal ejection fraction without any areas of akinesis. On Day 8 of admission, transcranial Doppler (TCD) values for the left middle cerebral artery (MCA) was 220 cm/s, right MCA was 204 cm/s, right anterior cerebral artery (ACA) was 191 cm/s, left ACA was 89 cm/s, and basilar artery was 102 cm/s. He was treated with milrinone (0.1 mg/kg bolus over 10 minutes; then 0.5-0.75 mcg/kg/min infusion). The repeat TCD on the same day at 6.5 hours after the initial TCD showed a reduction in mean flow velocities in all vascular territories. Transcranial Doppler (TCD) waveforms from the left MCA, right ACA, and basilar artery, showing the pre-milrinone waveforms and the post-milrinone waveform (Figure ).
Left MCA velocity decreased to 171 cm/s (22.27% reduction), right MCA to 156 cm/s (23.52% reduction), right ACA to 136 cm/s (28.79% reduction), left ACA to 84cm/s (5.61% reduction), and basilar artery to 63 cm/s (38.23% reduction) as cardiac function remained largely unaffected. Mean flow velocities in different blood vessels before and after milrinone therapy (Table ).
His cardiac output, as monitored on FloTrac (Edwards Lifesciences, Irvine, CA, US), remained unchanged at 7.8 L/min with a stroke volume variability (SVV) of 6%. Electrocardiography (ECG) was normal and cardiac troponin testing was negative. Magnetic resonance imaging (MRI) of the brain showed the known SAH and ICH with ischemia in the left MCA territory as a result of vessel clipping. There were no areas of ischemia. Over the next few days, his neurological examination remained poor. The family ultimately withdrew care. |
pmc-6122656-1 | A 34-year-old primigravida was referred to our tertiary care hospital with a suspicion of either a chorioangioma of the placenta or a placental teratoma on the second-trimester anomaly scan performed from a secondary care hospital. The patient had no known comorbidities apart from being diagnosed with pregnancy-induced hypertension. The conception was planned and was not assisted by any interventional or medical means. There was no history of congenital anomalies in the family or of twin pregnancies. Ultrasonography at our institution revealed a single intrauterine fetus, corresponding to 27 weeks and two days of gestation, displaying a normal interval growth from the previous ultrasound. The presence of a multiloculated cystic mass with septations and calcifications was also noted. This mass was devoid of any vascularity (Figure ).
On color Doppler examination, no vascularity was noted and the mass, reported as measuring 104 x 53 mm, appeared as arising from the anterior wall of the uterus. The differential diagnosis of placental teratoma, chorioangioma, hemorrhagic placental degeneration, or degenerating fibroid was considered. A repeat scan in the third trimester revealed the same findings.
At 36 weeks and five days of gestation, the patient gave birth, via C-section, to a fetus with good Apgar scores (9/1, 9/5). A second congenitally malformed fetus was also delivered, which was devoid of cephalic end structures. Only the feet and lower limbs of the fetus were discernable (Figure ). A single placenta measuring 515 grams was also delivered, containing two umbilical cords. The patient was discharged in a stable condition on the sixth day of admission.
A histopathological examination of the placenta revealed placental discs measuring up to 19.5 x 14 x 4 cm. The placental membrane measured 30 x 16 cm, with two umbilical cords. The separately lying fetus showed gross malformation with the absence of the head and both upper limbs. However, both lower limbs were partially formed. The heel to rump length was 18 cm. A diagnosis of chorioangiosis of the placental disc along with a malformed twin was made.
The post-mortem X-ray ( Figure ) of the malformed twin showed the incomplete formation of the lower limbs and sacrum with some calcifications present in the cephalic region. This lead to the diagnosis of an acardiac anencephalic twin. |
pmc-6122666-1 | A 49-year-old morbidly obese African-American female patient presented to the hospital with an initial complaint of fever, pain, redness, swelling and discharge in her left lower extremity. The pain was progressive and worsened to 10 out of 10 on the pain scale. It aggravated with movement and on weight bearing. There were no alleviating factors. She denied any recent history of trauma to her leg, chest pain, shortness of breath or any history of prolonged immobilization.
Her past medical history included morbid obesity with a Basal Metabolic Index (BMI) of 85. She also has a history of hypertension, lymphedema, hypersensitivity lung disease, obstructive sleep apnea, and chronic gastroesophageal reflux disease. Her past medical records showed a previous hospitalization for group G and beta-hemolytic streptococcal bacteremia three years ago that was properly treated.
Her family history included hypertension in her father and type two diabetes mellitus in her mother. She denied any consumption of alcoholic and tobacco products or any recreational drug use.
Physical examination showed a morbidly obese patient with a temperature of 101.4 F. Her heart rate was 120 beats per minute and respiratory rate of 33 per minute. Her oxygen saturation at normal air was 91%. Bilateral non-pitting lymphedema in both lower extremities was observed. Her left lower extremity showed erythema and swelling in her calf region with significant serosanguinous discharge. She had a restricted range of motion in her left lower extremity.
The patient was admitted for further investigations. Her complete blood count showed significant leukocytosis of 25,600 cells/mm3 with bandemia, elevated procalcitonin (PCT) levels of 8.33 ng/mL, elevated C-reactive protein (CRP) of 348.0 mg/L suggesting an acute infectious process. Her creatinine level was elevated at 1.22 mg/dL compared to her previous laboratory results of 0.8-0.9 mg/dL. She also showed signs of liver dysfunction with an elevated aspartate aminotransferase (AST) of 56 U/L, alkaline phosphatase (ALP) of 144 U/L, and of coagulopathy with an international normalized ratio (INR) at 1.21.
Left lower extremity Doppler ultrasound showed no evidence of deep venous thrombosis with limited evaluation for popliteal vein compression due to edema. There was Doppler flow within the popliteal vein. Significant edema was identified in the left popliteal fossa without any underlying abscess. Two separate blood cultures were tested positive for Streptococcus dysgalactiae subsp. dysgalactiae. The urine cultures grew no organisms.
The patient was administered a loading dose of Vancomycin in the emergency department and later started on Cefepime. Proper fluid hydration was included in her treatment plans. She was then shifted to Ceftriaxone when her blood cultures came back positive for SDSD. A transesophageal echo was ordered to rule out endocarditis and came back negative for vegetations. Her condition improved slowly as her white blood cell count went from 26,000 cells/mm3 to 14,000 cells/mm3 and other inflammatory markers such as PCT were back to normal. The pain, erythema, and edema in her left lower extremity also improved gradually.
She was discharged after one week of inpatient treatment at her own request and prescribed another one week of ceftriaxone that she received intravenously at her home. Her follow-up after two weeks showed major improvement. |
pmc-6122669-1 | History & examination
A 31-year-old African-American female with no significant medical history presented with a sudden onset of severe headaches that were highly suggestive of subarachnoid hemorrhage (SAH). The patient was initially evaluated in the emergency department where a neurological examination revealed no deficits.
Pathological findings
A computed tomography (CT) scan revealed a SAH filling the pre-pontine, crural, ambient, and quadrigeminal cisterns more prominently on the left side of the brain, with mild hydrocephalus (Figure ). A CT-angiography (CTA) showed an enlarged vessel within the left ambient cistern. Digital subtraction angiography (DSA) also revealed the large and irregular appearance of the left SCA in the ambient cistern. No immediate intervention was undertaken.
The patient was admitted to the neurosurgical intensive care unit (ICU) and treatment was initiated with regular neurological examinations and daily transcranial-doppler (TCD) studies. The patient remained intact, with TCD values showing only moderate vasospasm. The patient did not require any treatment for the mild radiographic hydrocephalus. On Day 14, the patient underwent a repeat DSA which showed a persistent vasospasm in the distal basilar and bilateral posterior cerebral arteries. Three-dimensional (3-D) reformatting also demonstrated a dissecting fusiform SCA aneurysm in the lateral ponto-mesencephalic segment (Figure ). Due to the persistent vasospasm, no intervention was undertaken at that time as definitive treatment measures were being discussed in a multidisciplinary board meeting.
Endovascular intervention
On Day 21, the patient underwent a successful placement of a low-profile visualized intraluminal support (LVIS Jr.) device (MicroVention, Tustin, CA) covering the fusiform aneurysm, which measured 3-mm wide and 18-mm in length. After premedication with aspirin and clopidogrel, a 7-Fr sheath was inserted into the common femoral artery and a 6-Fr guide catheter was inserted into the left vertebral artery. The left SCA was catheterized using the microcatheter and microguidewire. The LVIS Jr. device was then deployed successfully along the fusiform segment of the SCA without evidence of contrast extravasation. The treatment goal was to preserve the intraluminal flow with flow diversion from the aneurysm for reduction and eventual obliteration.
Postoperative course
At the three-month follow-up, the patient had no complaint and was neurologically intact on examination. A CTA performed at that time showed the SCA patency proximal and distal to the stent without evidence of persistent dilatation or an aneurysm (Figure ). A formal catheter angiogram was deferred by the patient. At the 10-month follow-up, a DSA demonstrated the interval healing of the aneurysm with preserved vessel patency as well as mild distortion caused by the stent in the SCA (Figure ). The patient remained neurologically intact on examination with no complaints. |
pmc-6122671-1 | A previously healthy 34-year-old man from La Espiga, Chorrera district, Province of West Panama, presented to our institution with ipsilateral, painless, erythematous, nodular ascending lesions in his left hand, forearm, arm, and axillary region. The lesions followed a lymphangitic path. The patient reported that one month before presentation, the lesions started as a cat scratch on the third finger of his left hand. The lesions were not associated with fever or signs of infection. The patient is a laundryman who is in regular contact with eight cats, and he has no history of trauma from the manipulation of plants, leisure, or occupational activities. Before presenting to our clinic, he went to a health center where he was administered topical silver sulfadiazine, but the condition did not improve.
On physical examination, we noted a nodular, erythematous, ulcerated lesion on the middle finger of his left hand with additional nodular, erythematous lesions that were not painful on palpation and had no differences in temperature. Some of those lesions were ulcerated. We found three similar lesions on the dorsum of his left hand. On the patient’s forearm, we found nine lesions on the posterior forearm, four lesions on the anterior forearm, and one on the medial forearm. On his arm, we found three lesions in the anterior area, seven in the medial area, and four in the lateral area (Figure ). We noted one nodular lesion in the patient’s axillary area.
The 72-hour Montenegro skin test yielded a negative result. On the day-10 follow-up visit, we scraped the lesion for polymerase chain reaction (PCR) testing, culture and smear for Leishmania, and an acid-fast bacillus (AFB, also known as bacillus acido-alcoolo résistants (BAAR)) smear for cutaneous tuberculosis. The result of the AFB test was negative.
We prepared Saboraud cultures to rule out sporotrichosis, placing the samples on two slides for visualization. On the first slide, we added a drop of 20% potassium hydroxide, in the other, a drop of lactophenol blue. After 10 minutes, we observed the slides at 400x and 1000x magnification for fungal structures. The positive sample was seeded on Saboraud agar and Micosel (CONDA Pronadisa, Spain).
After 15 days of incubation with notorious fungal growth, we incubated a culture. A 1-cm2 segment of sterile Saboraud agar was taken with a sterile scalpel and placed on a clean slide. This segment was then inoculated with a needle loaded with the fungal culture. A sterile slide was mounted and placed in a Petri dish with a paper towel wetted with sterile water as a wet chamber. The culture was incubated at room temperature until growth was observed on the coverslip, which was then carefully peeled off to mount it on a slide cleaned with 70% ethanol with a drop of lactophenol blue for microscopic observation for structures such as conidia, hyphae, or spores indicative of the S. schenckii complex.
The patient was treated with itraconazole 100 mg orally each day for 90 days and recovered with a full resolution of the lesions. |
pmc-6122673-1 | This case describes a 38-year-old G6P3114 at 23 weeks and five days GA with chronic abruptia and low-lying placenta who presented to the ED with vaginal bleeding. Her past medical history was significant for preterm pregnancy, preeclampsia, and three previous c-sections. Initial workup revealed placenta accreta and possible percreta (Figure ) []. The patient was placed on IM corticosteroids in anticipation of preterm delivery. As soon as the patient was stable, she was discharged home. She presented to a different hospital the next day with the same complaints.
The maternal fetal medicine (MFM), neonatal intensive care unit (NICU), and anesthesia teams were consulted on her case due to the concern of placenta accreta. A magnetic resonance imaging (MRI) was done and was significant for loss of the decidual line along the right lateral anterior uterus with myometrial thinning along the region of her previous c-section scar. There was no evidence of percreta on the MRI. Of note, her bedside transvaginal ultrasound (TVU) showed placenta accreta with low-lying anterior placenta with a short cervix and funneling, but ruled out placenta previa. Still, the patient continued to have vaginal bleeding presumably from chronic abruption (Figure ) []. She was transferred back and forth between labor and delivery (L&D) unit and the maternal fetal care unit (MFCU) with threatened PTL.
A few days later, the patient was complaining of leakage of fluid and while on sterile speculum examination (SSE), there was vaginal pooling. Standard diagnostic strategies (nitrazine blue testing and presence of ferning on microscopy of fluid) were used to determine whether the fluid was indeed amniotic and came up positive. Treatment for PPROM was started which included antibiotics as well as rescue steroids. Upon further assessment, it was found that amniotic fluid index (AFI) >7 cm. Subsequent amniotic fluid exam via repeat US the next day was consistent with oligohydramnios. It was thought that her low-lying placenta could have also caused retroplacental blood to accumulate. But, based on the finding of oligohydramnios, chronic abruptia oligohydramnios sequence (CAOS) was more likely the diagnosis than PPROM. Before any further evaluation could be done, the patient went into PTL that night, which ultimately was spontaneously arrested. Her PTL was then complicated by presumed uterine rupture at the site of her previous c-section, as indicated by deterioration of her FHR tracing to Category III.
The patient received general anesthesia for an emergent c-section in the setting of uterine rupture at 26 weeks GA. She then underwent a planned supracervical hysterectomy. The surgery was complicated by PPH as the patient's estimated blood loss (EBL) was about 4500 mL. She received one unit of packed red blood cells (pRBCs) preoperatively the night before, seven units intraoperatively, and two units postoperatively. She was also given four units of fresh frozen plasma (FFP), one unit of platelets, and one unit of cyroprecipitate. She was stable postoperatively and was discharged on POD eight in stable condition. |
pmc-6122675-1 | A 31-year-old Caucasian female presented with progressive dyspnea and palpitations for three months. The patient reported gradual onset, intermittent dyspnea aggravated with walking, relieved with rest, and associated with palpitations. Her past medical, surgical, and family history were non-contributory. The patient denied fever, cough, chest pain, orthopnea, diaphoresis, excessive caffeine intake, or smoking/alcohol/illicit drug use. The relevant findings on physical examination included a pulse rate of 96/minutes and a blood pressure of 135/89 mmHg. On cardiac auscultation, a diastolic murmur of grade 3/6 over the left fifth intercostal space in the midclavicular line was appreciated. The electrocardiogram (ECG) showed atrial flutter at the rate of 122 beats per minute with a rapid ventricular response.
Laboratory investigations, including complete blood cell count, electrolytes, thyroid profile, and liver enzymes were within the normal range. The erythrocyte sedimentation rate (ESR) was 56 mm/hr, c-reactive protein (CRP) was 12.6 mg/dl, lactate dehydrogenase was 587 U/l, and the N-terminal-pro-B-type natriuretic peptide was 1654 pg/ml.
Transthoracic echocardiography revealed an irregular heterogeneous mass in the left atrium, adhering to the posterior leaflet of the mitral valve, leading to mild-moderate mitral stenosis. Cardiac computed tomography (CT) confirmed the presence of an irregular solid mass attached to the posterior wall of the left atrium (Figure ). Systemic CT scans did not reveal any other masses. A diagnosis of atrial myxoma was considered and surgical resection was planned. Intraoperative examination revealed a mass adherent to the posterior wall of the left atrium and the posterior mitral leaflet. Complete resection could not be performed due to the extension of the tumor into adjacent structures. Surgery was well-tolerated and the patient was shifted to the floor.
Macroscopically, an irregular solid mass of 2.1×1.7×1.6 cm was found. The non-encapsulated tumor consisted of highly vascularized beige-to-pink tissue. Microscopically, the tumor was composed of polygonal cells with centrally placed round to oval nuclei and a prominent nucleolus. The cells were surrounded by thin-walled capillary-sized vascular structures and areas of coagulative necrosis. Mitotic activity was approximately 7-8/50 high-power field (Figure ). Immunohistochemically, the tumor cells were positive for vimentin and actin but were negative for desmin, CD34, and S-100. The final pathological diagnosis was de-novo intracardiac glomangiosarcoma. The patient recovered uneventfully and was discharged home in a stable condition. A follow-up visit after three months revealed normal radiological examination findings. |
pmc-6122676-1 | A 77-year-old Caucasian man with metastatic chromophobe renal cell carcinoma under treatment with an anti-PD1 mAb was admitted to our hospital with a severe persistent occipital headache of sudden onset 12 hours before. The patient’s past medical history included hypertension, type 2 diabetes mellitus, and obstructive chronic bronchitis. He was a former smoker and had no drinking history. He used to work in finance and had no relevant family or environmental history.
The patient’s daily medications included antihypertensive medications, oral antidiabetics, omeprazole, and prednisone 25 mg daily. The headache spread to the front and both sides of the head and was associated with nausea and asthenia. It worsened with coughing and other valsalva maneuvers such as lying down. It did not get better with nonnarcotic pain killers, preventing the patient from falling asleep. However, the patient did not have diplopia, photophobia, phonophobia, or any other related symptoms. On admission, his blood pressure was 154/68 mmHg, his pulse was 101 beats/minute, his temperature was 36.7 °C, and his arterial blood oxygen saturation was 98%. The results of his physical and neurological examinations were otherwise unremarkable.
At the time of admission, the patient had been on corticosteroid therapy (0.5 mg/kg/d) for 10 days for suspected immune-related hyperthyroidism. He had tachycardia and mild diarrhea, and the results of his thyroid function tests were compatible with subclinical hyperthyroidism with a suppressed thyroid-stimulating hormone (TSH) level of 0.01 μIU/ml (0.4–4.5) with a raised free T4 of 2.17 ng/dl (0.7–1.9) and a free T3 of 4.66 pg/ml (2.27–5). The last dose of the anti-PD1 mAb, the 11th dose, had been administered 3 weeks before.
A cranial computed tomographic (CT) scan showed an enlarged pituitary gland (15 × 20 × 14 mm), compatible with macroadenoma, without calcifications (Fig. and ). Taking into account the patient’s medical history, the initial diagnosis of an immune-related hypophysitis was assumed, and therefore we increased the corticosteroid dose to 1 mg/kg/d. Subsequently, a contrast-enhanced brain magnetic resonance imaging (MRI) scan revealed a pituitary lesion with hemorrhagic areas enlarging the sella, compatible with pituitary apoplexy (Fig. and ). In addition, the patient had a thyroid disorder with a previous thyroid function test compatible with subclinical hyperthyroidism (TSH of 0.01 μIU/ml [0.4–4.5], free T4 of 2.17 ng/dl [0.7–1.9], and free T3 of 4.66 pg/ml [2.27–5]). The patient’s anti-thyroid peroxidase antibody, antithyroglobulin, and anti-thyroid-stimulating immunoglobulin antibodies were negative. Additional imaging studies were performed to clarify the cause of the primary hyperthyroidism. Ultrasound showed heterogeneous thyroid tissue with focal hypoechoic regions and irregular uptake on thyroid scintigraphy (Fig. ). All of these findings, along with the patient’s palpitations and mild diarrhea, supported the hypothesis of immune-related subclinical hyperthyroidism in addition to a pituitary apoplexy. During the patient’s hospital admission, a hormonal reevaluation revealed a secondary hypothyroidism with TSH 0.11 μIU/ml (0.4–4.5), free T4 of 1.02 ng/dl (0.7–1.9), and free T3 of 1.53 pg/ml (2.27–5). Posterior evaluation of the hypothalamic-pituitary axis showed the following results: insulin-like growth factor 1, 136.1 ng/ml; growth hormone, 0.40 ng/ml; FSH, 8.73 mIU/L; LH, 6.18 mIU/L; testosterone, < 2.5 ng/dl; sex hormone-binding globulin, 3.50 mg/L, and prolactin, 5.2 ng/ml. These new findings suggested secondary hypothyroidism due to pituitary apoplexy.
Assuming the diagnosis of a primary immune-related hyperthyroidism, followed by a secondary hypothyroidism due to a macroadenoma complicated with a pituitary apoplexy, levothyroxine substitution was started along with the previous corticosteroid therapy. The patient gradually recovered from headache and asthenia and a few days later was released from the hospital with levothyroxine substitution (50 μg/d) and corticosteroid tapering. Six months later, aside from his chronic back pain, the patient remained asymptomatic. The whole-body CT scan carried out 1 week before the last visit showed a maintained partial response, and the last cerebral MRI showed a complete resolution of the hemorrhagic areas detected in the initial MRI. The results of the patient’s last thyroid function tests while receiving levothyroxine substitution (50 μg/d) were normal. |
pmc-6122714-1 | A 58-year-old male presented with decreased vision in his left eye, without redness or floaters, which had persisted for three days. His medical history detailed a diagnosis of nephrotic syndrome (membranous nephropathy), which had been treated with prednisone for a period of four months. Drug-induced diabetes was subsequently detected one month after the onset of corticosteroid treatment. The patient developed productive cough, pyrexia, and night sweats, and was further diagnosed with pneumonia three weeks before the admission. His medications at the time included prednisone 20 mg daily, insulin and oral cefdinir. He had no history of ocular trauma or surgery.
An ophthalmic examination revealed visual acuities of 20/20 in the right eye and counting fingers at 2 ft in the left. Pupils were 3 mm and reactive in each eye without relative afferent pupillary defect. The right eye was normal. Slit lamp examination of the left eye was unremarkable. Fundus examination showed clear media and a creamy-white and raised subretinal lesion located at the posterior pole, with the lesion being five disc diameters in size. Additionally, multiple retinal hemorrhages were seen in the overlying retina (Fig. ). The intraocular pressures were normal in both eyes. Optical coherence tomography (OCT) demonstrated a hyperreflective substance located in the subretinal space, between the outer retina and retinal pigment epithelium (Fig. ). Although a further diagnostic workup was requested on the follow day of presentation, the patient was lost to follow-up and presented five days later with reduced vision in the affected eye. On examination, slit lamp examination of the left eye showed mild conjunctival injection and anterior chamber cells of 2+. Fundus examination revealed mild vitritis and further, the area of the retinal lesion had expanded over the superior and inferior arcades (Fig. ).
The patient was admitted for further workup. All vital signs were stable and within normal range. The white cell count was 11.48 × 109/l, with 75.8% neutrophils, and the blood level of C-reactive protein was 59.9 mg/liter. Serum markers of human immunodeficiency virus (HIV), syphilis and tuberculosis were all negative. A chest computed tomography (CT) scan showed multiple bilateral nodules, some of them cavitated in the lungs, which suggested of multiple abscesses (Fig. ). In the context of his lung abscess, a presumptive diagnosis of endogenous endophthalmitis with subretinal abscess was made.
A vitreous tap along with empirical intravitreal injections of a combination of vancomycin (1 mg/0.1 ml) and ceftazidime (2 mg/0.1 ml) were performed on the day of hospitalization. The vitreous samples were sent for bacterial and fungal cultures, as well as bacterial, fungal and viral polymerase chain reaction (PCR). Blood and sputum cultures were also performed. Topical levofloxacin 0.5% and prednisolone acetate 1% eye drops were administrated four times daily, and in addition, oral prednisone and cefdinir were continued. Three days after initial intravitreal injections, the subretinal abscess had improved significantly (Fig. ) and a second injection was administered. The subretinal abscess gradually improved, leaving only a small inferior lesion a week later (Fig. ). Vitreous cultures and PCR were all negative, as were blood cultures. Nocardia, Heamophilus and Candida albicans were identified in sputum cultures. Based on the clinical data and the characteristic appearance of the ocular lesion, it was deduced that the causative organism was most likely Nocardia. As a result, a combination of oral trimethoprim and sulfamethoxazole (TMP-SMX) was administrated. Ten days after hospitalization, the third intravitreal injections were repeated, with the patient then being discharged for follow-up as an outpatient with directions to continue with oral prednisone 20 mg daily and oral TMP-SMX for an further month. The patient remained in stable condition over the following four weeks after discharge. Further fundus examination revealed the subretinal abscess had resolved, leaving some yellowish subretinal precipitates and chorioretinal scarring, with visual acuity of 1/10 (Fig. ).
Seven weeks after discharge, that is three weeks after cessation of TMP-SMX therapy, this patient was admitted to another hospital due to right extremity weakness and a lack of ability to walk or stand on his own for ten days. Magnetic resonance imaging (MRI) of the brain showed multiple cystic-enhancing lesions with surrounding edema over both cerebral hemispheres, suggestive of multiple abscesses, whilst the retina remained quiescent (Fig. ). A chest CT scan showed multiple lung abscesses. Blood cultures were positive for Nocardia, and as such disseminated nocardiosis was diagnosed. Based on sensitivity data, the patient was administered with intravenous imipenem/cilastatin and oral TMP-SMX, with intravenous therapy being continued for three weeks, followed by TMP-SMX monotherapy. The patient was discharged due to improvement in his systemic condition with the recommendation of close follow-up by an infectious disease specialist. Long-term oral TMP-SMX was also prescribed for the patient. Within follow-up chest CT and brain MRI carried out three months later, it was found that the previously detected foci had become smaller or had completely disappeared. A six-month follow-up indicated that the lung abscesses disappeared, and a brain MRI showed the previous residual lesions had almost completely resolved. |
pmc-6122718-1 | A 57-year-old Japanese woman presented with a 1.5-year history of right hip pain when she walked long distances. She had a history of bilateral developmental dysplasia of the hip and had undergone bilateral acetabular osteotomies in childhood. There was no history of trauma, anticoagulant use, or a collagen vascular disorder. She is a housewife. She has no medical history and family history.
A physical examination revealed a firm, immobile mass measuring 18 cm × 12 cm located on the right side of her ilium. An operation scar measuring 14 cm was found in the front of her hip joint. There was no redness of the skin or swelling of the inguinal lymph nodes. There were no neurological signs of motor or sensory disturbances in her limbs. She could walk with one axillary crutch on one arm and could stand on her right leg. The joint motions of her right hip joint were − 20° extension, 30° flexion, 20° abduction, and 10° adduction. There were no differences in the circumferences of her lower limbs. All laboratory data were within normal limits including coagulation studies: white blood cells (WBC) 7300/uL, hemoglobin 12.8, platelet 22.6 × 104/μL, C-reactive protein (CRP) 0.12 mg/dL, aspartate aminotransferase (AST) 15 U/L, alanine aminotransferase (ALT) 11 U/L, blood urea nitrogen (BUN) 11 mg/dL, creatinine 0.50 mg/dL, activated partial thromboplastin time (APTT) 27.8 seconds, and prothrombin time-international normalized ratio (PT-INR) 0.97 INR).
A plain radiograph revealed expanded deformity of her right ilium with marginal sclerosis and calcification inside the bone (Fig. ). Computed tomography demonstrated a heterogeneous mass around the ilium and an area of destroyed bone (Fig. ). On magnetic resonance imaging of the same sites, the lesion showed predominantly isointense or high signals on T1-weighted images, and a mixture of low and high signal intensities on T2-weighted images. There was visible heterogeneous enhancement of the mass on a T1-weighted image following the intravenous injection of gadolinium-diethylenetriaminepenta-acetic acid (Gd-DTPA) (Fig. ).
Based on these findings, our differential diagnoses were giant cell tumor of the bone, aneurysmal bone cyst, or low-grade malignant tumor such as telangiectatic osteosarcoma. Therefore, an incisional biopsy of the lesion was performed. An intraoperative examination revealed that the lesion had a thick capsule; when the capsule was incised, abundant blood was drained from inside. The intraoperative hemorrhage from the incisional biopsy was 500 ml; then, our patient needed a blood transfusion because her hemoglobin level decreased to 6.7 mg/dl from the preoperative level of 12.8 mg/dl. A histopathologic examination revealed large amounts of old clotted blood within the lesion. The capsule of the lesion was composed of dense, fibrous, connective tissue (Fig. ). There was no evidence of neoplasia (Fig. ). Therefore, CEH was suspected.
We discussed the treatment options of the current case because there was no previous example of a huge CEH of bone. Surgical treatment was not recommended due to inaccessibility based on our experience of the intraoperative massive hemorrhage at the previous biopsy. We selected non-operative management for the current case. A consecutive selective arterial embolization program was started and performed five times (Fig. ). In addition, our patient was submitted to an off-label treatment with denosumab, which is a monoclonal antibody and acts as an inhibitor of the RANK/RANKL pathway and diminishes bone turnover. Denosumab was administered using the regimen for giant cell tumors of bone and continued for 3 months. However, the lesion continued to slowly grow, and neuralgia of the femoral nerve occurred (Fig. ), so we suspected that it might be a malignant bone tumor and decided to perform surgical treatment. We expected that we would be unable to prevent and control the operative bleeding in curettage or volume reduction surgery in this case. Therefore, we performed an internal hemipelvectomy, including the capsule of the mass 2.5 years after the incisional biopsy.
At the operation, the mass was completely covered in a capsule, with no evidence of invasion of the neighboring muscle. On macroscopic examination, the lesion was encased in a thick capsule (Fig. ). After the lesion was excised, a hip transposition was done as a limb salvage procedure (Fig. ). On microscopic examination, the mass was composed of a mixture of fibrin, blood clots, and hemosiderin deposition with a fibrous layer containing degenerated muscle fibers and new capillaries. A histopathologic examination confirmed the diagnosis of CEH consistent with the diagnosis indicated by the incisional biopsy.
External fixation of her pelvis and her right femur was applied for 6 weeks postoperatively. After removing the external fixation, partial weight-bearing was permitted for 4 weeks, and full weight-bearing with one crutch was allowed 14 weeks postoperatively.
There was no recurrence of CEH at the most recent follow-up of 1 year and 8 months postoperatively. She can ambulate with the assistance of one crutch and a heel lift of 5 cm (Fig. ). |
pmc-6122747-1 | A 68-year-old female underwent phacoemulsification + intraocular lens implantation + pars plana vitrectomy (PPV) + ILM peeling + 18% sulfur hexafluoride (SF6) tamponade in January 2016 due to an epiretinal membrane and a lamellar MH. Unfortunately, macular hole retinal detachment (MHRD) occurred one month after surgery. She received PPV + extended ILM peeling + silicone oil tamponade in February 2016 and underwent removal of silicone oil in October 2016. The retina had attached well, although the MH became refractory, and her best-corrected visual acuity (BCVA) was 20/500. She underwent two PPV + free ILM flap transplantation + 15% C3F8 treatments in April 2017 and July 2017, with unsatisfactory results. Due to her repeated surgeries, an autologous free ILM flap could not be harvested. We decided to perform a neurosensory retinal free flap transplantation for the repair of this refractory MH after discussion with the patient.
A standard 25-g, 3-port PPV (Constellation; Alcon) was performed under general anesthesia. Endolaser photocoagulation was applied to outline the retinal free flap at the temporal retina. The neurosensory retinal free flap was approximately twice the diameter of the MH. The retina was cut with vertical scissors along the inner edge of the laser spots and was gently dissected with back-flush needle irrigation until a neurosensory retinal free flap with a 2-MH diameter area was harvested. The infusion was stopped temporarily to prevent turbulent flow. A drop of whole blood was placed within the MH, and the neurosensory retinal free flap was then placed on the blood. We performed fluid-gas exchange and flushed the vitreous cavity with 15% C3F8 at the end of the surgery (Fig. ). All of the techniques were performed under standard 25-g, 3-port PPV. We did not use a bimanual approach under chandelier illumination (see Additional file ). The patient was instructed to maintain a prone position for 14 days postoperatively and to avoid any unnecessary movement.
Three weeks after surgery, optical coherence tomography (OCT) revealed closure of the MH. The flap was visible on OCT and had filled the MH without overlapping of the neurosensory retina. The 2-month postoperative OCT examination still showed the MH closure. The patient reported an improvement of visual acuity and a decrease in her scotoma area. The patient’s BCVA improved from 20/500 preoperatively to 20/50 at 2 months postoperatively. |
pmc-6122751-1 | A nine-year-old male child, with a prior history of heart murmur at birth, was
admitted to our hospital on July 2, 2017. He presented with minor symptoms,
comprising low activity, frequent cold compared to normal children, minor cyanosis
and tachypnea after exercise. At the time of presentation, the heart rate was 105
beats/min, while the respiratory rate and blood pressure were 20 breaths/min and
109/67 mmHg, respectively. Short systolic II/6 rough noises were heard at the left
margin of 4-5 ribs of the sternum, along with signs of loud P2 pulmonary
hypertension. Post-admission arterial blood gases were 47.3 mmHg (partial pressure
of oxygen = PO2) and 29.2 mmHg (partial pressure of carbon dioxide =
PCO2). The computed tomography (CT) scan of the large thoracic and
abdominal vessels showed the following findings: no aortic coarctation occurred; the
right pulmonary artery originated from the ascending aorta; and the defect, which
measured approximately 2.10-2.16 cm, was located between the pulmonary and the main
artery ( and ). Echocardiography (ECHO) result showed an aortopulmonary
window (type I). The abnormal pathway (width: 1.73-2.09 cm) was found between the
ascending aorta and the pulmonary artery. The estimated pulmonary artery pressure
was 71 mmHg, with shunting from left to right. The electrocardiography (EKG) result
also indicated that a high-voltage sinus rhythm occurred at the left ventricle and
that the T wave changed on the anterior wall. Preoperative pulmonary artery
resistance was of 7 Wood units, which was measured during the heart catheterization
exam. Alprostadil (10 µg, with 0.17 µg/min intravenous infusion) and
milrinone (0.375 µg/kg.min, with 24 h continuous intravenous infusion) were
administered to reduce the pulmonary arterial pressure. Blood gases were found to be
55.7 mmHg (PO2) and 29.6 mmHg (PCO2) when retested after 14
days of hospital admission. Meanwhile, EKG results again showed the aortopulmonary
window (type I) with an abnormal pathway (width: 1.73-2.09 cm) between the ascending
aorta and the pulmonary artery. The estimated pulmonary artery pressure was 63 mmHg,
with shunting from left to right. The precordial murmur was louder than that before
admission.
The patient underwent aortopulmonary septal defect repair under general anesthesia 15
days after admission. Aortic cannulation was placed below the right arm artery
(cannulation of the superior and the inferior vena cavae). The ascending aorta was
blocked at 35ºC degrees, longitudinally cut, and cardiac protective solution
[custodiol / histidine-tryptophan-ketogluterate (HTK)] was poured
under direct vision. The review indicated that the right pulmonary artery originated
from the ascending aorta. The defect, which measured approximately 2.0-2.5 cm, was
observed between the ascending aorta and the pulmonary artery. The opening of the
right pulmonary artery was connected to the defect. We used a polyester patch to
separate the right pulmonary artery from communicating to the aorta and to correct
the aortopulmonary septal defect (,
and ). The aortic incision was then sutured and the heart re-warmed to
37ºC. The ascending aorta was opened after full exhaustion, and the heart was
automatically resuscitated. The use of alprostadil and milrinone was continued to
reduce lung pressure. The tracheal intubation was removed 4 hours after anesthetic
awareness. Postoperative recovery was successful. The heart color ultrasound on the
10th day presented the following result: no residual shunt was
observed after the repair of aortopulmonary septal defect, the pressure in the
pulmonary artery was slightly elevated, and the estimated pulmonary artery pressure
was 42 mmHg (). After the surgery, the
patient refused re-catheterization and ultrasound was performed for measuring
pulmonary artery resistance. The patient was discharged from the hospital with
indication to take oral captopril. The patient exhibited no symptom of discomfort
during the follow-up visit. |
pmc-6122771-1 | In July of 2009, a 56-year-old man with a 40 pack-year smoking history presented with a low-grade papillary urothelial (transitional cell) carcinoma at the right ureteral orifice (primary bladder tumor). He also had a high-grade urothelial carcinoma of the renal pelvis with focal squamous differentiation and extensive renal parenchymal involvement. His right ureter was filled with tumor but did not show intramuscular invasion. Venous and lymphatic invasion of this tumor was absent. The patient first underwent transurethral resection of the bladder tumor (TURBT) of right ureteral orifice for the bladder carcinoma and underwent an ureteroscopic resection of the right ureter. The final pathology report characterized the bladder tumor as low-grade, non-invasive transitional cell carcinoma, and the ureteral resection demonstrated low-grade transitional cell carcinoma. In August 2009 a month later, the patient’s upper urinary tract tumor was removed by hand-assisted laproscopic neproureterectomy. The final pathology on this tumor was pT3 pN0 with negative margins. The patient then underwent an intense course of 6 rounds of bacillus Calmette-Guérin (BCG) treatment in an adjuvant setting, followed by maintenance BCG treatment for 3 years.
In 2016 the patient returned with a lung tumor that, on pathologic evaluation, resembled the low grade right ureteral orifice bladder tumor (transitional cell) from July 2009. The lung tumor was surgically removed. Because low-grade bladder tumors rarely metastasize to distant organs, we consented the patient for an Institutional Review Board–approved research study to investigate the origin of the lung metastasis and also to identify genetic changes that could represent a therapeutic target for any future recurrence or metastasis.
Hematoxylin and eosin (H&E) review of the formalin-fixed paraffin-embedded
(FFPE) tumor biopsy specimens showed more than 70% tumor tissue within all the samples sent for exome sequencing (Fig. ). The identified variants are listed in Additional file : Table S1, Additional file : Table S2, Additional file : Table S3, Additional file : Table S4. We focused on missense and nonsense somatic mutations present in the three tumor samples. Multiple variants were shared by these three tumors, and others were unique to each individual tumor, as shown by the Venn diagram and heat map (Fig. ).
Phylogenetic analysis indicates that the lung metastasis and primary bladder tumor are most closely related, and that the upper urinary tract tumor may have developed first (the distances between normal tissue and upper urinary tract tumor and normal tissue and primary bladder tumor are very similar, 168 gain/loss of single nucleotide variants (SNVs) versus 171 (Fig. , Additional file : Table S5). No mutations in a known oncogene or tumor suppressor gene are shared by all three tumors; however, the primary bladder tumor and the lung metastasis share known oncogenic mutations frequently found in bladder tumors, such as mutations in the KMT2D and RXRA genes. The mutational signatures, histomorphology, and distinct anatomic sites indicate that the upper urinary tract tumor and the primary bladder tumor likely are unrelated. Conversely, based on mutational profile and our model of tumor evolution, the primary bladder tumor and the lung metastasis may be related.
With evidence that the lung metastasis may be derived from the primary bladder tumor, we analyzed the somatic variants present in the primary bladder tumor and the lung metastasis that might be responsible for tumor initiation and progression. Table lists some of the important variants shared between the primary bladder tumor and the lung metastasis and also variants that are unique to the lung metastasis. The primary and the metastatic tumor have mutations in the KMT2D and RXRA genes. KMT2D encodes the protein histone-lysine N-methyltransferase 2D which is a tumor suppressor [, ]. KMT2D is mutated in 28% of bladder tumors []. RXRA, which encodes retinoid X receptor alpha (RXR-alpha), is mutated in 10% of bladder tumors []. The RXRA S427F mutation present in these patient tumors is a hotspot mutation that predominantly occurs in urothelial tumors [–]. Initial studies show that this particular RXRA mutation regulates lipid metabolism via peroxisome proliferator-activated receptor gamma (PPARG) activation []. Among the mutations unique to the lung metastasis, a clinically actionable, activating mutation in mTOR (C1483F) was identified. This particular MTOR mutation is also present in the primary bladder tumor (Table ), but at a very low frequency (1%). This C1483F mTOR mutation has been shown to activate mTOR downstream signaling via phosphorylation of p70-S6K and 4E-BP1 []. Development or selection of a subpopulation of cells with this activating MTOR mutation may be the driving event for lung metastasis within the primary bladder tumor.
We carefully examined the mutations present in the patient tumors based on the base substitutions C > A, C > G, C > T, T > A, T > C, T > G to identify how the patient tumors correlate with known mutational signatures representative of various biological processes. Figure shows the mutational landscape in all the three tumors. More C > T and T > C mutations were found in the three tumors. Next we developed a mutational signature for the patient by combining all the mutations present in these three tumors (Fig. ). This mutational signature is characterized by predominantly C > T and T > C mutations (Fig. ). This patient’s mutational signature resembles published mutational Signature 1A/B and Signature 5 []. Mutational signature 1A/B is related to the relatively elevated rate of spontaneous deamination of 5-methyl-cytosine, which results in C > T transitions and which predominantly occurs at NpCpG trinucleotides []. Signature 1A/B exhibits strong positive correlations with age in majority of cancers []. Signature 5, characterized by C > T and T > C mutations, is caused by tobacco carcinogens []. Our patient had a 40 pack-year smoking history, which suggests that tobacco use played a role in initiation of his tumors.
Using the Drug Gene Interaction Database [], we identified candidate drugs targeting 12 of the 100 genes with SNVs in the lung tumor (Additional file : Table S6). Several FDA-approved anti-cancer therapies were identified, including the RXRA agonist bexarotene and mTOR inhibitors, such as everolimus. We note that this analysis does not consider whether the variant is activating or deleterious, and all candidate therapies need to be evaluated. Primary culture of the lung metastasis was established in the laboratory. Since the lung metastasis has an activating MTOR mutation, we treated these cells with mTOR inhibitor everolimus at two concentrations (10 and 50 nM). The treatment showed a marked inhibition of mTOR activity and downstream signaling via two of its effectors, p70 S6K and 4E-BP1, at both concentrations (Fig. ); however, AKT activity increased with everolimus treatment (Fig. ). AKT can function both upstream and downstream of mTOR, but an increase in AKT activity could be a mechanism of resistance to the mTOR inhibitor.
Cytotoxicity study showed that at very low concentration (0.1 nM) everolimus reduces viability of these cells by about 60% (Fig. ), but even at a high concentration 40% of cells remain viable, indicating a cell population resistant to the drug. |
pmc-6122775-1 | A 1-day-old white female newborn was admitted to the pediatric intensive care unit of our hospital because of persistent severe obstructive respiration with cyanosis of unknown etiology. She had been born in a peripheral hospital with a gestational age (GA) of 39 weeks, 1 day, with a birthweight of 2790 g and Apgar scores of 5 and 7 at 1 and 5 minutes, respectively. Pregnancy was uneventful with normal routine prenatal ultrasounds. Directly after birth, the girl showed apneas with profound desaturations. Respiratory support with continuous positive airway pressure (CPAP) was started without improvement. Also, antibiotic treatment was started for a neonatal infection. On admission, her central temperature was 38.2 °C, her heart rate was 145 beats per minute, her blood pressure was 65/40 mmHg, her oxygen saturation level was > 99% on room air and nasal CPAP, and her positive end-expiratory pressure (PEEP) was 3 cmH2O. On physical examination, she had a few dysmorphic features: small fontanelle, downward slanting eyes, low-set left ear, retrognathia, and sandal gap of both feet. Her heart rate was regular with normal heart sounds. Her voice was hoarse, and with CPAP she did not have an inspiratory stridor and showed no signs of increased work of breathing, with normal air entry of both lungs without rhonchi or crackles. Her neurological evaluation revealed no abnormalities. We considered the following in the differential diagnosis: upper airway disorder, congenital heart disorder with spells, intoxication, infection, neurologic etiology, and central hypoventilation syndrome.
Additional examinations were performed. Her blood test showed normocapnia with balanced electrolytes and no signs of infection. Her urine toxicology test did not show any intoxication with amphetamines, benzodiazepines, methadone, or opioids. Her cardiac ultrasound showed a structural normal heart with no signs of pulmonary hypertension, and an ultrasound of her brain did not reveal any abnormalities, and cerebral function monitoring showed no epileptic activity. Because of the dysmorphic features, genetic testing was performed, which showed a normal DNA profile with 46 chromosomes.
On day 2, a flexible bronchoscopy was performed, which demonstrated large arytenoids with relatively short vocal cords with sufficient residual lumen of the trachea. Gastroesophageal reflux therapy was initiated with esomeprazole, with no effect. Weaning from CPAP failed because obstructive apneas with profound desaturations returned. Subsequently, a rigid bronchoscopy was performed and demonstrated ongoing obstruction of the laryngeal airway by enlarged arytenoids and still short vocal cords in combination with an anatomic small larynx but without subglottic, tracheal, or main bronchus abnormalities. These findings in combination with retrognathia explained the obstructive breathing.
In the following period, weaning from CPAP failed, and respiratory support needed to be intensified to noninvasive ventilation (PEEP 5 cmH2O, pressure support 12 cmH2O, respiration rate [RR] 30 breaths per minute). A second flexible bronchoscopy (day 23) was performed to exclude an upper airway obstruction. It showed findings similar to those before. Whether this contributed to the obstructive apneas could not be excluded, because the patient was examined in upright position and not in supine position. No laryngeal and subglottic abnormalities were seen on a magnetic resonance imaging (MRI) study of the mouth and mandible.
Besides the obstructive apneas, the patient also increasingly developed central apneas without any signs of an infection. She was treated once with caffeine (loading dose) with no effect, and therefore maintenance was not continued. PSG was performed using American Academy of Sleep Medicine scoring criteria to assess the degree and duration of central apneas and the ratio of central to obstructive apneas []. PSG registration (15 hours) including electroencephalography (EEG) was performed on day 39 (GA 44 weeks), which showed both obstructive as well as mixed apneas and some isolated central apneas (central apnea index [CAI] 0.1/hour). The mixed apneas were most prominent and started mostly as a central apnea (length up to 40.6 seconds) and merged into an obstructive apnea (Figs. and ) leading to severe desaturation. The mixed apnea index was 5 per hour with an average length of 34.7 seconds (8.2–88.5 seconds). Furthermore, the patient’s obstructive apnea index was 4.1 per hour. OAHI without mixed apneas was 5.7 episodes per hour, and total apnea-hypopnea index (AHI) was 10.7 episodes per hour. Mean blood oxygen saturation (SpO2) was 98.4%, average desaturation was 10.3%, and lowest SpO2 was 30%. The percentage of time spent with SpO2 < 90% was 2.7% (22.7 minutes). Additionally, continuous transcutaneous CO2 (TCCO2) was recorded, which revealed mean TCCO2 of 53.6 mmHg with a highest value of 68.6 mmHg. A capillary blood gas investigation revealed pH 7.36, partial pressure of carbon dioxide 56.3 mmHg, bicarbonate level of 31.1 mmol/L, and base excess 4 mmol/L. The results of the TCCO2 recording and capillary blood gas analysis confirmed the presence of significant chronic hypoventilation. EEG registration showed reactive rhythmic changes preceding and during a desaturation but without any epileptic activity.
We concluded that our patient had moderate OSA based on OAHI, but when the number and severity of mixed apneas were taken into account, we determined that she had severe OSA with an AHI > 10 episodes per hour. Moreover, central apneas were, in general, part of the prolonged mixed apneas, starting as a central apnea and merging into an obstructive apnea. On one hand, the number and duration of isolated central apneas were within the normal range for the patient’s age. On the other hand, the number of mixed apneas and their length were abnormal for her age, especially the long central apnea preceding the obstructive apnea. To rule out cerebral pathology as a cause of central apneas, MRI of the brain was performed, which showed no signs of cerebral abnormalities. Also, central hypoventilation syndrome was unlikely because PSG confirmed mixed apneas and the patient had shown symptoms of obstructive instead of central apneas since birth.
The prolonged mixed apneas caused profound desaturations associated with severe desaturations and bradycardia. Therefore, our patient needed respiratory support (CPAP PEEP 5 cmH2O, pressure support 6 cmH2O, RR 15 breaths per minute) and repeatedly failed to wean. Without having an explanation for the prolonged central apneas, we finally decided to treat the girl with a tracheostomy. On day 46, tracheostomy was performed, and the procedure was noncomplicated. A tracheostomy tube (Bivona; Smiths Medical, Ashford, UK) with an internal diameter of 3.5 mm was inserted.
After surgery, no more obstructive or central apneas were observed clinically. A poly(somno)graphy (without EEG) was performed 4 weeks posttracheostomy and revealed only short central apneas (average length 6.5 seconds, longest 11.1 seconds) appropriate for her age. No more mixed or obstructive apneas and no profound desaturations were seen (AHI 3.4 episodes per hour, CAI 2.1 episodes per hour, average saturation 98.4%, oxygen desaturation index 9.1 episodes per hour). She was rapidly weaned from the ventilator and transferred to the pediatric ward.
Over a period of time, the patient’s auricular anomalies became more prominent, and she was diagnosed with deafness. In combination with dysphagia and developmental delay, CHARGE syndrome (coloboma of the eye, heart defects, atresia of the choanae, retardation of growth and development, genital and/or urinary abnormalities, and ear abnormalities and deafness) was considered. Whole exome sequencing (WES) was performed again, and coding regions of CHD7 (chromodomain-helicase-DNA-binding protein 7) were screened for mutations, which showed a de novo mutation deep in the intron (c.5405-17G>A), which confirmed the diagnosis of CHARGE syndrome []. |
pmc-6122888-1 | A male Caucasian patient, 12 years old, was referred by his orthodontist for evaluation of his TMJ, since the panoramic radiography showed bilateral flat condyles. Clinically, the patient showed micrognathia, retrognathia and anterior open bite (Figures 1A and D). Functionally, mouth opening, speaking and chewing were normal. During opening, closing and lateral excursion, no sounds, discomfort or symptoms were present. Since the patient did not complain of any symptoms or difficulty in lateral excursions, a three-dimensional computed tomography was requested. He was referred to a rheumatologist who requested several laboratory tests. Of these, the only positive result was for antinuclear antibody (ANA): 1:80 (reference value – 1:40), by the indirect imunofluorescence method.
The clinical diagnosis was inconclusive for JIA, systemic lupus erithematosus, or any other disease. However, the 3D-computed tomography findings showed major erosion of the head of both condyles (). Facial morphological alteration, retrognathia, micrognathia and condyle erosion, even without inflammatory signs and no pain, led to a JIA diagnoses. No invasive treatment was performed but the patient underwent annual follow-up.
After 2 years, the patient was examined and no clinical symptoms were observed. At this time, a new three-dimensional computerized radiography was requested. The erosion process seemed to be stabilized. The patient had no difficulties in lateral excursions, and no pain or signs of inflammatory process. The only difference was in the ANA laboratory test, showing positive result: 1:60 (reference value: 1:40), by the indirect imunofluorescence method.
Since the patient had no alterations in his radiographic or clinical status, no drugs were prescribed. Although the ANA reduced in the last 2 years, we asked the patient to be examined again by a rheumatologist. The diagnosis was inconclusive one more time.
Between the first appointment and the last clinical examination, magnetic resonance imaging was performed to evaluate bone and soft tissues changes, and there were no morphological modifications of the condylar region, and no modifications of the patient profile and anterior open bite. Since the aim of the treatment of patients with JIA is the control of the pain and inflammatory activity, no drugs were prescribed.
After 11 years since the first consultation, no signs of evolution of the disease was observed and the patient did annual check-ups (clinical and radiographic examination). |
pmc-6122909-1 | A 23-year-old man was admitted in the emergency department after a frontal car
collision. He had suffered severe blunt trauma, which included cervical
subcutaneous emphysema, bilateral pulmonary contusion, left hemothorax,
pneumomediastinum and complex fractures of both femurs. He was in hemorrhagic
shock and was immediately taken to the operatory room. After external fixation
of both femurs and reaching hemodynamic stability, he was transferred to the
Intensive Care Unit. The following morning the presence of a loud holosystolic
murmur was noted. The 12-lead electrocardiogram showed only sinus tachycardia. A
transthoracic and later a transesophageal echocardiogram (TEE) were performed
and both demonstrated a large muscular ventricular septal defect, located in the
mid anteroseptal segment with signs of dissection through the basal septum
(). It measured 19 mm on the
left ventricular (LV) side and 7 mm on the right ventricular (RV) side. The peak
left to right shunt gradient was estimated in 84 mmHg and the Qp/Qs ratio was
estimated in 1.8/1.0. Cardiac catheterization showed limited hemodynamic
repercussion (systolic pulmonary artery pressure of 35 mmHg and a Qp/Qs ratio of
1.9/1.0) and the patient remained clinically stable, so a conservative strategy
was decided at that time to allow the edges to heal and create a more delimited
defect.
He was released after recovering from orthopedic surgery.
Three months later the patient was reevaluated and remained asymptomatic. He
repeated cardiac catheterization, which showed a Qp/Qs ratio of 2.95/1.0.
Because the shunt increased significantly, it was decided to close the defect
percutaneously.
The procedure was done under general anesthesia and guided by transesophageal
echocardiography. Cardiac catheterization was performed using the right femoral
artery (6-Fr sheath) and vein (7-Fr sheath) and unfractionated heparin was
administered. Angiogram of the LV confirmed a VSD with an oblique entry from the
LV into the right ventricular outflow tract. The VSD was crossed using a
retrograde arterial approach with a floppy guidewire, which was advanced into
the pulmonary artery. The guidewire then snared and brought out the femoral
venous sheath. This created an arteriovenous loop to allow the delivery of the
closure device. A NuMed sizing balloon catheter was subsequently utilized to
measure the defect, but it was not possible to maintain it steady. Therefore,
the echocardiographic calculations were used to choose the device size. An 8-mm
Amplatzer septal occluder was first selected and loaded into the sheath. The
device was advanced across the VSD, but prolapsed back to the RV when it was
being released. After this failed attempt, a slightly different approach was
used. The VSD was crossed once more using the guidewire, this time in the
opposite direction into the right subclavian artery. Once again, it was snared
to make an arteriovenous loop, but on this occasion pulled out through the
femoral arterial sheath. For this second attempt, it was decided to employ a
10-mm Amplatzer septal occluder. The device was advanced through the venous
sheath and this time was successfully placed (). LV angiogram after the procedure revealed a mild residual
shunt and the Qp/Qs ratio reduced to 1.53/1.0.
A transesophageal echocardiography was repeated a month after the procedure,
which showed the device well adapted to the defect. Nevertheless, a residual
shunt remained in the superior border of the device with a peak gradient
estimated in 90 mmHg ().
Another complication of this procedure was the appearance of transient
self-limited hemolysis. Initial blood analysis showed a LDH value > 2000 UI/L
and haptoglobin < 6 mg/dL. The condition remained stable and resolved without
the need of blood transfusions.
The patient continued to be asymptomatic and has returned to his previous
professional life. |
pmc-6123144-1 | The patient detailed in this report is a 27-year-old pregnant female. She was simulated for treatment to her grade 3 astrocytoma resection cavity during gestational week 17. The patient was prescribed 50.4 Gy in 28 fractions to a primary target volume to be followed sequentially by a 9 Gy boost in five fractions to a smaller volume. Medical images with delineated target volumes are shown in Fig. . Standard departmental brain planning constraints were ordered for this patient, including D(0.03 mL) < 54 Gy for the brainstem, optic chiasm, and optic nerves; mean dose < 35 Gy and D(0.03 mL) < 40 Gy for the cochleae; D(0.03 mL) < 7 Gy for the lenses of the eyes; and D(0.03 mL) < 45 Gy for the spinal cord. At least 95% of the target volume was covered with 99% of the prescription dose in each treatment plan, and target hotspots were maintained less than 110%.
Fetal dose was assessed at four points of interest bracketing the distances where the fetus could conceivably be located during the patient's course of treatment: (a) the pubic symphysis, (b) the uterine fundus on the date of simulation, (c) the umbilicus, and (d) the uterine fundus projected to the end of the treatment course. At the time of CT simulation, the distances to the patient's umbilicus and pubic symphysis were measured from a fixed radio-opaque marker placed on her chin. Palpation of the uterine fundus was not achieved in our department; instead, a brief consultation with diagnostic radiology immediately prior to her CT simulation measured her uterine fundus to be 4 cm inferior to her umbilicus using a portable ultrasound unit. The total distance from each point of interest to the target volume was later determined by measuring the distance between the radio-opaque marker and the segmented target volume in the simulation CT image. Finally, we assumed superior progression of the patient's uterine fundus at a rate of 1 cm/week and that the patient would be treated during gestational weeks 19–25. Table shows the distances from the target volumes to the points of interest.
Our institution's Health Insurance Portability and Accountability Act (HIPAA) Privacy Officer has reviewed this manuscript to ensure compliance with our institution's standards for protected health information. Institutional Review Board review was not required. |
pmc-6123333-1 | We explained the case report and publication process to the patient and obtained his permission to publish this report.
A 61-year-old man was examined by a local physician for a chief complaint of constipation with abdominal pain. Computed tomography (CT) showed that the rectosigmoid colon wall was thickened, regional lymph nodes were swollen, and the obscure space-occupying lesion (SOL) was detected at S8, especially localized into the portal vein. He was admitted to our hospital for further treatment. Colonography revealed a type 3 tumor in the rectosigmoid colon. Laboratory data demonstrated elevated tumor marker levels (carcinoembryonic antigen, 74.4 ng/mL; cancer antigen 19-9, 53.5 U/mL). Because of obstructive colitis that was associated with his massive cancer, emergency colonostomy was performed. Prior treatment with systemic chemotherapy was performed for curative surgery with suspicion of PVTT: 6 courses of mFOLFOX6 + panitumumab chemotherapy (panitumumab was administered as a 60-min intravenous infusion before oxaliplatine at a dose of 6 mg/kg, leucovorin at 200 mg/m2, oxaliplatin at 85 mg/m2, and bolus fluorouracil at 400 mg/m2, all on day 1, followed by 2400 mg/m2/46 h, each 14-day cycle) were administered. Six months after admission, laparoscopic anterior resection was performed. On pathological assessment, the tumor was classified as a moderately differentiated adenocarcinoma (Rs, type 2, 60 × 40 mm in size, whole-circumferential growth, SS, P0, H0, M[−], ly1, v1, N2, D2, aw[−], ow[−], ew[−], CurA), and the final pathological stage was IIIb. Six courses of mFOLFOX6 chemotherapy (leucovorin at 200 mg/m2, oxaliplatin at 85 mg/m2, and bolus fluorouracil at 400 mg/m2, all on day 1, followed by 2400 mg/m2/46 h, each 14-day cycle) were administered as adjuvant chemotherapy, during which tumor marker levels were elevated. On positron emission tomography (PET), abnormal accumulation (maximum standardized uptake value [SUVmax], 5.8) at P8 was detected (Fig. ). CT showed low intensity in the portal vein (Fig. a, b). Magnetic resonance imaging (MRI) with gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid revealed that the nodule in the portal vein extended from segment 8 (S8) to S5 and had a ring-like high contrast (Fig. a, b). Therefore, right hemihepatectomy was performed (operation time, 364 min; bleeding volume, 300 mL). On histopathological analysis, the PVTT was from colon cancer, which had not invaded the hepatic parenchyma. The cut surface was free from tumor invasion (Fig. ). The patient had no specific postoperative complications, and he was discharged 13 days after the operation. Four months after hepatectomy, paraaortic lymph node recurrence occurred. The patient is currently undergoing systemic chemotherapy.
Venous tumor thrombosis occasionally occurs in patients with renal cell carcinoma, pancreatic carcinoma, gastric carcinoma, hepatocellular carcinoma (HCC), adrenal cortical carcinoma, and testicular carcinoma [–]. To the best of our knowledge, it is rare for a case to exhibit portal vein tumor recurrence without liver parenchymal invasion following surgical resection. In general, the recurrence sites of colorectal cancer are the lungs and liver, and in the absence of several risk factors for recurrence, curative resection could provide a good long-term prognosis []. Otani et al. reported 43 cases of colorectal cancer with adjacent drainage vein tumor thrombosis, and aggressive surgical resection was considered to improve long-term prognosis []. In our case, the primary rectal carcinoma itself did not show massive venous (v1) and lymphatic (ly1) invasion; therefore, even after systemic chemotherapy, PVTT could have occurred through this vascular invasion, or CTCs may have been implanted into the portal vein wall.
In the case of HCC, tumor thrombosis is often detected via pathological assessment after surgery, and the presence of portal vein invasion has been reported as a risk factor for recurrence [, ]. Surgical removal of the tumor thrombosis was the most effective curative treatment for HCC []. However, transcatheter arterial chemoembolization can be considered in patients with severe liver failure or a highly advanced tumor stage [, ]. The mechanism of PVTT is different between HCC and colorectal liver metastasis (CRLM). PVTT from HCC is derived from direct invasion, whereas CRLM is considered based on whether direct tumor invasion is through the blood stream or indirect tumor invasion through CTC implantation. The prognosis of patients with venous tumor thrombosis of colorectal cancer is unclear; however, evidence of hepatectomy for CRLM is well established []. In HCC, obstructive tumor thrombosis of the bile duct and portal vein thrombosis have been reported, and the dismal prognosis of these conditions could be beneficially changed with curative surgery []. Given that metastatic PVTT could be curatively resected, aggressive surgery could potentially be an efficient treatment.
In patients without other distant metastases and with good performance status, aggressive surgical resection should be considered. In our case, early recurrence was noted at the paraaortic lymph nodes, and systemic second-line treatment is currently being administered. Cohen et al. reported that during treatment for metastatic colorectal cancer, the number of CTCs is an independent risk factor for poor overall survival (OS) and progression-free survival. In patients with colorectal metastasis, those with unfavorable CTCs had a dismal prognosis of 3.7 months of OS compared to those with a low number of CTCs with 11.0 months of OS []. Even after curative surgery, intrahepatic recurrence occurred approximately 60% []. Until now, the relationship between CTC and CRLM remains unclear. Some studies have demonstrated that CTC is associated with long-term survival in various cancer types [–]. Given that most metastatic forms of colorectal cancer are liver metastasis, CTCs could be implanted into the portal vein, consequently resulting in PVTT. Early detection of recurrent disease when traditional clinical indicators, such as radiological findings are negative, is important to improve patient survival. Therefore, CTC investigation would be a breakthrough in cancer metastatic mechanism. In our case, the relatively better survival of 15 months following the first surgery could be achieved because of repeat surgical resection combined with systemic chemotherapy.
Radiological findings of tumor thrombosis are quite similar to those of venous thrombosis, but the precise diagnosis is quite difficult with dynamic-enhanced CT alone. Recently, PET yielded good efficacy for detecting venous tumor thrombosis when using intense radiotracer accumulation [, ]. Additionally, MRI plays an essential role in differentiating thrombosis and tumor thrombosis, and T2- and diffusion-weighted imaging were shown to be particularly accurate for diagnosis []. PET-CT has an important role in diagnosing cancer recurrence and characterizing a thrombus using abnormal accumulation (SUVmax) over time. The mean SUVmax values for bland thrombosis and tumor thrombosis have been shown to be significantly different. For differentiating tumor thrombosis from bland thrombosis, the measurement of SUVmax (cutoff value of 2.25) on PET is useful []. In the present case, tumor marker levels remained elevated during systemic chemotherapy. The diagnosis of tumor thrombosis was made based on a SUVmax value of 5.8 on PET-CT. PET-CT enabled the detection of tumor thrombosis recurrence by revealing an elevated SUVmax. |
pmc-6123337-1 | A 13-year-old girl presented with abdominal pain and bloody stool. For 3 months, she had repeated appearance of the abdominal pain and spontaneous disappearance of the symptom. At the beginning, the symptom was not strong and she had not seen a doctor. Her abdominal pain gradually got worse, and she determined to come to our hospital after she often had bloody stool. Imaging study showed a mass including the fecalith that occupied her pelvic and right lower abdominal cavity (Fig. ). Drainage of the abscess and appendectomy were performed by the preoperative diagnosis of an acute appendicitis with an appendiceal mass (Fig. ). Although the body of the appendix looked intact as well as the ileum and the cecum, the histopathological examination revealed PAA in the tip of the resected appendix. A radical operation for the residual tumor of PAA in the pelvic cavity was planned.
She then received the whole mass resection, ileocecal resection with lymph node dissection. At the first operation, we speculate that we resected body of the appendix but left the most of the mass and the tip of the appendix. Therefore, the mass which we resected in the second operation was derived from the tip of the appendix. The masses were tightly adherent with infiltration into the sigmoid colon, uterus, and right ovary. These organs were all dissected, and subsequent sigmoid colostomy was performed (Fig. ). We preserved the left ovary for her fertility. The pathological findings demonstrated negative margins and no lymph node invasions, and final pathological stage was pT4(SI)N0M0, stage II (TNM-7th edition 2009). Postoperative course was uneventful.
After the operation, she received the chemotherapy with 6 cycles of 5-fluorouracil (5-FU), leucovorin (LV), and oxaliplatin (mFOLFOX6) and subsequent 6 cycles of simplified LV and 5-FU (sLV5FU2). The patient is doing well till today on follow-up without progression of the disease 5 years after the operation. We performed the stoma closure operation 2 years after the tumor resection.
Primary adenocarcinoma of the appendix (PAA) is an extremely rare disease in clinical practice []. There are no established risk factors for the development of appendix cancer. Malignant appendix tumors most often present with acute appendicitis and are diagnosed incidentally at histologic assessment of the surgical specimen. Appendix cancers may also be asymptomatic and be found incidentally. When symptoms are present, the disease process is often advanced [].
Colorectal carcinoma in children, although rarely discovered, comprises approximately 1% of pediatric neoplasm []. It is also the most common primary gastrointestinal malignancy in children. However, due to the low awareness of the disease, diagnosis is usually delayed until the disease is in the advanced stage, causing prognosis to be extremely poor compared with that of adults [].
In addition, there is no consensus for the goal of the operation for PAA in children. Generally, functional preservation operation has often been emphasized in pediatric surgery. Therefore, it is not easy to decide the grade of the extension in the radical operation for colorectal cancer such as PAA in children as there is very little reports being published. Furthermore, we have no guideline about the postoperative treatment protocol such as the resume of the chemotherapy.
We reviewed some recent literature which has been published since 2000 and found seven cases of the colorectal adenocarcinoma in children who is under 15 years old (Table ). The tumors originate from the ascending colon in two cases, transverse colon in one case, descending colon in two cases, and rectum in two cases. Most of the cases received adjuvant chemotherapy. Although three cases had good postoperative courses, the patients in four cases died after the radical operation. The poor prognosis of the primary colorectal carcinoma in children has been re-recognized by this review [–].
Furthermore, Table shows the reports of primary adenocarcinoma of the appendix in the recent 10 years [–]. The mean age at presentation for PAA is about 50 years. There is no sex predominance. Most PAAs are well differentiated, are slowly growing, and have pushing rather than infiltrating margin. The traditional treatment is right hemicolectomy. However, in the case of intra-abdominal metastasis, the treatment consists of aggressive debulking followed by chemo-radiotherapy along with it.
In this report, we demonstrate a case of PAA with local invasion into adjacent organs in a child who was initially diagnosed as having an acute appendicitis. We performed radical operation and adjuvant chemotherapy. The patient is doing well without progression of the disease after 5 years. Although little has been understood about PAA, we believe our experience may provide new insights into the guideline of the standard treatment for PAA in children. |
pmc-6123917-1 | A nine-year-old Caucasian male with no significant past medical history, family history, medications, or allergies presented for an adenoidectomy due to hypertrophy. Two days later (day one of illness), he had a low-grade fever for 2 days, followed by 2 days of headache. Transient abdominal pain was noted on day five. On day six, he had swelling, warmth, tenderness, and decreased range of motion of his left knee and left foot. He was unable to walk and presented to the Emergency Department. Scattered petechiae were noted on his lower legs bilaterally. Left knee and foot x-rays were negative for fracture. CRP was 1.2 mg/dL (nl < 1) with a normal serum creatinine, complete blood count, and urinalysis. He was discharged home with supportive care for presumed Henoch-Schonlein Purpura.
On day nine, he saw his primary care physician (PCP) for follow-up. He continued to have intermittent swelling of his bilateral knees and ankles, low-grade temperatures (99-100F), and a non-blanching rash on his lower extremities. A slightly red posterior oropharynx was noted, however rapid throat swab for Group A streptococcus was negative. Later that day, he developed severe abdominal pain and returned to the Emergency Department.
Upon arrival, he was afebrile and received fentanyl for pain control. Laboratory results included CRP 5.1 mg/dL (0–1), ESR 10 mm/hr. (0–15), ASO antibody 530 IU/mL (0–200), Anti-DNase B antibody 588 U/mL (0–170), negative ANA, RF 6.5 IU/mL (0–13.9), C4 44 mg/dL (14–44), C3 183 mg/dL (82–167), and positive Rhinovirus/Enterovirus from a nasal washing. Gamma-glutamyl transferase level, complete metabolic panel, complete blood count, blood cultures, and urinalysis were all unremarkable.
Abdominal ultrasound suggested mild bowel wall thickening in the left upper quadrant at the site of point tenderness. An echocardiogram, ordered by his PCP to rule out acute rheumatic fever, revealed dilation of the left main coronary artery (LMCA: 5.32 mm, Z score + 4.25) and left anterior descending coronary artery (LAD: 3.51 mm, Z score + 2.64) with no other abnormalities (Fig. ). EKG was unremarkable. He ultimately had a skin biopsy of his lower extremity rash that revealed leukocytoclastic vasculitis with positive IgA staining (Fig. ).
The patient met criteria for HSP given his palpable purpura, abdominal pain, arthritis and skin biopsy. He did not meet criteria for typical (or atypical) KD, given his lack of persistent fever. Nevertheless, KD treatment was initiated, per Infectious Disease and Cardiology, given the potential sequelae of untreated inflammatory-mediated dilation of the coronaries. He received high dose aspirin, 2 g/kg of IVIG over 10 h, and 5 mg/kg of infliximab as per our hospital protocol. His CRP normalized and his abdominal pain improved. He was discharged with Cardiology follow-up for an echocardiogram and a PCP appointment to monitor blood pressure and kidney function. Of note, Group A streptococcus culture turned positive during his admission and thus amoxicillin was started.
By day 17, his arthritis resolved, his rash improved, and his energy and appetite returned. Repeat echocardiogram on day 21 showed persistent dilation of his LMCA (5.24 mm, Z score + 3.91) and LAD (3.74 mm, Z Score + 3.07). He remained on daily low dose aspirin until his next echocardiogram 3 months later revealed normal coronary dimensions. He had no evidence of hypertension, hematuria or proteinuria. |
pmc-6123928-1 | We present a case of a healthy 26-year-old female of Philippine origin who presented to our outpatient clinic with a progressive eruption of cutaneous papules and nodules. Her medical history reported nodules/papules on the hands 7 years before, for which she successfully received prednisone in the Philippines with only a few residual lesions. Recently, over a course of 2 months, she noticed an increasing number of cutaneous nodules and papules; starting on her hands subsequently spreading to her wrists and forearms. Pain arose from these nodules when bumped onto a surface. Simultaneously, our patient suffered from pain and stiffness in hands, feet, elbows, shoulders and knees. Over these 2 months she felt increasingly tired. Our patient also reported a red, warm rash covering her cheeks at the start of the symptoms, which had subsided by the time of investigation. There were no signs of systemic illness, inflammation or preceding infections.
Three weeks before our initial investigation she had tried prednisone 30 mg for 3 days. Since then, she reported the occurrence of new skin lesions, a swollen face and palpitations. At the time of investigation she only sporadically used NSAIDs to control the pain.
On clinical examination numerous firm, either reddish-brown or skin-colored papules and nodules were seen and felt mainly on the hands and forearms, varying in size from 0.5 to 1 cm (Fig. ). In addition, papules were found in pre-existing scars on the left shoulder and both knees. Apart from these papules and nodules, a few patches of grouped, flat, red/brown papules were seen on the inner side of the upper arms, on the hips, thighs and neck (Fig. ).
At the time of examination, pain was present on palpitation of many of the small hand joints [distal interphalangeal (DIP), proximal interphalangeal (PIP) and metacarpophalangeal (MCP)], wrists, elbows and knees. Arthritis was present in several PIPs and in the wrist. Furthermore, her face appeared to be swollen. There was no lymphadenopathy. Laboratory examination revealed a normal level of ESR (erythrocyte sedimentation rate), negative antinuclear (ANA) and anti-cyclic citrullinated peptide (anti-CCP) antibodies and the IgM Rheumatoid factor was borderline positive (6.3, ref < 5.0 IU/ml). Other serum and urine laboratory tests were unremarkable. Radiographs of the hands and feet, however, showed impressive erosions and destruction of many small joints (Fig. ) and a radiograph of the lungs showed a closed right pleural sinus.
Punch biopsies were taken from the nodules on the hands and from the plaque on the upper arm. Initially, a histological pattern of dermal scarring/fibrosis was found, without histological features of multicentric reticulohistiocytosis. However, additional biopsies showed CD-68 positive macrophages and eosinophilic granulocytes between the collagen fibers in the dermis, in agreement with a form of non-Langerhans histiocytosis (Fig. ).
The PET/CT scan revealed FDG-avidity in the muscles of the thighs and buttocks, the corresponding points were painful to the touch according to our patient. Also, painful joints showed slightly more uptake when compared to the representative opposite joints.
Because of the reported association with underlying malignancies [–], additional investigations were performed. Malignancy became very unlikely after laboratory tests, ultrasound of the abdomen, mammography, PET/CT scan and an additional MRI scan for further imaging of suspicious lesions in one of the mammae.
The initiated therapy consisted of prednisone, methotrexate and risedronate together with folic acid and calcium/vitamin D. This choice was based on an overview of different treatment regimens and outcomes published recently []. Prednisone was started on 30 mg and tapered to 7.5 mg in 9 weeks. Methotrexate was introduced to a final dosage of 25 mg/week over 8 weeks. Risedronate was chosen as bisphosphonates are considered to be of additional benefit in the treatment of multicentric reticulohistiocytosis []. Since the patient is in her reproductive age, we chose the bisphosphonate with the least implications for future pregnancy.
After 8 weeks of therapy, the joint pain had subsided and our patient was better able to move without pain. The skin lesions, however, persisted over these first 2 months of therapy. A few months later, arthritis of the right elbow was identified but the skin lesions seemed to improve and there were less complaints of itchiness. |
pmc-6123933-1 | A 52-year-old male from southwest China presented with obstructive jaundice for 3 years, melena for 5 months and hematemesis for 10 days. The patient had been diagnosed with type 2 diabetes mellitus for 4 years, which was treated with metformin. The patient was a chronic tobacco (10 cigarettes per day) and alcohol consumer over the previous 20 years but had quit smoking and drinking for the past 3 years. Three years prior to admission to our hospital, he developed obstructive jaundice, which was investigated with abdominal computed tomography (CT) and revealed multiple hypodense lesions in the liver and pancreatic head mass. He underwent cholecystectomy, choledochojejunostomy and biopsies from the liver and pancreatic lesions. Histopathology revealed chronic cholecystitis with lymphocytic, plasmacytic and eosinophilic infiltration of the gallbladder, liver and pancreatic parenchyma.
The physical examination was unremarkable (height − 165 cm, weight – 50 kg). Laboratory tests revealed hemoglobin levels of 75 g/L, a platelet count of 80 × 109/L, 30.0 g/L albumin levels, and serum potassium levels of 3.20 mmol/L (Table ). The fecal occult blood was positive.
On the day of admission, the patient developed repeated painless hematemesis of about 2100 mL, which was associated with hypotension and tachycardia. He was resuscitated with intravenous, blood and norepinephrine infusions. Laboratory tests revealed hemoglobin levels of 47.5 g/L, platelet count levels of 38 × 109 L and serum albumin 25.8 g /L. The day after admission, the patient again developed hematemesis of about 500 mL, for which he was treated with somatostatin, terlipressin and pantoprazole infusion. Sengstaken-Blakemore tube were placed to hemostasis by compression and tube feeding hemostatic medicine. After 4 days of medical intervention, the patient’s gastrointestinal bleeding gradually stopped. Esophagogastroduodenoscopy revealed a duodenal ulcer (A1 stage) with active bleeding, gastric mucosal erosions and esophageal varices (mild). Contrast enhanced computed tomography of the abdomen with three-dimensional reconstruction exposed multiple nodular dense shadows with dilatation of the main pancreatic duct in the tail region (Fig. ). Images of the liver showed numerous hypodense nodules with mild contrast enhancement, ascites and intrahepatic bile duct dilatation (Fig. ). Additionally, there were multiple enlarged lymph nodes in the hepatoduodenal ligament around the abdominal aorta (Fig. ) and mesenteric lymph nodes with bilateral pleural effusion (Fig. ). In view of the liver disease with portal hypertension and esophagogastric varices, a transjugular intrahepatic portosystemic shunt (TIPS) procedure was performed under local anesthesia and regional portal hypertension, splenic vein and portal vein obstruction were detected. Subsequently, the patient re-bleed both 14 days and 20 days after admission, about 600 mL and 400 mL, respectively. The patient was treated with somatostatin, pantoprazole infusion and blood transfusion. Gastroscopy identified an ulcer (1.5 cm × 1.2 cm) in the anterior wall of the duodenal bulb that was not actively bleeding (Fig. , Fig. ). Pathological examination of the ulcer biopsy verified a moderate degree of chronic mucosal inflammation.
When investigating the recurrent bleeds, serum IgG4(0.035–1.500 g/L)and IgG(8~ 15.5 g/L)were found to be 29.200 g/L and 24.50 g/ L respectively and IgG4 disease was suspected (Table ). The patient’s prior surgical pathology specimens were retrieved for IgG4 immunohistochemical examination. Immunohistochemical staining revealed increased IgG-positive and IgG4-positive plasma cells in the liver lesions (IgG4 positive cells 30–60/ high power field (HPF); Fig. ), pancreas (IgG4 positive cells 30–80/HPF; Fig. ) and gallbladder (IgG4 positive cells 30–80/HPF; Fig. ). Staining of the duodenum ulcer biopsy also showed more than 100 IgG4-positive cells per HPF (Fig. ). Based on these findings, a definitive diagnosis of IgG4-RD was made.
The patient was administered 40 mg/d prednisone intravenously for 7 days without any side effects followed by oral prednisolone 40 mg/d for 1 week. Laboratory tests indicated a reduction in the serum IgG4 levels 8 days after initiating prednisone but the liver function continued to be impaired (Table ). As the patient improved symptomatically, he was discharged on a regime of prednisolone and mycophenolate mofetil.
Since discharge until the time of writing, during the 11 monthly visits since starting steroid therapy, laboratory tests indicate significant improvements in the patient’s serum IgG4 subtype, liver function and hemogram tests (Table ). |
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