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pmc-6109567-1 | An 82-year-old African American female with history of hypertension, chronic active smoker for 60 years along with prior surgical history significant for a laparotomy more than 20 years previously for unknown reason who was initially admitted to the medical service after a fall. She had a long history of nonspecific lower abdominal pain. As per her family, she had not seen a doctor for 10 years and never had a colonoscopy. She reported unintentional weight loss. Vital signs at the time of presentation were stable. On physical examination, she appeared cachectic and dehydrated. Her abdomen was soft, non-tender with audible bowel sounds. Mild right lower quadrant tenderness was noted. Labs were significant for microcytic hypochromic anemia and urine analysis positive for leukocyte esterase. Liver function test was normal. Chest X-ray showed cardiomegaly. Abdominal US revealed mild ascites and dilated common bile duct to 1 cm. The patient was admitted to medical service with a diagnosis of dehydration, failure to thrive, and for work-up of an occult gastrointestinal malignancy. She was scheduled for EGD and colonoscopy by gastroenterology team. In addition to all of this, her CEA was 12.2 ng/ml (normal less than 3 ng/ml). While the patient was on the medical service, her hemoglobin dropped to 6.2 gm/dL requiring blood transfusions. During the second unit of blood transfusion, the patient became hypoxemic and tachypneic. She was transferred to Medical Intensive Care Unit (MICU) and subsequently intubated for acute respiratory failure. Chest X-ray at this point showed bilateral infiltrates, and the patient was started on IV antibiotics for possible pneumonia. The scheduled GI procedures were cancelled due to critical health status. She had echocardiography in MICU which revealed mitral stenosis and severe pulmonary hypertension, with normal ejection fraction. Her respiratory status improved, and she was transferred back to medical floor after staying four days in MICU. She also had urine culture which grew klebsiella. Three days later after being transferred from MICU, she developed abdominal distension. A CT scan of the abdomen without contrast was obtained which revealed gastric, small bowel, and colonic distension. There was copious amount of stool in the colon. She was transferred to the surgical service for management of possible ileus/stool impaction pending colonoscopy to rule out colonic lesion. She was managed with nil per os, nasogastric tube suction, intravenous fluid hydration, and enemas. Nasogastric tube output was minimal but the patient's abdomen remained distended while on surgical service. The patient became hypotensive and tachycardic and less responsive. After fluid resuscitation, another CT of the chest and abdomen with oral and intravenous contrast was performed one week from prior CT, which revealed persistent dilation of the stomach, small bowel, and large bowel, a left colonic mass, and large amount of retroperitoneal free fluid in the region of the duodenum and pancreas (Figures and ). She was taken to the operating room for exploratory laparotomy. A midline laparotomy was performed, and numerous adhesions from the previous laparotomy were seen. The patient had a high-grade small bowel obstruction with a transition point in the mid ileum caused by adhesions. Lysis of adhesions was performed. There was a large left descending colonic mass invading the lateral abdominal wall causing partial large bowel obstruction. The transverse colon was attached to the left colon mass with adhesions, creating a space through which there was herniation of dilated small bowel. However, this did not cause an obstruction. These dilated bowel loops were reduced. Because of the finding of free air in the retroperitoneum of the upper abdomen, we decided to explore that area. Generous kocherization of the duodenum was performed. The head of the pancreas and hepatic flexure were mobilized and found to be normal. With further mobilization of the duodenum, a perforated duodenal diverticulum was noticed in the third part of the duodenum. There was a leak of bile in the area. There was extensive retroperitoneal necrosis extending across the upper abdomen to the tail of the pancreas. The duodenal diverticulum was broad based, inflamed, and closely attached to the superior mesenteric artery. The diverticulum was dissected off, stapled, and sent for pathology (). The third part of the duodenum became dusky, and we decided to resect it with a GIA. At this point, the patient was hypotensive and acidotic. A decision was made to perform damage control and a temporary abdominal closure and to transfer the patient to ICU for resuscitation. In the ICU, she was aggressively resuscitated with correction of her acidosis, coagulopathy, and hypothermia. She was brought back to the OR the following day. There were no signs of bowel ischemia, and the small bowel obstruction had resolved. An end to side duodenojejunostomy was performed using an EEA. The anastomosis was protected with a Stamm's gastrostomy through which a feeding jejunostomy was passed distal to the anastomosis. A drain was left in the right upper quadrant. We then performed a transverse colon loop colostomy to divert the colonic tumor. Blood cultures later grew pseudomonas and yeast. The patient subsequently developed multiorgan failure, and the family requested DNI/DNR. Their after family requested terminal extubation 12 days after the last operation. |
pmc-6109574-1 | A 24-year-old woman with no past history of disease or surgery was transferred to the Emergency Department of the Orthopedic Clinic of a General Hospital in Thessaloniki, Greece, after a car accident a year ago. She presented with an open fracture of the right tibia and the right humerus classified as Gustillo II []. Laboratory examination revealed white blood cell count 5.800/mm3 (75% neutrophils), hemoglobin 10.2 g/dL, platelet count 108,000/mm3, glucose 85 mg/dL, creatinine 0.62 mg/dL, and C-reactive protein 1.5 mg/L (normal reference < 0.5 mg/L). The patient presented no markers revealing any kind of immunocompromise (negative for human immunodeficiency virus (HIV) and hepatitis B + C, negative Mantoux test, no diabetes mellitus, and normal kidney function). Surgical debridement, open reduction, and internal fixation of the humeral fracture with 4.5 mm locking compression plate were performed. The tibial fracture was treated with intramedullary nailing. Cefoxitin, amikacin, and metronidazole were administered for 3 days. X-rays taken each month showed delayed union of the humeral fracture. One year after surgery, she was readmitted to the hospital, due to a nonunion appearing on the X-rays. The clinical examination and the inflammatory markers were normal. Surgical debridement, revision of the internal fixation (two screws were removed), and filling the nonunion site with iliac crest cancellous autograft were performed. During surgery, 3 culture specimens from superficial layers, deeper layers, and the nonunion site were taken. R. radiobacter was isolated only from the nonunion site, while the other two cultures came out negative. The antimicrobial susceptibility to antibiotics showed sensitivity to amikacin, ciprofloxacin, carbapenems, doxycycline, tigecycline, colistin, and co-trimoxazole ().
The patient initially was treated with intramuscular administration of amikacin for 3 weeks (500 mg/day) and then with doxycycline per os for 8 weeks (100 mg/day). She came back 3 months later showing complete remission of the infection, substantial improvement, and union on the X-ray images.
Regarding the initial fracture management, open humeral shaft fractures are commonly treated with open reduction and internal fixation using a compression plate with excellent results [, ]. This procedure was followed in our case and the patient had regular follow-up. During this time, the fracture failed to unite and by one year it was considered a nonunion []. The treatment choice of a locking compression plating and cancellous bone grafting is a reliable option in these cases []. The internal fixation was proven stable intraoperatively, so the revision of the osteosynthesis was relatively minimal (two screws removed), and the main surgical intervention was the nonunion fibrous tissue debridement and the filling with cancellous bone autograft harvested from the patient's iliac crest. Three months after the operation, union of the humeral shaft was achieved with a callus formation showing in the X-rays, while in other reports, the union needed more than five months in order to be achieved []. shows X-rays before and after the nonunion treatment and an intraoperative picture. The patient scored 90 points on the constant score for the shoulder evaluation, which is an excellent result, while having a full range of motion in her elbow [].
All culture specimens were processed by Gram staining and worked out with conventional methods. Only the Gram stain from the nonunion site showed Gram-negative rods, with some appearing to have been internalized by neutrophils. Gram stains from the other two specimens were negative. Culture from the nonunion site grew a nonfermenting, Gram-negative bacillus, producing dry, tenacious colonies on blood, chocolate, and MacConkey agar, while the other two specimens were negative. The organism was identified as R. radiobacter using the automated system Vitek II (bioMerieux, Marcy-l'Etoile, France) and confirmed by the conventional biochemical methodology (). The antibacterial susceptibility (minimum inhibitory concentration (MIC) determination) of the isolate was performed by E-test (AB Biodisk, Solna, Sweden). Clinical Laboratory Standard Institute (CLSI) interpretive criteria for nonfermentative Gram-negative bacteria [, ]. The isolated R. radiobacter was sensitive to ciprofloxacin, amikacin, and doxycycline (). |
pmc-6109575-1 | A 49-year-old man collided with a car while riding a motorcycle. After the collision, the man was run over by the car. His vital signs were stable on admission, and the patient had no consciousness disorder (blood pressure (BP) 117/56 mmHg; heart rate (HR) 87 bpm; Glasgow coma scale (GCS) E4V5M6). Hematological examination revealed a white blood cell count of 8050/μl, hemoglobin 10.7 g/dl, and platelet 12.4 × 109/l. However, the patient went into shock during care in the emergency room. After volume resuscitation, contrast-enhanced computed tomography (CT) was performed and showed extravasation of the contrast medium and a pseudoaneurysm around the distal arch of the aorta. Additionally, the patient presented with fracture of the Th12 and L1 vertebras, hemothorax, and tear of the right Achilles tendon (). A drain was placed in the left thorax, and mechanical ventilation was started under sedation.
After these procedures, TEVAR with a 31 × 26 × 100 mm stent graft (Conformable GORE TAG, W. L. Gore & Associates, Newark, DE) was performed successfully. Heparin was not administered during surgery. After the operation, the circulation and respiratory systems were stable. One day after the operation, the patient was weaned from the ventilator without any neurological disorder. Follow-up with enhanced CT showed that the pseudoaneurysm had disappeared (). The patient was transferred to a rehabilitation facility without TEVAR-related complications, including any neurological symptoms. |
pmc-6109575-2 | A 69-year-old man fell from a ladder. At arrival to the hospital, his vital signs were stable and his consciousness was clear (BP 160/87 mmHg; HR 109 bpm; GCS E4V5M6). He complained of chest and back pain which moved from the shoulder to the chest and back. Enhanced CT was performed which revealed aortic dissection with intramural hematoma. Extravasation and pseudoaneurysm were not observed ().
We commenced conservative therapy which consisted of blood pressure control (target, systolic pressure < 140 mmHg), bed rest for 14 days, and close observation using enhanced and plain CT on hospital days 1, 3, 5, 9, and 14. After this protocol was completed, we performed TEVAR on hospital day 16 as a scheduled operation. We placed 22 × 22 × 100 mm (Valiant Captivia Thoracic Stent Graft, Medtronic, Medtronic, Santa Rosa, CA) and 30 × 26 × 150 mm (Relay Plus, Bolton Medical, Sunrise, FL) stent grafts (). During the procedure, we administered heparin with an activated clotting time (ACT) goal of 250 s. At the end of the procedure, heparin was neutralized by an equal amount of protamine.
The patient recovered from anesthesia without any neurological disorder. He was discharged walking, to his home on postoperative day 14, which was hospital day 30. Enhanced CT performed 1 month after the procedure revealed that the thickness of the intraluminal hematoma had decreased (). |
pmc-6109575-3 | A 60-year-old man was hit by a car while walking. His hemodynamic status on arrival to the hospital was stable (BP 120/62 mmHg, HR 85 bpm), but his consciousness was impaired (GCS E1V1M1). After standard Advanced Trauma Life Support with endotracheal intubation, fluid resuscitation, blood transfusion, and CT were performed. Contrast-enhanced CT showed subarachnoid hemorrhage, free air in the abdomen, aortic dissection, and a pseudoaneurysm around the distal arch (). However, the patient was hemodynamically stable.
Emergency explorative laparotomy was performed, and a diaphragm tear was observed and repaired. Conservative therapy and close observation were applied for the subarachnoid hemorrhage and BTAI. After 6 hours of observation, CT was performed again and the subarachnoid hemorrhage appeared not to progress. The patient was transferred to the operating room, and TEVAR was performed with a 26 × 22 × 150 mm (Valiant Captivia Thoracic Stent Graft, Medtronic, Medtronic, Santa Rosa, CA) stent graft. During the procedure, heparin was administered with an ACT goal of 250 s and was neutralized after surgery by an equal amount of protamine.
After surgery, the patient's hemodynamics were stable. The patient was returned to the intensive care unit (ICU) on artificial ventilation. He recovered consciousness in the ICU. After extubation, the patient had muscle weakness of both lower limbs which were associated with the TEVAR; however, the weakness disappeared spontaneously. The patient was subsequently discharged to the rehabilitation facility. |
pmc-6109582-1 | A 65-year-old female presented with a breast lump, diagnosed to be oestrogen and progesterone receptor positive, HER2 negative, and T1cN1bM0 moderately differentiated infiltrating ductal carcinoma. She had a platelet count of 600 thou/cu mm. There was no history of thrombotic or bleeding episodes.
Further testing showed that JAK2 mutation was positive and t(9;22) mutation was negative. Her bone marrow biopsy showed increased megakaryocytes. Her other lab workup was unremarkable including iron panel and liver function tests. She had no splenomegaly on ultrasound. She was diagnosed with ET in the setting of breast cancer.
Aspirin was commenced but held seven days prior to her breast conservation surgery, restarted postoperatively and continued thereafter. Postoperative thromboprophylaxis with low-molecular weight heparin (LMWH) was continued until the patient was fully ambulatory. Aspirin was restarted on day 7 after the surgery. Anticipating thrombocytopenia during chemotherapy, and given the absence of data combining hydroxyurea with standard chemotherapy used for breast cancer (in this case docetaxel and cyclophosphamide), we felt it prudent to delay cytoreductive therapy for her ET until after completion of breast cancer treatment. Her indication for cytoreductive therapy was >60 years. She was treated with adjuvant docetaxel and cyclophosphamide and continued on aspirin 81 mg for the entire duration of her chemotherapy. She tolerated the 6 cycles of chemotherapy well.
Following the completion of her chemotherapy, she was started on letrozole and radiotherapy with the aim to continue the letrozole for 5 years. Hydroxyurea (500 mg) was also started and titrated to a goal to 400–450 thou/cu mm platelets. Zoledronic acid was started for osteoporosis prevention.
Her average platelet count during chemotherapy was 480 thou/cu mm with the lowest being 377 thou/cu mm (). Her platelet count remained at goal between 300 and 350 thou/cu mm after four months of hydroxyurea (). Throughout her treatment, there were no bleeding or thrombotic complications. After one year on letrozole, hydroxyurea, and aspirin, the patient was doing well without complications with platelet counts at goal. |
pmc-6109837-1 | A 40-year-old female presented at the emergency department with painful rash associated with intermittent fever and joint pain for 5 days (). The rash was recognized initially over the neck and bilateral upper extremities, which subsequently spread to the legs. Multiple tense raised vesicles and bullous lesions were noticed bilaterally over the forearm and arm with several lesions associated with drainage and others crusted. Some of the bullous lesions had surrounding erythema. Laboratory examination revealed a white blood cell (WBC) count of 15.5 × 103/µL with an absolute eosinophil count (AEC) of 1600 cells/µL. The coccidioidal serology was positive by immunodiffusion for immunoglobulin M antibody (ID-IgM). The complement fixation (CF) antibody titer was <1:2. Chest X-ray revealed right upper lobe infiltrate. She received fluconazole 800 mg daily, and subsequent follow-up showed a nonreactive ID-IgM but weakly reactive ID-IgG and CF titer of 1:2. The punch biopsy of the drained bullous lesions of the right leg () showed superficial dermal edema enriched with lymphohistiocytic inflammation (). The periodic acid–Schiff stain and Gomori methenamine silver nitrate stain were negative for fungal organisms. |
pmc-6109837-2 | A 45-year-old female presented with skin rash for 8 days (). Rash was initially noticed on the right arm, which spread to the left arm and trunk. The patient complained of nonproductive cough, arthralgia, and weight loss. On examination, vesiculobullous, pruritic rashes with tenderness around the lesions were noticed. Biopsy of the forearm bullae lesion revealed histiocytes and neutrophils in the subepidermal layers with break in the epithelial lining. She received fluconazole 400 mg. Laboratory examination revealed a WBC count of 12.1 × 103/µL with an AEC of 1100 cells/µL. The coccidioidal serology showed weakly reactive ID-IgM and ID-IgG. CF antibody titer was 1:2. One month later she returned to the clinic with complete resolution of the rash. |
pmc-6109837-3 | A 47-year-old female presented with skin rash for 17 days (). Initially the vesicular rash involved both forearms, which subsequently spread to the neck and both legs. The rash was notable for pruritic erythema around vesicular lesions. Biopsy of the lesions in the neck revealed granulomatous inflammation in the dermis (). Laboratory tests revealed WBC count of 12.7 × 103/µL and AEC of 900 cells/µL. The coccidioidal serology was weakly reactive for ID-IgM and ID-IgG, and CF antibody titer was <1:2. Chest X-ray showed small right lower lobe infiltrate. The rash resolved in the next 2 weeks. |
pmc-6109837-4 | A 42-year-old male presented with painful, pruritic vesiculobullous rash on his bilateral forearms for 15 days (). The rash was red, raised, tense and vesiculobullous, and tender. He complained of fever and cough. Biopsy of the left forearm lesion revealed granulomatous inflammatory cells in the dermis with minimal subepidermal edema (). The laboratory examination revealed WBC count of 12.3 × 103/µL and AEC of 800 cells/µL. The coccidioidal serology showed reactive ID-IgM and ID-IgG with CF antibody titer <1:2. The chest X-ray showed right lower lobe infiltrate. The skin biopsy showed subepidermal vesicular dermatitis with neutrophils and histiocytes. In the next 2 weeks, the rash resolved completely. |
pmc-6109837-5 | A 45-year-old male presented with fever and diffuse maculopapular rash that started on bilateral forearms then over 4 days spread to lower extremities, shoulder, and posterior thorax (). He complained of dry cough and mild pruritus over the chest. The laboratory examination showed WBC count of 16.7 × 103/µL with an AEC of 1600 cells/µL. Biopsy of the lesions in the posterior right arm revealed dermal edema and subepidermal vesicle with fibrin and irregular brown pigmentation in the epidermis (). The coccidioidal serology showed weakly reactive ID-IgM and ID-IgG, and CF antibody titer was <1:2. Chest X-ray showed bilateral infiltrates worse on the left lower lobe. The rash resolved in the next 2 weeks. |
pmc-6109837-6 | A 27-year-old Caucasian male presented with rash associated with myalgia and fever for 7 days (). Multiple open and intact vesicles associated with erythematous subcutaneous tender nodules on both arms, legs, neck, and forehead were noted. There was clear, serous discharge from the vesicles. Biopsy of the crusted lesion over the left knee revealed vesiculated subepidermal layer with histiocytic inflammation of the dermis (). Laboratory examination showed WBC count of 11.7 × 103/µL with an AEC of 1200 cells/µL. The chest X-ray showed right upper lobe inflammatory infiltration. The coccidioidal serology showed reactive ID-IgM and weakly reactive ID-IgG, and CF antibody titer was <1:2. The patient was discharged but lost to follow-up (see ).
Laboratory results are summarized in . |
pmc-6109839-1 | An 18-year-old male without any significant past medical history presented to the emergency department with the complaint of abdominal pain. Pain described as generalized abdominal pain, more on the left flank that started 5 days ago, nonradiating, constant, 4/10 intensity. He denied dysuria, hematuria, groin pain, fever, chills, nausea, vomiting, abdominal pain, diarrhea, constipation, decreased oral intake, joint pain, leg swelling, or redness. He denied any medication use or any history of illicit drug use. The patient reported history of motor vehicle accident (MVA) 1 week prior to his presentation. He was a front seat passenger wearing a seatbelt when the car accidently went into a ditch. Airbags were deployed and patient briefly lost consciousness.
There was no reported family history of kidney disease or blood clots. Physical examination revealed left flank tenderness but no evidence of ecchymosis. Laboratory tests including complete blood count, basic metabolic panel (BUN [blood urea nitrogen] 20 mg/dL, creatinine 1.1 mg/dL), sedimentation rate, urine drug screen, and complete urinalysis were unremarkable, except trace proteinuria without evidence of microscopic hematuria. Contrast-enhanced CT (CECT) of the abdomen was performed as no diagnosis was clear on clinical evaluation. CECT showed multiple, confluent, focal areas of hypoperfusion of the renal medulla and cortices bilaterally (). Given the CT findings of bilateral renal hypoperfusion, the patient was admitted to the hospital and an extensive workup was performed to rule out cardioembolic etiology. Transthoracic echocardiogram and renal ultrasound were unremarkable. Hypercoagulable workup including prothrombin time, partial thromboplastin time, dilute Russell viper venom test screen, fibrinogen level, antithrombin III activity, protein C activity, protein S antigen, and prothrombin gene mutation was unremarkable. Mild D-dimer elevation was noted, 285 ng/mL (normal 0-250 ng/mL). Vasculitis panel including ANA, ANCA, complement levels, rheumatoid factor, and hepatitis serology was unremarkable.
Magnetic resonance angiography of the abdomen revealed widely patent renal arteries and normal perfusion in all branches of abdominal aorta without evidence of thrombosis (). The CT findings of renal hypoperfusion were considered secondary to transient hypoperfusion from blunt trauma. Abdominal pain was considered musculoskeletal in origin due to blunt trauma, which resolved with ibuprofen and he was discharged to home.
The patient was followed up as an outpatient a few weeks after discharge. He was asymptomatic with a normal physical examination. On follow-up testing, renal function was normal (BUN 9 mg/dL, creatinine 0.9 mg/dL). Complete urinalysis was unremarkable, with resolution of previously noted trace proteinuria. Follow-up abdominal CT scan with contrast showed normal kidneys with complete resolution of previously noted renal hypoperfusion (). |
pmc-6109974-1 | A 52-year-old Caucasian man who had no medical history presented with sacral region pain that had continued for 3 months in April 2012. There was no significant family or psychosocial history. He did not take any medications. He was a computer engineer and his job scope was mainly office work. He lived with his wife and one child in a small flat in Istanbul. He was an active tobacco smoker with a 10 pack year smoking history. Currently, he smoked five cigarettes a day. He did not consume alcohol. His physical examination revealed tenderness and swelling in the sacral region. His vital signs were stable with blood pressure 125/65, pulse rate 70/minute, and temperature 36.2 °C. A systemic examination was normal and no neurological abnormality was detected. Vertebral magnetic resonance imaging (MRI) showed a pathological fracture in L5. After a Tru-Cut biopsy, he was diagnosed as having chondroid chordoma. He was treated with preoperative stereotactic radiotherapy to L5 vertebra at a total dose of 15 Gray in two fractions with CyberKnife followed by surgery in May 2012. We aimed to reduce surgical complications by preoperative stereotactic radiotherapy. Two years later, in May 2014, he presented with lumbosacral region pain and MRI suggested recurrent tumor involving L4, L5, and S1 vertebrae. He was not eligible for surgery and was treated with definitive radiotherapy with intensity-modulated radiotherapy (IMRT) mainly for palliative intent. Between 7 July 2014 and 8 August 2014, he received 40 Gray to L4, L5, and S1 vertebrae in 20 fractions 5 days a week for 4 weeks. In January 2016, he presented with paraplegia. Control imaging showed local recurrence, multiple lung nodules, and sternal metastasis. Imatinib 400 mg was started in February 2016 and continued until July 2017 when control imaging showed the progression of his disease. He received a total of 16 months of treatment. During this period, he received 400 mg/day of imatinib and no dose reduction was done. The laboratory results are given in Table . Overall, he tolerated treatment well and did not report any side effects. The best supportive care was offered. He was treated with best supportive care until May 2018. He died on 25 May 2018. |
pmc-6109974-2 | A 72-year-old Caucasian woman who had type 2 diabetes and hypertension presented with diplopia in February 2010. Her vital signs were abnormal. Her blood pressure was high (150/95 mmHg), and her pulse rate and temperature were 65/minute and 37.1 °C. A neurological examination showed preserved muscular and neurological function and no signs of paresthesia or hypoesthesia; a general examination showed no other abnormality. There was no significant family or psychosocial history. She was taking perindopril 10 mg/day, metformin 2000 mg/day, and nateglinide 360 mg/day. She was a housewife and lived with her husband in a small town. She never smoked tobacco and did not consume alcohol. A brain and sella MRI showed a 3 cm x 2 cm x 2 cm mass in the sellar and parasellar region. She was operated on via transsphenoidal surgery. A postoperative pathology examination revealed chordoma. After the surgery, gamma-knife radiotherapy was performed. She came back in March 2014 and a 12 mm × 30 mm clivus mass was revealed on her brain MRI. She was operated on again and a pathology examination revealed chordoma. Postoperative stereotactic radiotherapy to residual mass in her clivus at a total dose of 12 Gray in one fraction with gamma-knife was done. Two years later, she had a recurrent mass in her clivus. As neither further surgery nor radiotherapy were suitable for her, sunitinib 37.5 mg per day was started in April 2016 and she has been receiving the same treatment ever since. The laboratory results are given in Table . She reported intermittent grade 1 nausea and grade 1 fatigue; no serious side effects were reported. The best response to sunitinib treatment was assessed as stable disease. In June 2018, she continues with the same dose of treatment. There is no detected progression of her disease. |
pmc-6109974-3 | A 38-year-old Caucasian woman who had no medical history presented with a headache of 2 months’ duration in August 2012. There was a family history of malignancies. She had no psychosocial history. She did not take any medications. She was a housewife. She lived with her husband and three children in a flat in the city center of Istanbul. She never smoked tobacco and did not consume alcohol. Her vital signs were stable with blood pressure 110/70 mmHg, pulse rate 82/minute, and temperature 36.5 °C. On neurological examination, there was a limitation of temporal movement in her right eye. There were no signs of paresthesia or hypoesthesia. A general examination showed no other abnormality. Brain MRI showed 34 mm × 10 mm and 20 mm × 19 mm masses in her clivus. She was operated on and a pathology examination showed chordoma. Postoperative stereotactic radiotherapy to clivus at a total dose of 24 Gray in one fraction with gamma-knife was performed. In March 2014, she had a recurrence in her clivus and then she underwent another operation. A pathology examination revealed chordoma. She presented with diplopia for 1 month in January 2015. Brain MRI detected a recurrent mass in her clivus and invasion to the pons. She was treated with external cranial radiotherapy for palliative intent. She received a total of 30 Gray to recurrent mass in ten fractions during 10 days. In March 2015, a residual mass in her clivus was seen in MRI. She was started on daily 400 mg of imatinib in April 2015. The best response to imatinib was stable disease. Overall, imatinib was well tolerated; she reported periorbital edema, grade 1 skin rash on her legs, and nausea grade 2. She complained of visual loss in her left eye in May 2017. Brain MRI confirmed progressive disease (Fig. ). Imatinib was stopped and sunitinib 37.5 mg per day was started in June 2017. She received sunitinib until December 2017 when she had radiological and clinical progression (Fig. ). Four weeks later, her sunitinib dose was lowered to 25 mg/day due to ongoing grade 2 nausea and vomiting. Other reported symptoms included grade 2 fatigue and grade 1 hand-foot syndrome. The laboratory results are given in Table . She received a total of 25 months of imatinib therapy and 6 months of sunitinib treatment. She continued her follow-up with best supportive care until April 2018. She died on 23 April 2018. |
pmc-6109996-1 | An 81-year old female with a history of coronary artery disease, hypertension, and thrombocytosis suffered a witnessed trip and fall onto a nightstand. The patient took 75 mg of clopidogrel daily in addition to an 81 mg aspirin tablet. She reported a mild headache however had no change from her baseline mentation per family members with no evidence of obvious injury aside from a small area of ecchymosis near a small forehead laceration. She remained up and ambulatory with no further complaints. Ten hours after her injury the patient presented to the Emergency Department with stridorous and agonal respirations with a profoundly decreased level of consciousness. She was noted to have developed extensive ecchymosis on the anterior portion of her neck and chest. Her symptoms had begun rapidly shortly prior to arrival while lying in bed. Family reported that she had been in the constant company of her husband with no further falls or injuries that had occurred since her fall. The patient was intubated upon hospital arrival due to respiratory extremis with obvious swelling and crepitus noted on neck examination. A noncontrast CT scan of head was unremarkable while there was demonstration of a large retropharyngeal hematoma measuring 3.6 cm by 5.3 cm by 20 cm on a CT of the cervical spine with no evidence of fracture. Her hemoglobin was 9.5 gm/dL and platelets were 1234 per deciliter, with an INR of 3 and a slightly below normal and activated partial thromboplastin time of 23.9 seconds (reference range 25-35 seconds). A CT angiogram of the neck was subsequently obtained demonstrating active bleeding from the anterior ligaments of the vertebral column that was not felt to be amenable to embolization (). Given the extent of the hematoma intraoral surgical evacuation was performed with bleeding from the anterior vertebral spine controlled with Bovie cauterization, placement of topical thrombin, and drain placement. No reaccumulation of hematoma was noted during her hospital course. The patient unfortunately expired 12 days from the date of admission from presumed aspiration pneumonia and multisystem organ failure. |
pmc-6110011-1 | A 21-year-old white female was referred to our Allergy-Immunology Clinic for a history of multiple intractable cutaneous abscesses and cysts for several years. She had undergone multiple incision and drainage and had been treated with antibiotics as well as topical and systemic steroids intermittently with minimal relief and developed methicillin resistant staphylococcal aureus (MRSA) colonization during the same period. She was at the time clinically diagnosed as Hidradenitis Suppurativa. Her medical history was significant for hypertension, diabetes mellitus type II, hyperlipidemia, obesity, and anxiety.
On further questioning, she reported more than fifteen hospitalizations for pneumonias. According to her mother, she had recurrent pneumonias, upper respiratory tract infections, sinusitis, mastoiditis, and oral candidiasis since early childhood. The patient denied any history of atopic dermatitis, other types of eczema, or food allergy. Evaluation for cystic fibrosis and hypogammaglobulinemia at the time had been negative. More recently, she had been admitted for septic shock secondary to septic arthritis of left hip. She also had multiple fractures with minimal trauma since childhood and was clinically diagnosed with osteogenesis imperfecta. She also reported history of primary teeth retention for which she had underwent orthodontic surgery at the age of 12 years. She had a normal birth history with normal documented developmental milestones and was up-to-date with her immunizations. She had Penicillin and Trimethoprim-Sulfamethoxazole (TMP-SMX) listed as allergy after she developed rash with their use when she was a toddler.
Family history was pertinent for her paternal grandmother with recurrent pneumonias, who passed away at 40 years of age secondary to a severe lung infection. Her biological brother had a history of recurrent skin boils.
Important physical findings included coarse facial feature with exacerbated pore size, deep set eyes, broad nasal bridge, high arched palate, and multiple scattered healed scars on skin with some remnant cold abscesses. She had mild thoracic scoliosis. Pulmonary and cardiovascular exam were unremarkable.
Laboratory investigations revealed a normal complete blood count with no eosinophilia. IgE level was elevated at 5,842 IU/ml, with erythrocyte sedimentation rate of 64 mm/hr and C-reactive protein of 1.56 mg/dl. IgG, IgM, and IgA levels were within normal limit. Tetanus and pneumonia titers were normal. Total complement (CH50) levels were normal and testing for chronic granulomatous disease was unrevealing. Due to history, physical findings, and these initial labs, we suspected Hyper-IgE Syndrome. A calculated HIES score was 63 (>40 required for diagnosis). With a high suspicion of AD-HIES, mutation analysis of STAT3 gene was sent which detected a novel pathogenic mutation, C.1388 T>A (pVal463Glu) at DNA-binding domain of STAT3 gene. Although this mutation in STAT3 gene has never been published as a pathogenic mutation leading to AD-HIES, missense variants in nearby residues have been reported in association to those reported in the Human Gene Mutation Database in association with HIES [].
Penicillin allergy testing and TMP-SMX oral challenge were performed in the clinic. With a normal response, she was started on TMP-SMX (800mg-160mg) once daily prophylactically for prevention of infections (MRSA sensitive to TMP-SMX).
Patient was advised to follow up for clinical response and monitoring tolerance to treatment. She was asked to have regular dental exam, chest imaging, bone density scan, and pulmonary function test screening. She was also advised to have genetic counselling. Genetic testing for her biological brother was offered. |
pmc-6110037-1 | The patient involved provided written consent for reporting of this case.
A 63-year-old woman with medical history of super morbid obesity (BMI 54) and atrial fibrillation for which she was anticoagulated with apixaban presented for an open reduction internal fixation (ORIF) of an ankle fracture. Significant medical history included diabetes mellitus type 2, obstructive sleep apnea, chronic obstructive pulmonary disease, and diastolic heart failure. The patient's last dose of apixaban was 48 hours prior to surgery. Other than moderate anemia (hemoglobin 8.8 g/dL), all laboratory studies, including a coagulation profile, were normal.
Prior to surgery, the patient was offered a sciatic nerve catheter and an adductor canal block as part of a multimodal postoperative analgesia strategy. Because of her many, serious medical conditions, we concluded that a peripheral nerve block offered the best opportunity to provide satisfactory postoperative analgesia. Specifically, we were concerned that the postoperative pain management primarily with opioid medications would pose increased cardiopulmonary risk to the patient. We were careful to explain the risks associated with peripheral nerve blocks, including the risk of bleeding and hematoma formation, and verbal consent was obtained.
The surgery was performed under general anesthesia and her intraoperative course was uncomplicated. Upon arrival to the recovery room, our acute pain service was contacted to evaluate her for peripheral nerve blockade. We positioned the patient in the lateral decubitus position and placed a sciatic nerve catheter. Though technically challenging due to body habitus, this sciatic nerve block was performed successfully and without any complication. The patient was then positioned supine for the adductor canal block. The leg was externally rotated and the knee slightly flexed for optimal positioning. A high-frequency linear array ultrasound transducer was applied to the mid-thigh in short-axis and the adductor canal was identified. Imaging was again challenging given the patient's habitus, but with firm compression of the ultrasound transducer, the important anatomical structures were clearly identified. The superficial femoral artery (SFA) was visualized dorsal to the sartorius muscle and a hyperechoic structure anterolateral to the artery was identified as the adductor canal and saphenous nerve [, ]. The skin adjacent to the probe was cleansed with a chlorhexidine and alcohol solution. A 20-gauge × 4-inch beveled, echogenic needle was inserted using an in-plane technique. The needle was visualized continuously as it coursed between the vastus medialis and sartorius toward the adductor canal. The needle was positioned lateral to the SFA within the canal and a bolus of 20 ml of 0.25% bupivacaine with 5 mcg/ml epinephrine was administered with negative heme aspiration checks after every 5 ml injection. Spread of local anesthetic within the adductor canal was clearly observed under ultrasound visualization. There was no evidence of intravascular injection of epinephrine while monitoring the patient. Upon needle withdrawal, brisk bleeding was noted at the skin insertion site but with direct manual pressure for approximately 60 seconds, bleeding ceased completely.
Shortly after the blocks were performed, the patient reported complete resolution of her ankle pain and was transferred to her hospital room. Approximately 6 hours after surgery, the patient reported new anterior thigh pain on the operative leg, which was treated by her nurse with intravenous hydromorphone. Roughly 13 hours after surgery, the patient's nurse finally contacted the orthopedic surgery team due to unmanageable mid-thigh pain. The orthopedics team initially believed the pain was due to tourniquet compression pain which occurred during surgery. Upon further physical examination, a hematoma was noted in the anterolateral mid-thigh. Vital signs were within normal ranges and distal pulses were intact. A CT scan with contrast was ordered and revealed a 14-cm hematoma in the right thigh (). Lab studies showed a drop in hemoglobin from 8.8 g/dL preoperatively to 6.9 g/dL the morning of postoperative day (POD) 1. Coagulation studies at that time were within normal limits including partial thromboplastin time, prothrombin time, and international normalized ration, as well as platelet count. The patient's primary medicine service transfused 1 unit of packed red blood cells, which improved her hemoglobin to 7.6 g/dL.
Interventional radiology was consulted on the morning of POD 1 for management recommendations for the hematoma. A CT angiogram was performed revealing active extravasation from a small superficial branch of the SFA (). Embolization with coil and gel foam was performed and compressive dressings were used to apply direct pressure. Throughout the day, the patient's hemoglobin remained stable and the hematoma showed no evidence of further expansion.
On POD 2, further consultation from the vascular surgery and interventional radiology teams was sought for possible hematoma evacuation versus drain placement given the massive size. Vascular surgery recommended conservative management with application of direct pressure. Interventional radiology, however, recommended placement of a drain within the hematoma. A pigtail catheter was placed and fluid cultures were obtained. Minimal output from the drain was observed, so beginning on POD 3, tissue plasminogen activator (TPA) was administered through the catheter daily to facilitate hematoma drainage. Follow-up ultrasound on POD 6 showed a persistent hematoma despite TPA administration. Hematoma cultures resulted negative for infection. On POD 7, she was discharged to a rehabilitation facility with the drain in place and care team instructions to flush 5-10 ml saline twice daily until evaluation with interventional radiology one week later.
On POD 14, the drain was inadvertently pulled out requiring a return visit to interventional radiology and drain replacement. On POD 19, the hematoma cavity had decreased to an acceptable size so the drain was removed. One week later, on POD 26, she returned to interventional radiology due to increased pain and swelling at the hematoma site. A recurrent fluid collection was noted on ultrasound examination so the drain was replaced a third time and aspirated fluid was sent for culture, which grew staphylococcus aureus. She was treated for hematoma superinfection with a five-day course of levofloxacin and when she returned two weeks later, the abscess had resolved and the drain was removed. |
pmc-6110053-1 | A 32-year old man was admitted to a Danish hospital due to right sided flank pain of four days duration. He had no confirmed medical diagnoses, but had previously been tested for Sarcoidosis, Polycythemia vera, stroke and acute coronary syndrome. He also had a history of former steroid-use. The available medical records did not state his vaccination status or previous childhood infections. At hospitalization, he presented with intermittent right sided flank pain, turning into constant pain of VAS 7-8 and radiating to the right side groin. Additional symptoms were nausea, chills, and observation of blood in the urine. Physical examination revealed right sided abdominal and renal pain and a temperature of 38.0 degrees Celsius. His urine tested positive for leucocytes, erythrocytes, nitrite and protein 1 g/L and blood samples showed normal urate levels, elevated ionized calcium levels 1.56 mmol/L, creatinine 122 µmol/L, leukocytosis of 15.9 x 109 /L and CRP 6.4 mg/L increasing to 172 mg/L the next day. CT scan showed bilateral nephrolithiasis as well as right side ureterolithiasis causing obstruction Fig. (). Direct microscopy on three out of three blood culture bottles revealed small gram-negative pleomorphic rods within 24 hours of incubation. Mass spectrometry (Bruker Daltonics using MBT Compass software version 4.1 that contains 6903 MSP´s) identified the strain as H. influenzae with a score of 2.24. Microbiology testing of urine routinely cultured on a 5% blood agar plate and a UTI chrome agar plate showed 105 growth of H. influenzae confirmed by MALDI-TOF MS (score of 2.15). The strain was found to be a non-capsulated biotype II, susceptible to all antibiotics tested by disc diffusion: penicillin (1 unit, zone diameter: blood = 15 mm, urine = 15 mm), amoxicillin-clavulanate (3 µg), ampicillin (10 µg), ciprofloxacin (5 µg, zone diameter: blood = 35 mm, urine = 41 mm), cefuroxime (30 µg) and piperacillin-tazobactam (36 µg) using EUCAST disc diffusion recommendations. After microbiology samples had been collected, the patient started antibiotic treatment with intravenous ampicillin 1 g x 4 daily and a right sided JJ ureteric stent was surgically inserted. The patient received two doses of ampicillin, but due to subjective discomfort, treatment was changed to cefuroxime 1500 mg x 3 daily. After three days, the patient was discharged with 5 days of peroral ciprofloxacin 500 mg x 2 and a scheduled ambulant stone-removal surgery. |
pmc-6110074-1 | The patient is a 46-year-old right-hand dominant male who presented for left shoulder pain, stiffness, and mechanical symptoms. He underwent arthroscopic SLAP repair and open subpectoral biceps tenodesis 2 years ago for long-standing left shoulder pain without any history of trauma. He stated that his pain and dysfunction were worse at this time than before the index surgery. Golf was his main recreational activity before the surgery, but now he has problems doing activities of daily living. He has not improved with physical therapy. He has been to two other orthopaedic surgeons and was diagnosed with subacromial impingement.
On physical exam, the patient’s left shoulder was slightly more protracted and he had mild scapular dyskinesia. He was tender to palpation at the acromioclavicular joint, greater tuberosity, and glenohumeral joint. He actively forward elevated to 130 degrees compared to 160 degrees on the right; same with passive elevation. He internally rotated to L1 on the left and T6 on the right. He externally rotated to 70 degrees at the side bilaterally. He had full abduction which was symmetric to the other side. Internal rotation in the scapular plane was 20 degrees compared to 60 degrees on the right. External rotation in the scapular plane was 80 degrees on the left and 100 degrees on the right. Impingement tests with Neer, Hawkins, and Kim were all positive. Strength testing of all 4 rotator cuff muscles were 5/5 and symmetric. However, he had some pain with Jobe and bear hug tests. Crossbody adduction test and O’briens were positive. Instability tests were all negative and he did not have any signs of hyperlaxity per Beighton criteria. His American Shoulder and Elbow Surgeons Shoulder (ASES) score at this time was 26.6.
MRI prior to surgery reported a type VII SLAP (Snyder type II). Surgery report states that this was repaired with 2 suture anchors; 1 placed anterior to the biceps and another placed posteriorly and knots were tied. Additionally, there was a partial articular subscapularis tear that was debrided and decision to do the subpectoral biceps tenodesis was based on the subscapularis tear suggestive of biceps instability with compromise of the medial sling. The bursa was excised and a bursal sided rotator cuff tear was debrided of about 10%. MRI 1 year later shows intact superior labrum repair and biceps tenodesis. There was a progression of tendinosis, mild acromioclavicular (AC) joint arthrosis, and mild degenerative changes along the inferior glenoid with osseous spurring and mild chondral loss. X-rays showed a type III acromion with a large subacromial spur (Fig. ). Based on these findings, the patient was consented for left shoulder arthroscopic subacromial decompression, distal clavicle excision, possible removal of anchors, and possible capsular release.
During surgery, patient was placed in lazy lateral decubitus position. Kim’s posterior portal was established. ESR and CRP were obtained pre-operatively and were negative. However, before turning on the fluid, a needle was placed in the rotator interval and intra-articular joint fluid was aspirated and sent to pathology (Fig. ). Prophylactic antibiotics were then started and fluid was turned on. An anterior portal was established in the rotator interval. The superior labrum had healed. There were no proud anchors and the knots were away from the articular surface. The rotator interval was thickened and scarred and the MGHL was thick and tight. The knots were removed using an open knot cutter. A superior capsular release was performed with an arthroscopic tissue liberator knife between the interval of the labrum and rotator cuff at the glenoid (Figs. -). The SGHL was released. The MGHL was resected with a meniscal punch (Fig. ) as well as the rotator interval and CHL. The anterior capsule had normal pliancy and was not thick and fibrotic as seen typically with adhesive capsulitis and therefore, the capsular release was not extended anteroinferiorly.
In the subacromial space, there was thickened bursa and a bursectomy was performed. Adhesions were removed in the anterior, lateral, and posterior gutters. A subacromial decompression (Figs. -) and distal clavicle excision were performed.
He was discharged home the same day with a sling for comfort and noted that he was able to raise his arm overhead on POD 0 which he was not able to do previously. The patient was given 3 weeks of oral penicillin until final cultures came back. He started immediate physical therapy with a range of motion exercises and periscapular strengthening and progressive cuff strengthening. Final cultures at 3 weeks were negative.
On his last follow up at 6 months post-operative, he was able to actively forward flex to 160 degrees, internally rotate to T8, externally rotate to 70 at the side, externally rotate in the scapular plane to 90 degrees, and internally rotate in the scapular plane to 60 degrees. Neer and Kim impingement tests were negative while Hawkins was mildly positive. He had symmetric strength of all four rotator cuff muscles. His final ASES score was 86.6. |
pmc-6110164-1 | The proband (Figure ) was a 12-year-old girl, born at full-term (birth weight, 3,600 g) as the first child of consanguineous parents, referred to the Universidade Federal do Ceará Clinical Hospital, Fortaleza, Brazil for clinical assessment of short stature and learning disabilities that manifested since age 8. Physical examination revealed reduced fat in the arms, legs, and gluteal region, muscular hypertrophy, and acanthosis nigricans as well as macroglossia, dry and thickened skin, short stature, and pubertal stage Tanner 1. Proband was 118.7 cm (Z-score, −5.2) in height, weighed 27 kg, and had a body mass index (BMI) of 19.1 kg/m2. Thyroid function tests revealed severe primary hypothyroidism (TSH > 100 uU/mL and free T4 = 0.01 ng/dL) and thus the proband was started on levothyroxine resulting in catch-up growth and normal pubertal development with menarche by age 14.8. After hypothyroidism treatment, the selective loss of subcutaneous fat tissue in limbs, gluteal region, and abdomen became evident over time, leading to the diagnosis of lipodystrophy. At age 12, she presented with moderate hepatomegaly, umbilical hernia, hypertriglyceridemia (509 mg/dL), and acanthosis nigricans in the neck and axillary regions. One year later, at age 13, hypochromic and atrophic cutaneous plaques were observed distributed throughout the body. Skin biopsies revealed localized scleroderma (morphea). Some years later in adulthood, remarkable fat accumulation in the neck, face, and axillary and dorsocervical regions was observed, along with the worsening of subcutaneous fat atrophy in limbs and abdomen, indicating partial lipodystrophy diagnosis.
At age 23, the proband was diagnosed with diabetes and albuminuria. Currently, she is 26 years old and presents with uncontrolled diabetes, hepatomegaly (10 cm below the costal margin), and irregular menses. She is 145 cm in height, weighs 42 kg, and has a BMI of 20.0 kg/m2. A formal assessment of intelligence quotient is not available, but she shows a slight degree of intellectual impairment. Standard serum determinations are listed in Table . |
pmc-6110280-1 | 42-year-old man presented with proximal muscle weakness of 1.5 years
duration. Muscle biopsy demonstrated polymyositis. High dose PDN and MTX were
initiated; however, no significant improvement was appreciated. After a year on
PDN and MTX, the patient developed worsening proximal muscle weakness and
difficulty in swallowing. PDN dose was increased and azathioprine (AZA)
commenced. Two doses of intravenous immunoglobulin (IVIG) were administered.
Given the lack of response to the new regimen, the patient transferred his care
to our hospital. Physical exam was notable for 2/5 strength for neck flexors,
deltoid, biceps, hand grip, hip flexors and quadriceps. His hands appeared
swollen with muscle wasting.
After comprehensive case review, PDN 75 mg/day and TAC 2 mg twice daily
were started. Biologics could not be prescribed due to non-medical reasons. TAC
dose was increased to 4 mg twice daily, based on trough goal of 6–10
ng/mL []. After a month of initiating
tacrolimus, mycophenolate mofetil (MMF) 1500 mg twice daily was added without
complications. Six months after TAC and MMF combination had started, muscle
enzymes decreased significantly (CK 4419 U/L to 732 U/L and LDH 1402 U/L to 513
U/L) and clinical improvement was appreciated. PDN was tapered to 30 mg/day.
Blood pressure and glycemic levels were monitored at every clinic visit. Eleven
months after TAC and MMF were started, LDH and CK normalized; patient had 3/5
strength on neck flexors and 4/5 strength on hip flexors and quadriceps. No
adverse effects have been reported (). |
pmc-6110280-2 | 39-year-old man with history of dermatomyositis (DM) presented to our
hospital. Six months before, patient had developed typical skin rash and
proximal muscle weakness. Work-up including muscle biopsy led to a diagnosis of
DM. Intravenous methylprednisolone had been administered. Patient was lost to
follow-up. On presentation to our hospital the patient had worsening proximal
muscle weakness, rash, dysphagia, an elevated CK of 389 5U/L, and elevated liver
enzymes (AST 242 U/L, ALT 191 U/L, ALP 146 U/L). The acute episode was treated
with pulse steroids and IVIG. Patient was placed on MMF 2 g/day, PDN 70 mg/day
with plans for rituximab infusions.
Three months after disease onset, the patient reported improvement of
skin lesions on his hands but continued to have significant proximal muscle
weakness evidenced by difficulty standing from a seated position and inability
to lift his arms above his head. CK was 1352 U/L and LDH was 617 U/L. Despite
MMF was increased to 3 g/day, the patient continued to have little improvement.
Rituximab was given in the interim. Five months after presentation, proximal
muscle weakness recurred. CK (1495 U/L), LDH (495 U/L), and ESR (42 mm/hr)
remained elevated; TAC 2 mg/day was added to the existing regimen and PDN was
slowly tapered.
Three months after tacrolimus had been started, the patient was able to
stand from a seated position. Labs revealed down trending CK (806 U/L), LDH (459
U/L), ESR (27 mm/h). At this point, TAC level was 2.5 ng/mL, so TAC was
increased to 3 mg twice daily. Five months after TAC initiation, there was
significant clinical and laboratory improvement. TAC dosage was adjusted to
achieve therapeutic level and PDN was eventually tapered off. Eleven months
after TAC initiated, muscle weakness had significantly improved and labs
normalized (CK 102 U/L and LDH 183 U/L). Patient was able to return to work
(). |
pmc-6110280-3 | 51-year-old woman with a history of hypertension, hyperlipidemia, and
stroke presented with a two-month history of muscle weakness; she reported a
remote exposure to statins. Examination revealed 2/5 strength on the left side
and 4/5 on the right. CK was 28,885 U/L; necrotizing myositis was suspected.
Patient was treated with IV methylprednisolone followed by PDN 60 mg/day.
Extensive proximal muscle edema was seen on MRI. Vastus medialis biopsy showed
necrotizing features without inflammation. Hydroxy-Methyl-Glutaryl Coenzyme A
reductase (HMG CoA) antibodies were strongly positive. One month after
presentation, there was a modest improvement in motor weakness; CK had dropped
to 5,546 U/L. IVIG (5 days) was given and MMF 1 g/day were started. Patient
continued to experience weakness and CK remained elevated. Two months after
presentation, rituximab was added to the regimen of MMF (3 g/day) and prednisone
(60 mg/day). Two doses of IVIG were given as a bridge therapy. After an initial
response, the patient’s muscle weakness returned. Three months after
presentation, CK remained elevated (3,178 U/L). TAC 4 mg/day was added to MMF (3
g/day) and PDN 40 mg/day. On follow up visits, TAC dose was increased to 6
mg/day and PDN was tapered slowly. Eight months after TAC was initiated,
weakness improved markedly and labs normalized (CK 117 U/L, LDH 251 U/L). One
year after tacrolimus and MMF, the physical exam was normal with full strength
throughout. PDN had been reduced to 5 mg daily (). |
pmc-6110409-1 | The present case is a 12-year-old girl with progressive metastatic rhabdomyosarcoma-left forearm primary. Metastasis was identified on the right lumbar paraspinal muscles, left femur, and left jaw. Multiple magnetic resonace imaging (MRI) and computed tomography (CT) scans showed no involvement of the spinal cord. She did not receive more chemotherapy or radiation therapy. She had a very significant cancer-related pain, especially in her lower extremities and jaw, which was not amenable to hospice management at home with hydromorphone patient controlled analgesia (PCA). She was admitted to the hospital due to poor pain control and the pain team was consulted for better pain management options. Her life expectancy is very short and a decision had to be made to place a tunneled epidural catheter to send her home. Due to significant debilitating headaches and the possibility of cerebral spinal fluid leak and postdural puncture headaches during an intrathecal catheter placement, this therapy was not considered as the first option. Her parents are hoping that with the epidural she will be less sedated than with the hydromorphone PCA. The patient received a transfusion of fresh frozen plasma to get a normal prothrombin time (PT), partial thromboplastin time (PTT), and international normalized ratio (INR). She also needed a platelet transfusion, which brought her level to 109,000 during the morning time of the procedure. Her initial hemoglobin level is 9.1 g/dL on the day of the procedure. She was brought to the operating room for sedation. The epidural catheter is placed without complication; the catheter tip is confirmed at the L2-L3 level with fluoroscopy and 1 millimeter (ml) of contrast dye (Omnipaque 300, GE Healthcare, Cork, Ireland) and subcutaneously tunneled completely under the left paraspinal muscles with a Touhy 18-gauge 3.5 inches needle (B. Braun Medical, Inc., PA, USA). The needle was removed carefully keeping the catheter in place, and no signs of bleeding were observed after the needle was removed. The patient reported analgesia from epidural and PCA dose was weaned down. Overnight she started leaking from the epidural and tunneled sites; coagulation parameters were normal. A neuro check was normal after stopping the epidural infusion for two hours. On the second day, the bleeding was more pronounced, her platelets were 96,000 INR 1.2, and the surgical hemostat was applied with pressure dressings. The neuro checks continued to rule out epidural hematoma and spinal cord injury. Aspiration of the epidural catheter was bloodless, and a test dose of 3 mm of lidocaine 1.5% with epinephrine 1:200,000 was negative, ruling out migration to a vessel. On the third day, the patient had massive bleeding, which came from the tunnel site developing big clots around the dressings. Aspiration of the epidural catheter was bloodless, and a test dose of 3 mm of lidocaine 1.5% with epinephrine 1:200,000 was negative. Thrombin, Stat Seal disc (Biolife, LLC, Sarasota, FL, USA), Quick Clot (Z-MEDICA, LLC, Wallingford, CT, USA), and all hemostatic agents were applied, without any success. The patient was transfused with platelets (her count was 76,000), fresh frozen plasma, and packed red blood cells because at this point, her hemoglobin level was 5.4 g/dL. Bleeding resolved after removing the epidural catheter. |
pmc-6110410-1 | A 56-year-old female, with a history of a repaired Tetralogy of Fallot and pulmonary embolism while on warfarin, presented with epigastric pain and melena. The patient was febrile (101.2℉) but hemodynamically stable and did not appear to be septic. Labs on admission are shown in Table .
The patient was given 10 mg of vitamin K intravenously and six units of fresh frozen plasma. The esophagogastroduodenoscopy (EGD) showed two nonbleeding duodenal arteriovenous malformations (AVMs). Her total bilirubin level increased to 3.0 mg/dL on day three of her hospital stay. An abdominal ultrasound (US) scan and a CT scan with/without contrast (Figure ) showed acute portal vein thrombosis extending into the splenic vein and segmental branches of the right and left hepatic lobes. No abscesses or other sources of infection were noted.
The patient was started on 1 mg/kg enoxaparin daily (INR 1.5 on day three). The patient’s initial fever and leukocytosis were attributed to portal vein thrombosis; thus, no antibiotics were given, pending blood cultures. The next day, the blood cultures grew Gram-positive cocci and rods (Micromonas miros and Actinomyces turicensis, respectively). She was started on IV vancomycin. However, she continued to spike fevers with worsening leukocytosis (Figure ). An echocardiogram did not show any valve vegetation. A tagged WBC scan showed no evidence of infection, making infective endocarditis unlikely. Her dental evaluation showed poor oral hygiene, multiple retained roots, pulpal necrosis, and mobile teeth. Repeated blood cultures grew Actinomyces meyeri. Both the hepatology and infectious diseases teams agreed this was likely a septic pylephlebitis secondary to Actinomyces bacteremia (likely stemming from the oral cavity). She was switched to IV penicillin G, after which her WBC count improved (Figure ) and repeated blood cultures came back negative. She was discharged on IV ertapenem for six weeks followed by six weeks of oral amoxicillin and a follow-up appointment for oral surgery. |
pmc-6110411-1 | A 31-year-old male presented to the emergency department with a five-week history of right-sided chest pain, right upper quadrant abdominal pain, and associated shortness of breath. On initial clinical review, he claimed to be otherwise healthy with no prior medical or social history. The patient denied any prior history of renal disease. He claimed to have sustained a fall at work five weeks prior to presentation and started noticing gradually worsening right-sided chest pain. On initial presentation, he was tachycardic with a pulse rate of 104 beats/minute, blood pressure 121/76 mmHg, and oxygen saturation of 100% on room air. The cardiac examination was unremarkable with no additional sounds and murmurs. He was tender over lower four right ribs. Lungs were clear to auscultation with no rales or rhonchi. The abdomen was soft and non-tender, with no evidence of organomegaly, and there was no peripheral edema.
His important baseline investigations are listed in Table :
He underwent a chest X-ray that suggested a pleural lesion in the right hemothorax (Figure ). Computed tomography (CT) showed an expansile lytic lesion corresponding to the pleural lesion (Figure ). Multiple lytic deposits were also seen on the CT scan (Figures -). A subsequent skeletal survey revealed multiple lesions on the skull, pelvic bone, and proximal right femur. The lytic lesions were investigated further and revealed normocytic anemia with hemoglobin of 113 g/L, mean corpuscular volume (MCV) of 83.6 fL and 3+ rouleaux formation on peripheral blood smear, and normal white cell and platelet count. Corrected calcium was 4.43 mmol/L, and creatinine was 621 μmol with urea of 23.6 mmol/L. Urine microscopy was positive for protein and negative for blood.
On serum protein electrophoresis, total protein was 114 g/L with high gamma globulin 47.5 g/L (6.0-18.0 g/L) and a monoclonal band (M-spike) 44.6 g/L. Immunoglobulin panel revealed IgG 62.40 g/L (5.52-17.24 g/L), and immunofixation electrophoresis revealed monoclonal IgG, type kappa (k). Immunofixation of urine revealed Ig G (k) of 0.24 g/d. The patient consequently underwent a bone marrow core and aspirate biopsy of the iliac crest. The aspirate was suboptimal for evaluation for flow cytometry. The biopsy revealed sheets of plasma cells and interstitial infiltrate involving approximately 50% of the biopsy cellularity. Immunohistochemical staining was positive for CD 138 (suggestive of plasma cells). The results were consistent with a diagnosis of multiple myeloma based on diagnostic criteria by International Myeloma Working Group (IMWG).
He was started on the cyclophosphamide-bortezomib-dexamethasone (CyBorD) regimen and received four cycles of therapy. He had an excellent renal response but a partial hematologic response and relapsed after four months of therapy. The biochemical and hematologic response is documented in Table . He is now being treated with lenalidomide and dexamethasone, and once he achieves hematologic remission, he will undergo autologous stem cell transplant. |
pmc-6110412-1 | A 38-year-old male presented to the otorhinolaryngology clinic with the complaint of right-sided neck swelling in February 2013. This swelling had been progressively increasing for three months. There was no associated pain, fever, or difficulty in swallowing. He also reported having a painless swelling on the scalp which had been there for 20 years. On examination, there was a firm, fixed, non-tender mass palpable on the right side of the neck at level II. It measured 3 x 3 cm in size. Another lump was appreciated on the scalp, which was soft in consistency, non-tender, mobile, and 4 x 4 cm in size.
Considering these clinical findings, he underwent excisional biopsy of the right nodal mass which suggested hidradenocarcinoma. Histopathologic evaluation revealed sheets of tumor cells showing pleomorphic cells and frequent mitotic figures. On immunohistochemical staining, tumor cells showed positivity for cytokeratin 7, epithelial membrane antigen (EMA), and p63 (Figure ). A panendoscopy showed no abnormality in the pharynx, nasal cavity, or larynx. The locoregional extent of the disease was evaluated by a computed tomography (CT) scan of the head and neck that showed multiple enlarged lymph nodes on the right side of the neck (Figure ), along with a well-defined lobulated cystic mass over the right side of the scalp (Figure ). CT scans of the chest and abdomen were negative for any distant metastasis (Figure ).
The case was discussed in the head and neck multidisciplinary tumor board meeting at our hospital. On the basis of the available evidence, the consensus was to go for a wide local excision of the scalp lesion, along with a right-sided neck dissection. The histopathology of the scalp lesion was reported as malignant hidradenocarcinoma. The size of the lesion was 4.2 x 3.5 x 2.2 cm with a closest resection (deep) margin of 0.1 cm. A total of 56 lymph nodes were recovered from the right side of the neck, out of which two were positive for tumor metastasis at level II, the largest deposit being 2.3 cm in size.
Postoperatively, the case was again discussed in the tumor board meeting where the consensus was to offer concurrent chemoradiation. Radiation therapy was offered in two phases to a total dose of 60 Gy in 30 fractions. In phase 1, a radiation dose of 50 Gy was given to the scalp and ipsilateral neck from level II to level IV. A boost dose of 10 Gy was delivered in phase 2 to the deep margin in the scalp and level II neck only. Concurrent cisplatin was given with the radiation at a dose of 100 mg/m2 as a radiosensitizer. After completion of treatment, he was followed up with clinical examination and serial imaging of the head and neck. Currently, he has completed five years of follow-up and is disease-free, both for local and distant metastasis. |
pmc-6110413-1 | A 76-year-old female with past medical history of well-controlled hypertension, coronary artery disease presented with subacute progressive shortness of breath for two weeks. On presentation, blood pressure (BP) was 238/146 mm Hg, heart rate (HR) of 75 beats per minute (bpm), SaO2 (oxygen saturation) to 80% and was placed on 4 L nasal cannula (NC) with improvement in her oxygenation. Physical exam was remarkable for pulsus paradoxus, distant heart sounds without murmurs or gallops, marked jugular venous distension, diminished breath sounds at the bases and mild bilateral lower extremity pitting edema. Electrocardiogram (EKG) showed only low voltage (Figure ).
Chest radiograph showed enlarged cardiac silhouette and bilateral moderate pleural effusions. An echocardiogram demonstrated moderate to large pericardial effusion with tamponade physiology (Figures , , ).
The patient remained significantly hypertensive despite adding three antihypertensive medications requiring labetalol drip with failure to control her blood pressure. She underwent pericardiocentesis with the removal of 1200 cc bloody fluid. Right heart catheterization was also done prior and after the pericardiocentesis, which indicated severely elevated right-sided pressures and equalization of right atrial, right ventricular and pulmonary capillary wedge pressure with diminished cardiac output. There was a significant improvement in right-sided pressures following pericardial drainage, with a mean right atrial pressure of 10 mm Hg down from 21 mm Hg. Systemic blood pressure normalized after pericardiocentesis. Follow-up echocardiogram showed resolution of the pericardial effusion. Further workup was done to identify the etiology of the pericardial effusion, including fluid cytology, culture, lactate dehydrogenase (LDH), serum antinuclear antibodies (ANA), serum complement, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), anti-double-stranded DNA (dsDNA), and anti-Smith antibody. Analysis of the pericardial fluid showed exudative fluid and it was negative for malignant cells. |
pmc-6110414-1 | A 32-year-old female, gravida 2 para 1 at gestational age of 36 weeks and two days, presented to the Overlook Medical Center at 2:57 am complaining of nausea and contractions, which had started earlier in the night and worsened. Prenatal records were unavailable. Her previous pregnancy was complicated by premature rupture of membranes, and she delivered vaginally a healthy infant at 36 weeks of gestational age.
During intake, the patient sat upright, appearing uncomfortable, and complained of epigastric pain and vomiting. The physical examination was remarkable for a blood pressure of 202/101 mmHg. Initial laboratory results were significant for the following: white blood cell count (WBC) 13.6 x 103/µL, urine protein of 300 mg/dL, hemoglobin (HGB) 15.6 g/dL, platelets (PLT) 182 x 103/µL, lipase 200 IU/L, total bilirubin (T bili) 0.2 mg/dL, aspartate transaminase (AST) 56 IU/L, alanine transaminase (ALT) 40 IU/L, alkaline phosphatase (ALP) 162 IU/L, and albumin 2.3 g/dL.
Upon a diagnosis of severe preeclampsia, the patient was started on intravenous (IV) magnesium sulfate for seizure prophylaxis at 2 g/h and was given IV labetalol to control blood pressure. The fetal non-stress test was reactive and category 1. The patient was scheduled for emergent cesarean section, which was carried out without complications three hours after admission, resulting in the delivery of a vigorous 1.645 kg male infant, with appearance, pulse, grimace, activity, respiration (APGAR) scores of 8/9 at one and five minutes, respectively. The placenta was delivered complete, and the blood loss during surgery was 680 mL. In the recovery room, the patient continued with high blood pressure values in the 190s/110s mmHg and was given boluses of 10 mg of hydralazine IV in addition to IV labetalol.
Two hours post-operation (post-op), the patient reported severe right upper quadrant pain with worsening nausea and vomiting. Laboratory data at that time revealed up-trending liver enzymes (AST of 1054, ALT of 687, ALP of 134 IU/L), a T bili that had risen but was still in the normal range of 0.8 mg/dL, worsening of her hypoalbuminemia at 1.7 g/dL, anemia of 11.2 g/dL, thrombocytopenia of 59 x103/µL, and worsening leukocytosis with neutrophilia (19.9 x103/µL and 87.3%). Prior to this point, the patient had received 1.6 L of IV fluids. The international normalized ratio (INR) was slightly elevated at 1.19, and the fibrinogen was decreased at 192 mg/dL, with fibrin degradation products ≥20 µg/mL. The patient was then transferred to the intensive care unit (ICU) with the diagnosis of HELLP syndrome. A chest x-ray to rule out pulmonary edema reported no significant findings.
Six hours post-op, the patient still complained of right upper quadrant pain and nausea, but these were slightly improving. Her physical exam was remarkable for decreased breath sounds bilaterally at the lung bases and diffuse abdominal tenderness, which was more prominent on the left side. Subsequent laboratory values reported worsening transaminitis with AST of 1332, ALT of 663, ALP of 146 IU/L, increased T bili of 1.1 mg/dL, WBC of 20.5 x103/µL, and worsening PLT of 38 x103/µL. An elevated lactate dehydrogenase (LDH) of 1881 IU/L and a decreased haptoglobin of <8 mg/dL pointed to a hemolytic process consistent with HELLP syndrome. Although the patient was afebrile, empiric antibiotic coverage with IV cefazolin 2 g every eight hours was initiated out of concern for endometritis given her recent delivery. Her fibrinogen levels had improved, however, to 228 mg/dL. Magnesium levels were monitored, and the magnesium infusion was adjusted accordingly. Blood pressure levels showed signs of better control, with values in the 150s/105s mmHg, and she was maintained on an IV labetalol infusion. A chest x-ray was ordered, and was reported clear. Worsening thrombocytopenia and liver function tests prompted an abdominal computed tomography (CT) scan, which revealed a small volume of complex abdominal and pelvic ascites, mild bilateral pleural effusions and bibasilar atelectasis, and no evidence of subcapsular hematoma, liver, or gallstone pathology. Upon further review of the CT scan, it was felt that the pancreas appeared prominent, which prompted further workup. We include an image of the CT scan below in Figure .
Twelve hours post-op, the patient had improved blood pressure values in the 130s/90s mmHg. Pancreatitis was confirmed with a lipase of 2365 IU/L, which had risen from 200 IU/L on admission. Laboratory findings also showed increased lactic acid of 2.9 mmol/L, bicarbonate (HCO3-) of 22 mEq/L, worsening anemia with HGB of 10.1 g/dL, down-trending liver enzymes (AST of 944, ALT of 536 IU/L), and improved leukocytosis (WBC of 17.3 x103/µL). The labetalol infusion was discontinued at this point, given her lower blood pressure values. Labetalol, as needed, was ordered to maintain a blood pressure goal of below 150s/110s mmHg.
In the morning of the second day after admission, the patient´s blood pressure improved to 145-118 /92-79 mmHg, her right upper quadrant pain was reduced, and her physical exam revealed decreased abdominal tenderness. Laboratory values showed down-trending transaminitis (AST of 573, ALT of 415, ALP of 111 IU/L), and decreasing LDH of 1030 IU/L. The anemia and thrombocytopenia had worsened to HGB of 9 g/dL and PLT of 36 x103/µL, with increasing WBC 15.6 x103/µL. The lipase level had increased to 2509 IU/L together with the lactic acid 3.9 mmol/L, yet her HCO3- level remained normal at 23 mEq/L. On the evening of hospital day 2, she started tolerating clear liquids with only mild nausea. Laboratory results eventually showed normalization of the lipase at 186 IU/L, and her liver enzyme levels continued trending downward, along with trends toward normalization of her other laboratory values.
On the third day after admission, the patient maintained normal blood pressure values (110s/80s mmHg) with oral labetalol. Her abdominal pain continued decreasing and her nausea stopped. She remained on the magnesium sulfate infusion and was transferred from the ICU back to the obstetrics floor. The patient continued to improve on her fourth day, with decreasing liver enzymes (AST of 84, ALT of 113, ALP of 99 IU/L), increasing platelets (PLT 80 x103/µL), and decreasing WBC at 13.3 x103/µL, but her HGB dropped to 7.9 g/dL. The patient was not transfused, as she was hemodynamically stable. Importantly, her creatinine levels remained below 1.1 mg/dL throughout her hospitalization. The patient was subsequently discharged on the fifth day after admission, with improved HGB of 8.5 g/dL, PLT of 127 x103/µL, WBC of 11.7 x103/µL, and normalization of her transaminitis. |
pmc-6110417-1 | A 25-year-old female with gestational amenorrhea for 32 weeks presented to our outpatient department with complaints of a recurring headache along with pain and weakness in the legs for the past seven months. The headache was described as a bilateral, dull and persistent pain that fluctuated between mild to moderate in intensity. She also described neck stiffness along with her chief complaints but denied any nausea, vomiting, and changes in gait or memory. The pain in her legs waxed and waned over time, although progressively increasing in intensity with each passing episode. At the outset of this predicament, pain was localized to her left leg, eventually became symmetrical and later progressed to afflict both arms. She denied numbness or paresthesia. She was eventually brought to our clinical setting following an aggravation of her symptoms over the previous two weeks that lead to a restriction in mobility. At the time of this presentation, she also complained of double vision that was gradually worsening. She also added that she experienced fluctuating fevers, undocumented weight loss, and episodes of night sweats for the last four months.
Initial assessment found the patient to be alert and well-oriented, with a Glasgow Coma Scale score (GCS) of 15/15, albeit thin, emaciated, and noticeably distressed due to her clinical predicament. Her heart rate (HR) was 102/minute with a respiratory rate (RR) of 18/minute, a temperature of 98.4°F and a blood pressure (BP) of 110/175 mm Hg. A neurological examination revealed generalized weakness and a bilaterally diminished muscle tone. A strength assessment revealed that she had reduced power in her upper (right arm; 2/5, left arm; 4/5) and lower (right leg; 1/5, left leg; 3/5) extremities. There was a complete absence of all deep tendon reflexes except the biceps. A comprehensive ophthalmological exam demonstrated normal visual acuity, with notable issues in the right eye which included ptosis, fixed and dilated pupil, and diplopia which manifested with the right-sided gaze. A funduscopic examination showed normal definitions. She also had a bilateral facial nerve palsy which affected the lower half of the face, along with reduced sensation along the distribution of the maxillary and mandibular divisions of the trigeminal nerve. This deficit was more pronounced on the right side of the face. On abdominal examination, an appendectomy scar was visible on the right iliac fossa. The abdomen was protuberant, soft and non-tender. Bowel sounds were audible and inguinal lymph nodes were not palpable.
Initial laboratory investigations were within normal limits, with the exception of an elevated erythrocyte sedimentation rate (ESR) of 128 millimeters/hour. A magnetic resonance imaging (MRI) scan of the brain ruled out any local pathology that could explain her neurological deficits. A cerebrospinal fluid (CSF) analysis following a lumbar puncture revealed a white blood cell (WBC) count of 1500 with neutrophilic predominance, which leads to the initiation of empirical therapy for bacterial meningitis. Two days after the initiation of antibiotic therapy, she complained of dull abdominal pain and fullness. She was investigated with an abdominal ultrasound which revealed a thickened descending colon with a well-defined heterogeneous lesion measuring 89 mm by 94 mm in the left adnexal region that impinged on the uterus and urinary bladder due to its mass effect. The lesion was further investigated using a computed tomography (CT) scan which disclosed a circumferential mural thickening in the distal third of the descending colon with no luminal narrowing at the site. Multiple enlarged para-aortic lymph nodes were also appreciated, with the largest measuring 17 mm by 10 mm at the level of the left renal hilum.
Following patient stabilization, the adnexal mass was biopsied which showed an atypical infiltrate composed of small to medium cells exhibiting immature chromatin, irregular nuclear folds, and increased mitosis. Immunohistochemistry showed this infiltrate to be CD3 (+), TdT (+), CD99 (+), PAX-5 (-) and CD20 (-), consistent with precursor T cell lymphoblastic lymphoma (Figures -).
In lieu of her newly diagnosed malignancy, we suspected that her neurological deficits could be attributed to a paraneoplastic syndrome. A workup for autoimmune etiologies was unrevealing based on a negative serum electrophoresis, negative anti-ganglioside profile and a negative anti-neuronal profile (Tables -).
The patient eventually underwent a nerve conduction study that revealed severe sensory-motor axonal neuropathy involving the left tibial, left peroneal and right facial nerve.
An eventual diagnosis of paraneoplastic MM was formulated based on a combination of the physical findings and documented nerve damage that simultaneously affected two separate nerve areas. She was treated with plasmapheresis which eventually led to a resolution of her neurological discrepancies. The patient remains asymptomatic till date from a neurological standpoint. |
pmc-6110419-1 | A previously healthy 41-year-old male, presented to the emergency department (ED) complaining about involuntary movements of the left arm and abrupt onset that had started 12 hours prior to the admission. He complained of asthenia, adynamia, polyuria, and hyporexia for the last three days. Upon arrival, his blood pressure was 129/82 mmHg with a heart rate of 101 beats per minute; the respiratory rate was 20 breaths per minute and the temperature was 36.4°C. The capillary glucose level was 566 mg/dL. On physical examination, his left arm had a persistent and arrhythmic violent high-amplitude movement, mainly affecting the proximal muscles, which were consistent with monoballism (Video ). The patient was alert and co-operative. Speech, cranial nerves, strength, muscle stretch reflexes, and cerebellum examination were unremarkable.
The patient’s initial blood workup showed a serum sodium of 145 mmol/L (normal range: 135–145) with a corrected sodium of 152 mmol/L for a glucose of 517 mg/dL; potassium 3.7 mmol/L (normal range: 3.6–5), chloride 88 mmol/L (normal range: 98-107), magnesium 0.73 mmol/L (normal range: 0.66-1.85), calcium 2.5 mmol/L (normal range: 2.15-2.5), and serum lactate 1.8 mmol/L. An arterial blood gas analysis showed a moderate metabolic acidosis with a pH of 7.4 and a bicarbonate of 8.7 mmol/L; a calculated osmolarity of 332 mOsm/L (normal range: 285–295) and a high anion gap of 48 mmol/L (normal range: 8-16). Urinalysis was relevant for glycosuria (1,000 mg/dL) and ketonuria (80 mg/dL). These findings were consistent with a mixed hyperglycemic state (ketoacidosis and hyperosmolar state). Complete blood cell count and renal function tests were within the normal range.
The magnetic resonance imaging (MRI) of the brain was normal (Figure ), without any evidence of ischemia or hemorrhage. In the ED, the patient was treated with normal saline and insulin infusion, which resolved the acute hyperglycemia and the acid base disorder. After resolving the latter, the patient was moved to the internal medicine department. Monoballism resolved 48 hours after correction of the metabolic abnormalities and the patient was discharged four days after admission with insulin as the treatment for his new-onset diabetes. |
pmc-6110421-1 | A 61-year-old male, with a history of emphysema, obstructive sleep apnea, and hypertension, presented to the emergency room with worsening shortness of breath over a three-month period. The patient also complained of orthopnea, paroxysmal nocturnal dyspnea, and progressively worsening lower limb edema. On examination, the patient had jugular venous distension, bilateral lower extremity edema, and bibasilar crackles. The laboratory evaluation showed a B-natriuretic peptide level of 11,065 pg/ml and a troponin level of < 0.04 ng/ml. A transthoracic echocardiogram showed a reduced left ventricular ejection fraction (LVEF) of 20%-25% with prominent hyper-trabeculations noted in the left ventricle, most prominent in the lateral and apical walls. These findings were concerning for LVNC. Cardiac magnetic resonance imaging (CMRI) showed a non-compacted to compacted myocardium ratio of 5:1 at the left ventricular apex (Figure ), confirming the diagnosis of LVNC. The patient underwent left heart catheterization, which did not show obstructive coronary disease as an etiology for the cardiomyopathy. The patient was managed with guideline-directed therapy for heart failure, including carvedilol, losartan, furosemide, hydralazine, and isosorbide mononitrate. He was also started on warfarin due to the increased risk of thromboembolism associated with LVNC. He had episodes of non-sustained ventricular tachycardia during his admission and was subsequently evaluated by electrophysiology (EP). He was discharged home with a wearable cardioverter defibrillator with instructions to follow up with EP in three months for an evaluation of implantable cardioverter defibrillator (ICD) placement for primary prevention. |
pmc-6110626-1 | A previously healthy right-handed 24-year-old woman developed a headache three days before admission in the left frontal region with an 8/10 intensity accompanied by retro-ocular pain and phosphenes. Twenty-four hours later, she developed a speech disorder and was presented to the emergency department. Upon arrival, her blood pressure was normal (110/70 mmHg), tachycardic with a heart rate of 94 beats per minute, normal respiratory rate (14 breaths per minute) and temperature (36.2°C). The neurological examination showed normal mental status, with fluent speech and no paraphasias. The patient had normal nomination, and she was able to understand and obey simple commands. She was able to read-out loud and write, but could not repeat simple phrases; the rest of the examination was normal. Her blood work revealed hemoglobin of 8.9 g/dL and 4,390 leukocytes mm3/mL, human immunodeficiency virus type one and two antibodies detection were negative; rest of the blood work was normal. A chest X-ray was performed and it revealed generalized symmetrical interstitial infiltrates. Acontrast-enhanced magnetic resonance image (MRI) of the brain showed multiple edematous nodular lesions in the left parietal lobe and cerebellum on the T1-weighted sequence (Figure ).
Transthoracic echocardiogram, carotid and vertebral Doppler ultrasound examination were normal. Cerebrospinal fluid (CSF) analysis showed 88 cells mm3/mL of which 65% were mononuclear with low glucose of 36 mg/dL, a central glucose of 116 mg/dL (ratio 0.31), and elevated proteins of 201 mg/dL. The CSF smear was negative and Gene Xpert (Cepheid Inc., Sunnyvale, CA, USA) MTB/rifampicin (RIF) in the CSF was positive for MTB. She was started on first-line antituberculosis drugs (isoniazid, rifampicin, pyrazinamide and ethambutol) and dexamethasone (0.4 mg/kg/day). The patient was discharged on the 11th day of hospital stay. After her three-month follow-up, she still had CA. |
pmc-6110627-1 | A 46-year-old female had symptoms of right ear congestion accompanied by pulsatile tinnitus and mild hearing loss. Neurological examination revealed weakness of cranial nerves X and XII. Magnetic resonance imaging (MRI) identified a 4.2 x 4.7 x 4.1 cm lobulated mass centered at the cerebellopontine angle that was hypointense on T1-weighted, heterogeneous on T2-weighted, and avidly enhancing on post-contrast images (Figure ). No significant component was noted within the internal auditory canal. An Octreoscan was performed, which showed intense increased tracer uptake in the mass centered in the region of the right jugular foramen, thereby supporting the suspected diagnosis of paraganglioma (Figure ).
Digital subtraction angiography (DSA) demonstrated a surprising lack of vascularity associated with the tumor. However, there was an incidental discovery of a Cognard IIa+b dural arteriovenous fistula in the right posterior fossa associated with an occluded right sigmoid sinus (Figure -).
Due to the extensive volume of tumor, the patient underwent a staged surgical resection. The first surgery included a modified radical right neck dissection, right superficial parotidectomy with facial nerve dissection, as well as the initial approach to the tumor and partial extradural resection. One week later, the patient underwent the second stage surgery where the tumor was radically resected using a right transcochlear approach. The right sigmoid sinus was ligated. The facial nerve was mobilized and transposed. Postoperative MRI confirmed complete resection of the tumor (Figure ). Histological analysis of samples from both surgeries confirmed the tumor not to be a paraganglioma, but instead a schwannoma (Figure ).
She had a long recovery from the surgery due to the lower cranial nerve palsies but has shown gradual improvement. Her latest follow-up MRI (48 months from surgery) (Figure ) showed no evidence of recurrent tumor; however, there was some residual posterior fossa DAVF. At that time, she also reported bothersome pulsatile tinnitus that she perceives on the right despite a complete hearing loss on the right side. DSA revealed new large feeders from the right middle meningeal artery (MMA) and occipital arteries into the residual DAVF (figure ), which were not present on initial presentation (Figure ). The DAVF was embolized utilizing Onyx in the right MMA. Final right common carotid artery (CCA) angiogram demonstrated resolution in arteriovenous shunting (Figure ). Vertebral artery injection after embolization demonstrated minimal residual shunting via the right anterior inferior cerebellar artery (AICA) (Figure ). A further intervention was declined by the patient and angiographic follow-up in one year has been scheduled. |
pmc-6110681-1 | A 55-year-old right-hand-dominant male with a history of acute inflammatory demyelinating process and a 3-month history of a left volar wrist and hypothenar soft tissue mass presented for evaluation. The patient was admitted to the hospital with generalized weakness, ataxia, and multiple sensory deficits, including complete lack of sensation in the left small finger and ulnar side of his hand. Although his sensory deficits were initially thought to relate to his generalized demyelinating disorder, on examination, the ulnar deficit was thought to be related to the mass in his hand. The mass was soft, nontender, and did not limit range of motion. Two-point sensation was absent in the ulnar nerve distribution distal to the wrist, and grip strength, while not measured objectively, was decreased compared with the contralateral side. There was no history of trauma, previous surgery, or other masses, and radiographs of the left upper extremity were normal. A lipoma was the suspected initial diagnosis. Magnetic resonance angiography of the left hand showed a soft-tissue mass of unclear etiology (Fig. ).
Operative excision was performed under general anesthesia. A longitudinally oriented ulnar-sided skin incision was made over the mass, with dissection through the palmar fascia. The ulnar nerve and artery were dissected free from the mass, and Guyon’s canal was released. The mass was noted to be arising from beneath the hypothenar musculature. Grossly, it was tan-white, rubbery, and lobulated (Fig. ). Pathology confirmed the mass to be a benign myxoma (Fig. ). There were no postoperative complications. At 5 weeks postoperatively, the patient reported marked improvement in his numbness and weakness. He was found to have intact sensation in the ulnar nerve distribution distal to the site of the excised mass, and improved grip strength. The patient was asked to return in several months for repeat sensorimotor assessment, but was subsequently lost to follow-up. |
pmc-6110811-1 | The child, a Chinese boy with birth weight of 3,450 g and gestational age of 39+6 week (his mother was 28-year-old, G1P1, with normal pregnancy), was screened in Genetics and Metabolism Department of the Obstetrics and Gynecology Hospital affiliated to the Nanjing Medical University at 3th day after birth. The results are shown in Table . MS/MS showed that he had elevated C3/C2 but C3 and 3-hydroxypropionate remained almost normal. In order to identify the etiology, the patient and his families were diagnosed by Genetic diagnosis panel in our hospital on 16 June 2016. Parents were healthy and non-consanguineous.
Genetic diagnosis panel of genetic metabolic disease covers 51 diseases and 98 genes, of which Panel 1 covers 18 amino acid metabolism diseases and 35 genes, Panel 2 covers 17 diseases, and 42 genes of organic acid metabolic diseases and glycogen metabolism diseases, and Panel 3 covers 16 fatty acid metabolism diseases and 21 genes. Genomic DNA was extracted from the peripheral blood of the families using the OMEGA Genomic DNA Extraction Kit (OMEGA Biotech, USA). All mutations were verified by Sanger sequencing. Ion Torrent data extraction, sequence alignment and SNPs and Indels extraction were performed by using Ion Torrent Suite v3.0 software. After the resulting SNPs and indels were filtered by the dbSNP 137 database, HGMD, LOVD and other databases and Pubmed related literatures were retrieved, matching the reported pathogenic sites. Two pathogenic mutations (c.802C>T/c.827delG) were detected in the PCCA gene (Table , Figure ), among them, the variation rs774738181 (c.802C>T) was present on the dbSNP database which appeared to be “Likely pathogenic” in GenBank dbSNP (). we propose that this variation may be pathogenic. ().
c.827delG was a frameshift mutation, leading to p.Gly276ValfsX46 mutation of amino acid sequence, which has not been reported. According to the ACMG principle, the mutation was a highly reliable pathogenic mutant type. The protein function was predicted by SIFT and PolyPhen, and the results were all harmful. The identified pathogenic mutations and suspected pathogenic mutations were confirmed by Sanger sequencing.
Although two pathogenic mutations were detected in PCCA, two mutations were not reported before, and the 3-Hydroxypropionate in urine was only slightly increased. Therefore, the treatment was postponed and frequency of follow-up was increased.
The patient underwent 1 year of follow-up. MS/MS and GC/MS detection results were shown in Table . He remained asymptomatic and his blood ammonia and liver function were normal.
When the child was 1 year old (in May of 2017), C3 and 3-Hydroxypropionate sudden elevated significantly, indicating the pathogenicity of c.802C>T and c.827delG. Thus we suggest that c.802C>T and c.827delG may be linked to late-onset PA. |
pmc-6111297-1 | This case study was approved by the Institutional Review Board (07-CR-085) of Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation.
A 61-year-old G2P1AA1 woman presented with intermittent, progressive lower abdominal pain for three years. She had a medical history of hypertension that was controlled with medication. In 1993, she was diagnosed as having a uterine leiomyoma with leiomyomatosis of retroperitoneal tumors. Because of her desire to bear children in the future, she underwent myomectomy at that time. Subsequently, recurrent DPL developed two years later due to an enlarged palpable mass in the abdomen with intermittent abdominal pain. She underwent abdominal hysterectomy with left-sided oophorectomy and right ovary wedge resection in 1996. Results of the pathological report showed a borderline mucinous ovarian tumor of the left ovary. In 1998, recurrent DPL with left ureter involvement was noted, and the third operation involving debulking surgery and reteroneocystostomy was performed. Results of that pathological report showed no significant malignancy. She was regularly followed up at gynecologic clinics. In 1999, a 9 × 9-cm2 palpable pelvic mass was observed, and recurrent leiomyomatosis was suspected. A fourth laparotomy for tumor excision was suggested to the patient, but she refused. Hormone therapy with medroxyprogesterone (5-mg tablet daily) was performed until 2014 because of the progression of a thyroid nodular goiter and hypertension. After stopping hormone therapy, she reported intermittent, progressive lower abdominal pain, and a growing palpable mass was observed in the abdomen.
On admission, her temperature was 36.6 °C, blood pressure was 123/69 mmHg, heart rate was 83 beats/min, body weight was 59.8 kg, body height was 155.5 cm, and body mass index was 24.7 kg/m2. On pelvic examination, a huge tumor was palpable in the pelvis. Transvaginal ultrasonography showed huge solid tumors measuring about 15.17 × 24.48 × 10.51 cm3 in the pelvic field without free fluid in the cul-de-sac region (A–D).
The laboratory evaluation showed the following: white blood cell count, 13,520 µL; hemoglobin level, 7.8 g/dL; fibrin degradation product level, >10,000 ng/mL; follicle-stimulating hormone level, 15.98 mIU/mL; progesterone level, 1.58 ng/mL; and, estradiol level, 32.84 pg/mL. No significant sign of infection or internal bleeding was indicated by the laboratory data. There were no significantly increased tumor markers, such as the carbohydrate antigen 125 level (20.2 IU/mL), carbohydrate antigen 19–9 level (10.20 IU/mL), and carcinoembryonic antigen level (0.649 ng/mL). The chest X-ray showed nodular densities in the right lower lung ().
Contrast-enhanced whole-body computed tomography was performed and revealed three heterogeneous pelvic tumors, which were measuring approximately 9.4 × 8.6 × 9.3 cm3, 7.1 × 6.1 × 6.0 cm3, and 11.1 × 7.5 × 9.1 cm3, with multiple pulmonary nodules and multiple heterogeneous hepatic tumors. Therefore, distant metastasis was suspected. Severe hydronephrosis of the right kidney was obvious due to tumor compression (A–E).
Exploratory laparotomy was recommended and performed. Three individual bulky tumors were encountered in the retroperitoneal pelvic cavity, which were found by the direct compression of the urinary bladder and both ureters. A solitary tumor mass measuring about 14.5 × 12 × 9 cm3 and weighing 1400 g was excised from the left paracolic gutter with extensive abdominal peritoneal carcinomatosis. The smooth-surfaced tumor seedings were suspected to be benign myomatous lesions. The right ovary was found in the right pelvic cavity and adhered to the interbowel loops. The pelvic tumor partially invaded the urinary bladder (A–D). Nearly complete cytoreductive surgery was performed. The three individual bulky tumors were resected with the left ovary, right adnexa, paracolic gutter tumor, and cul-de-sac cells for cytology. Unlike complete staging surgery, she did not undergo omentectomy, appendectomy, and lymph node assessment.
Results of the final pathology report showed that the largest encapsulated tumor had many spindle cells with multinucleated pleomorphic nuclei, extensive necrosis, and a mitotic index of 11/10 per high power field, which is consistent with high-grade leiomyosarcoma (differentiation score = 3, mitotic score = 2, necrotic score = 2, total score = 7; French Federation of Cancer Centers Sarcoma Group histologic grade 3). Immunohistochemistry staining showed that the tumor cells were reactive with desmin, negative with cytokeratin and CD117 (c-kit), and negative for estrogen and progesterone receptors. The immunohistochemical profile confirmed leiomyomatous differentiation in other small nodules that were seeding in the peritoneum and omentum, smaller pelvic masses with hypercellular spindle cell tumors, and minimal nuclear atypia, which were all indicative of leiomyomatosis. She was diagnosed as having a leiomyosarcoma arising from DPL at 61 years of age. Chemotherapy with doxorubicin caused the leiomyosarcoma.
Unfortunately, she died approximately one month after the diagnosis because of rapid progression of pleural effusion due to malignancy. |
pmc-6112024-1 | The patient was a 75-year-old woman, who had developed left shoulder pain five years earlier without any known precipitating factor. She presented to our department because of gradual difficulty in raising her left arm and worsening pain. Physical examination on presentation did not reveal any swelling or feeling of heat in the left shoulder. The range of motion of the left shoulder showed extremely severe restriction; namely, flexion 80°, abduction 60°, and external rotation 0°, and prominent impingement symptoms were found. On plain radiographs and computed tomography (CT), prominent shoulder arthropathic changes and numerous calcified lesions around the joint were found. On plain magnetic resonance imaging (MRI), around the shoulder an irregular hypointense region was identified in the center on T1-enhanced images and on T2-enhanced images (). Routine blood examinations did not reveal any obvious abnormalities. This patient was diagnosed with synovial osteochondromatosis associated with a massive tear of the rotator cuff and shoulder arthropathic changes, for which the treatment RSA was chosen.
Intraoperative findings: A delto-pectoral approach was used. Full-thickness tears of the supraspinatus and infraspinatus tendons were found. When the joint capsule was incised, synovial proliferation and a whitish mass-like lesion, seemingly adherent to the synovium, were found. The intraarticular mass was resected to the extent possible, but the cartilage in the humeral head was severely damaged, while that in the glenoid cavity had almost disappeared. After loose body resection, RSA was performed.
The postoperative course was uneventful, with the left shoulder pain disappearing from early in the postoperative period. At one year postoperatively, there was no recurrence of pain and the left shoulder range of motion showed improvement to flexion 140°, abduction 130°, and external rotation 30°. Moreover, no complications such as recurrence of osteochondromatosis, implant loosening, or infection were seen.
The loose body was found to consist of a cartilage component and bone tissue with hyalinization (). No findings indicative of malignancy were evident, and since nodular cartilage arrangement was found, primary osteochondroma was diagnosed. Synovial osteochondromatosis could be diagnosed. |
pmc-6112072-1 | An eight-year-old boy initially presented to us in 2008 with progressive headache and visual disturbances. His imaging revealed a giant pituitary tumour (59 x 45 x 42 mm) with extrasellar extension () with initial prolactin of 91,800 μg/L confirming the diagnosis of giant prolactinoma. Initially, he responded well to high doses of cabergoline (7 mg/week) with normalization of prolactin and total tumour shrinkage. A few years later, he developed recurrence of the tumour, which was resistant to cabergoline therapy (), and underwent transcranial excision of the tumour in 2013. During the immediate postoperative period, he developed recurrent hypoglycaemic episodes, which was confirmed to be endogenous insulin dependent hypoglycaemia biochemically (insulin was 15.9 µIU/mL and C-peptide was 3.94 ng/mL when random blood glucose was less than 2.1 mmol/L). Imaging located a well circumscribed lesion (20 x 12 x 10 mm) in the head of pancreas. He underwent enucleation of the tumour, and that was confirmed as an insulinoma histologically with benign characteristics (Ki67<1%). Six months after the pituitary surgery he received three-field radiotherapy (4500 cGy) and continued on cabergoline (3.5 mg/week) resulting in declining prolactin levels. His baseline echocardiography was normal. He had normal calcium at presentation, but currently he is being evaluated for new onset primary hyperparathyroidism (total calcium 2.98 mmol/L [normal range: 2.40-2.55], intact PTH 88.2 pg/L [12-60]). |
pmc-6112084-1 | A 21-year-old male presented to an emergency department (ED) with a two-day history of purulent drainage from his umbilicus. He denied pain. He reported that he had experienced a similar episode one year prior which was diagnosed in an ED as umbilical cellulitis and resolved with oral antibiotics. Interestingly, the patient noted that since childhood he had recurrent episodes of what he described as a “pulling sensation” in the umbilicus and suprapubic areas. The patient had seen multiple specialists regarding the sensation but the workups had been unremarkable.
The patient had no pertinent medical or surgical history. The family and social history were unremarkable. He did not take any medications and denied drug and alcohol use.
Vital signs on presentation were blood pressure 139/82 torr, heart rate 55 beats per minute, respiratory rate 15 breaths per minute, and temperature 98.5 degrees F. (oral temperature) with a pulse oximetry reading of 100% on room air.
Yellowish discharge was noted from center of the umbilicus. The periphery of the umbilicus was erythematous with mild tenderness to palpation. The physical examination was otherwise unremarkable.
The complete blood count and basic metabolic panel were within normal limits. The urinalysis was unremarkable.
A computed tomography (CT) scan of the abdomen and pelvis with oral and intravenous contrast revealed an urachal remnant arising from the anterior/superior margin of the bladder and extending to the umbilical region. The remnant consisted of a thin fibrous band of tissue measuring up to 4.6 mm in thickness near the umbilicus. The band narrowed to a minimum of 2 mm along its course. No umbilical fluid collection was identified. The abdominal fat posterior to the umbilicus showed no inflammatory reaction (Figures and ).
An infected umbilical-urachal sinus was suspected. The patient was treated with oral antibiotics since the patient had success with a similar presentation a year prior to the ED visit. He was instructed to follow up with a urologist in the outpatient setting for definitive treatment. His infection was resolved. He later underwent an excision of the urachal remnant. Histology showed no evidence of malignant transformation. |
pmc-6112089-1 | A 26-year-old Italian Caucasian male had a trauma from a fall on July 2014, with multiple fractures including left hemipelvis with luxation of coxofemoral joint (managed with reduction and osteosynthesis of the posterior acetabular wall), distal third of the right femur (treated with an osteosynthesis with plate and screws), and distal diaphysis of the right fibula (osteosynthesis plate and screws) along with facial skull trauma and chest trauma. All surgeries were executed in late 2014, and only perioperative antibiotic prophylaxis had been administered.
He also had a history of fracture of the left femur at 11 years of age treated with osteosynthesis with a rod that was subsequently removed, Von Willebrand disease, and depressive disorder.
On July 11, 2016, he was admitted to orthopedic surgery for redness and swelling of the right knee joint with a fistula on the right distal limb.
Magnetic resonance imaging (MRI) of the right knee and femur showed osteomyelitis of the distal femur ().
The patient underwent surgery with removal of implants, a fistulectomy of the right femur was performed, biopsies were collected, sonication of the plate was performed, and a knee brace was placed.
The same CRKP strains were isolated both on cultures of biopsies and on prosthetic material after sonication. Bacterial identification and antimicrobial susceptibility testing were performed using the Phoenix Automated Microbiology System (Becton Dickinson Diagnostic Systems, Sparks, MD, USA). Confirmatory MIC testing for imipenem and meropenem was carried out by gradient test for MIC determination (Etest Liofilchem, Roseto degli Abruzzi, Italy) and interpreted in accordance with the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints [].
The Klebsiella pneumoniae isolate was further evaluated for the presence of carbapenemase using a phenotypic assay (Rosco, Stamford, CT, USA) containing discs of meropenem (10 μg), meropenem + phenyl boronic acid (PBA), meropenem + dipicolinic acid (DPA), and meropenem + cloxacillin (CL). The organism was confirmed as a class A (KPC) carbapenemase enzyme producer. In detail, KPC enzymes are inhibited by phenylboronic acid.
A real-time PCR, detecting several genes involved in carbapenem resistance (Xpert Carba-R; Cepheid, Sunnyvale, CA, USA), was performed to confirm the results of the phenotypic test. More specifically, this method allows for the detection and differentiation of the most frequent carbapenemases gene families (bla, bla, bla, bla, and bla) in Gram-negative bacteria. The real-time PCR resulted positive for KPC and negative for VIM, OXA-48, IMP-1, and NDM.
On July 20th, the patient was started on colistin-fosfomycin and trimethoprim-sulfamethoxazole and then transferred to the Infectious Disease (ID) ward. We switched antibiotic therapy to colistin (loading dose of 9 million IU, and then 4.5 million IU BID), fosfomycin (4 g every eight hours), and tigecycline (loading dose of 100 mg, and then 50 mg BID). After the switch, he reported frequent nausea, while renal function remained normal and acute phase reactants remained elevated. shows the kinetics of white blood cells and acute phase reactants, and the antibiotics susceptibility test.
On August 4th, the patient was transferred to Orthopedic Surgery for resection of the distal femur along with minimal resection of the proximal fibula with positioning of a cemented Stage one® (Zimmer Biomet, Warsaw, IN, USA) spacer with an intramedullary rod in the femur. Samples of both bones were cultured, and tissue collected during surgery was negative. On August 5, the patient was transferred back to ID ward, and because of the onset of fever, poor tolerance of antibiotic therapy, and increase of acute phase reactants, we requested susceptibility testing for ceftazidime/avibactam (C/A) to our Bacteriology Laboratory. Sensitivity to C/A was confirmed using the specific disc (BD) provided by AstraZeneca, Molndal, Sweden. Resistance to carbapenems was further confirmed with the Xpert® Carba-R molecular diagnostic system (Cepheid, Sunnyvale, CA, USA). On August 19 after approval from our ethics committee for off-label use, we started treatment with ceftazidime/avibactam at a dose of 2.5 g TID for 2 weeks. In the subsequent days, the patient's clinical condition and laboratory tests improved with healing of the wound except for a fistula in the middle of the wound (fistula and rectal swabs were negative for CRKP). On September 2, a technetium-99 bone scan was performed showing distal uptake in the site of surgical intervention (which was deemed normal given that less than 12 months had elapsed from surgery). On September 16, the patient was transferred to the Orthopedic Surgery ward for a surgical curettage of the fistula. After being transferred back to the ID ward, the patient remained afebrile and daily care of the wound showed no discharge and no fibrosis. Cultures of samples taken during the curettage were negative. On October 14, the cemented spacer was removed in the Orthopedic Surgery ward and definitive knee prosthesis was positioned.
The patient was discharged from the ID ward on September 20, 2016. shows a timeline reviewing the events presented in this case report. During the latest orthopedic follow-up visit on February 23, 2017, the patient had no signs and symptoms of infection, was walking with the help of crutches, and continued being treated with physical therapy. |
pmc-6112140-1 | We report a case of a 69-year-old male patient with post-radiotherapy laryngeal edema. The patient was treated with tumor resection, right selective neck dissection of levels II to IV, and adjuvant radiotherapy due to a pT2N1M0R0 oropharyngeal squamous cell carcinoma of the right tonsil. In the 2 years following radiotherapy, the patient was treated six times as an inpatient due to acute dyspnea. The endoscopic findings of the larynx always revealed a massive edema of the arytenoid area (Fig. , upper). Treatment included corticosteroid/adrenalin inhalation with systemic corticosteroids. Each time, subjective and objective recovery were transient. The endoscopic and radiologic findings revealed no indications of tumor recurrence. As an outpatient, the patient underwent multiple sessions of lymphatic massage drainage without improvement. Treatment with proton pump inhibitors also showed neither subjective nor objective benefits.
Two and a half years after radiotherapy, the patient underwent transoral laser microsurgery of the arytenoid area. An erbium laser was used. The laser was set at 103 J/cm2 and 10 Hz. To prevent postoperative synechia and/or webs, only the right arytenoid was assessed. This intervention aimed to minimize the edema without causing severe thermal tissue damage, which could lead to additional edema. Therefore, the cranial surface of the right arytenoid was pulse targeted to achieve a shrinking effect. Subsequently, multiple targeted holes were made in the tissue. Edema fluid was emptied from the channels. The intraoperative effect was slightly obvious (Fig. ). The patient remained under general anesthesia. The day after the procedure, microlaryngoscopy was performed. No additional edema was observed. The right arytenoid was still shrunken, and the patient was extubated.
The patient was admitted 2 weeks later to our department due to acute dyspnea. However, endoscopic examination of the larynx revealed a slight edema reduction of the right arytenoid. After conservative treatment with inhalation and systemic corticosteroids, the same procedure was performed for the left arytenoid, resulting in similar intraoperative edema reduction (Fig. ). In January 2015, 2 months later, endoscopic findings revealed a slight edema reduction of the left arytenoid area, whereas the postoperative status of the right arytenoid remained stable. No synechiae, webs, or local swelling were observed. The patient also noted a slight improvement of the dyspnea. Thus, a new procedure was performed using the same surgical technique, this time in both arytenoids, with the same intraoperative findings. Again, no synechiae or webs were observed postoperatively.
During the next 6 months, the patient underwent three procedures in both arytenoids using the same surgical technique, with the same intraoperative findings. The erbium laser settings varied between 100 and 200 J/cm2 and 3 and 10 Hz, depending on the precise exposure of the cranial surface of the arytenoid area. No complications were observed. Endoscopic findings of the larynx at 2 months after the final procedure revealed a massive improvement. The patient experienced no symptoms. Thirty months after the final procedure, no additional edema was observed (Fig. , bottom). |
pmc-6112214-1 | The patient was an 81-year-old man with a history of left total hip replacement, open discectomy at the L4/5 level more than 10 years prior, percutaneous coronary intervention 3 years prior, and periodontitis detected 1 month before presentation. He suffered from severe back pain of 2-day duration. Plain lumbar spine radiographs showed spondylosis but no signs of fractures (). Laboratory tests were significant for a white blood cell count of 1.2 × 104 cells/μl and C-reactive protein level of 13.8 mg/dl (). He was admitted for treatment. Two days after admission, magnetic resonance imaging of the lumbar spine revealed discitis at the L5/S level (). Punctures of the disc were performed from both the left and right side under fluoroscopy, and two samples were obtained. Two sets of blood cultures and urine cultures were collected at the same time. Empiric therapy was started with vancomycin 1 g every 12 hours and ceftriaxone 1 g every 24 hours combined with lumbosacral orthosis. The culture of the disc aspirate was positive after 6 days, with the causative agent identified as G. morbillorum based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis, performed with a Bruker Daltonics Microflex LT system (Bruker Daltonics, Germany). Blood and urine cultures were negative. Transthoracic echocardiogram showed no evidence of endocarditis. We could not perform the broth microdilution method for susceptibility testing because the isolate did not grow in the wells. Instead, we used the E-test method (SYSMEX bioMérieux) for determining susceptibility to penicillin G. Susceptibility of the isolate was interpreted by applying the Clinical and Laboratory Standards Institute (CLSI) M45-ED3. The minimum inhibitory concentration (MIC) of the isolate for penicillin G was 0.012 μg/ml, which was interpreted as susceptible. Nine days from the initial treatment, antibiotic therapy was changed to ampicillin 2 g every 6 hours for 4 weeks. Then, oral amoxicillin was administered for 3 weeks. Lumbago resolved after 4 weeks of treatment. The patient was discharged from the hospital after 6 weeks of treatment. The isolate was referred to the Department of Clinical Laboratory Medicine, Kyoto University Graduate School of Medicine, for 16S ribosomal RNA sequence analysis. A BLAST search for the sequence in GenBank database gave 99.86% identity (1418/1420 bp) as G. morbillorum (GenBank accession number L14327). |
pmc-6112268-1 | A 13-year-old female of the Marshallese origin presented to the emergency department with complaints of nausea; nonbloody, nonbilious vomiting; and abdominal pain []. The patient denied any recent fevers, and no rash was reported. Review of systems was notable for the left ear drainage. Immunization status was unknown, and she was not reported to have been previously treated for any significant illness, though the history was limited by the patient's custodial circumstances. She lived in a small house in rural North Carolina with 21 other Marshallese immigrants and was cared for by relatives who had assumed care for her at the time of her immigration five years before.
Examination during the initial hospital visit revealed dehydration and acute otitis media with rupture of the tympanic membrane. Laboratory results revealed leukocytosis, prerenal azotemia, elevated liver enzymes, and mildly elevated lipase (). Computed tomography (CT) showed scattered focal pulmonary infiltrates, splenomegaly, and a markedly distended stomach without an obvious focus of mechanical obstruction (). Cytomegalovirus and Epstein–Barr virus serology were requested with results suggesting prior exposure. She was admitted with a presumptive diagnosis of gastroparesis secondary to a nonspecific viral infection and possible mild pancreatitis. An NG tube was placed resulting in high volume output. Her symptoms gradually improved over several days with IV fluid support and bowel rest; her NG was successfully removed, and she was discharged home tolerating a regular diet.
Two days after discharge, the patient returned with recurrence of her prior symptoms. The patient appeared acutely ill with dehydration. On lung exam, scattered crackles were noted. She was also noted to have diffuse small nodular lesions most apparent on her hands, feet, lower legs, and face (). An advocate placed with the family reported her concern for additional symptoms of chronic weight loss and productive cough with posttussive emesis and reported the skin changes to have been present for months. Prior exposure to or testing for tuberculosis was unknown. The patient did not report symptoms of peripheral neuropathy.
Laboratory results revealed a relatively increased white blood cell count (21.4 × 109 per liter) with significant worsening of her renal function (creatinine of 2.45 mg/dL which had previously been normalized with rehydration) and persistent mild elevation in liver enzymes and lipase. Respiratory viral screening was positive for rhino/enterovirus. Repeat CT imaging showed persistent gastric dilation and splenomegaly ().
The patient was placed on empiric antibiotics for community-acquired pneumonia and put on reverse isolation with concern for tuberculosis. Skin biopsies of multiple lesions were obtained and sent for pathology and culture (). Because multiple attempts to place an NG tube failed and vomiting failed to respond to conservative measures, endogastroduodenoscopy was pursued. The scope passed into the stomach and through the pylorus easily, reaching a normal-appearing proximal duodenum. However, a feeding tube could not be passed beyond the pylorus and was left just proximal to the pylorus for decompression. Stomach mucosa was described as having a “cobblestone” appearance in places, with one area of ulceration possibly due to prior nasogastric tube. Stomach biopsies revealed Helicobacter pylori and chronic active gastritis, but were negative for AFB.
Due to persistent evidence of gastric outlet obstruction, an upper gastrointestinal study was performed which suggested gastric volvulus. The patient proceeded to gastropexy via open gastrostomy tube placement. The surgeons reported an extremely large and patulous stomach that had twisted mesenteroaxially. Gastric aspirates were negative for AFB.
Biopsies of the skin lesions confirmed the presence of many AFB with changes consistent with lepromatous leprosy due to M. leprae (). Additionally, the serial sputum samples were positive for AFB, and culture of the skin sample for AFB showed evidence of growth within a few days, suggesting Mycobacterium tuberculosis (MTB) pulmonary infection and possibly disseminated MTB given selectivity of the culture medium.
In coordination with the health department and the infectious disease service, the patient was initiated on treatment for presumed disseminated MTB, noting that this would also provide coverage for M. leprae. However, polymerase chain reaction (PCR) testing from the sputum samples and skin samples failed to demonstrate MTB, while PCR testing performed at the Hansen's Disease Center of skin samples was positive for M. leprae. Retrospectively, it was felt that growth detected on the AFB culture was due to metabolism by an unusually large inoculum.
Gradually, the patient's oral intake improved. With hydration, her renal function again returned to normal. After several weeks of inpatient treatment, the patient discharged to complete therapy through the health department. Symptoms of gastric outlet obstruction have not returned. |
pmc-6112871-1 | In October 2017, a 71-year-old man visited our hospital due to moving difficulties and visual hallucination after experiencing general fatigue for 3 months. He reported dizziness and increased fatigue, 3 weeks prior to presentation, followed by urinary frequency, urinary incontinence, and a fall, 2 weeks later. To investigate his symptoms, head computed tomography (CT) and blood examination were conducted, which revealed a sodium level of 119 mEq/L, and he was hospitalized. Upon admittance, the patient underwent a physical examination that revealed a height of 138.5 cm, a weight of 49.0 kg, and a body mass index of 25.5 kg/m2. His temperature was 36.2°C and blood pressure 127/67 mm Hg. Pigmentations were detected, which were more visible around the lips, on the tongue, and fingers. Although the penis and scrotum were normal in size, the testicles measured small on an ultrasound scan.
His medical history revealed a growth spurt at approximately 8 years of age and the appearance of pubic hair at 10. His height did not increase past 139 cm from the age of 12. In his thirties, he suspected infertility, which was not investigated. At 49 years old in January 1996, he underwent a left adrenalectomy because of a heterogenous incidentaloma, with a size of approximately 3 to 4 cm. Laboratory investigations at the time revealed adrenocorticotropic hormone (ACTH): 102.2 (7.2–63.3) pg/mL, cortisol: 14.6 (6.24–18.0) μg/dL. 17-Ketosteroids (17-KS) were also reported to be elevated. The detailed results of these tests are summarized in Table . Because malignancy could not be fully excluded, adrenalectomy was performed. The mass was pathologically diagnosed as an adenoma and not malignant. After operation, although he was prescribed prednisolone, he did not keep up with his follow-up visits at the hospital because of no symptoms.
Abdominal CT revealed almost normal right adrenal gland (Fig. ). Laboratory evaluations revealed ACTH level of 1820 (7.2–63.3) pg/mL and cortisol level of 3.11 (6.24–18.0) μg/dL. The results of the other tests are presented in Table . Therefore, a diagnosis of primary adrenal insufficiency was suspected, and the patient immediately received a dose of 100 mg hydrocortisone intravenously. This initial dose was followed by a maintenance regimen of intravenous hydrocortisone diluted in saline as follows: 200 mg for 2 days, 150 mg for 3 days, 100 mg for 3 days, and 50 mg for 3 days. Thereafter, he received 15 mg hydrocortisone orally. During this time, the patient also received approximately a liter of physiologic saline per day. Sodium levels were monitored and reached 126 meq/L on day 2, 131 meq/L on day 3, and 138 meq/L on day 7 after hospitalization. As a result, the patient's symptoms improved after a few days. An ACTH-stimulating test was performed, with the results revealing low response of cortisol 17-hydroxyprogesterone (17-OHP). The basal levels were low in the former and high in the latter. The complete results are summarized in Table . Therefore, a diagnosis of primary adrenal insufficiency was made. No anti-adrenal cortex antibody was detected. The patient was discharged on day 34 with a daily oral dose of 15 mg of hydrocortisone.
We suspected nonclassical 21-OHD, and searched for the most common CYP21A2 mutations by polymerase chain reaction (PCR) as per previous studies,[ using the primers previously reported for these mutations,[ after obtaining the patient's informed consent, looking for the large gene deletion or conversion, and the following 9 micro conversion-derived mutations: P30L in exon 1, 656A/C > G in intron 2, I172N in exon 4, V281L in exon 7, Q318X in exon 8, R356W in exon 8, the cluster I236N, V237E and M239K in exon 6, L307+T in exon 7, and 8 bp-del in exon 3.[ The mutations positive in our patient were micro mutation I172N and heterozygous large gene deletion or conversion leading to the diagnosis of nonclassical 21-OHD. |
pmc-6112881-1 | A 50-year-old man presented to the emergency department following 2 days of lightheadedness, abdominal pain, and melena. His distant past medical history was significant for hypertension and transfusion-requiring erosive gastritis. In addition, he reported having been diagnosed with AIP 2 weeks prior at a geographically-proximate academic medical center, where a mass at the head of the pancreas was identified after he presented with abdominal pain, elevated lipase, and hyperglycemia. At that time, he was prescribed prednisone 20 mg PO b.i.d., therapy with which he was compliant. Additional medications prior to admission were diltiazem and tramadol. He has no history of drug or alcohol abuse and denies use of nonsteroidal anti-inflammatory drugs.
On presentation, the patient was in no apparent distress, afebrile, and not hypoxic with a blood pressure of 175/39 mm Hg, a pulse of 140, and a respiratory rate of 18. On physical examination, bowel sounds were normoactive and the abdomen was soft without guarding or rigidity, but significant for marked epigastric tenderness without rebound. There was no palpable splenomegaly, Castell sign was negative and percussion of Traub Space was tympanic. There was no appreciable jaundice on the integument, the sclera, or the oral frenulum. Melena was present on rectal examination. Complete blood count revealed a white blood cell count of 46,000/mL, a hemoglobin of 9.2 mg/dL (baseline 11), and platelets of 96,000/mL. We attributed the leukocytosis to a combination of steroid therapy and stress response to the gastrointestinal bleed. The patient's metabolic panel was significant for a creatinine of 1.8 mg/dL, aspartate aminotransferase of (AST) 40 U/L, alanine aminotransferase of (ALT) 59 U/L, a total bilirubin of 0.7 mg/dL, serum glucose of 300 mg/dL, and a lipase of 31 U/L. IgG4 levels were not drawn as they were not pertinent to the immediate management of the patient's acute gastrointestinal bleed. The patient became acutely hypotensive, at which time an electrocardiogram revealed sinus tachycardia at a rate of 120 beats per minute. Following fluid resuscitation, the hemodynamic compromise resolved. Subsequent hemoglobin measurements revealed a temporal decrement from 9.2 to 7.8 mg/dL. Following initiation of maintenance fluids and a famotidine drip, the patient was admitted to the intensive care unit, where he also received blood transfusions. Due to concerns regarding diagnostic clarity and the veracity of the AIP diagnosis in the setting of gastrointestinal bleeding, the steroid therapy was discontinued.
On hospital day 2, the patient had continued abdominal pain and an additional episode of transfusion-requiring melena, absent vital sign abnormalities. The remainder of laboratory studies were significant for a platelet count of 79,000/mL, a hemoglobin A1c (HbA1c) of 7.0, and a reduction in leukocyte count to 24,500/mL, as expected following discontinuation of steroid therapy. The maintenance fluids and famotidine drip were continued with morphine as needed for abdominal pain.
On hospital day 3, esophagogastroduodenoscopy (EGD) revealed multiple erosions in the duodenal bulb with surrounding mucosal edema and a 3.5 cm ulcer with an adjacent crater and exudate in the bulb on the anterior wall. Erosive gastritis was also present in the antrum, body, and fundus of the stomach; tissue biopsy was negative for H Pylori. Grade 2+ gastric varices were found along the gastric fundus (Fig. ) and grade 1+ nonbleeding varices were present in the distal esophagus. Abdominal ultrasound with Doppler studies demonstrated moderate splenic enlargement, but patency of the splenic, hepatic, and portal veins.
The patient remained in stable condition throughout hospital days 4 to 7. The remainder of his hospital course was unremarkable with the exception of intermittent melena. He was discharged on hospital day 7, tolerating a full diet. Discharge medications were pantoprazole, prednisone 20 mg PO b.i.d., propranolol, sucralfate, and tramadol as needed for abdominal pain. In the outpatient setting, his care team titrated the dose of propranolol to avert significant heart rate decrement. |
pmc-6112910-1 | A 25-month-old female patient presented with recurrent mass lesion of the sinonasal tract. According to her history, she had feeding difficulties and nasal obstruction since birth. Microphthalmia on the right side was also noticed. Examination revealed mass lesion in the right nasal cavity and maxilla, however, biopsy was noninformative. Then, in October 2015 at the age of eight months, the patient was admitted to the department of maxillofacial surgery of local pediatric hospital. Computed tomography (CT) scans were obtained demonstrating a widespread tumor in the right nasal cavity with severe dislocation of the nasal septum, involving the right maxilla, ethmoid labyrinth, orbit, and cranial base (Figure , , ). In November 2015, the lesion was resected via a lateral rhinotomy in a piecemeal fashion until the bony boundaries of the maxillary antrum were reached around the tumor mass. Postoperative CT scans showed tumor remnants along the lateral nasal wall in proximity to the orbit (Figure ). No complications occurred after surgery. Histologic examination diagnosed chondromesenchymal hamartoma.
The patient presented at N.N. Burdenko National Research Center for Neurosurgery (Moscow, Russia) to obtain consultations concerning the management of the remaining lesion. New MRI obtained in August 2016 (Figure , left) showed remnants of the tumor without any deficit, and further follow-up was recommended.
The histological specimens were examined in the pathology department, and the diagnosis of NCMH was confirmed.
On low magnification, the resected material showed different histological patterns. It consisted of cellular cartilaginous islands and areas that contained fibro-osseous and mesenchymal components (Figure ). The cartilaginous component was composed of cellular cartilage foci with a hyaline cartilaginous matrix. The cells of that foci had a very low level of mitotic activity, and no signs of atypia were found (Figure ).
A mesenchymal component was represented by quite cellular zones consisting of plump fibroblast-like cells without any mitotic figures and atypia (Figure ). Multiple bone trabeculae (Figure ) and irregular osteoid matrix (blue on Masson – Figure ) were found upon the connective tissue background. Areas of preexisting bone tissue with lamellar structure were present (Figure ).
Immunohistochemical study with antibodies to SMA, S-100 protein, vimentin, MDM2, CDK4, desmin, CD34, and Ki-67 was performed. The cells of the cartilaginous component were strongly positive for vimentin (Figure ) and S-100 protein (Figure ). The cells of the mesenchymal component are positive for vimentin and focally positive for SMA (Figures and 4D). Immunohistochemical reactions with MDM2 (Figure ) and PanCK (AE1/AE3) were negative, positive control for PanCK was present in the mucosal epithelium (Figure ). Proliferative activity was very low according to Ki67 expression (Figure ).
In January 2017 (Figure , right) the next follow-up MRI study showed a progression of the lesion, and surgical treatment was indicated. Since the tumor was limited to the nasal cavity, ethmoid labyrinth, maxillary sinus, and was situated extradurally, the second surgery was performed using endoscopic endonasal technique (March 2017). No distinct margins of the lesion were detectable intraoperatively, therefore the superior portion of the tumor was left in order to avoid skull base penetration. Post-operative course was uneventful, no cerebrospinal fluid leak was detected.
The material from the second surgery was represented by hypocellular connective tissue with reactive inflammatory infiltration (Figure ), and the same irregular osteoid matrix (Figure ). In this case, the cartilaginous component was not found.
At six months of follow-up, the magnetic resonance imaging (MRI) demonstrated clear nasal cavity and remaining tumor mass in the ethmoid roof and sphenoid sinus (Figure , top). At one year, after the second surgery inflammatory changes had regressed, the tumor is stable and exhibits no increase in the volume (Figure , bottom). |
pmc-6113042-1 | The patient is a 52-year-old woman, who first presented to our clinic on November 30, 2016, with complaints of redness, red rash, and increased sebum excretion of the nose. These symptoms were sometimes accompanied by repeated occurrences of itching, papules, and pustules, and had been present for 1 year. Her symptoms were triggered by unknown causes and worsened after eating any greasy food. She was diagnosed with rosacea and tried medical treatments in other hospitals with metronidazole cream, antifungal drug, and steroidal ointments, but the therapeutic effect was poor. She made the decision to try acupuncture; she ceased receiving any medical treatment 1 month before she received the acupuncture treatment on March 13, 2017. |
pmc-6113049-1 | The patient was a 44-year-old female patient who had presented with thyroid nodules for at least 5 years, had a history of atrial premature beats, and who had undergone an ovariohysterectomy almost 10 years previously. There was no history of hypertension, diabetes, or other infectious disease and allergies, except for hepatitis B. Thyroid ultrasound suggested a 15 × 35 mm solid cystic nodule located in the upper dorsal side of the right lobe of the thyroid gland (Fig. ). The nodule was well defined with regular form. Streaky bloodstream signals were observed in the interior and edges of the nodule. Pre-MWA thyroid function tests showed a thyroid-stimulating hormone level of 0.912 uIU/mL, free T3 of 4.61 pmol/L, free T4 of 13.30 pmol/L, thyroglobulin antibody of 14.46 IU/mL, and thyroid peroxidase antibody of 37.61 IU/mL.
After being admitted from the outpatient department, the patient completed the remaining pre-MWA examinations. The results of an electrocardiogram, laryngoscopy, and lung computed tomography scan were all normal. The patient was given a principal diagnosis of nodular goiter. We decided to perform MWA given the small volume and benign character of the nodule. We used a MWA instrument (ECO-100A1; YIGAO Microwave System Engineering Co. Ltd, Nanjing, China), matched aseptic disposable MWA needle (ECO-100AL3; 100 mm in length, 1.6 mm in diameter), and 500 mL normal saline for cold fluid circulation for the ablation procedure. The output power setting was 35 W with a frequency of 2450 MHz. Moreover, ultrasound (GE, LogiQ-E9) was used for guidance before, during, and after the ablation.
The patient underwent MWA in November 2017. Considering that local anesthesia would not adequately reduce pain, talking, or coughing during the MWA procedure, we injected lidocaine into the skin puncture site with the assistance of intravenous anesthesia. The patient subsequently fell asleep and therefore, we did not monitor ptosis during the procedure. After confirming the effect of the anesthesia, we set up a liquid-isolating zone by injecting 10 mL normal saline into the space between the anterior capsule of the thyroid gland and the cervical anterior muscles, between the lateral capsule of the thyroid gland and the carotid artery, between the posterior capsule of the thyroid gland and the recurrent laryngeal nerve crossing area, and between the esophagus and the parathyroid gland. Next, we performed MWA from the deep to the shallow part of thyroid gland. The procedure was completed successfully.
Subsequently, we advised the patient to remain laying down and abstain from drinking water for at least 2 hours. About 4 hours after MWA, the patient showed mild miosis and eyelid ptosis in her right eye but no enophthalmos, anhidrosis, or vascular dilatation. Her symptoms became more serious a day later and therefore, the patient underwent brain magnetic resonance imaging and examination by a neurological physician. Along with the clinical presentation, these assessments ruled out the possibility of oncothlipsis and the patient was finally diagnosed with HS as a rare complication of MWA (Fig. ). Therefore, routine treatment with mecobalamin was administered immediately.
After 42 days of MWA, the patient's nodule showed a reduction in volume with ultrasound (Fig. ). However, after 5 months of follow up, the patient's miosis and ptosis had not been completely alleviated. |
pmc-6113389-1 | Case 1 is a 65-year-old, right-handed male with 84 cytosine-guanine-guanine (CGG) repeats, who denied tremor and ataxia. On examination his blood pressure was 177/87 mmHg and his heart rate was 62 bpm. This was consistent with reported history of and treated with metoprolol and candesartan. His body mass index (BMI) was 29.3. On neurological examination, finger-to-nose touching was without tremor and his arm movements were normal. His deep tendon reflexes were 1 to 2+ in the upper extremities, 3+ at the knees, and 2+ at the ankles. His temperature sensation was normal and his vibration sensation was absent in both great toes. Tandem walking was performed normally. No cognitive abnormalities were present on neuropsychological examination and no psychiatric symptoms were reported.
His MRI demonstrated the emergence of a faint MCP sign (Figure ). His CC was slightly thin with minimal hyperintensity of the splenium of the CC. There was no significant atrophy but there was a hint of white matter hyperintensity in the insula bilaterally. |
pmc-6113389-2 | Case 2 is a 50-year-old, right-handed male carrier with 102 CGG repeats who denied tremor and ataxia. He had a history of multiple concussions from sports injuries in high school and college.
On examination his blood pressure was 147/82 mmHg and his heart rate was 48 bpm. His BMI was 25.8. Finger-to-nose touching was without tremor, and deep tendon reflexes were symmetrical and 1+ at the upper extremities, 2+ at the knees, and 2+ at the ankles. His vibration sense was mildly decreased in the lower extremities. His tandem gait was normal. No cognitive abnormalities were present on neuropsychological examination and no psychiatric symptoms were reported.
He presented with the MCP sign on MRI (Figure ). He also had deep cerebellar white matter disease adjacent to the dentate nuclei, white matter hyperintensity in the splenium of the CC, mild volume loss involving the vermis and cerebellar hemispheres, and mesencephalic changes with widened third ventricle. In addition, an indentation in the superior aspect of the CC was thought to relate to a small vascular malformation or aneurysm. |
pmc-6113389-3 | Case 3 is a 62-year-old, right-handed male carrier with 86 CGG repeats who denied tremor and ataxia. On examination his blood pressure was 125/88 mmHg and his heart rate was 88 bpm. His blood pressure was being controlled with irbesartan and hydrochlorothiazide. His BMI was 26.9. Finger-to-nose touching showed no tremor and his tandem walk was without difficulty. He had slight increased tone on the right and left extremities with symmetrical movement. Deep tendon reflexes were normal, and he scored a 2+ in all four extremities. His vibration sense, tactile sensation, and cold sensation were also normal. No cognitive abnormalities were present on neuropsychological examination and no psychiatric symptoms were reported.
The MRI revealed the MCP sign (Figure ). Additional white matter changes were seen in the splenium of the CC. |
pmc-6113389-4 | Case 4 is a 60-year-old right-handed, male carrier with 74 CGG repeats who denied tremor and ataxia. On examination he had a blood pressure of 152/86 mmHG and a heart rate of 89 bpm. He had a BMI of 27.9. His neurological examination showed decreased vibration sense in the lower extremities. Deep tendon reflexes were 1–2+ in the upper and 2+ in the lower extremities. He had no rest or action tremor, gait ataxia, or dystonia. No cognitive abnormalities were present on neuropsychological testing and no psychiatric symptoms were reported.
The MRI showed mild cerebellar volume loss, with MCP sign bilaterally (Figure ) and subtle inferior cerebellar white matter changes. |
pmc-6113389-5 | Case 5 is a 61-year-old, right-handed male carrier with 89 CGG repeats, who denied any history of tremor. He noted that he had no history of falling but he experienced some instances of unsteadiness when turning around, possibly attributable to a 4 cm difference in leg lengths secondary to a congenital vascular malformation in one leg that impacted growth. On examination, his blood pressure was 107/68 mmHg and his heart rate was 55 bpm. He had a BMI of 26.5. There was no sign of tremor during finger-to-nose touching. Along with having mild balance problems while turning, he had instability on tandem walking during the first few steps. With practice, he was able to perform at least 6 steps without missteps. He had normal reflexes in his upper extremities and knees, all +2. His right ankle reflex was 1+, and there was no reflex in his left ankle. He had decreased vibration sense bilaterally in both big toes but normal vibration sense at the ankles bilaterally. Additionally, pinprick sensation was slightly decreased in the great toe. No cognitive abnormalities were present on neuropsychological examination and no psychiatric symptoms were reported.
On MRI, the T2 images showed the MCP sign (Figure ) and white matter hyperintensity in the splenium of the CC. He also had mild brain atrophy. |
pmc-6113740-1 | A 12-year-old male castrated domestic shorthair cat was referred to the
Virginia-Maryland College of Veterinary Medicine Veterinary Teaching Hospital (VTH)
for weight loss of 10 months’ duration and anemia of 3 weeks’ duration.
Abnormalities identified by the primary veterinarian 3 weeks prior to admission
included a thin body condition and a grade II/VI holosystolic heart murmur. Serum
biochemical profile and total thyroxine were within normal limits. Complete blood
count (CBC) revealed a normocytic, normochromic, regenerative anemia (hematocrit
[HCT] 17.2%, reference interval [RI] 30.3–52.3; 66,500 reticulocytes/μl, RI
3000–50,000) and thrombocytopenia (142,000 platelets/μl [RI 151,000–600,000]). A PCR
panel testing for Mycoplasma haemofelis (MH),
Candidatus Mycoplasma turicensis (CMt) and
Candidatus Mycoplasma haemomintum (CMh) was submitted. The cat
was administered orbifloxacin 3.4 mg/kg by mouth once daily pending results of the
PCR panel and oral vitamin B supplementation (unknown type and dose) in the
meantime.
The CBC 1 week later revealed improved normocytic and normochromic anemia and
reticulocytosis (21% HCT and 94,600 reticulocytes/μl, respectively) and resolved
thrombocytopenia (159,000 platelets/μl). The PCR panel was negative. The cat
continued to receive orbifloxacin and vitamin B supplementation due to clinical
improvement.
Over the following 2 weeks, the packed cell volume (PCV) ranged from 20.1–22.5% and
reticulocyte count from 58,000–80,600 reticulocytes/μl. The cat also tested positive
for feline immunodeficiency virus (FIV) and negative for feline leukemia virus
(FeLV) on a lateral flow ELISA test kit (SNAP FIV/FeLV Combo) during this period of
time. The cat was vaccinated for FIV 7 years prior to testing. One year prior to
vaccination, the cat had tested negative for FIV through unknown diagnostic
methods.
The cat presented to the VTH 1 week later. Abnormalities on physical examination
consisted of a body condition score of 4/9 and a grade II/VI systolic parasternal
heart murmur. CBC revealed a normocytic, normochromic, mildly regenerative moderate
anemia (19.5% [RI 33.7–47.5%]; 83,500 reticulocytes/μl [RI 13,100–71,600
reticulocytes/μl]), marked thrombocytopenia (34,000 platelets/μl with platelet
clumping; RI 149,000–532,000 platelets/μl), a neutrophilic left shift (185 bands/μl;
RI 0–0 bands/μl) and lymphopenia (739 lymphocytes/μl; RI 804–9240 lymphocytes/μl)
with reactive lymphocytes. Mild cardiomegaly was present on thoracic radiographs.
Abdominal ultrasound identified mild splenomegaly and hypoechoic splenic parenchyma.
Fine-needle aspirate cytology of the spleen demonstrated moderate macrophagic
infiltration with phagocytosis of erythrocytes and erythroid progenitors and
extramedullary hemato poiesis. Cytological evaluation of a bone marrow aspirate
showed similar findings with moderately increased macrophages and phagocytosis of
erythroid progenitors and erythrocytes. Erythroid hyperplasia was also noted. Rare
phagocytosis of myeloid progenitors and megakaryocytic hyperplasia was also noted.
The macrophages were similar in appearance to those observed in the spleen. The
macrophages did not exceed 20% of the population. A bone marrow core biopsy was also
collected, but a definitive diagnosis could not be obtained with the sample owing to
low cellularity. Primary differentials at this point were hemophagocytic syndrome
and hemophagocytic histiocytic sarcoma.
In 2 weeks, the cat’s heart murmur progressed to a grade IV/VI parasternal systolic
murmur. Splenomegaly was now identifiable on abdominal palpation. CBC revealed
progression of anemia (15.6% HCT; 46,200 reticulocytes/μl), leukopenia (3500 white
blood cells [WBCs]/μl; RI 4250–14,610 WBCs/μl) characterized by neutropenia (2065
neutrophils/μl; RI 2272–9639 neutrophils/μl) and a left shift (105 bands/μl) and
mild thrombocytopenia (90,000 platelets/μl with manual estimate of 130,000
platelets/μl). Echocardiogram identified moderate, irregular, left ventricular
hypertrophy with left atrial enlargement and left ventricular chamber enlargement,
right ventricular chamber enlargement and right atrial enlargement. Small-volume
pericardial effusion with pericardial thickening and pleural effusion were also
noted. Primary differentials for these findings included either infiltrative disease
of the heart secondary to infection, inflammatory disease or neoplasia, hypertension, or hypertrophic cardiomyopathy. Chronic anemia may also have played a role in the cat’s cardiomegaly as
anemia has been associated with increased cardiac troponin 1 concentration, which is
suggestive of cardiac myocyte damage. Blood pressure was not evaluated. Thoracic radiographs revealed progression
of cardiomegaly but no evidence of congestive heart failure. Tests for
Histoplasma species antigen in urine and serum IgM and IgG to
Toxoplasma gondii were negative. Whole blood was tested using
PCR for Anaplasma phagocytophilum, Bartonella henselae, Bartonella
clarridgeiae, Bartonella quintana, Ehrlichia species, MH, CMh, CMt,
Rickettsia rickettsii and Rickettsia felis,
and was negative. In order to further differentiate between hemophagocytic syndrome
and an underlying neoplastic condition, splenectomy was recommended.
Approximately 2 weeks later, splenectomy was performed without complication. The cat
received buprenorphine 0.02 mg/kg IV q8–12h as needed for analgesia after surgery.
Liver biopsies were collected at the time of surgery. Recheck echocardiogram prior
to anesthesia revealed similar findings with progression of pericardial effusion and
mild cardiac tamponade. Repeat thoracic radiographs did not reveal any evidence of
pleural effusion or pulmonary edema, making congestive heart failure unlikely. The
cat had type A blood and was given 20 ml blood-type-compatible packed red blood
cells prior to surgery, which resulted in an increase in PCV from 18% to 21.5%.
Postoperative PCV was stable at 23.5%. The cat was discharged and returned 1 week
later for a recheck. The cat appeared more lethargic and the PCV had decreased to
15%.
Histopathology of the spleen revealed multifocal aggregates of mononuclear cells with
moderate amounts of eosinophilic cytoplasm, occasional variably sized
intracytoplasmic vacuoles and distinct cell borders (). Occasionally, macrophages within
the aggregates were observed phagocytizing erythrocytes (). There were also large numbers of
megakaryocytes and both myeloid and erythroid precursors throughout the splenic
parenchyma. Increased numbers of metarubricytes and rubricytes resulted in a myeloid
to erythroid ratio of approximately 1:2. Multifocal regions of red pulp contained
distinct sinuses void of erythrocytes. The hemophagocytosis within the spleen,
paired with the extramedullary hematopoiesis, was suggestive of hemophagocytic
syndrome. The macrophages did not exhibit characteristics of malignancy, which
lowered the suspicion of hemophagocytic histiocytic sarcoma. The splenic
histopathology was reviewed by five anatomic pathologists, who agreed with a
diagnosis of non-neoplastic hemophagocytic histiocytosis. Histopathology of the
liver was consistent with mild, multifocal extramedullary hematopoiesis. A diagnosis
of hemophagocytic syndrome was made. PCR testing for FIV was performed on the
splenic tissue and was found to be negative.
After splenectomy, there was no improvement in the anemia over the next 4 weeks, with
PCV ranging from 15–17%. The cat was started on lomustine at 41.6 mg/ m2
orally every 3 weeks. The cat’s PCV fluctuated between 22% and 25% over the following 2 months.
Evaluation with echocardiogram after the second lomustine treatment indicated stable
cardiac disease. A grade 3 non-febrile neutropenia (864 neutrophils/μl) was
encountered after the third treatment, so the treatment interval was extended to every 4 weeks. Lomustine was
otherwise well tolerated.
Three months after initiating lomustine, disease progression characterized by
thrombocytopenia, worsening anemia, ascites, pleural effusion, severe left atrial
enlargement and static pericardial effusion was noted. There was concern that the
cat may be in congestive heart failure owing to the presence of severe left atrial
enlargement, pleural effusion and ascites. Abdominal fluid analysis was consistent
with a protein-poor transudate. The cat was treated with vincristine 0.5
mg/m2 IV once and furosemide 1.5 mg/kg PO q12h. Over the following 6
days, a 25% reduction in body weight was noted, attributed to fluid loss and muscle
wasting. The thrombocytopenia improved but the cat was considered too debilitated to
receive any further chemotherapy. Owing to poor response to treatment, the cat was
euthanized and no necropsy was performed. |
pmc-6113765-1 | The patient is a 49 year old man with psoriasis and idiopathic anaphylaxis—generalized frequent type who developed an upper extremity deep vein thrombosis (DVT) after recurrent and protracted episodes of anaphylaxis without clinical signs of shock. The patient denied a family or personal history of coagulation disorders or unprovoked blood clots.
The events leading to his DVT started weeks prior when he experienced urticaria and angioedema of his face, body, and extremities without association of additional systemic symptoms. The urticaria and angioedema was initially responsive to steroids and antihistamine treatment, but within weeks became refractory and progressive. A subsequent sudden episode of respiratory distress with hypoxia resulted in an emergent crico-thyroidotomy.
During his hospitalization subject 2 had recurrent anaphylaxis. Multiple physicians reported bilateral wheezing and poor air exchange during respiratory distress episodes. The events were unresponsive to tracheotomy hygiene and albuterol, but resolved after IM epinephrine. One incident required an epinephrine drip for 12 h. Within 24 h of an anaphylaxis episode he developed an acute occlusive left upper extremity DVT. He has had a total of four hospital admission within 1 year for anaphylaxis. During his third admission he developed an acute worsening of his chronic left upper arm DVT. With each anaphylactic attack a drop in his platelet levels were seen (Table ).
His work-up for a trigger of anaphylaxis has been negative to date. His tryptase levels at baseline, during protracted anaphylaxis, and an hour after anaphylaxis have never been above 9. All histamine and histamine metabolites have also been negative to date. Investigations into malignancy, mast cell disorders, autoimmune diseases have been negative to date with the exception of his psoriasis. |
pmc-6113765-2 | An 18 years old female undergoing chemotherapy for acute myeloid leukemia (AML) was found to be allergic to her pentamidine treatments. She developed nonocclusive thrombus involving the celiac trunk, proximal hepatic, and splenic arteries shorty after her first pentamidine administration. She originally started intravenous (IV) pentamidine after developing a nonspecific rash (without mucosal involvement) initially attributed to trimethoprim/sulfamethoxazole.
Twenty minutes into her first administration of IV pentamidine she developed severe crippling abdominal pain, emesis, diarrhea, and light headiness followed by near-syncope. Abdominal X-ray showed non-obstructive gas patterns with small bowel wall thickening. After resolution of her abdominal pain she was given a platelet transfusion for thrombocytopenia (Table ). During the platelet infusion, she developed intense abdominal pain, hypotension, and poor perfusion. Treated with intramuscular epinephrine yielded a positive response.
An abdominal CT scan showed colonic wall thickening with surrounding inflammatory changes and concern for ischemic colitis. An MR enterography revealed a nonocclusive thrombus involving the celiac trunk, proximal hepatic, and splenic arteries. The patient underwent a partial colectomy from the mid transverse colon to mid distal colon. The pathology results showed patchy transmural ischemic colitis without evidence of local thrombosis or emboli. Continued treatments of IV pentamidine every 2 weeks were noted to have immediate production of a range of symptoms mostly commonly: abdominal pain, emesis, pruritus (originally urticaria was rarely noted), diarrhea and headaches. Pentamidine allergy was established and desensitization protocol was subsequently used. Isolated urticarial flares with each desensitization was reported without any other clinical systemic involvement.
Combined using a paired two tailed Wilcoxon test on the Pre- and Post-anaphylactic platelets levels of all 3 case's showed the overall P < 0.0001(Figure ). A Spearman test on the pairing had a rs value of 0.9344 with a P < 0.0001.
For Case 3, her platelet count post BMT remained in the low 30–50's. Laboratory analysis of known specific antibodies to platelets were negative. With spacing out her pentamidine treatments to every 4 weeks her counts marginally improved to the 40–60's. Once off pentamidine, trimethoprim/sulfamethoxazole (TMP-SMX) was restarted. Her thrombocytopenia again incrementally improved to the 80–100's. A Kruskal-Wallis test on her platelet levels with respect to the frequency of her pentamidine infusions and off pentamidine showed a P < 0.0001 (Figure ). |
pmc-6113981-1 | An 82-year-old Japanese man underwent esophagogastroduodenoscopy for a routine health checkup. The patient had been taking vonoprazan, dimethicone, acotiamide, sitagliptin, candesartan, dutasteride, etizolam and zolpidem for reflux esophagitis, functional dyspepsia, diabetes, hypertension, benign prostatic hyperplasia and insomnia. Physical examination revealed no abnormalities in his abdomen. All laboratory findings were within the normal ranges, except for elevation of plasma glucose (256 mg/dL), haemoglobin A1c (7.1%) and gastrin levels (844 pg/mL, normal range: 42–200 pg/mL). He tested negative for Helicobacter pylori (H. pylori) IgG antibody.
Endoscopy revealed multiple white spots in the fornix () and body () of the stomach. Magnifying endoscopy observation () and blue laser imaging () showed a slightly elevated, round, white substance. Microvasculature was also seen on its surface, suggesting deposition of the white substance within the mucosa. Atrophic gastritis was also observed during esophagogastroduodenoscopy. No inflammation was observed in the oesophageal mucosa. Biopsy from the gastric mucosa that contained white spots revealed cystic dilation of the gastric fundal gland with a 400 μm diameter (, ). Parietal cell protrusion was also noted (, arrows). Xanthoma cells were absent in the biopsied specimen. |
pmc-6113981-2 | A 74-year-old Japanese woman underwent esophagogastroduodenoscopy for investigation of epigastric pain and throat discomfort. She had been taking esomeprazole, rebamipide, sitagliptin, candesartan, ezetimibe, mirabegron, levocetirizine, zolpidem and lactobacillus preparation for reflux esophagitis, diabetes, hypertension, hyperlipidaemia, urticaria and insomnia. The patient had also been using flurbiprofen poultice for chronic lumbar pain. She is allergic to multiple medications, including antibiotics. Although the patient underwent eradication treatment for H. pylori 2 years previously, she discontinued taking the medication due to epigastric discomfort, and eradication failed. Physical examination revealed no abnormalities in her abdomen. Laboratory findings revealed elevated levels of total cholesterol (254 mg/dL), triglyceride (130 mg/dL), haemoglobin A1c (7.7%) and immunoglobulin E (598 IU/mL, normal range: 0–170 IU/mL). Gastrin levels were not measured in this patient. H. pylori IgG antibody was positive.
Esophagogastroduodenoscopy revealed multiple white spots in the gastric fornix (, arrows), body (, post-indigo carmine spraying) and antrum. Magnifying endoscopy observation () and blue laser imaging () showed small, round, white deposits that were similar to the substances observed in case 1. Other endoscopic findings included atrophic gastritis and oesophageal hiatal hernia. Cystic dilation of the gastric fundal gland was identified in the biopsied specimen obtained from the white spots, which contained debris in the dilated duct (, ). The dilated duct was approximately 600 μm in diameter. In addition, parietal cell protrusions and dilated glands forming microcysts were present (). |
pmc-6113983-1 | A 53-year-old Caucasian woman was referred to our institution because of the suspicion of peritoneal carcinomatosis, raised by the findings of ascites at a transvaginal ultrasound performed as a yearly routine exam; a pre-surgical staging exam with computed tomography (CT) scan show thickening of the gastric walls, multiple omental nodules and ascites ().
Her previous personal history was unremarkable and she denied any clinical symptom or cancer history.
At our hospital, she underwent an esophagogastroduodenoscopy and colonoscopy, with results negative for gastric/colon cancer.
Her comprehensive metabolic profile revealed mild liver dysfunction with an alanine transaminase of 77 U/L and aspartate transaminase of 71 U/L. When tumour markers were assessed, CA125 demonstrated increased levels of 290 U/mL (normal values <35 U/mL), whereas carcinoembryonic antigen, CA 19.9 and other immunohistochemical markers were within the normal ranges. Serological assessment of HIV, hepatitis C virus and hepatitis B virus were negative.
Ten days later, the patient underwent an ultrasound-guided biopsy () with a diagnosis of suspicious carcinoma from the an unknown primary site.
After 2 weeks, the patient received a CT scan of the thorax (to complete pre-operative staging), demonstrating a spontaneous (with no therapy) dimensional and numerical reduction of peritoneal lesions in the upper abdomen, partially included in the chest CT scan, as well as resolution of peri-hepatic and peri-splenic ascites ().
Since there was no evidence of primary cancer at pre-operative examinations and the second CT scan revealed a partial resolution of peritoneal implants and ascites without therapy, the suspicion of an infectious disease was raised.
The pathological evaluation of the biopsies performed on the omentum and peritoneum revealed the presence of lymphoid aggregates with a central core of epithelioid cells with large eosinophilic cytoplasm, without atypia or mitosis () and with no immunohistochemical marker of oncologic malignancy. Due to the presence of necrotic nodules with histiocytes and giant cells, a Ziehl–Neelsen stain was performed to identify bacilli (), whose presence was then confirmed with molecular assays.
Because of the uncertain result of the biopsy and the conflicting results of the 2 CT scans, in order to rule out malignancy with certainty, the patient underwent a laparoscopic surgery in 2 weeks.
Definitive histological diagnosis excluded the presence of malignant cells and reported a necrotising inflammation caused by non-tuberculous mycobacteria. Hence, the patient was sent to a hospital with expertise in infectious diseases.
A follow-up CT scan performed 1 year later confirmed a complete recovery of peritoneal findings. |
pmc-6113986-1 | A 4-year-old male Caucasian patient with no prior family history of neoplasms presented in fair general condition with weight loss and loss of appetite, which, according to his parents, had developed over 2 months. Clinical evaluation showed evidence of abdominal pain and distention in addition to hepatomegaly. A full work-up was requested, significant findings were anaemia, very high levels of α-fetoprotein (352,050 ng/mL, normal range: <20 ng/mL), low levels of chorionic gonadotropin subunit beta (1.9 mIU/mL) and elevated levels of lactate dehydrogenase (1,615 IU/L). Tests on the levels of catecholamines in the blood and urine were negative. An abdominal ultrasound was performed, which showed irregular hepatomegaly with a heterogeneous echotexture due to the presence of multiple, randomly distributed echogenic nodules, suggestive of metastasis. The pancreas could not be evaluated. This was followed by an abdominal and pelvic CT scan with and without contrast dye: this showed a heterogeneous tumour in the body and tail of the pancreas that had defined borders, hypodense areas inside (suggestive of necrosis) and an apparent pseudocapsule. This measured: anteroposterior diameter 75 × transverse diameter 57 × longitude 101 mm, displacing the left kidney and the splenic artery in the head and rear directions, the left ureter in the dorsal direction and the bowel in the caudal direction. Enlarged heterogeneous liver, due to the presence of multiple hypodense nodules. The full body bone scan pathology did not show focal uptake. The adrenal glands showed no significant changes.
The patient’s condition deteriorated: he presented an acute abdomen requiring surgery, for which an exploratory laparotomy was performed. This revealed a hepatic nodular lesion in the left lobe, with surface erosion and bleeding, from which biopsies were taken. The histopathological study with Haematoxylin–Eosin (H & E) staining showed limited liver trabeculae, infiltrated by a poorly differentiated malignant neoplastic proliferation consisting of medium-sized round or polygonal cells with large cytoplasma, with areas of necrosis and haemorrhage. Immunohistochemistry procedures were run, revealing neoplastic cells: positive for vimentin, Cytokeratin (AE1–AE3), β-catenin, Ki-67 (in 80% of the neoplastic nuclei) and, focally, carcinoembryonic antigen. In contrast, the tests were negative for neuron-specific enolase, Chromogranin and Hep Par-1. The earlier findings, together with the patient’s clinical context, suggested liver metastasis due to pancreatoblastoma.
The patient went into intensive care and, upon returning to the ward, started a course of chemotherapy, using cisplatin 56 mg/m2 and doxorubicin 21 mg/m2.
Following neoadjuvant treatment, the patient underwent schedule surgery for excision of a pancreatic tumour. The surgical approach was through the lesser sac, locating it in the tail and body of the pancreas. We proceeded to the lower margin, releasing the relevant vessels, to the posterior for unaffected pancreatic tissue and, finally, to the upper margin respecting the splenic vessels. A circumscribed, nodular lesion of 7 × 6 cm and weighing 150 g was obtained in the aforementioned procedure (pancreatectomy of the body and tail). The site of incision had a yellowish surface with solid areas and a friable central section. Histological sections showed the presence of a pancreatoblastoma, with large areas of necrosis and two residual peripheral nodules. Additional immunohistochemical techniques demonstrated the membrane positivity for E-cadherin and vascular endothelial growth factor (VEGF).
At present, the patient is receiving medical follow-up and is in a liver transplant programme. |
pmc-6114031-1 | A 19-year-old male presented to the emergency department at 10:42 a.m.,42 min after the sudden onset of slurred speech with weakness of his right upper and lower extremities. He reported no headache, dizziness, nausea, vomiting, fever, or convulsions. He denied any significant medical history, drug abuse, or high-risk sexual behaviors. He had no history of migraines, trauma, insect bites, exposure to chemicals, or use of medications. Apart from cigarette smoking for 1 year, he denied other risk factors for stroke. There was no history of early cardiovascular disease in the family.
On physical examination, the patient’s vital signs were normal. His weight was 65 kg (69 kg, 3 weeks ago), body mass index (BMI) 21.47 kg/m2. His chest examination was clear, and no additional murmurs were detected upon cardiac examinations. The liver, spleen and cervical lymph nodes were not enlarged; no skin or mucosal lesions were seen.He was alert and oriented to person, place, and time. The pupils were equal and reactive to light and accommodation. He had mild right hemiplegia with strength of 4:5 in the right upper and lower extremities; slight dysarthria and right lower facial paresis were also noted. The neurologic examination was otherwise unremarkable. The National Institutes of Health Stroke Scale (NIHSS) score was 3.
Rapid blood glucose was in the normal range (6.3 mmol/L). Complete blood count results showed white blood cell (WBC) count 3.0 × 109/L, hemoglobin 11.9 g/dL, and platelets 273 × 1012/L. Stroke was first considered. As he was then in the 4.5-h time window for IV-rtPA, an urgent brain CT with computed tomography angiography (CTA) of intra–extracranial vessels and whole-brain computed tomography perfusion (CTP) imaging were performed in the emergency department. The nonenhanced CT (NECT) scan (Fig. ) and CTA (Fig. ) were normal. CTP showed hypoperfusion in the left hemisphere with prolonged mean transit time (MTT) and time-to-peak (TTP), slightly increased cerebral blood volume (CBV), and relatively preserved cerebral blood flow (CBF) (Fig. -). A diagnosis of acute ischemic stroke was made. After excluding absolute contraindications for intravenous thrombolysis, 58.5 mg (0.9 mg/kg) rtPA was given at 12:30 a.m., immediately after the patient signed the informed consent. After 1 h of rtPA, his symptoms were alleviated, and the NIHSS score was decreased to 1, with slight asymmetry of the nasolabial sulcus. The patient was then admitted to the department of neurology for further investigations and treatment. Within 60 min after admission, the clinical neurological examination had completely normalized.
On the next day, the patient had no complaints of discomfort. The NIHSS score was 0. Cerebral magnetic resonance imaging (MRI) was performed, and no acute lesion was seen in the diffusion-weighted image (DWI) sequences (Fig. ). Doppler ultrasonography of carotidal and intracranial arteries showed no abnormality. Electrocardiogram, electroencephalogram (EEG) and chest CT scan were all normal. Echocardiography showed that the left and right heart chambers were within normal size and function(left ventricle ejection fraction 70%). His laboratory tests showed WBC count 2.2 × 109/L, hemoglobin 10.4 g/dL, platelets 210 × 1012/L, ESR 18 mm/h (normal 0–15.0), CRP 0.66 mg/L (normal 0–8.0), homocystein 10.4 umol/L (normal < 15.0), and mild impairment of liver function (ALT 132 U/L (normal 5–40), AST 106 U/L (normal 8–40), GGT 257 U/L (normal 11–50), ALP 127 U/L (normal 40–150)). Serologies showed the following: rapid plasma reagin, negative; antinuclear antibody and antineutrophil cytoplasmic antibody, negative; complement level including C3, C4 levels, normal; anticardiolipin immunoglobulin G(ACL-IgG), ACL-IgM, and ACL-IgA antibody levels, normal; β2 glycoprotein I immunoglobulin G (β2-GP1- IgG) and β2-GP1- IgM antibody levels, normal; high β2-GP I-IgA antibody level, 67.16 units/mL (normal 0–18). HIV enzyme-linked immunosorbent assay and Western blot confirmed HIV infection with CD4 cell count of 7 cells/uL; the CD4:CD8 T cell ratio was 0.04 (7/173). Hepatitis B virus surface antigen and hepatitis C antibody were unremarkable.
On the third day of admission, the patient received a lumbar puncture with pressure of 140 mmH2O. Cerebrospinal fluid (CSF) studies showed normal-range white cell and red cell counts but a high protein level at 1185 mg/L. The CSF glucose and chloride were in the normal range. CSF viral PCRs (including herpes simplex virus, varicella zoster, Epstein Barr, cytomegalovirus and JC virus), cryptococcal antigen, and bacterial and fungal cultures were all negative. CSF syphilis TRUST and TPPA tests were also negative. There was no meninges or brain parenchymal enhancement on his brain contrast-enhanced MRI (Fig. ).
The patient was diagnosed with aborted stroke and HIV infection. Oral aspirin 100 mg and atorvastatin calcium 20 mg daily were given. For further treatment, the patient was transferred to the HIV/AIDS ward on the fourth day of admission. On follow up 2 months later, he reported no similar symptoms. |
pmc-6114032-1 | A man in his 80s presented with 2 years of recurrent cutaneous squamous cell carcinoma of the left temple (Fig. ) with zygomatic bone metastasis. He also had significant unilateral hearing loss secondary to perineural involvement. The 2 years of therapy preceding evaluation in our oncodermatology clinic is described below. In addition to Mohs micrographic surgery, the patient had also received two rounds of adjuvant radiotherapy. In the first round of radiotherapy, the patient received a total dose of 5000 cGy in 25 fractions delivered with 3D conformation irradiation to the tumor bed and facial nodal basins. Eight months later, a bony metastasis of the mandible led to another 5000 cGy dose, which was delivered in 25 fractions using intensity-modulated irradiation tracking along the V2 branch of the trigeminal nerve to the ipsilateral skull base and encompassing the cavernous sinus. Yet another bony metastasis was discovered 5 months later, at which time he consented to 5 cycles of off-label, palliative, compassionate-use nivolumab monotherapy. However, following 2 months of nivolumab treatment, repeat MRI showed continued tumor progression. At this time he presented to our clinic complaining of a 3 week history of a rapidly enlarging painful nodule over his left zygoma. Tumor genomic analysis of the nodule using next-generation sequencing (FoundationOne®, Cambridge, MA) revealed a somatic missense (R135C) mutation in the ERBB3/HER3 gene, as well as multiple other mutations (Table ) and a high tumor mutation burden (75 mutations per megabase).
In an effort to target the ERBB3/HER3 mutation, therapy with 1,250 mg of lapatinib daily in combination with 240 mg nivolumab every 2 weeks was initiated. Additional tumor debulking in conjunction with cryotherapy to the base of the lesion was performed by our Mohs surgeon. Significant improvement in the clinical size of the lesion was noted after 2 months of lapatinib therapy. After 6 months, there was continued clinical improvement (Fig. ) and MRI showed significant regression of muscle, nerve, and bone involvement (Fig. ). The patient experienced a significant decrease in narcotic pain medication dependence and improvement in hearing of the ipsilateral ear. Other than fatigue, he experienced no side effects from this therapy. |
pmc-6114043-1 | A 64-year-old man noticed an acne-like nodule in the left parotid region 2 years prior to this presentation. It was painless, but it increased up to a maximum diameter of 4.5 cm. Clinically, left parotid gland carcinoma was suspected, and FNA cytology was performed from the left parotid region. Clusters of epithelial cells were observed in a necrotic and hemorrhagic background. These cell clusters had a sheet-like arrangement and high nuclear-cytoplasmic ratio. The nuclear shape was ovoid with hyperchromasia. Neither nuclear membrane thickening nor irregular-shaped nuclei were noted. One obvious nucleolus was observed in the central portion of the cytoplasm (Fig. ). Small lymphocytes, histiocytes and multinucleated giant cells were also seen. Malignant epithelial cells derived from salivary glands, including squamous cell carcinoma, myoepithelial carcinoma and carcinoma ex pleomorphic adenoma, were suspected. Magnetic resonance imaging (MRI) revealed a well-defined multilocular tumor located close to the outside of the left parotid gland. On T1- and T2-weighted imaging, low-intensity and heterogeneous gadolinium enhancement was seen (Fig. ). Radiologically, parotid gland cancer was suspected.
One month later, tumor resection of the left parotid region and superficial parotidectomy were performed. The cut surface showed a well-defined lobulated tumor containing yellowish-muddy materials (Fig. ). Histologically, the resected tumor was diagnosed as proliferating pilomatricoma composed of basophilic cells and shadow cells apart from the left parotid gland. The tumor was encapsulated by fibrous tissue without stromal invasion. Approximately 60% of the tumor cells consisted of shadow cells, and basophilic cells were confirmed at the periphery of the tumor. The basophilic cells were oval-shaped with a high nuclear cytoplasm ratio and had an obvious nucleolus. Two mitoses were observed per high-powered field. Focal squamous metaplasia, coagulative necrosis and apoptotic cells were also observed. Eosinophilic-stained shadow cells showed nuclear concentration and disappearance. Transitional histological findings were identified between basophilic cells and shadow cells, and supramatrical cells characterized by incomplete nuclear disappearance were also seen (Fig. ).
Immunohistochemically, basophilic cells and shadow cells were negative for anti-pan cytokeratin antibody (AE1/AE3, diluted 1:800; Leica) and high-molecular-weight keratin (34βE12, diluted 1:200; DAKO), but squamous metaplastic cells were positive. β-catenin (3-caten, diluted 1:400; DAKO) was positive for basophilic cells with nuclear and cytoplasmic staining. Ki-67 (MIB-1, diluted 1:30; Biogenex) labeling index for basophilic cells and shadow cells were 46.2% and 0%, respectively, and the p53 (Bp53–12, diluted 1:200; IBL) labeling index were 94.8% and 0%, respectively. S-100 protein (2A10, diluted 1:400; IBL), HMB-45 (HMB-45, diluted 1:200; DACO) and Ber-EP4 (Ber-EP4, diluted 1:400; DAKO) were negative for basophilic cells and shadow cells. Fibrosis, calcification, foreign body granulomatous reaction, foamy macrophage aggregation, and lymphocyte infiltration were observed in the tumor stroma. The tumor was completely resected. There was no metastasis to the lymph nodes around the parotid gland.
On a re-evaluation of the cytological specimens, the ovoid-shaped epithelial cells were considered to be basophilic cells. Shadow cells with nuclear disappearance were also confirmed. Keratin fibers were found in the cytoplasm of the shadow cells (Fig. ). Ultimately, we concluded that these cytological findings were consistent with pilomatricoma. |
pmc-6114064-1 | A 63-year-old Caucasian male patient sought an otorhinolaryngology treatment in São José do Rio Preto, Brazil, complaining of continuous hoarseness. Patient reported being smoker and alcoholic for 40 years and having stopped smoking for five years and denied any systemic or local diseases. Clinical examination showed lesions in the piriform sinus during nasofibroscopy. Lesions were biopsied and the pathological diagnosis was moderately differentiated and invasive squamous cell carcinoma (SCC). Within a month, a laryngectomy was performed with a selective right cervical dissection followed by radiotherapy.
At the first routine monitoring, 12 months later, patient presented a vegetating lesion on soft palate, diagnosed as moderately differentiated, and invasive SCC, a second neoplasm. The excision of the soft palate and complementary radiotherapy were performed. Twenty-four months after the first diagnostic, patient presented erythematous lesions on the soft palate and left tonsillar pillar, both identified as moderately differentiated SCC, third and fourth malignant tumors. Thirty-six months after the first diagnostic, patient had an ulcerative-infiltrative lesion in right tonsillar pillar, diagnosed as SCC, which is the fifth malignant tumor. Forty-six months after the diagnostic, the first malignancy the patient developed symptomatic lesions in base of tongue was diagnosed as nonspecific chronic glossitis. The tissue adjacent to the lesion was evaluated with immunohistochemical staining for p53 () with some focal areas in the basal and suprabasal layer with weak nuclear staining and Ki-67 () with the positivity of basal and suprabasal layer.
A month later, another surgery was executed to remove a lesion located in the uvula, also diagnosed as moderately differentiated SCC, being the sixth malignancy. Likewise, immunohistochemical investigation was performed for p53 and Ki-67, contiguous to the lesion of the uvula and all lesions that preceded it. The tissue adjacent to the uvula expressed diffuse immunoreactivity for p53 () and Ki-67 () with strong nuclear staining in the basal and suprabasal layer. None of the neoplasms was accompanied by lymph node metastases. At the patient's return, 60 months after the first diagnostic, there was no evidence of other malignancies. |
pmc-6114066-1 | A 75-year-old man was referred to our hospital for abdominal fullness and nausea since 2 months. He had a medical history of hypertension and hyperlipidemia and a surgical history of the right inguinal hernia. The patient's laboratory findings were within normal limits. Abdominal computed tomography (CT) revealed a well-demarcated oval isodensity mass of 25 mm at the tip of his appendix. Contrast-enhanced CT revealed a lesion with gradual homogeneous contrast enhancement from the arterial phase to the equilibrium phase (). No abnormal findings were found in the root to the middle of the appendix. Abdominal ultrasonography (US) revealed a well-demarcated hypoechoic tumor. The tumor size was 22 mm × 18 mm × 18 mm, with some cystic area and blood flow (). Colonoscopy findings were normal. The patient's symptoms naturally alleviated during examination period.
Preoperative diagnosis indicated appendiceal neuroendocrine tumor (NET) G1 or gastrointestinal mesenchymal tumors, such as GIST. Malignancy could not be ruled out; therefore, laparoscopic ileocecal resection with D3 lymph node dissection was recommended. Intraoperative findings revealed a well-demarcated tumor at the tip of the appendix, with no invasion into the surrounding tissue. This observation was similar to the preoperative imaging findings. According to another intraoperative finding, dissecting the adhesion between the terminal ileum and the peritoneum, which was the effect of the past herniorrhaphy, was necessary. The operation time was 167 min, and the amount of blood loss was 100 ml.
Pathological findings revealed a well-demarcated tumor originating from the muscular layer at the tip of the appendix and spindle-shaped heterotypic cells proliferating in a bundle. Vascular invasion and lymph duct invasion were not detected. No tumor cells were found in the dissected lymph node. Immunohistochemical studies revealed negative values for KIT and CD34 and positive values for S-100 protein (), which confirmed the schwannoma of the appendix. The patient was discharged on the 9th day after surgery without any complication requiring medical treatment. The patient is presently doing well without any evidence of recurrence at 3 months after surgery. |
pmc-6114068-1 | A 42-year-old Japanese woman was admitted to our hospital for evaluation of severe thrombocytopenia. At the age of 34, SLE was diagnosed on the basis of a malar rash, oral ulcers, arthritis, and positivity for anti-double-stranded- (ds-) DNA antibody. Prednisolone was started at a dose of 30 mg/day, after which tacrolimus was added at 3 mg daily. Her SLE improved, and prednisolone was tapered to 3 mg/day. One month before admission, proteinuria increased to 2.34 g daily. Serum albumin was 2.0 g/dL (normal: 3.9–5.2), and creatinine was 2.3 mg/dL (normal: 0.46–0.78). Anti-ds-DNA antibody showed an increase to 90 IU/mL (normal: <12). The platelet count was decreased to 4.4 × 104/μL, and CH50 was 5 U/mL (normal: >30 U/mL) (). Antiplatelet drugs or any other drugs that could adversely affect platelet numbers were not taken. Intravenous methylprednisolone pulse therapy (1000 mg/day for three days) was initiated, followed by methylprednisolone at 48 mg/day. She also received five monthly cycles of intravenous cyclophosphamide (IVCY) pulse therapy (500 mg per cycle). Although her renal function, complement levels, and the anti-ds-DNA antibody titer all improved, thrombocytopenia became worse and the patient was admitted to our hospital ().
On admission, she had diffuse purpura on the anterior chest and limbs. The lungs were clear on auscultation. The liver and spleen were not palpable, and there was no evidence of arthritis or pathological bleeding such as epistaxis. Pitting edema of both legs was noted.
Laboratory findings were as follows (): the white blood cell count was 6,300/μL (86.5% neutrophils and 7.5% lymphocytes), hemoglobin was 8.7 g/dL, reticulocyte count was 9.3 × 104/μL (3.5%), and platelet count was 0.8 × 104/μL (10.5% immature platelets). The direct Coombs test was negative. Anemia secondary to chronic inflammation caused by SLE was considered. In addition, serum albumin was 3.1 g/dL, blood urea nitrogen was 33 mg/dL (normal: 8–21), creatinine was 1.2 mg/dL, and eGFR was 38.8 ml/min/1.73 m2. C-reactive protein was 0.0 mg/dL. Antinuclear antibody (ANA) was positive at 1:40 with a speckled pattern, while anti-ds-DNA antibody was elevated to 18 U/mL (normal: <12). The lupus anticoagulant assay was consistently negative, and anticardiolipin antibodies were not detected throughout the clinical course. ADAMTS13 activity was 87% (normal: >10%), and inhibitors were not detected. Total urinary protein excretion was 1.55 g/day. The urine sediment contained 6–10 erythrocytes per high-power field (HPF). Bone marrow examination showed normocellular marrow, and megakaryocyte number was within normal range with 12 (normal range: 10 to 50) number/mm2. There was no hepatosplenomegaly on computed tomography of the abdomen. |
pmc-6114227-1 | A 55-year-old gentleman with a history of diabetes mellitus, hypertension, cocaine, and marijuana use presented to the emergency department (ED) with complains of chest pain and dyspnea for past 6–8 months, as well as lower extremity edema and weight loss. On admission to the hospital, his vital signs were stable. Physical examination revealed obesity, decreased breath sounds bilaterally, and mild tachycardia, and point of maximal impulse was enlarged and displaced at the presence of edema on bilateral lower extremities. The patient has poor dentition with cavity in the left second molar tooth. The rest of the examination was otherwise unremarkable. Complete blood count revealed a hematocrit of 33.1%, hemoglobin 9.7 g/dL, platelet count 232,000/mL, and white blood count 8.6 × 103. Blood chemistry was unremarkable. B-type natriuretic peptide was 613 pg/mL.
Because of his chest pain and associated signs, the patient underwent a computed tomography (CT) scan of the chest with intravenous contrast, which revealed a very large pericardial effusion, compressing the right and left ventricles and the right atrium (). In addition, there was consolidation in the left mid lung, bilateral pleural effusions, and bilateral pulmonary embolism. A 2D echocardiogram revealed cardiac tamponade with right ventricular diastolic collapse, with a large fibrinous exudative pericardial effusion (). The patient underwent an emergent pericardial window due to his clinical signs and symptoms consistent with cardiac tamponade. The pericardial drainage showed a significant amount of yellow creamy pus with thickened pericardium. Anaerobic culture reported the presence of Capnocytophaga species. The pathology specimen showed acute necrotizing and exudative changes including frank abscess formation with no specific organism detected and no evidence of malignancy (Figures and ).
The patient's condition improved postoperatively and was placed on piperacillin and tazobactam for four weeks. His pulmonary embolism and acute deep vein thrombosis were treated with systemic anticoagulation. The patient was discharged home on apixaban and has been seen on the follow-up visit with significant improvement in his symptoms. |
pmc-6114237-1 | A 21-year-old woman pregnant with twins at 29 weeks of gestation was admitted to the previous hospital for preterm labor. After one week of tocolysis with intravenous ritodrine, she developed acute dyspnea and was referred to our hospital. Ritodrine was stopped immediately, and computed tomography of the chest revealed no pulmonary embolus, but bilateral pleural effusion was present. On admission, she also presented with hypertension (152/112 mmHg) and proteinuria (3.8 g/day). She was diagnosed with severe preeclampsia, and magnesium sulfate was initiated, and betamethasone was administered for accelerating fetal lung maturation. After starting magnesium sulfate, her systolic blood pressure did not exceed 140 mmHg, and no further antihypertensive agent was necessary. On day 3 of admission, her SpO2 fell to 95% with 5 liters of supplemental oxygen, and NPPV was initiated. After implementation of NPPV, her subjective dyspnea improved, and her SpO2 rose to 99% on room air. Pulmonary edema was also ameliorated on her chest X-ray. However, her serum creatinine level was increased to 1.0 mg/dl at 33 weeks of gestation, indicating reduced kidney function. Other symptoms, such as increase in liver enzymes, platelet reduction, and gastrointestinal or neurological symptoms, were not detected. Fetal conditions in utero were favorable. She underwent a cesarean section at 33 weeks and 1 day of gestation due to initiation of labor. The patient delivered healthy male twin infants weighing 1496 g and 1876 g. NPPV was continued intermittently after delivery until she was successfully weaned off of it. |
pmc-6114237-2 | A 36-year-old primigravida at 17 weeks and 4 days of gestation was admitted for hypertension (152/99 mmHg), proteinuria (1.8 g/day), and elevated liver enzymes (AST 75 U/L, ALT 121 U/L). Careful examination revealed no evidence of secondary hypertension or primary renal disease. Furthermore, serum levels of soluble fms-like tyrosine kinase 1 (sFlt1) were very high (8.41 ng/mL) at 18 weeks of gestation. Subsequently, we classified this case as extremely early onset preeclampsia []. Nifedipine and magnesium sulfate were administered. Ascites, pleural effusion, and pulmonary edema were detected at 19 weeks of gestation. NPPV was initiated for worsening pleural effusion at 20 weeks of gestation due to desaturation (94% SpO2 on room air). After NPPV implementation, the patient's SpO2 rose to 99% with 1 liter of supplemental oxygen. Chest X-ray showed no progression of pulmonary edema, although ascites gradually increased, resulting in an emergency cesarean section at 23 weeks and 3 days of gestation due to deteriorating dyspnea, and nonreassuring fetal status, specifically reversed end-diastolic umbilical artery flow and absence of atrial-flow in ductus venosus. A 285 g male infant was delivered. NPPV was discontinued on day 2 after delivery. |
pmc-6114237-3 | A 40-year-old primigravida at 24 weeks of gestation was referred to our hospital for severe hypertension (170/95 mmHg) and proteinuria (8.8 g/day). On admission, she received magnesium sulfate, methyldopa, and nifedipine. On day 2 of admission, she developed respiratory distress with mild desaturation (95% SpO2 on room air), and chest X-ray showed bilateral pleural effusion. Blood exam revealed elevation of liver enzymes (AST 133 U/L, ALT 161 U/L), and partial HELLP syndrome was diagnosed. Corticosteroids were administered intravenously, and NPPV was initiated. The patient's SpO2 rose to 99%, and pleural effusion did not increase further. However, ascites gradually increased, and her general fatigue became intolerable. As a result, a cesarean section was performed at 25 weeks and 2 days of gestation. Before delivery, the fetal condition in utero was reassuring, in terms of fetal heart rate monitoring and biophysical profile score. A 532 g female baby was delivered. We applied NPPV postoperatively, and she was discharged on day 12 after delivery without any complications. |
pmc-6114244-1 | A 53-year-old patient was recently diagnosed with pancreatic cancer with obstructive jaundice, for which he underwent a Whipple procedure. Unfortunately, the procedure was complicated with a pancreatojejunostomy anastomosis leak, deep vein thrombosis deep vein thrombosis (DVT), and postoperative-bleeding. He was taken for exploratory laparotomy and a revision of gastrojejunostomy anastomosis without the successful localization of the source of the bleeding; later the same day, the patient underwent diagnostic DSA, which also failed to localize the source of the bleeding. GIBS was requested for better localization of the GI bleeding source.
The study was positive for active bleeding, which had started primarily high in the right upper abdomen, supposedly from the region of the hepaticojejunostomy (Figures and ). Therefore, the patient was transferred to the angiography suite for another diagnostic and therapeutic DSA. Selective catheterization of the superior mesenteric artery was performed followed by an angiogram, which showed no active contrast extravasation and identified no abnormality. Then selective catheterization of the celiac trunk was followed by an angiogram, which showed small contrast extravasation originating from the proximal common hepatic artery, most likely from the gastroduodenal artery stump (). Using a coaxial microcatheter/microwire utilizing an Echelon catheter and synchro-wire, contrast was injected for the selective catheterization of the small arterial branches originating from the proximal main common hepatic artery. A small extravasation was confirmed, and while the catheter remained in the same position, coil embolization was performed utilizing three coils measuring 2 mm. After that, an angiogram was performed that showed no extravasation and no abnormality (). And upper abdominal angiogram was also performed, again demonstrating no abnormalities. No immediate complications were encountered. |
pmc-6114246-1 | Our patient is a 5-year-old female who was referred for evaluation and management of recurrent episodes of cellulitis in the left scapular region. A small cystic lesion had first been noted at the age of 2 years. While this had initially been an asymptomatic, small lump that grew in size over time, it first became symptomatic when the patient was 4 years old. The lesion developed surrounding induration and erythema, as well as purulent drainage and tenderness. Over the next 1-year period, she went on to develop 3 such episodes of cellulitis. This was treated with a 10-day course of cephalexin by the patient's family physician, and it was due to these recurrent episodes of infection that we saw the patient in consultation.
Physical examination revealed a playful and well-appearing 5-year-old female, weighing 24.8 kg and measuring 114.5 cm in height. Review of systems and cardiorespiratory examinations were unremarkable. On inspection of the left scapular region, approximately 7 × 5 cm area of cellulitis was noted, with a small opening and associated purulent drainage. The surrounding skin was tender to palpation, but there was no appreciable fluctuance. Thus, the initial working diagnosis was infected epidermoid cyst. An ultrasound of the affected area showed a complex cystic mass measuring 3.9 × 2.9 × 3.7 cm within the subcutaneous fat (). Deeper margins of the mass were poorly demarcated due to the degree of inflammation, and the lesion appeared to abut the underlying musculature. Since these findings were nonspecific, an MRI was obtained to further characterize the lesion. The MRI revealed the presence of a subcutaneous cystic lesion just superior to the scapula measuring 1.6 × 3.5 × 2.8 cm. While the mass abutted underlying muscular fascia, there was no extension into the underlying trapezius muscle itself (Figures and ). Thus, the decision was made to pursue surgical excision of the lesion. This was performed under general anesthesia, which the patient tolerated well. Intraoperatively, we noted that the mass was quite soft, cystic, irregular in shape, and not well circumscribed. Nonetheless, we were able to excise the lesion in its entirety. Histopathology from this specimen revealed a benign cyst lined with ciliated columnar epithelium (). In addition, the cyst wall itself contained smooth muscle, small mucous glands, and clusters of lymphocytes. Thus, these findings were in keeping with a bronchogenic cyst and not an epidermoid cyst as was initially suspected. On 1-year postoperative follow-up, the patient is doing well, with no recurrence of infection or other symptoms. |
pmc-6114280-1 | 52-year old woman with a history of chemotherapy for coat cell lymphoma in 2011, splenectomy in 2013 and autologous bone marrow transplantation in 2014 was admitted to the medical intensive care unit (ICU) after having fever up to 38.7 °C and malaise for 24 h. On admission, she was somnolent; the skin was cold, wet and pale; body temperature was 38 °C, blood pressure 50/40 mmHg and puls 120/min. She was eupnoeic with oxygen saturation (SatO2) of 100% by pulse oximetry, inspiring 2 L of oxygen by nasal cannula. Clinical examination revealed rales over both lungs and tachycardia without heart murmurs. Abdomen was soft and painless with audible peristalsis. Standard electrocardiogram (ECG) showed sinus tachycardia of 125/min.
On admission, we started continuous ECG monitoring, pulse oximetry, non-invasive blood pressure measurements and inserted central venous, arterial and urine catheters to measure central venous pressure intermittently, arterial blood pressure continuously and diuresis per hour.
We suspected sepsis with septic shock and immediately started treatment of shock and diagnostic procedures for sepsis. We managed shock initially by rapid infusion of crystalloids until we confirmed fluid unresponsiveness by ultrasound of inferior vena cava, demonstrating its diameter of 2.2 cm, that did not change with inspiration. Therefore, we started noradrenalin infusion within the first 15 min and up titrated it to 66μg/min. In addition, bedside echocardiography showed decreased ejection fraction (EF) of the left ventricle to 20%. We added dobutamine infusion, but also glucocorticoids and later on vasopressin to reach normotension.
From the very start we suspected pneumonia on clinical grounds and confirmed it by bilateral infiltrates on chest rentgenograph. Among admission laboratory data we observed lactacidosis (arterial pH 7.24, bicarb 13.4 mmol/l, pCO2 4.24 kPa, pO2 13 kPa, lactate 7.5 mmol/l), thrombocytopenia (62 × 103/μL), leucocytosis, increase of procalcitonin to 100 ng/ml, C-reactive protein (CRP) to 166 mg/l, N-terminal-pro brain natriuretic peptide (NT-proBNP) to 2114 pmol/l, myoglobin to 482μg/l, and serum creatinine to 288 μg/l. Admission SOFA score was eight. We collected hemocultures, urinoculture and aspirates as soon as possible and after that immediately administered imipenem 500 mg/6 h IV.
After the first 24 h positive pneumococcal urine antigen confirmed streptococcal pneumonia. We continued imipenem therapy and adjusted the dose to renal failure. Other microbiological cultures remained negative. Together with the specialist for infectious disease we decided to continue imipenem therapy due to prior disease, including splenectomy.
After 24 h of ICU-stay the patient needed 40% oxygen by mask to achieve satisfactory blood gases (pH 7.2, bicarb 15 mmol/l, paCO2 5.35 kPa, paO2 8.5 kPa), her body temperature was 38 °C. SatcvO2 was 76.1%. Luckily, the patient did not need neither non-invasive, nor invasive ventilation during the entire ICU stay.
In spite of all treatments, after the first 24 h multiorgan failure syndrome persisted, including severe systolic myocardial dysfunction with left ventricular EF of 20%, measured by echocardiography. SOFA score at that time was 12.
After 36 h of ICU stay resistant septic shock with high-dose catecholamine support, left ventricular dysfunction with EF of 20% persited and renal failure (serum creatinine 379μmol/l, daily urine output < 500 ml) worsened. SatcvO2 was 78%, body temperature 37 °C and SOFA score increased to 13.
In addition to echocardiography, Pulse Contour Cardiac Output (PiCCO) catheter was inserted to improve hemodynamic monitoring and demonstrated cardiac index (CI) of 3.3 l/min/m2) with stroke volume (SV) of 50 ml, increased global end-diastolic index (GEDI) to 1023 ml/m2 and extra vascular lung water index (ELWI) to 13.3 ml/kg and decreased systemic vascular resistance index (SVRI) of 1672 dyn.s.cm− 5.m2.
Persistant hemodynamic instability and worsening renal failure led to the decision to start continuous veno-venous hemofiltration (CVVH) combined with hemoadsoption treatment by CytoSorb® membrane for the next 24 h. The goal was to improve hemodynamic situation and modulate the inflammatory response in our splenectomised septic patient. Before the start of blood purification therapy, we measured serum IL-6 level, which was 114 pg/ml.
After only 24 h of CVVH with concomitant use of a single CytoSorb® membrane EF increased to 45%. PiCCO measurements improved as follows: GEDI changed to 805 ml/m2, ELWI to 11.2 ml/kg, SVR to 1888 dyn.s.cm− 5.m2 and CI to 3.95 min/m2 and SV to 61 ml. The patient’s temperature was 37 °C and SOFA score 11. IL-6 dropped from 114 pg/ml to 14,2 pg/ml after termination of hemoadsoption therapy.
We could stop the use of dobutamine, norepinephrine and vasopressin. The next day SOFA score was seven. Serum lactate and arterial pH turned to normal within few days, as well as CRP, procalcitonin (Fig. ), leucocyte and platelet count after 14 days (Fig. ). Table presents the course of the treatment.
For regeneration of the kidney function the patient received CVVH intermittently for another 21 days. She was discharged from ICU after 10 days and from the hospital after 76 days. |
pmc-6114482-1 | A 12-year-old boy with SCD was presented with fever, periocular pain, and diplopia after returning from Taif, Jeddah. Taif (means “encompassing”) is located in the Hejaz Mountains of Saudi Arabia. It is considered as a high-altitude area because it is 6000 ft above the sea level []. The patient had a previous history of similar attacks that resolved after conservative management at another hospital in the same city few years ago (Fig. ).
On admission, the patient looked sick, drowsy, and pale. The temperature of patient was 38.2 °C, heart rate was 115/min, respiratory rate was 25/min, blood pressure was 100/65, and oxygen saturation was 90% on room air. The patient weighted 38 kg. Ocular examination showed right eyelid edema, peri-ocular soft tissue swelling, proptosis, and limitation in elevation of the right eye. On admission, the visual acuity of right eye was 20/30 and left eye was 20/20. Color vision was evaluated using the color plates that came out to be normal. The pupils were equal in size and reactive to light. Swinging light Reflex showed normal reaction of both pupils. There was no afferent pupillary light reflex defect (APD). The intra-ocular pressure was normal in both eyes. Fundus examination revealed normal disc, blood vessels, and macula. A complete systemic evaluation was conducted.
The systemic evaluation revealed hemolytic anemia, thrombocytopenia, stable coagulation profile, and negative blood culture. Laboratory results showed hemoglobin level of 89 g/ L, mean cell volume was 84.2 FL, white blood cell count was 24.04X109/L with neutrophils 21.81X109/L, and mean platelets volume 10.30 FL. Serum bilirubin was measured to be 95.5 mmol/L, albumin was 26 g/L, blood urea was 3.8 mmol/L, and serum creatinine was 39 mmol/L. The erythrocyte sedimentation rate was 40 mm/h (normal < 15 mm/h), and C-reactive protein was 8.2 mg/dL (normal < 0.5 mg/dL) (Table ).
The coagulation parameters revealed a prothrombin time (PT) of 14 S (normal 10–12.8), International Normalization Ratio (INR) 1.2 (normal 0.9–1.2) and activated partial prothrombin time (aPTT) 33.4 S (normal 25.3–38.4). Hemoglobin electrophoresis showed HbS 58%, HbA 36%, HbF 2%, and HbA2 4% (consistent with sickle b thalassemia). Urine analysis was normal, and the culture report was negative. Magnetic Resonance Imaging (MRI) of the right orbit demonstrated peri-orbital edema and a mass adjacent to the right orbital wall. This condition was identified as a superior subperiosteal haematoma with evidence of orbital bone and bone marrow abnormal signals consistent with orbital wall infarction (Fig. ).
The bone abnormality was further investigated to explore the possibility of the presence of primary or metastatic tumors that are susceptible to bleeding. Therefore, CT-imagery was utilized to explore this area of interest. However, as may be seen from the CT images, there was no evidence of primary or metastatic bone tumors (Fig. ).
The patient received intravenous fluids, analgesics, broad spectrum antibiotics, and pulse methylprednisolone immediately. The patient responded well to medical management with complete recovery and was discharged after the condition was stabilized. This case has highlighted the importance of considering orbital wall infarction in the differential diagnosis of orbitopathy among the patients with SCD, along with osteomyelitis and orbital abscess. Careful evaluation, diagnosis, and the prompt initiation of the appropriate supportive care are highly recommended in order to prevent permanent visual loss. |
pmc-6114485-1 | The patient was a two-year eleven-month old boy born to non-consanguineous 21-year-old primigravida mother of Ashkenazi Jewish descent and 25-year-old father of Ashkenazi Jewish and Irish descent. Pregnancy was uncomplicated and he was born at 41 + 4 weeks gestation via spontaneous vaginal delivery. Apgar scores were 9 at 1 and 5 min. Birth weight was 3.834 kg (50-75th centile). Neonatal course was unremarkable.
Developmental concerns arose in early infancy. He sat unsupported after twelve months of age and walked independently at twenty-two months of age. At 2 years, 3 months of age, he could go upstairs with two-hand support and climb furniture. Gait was ataxic. He had a palmer grasp, could hold objects at the midline for thirty seconds, and could not transfer objects. He did not have any words but had recently started using gestures. Reception was limited to one step commands. He was easily excitable but demonstrated good socialization attempts with other children.
Medical history was significant for myoclonic seizures starting between 2 to 3 years of age, requiring anti-epileptic medications. He preferred pureed foods, with occasional choking episodes. He also displayed preference for specific textures, and a fascination for water. Sleep was disrupted with frequent awakenings, thought to be behavioural. Echocardiogram, abdominal ultrasonography, brain magnetic resonance imaging (MRI), and genetic testing for Angelman syndrome were normal.
At 2 years, 3 months of age, weight was 12.1 kg (15-50th centile), height was 87.5 cm (15-50th centile) and head circumference was 48 cm (− 1 SD). He had deep-set eyes, down slanting palpebral fissures, prominent nasal root and tip, prominent ears, with a myopathic expression (Fig. ). An intention tremor and ataxic gait were noted.
Family history was notable for maternal anxiety, and attention deficit disorder in two maternal cousins. His mother and maternal grandfather had completed college and post-graduate professional education respectively. There was no family history of GDD, ataxia, other neurological disorders, infertility or multiple miscarriages. As the father was no longer involved in the child’s care, further detailed paternal history was unavailable. |
pmc-6114493-1 | A 72-year-old woman was referred to our hospital with one-month history of a palpable mass with burning sensation in her left breast. Mammography revealed a nodular increased density of the upper inner quadrant of the left breast considered to be suspicious of malignancy, Breast Imaging Reporting and Data System category 5 (BI-RADS-5).
Ultrasound revealed a hypoechoic mass with irregular and poorly defined margins measuring 23 mm × 14 mm. The ipsilateral axillary lymph nodes were normal. After a diagnosis of malignancy on core needle biopsy, the patient underwent simple mastectomy of the left breast and sentinel lymph node biopsy.
On gross examination, two neighboring foci were found measuring together 28 mm × 17 mm. There were ill-defined whitish lesions with soft red-brown areas inside. No nipple and periareolar lesion were seen. Histologically, both tumor foci were identical, and similar features were observed in the 6 sections examined. The tumor showed high cellularity arranged in sheet of discohesive cells with large cytoplasm and marked nuclear atypia. The tumour cells showed 15 mitosis per high power microscopic field. The lesion included numerous osteoclast-like giant cells containing many small uniform nuclei and hemosiderin-laden macrophages. The stroma was loose, highly vascular with hemorrhagic areas and foci of chronic inflammatory infiltration. Some carcinomas in situ foci were also identified at the periphery of the infiltrating tumour (Fig. ).
One of the three sentinel lymph nodes analyzed using routine intraoperative One-Step Nucleic Acid Amplification (OSNA) assay showed metastasis (17,000 copies/uL). Subsequently, ipsilateral axillary dissection was performed and no additional metastases were found in 14 additional lymph nodes resected.
The immunohistochemical study (see Additional file : Table S1) demonstrated the epithelial nature of the neoplasia, since the tumour cells expressed both cytokeratins AE1/AE3 and CK19 that were positive. Due to the discohesive nature of the cells, immunostaining for E-cadherin was performed and demonstrated complete absence of expression in both, the in situ and the invasive components. On the contrary, giant cells were negative for cytokeratin expression but were strong positive for the histiocytic marker CD68. With these features, the diagnosis was of invasive pleomorphic lobular carcinoma (histological grade 3) with OGCs (Fig. ).
Biomarker analysis demonstrated that the carcinoma was estrogen receptor (ER) positive (strong positivity in 90% of tumor cells); progesterone receptor (PR) negative (complete absence of expression); and demonstrated lack of overexpression of human epidermal growth factor receptor type 2 (HERCEPTEST 1+). The Ki67 cellular proliferation index was 18%. The analysis of immune related markers demonstrated that, after counting at least 10HPF, the tumors has a mean of 34 CD3+ lymphocytes per 1HPF, 22 CD8+ lymphocytes per 1HPF, 2 CD4+ lymphocytes per 1HPF, and 1 CD20+ lymphocyte per 1HPF. Only occasional tumor cells (less than 1%) were PDL-1 + .
The tumor was subjected to molecular analysis by targeted next generation sequencing. DNA was extracted from a punch focused on the area with greater tumour cell density by using QIAamp® DNA FFPE Tissue Kit (QIAGEN). Quantification (447 ng/μl) and qualification (DIN = 4.6) of the DNA was performed using a Tape Station 2200 (Agilent) and the Genomic DNA kit. We used an in-house panel based on hybrid capture for sequence enrichment including the 34 genes frequently mutated in breast cancer (AKT1, ARID1A, ARID1B, BRCA1, BRCA2, CASP8, CCND1, CDH1, ERBB2, ESR1, FGFR1, GATA3, GRB7, GSDMB, MAP2K4, KRAS, MAP3K1, MLL3, MYC, NCOR1, NF1, PGAP, PIK3CA3, PNMT, PTEN, RB1, SF3B1, STARD3, TBX3, TCAP, TP53, VGLL1, ZNF217, ZNF703) and regions in chromosome 8 (targeting amplification of FGFR1 and MYC), chromosome 11 (targeting amplification of CCND1), chromosome 17 (targeting amplification of ERBB2) and chromosome 20 (targeting amplification of ZNF217). With this technique, we identified a deleterious mutation (C.del866C) in CDH1 (the gene coding for E-cadherin protein) (Fig. ).
The patient was enrolled in a trial that studies giving tamoxifen with or without combination chemotherapy in postmenopausal women who have undergone surgery for breast cancer. The patient was randomized on the arm for receiving only hormone treatment. The patient remains well without evidence of recurrence or metastases two years after surgery. |
pmc-6114516-1 | A 65-year-old white male presented 10 days after the onset of a central scotoma in the left eye (LE). BCVA at presentation was 20/20 in the right eye (RE) and 20/32 in the LE. Fundus examination of the LE revealed an area of RPE atrophy in the inferonasal macula with foveal sparing (Fig. ). FAF in the left eye revealed a trizonal pattern and a demarcating hyper-FAF line between the involved and uninvolved retina (Fig. ); these findings were consistent with AZOOR [].
Ten days later, he returned complaining of distortion. Fundus examination revealed zonal lesion expansion, which was confirmed by FAF. The OCT revealed mild subretinal fluid (SRF) which explained his metamorphopsia. The patient returned a week later. At this time, visual acuity had reduced to 20/60, and two perilesional haemorrhages were observed along with a hypo-FAF zonal lesion expansion which included the fovea (Fig. ). The OCT showed a significant increase of subretinal fluid. These findings were consistent with a type 2 (subretinal) CNV which was confirmed by fluorescein angiography. Consequently he received 3 monthly intravitreal bevacizumab injections. One month after the first injection, FAF revealed zonal progression (Fig. ) and OCT revealed a worsening of SRF (Fig. ). One month after the third injection, BCVA in the LE was 20/70 and the patient reported stabilization of his central scotoma. At month 5, BCVA was 20/60; OCT scan showed resolution of SRF, while FAF revealed minimal advancement of zonal lesion size. During follow-up the zonal lesions stabilized; the patient received 11 intravitreal bevacizumab injections on a treat and extend regimen for 4 years and maintained a BCVA of 20/60 in the LE. |
pmc-6114516-2 | A 69-year-old white male was referred for sudden onset scotoma with blurriness and photopsia in the LE. BCVA was 20/20 in the RE, and 20/40 in the LE. Fundus examination revealed bilateral peripapillary atrophy and retinal swelling at the macula of the LE (Fig. ). OCT scan and FA revealed a juxtafoveal type 2 CNV in the LE. One intravitreal bevacizumab injection was administered in the LE. Four 4 weeks after the injection, BCVA was stable; in the RE the peripapillary lesion extended and new zonal lesions were visible temporal to the fovea (Fig. ); in the LE the peripapillary and the macular defect extended and merged appearing as a single, large zonal defect involving the fovea. FAF in both eyes revealed a trizonal pattern and a demarcating hyper-FAF line between the involved and uninvolved retina (Fig. ); these findings were consistent with AZOOR [].
FA showed persistence of leakage from the CNV and two additional intravitreal bevacizumab injections were administered. One month after the third injection, further progression of the zonal lesions was observed in both eyes (Fig. ). SD-OCT scan showed complete resolution of the subretinal fluid with persistent well-defined subretinal hyperreflective material (Fig. ). Since then, the patient has maintained a BCVA of 20/50 in the LE (and 20/25 in the RE) with no evidence of progression of the zonal lesions and CNV stabilization during 2 years of follow-up. |
pmc-6114516-3 | A 33 year-old white female presented with central scotoma and distortion in the RE for 2 months. She was 3 months post-partum and nursing at the time of presentation. BCVA was 20/30 in the RE and 20/20 in the LE. Dilated fundus examination showed multiple, well-demarcated zonal areas of outer retinal atrophy at the posterior pole and at the mid periphery of both eyes (Fig. ). There were pigmented brownish dots located mainly at the margins of the atrophic areas but also within the lesions bilaterally. FAF in both eyes revealed a trizonal pattern and a demarcating hyper-FAF line between the involved and uninvolved retina (Fig. ); these findings were suggestive of AZOOR []. After 2 months, a progression of the zonal lesions was found in both eyes; in the RE, the progression occurred around the disc and towards the fovea and development of a subfoveal type 2 CNV was noted (Fig. ). Over a course of 3 years the patient underwent intravitreal anti-VEGF injections on a treat-and-extend regimen (12 ranibizumab and 5 aflibercept injections) and her vision has stabilized to 20/40 in the RE. During treatment there was zonal progression at the right macula (Fig. ). In the LE the zonal lesion at the posterior pole remained stable with fovea sparing and patient remained asymptomatic with a BCVA of 20/20. |
pmc-6114516-4 | In 2004 a 47 year-old white male presented with 2 months history of blurred vision in the RE, associated with photopsias. BCVA was 20/50 in the RE and 20/20 in the LE. Fundus examination of the RE showed a peripapillary lesion. Fundus examination of the LE was unremarkable. FAF of the right peripapillary lesion showed a trizonal pattern and a hyperautofluorescent border between the involved and uninvolved retina []. Upon consultation of the recent literature at the time [], the diagnosis of AZOOR was made. Small haemorrhages were observed at the temporal side of the lesion and fluorescein angiography showed the presence of a choroidal neovascularization. Decision was made to perform a standard PDT with a single spot of 2.5 mm focused on the temporal part of the zonal lesion. Three months after treatment no improvement of visual acuity was recorded. The PDT was not repeated and during follow-up the CNV enlarged resulting in macular scarring. In 2005 there was a central fibrotic pattern with persistent peripheral haemorrhages and subretinal fluid. In the RE BCVA improved from 20/100 to 20/40, with an eccentric viewing; this eye had no longer a reading ability. From 2005 to 2015, a progressive enlargement of the scar was noted in the RE (Fig. ). In 2009 small peripapillary lesions were found in the LE. FAF features of these lesions were consistent with AZOOR []. These zonal lesions increased in size during follow-up (Fig. ) and remained stable thereafter. At the last follow-up visit in 2015 the left eye eye maintained a BCVA of 20/20, without any symptoms. |
pmc-6114535-1 | A healthy 32-year-old Asian woman presented to the emergency department with pain, photophobia and blurred vision in the right eye. There were no associated illnesses, history of retinotoxic exposures (medications, light), or family history of eye disorders. Written informed consent was obtained; the procedures adhered to the Declaration of Helsinki, and the study was approved by the institutional review board of the Wuhan University Renmin Hospital.
Her uncorrected visual acuity was 20/200 in the right eye, 20/25 in the left eye. Intraocular pressure (IOP) was 31 mmHg in the right eye and 16 mmHg in the left. Neuro-ophthalmic examination was RAPD positive in the right eye. Mid-dilated fixed pupil in the right eye (Φ ≈ 4 mm). Tyndall phenomena were observed, vitreous were normal without cells; fundus examination results were also normal. The anterior segment image present with iris pigment detachment at 9 o’clock in the right eye (Fig. -). Results of anterior segment optical coherence tomography (ASOCT) showed slightly shallow anterior chamber in right eyes (Fig. -). The unharmed left eye also show slightly shallow anterior chamber (Additional file : Figure S1). On subsequent questioning, the patient disclosed that she received an intense-focused ultrasound (IFUS) in a cosmetic surgery center to lift and tighten the upper eyelid. Ultrasonic probe was applied at the eyebrow area. She immediately complained of painful blurry vision, the treatment was stopped and she was transferred to hospital.
After anti-glaucoma treatment for 1 day, IOP of the right eye dropped to normal range (21 mmHg). Uncorrected visual acuity in the right eye was improved to 20/160. Best-corrected visual acuity (BCVA) of right eye was 20/20 with refraction of − 1.50 DS/− 1.0 DC × 165. At 3 days follow-up, spectral-domain optical coherence tomography (SD-OCT) was performed using an SD-OCT/scanning laser ophthalmoscope system (Heidelberg Engineering). Automated light-adapted static perimetry (HFA II-I; Carl Zeiss Meditec) using a 30–2 protocol confirmed a pericentral scotoma corresponding to the abnormality in the right eye (Fig. ), which could be causal by acute increase of IOP induced optic nerve edema; the left eye finding was unremarkable. Standard full-field flash electroretinography (ERG), and visual evoked potential (VEP) was normal, ruling out retina and brain disease. Optical Quality Analysis System (OQAS) exam showed that the objective scatter index (OSI) was 1.0 in the right eye and 0.7 in the left, modulation transfer function (MTF) cut-off was 23.831 in the right eye and 28.694 in the left; indicating comparable worse vision quality in the right eye (Additional file : Table S1), at 1 month’s follow-up.
At presentation to us on the 3 months of her symptoms, the patient still complained with headache, blur vision with photophobia in the right eye. Her iris damage was remained, with IOP measurement in normal range. Acquired myopia became her major complain. A comprehensive eye exam was further performed by an optometrist. Negative and positive relative accommodation (NRA/PRA), and accommodation amplitude was measured. Clearing additional plus lens power was difficult for this patient, indicating accommodation spasm in the right eye.
Accommodative spasm is a rare condition occurring in children, adolescents, and young adults. It can be caused by trauma [], emotional problems, and other causes. In our case, further exam confirmed her accommodative spasm which was partially reversed by cycloplegia drops and bifocals.The patient was put on 1% tropicamide eye drops once a day and flipper lenses training was applied to treat her accommodation spasm. After 1 month, the patient achieved better uncorrected vision acuity at distance in the right eye (20/40) (Additional file : Table S2).
Safety and efficacy of IFUS in the aging eyelids have been studied and reported in the previous study []. Tightening of infraorbital laxity and skin can be achieved using the IFUS, is performed by heating the dermis and underlying tissue, where protein around the focal point will reach over 65 °C and denatured within milliseconds []. After the initial heat effects, the skin initiates a wound healing response, resulting in the formation of new collagen, which provides longer-term tightening of the skin []. In this case, the acoustic energy rays might have threaded through the eyelid, caused dysfunction of the ciliary muscle, which affected the zonular tension, causing acute increase of IOP and acquired myopia. The excessive curvature of refractive lens surface leaded to curvature myopia and accommodation spam (Fig. ). Heat-caused injuries may be associated with a transient IOP increase due to acute trabecular meshwork changes. |
pmc-6114698-1 | This present case involved a 22-year-old female who became aware of leukocoria in both eyes. Upon examination at another eye clinic, a vitreous strand was detected in her left eye, with a suspected diagnosis of PFV, and she was referred to the Department of Ophthalmology at Osaka Medical College Hospital, Takatsuki-City, Japan for a more detailed diagnosis and subsequent treatment.
The patient had previously been diagnosed with strabismus when she was 2 years of age. She was delivered at full term, with a birth weight of 3320 g, and she had no history of oxygen administration. We did not perform genetic investigation (i.e., sequencing) on the patient in order to diagnose PFV. In addition, her relatives had no previous history of visual impairment.
At initial visit, the clinical findings of a slit-lamp examination revealed a shallow anterior chamber in both eyes. In her right eye and left eye, the diameter of the cornea was 8 mm and 9 mm and the axial length was 15 mm and 19 mm, respectively, and microphthalmus was observed in both eyes. In her right eye, the fundus was not visible due to a cataract, and ultrasonic B-mode examination revealed total retinal detachment (Fig. ). A magnetic resonance imaging scan of the patient’s head revealed no calcification in the right eye and no abnormalities in her brain. In the left eye, retrolental fibrovascular proliferation was found around the temporal side. The fundus exhibited FRD from the optic disc to the inferior-temporal side (Fig. ). Most of the peripapillary retinal vessels were involved in the retinal folds, and a part of the nasal retina covered-over the optic disc. In the periphery of the fundus, retinal avascular area was observed over the entire circumference, and pigmentation was also observed in a wide range on the temporal side. An oscillating nystagmus was observed in both eyes, and was found to be prominent in the left gaze and less conspicuous in the right gaze when her face was turned to the left.
During the clinical course, cataract and corneal opacification progressed, ultimately becoming phthisis bulbi in her right eye. On the other hand, from the age of 6 to 22 years, her left eye retained a corrected visual acuity of 0.08, and no significant change of the fundus was observed during that 16-year period (Fig. ). OCT images obtained when she was 22 years of age revealed bundle shading at the optic disc, combined with the finding that the nasal retina was overlaid on the optic disc (Fig. ). However, the layer structure of the surrounding retina was well preserved (Fig. ). On the temporal side of the optic disc, the elevated stalk of the fold protruding into the vitreous was observed at the site of the FRD, yet the upper and lower retinal layered structures were relatively well retained (Fig. ). However, on the temporal peripheral side, the retina was remarkable thinned, the layered structure was unclear, and the ellipsoid zone could not be clearly identified (Fig. ).
Goldman kinetic visual field examination findings, with an isopter of V− 4, obtained when the patient was 22 years of age exhibited 50-degrees upwards, 40-degrees to the nasal side, 60-degrees downward, 75-degrees to the temporal side, and 80-degrees to the inferior-temporal side (Fig. ). The patient is currently undergoing yearly follow-up observations (i.e., once per year). |
pmc-6114735-1 | Patient A was a 36-year-old woman of Mauritanian ethnicity who presented for an initial hospital-booking visit at 13 weeks’ gestation. She had no known medical conditions and a non-consanguineous partner of Nepalese descent. Her obstetric history included a 35-week morphologically normal stillbirth of unknown etiology. The pregnancy with which she presented had a low-risk result for the first-trimester aneuploidy antenatal screening in the nuchal translucency program. A fetal morphology scan attended at 19 weeks identified potential fetal anomalies, leading to a tertiary referral for review. A detailed sonogram at 21 weeks’ gestation confirmed left microphthalmia (Fig. ) and a small biparietal diameter (< fifth centile).
A range of investigations and management options were offered and consented to, including: genetic counseling, amniocentesis, single nucleotide polymorphisms (SNP) array testing, placental histopathological testing, preservation of cell line, and a full postmortem. A magnetic resonance imaging (MRI) examination was declined by the parents. Amniocentesis and chromosomal microarray showed a chromosomally normal male and genetic counseling was organized. The couple had significant concerns regarding the uncertain prognosis, leading to a decision for an elective termination. The fetal postmortem showed left-sided microphthalmia (Fig. ), with associated persistent hyperplastic primary vitreous, probable hypoplasia to the left side of the face, and a thin left optic nerve compared to the right. Placental histopathological results were normal. |
pmc-6114735-2 | Patient B was a 31-year-old Caucasian woman with a non-consanguineous Caucasian partner and a history of a term normal birth followed by a first trimester miscarriage. She had no significant medical or family history and stated no illicit substance use. She presented with an uncomplicated pregnancy with a low-risk screening result on nuchal translucency for aneuploidy. At the 20-week fetal anomaly morphology scan, an absent right globe was identified (Fig. ) with mild bilateral ventriculomegaly. Fetal MRI at 20 weeks further delineated the absent right globe, dysplastic ventricular system (Figs. and ), and confirmed diagnosis.
A screen for toxoplasmosis, rubella, cytomegalovirus, herpes simplex virus, listeria, parvovirus, and human immunodeficiency virus (HIV) (TORCH screen) completed at the time of diagnosis was negative. Our patient had no family history of fetal anomalies. Amniocentesis and microarray results showed no chromosomal anomalies in a male fetus. Our patient chose not to continue the pregnancy and a termination was performed without complication. An autopsy revealed right-sided anophthalmia with right optic nerve atrophy and mild bilateral ventriculomegaly. Placental histopathological results were normal. Genetic counseling and testing was organized. |
pmc-6114737-1 | A 72-year-old male with a past medical history of ESRD, chronic atrial fibrillation (AF) and rheumatic heart disease (RHD) status post mechanical mitral and aortic valve replacements presented to his primary care doctor complaining of left thigh erythema with skin induration. The patient had been on warfarin therapy for anticoagulation of his mechanical heart valves as well as prophylactically for underlying AF for greater than 20 years. He was initially diagnosed with cellulitis and treated accordingly with antibiotics. Despite multiple antibiotic regimens, the skin lesions did not improve and instead progressed into painful, necrotic ulcers. The lesions were evaluated by his nephrologist 2 months later who deemed cellulitis to be a misdiagnosis and recommended a biopsy of the skin lesions. The biopsy revealed pathology consistent with calciphylaxis, a lethal disease typically associated with ESRD.
The disease is known to be exacerbated by certain medications including warfarin, vitamin D analogs, calcium-based binders and glucocorticoids []. Other risk factors in ESRD patients include diabetes, hyperphosphatemia, obesity, hyperparathyroidism and hypercalcemia. The patient was on warfarin therapy and vitamin D analogs. He was also taking sevelamer, a non-calcium-containing phosphate binder, to prevent hyperphosphatemia.The vitamin D supplementation was discontinued but the cessation of warfarin was controversial.
Since warfarin contributes to the development of calciphylaxis, it should have been exchanged for another form of anticoagulation to avoid progression of the non-healing, necrotic ulcerations. It was not accomplishable in this circumstance since LMWH is not Food and Drug Administration (FDA) approved in ESRD and is associated with serious bleeding and the need for frequent dose adjustments and monitoring []. The only other option for long-term anticoagulation was UFH administered subcutaneously but this approach was not taken. It is difficult to maintain therapeutic levels with UFH as it requires massive doses to do so. Because it was believed that the risk of two mechanical valve thromboses outweighed the risk of the discontinuation of anticoagulation, the warfarin was continued. Unfortunately, the lesions progressed over 1 year and the patient suffered from the sequelae of calciphylaxis despite the addition of sodium thiosulfate infusions to each hemodialysis session. With the advancement of the ischemic ulcerations, the patient developed superinfections and debridement was not sufficient to control the sepsis. He eventually expired due to septic shock. |
pmc-6114742-1 | A 71-year-old man with previously known keratoconus presented with bilateral cataract (Fig. ). In the left eye, PKP had been performed when the patient was 25 years old because of keratoconus (Fig. ). No surgery had been done in the right eye. Because of discomfort with contact lenses, the patient wore glasses both for near and far distance. The patient had a medical history of a transient ischemic attack and medicated with acetylsalicylic acid. The right eye presented with advanced keratoconus including Vogt striae (Fig. ) in the cornea and moderate senile nuclear cataract but no other pathology. The left eye presented with a clear corneal graft and moderate senile nuclear cataract but no other pathology. First surgery was only planned in the left eye. After more than 1.5 years surgery was also performed in the right eye. Written informed consent was acquired from the patient.
Preoperatively, best corrected visual acuity (BCVA) was 20/40, with − 0.25 sph − 5.0 cyl 50°. The cornea exhibited regular astigmatism (K1 44.5 D, K2 48.5 D, astigmatism 3.9 D) (Fig. ) based on corneal tomography performed with Scheimpflug imaging (Pentacam, Oculus, Germany). The toric IOL AcrySof IQ Toric SN6AT8 (Alcon, USA), 22 D was implanted with target refraction − 2.26 D. The target refraction was chosen to match the more myopic right eye. Biometry was performed with the IOLMaster (Carl Zeiss Meditec, Germany) and Haigis formula was used. Preoperative marking of the toric IOL axis was performed with the patient in upright position to avoid misalignment due to cyclotorsion, using the RoboMarker (Surgilum, USA). Phacoemulsification and lens implantation were performed through a 2.2 mm limbal incision. One day postoperatively, BCVA was 20/40 with − 2.0 cyl 90°. Five weeks postoperatively BCVA was 20/30 with + 0.5 sph − 2.75 cyl 71°. Nine months postoperatively BCVA had improved to 20/25 with − 3.25 cyl 90° and the astigmatism was still regular (Fig. ) based on corneal tomography performed with Scheimpflug imaging. Two years postoperatively BCVA was still 20/25 with − 0.5 sph − 3.25 cyl 80°. The spherical equivalent 2 years postoperatively only differed − 0.135 D from the intended target refraction. During all postoperatively controls the toric IOL only misaligned 1° (from 139° to 140°) from the implanted axis and the corneal graft remained clear. The patient was very satisfied with the visual result from day one postoperatively.
Preoperatively, BCVA was 20/150, with − 5.75 sph − 9.75 cyl 72° and the cornea had irregular astigmatism (K1 53 D, K2 57.7 D, astigmatism 4.7 D) (Fig. ) based on corneal tomography performed with Scheimpflug imaging. In the right eye, the astigmatism was judged as being too irregular for toric IOL implantation and cataract surgery was performed with the spherical IOL Acrysof Multipiece MN60MA (Alcon, USA), 5 D. Conventional biometry (IOLMaster) and Haigis formula was used to calculate the power of the spherical IOL. Two months postoperatively, BCVA was 20/80 with + 1.25 sph − 3 cyl 65°, spherical equivalent − 0.25. Target refraction prior to surgery was − 2.33 D, however the patient was pleased with the obtained result. He continues to wear glasses for far distance but does not require glasses for near distance. |
pmc-6114781-1 | A 33-year-old previously healthy mother in her 2nd pregnancy, was admitted at 38 weeks of gestation with a one-day history of high fever with chills, myalgia, arthralgia, and headache. Her first pregnancy ended up as lower segment caesarian section (LSCS) due to the unfavorable cervix. On admission, she was febrile (102 °F). Her pulse rate (PR) and blood pressure (BP) were 88 beats per minute and 94/60 mmHg respectively. Rest of the cardiac and respiratory examination was unremarkable. Abdominal examination revealed a soft abdomen with a single live fetus and symphysiofundal height was compatible with gestational age. Vaginal examination revealed an unfavorable cervix. Laboratory investigation results were as follows: total white cell count (WBC) 7100/mm3, platelet count (PLT) 112,000/mm3, haemoglobin (Hb) 11.5 g/dl, packed cell volume (PCV) 30%, C reactive protein (CRP) 31 mg/l and positive NS 1 antigen. Liver function and renal function tests were normal. Cardiotocograph (CTG) was normal and the fetal biophysical profile was compatible with the period of gestation (POG). There was no ultrasound evidence of free fluid in the abdomen or pelvis. The diagnosis was made of uncomplicated dengue and managed according to current national dengue management guidelines.
On the 2nd day, she developed two episodes of vomiting and had mild intermittent abdominal pain. Her PR was 98 beats per minute and blood pressure was 90/64 mmHg. There was mild right hypochondriac tenderness. Complete blood count (CBC) showed WBC 6900/mm3, PLT 72000mm3 and PCV 32%. Ultrasonically, there was no free in abdomen or chest. A multidisciplinary meeting was convened and a decision made to deliver her baby by urgent LSCS. Blood, fresh frozen plasma, and platelets were preserved and LSCS was performed under spinal anaesthesia. A healthy male baby weighing 3.0 kg was delivered with an uneventful intraoperative period. Although there was no significant bleeding as a prophylactic measure B lynch sutures were applied and an abdominal drain was also inserted. She was then transferred to intensive care unit (ICU) for further management.
On the 3rd day, fever was persisting and she continued to complain of right hypochondriac pain. She became tachycardic with PR of 105 beats per minute. BP was 92/66 mmHg. CBC revealed WBC of 5300/mm3 with PLT of 63,000/mm3 and PCV of 35%. Ultrasound (USS) examination showed pericholecystic oedema with a thin layer of free fluid in the hepatorenal pouch. The diagnosis of dengue hemorrhagic fever was made and observations conducted according to the observation chart for management of dengue in adult patients with fluid leakage. A 3 hourly PCV monitoring, hourly capillary refill time (CRFT), PR, supine BP and urine output was conducted. CBCs were performed twice daily with daily alanine transaminase (ALT) and aspartate transaminase (AST). Serum albumin was found to be low and 2D ECHO was normal. To cover unexpected nosocomial infections, IV of 4.5 g Piperazillin tazobactam, 8 hourly, was started. The summary of investigations is shown below (Table ).
During the first 12 h of the critical phase (CP), vital parameters were stable and a flat rate of fluid administration was continued. Towards the peak of the leaking phase, her PR started to rise with a narrowing of pulse pressure. As there was a sudden drop in PCV, possible intra abdominal bleeding was suspected and 500 ml of packed cells was transfused. Although the abdominal draining was absent, USS confirmed the high possibility of the presence of blood in the peritoneal cavity. Haemodynamic parameters were improved following transfusion. At the same time, intravenous (IV) tranexamic acid 1 g was also given. Although there was a further drop in platelets, clotting studies were well within the normal range. At the beginning of the second half of the critical phase, she had developed pedal edema, mild ascites with right-sided mild pleural effusion without respiratory compromise. Around the 36th hour of CP, urine output dropped to less than 0.5 ml/kg/hour. Due to the high possibility of fluid overload, IV dextran 350 ml was given. Thereafter she had an uneventful recovery from rest of CP. She was then transferred to the high dependency unit and later to the postnatal ward, for further care. During the recovery phase, she became fever free and went into polyuric phase. Her CBC showed WBC 10000/mm3, PLT 238000/mm3 and Hb 9.8 g/dl. IV antibiotics were stopped after completion of the one week course following the negative urine and blood culture reports. Throughout the illness, her clotting studies and renal functions were normal. Later, she was discharged and underwent an uneventful recovery.
During her ICU stay, the baby was kept in the special baby unit (SBU) for the continuation of feeding and observation. He was never taken out of SBU and had no history of mosquito bites. The neonate was well until the 5th day of life but suddenly developed a high fever with jaundice. Sepsis or congenital dengue infection was suspected. Laboratory investigation results were as follows: WBC 5800/mm3, Hb 13.8 g/dl, PLT 126000/mm3, positive dengue NS 1 Antigen, AST 87 U/L, ALT 23 U/L, CRP 5.8 mg/l with normal liver and renal functions with the exception of an elevated indirect bilirubin of 35 micro mol/L. Diagnosis of dengue fever was made and managed according to current guidelines. Later, on the 7th day of life, his PLT count dropped from 86,000/mm3 to 43,000/mm3 and he developed malena. However, bedside USS revealed no evidence of fluid leakage or intracranial bleed. Haemodynamic parameters were within normal ranges except tachycardia of 170 bpm during the period of malena. 30 ml of PLT and 45 ml of packed red cell transfusion were done. With close monitoring and judicious fluid balance, the baby improved and was discharged from the SBU with PLT of 146,000/mm3 and Hb of 12 g/dl on the 11th day of life. However, his body weight had dropped to 2.580 kg upon discharge. On the 25th day of life, clinic review revealed weight gain up to 2.780 kg with age-appropriate milestone levels. |
pmc-6114782-1 | A 59-year-old Italian male, weighting 69 kg and 173 cm tall, came to our attention for an ulcerative lesion of the left lower lip (Fig. , Panel A). He had already received antibiotic treatment with amoxicillin/clavulanate plus antiviral acyclovir for 10 days in other outpatient facilities without any clinical improvement. His clinical history was remarkable for hepatitis B (HBV) and Genotype 3 hepatitis C (HCV) co-infection, which led to OLT due to HCC, and several years spent in foreign countries. In fact, when he was in his late 40 he had spent 6 years in Nigeria and one and a half year in the South of China where he worked at sea as a kitchen supervisor. The patient was HIV negative. Six months before the OLT he had received treatment with daclatasvir (60 mg/die), sofosbuvir (400 mg/die) and ribavirin (1000 mg/die) for HCV, successfully reaching sustained virological response (SVR) 12 weeks after the end of treatment. A QuantiFERON®-TB Gold In-Tube (QFT-G) was performed among the pre-transplant screening and resulted positive.
Neither before nor after OLT, latent TB infection (LTBI) therapy was administered.
Patient received OLT and 14 months post-transplant presented with a lower lip lesion. At the time of presentation patient was on the following medications: entecavir1000 mg daily for chronic HBV with lamivudine resistance, tacrolimus 3 mg daily and everolimus 1 mg twice a day for immunosuppression.
A punch biopsy of the lower lip lesion was performed and submitted for extended microbiology and histological examination.
The histological examination suggested chronic granulomatous inflammation (Fig. , Panel B).
Real time PCR (Xpert MTB/Rif™– Cepheid Sunnyvale, CA United States) was positive for MTB by high grading, implying a high bacterial load in the analysed specimen. No rpo-B mutation, affecting rifampicin resistance, was detected. Conventional microbiological investigations were also carried out: smear microscopy and automated liquid cultures (Bactec MGIT960™– Becton and Dickinson Franklin Lakes, NJ) were positive and the subsequent susceptibility testing showed sensitivity to all first-line drugs tested. A total body CT scan was performed to rule out presence of granuloma or signs of pulmonary or other extra-pulmonary site involvement. Moreover, Xpert MTB/Rif™–, Ziehl Neelsen and MTB colture on sputum resulted negative.
A treatment with rifabutin (450 mg/daily), isoniazid (300 mg/daily), ethambutol (1200 mg/daily), pyrazinamide (1500 mg/daily) and daily supplementation of B6 vitamin was started for the intensive phase of 2 months. The therapeutic regimen was then simplified to rifabutin (300 mg/daily) plus isoniazid (300 mg/daily) for the following 4 months.
Liver function and level of immune-suppressive treatment were monitored weekly. No increase in transaminases was observed and only a slight decrease in both tacrolimus (from5 μg/L to 3; normal value 5–7 μg/L) and everolimus (from 3 μg/L to 1.9 μg/L; normal value 2.5–3 μg/L) was noticed after 1 month of treatment; therefore, to achieve satisfactory blood-level concentrations, tacrolimus dosage was increased to 6 mg/ daily and everolimus was progressively titrated to 2.75 mg/ daily in two doses. After 3 weeks of therapy, a dramatic clinical improvement was observed and after 6 months of treatment the lesion was cured (Fig. , Panel D). |
pmc-6114836-1 | A 32-year-old man presented with the symptoms of foreign body sensation and blurred vision in the left eye 3 days before presentation. The best-corrected visual acuity (BCVA, in decimal values) was 1.2 in the right eye and 0.6 in the left eye. Slit-lamp biomicroscopy (BX-900, Haag-Streit AG, Koeniz, Switzerland) of the left eye revealed an intracorneal foreign body, localized at the paracentral region, obliquely protruding to Descemet membrane with no penetration into the anterior chamber (Fig. ). The original entry path of the foreign body had sealed and epithelialized, leaving a sub-epithelial opacity and edematous stroma (Fig. ). The shadow effect shown in the anterior segment optical coherence tomography (AS-OCT, RTVue XR, Optovue, Inc., Fremont, CA) corresponded to the location of the intracorneal chestnut (Fig. ). The corneal thickness was approximate 755 μm at the site of lesion, of which 152 μm distance from the sealed corneal epithelium to the chestnut (Fig. ). The white ulcers with feathery edges or satellite infiltrates were not observed. The intraocular pressure, anterior chamber, lenses and the fundi appeared normal. No signs of systemic disorders were found in the presented case.
This study conformed to the principles of the Declaration of Helsinki and was approved by the Institutional Ethics Committee of Guangdong General Hospital and Guangdong Academy of Medical Sciences. After discussing with the patient and informed consent was obtained, femtosecond laser was applied using the protocols of IntraLase Enabled Keratoplasty (IEK, iFS™ Advanced Femtosecond Laser System). Following parameters were used: 300 μm lamellar depth, 7.5 mm diameter, 1.20 μJ energy, and cut angle with 180 degrees from 12 o’clock to 6 o’clock in the left eye (Fig. ). Under strict aseptic precautions, IEK was performed to create an anterior lamellar flap according to the routine procedures. The lamellar flap was easily separated with a flap lifter to expose the superior side of the chestnut. As shown in Fig. , the chestnut was then removed entirely with a pair of forceps under a surgical microscope (OPMI LUMERA 700, Carl Zeiss Meditec, Jena, Germany). After removal of the chestnut, no fluorescein leakage was found with the Seidel test and the wound was washed with 250 mL normal saline containing 40 mg gentamycin. The edges were dried for 3 min using a surgical sponge, and a soft contact lens (Extended wear, PureVision. Bausch and Lomb, NY) was applied over the surface. No suture was applied. The chestnut, shown in Fig. , was inoculated onto Sabouraud glucose agar and chocolate agar to detect potential growth of fungi and bacteria.
Before the surgery, Levofloxacin (Santen Pharmaceutical Co., Ltd. Japan) was prescribed for four times per day, and postoperatively, TobraDex (tobramycin 0.3% and dexamethasone 0.1%, s.a. Alcon-Couvreur n.v. Puurs, Belgium) was included and tapered weekly over a month. In 3 days after surgery, the patient complained of mild pain and blurred vision. These symptoms were relieved after treatment with the eyedrops. At three-month follow-up, a dot-like haze was noted in the cornea, which was corresponded to the scarring formation at the site of foreign body removal (Fig. ). As shown in Fig. , assessment with corneal topography (Oculus Pentacam Typ 70,700, Topcon, Tokyo, Japan) demonstrated that there was no surgical induction of corneal astigmatism compared to the preoperative astigmatism (Pre-Op, K1 = 42.1D, K2 = 42.9D, Axis: 166.7o vs 3-month Post-Op, K1 = 41.4D, K2 = 42.7D, Axis: 160.6o), and the Post-Op decimal BCVA in the left eye was improved gradually from 0.3 to 1.2. The results in microbiological culture of fungi and bacteria were negative. |
pmc-6114853-1 | Our patient was a 27-year-old Australian woman with grade IV OA confirmed by X-ray images of her pelvis; ultrasound scans showed right knee joint effusion, enthesitis, and synovitis; a CT scan of her spine indicated annulus bulges at L3/4 and L4/5, and bilateral grade 2 sacroiliitis changes; a background of AS (human leukocyte antigen-B27 negative) confirmed by MRI imaging; chronic pain syndrome with pain amplification; and post-traumatic stress disorder. Her body mass index (BMI) was 39.4 kg/m2. She did not have any: infection with hepatitis B, hepatitis C, or human immunodeficiency virus (HIV); malignancy; previous history of allergic reaction to any component of our therapeutic measure; active cardiac, respiratory, neurologic or endocrine disease necessitating receipt of medication. She was not pregnant or in lactating condition. A written and informed consent was obtained from our patient. Arthritic symptoms were measured using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Hip Disability and Osteoarthritis Outcome Score (HOOS) by scoring for pain intensity, walking ability (distance), joint stiffness, physical function, sports and recreation, and quality of life. Changes to her AS symptoms were measured using the Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire. For liposuction and stem cell treatment, she was admitted to Macquarie Stem Cells. Under light sedation and using aseptic technique, 450 ml of fat was harvested from her abdomen. Cell isolation was performed in PC II safety cabinet. Cells were isolated using collagenase digestion using Liberase GMP grade (enzyme blend).
Our patient’s preoperative HOOS score (baseline score) for both hips was 122 (range 0–168), WOMAC for her right knee was 70 (range 0–90), and the baseline ASQoL questionnaire was 18 (range 0–18). We obtained 2.058 billion nucleated cells with a viability of 89.10% using Muse® Cell Analyzer. A total of 738 million cells were injected on the day: 100 million cells injected into each hip and right knee intra-articular under ultrasound guidance, and 438 million cells were administered as an intravenous infusion. The remaining 1.320 billion cells were cryogenically frozen into four separate vials of 330 million cells following the protocols of Thirumala et al. []. Follow-up intravenous infusions of 330 million cells were provided at 3 months, 12 months, and 36 months. Our patient’s follow-up intervals were performed at 1 day, 3 months, 6 months, 12 months, 24 months, and 36 months respectively. Neither local nor systemic adverse events were observed during the follow-up and she was satisfied with the therapy after 3 months with an increasing trend over the period. At 3-month post-treatment, she exhibited increased mobility. Her HOOS and WOMAC scores decreased to 82 and 37, respectively from her baseline scores. She also noted that pain in her spine, hips, and right knee associated with OA and AS had decreased. Interestingly, in addition to her decreased pain and increased mobility, she was feeling more energetic. Within 6 months after the first SVF infusion, her HOOS and WOMAC questionnaire scores had decreased to 79 and 31, respectively. She showed dramatic improvements over 2 years after her first SVF infusion and presented with decreased dependency on a wheelchair or walking stick (HOOS and WOMAC scores not available). Her dependency on pain relief and anti-depressant medications was found to be decreased as is evident from Table . At the 36-month follow-up, she presented significant improvements overall. She remained free from NSAIDs and her pain levels were minimal. Follow-up HOOS and WOMAC scores had decreased to 32 and 20, respectively. Her pre-treatment to post-treatment ASQoL score had decreased to 3 signifying increased quality of life. She still presents some symptoms of depression; however, her anxiety appears to have resolved almost completely. Her progressive improvement is observed over 3 years with WOMAC, HOOS, and ASQoL (Fig. ). |
pmc-6114880-1 | A 67-year-old woman, in good health other than systemic hypertension, lost consciousness soon after complaining of severe epigastric pain at her workplace. The ambulance crew found the patient in cardiopulmonary arrest and paramedics immediately started CPR by manual chest compressions; return of spontaneous circulation and recovery of consciousness occurred 4 min later. On arrival at the emergency room, the patient’s level of consciousness was 14 on the Glasgow Coma Scale, blood pressure was 102/74 mmHg, and pulse rate was 103/min. No cardiac murmur was detected, but vesicular breath sounds were moderately diminished in the left lung field. Cardiac enzyme studies were not consistent with a diagnosis of myocardial infarction. An ECG showed a normal sinus rhythm, and no arrhythmias or signs of myocardial ischemia were observed. A chest X-ray revealed massive left pleural effusion with no right pleural effusion, while cardiomegaly and pneumothorax were not identified. Transthoracic echocardiography demonstrated normally functioning ventricles and valves, and mild pericardial effusion. Computed tomography (CT) showed a type A acute aortic dissection (AAD) with thrombotic occlusion of the false lumen and an ulcer-like projection in the proximal arch, along with mild pericardial effusion and massive left pleural effusion (Fig. ). Occlusion of the branch vessels of the aortic arch and pulmonary emboli were not detected. Immediately after the CT, the patient fell into circulatory collapse. After drainage of bloody effusion from the left pleural space, an emergency operation was begun through a median sternotomy. No sternal fracture and bleeding in the mediastinum were found. When the pericardium was opened, a small amount of bloody effusion was present, but cardiac injury was not observed. In addition, a large laceration (10 cm) was found in the left posterolateral pericardium at the phrenico-pleural junction, through which the pericardial cavity communicated to the left pleural space (Fig. ). Neither injuries of other intra-thoracic organs such as the lung, vessels, or chest wall causing the hemothorax nor external rupture of the dissection were detected. Under cardiopulmonary bypass and cardiac arrest, the aorta was opened. The dissection with the thrombosed false lumen extended from the aortic root to the aortic arch. A primary tear was present on the lesser curvature of the proximal arch. Hemiarch replacement including the primary tear was performed without difficulty, but a large amount of inotropic agents was necessary for weaning off cardiopulmonary bypass. The postoperative course was complicated with severe low cardiac output syndrome, and the patient eventually died of multi-organ failure on postoperative day 30. An autopsy was not permitted. |
pmc-6114890-1 | A 53 year old Pakistani lady presented to the Medicine clinic of a local hospital in 2004 with a history of heel pain and lower back pain for 5 months. In this period, the patient had sustained a rib fracture and left humeral fracture. There was no history of diabetes, hypertension or any other chronic disease. She had not been on any form of medication, including steroids and traditional drugs widely available and prescribed in the region, prior to the onset of pain. At the time of the fractures, she had been placed on non steroidal anti inflammatory agents, acetaminophen and tramadol. There was no history of illicit drug use and she was a non smoker. Family history was unremarkable, particularly in the context of bone disease, and malignancy.
Initial laboratory investigations had shown a mildly elevated total calcium level of 10.8 mg/dL {2.7 mmol/L}-(no albumin level result available from that time for correction). Parathormone levels (PTH) had not been determined. There was no vitamin d or renal function report available from that time. X-Ray pelvis revealed lytic lesions in the right iliac bone (Fig. ). A magnetic resonance imaging (MRI) of the lumbosacral spine showed some signal changes. The differentials based on the MRI were metastatic bone disease or multiple myeloma.
Serum protein electrophoresis was normal. The patient then got lost to follow-up. Her work up was resumed 4 years later when her bone pains had started flaring up. Bone marrow examinations done back in 2007, and later in 2009, were negative for multiple myeloma. A bone scan in November 2009 showed generalized increased tracer uptake over the skull and both the axial and appendicular skeletons- findings in favor of metabolic bone disease (Fig. a). An initial planar parathyroid sestamibi scan requested by a general practitioner in November 2009 was negative for any functioning parathyroid adenoma in the neck or superior mediastinum. No serum PTH report was available from this time either. Following this workup, the patient was treated empirically for bone pains with calcium supplements, an empiric vitamin d injection, and intravenous zoledronic acid 5 mg (without prior bone mineral density assessment via DXA scan). This empiric treatment was instituted by an orthopedic surgeon whom she had been referred to. The patient experienced only a slight improvement in bone pains with this treatment and also developed nausea, vomiting and anorexia. Subsequently, she sought care at the National Institute of Diabetes and Endocrinology, Dow University Health Sciences, Karachi, Pakistan.
At presentation, the patient was well oriented and of functional class 3 (wheel chair bound, able to walk only with support). Her blood pressure was 110/70 mmHg. Neck examination revealed no mass or lymphadenopathy. She had a significant proximal myopathy as well as curved thighs. She had shortened fingers, and spinal scoliosis was evident. Severe generalized bone tenderness was elicited. There was no focal deficit. Laboratory investigations at this time showed a calcium level of 15.1 mg/dL{3.775 mmol/L}, (corrected for albumin of 3.6 mg/dL{36 g/L}); Vitamin D3 level of 33.92 ng/mL{84.664 nmol/L}; phosphorus 2.3 mg/dL {0.743 mmol/L}and alkaline phosphatase of 1298 IU/L {21.633 µkat/L}. Her 24 h urine calcium was 155 mg/day {3.875 mmol/day}, with urine calcium to creatinine ratio of 0.02. Her creatinine level was 1.3 mg/dL {114.92 µmol/L}(Table ). The estimated glomerular filtration rate (calculated through Cockcroft-Gault equation) was 50 mL/min {0.835 mL/second).
Following these tests, the patient’s PTH level was ordered and determined to be 2105 pg/mL {2105 ng/L} [Table ]. Ultrasonography of the neck showed a solid hypo echoic, well-circumscribed mass lesion, measuring 1.8 × 1.2 cm at the lower pole of the right lobe of thyroid. There were no calcifications or lymphadenopathy. Appearances were suggestive of parathyroid adenoma. Both lobes of the thyroid appeared normal. A repeat planar sestamibi scan, (requested from a different institute in the city), revealed areas of tracer retention over upper and lower poles of the right lobe of thyroid. The intensity of retained tracer was more over the right inferior parathyroid gland. The findings were highly suggestive of hyperparathyroidism (Fig. ).
A bone mineral density scan showed a T score of − 2.9 in the spine, − 3.8 in the hip and − 4.5 in the distal forearm, consistent with severe osteoporosis. The Z scores at the spine, hip and distal forearm were − 2.0, − 3.1 and − 3.6, respectively (Table ).
Ultrasonography of the kidneys revealed a single renal stone (0.6 cm) and no neprocalcinosis.
Based on the biochemistry results of hypercalcemia, associated with elevated PTH levels, a diagnosis of primary hyperparathyroidism was made. Subsequent sestamibi scan and neck imaging facilitated us to localize the abnormal parathyroid gland. The DXA scan was useful for evaluation of the bone mineral density. In view of the phenomenally high levels of parathyroid hormone, (more than 10 times upper limit of normal), the pre-operative suspicion of parathyroid cancer was high [, ]. The patient was rehydrated with intravenous fluids. Subcutaneous calcitonin injections at a dose of 4 units/kg every 12 h were administered to tide her over until the surgery. Once her calcium levels had come down to 10.5 mg/dL {2.625 nmol/L}L, she was operated upon. At surgery, right hemithyroidectomy and inferior parathyroidectomy with level six lymph node resection was done. The lymphadenectomy was performed as there was evidence of enlarged lymph nodes at neck exploration. The size of the lesion was measured as 2.5 × 1.5 × 1 cm. Histopathology showed features consistent with parathyroid cancer (Fig. a–d). Capsular invasion and focal vascular invasion were noted. However, margins of excision were tumor free. The excised lymph nodes did not show evidence of tumour infiltration. The patient was not given external radiation therapy postoperatively. Literature review revealed that post operative adjuvant radiation therapy may only have a role in the management of patients with a histologically positive margin following en bloc resection, or in those with lymph node metastases [, , ].
Postoperative PTH level, performed on the second day of surgery, was 59 pg/mL {59 ng/L} (16–87). On the third postoperative day, the patient’s serum corrected calcium declined to 6 mg/dL {1.5 mmol/L}. This was associated with paresthesias around her mouth and carpo-pedal spasm. There were no seizures, although there was some confusion in terms of time and place. Intravenous calcium (2 g calcium gluconate, equivalent to 180 mg elemental calcium, in 50 mL 5% dextrose water) was infused over 20 min. Re-monitoring of calcium levels revealed persistent hypocalcemia. A slow infusion of calcium was initiated at an initial rate of 50 mL/h. This was prepared by adding 100 mL of 10% calcium gluconate (equivalent to 900 mg elemental calcium) to 1000 mL 5% dextrose water. The infusion rate was adjusted, with a goal to maintain calcium levels at lower end of normal range. On the fifth post-operative day, the calcium level had risen to 9.0 mg/dL {2.25 nmol/L}. Neurologic examination was normal and she was tolerating oral diet. Oral calcium supplementation was initiated (Qalsan D four times daily-equivalent to 2 g elemental calcium per day). She was discharged on oral calcium and vitamin D supplementation with active vitamin D, (calcitriol) 0.25 µg twice daily, in a stable condition.
At follow-up, her appetite and mobility had improved significantly, although she continued to experience bone pains. Corrected calcium was 9.5 mg/dL {2.375 nmol/L}. A repeat skeletal scintigraphy done 3 months after parathyroidectomy did not demonstrate a significant change in the lytic lesions (Fig. a, b). A repeat DXA scan 2 years down the line revealed a significant improvement in bone mineral density at all sites, though more so at the spine and hip, than at the forearm (Table ). Thereafter, we followed her clinically, as she was not keen to have further radiologic testing done. We have been monitoring her calcium and PTH levels on an annual basis. They have remained within their normal range till date (2018). She is now functional class 2, (no longer wheel chair bound), and on regular calcium and vitamin D supplements (patient perspective, attached as Additional file ). |
pmc-6115318-1 | A 71-year-old man was admitted to our hospital because of the detection of an esophagogastric (EG) junction tumor on regular upper endoscopy screening. He had no symptoms, such as dysphagia, epigastric fullness, and gastroesophageal reflux. His medical history included hepatolithiasis, and he had undergone hepatic left lateral segmentectomy at 50 years of age. Physical examination showed no remarkable findings, and laboratory examinations, including assessment of serum tumor markers, such as carcinoembryonic antigen and carbohydrate antigen 19-9, were normal. Endoscopy revealed a sliding hiatal hernia and an approximately 10 mm elevated mass at the EG junction (Fig. ). Endoscopic ultrasonography showed a mass having mixed echogenicity in the esophageal wall, with partial invasion of the submucosal layer (Fig. ). Upper gastrointestinal imaging showed an elevated lesion at the EG junction (Fig. ). A biopsy specimen was obtained, and the pathological diagnosis on analysis of the specimen was a differentiated tubular adenocarcinoma. Computed tomography did not indicate lymph node metastasis or distant metastasis. The clinical diagnosis was esophageal cancer (cT1bN0M0 cStage I according to the eighth edition of the Union for International Cancer Control classification) []. Proximal gastrectomy with D1 lymph node dissection was performed along with jejunal interposition.
Macroscopically, the surgical specimen showed an elevated mass (10 × 8 mm) in the EG junction (Fig. ). Microscopic examination revealed a carcinoma associated with BE. The carcinoma, Barrett’s epithelium, and stratified squamous epithelium are indicated in Fig. . Hematoxylin-eosin staining showed that the tumor was composed of small-to-intermediate cells with scant cytoplasm and irregular hyperchromatic nuclei and was growing with nuclear palisading and tubular structures. A well-differentiated adenocarcinoma component was present independently. The neoplasm arose in Barrett’s epithelium (Fig. and ). Infiltration of the submucosal layer to a depth of < 200 μm was noted. Lymphovascular invasion was not identified. The margins of the specimen were free of tumor cells. On immunohistochemical staining, the tumor was positive for chromogranin A and synaptophysin (Fig. and ). Ki-67 was positive in 40% of the tumor cells. Thus, the histological diagnosis was an NEC with a well-differentiated adenocarcinoma component arising in BE. No metastasis in the lymph nodes was noted on histological examination. The pathological diagnosis was esophageal cancer (pT1bN0M0 pStage I). The resection margins were free of tumor cells (R0 resection). The patient’s postoperative course was good, and he was discharged on the twentieth postoperative day. He has remained free of the disease at 36 months postoperatively. |
pmc-6115321-1 | A 63-year-old woman with decompensated liver cirrhosis secondary to hepatitis B virus (HBV) infection was referred as a candidate for LDLT. She had been diagnosed with hepatitis B 20 years before, but it had not been actively treated. She had received best supportive care, but she and her family chose to proceed with LDLT. Laboratory findings before LDLT were as follows: serum total bilirubin, 8.4 mg/dL; serum albumin, 2.5 g/dL; prothrombin time, 40%; platelet count, 84,000/μL; and Model for End-stage Liver Disease score, 17. A large amount of ascites, liver atrophy, and collaterals were observed on computed tomography scan. At the time of admission, her urine volume was decreased to 50 mL/day, and continuous hemodiafiltration treatment was started for renal failure. The predictive risk score [] was 0.80, which was lower than the score of 1.3 which predicts a poor prognosis, and the risk of postoperative mortality was therefore expected to be high. After obtaining full informed consent from both the donor and the recipient and approval from the Liver Transplantation Committee of Kyushu University, the patient was prepared for LDLT using a right posterior section graft.
The donor was the patient’s husband, who was 63 years old and had an identical blood type B. The surgical techniques were carried out as described previously []. The graft weight was 581 g, which was equivalent to 56.8% of the recipient’s standard liver volume (graft–recipient weight ratio, 1.12%). The hepatic arterial flow in the RHA was 87 mL/min, and the portal venous flow was 510 mL/min after reperfusion. The portal system pressure was 18 mmHg at the end of surgery, and splenectomy was not performed. The anhepatic time, and cold and warm ischemic times were 158 min, 92 min, and 49 min, respectively. The surgical time was 10 h, and the estimated blood loss was 4440 g. Ten units of red blood cells, 16 units of frozen plasma, and 40 units of platelets were transfused during surgery.
The post-transplant course is shown in Fig. . The patient received post-transplant immunosuppression with tacrolimus, steroid tapering, and mycophenolate mofetil. On postoperative day (POD) 7, the patient developed SFSS with serum total bilirubin 20.0 mg/dL and abdominal ascites 2000 mL/day [], indicating prolonged cholestasis and intractable ascites []. Tests for HBV DNA and cytomegalovirus (CMV) were negative, and repeated blood cultures were also negative until POD 24. There were no signs of abnormal hepatic flow or surgical complications detected by daily Doppler echo until POD 14 and by routine computed tomography scan on POD 7. There was also no notable elevation of hepatobiliary enzymes, thus ruling out the possibility of graft rejection.
The patient developed a fever above 39 °C on POD 9, and laboratory findings showed a white blood cell (WBC) count of 1120/μL and a platelet count of 40,000/μL, which fell to 300/μL (neutrophils, 30/μL) and 25,000/μL, respectively, on POD 11. She was treated with a combination of G-CSF and intravenous immunoglobulin, but her leukocytopenia/neutropenia failed to improve. Bone marrow aspiration was performed on POD 12, and histology revealed many macrophages and phagocytosis of hematopoietic cells (Fig. ). The patient was therefore diagnosed with HPS following LDLT. Steroid pulse therapy with 1000 mg/day methylprednisolone was initiated on the same day and continued for 3 days. Her WBC count increased to 4290/μL on POD 15, suggesting an improvement in her peripheral blood leukocytes. However, the patient developed sepsis with a fever above 39 °C on POD 24, and blood cultures were positive for Enterococcus faecium and Escherichia coli infections. She recovered rapidly with empiric antibiotic therapy including carbapenem and vancomycin, but her graft dysfunction was prolonged with a consistent serum bilirubin value of around 30 mg/dL, and her renal failure never improved. She also had several episodes of bacterial pneumonia. Splenic artery embolism was performed on POD 84 but failed to improve her graft dysfunction. Regarding immunosuppressive treatment to control infections, mycophenolate mofetil was stopped on POD 8 and not restarted, and the minimum dose of tacrolimus was administered to maintain a trough blood concentration of 3–5 ng/mL. The patient underwent a tracheotomy, and her liver function was expected to improve with long-term management; however, she developed bacterial sepsis and died of liver failure on POD 146.
HPS, also referred to as hemophagocytic lymphohistiocytosis, is a rare and often fatal disease despite treatment [], characterized by a variety of symptoms including fever, lymphadenopathy, hepatosplenomegaly, jaundice, and skin rash []. We report a rare case of a 63-year-old woman who developed HPS 2 weeks after LDLT with a right posterior section graft, who was treated with steroid pulse therapy following an early diagnosis via biopsy. This case may help to shed light on the relationship between HPS and graft dysfunction, including prolonged SFSS.
HPS is defined as a proliferation of phagocytic macrophages in the bone marrow, spleen, or lymph nodes, with clinical findings including fever for ≥ 7 days with peaks ≥ 38.5 °C, cytopenia (at least two of three lineages), and splenomegaly []. However, this definition is based on infant HPS and may be difficult to apply in adults and patients with various basic diseases such as liver cirrhosis or after LDLT. It is therefore necessary to perform bone marrow aspiration immediately to reach an early diagnosis of HPS in these patients []. The laboratory findings in the current patient showed WBC counts of 1120/μL on POD 9 and 300/μL on POD 11. Apart from HPS, other differential diagnoses such as medicine-induced disease, infections such as sepsis, hypersplenism, leukemia, and lack of vitamin B12 were unlikely and bone marrow aspiration on POD 12 showed typical HPS characteristics of phagocytic hematopoietic cells. This rapid diagnosis allowed early treatment with steroid pulse therapy, which contributed to an improvement in the patient’s peripheral blood leukocytes.
HPS is a rare complication after liver transplantation with a prognosis for patient survival of 50% [, ]. Fifteen patients, including the present case, have been reported to date (Table ) [, , –], only four of whom survived. About a third of secondary HPS cases are associated with virus infection, half with lymphoma, and the remainder with bacterial and fungal infections. Given that HBV DNA and CMV tests on POD 7 were negative and blood cultures were also negative until POD 24, it was considered highly unlikely that the secondary HPS in the current patient was associated with a viral or bacterial infection. The combination of anemia and thrombopenia also added the possibly of thrombotic microangiopathy as a differential diagnosis, but no typical hemolytic anemia was detected in the bone marrow biopsy and there was no sign of encephalopathy. Thrombotic microangiopathy was thus discounted as a possible cause of HPS, and leukopenia was therefore considered the most likely cause. However, liver biopsy after LDLT and measurement of ADAMTS-13 were not performed in the present patient.
In general, patients may develop secondary HPS via hypercytokinemia [] due to systemic inflammatory response syndrome associated with a viral or bacterial infection. The current LDLT recipient had SFSS, which might have been associated with the donor’s older age (63 years) []. SFSS can also induce oxidative stress and hypercytokinemia [].
Based on this hypercytokinemia theory, 10 of the past 15 cases (66.7%) were treated with steroids, 10 (66.7%) with intravenous immunoglobulin, and four (26.7%) with plasma exchange. The present patient started combination therapy with intravenous immunoglobulin, G-CSF, calcineurin inhibitor conversion, and steroid pulse therapy on POD 12, with subsequent improvement in her peripheral blood leukemia. However, her course was complicated by bacterial sepsis on POD 24. The causal relationship between steroid pulse therapy and sepsis could not be clarified, but the possibility of a septic attack is always present.
In addition, the relationship between SFSS and HPS was not unknown in the present case, and the possible causative effect of SPSS remains speculative. To reduce the risk of HPS, it is necessary to avoid developing viral and bacterial infections and hypercytokinemia, which induce secondary HPS, while the use of elderly donors might also increase the risk of SFSS. However, it may not be possible to avoid these factors in the setting of LDLT. Further studies on the mechanism of hypercytokinemia-induced HPS and more basic studies are needed to confirm the optimal treatment for HPS. |
pmc-6115322-1 | A 54-year-old man with a history of diabetes mellitus and hypertension was admitted to a regional hospital because of high fever and right hypochondriac pain. Hepatitis B virus surface antigen and hepatitis C virus antibody were both found to be negative, but he showed evidence of an excessive inflammatory reaction. A diagnosis of liver abscess was carried out that was managed by immediately performing a percutaneous puncture with drainage. Laboratory evaluation (Table ) found poor liver function and very high levels of alpha-fetoprotein (AFP, 45,928 ng/ml; normal, ≤ 20 ng/ml), protein induced by vitamin K absence or antagonist-II (PIVKA-II, 125,350 mAU/ml; normal, ≤ 40 mAU/ml), and AFP-L3 (38.3%, normal, ≤ 10%). The patient was diagnosed with HCC and with the triple-positive tumor marker status indicating highly malignant disease [, ]. The patient was also found to have a portal vein tumor thrombosis in the right posterior branch of the portal vein (Fig. ). Although a right hepatectomy was indicated for curative resection, residual liver function of the remnant volume was estimated to be insufficient [, ].
The patient was initially treated with chemoembolization (Table ) using a HAIC of cisplatin (50 mg/100 ml/10 min) and 5-FU (1000 mg/100 ml/10 min), followed by cisplatin (50 mg) suspended in lipiodol (5 ml) and starch microspheres (300 mg) containing mitomycin C (4 mg) [, ]. After the first round of chemoembolization, examination showed incomplete lipiodol accumulation within the tumor. Additionally, as the PVTT progressed to the right main portal vein, surgical PVL was performed to avoid involvement of the left portal vein. Three disseminated peritoneally nodules were also removed. Three additional rounds of transient chemoembolization were performed after the initial surgical procedure.
At the time of the fourth chemoembolization, the tumors responded to the treatment and markedly reduced in size without enhancement (Fig. ). Further, no new tumors were found in the liver, and the tumor markers returned to their normal levels (Fig. ). A suspicious lesion (2 cm in diameter) recurred at15 months after the initial treatment, which was treated with percutaneous radiofrequency ablation. The patient is alive at 2-year post-procedure and shows complete remission, as defined by the modified response evaluation criteria in solid tumor criteria.
This patient achieved complete remission after chemoembolization, surgical PVL, and extirpation of peritoneally disseminated nodules. The case was complicated by the poor prognostic factors, including the macroscopic diffuse-type classification, a macroscopic PVTT, the peritoneal dissemination, and triple-positive tumor marker status [–]. A tumor biopsy was not performed, but the presence of a poorly differentiated HCC was strongly suggested by the tumor marker status and diagnostic imaging [–].
In patients with HCC and macroscopic PVTT, multidisciplinary treatment, including liver resection, provides an excellent prognosis []. Moreover, a recent nationwide survey in Japan indicated that liver resection was more effective than non-surgical treatment in cases with a PVTT that is limited to the first- or second-order branches []. Multiple measurements of the liver function and functional liver volume after PVL [, , ] in our patient indicated that liver resection was not a viable option. For such HCC patients, other treatment options such as HAIC with chemoembolization and sorafenib also result in poor median survival times of 3.5–10.2 and 8.1–8.9 months, respectively [, ]. However, right portal vein occlusion can prevent both progression of the right PVTT into the left or main portal vein and intrahepatic metastasis into the left liver [, , ], and it may also enhance the effectiveness of HAIC because capsular invasion and satellite nodules could be supplied by the portal vein with hepatic artery [, ]. While formulating the treatment strategy, we also considered the fact that PVE is not indicated in patients with a PVTT that is in close proximity to the bifurcation.
Peritoneal dissemination of HCC can occur after tumor rupture or due to therapeutic interventions. The standard treatment for dissemination of HCC would be systemic chemotherapy, and if dissemination is localized to abdominal cavity or abdominal wall, then the surgical removal for dissemination of HCC might be a challenging option [, ]. In this patient, iatrogenic seeding may have occurred by tumor puncture when drainage was started. However, the spread was limited, and all lesions could be isolated and surgically removed.
Our patient was treated by HAIC followed by transient chemoembolization. Cisplatin and 5-FU are effective for HCC, evidently in intra-arterial infusion [, ]. In fact, some patients with advanced HCC and PVTT have reportedly shown complete clinical remission or pathological response after this regimen [–]. Cisplatin modulates 5-FU activity, and the two drugs seem to have a synergistic effect. Further, as cisplatin infused via the hepatic artery is not trapped in the liver parenchyma, it would also be effective as systemic chemotherapy. Essentially, cisplatin suspended in lipiodol is a highly effective embolic material that is also used in HCC treatment [, , ]. Mitomycin-C and degradable starch microspheres provide temporary occlusion, which may also increase drug concentration [].
Sorafenib is effective in HCC patients with macroscopic vascular invasions, extrahepatic spread, or both, but a recent trial has reported a response rate of 2% and a median survival time of only 10.7 months []. However, a few cases of complete remission after sorafenib therapy have been reported [, ]. In our patient, dynamic imaging detected no viable HCC and persisting normalization of the three tumor markers. Previous reports suggest that HAIC with a cisplatin–lipiodol suspension combined with 5-FU can lead to better response rates and overall survival rates (without extrahepatic metastasis) compared to only sorafenib in patients with advanced HCC and PVTT []. Thus, it would be possible to administer additional chemoembolization or radiofrequency ablation for intrahepatic recurrence and sorafenib therapy for extrahepatic metastasis. It has similarly been reported that sorafenib is effective in patients with HCC refractory to chemoembolization [] and that sorafenib and HAIC with cisplatin may have synergistic effects [].
The maintenance of liver function is the key to achieving longer survival in advanced HCC patients, and it is known that effective treatment for advanced HCC can improve liver function []. Further, it has been reported that a Child–Pugh score of ≤ 7 shows a better response to HAIC with better prognosis compared with Child–Pugh score of 8 or 9 []. However, our patient had a Child–Pugh score of 8 at admission, which improved to 6 after multidisciplinary treatment, indicating that the treatment regimen was effective. |
pmc-6115325-1 | A 69-year-old male was admitted to a hospital in June 2016 because of right arm asthenia and dysarthria and was diagnosed as having cerebral infarction in the left middle cerebral artery area along with deep vein thrombosis. ECG demonstrated normal sinus rhythm and echocardiography revealed no intra-cardiac thrombus or vegetation. The patient was discharged from the hospital following administration of apixaban.
In August 2016, the patient was readmitted to the hospital because of recurrent right arm asthenia and dysarthria. MRI revealed multiple cerebral infarctions in not only the bilateral cerebral hemispheres but also the cerebellum. Trousseau’s syndrome was suspected at this time. Apixaban administration was stopped and an intravenous drip of heparin was started. Echocardiography revealed mild mitral regurgitation with vegetation on the mitral valve. Although the laboratory data suggested no evidence of infection, ceftriaxone and gentamicin were added as a precaution against infective endocarditis. The patient was then referred to our hospital for surgery.
A CT scan revealed a left renal infarction and multiple swollen lymph nodes around both the abdominal aorta and stomach with antral hypertrophy, suggesting an advanced gastric cancer or lymphoma. As the vegetation showed no change despite the heparin and antibiotics therapy, cardiac surgery was performed on day 5 after referral. Extracorporeal circulation was instituted employing aortic and bicaval cannulation. After aortic cross-clamping, the mitral valve was exposed via a left atriotomy. Both mitral leaflets had vegetation on the surface, and major vegetation 15 mm in width was evident on the anterior leaflet (Fig. ). These were resected in their entirety and replaced with a 25-mm Epic bioprosthesis (Abbott). Continuous intravenous heparin administration was resumed on the following day, aiming for an activated partial thromboplastin time of between 40 and 50 s. Histologic analysis revealed that the vegetations were thrombi covered with vascular endothelium and that the mitral leaflet tissue was not damaged (Fig. ). On the basis of these findings, the patient was diagnosed as having NBTE.
An endoscopic stomach biopsy was performed on the seventh postoperative day, and histologic analysis revealed non-solid poorly differentiated adenocarcinoma with components of signet-ring cell carcinoma and moderately differentiated tubular adenocarcinoma. The patient was definitively diagnosed as having Trousseau’s syndrome and, subsequently, transferred to the department of surgery. A Billroth I distal gastrectomy was performed, and a continuous intravenous heparin drip was employed during the operation. Histologic analysis revealed poorly differentiated adenocarcinoma with a component of moderately differentiated tubular adenocarcinoma and metastatic tumor cells in the dissected lymph nodes (T4aN3bM0; stage IIIb). Further histologic analysis using alcian blue staining confirmed the presence of mucin in the tumor.
Subcutaneous heparin injection was introduced on day 8 after the gastric surgery, and the patient was discharged from our hospital in October after acquisition of the self-injection technique. During this long hospitalization, no thromboembolic events were observed. Chemotherapy was started in November. The patient has survived for 18 months after the diagnosis of Trousseau’s syndrome without any recurrence of thromboembolism. |
pmc-6115549-1 | A 47-year-old man presented with a 10-day history of right scrotal pain, swelling and erythema. He had malodorous drainage from right scrotum for two days. He had no diabetes mellitus (DM), hypertension or any other co-morbid diseases; also there were no any risk factors including drug-use, immunodeficiency, genito-urinary or anorectal trauma and infection in his medical history. Massive edema in both of two hemiscrotum and black necrotizing area with malodorous pus drainage in the bottom of the right hemiscrotum was detected in his physical examination (). His anorectal examination was normal. Laboratory analysis revealed as a serum creatinin 0.9 mg/dl, hemoglobin 14.9 g/dl, glucose 486 mg/dL, CRP 156 mg/L, WBC14.5x106 cells/mL, sodium 132 mmol/L. There was no infection sign in bilateral testis, but their sizes were found smaller in scrotal ultrasound (right testis 25x20 mm, left testis 20x20 mm). Intravenous crystallized insulin therapy was given for decreasing serum glucose levels and intravenous imipenem 4x500 mg and Clindamycin 4x600 mg were started prophylactically to the patient according to the infectious disease consultation. All necrotizing tissues were debrided in right scrotum. Right hemiscrotectomy was performed and right testis had a normal blood supply appearance in operation (). Open wound dressing with the nitrofurazone and rifamycin was performed in first three days after operation. The vacuum-assisted closure technique (VAC) (a technique that keeps the wound environment under sterile condition and decreases the frequency of changing protective covers of wound) was performed to the patient in postoperative 3rd day to postoperative 15th day. VAC dressing makes its function by creating mechanical stress with negative pressure of the vacuum system; wound edges diminish, granulation formation accelerates, cellular proliferation and neoangiogenesis increases.
Pathological result revealed as Fournier gangrene and Rhizobium radiobacter was isolated from both of the tissue and abscess cultures. Rhizobium radiobacter was only resistant to trimethoprim sulfamethoxazole and sensitive to ceftazidime, cefepime, imipenem, meropenem, ertapenem, amikacin, gentamycin and tetracycline; therefore same antibiotics were continued to the patient. Control tissue culture was done at postoperative 13th day and by the results revealed as negative wound site was sutured primarily at postoperative 15th day. Patient was discharged at postoperative 18th day with the suggestion of endocrinology consultation for a new diagnosed diabetes mellitus. Patient had come to third month control, he had no symptoms and his scrotum was normal. |
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