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pmc-6123965-1 | A 30-year-old Brazilian male was brought to our ED from a local jail because of agitation. He had been arrested by Swiss authorities because of suspected internal concealment of drugs of abuse (body packing), which had been confirmed by abdominal CT scan in our hospital approximately 12 h before (Fig. ). During this first visit, the patient had presented asymptomatic and had admitted to carrying cocaine-containing body packets. In addition, he had reported recreational use of marijuana and cocaine. It was also noted that the patient was transsexual; he had breast implants. The patient’s past medical history was unknown. Standard operating procedure in such a case is to perform a CT scan without a consultation at the ED. During the second visit approximately 12 h later, the patient presented with psychomotor agitation, mydriasis and tachycardia. His heart rate was 116 bpm, blood pressure was 116/68 mmHg, respiratory rate was 40/min, oxygen saturation by pulse oximetry was 99% on ambient air and auricular temperature was 38.0° Celsius. Communication with the patient was impossible because of his altered mental status and because he spoke a foreign language. The physical examination of heart, lungs and abdomen revealed no pathologies. Neurological examination showed symmetrical spontaneous movement of all extremities and symmetrical gaze to both sides prompted by speech or touch. Glasgow coma scale was 11. An electrocardiogram showed sinus tachycardia without signs of ischemia. Due to our knowledge of the ingested body packets, we first suspected cocaine intoxication because of package rupture. We treated the patient with repeated doses of intravenous midazolam and performed an emergency abdominal CT scan to guide potential emergency surgical decontamination. The CT scan showed 60–70 packets in the gastrointestinal tract without signs of gastrointestinal obstruction or perforation. Laboratory results showed an increased C-reactive protein (CRP) level (231 mg/l, norm < 5 mg/l), an increased creatinine level (181 mcmol/l, norm 62–106 mcmol/l), an increased creatine kinase (CK) level (1000 U/l, norm < 190 U/l), a slightly increased troponin level (16 ng/l, norm < 14 ng/l), hypoglycemia (2.8 mmol/l), mild hyponatremia (128 mmol/l, norm 136–145 mmol/l), hyperkalemia (5.8 mmol/l, norm 3.3–4.5 mmol/l) and hyperphosphatemia (1.68 mmol/l, norm 0.87–1.45 mmol/l) (Table ). Urine analysis showed no evidence of urinary tract infection. A qualitative urine toxicological test was positive for cocaine and benzodiazepines.
Given the clinical presentation of our patient with remarkable hypotension despite cocaine intoxication and elevated inflammatory markers, we suspected infection rather than massive cocaine intoxication to be the main problem. Thorough review of the abdominal CT scans revealed rapidly progressive pulmonary infiltrates in the lower left lobe and lingula, diffuse lymphadenopathy and hepatosplenomegaly (Fig. ). To assess the extent and morphology of the pulmonary infiltrates and to investigate for thoracic lymphadenopathy or solid tumors, we performed a thoracic CT scan. Compared to the abdominal CT scan 4 h before, it showed progression of the pulmonary infiltrates in the lower left lobe and lingula, multiple nodular pulmonary consolidations in both upper lobes compatible with septic emboli or tuberculous foci as well as diffuse cervical, mediastinal and axillary lymphadenopathy.
Due to the above named findings, we withheld emergency laparotomy and started broad-spectrum antibacterial treatment with ceftriaxone and clarithromycin according to our hospital’s guidelines for severe pneumonia. Given the rapid progression of the pulmonary infiltrates in the course of few hours on the thoracic CT scan, we considered the possibility of toxic rather than infectious infiltrates. Because of the patient’s poor general condition we therefore decided to broaden the antibacterial treatment as for sepsis with unknown focus – especially taking into account an abdominal source – to piperacillin/tazobactam instead of ceftriaxone according to our hospital’s guidelines. Based on the elevated creatinine level we diagnosed acute kidney injury, most probably caused by dehydration precipitated by infection and cocaine intoxication. The patient also had an elevated CK level. Cocaine-induced rhabdomyolysis could therefore be an additional cause of the acute kidney injury. Therefore we treated the patient with intravenous fluids.
The patient was admitted to our intensive care unit and isolated for possible pulmonary tuberculosis. In the course of his hospitalization, further diagnostics were available: Pneumococcal urinary antigen test was positive. Screening and confirmatory test for HIV-1 were positive and CD4+ T-cell count was 144/μl, so we diagnosed CDC stage A3 HIV infection. Blood and urine cultures didn’t show any bacterial growth. The diagnosis of pneumococcal pneumonia and sepsis could thus be confirmed, with underlying untreated HIV infection as risk factor. Active pulmonary tuberculosis was excluded by three negative sputum smears and three negative sputum cultures.
With the aid of an interpreter, the patient told us in the course of the hospitalization that one of the drug packages had ruptured in his mouth during swallowing, but that he had been able to spit out most of the cocaine. The exact time of this event remained uncertain.
Upon diagnosis of pneumococcal pneumonia, the antibacterial therapy was changed from piperacillin/tazobactam back to ceftriaxone. As beta-lactam resistant pneumococci were a concern because of the patient’s geographical origin, vancomycin was added to ceftriaxone. This regimen was continued for 7 days. Clarithromycin was stopped after diagnosis of pneumococcal pneumonia. After 9 days, the patient was discharged into custody of the Swiss authorities. Antiretroviral therapy was established in an outpatient setting after ruling out active pulmonary tuberculosis. The patient recovered uneventfully.
Figure shows the key diagnostic findings and interventions on a timeline. |
pmc-6123975-1 | We report the case of a retired Caucasic 84-year-old woman who required a VIV procedure due to the degeneration of a previously implanted aortic bioprosthesis. Her cardiologic history started in 2006 when she experienced syncope and was then diagnosed as having severe aortic stenosis (mean transvalvular gradient 44 mmHg) and severe mitral regurgitation. She reported no previous clinical events. She underwent aortic valve replacement with a Mitroflow number 21 bioprosthesis and a Carpentier-Edwards Physio mitral annuloplasty ring implantation. After surgery, she suffered from brady-tachy syndrome and needed a pacemaker implantation.
The initial signs of prosthesis degeneration were found at a routine transthoracic echocardiography (TTE) in 2011, with a transvalvular mean gradient of 26 mmHg. However, she was asymptomatic and meanwhile she was diagnosed as having an indolent myeloma, thus a conservative approach was chosen.
In January 2014, she started complaining of epigastric discomfort and dyspnea for minimal exertion. A TTE was repeated and showed a further increase of the mean transvalvular gradient (35 mmHg) and occurrence of moderate paraprosthetic regurgitation due to detachment of the anterior edge of the aortic prosthesis ring.
In February 2014 she was admitted to our department for an episode of pulmonary edema with angina. A physical examination revealed bilateral crackles, 3/6 systolic ejection murmur, and leg swelling. Neurological evaluation was normal. Her electrocardiogram showed transient diffuse ST segment depression and troponin values were slightly elevated (peak, 0.08 ng/ml; reference values, < 0.015 ng/ml). In addition, laboratory tests showed a mild anemia (hemoglobin values, 11 g/dl; reference values, 13–17 g/dl) and a stage 3 chronic kidney disease (serum creatinine, 1.1 mg/dl; reference values, 0.5–1 mg/dl; and glomerular filtration rate, 47 mg/dl). Her hepatic function was normal, as well as white blood cells and platelets count (white blood cells, 6500/ml; reference values, 4500–9800; and platelets count, 300 000/ml; reference values, 150,000–450,000).
A transesophageal echocardiogram (TEE) showed hypomobility of the non-coronary cusp, moderate paraprosthetic regurgitation, and severe intraprosthetic regurgitation. Due to the frailty of our patient, in consideration of age, previous cardiac surgery, and concurrent hematologic disease, after a Heart Team discussion, a VIV TAVI was proposed. Pre-procedural investigations included a coronary angiogram, showing absence of coronary artery disease, and a computed tomography (CT) angiography to calculate the diameter of the Mitroflow prosthesis (17 mm) and the LMCO height from the valvular annulus (11.6 mm).
VIV implantation was performed via right femoral artery using a CoreValve® prosthesis number 23 (Additional file ). A 6 Fr guide catheter, via right omeral artery, was used for the left main coronary artery cannulation as protection (Figs. and ).
Post-procedural angiography confirmed maintained coronary perfusion (Fig. ), even after the removal of the guide wire. It also showed correct position of the prosthesis and its normal functioning with a transvalvular gradient of 12 mmHg and a mild intraprosthetic regurgitation (Fig. ).
Our patient was hemodynamically stable and was transferred to the cardiothoracic intensive care unit. Two hours after the end of the procedure, she experienced a sudden cardiac arrest with asystole and electromechanical dissociation. Resuscitation maneuvers were ineffective.
An autopsy was performed to investigate the cause of death. The CoreValve® prosthesis was removed from the aortic root with no signs of damage or thrombus formation (Fig. ). The underlying Mitroflow valve appeared free of calcium or thrombi, but its leaflets appeared higher than the LMCO (Fig. ). No other possible cause for the sudden cardiac death could be found. Our hypothesis was: a delayed occlusion of the LMCO by the Mitroflow leaflets, pushed upward by the late expansion of the CoreValve® prosthesis. |
pmc-6124007-1 | A 6-year-old boy presented with right-sided neck pain for 6 months was admitted in our institution on July 2007, with no history of recent trauma, fever or infection. The pain localized in the right side of neck, without radiating pain. The pain exacerbated for several days and not alleviated by using analgesics. Visual Analogue Scale (VAS) for cervical pain was 7.0. Physical examination revealed no palpable masses or torticollis. Neurological examination revealed nothing abnormal. Laboratory tests revealed normal white blood cell count (6170/mm3, normal range: 5000–12,000/mm3) and elevated ESR (69 mm/h, normal range: 0 to 20 mm/h) and CRP (11.80 mg/L, normal range: 0 to 5 mg/L). Radiograph and CT showed calcification of intervertebral disc at C2/3 and C3/4 levels, accompanied by C3/4 level OPLL (Fig. and ). MRI revealed decreased signal intensity of C2–4 discs and C3/4 posterior longitudinal ligament on T2-weighted images, with slight dura compression (Fig. ). The patient was treated with analgesics for 2 weeks, interrupted cervical traction for 2 weeks and cervical collar for 1 month. After a one-month conservative treatment, the patient’s symptoms greatly improved. VAS for cervical pain decreased to 1.0.
Nineteen months later, in March 2009, the boy complained no discomfort. Laboratory tests (including white blood cell count, ESR and CRP) revealed nothing abnormal. C3/4 intervertebral disc calcification and OPLL had disappeared, only minor calcification at C2/3 intervertebral disc left (Fig. and ). MRI demonstrated restoration of T2-weighted signal intensity of C2/3 and C3/4 discs (Fig. ).
When last seen in October 2016, there was still no discomfort. Laboratory tests revealed nothing abnormal. No sign of C3/4 intervertebral disc calcification and OPLL was observed (Fig. and ). Minor calcification at C2/3 intervertebral disc remained (Fig. and ). MRI demonstrated loss of T2-weighted signal intensity of C2/3 disc and decrease of T2-weighted signal intensity of C3/4 disc (Fig. ). Narrowing of C2/3 intervertebral space, flatting of C3 body, widening of posterior edge of C3/4 disc were observed in CT scan (Fig. and ). |
pmc-6124168-1 | A 20-year-old woman with Noonan syndrome—a genetic disorder that presents with short stature, distinctive facial features, chest deformity, and congenital heart disease—was diagnosed with giant cell tumor of the bone (GCT) localized to the ramus regions of the jaw in 2002. The tumor was found on exam by an otolaryngologist who was treating the patient for an acute bout of sinusitis. She was referred to an oral surgeon who subsequently biopsied the lesion and confirmed a diagnosis of GCT. Despite six dental extractions, deemed necessary in the context of the expansile and lytic nature of the lesion, and an 18-month course of subcutaneous calcitonin 100 IU daily, she developed progressive disease.
The patient had no personal or family history of metabolic bone disease and did not receive any growth hormone for her short stature. She reached an adult height of 5 feet 0 inches. In March 2002, imaging showed a new mandibular lesion in the anterior mandible with irregular borders measuring approximately 28.4 mm (width) × 21.8 mm (height). Biopsy showed central giant cell lesions with associated perivascular hyalinization (Fig.
A, B). Initial workup showed a 25-OH vitamin D level of 9.8 ng/mL and ergocalciferol 50,000 units weekly was started. N-terminal telopeptide of type 1 collagens (NTx) was 48 nM BCE/mM creatinine with normal range being 4 to 64 nM BCE/mM creatinine in premenopausal females. PTH, bone-specific alkaline phosphatase, and phosphorus were within expected reference ranges.
Based on the patient's age and the lack of published data specifically addressing GCT affecting the jaw, we opted to begin at conservative doses while monitoring for any potential adverse reactions. The decision was made to start treatment with a lower dose of subcutaneous denosumab (60 mg monthly) as opposed to dosages used in open-label, phase 2 study (120 mg monthly with loading doses on day 8 and 15 of month 1). NTx, 25 OH-D, bone-specific alkaline phosphatase, comprehensive metabolic profile, and phosphorus were monitored intermittently throughout her therapy.
No adverse reactions were reported by the patient and evaluation after 1 year of treatment showed radiologic and pathologic resolution of Giant Cell Tumor of Bone (GCTB) (Fig.
C, D). Current dosage intervals have increased to denosumab 60 mg every 6 months. |
pmc-6124168-2 | A 34-year-old man in generally good health developed right lower jaw pain in February 2014. He had no history of calcium or other metabolic bone disorders, including Paget's disease, and was not on any chronic medications. He denied any history of radiation exposure. The patient was referred to our center by his oral surgeon who diagnosed a giant cell lesion of the jaw. Panoramic dental X-rays showed a 25 mm × 15 mm radiolucent lesion in the right posterior mandible (Fig.
A) with biopsy confirming giant cell granuloma associated with reactive bone.
On initial workup, his calcium level was 9.5 mg/dL, PTH 12.5 pg/mL, bone-specific alkaline phosphatase 9.4 μg/L, C-terminal telopeptide (CTx) 70 pg/mL, and NTx 20 nM/BCE/mM creatinine, which were all within reference ranges. He had vitamin D insufficiency with a value of 22.6 ng/mL.
We began supplementation with vitamin D 1000 IU daily and initiated denosumab 120 mg monthly. The treatment decision was made to start at 120 mg based on the patient's age and extent of disease. Loading doses were not administered. At 7 months of treatment, repeat imaging (Fig.
B) showed a denser lesion although there was no regression in size. Repeat biopsy 1 year after the patient's initial treatment dose showed thickened cortical bone with subjacent trabeculae exhibiting bone on bone pattern in a background of adipose tissue. There was no evidence of CGCG. NTx levels were monitored throughout the course of therapy and, given the low NTx levels, the decision was made to decrease treatment dose and increase dosing interval to denosumab 60 mg every 3 months. |
pmc-6124168-3 | The third patient is a 14 year-old male with no significant personal or family history of metabolic bone disease who was found to have a mandibular jaw lesion on routine orthodontic exam. The patient denied any significant pain but did mention that he felt some “loosening of the teeth.” He had normal growth and development during childhood as reported by his mother. Pubertal development was appropriate for sex and age as well.
Panoramic dental X-rays showed a large, destructive, expansile lesion with ill-defined borders. There was a permeative moth-eaten pattern indicating a more aggressive lytic lesion. The lesion measured 36 mm × 23 mm × 28 mm and protruded into the right floor of the mouth including the dental roots (Fig.
A). Based on the imaging, differential diagnosis included aggressive bone tumors such as an osteosarcoma, aneurysmal bone cyst, or a GCT. Pathology results reviewed at our institution showed bland-appearing spindle cell proliferation with giant cells. The case was submitted to an outside expert for consultation and the final diagnosis was a giant cell granuloma.
Initial laboratory workup was within normal reference ranges except the NTx level, which was 157 nM/BCE/mM creatinine, and a 25 OH D of 14.2 ng/mL.
We started treatment with denosumab 120 mg monthly. After two doses, NTx levels decreased to 14 nM/BCE/mM creatinine. The following year, repeat imaging showed marked improvement and improved bone quality (Fig.
B). He had received six consecutive doses of denosumab 120 mg every 4 weeks and interval frequency was increased to a lower dose of denosumab 60 mg every 3 months. |
pmc-6124168-4 | A 31-year-old man with no personal or family history of metabolic bone disorders was referred to our institution for evaluation and treatment of a GCT of the jaw. He was diagnosed in 2015 when he presented to his orthodontist with a lower jaw lesion and difficulty chewing food. CT scan showed an expansile lesion measuring 25 mm × 25 mm × 22 mm (Fig.
A, B). The lesion was described as being lytic in nature and expansile. Buccal cortex was absent and lingual cortex was almost completely absent. Prior to establishing endocrine care, he had received steroid injections with Kenalog 40 mg/mL weekly. After 6 weeks of treatment, little effect on tumor size was observed.
This patient's initial laboratory workup was within normal limits and denosumab 120 mg monthly was started. He completed 7 months of treatment with no reported adverse events and surveillance imaging repeated this year showed calcifications of the lesion (Fig.
C, D). |
pmc-6124168-5 | A 15-year-old female with a history of presumed autosomal dominant cherubism (two sisters with a diagnosis of cherubism) and mandibular lesions since 6 years of age presented with loosening of her teeth and numbness to the lesion site. She had normal growth and development with menarche at 11 years of age. At the time of examination, she had achieved height of 5 foot 9 inches without growth hormone treatment—reportedly taller than her parents or siblings. The patient was diagnosed as having GCT of the jaw with concomitant enlargement of the mandible. Pathology confirmed giant cell lesion consistent with cherubism.
Cherubism is a rare benign condition characterized by bilateral expansion of the mandible and/or maxilla that becomes noticeable within the first several years of life. It becomes progressively pronounced until puberty, with gradual involution by middle age. Histologically, the lesions contain numerous multinucleated giant cells scattered throughout a fibrous tissue stroma. In some cases, lesions resolve without treatment. However, the frequency of occurrence is unknown because most cases have been surgically treated before reaching puberty. For patients with extensive lesions and risk of fracture, segmental mandibulectomy followed by reconstruction with a fibular flap has been suggested. Medical therapy including calcitonin and low-dose interferon alpha have also been used.
The decision was made to start denosumab 120 mg monthly because the patient had progressive lytic lesions and numbness with core biopsy revealing giant cell pathology. Further, we considered investigating genetic testing for mutations in the SH3 binding protein (SH3PB2) on chromosome 4p16.3, which causes cherubism, but did not pursue due to accessibility of the test, as well as it having little direct clinical impact on our management.
After 5 months of treatment, dental imaging showed significant ossification of the giant cell defects. A second biopsy to confirm response to therapy is pending. |
pmc-6124168-6 | A 19-year-old female with a previous dental implant who presented to her orthodontist with related complications, and biopsy confirmed CGCG of the jaw.
Patient is tolerating denosumab 120 mg monthly. Surveillance is ongoing, imaging and repeat biopsy are planned for the 1-year treatment mark. |
pmc-6124168-7 | A 12-year-old male with CGCG of the jaw post presented to our care after resection of a 2-cm lesion with recurrence.
Treatment was initiated with denosumab 60 mg, which was determined based on shared-decision making with family, who had concerns that higher doses may affect growth and bone quality during formative pubertal/developmental years. The patient received a single dose of medication then developed paresthesia and back pain 1 month later. Pretreatment calcium was 9.9 mg/dL, PTH 63 pg/mL, and 25 OH D 20.2 ng/mL while he was on supplementation with vitamin D 1000 units daily. On laboratory evaluation for his acute symptoms, the patient was found to have secondary hyperparathyroidism with a serum calcium of 6.3 mg/dL (albumin of 4.6 g/dL), PTH of 292 pg/mL, and 25 OH D 23.4 ng/mL. Calcium 600 mg three times a day was started along with ergocalciferol 50,000 units weekly. Denosumab was held and paresthesia and back pain have improved. The most recent calcium level was 9.6 mg/dL (albumin of 4.6 g/dL) and family is considering restarting treatment with denosumab at lower doses.
Table is a summary of the characteristics of the seven cases discussed herein. |
pmc-6124177-1 | A 62-year-old male patient diagnosed with chronic glomerulonephritis was maintained on hemodialysis for the previous 12 years, twice per week, with felodipine to control his hypertension. Three years ago, an abrupt surge in his blood serum intact parathyroid hormones (iPTH) levels was observed. One year later, the patient's clinical condition started to deteriorate, showing whole-body bone deformation and metamorphosis of the lower jaw, chest, and lower limbs. Last year, his serum iPTH was 477 pg/mL, and he was prescribed calcitriol 0.25 µg daily (qd); however, his symptoms continued to be worsen. The patient showed noticeable craniofacial deformities (Fig. A), dysphonia, severe bone pain, itching of the skin, inability to walk, and a decrease in body height from 170 cm to 150 cm. The patient mentioned a spontaneous fracture of the left humerus that had occurred 1 year prior though he claimed that he had not had any related accidents. The pretherapeutic blood tests showed severe anemia and hypoalbuminemia, and the patient was given an emergency infusion of red blood cells and albumin. Routine physical examination showed the following: temperature 36.5°C, pulse 66/min, respiration rate 18/min, and blood pressure 140/80 mmHg. Physically, the patient seemed to suffer from malnutrition, lion face/leontiasis (upper mandibular enlargement and deformity), and the oral hard palate showed non-hardened hyperplasia; there was also severe deformation of the chest known as pectus carinatum (Fig. B), kyphosis, and deformity of the lower limbs (Fig. C). After admission, routine blood examination showed the following: serum hemoglobin 118 g/L, erythrocyte count 3.33 × 1012/L, hematocrit 0.327, serum total protein 59.7 g/L, serum albumin 36.2 g/L, blood urea nitrogen 23.79 mmol/L, creatinine 606.1 µmol/L, serum calcium 2.78 mmol/L, serum phosphorus 1.64 mmol/L, serum iPTH 2183.2 pg/mL, serum alkaline phosphatase (ALP) 1138.7 U/L, serum osteocalcin 244.9 ng/mL, and serum 25-(OH) vitamin D 37.4 nmol/L.
Auxiliary examinations were as follows: head and cardiac CT scans demonstrated thickening of most cranial bones (Fig. A), the maxilla, mandible (Fig. B), thoracic deformity, and vascular and heart valve calcification. The Agatston scores (measured in Hounsfield units) of the left main artery (LMA), left anterior descending (LAD) artery, right main artery (RCA) (Fig. A) and left circumflex artery (CX) (Fig. B) were 163.3, 333.5, 444.1 and 204.2 respectively. The emission computed tomography (ECT) showed hyperparathyroid tissue development (left and right sides, superior and inferior sides of parathyroid glands were detected on the posterior part of the thyroid gland). B-ultrasound revealed bilateral hypoechoic areas and hyperplasia of the parathyroid. The sagittal and coronal reconstruction images of noncontrast CT showed reduced density of pyramids, multiple thoracic and lumbar vertebral compression fractures (Fig. A), multiple pyramidal instability and wedge deformity of T12 vertebra (Fig. B).
Technetium-99m-methylene diphosphonate (99mTc-MDP) bone scintigraphy indicated an increase in radiotracer uptake especially in the axial skeleton, calvaria, mandible, costochondral junctions, and long bones, and a “tie sign” sternum together with an increased ratio of bone to soft tissue (Fig. A). The bone scan showed a higher radionuclide uptake in the left humerus due to prior fracture, spinal kyphosis deformity caused by multiple thoracic and lumbar vertebra compression fracture, and severe bowing of the legs (Fig. B). The patient was diagnosed with chronic kidney disease–mineral and bone disorder (CKD-MBD), SHPT, chronic glomerulonephritis, CKD stage 5, renal anemia, leontiasis ossea, renal osteodystrophy, left humeral fracture, and malnutrition.
The patient underwent parathyroidectomy in which five glands, including one supernumerary parathyroid gland (SPG) were dissected and removed. The glands weighed 1.9 g, 1.4 g, 1.0 g, 0.2 g, and 0.2 g, respectively. The pathology report after surgery confirmed all the resected intraoperative frozen sections were parathyroid glands. The forearm without arteriovenous fistula was selected for the site of implantation where the smallest parathyroid gland was sliced into eight pieces (1 × 1 × 1 mm3). Venous blood levels of iPTH were determined preoperatively, 10 min, 20 min, 1 day, and 4 days postoperatively, as shown in Fig. . Serum iPTH levels were measured using a UniCel DxI800 Access Immunoassy System (Beckman Coulter, Inc., Fullerton, CA, USA). Vitamin D and calcium (Ca) supplements were prescribed. The patient's clinical condition improved within 10 months of follow-up, with alleviation of bone pain and cessation of bony overgrowth on the face; however, the deformity of the lower limbs have not yet been corrected, resulting in the inability to walk. His blood pressure returned to normal, without the use of antihypertensive drugs. Blood examination revealed a drop in serum iPTH to 57.2 pg/mL, Ca to 8.8 mg/dL, P to 2.08 mg/dL, and ALP to 297 U/L. |
pmc-6124189-1 | On 30 May 2018, a Greek male in his late 40s returned to Greece after spending 23 days in a forested area in Blagoevgrad province, south-western Bulgaria, where he was working in bridge construction. Three days earlier (27 May, day 1), while in Bulgaria, he developed fever, severe headache, myalgia (mainly in the lower extremities), malaise and loss of appetite; on 28 May he visited a local hospital and received symptomatic treatment as an outpatient. As his condition deteriorated (onset of photophobia and abdominal pain) he returned to his permanent residence in northern Greece. On 31 May (day 5), the patient was admitted to a local hospital. He was transferred to the university hospital in Alexandroupolis the next day because he presented severe thrombocytopenia and leukopenia; elevated levels of liver enzymes, creatine phosphokinase (CPK) and lactate dehydrogenase (LDH); and prolonged activated partial thromboplastin time (aPTT) (). On day 6, his headache was resolved but his fever (38.2 °C), malaise and myalgia were ongoing. The main laboratory findings were thrombocytopenia, prolonged aPTT (82 s) and increased level of aminotransferases. His laboratory parameters indicated rhabdomyolysis (CPK 1,739 U/L) and slightly elevated urea and creatinine levels (Table). A bone marrow biopsy showed haemophagocytosis.
On day 6, the first day after admittance to the hospital in Alexandroupolis, the patient was asked about any recent tick bites; he mentioned that on 26 May he had found and removed a tick from his abdomen (he had not reported it to the hospital in Bulgaria or the first hospital in Greece). Rickettsiosis was suspected and treatment with oral vibramycin (100 mg x 2) was started. One day later (day 7), he presented with a progressively extended haematoma on his left upper arm (bleeding from venipuncture sites) and on his lower back (). The patient’s clinical condition deteriorated rapidly, and on day 8 he presented with an abrupt drop in haematocrit, further elevation of transaminases and low fibrinogen (< 100 mg/dl), haemodynamic instability and altered mental status (lethargy). The laboratory findings in serial samples can be seen in . An abdominal computed tomography scan showed retroperitoneal haematoma and extensive haematomas in muscle groups at the site of bone marrow biopsy.
Based on the patient’s clinical presentation, and as he was bitten by a tick in an area of Bulgaria where CCHF cases have been reported previously, CCHF was highly suspected. Typically, the incubation period of CCHF after a tick bite is short (1–3 days), but the exact date of the bite was unknown in this case. The treating physician contacted the National Reference Centre for Arboviruses and Haemorrhagic Fever Viruses in Thessaloniki and the suspected case was immediately notified to the Hellenic Center for Disease Control and Prevention (HCDCP). |
pmc-6124378-1 | A seven and half year-old boy visited the outpatient clinic of Pediatric Dentistry Department, Faculty of Dentistry, Cairo University in June 2015 with a chief complaint of pain on the lower right molar area. The patient’s mother stated that the pain was at times throbbing in nature, and child is not able to chew on this side.
Clinical examination showed a badly decayed, lower second primary molar with related localized intraoral abscess, where the lower first primary molar was intact. The patient had poor oral hygiene; he had not received any professional dental care, and was very apprehensive.
Radiographic examination revealed root resorption and bone rarefaction related to lower second primary molar. The interesting finding was a considerable amount of root resorption of the distal root of the adjacent lower first primary molar (
).
The case was managed by performing pulpectomy
to the lower second primary molar, with root canals filled with calcium hydroxide paste with iodoform (Metapex, Meta Biomed, Republic of Korea). The tooth was then restored with high viscosity glass ionomer (GC Fuji IX GP capsule, GC corporation, Tokyo, Japan) (
). The lower first primary molar was not touched and instead monitored. No antibiotics or analgesics was prescribed.
Unfortunately, the patient’s mother did not want follow-up appointments in person, however, she was contacted on the phone, after 2 weeks, 3 months and 6 months, and she said everything was fine and there was no swelling or pain.
At about 8 months from the treatment appointment, the patient’s mother visited the outpatient clinic with the patient for other reasons, and decided to pass by the Pediatric Dentistry Department for patient follow-up. Clinical examination showed no signs or symptoms, occlusal restoration was intact, and radiographic examination revealed arrested root resorption, on both molars, and an increase in the density of bone although this was not at a normal level yet (
).
shows the patient’s timeline of symptoms, treatment and follow-up. |
pmc-6124770-1 | On August 10, 2015 a 14-year-old boy was admitted to the psychiatric department of the Regional Hospital of Banfora for psychiatric disorders primarily characterised by logorrhea, hypersomnolence and a persistent fever. For at least five months before admission, the patient visited several peripheral health care facilities close to his village with the same symptoms. However, no health professionals considered the possibility of HAT since the disease is no longer regarded to be a threat in this area. The symptoms then progressively became aggravated and the parents said they believed that their child was “possessed by spirits”. They visited some traditional healers but his health deteriorated further, and the parents were not sure how to save their child. Fortunately, the patient’s uncle, a teacher, convinced the parents to take him to the Regional Hospital of Banfora, a preeminent health care centre in the region.
Based on the above described signs and symptoms, and thanks to the fact that a doctor had recently been trained for HAT clinical suspicion, a HAT RDT (SD Bioline HAT) was performed on August 11, 2015 and the patient turned out to be positive. The serological suspicion was subsequently reinforced by a positive TL test (on August 17) using the LiTat 1.3 variant antigenic type (VAT) performed on blood that had been dried on filter paper and by a positive Card Agglutination Test for Trypanosomiasis (CATT; on August 19) preformed on whole blood and an end titer of 1/32 in CATT performed with twofold plasma dilutions (CATT pl). Parasitological investigations conducted on August 19 revealed the presence of trypanosomes in the blood with the mini Anion Exchange Centrifugation Technique performed on 350 μl of buffy coat [] (20 trypanosomes) and in the cerebrospinal fluid (CSF) using the Modified Simple Centrifugation (MSC) performed with 3.5 ml of CSF [] (5 trypanosomes). For CSF white blood cell count, a Uriglass counting chamber was used, revealing 174 cells/mm3. On the basis of these results, the patient was classified in stage 2 of the disease and treatment with eflornithine (DFMO), according to the national procedure, was started on August 25. The patient stayed for 2 weeks in the Regional Hospital of Banfora. His 6-month post-therapeutic follow-up confirmed that treatment was successful, as no trypanosomes were detected in the blood or CSF, fewer than 5 cells/mm3 were found in the CSF, and his general clinical condition was normal. |
pmc-6125262-1 | A 31-year-old man was admitted to our hospital, complaining of hematochezia which had lasted for 1 month. His past history involved a high anterior resection of the rectum in our hospital due to intussusception caused by Peutz-Jeghers polyposis (Fig. ). He was hospitalized for 1 month after the procedure. Unfortunately, details of the surgical procedure that had been performed and the reason for his extended postoperative hospitalization were unknown, because clinical records from his previous admission were not available. He was followed up for 3 years after the procedure, during which he had no abdominal symptoms. He remained symptom-free until the month prior to readmission when he began to suffer from hematochezia. On this admission, hematochezia was his only symptom and there were no abnormal abdominal findings on physical examination. Blood test results, including levels of tumor markers, were all within normal limits. Colonoscopy revealed a hemorrhagic tumor with a smooth surface protruding from the anastomosis of the previous high anterior resection, at a distance of 10 cm from the anal verge; a second examination 4 days later revealed that the tumor had disappeared (Fig. ). The biopsied tumor and other small polyps were histologically diagnosed as adenocarcinoma and hamartomatous polyps, respectively (data not shown). We performed a low anterior resection of the rectum, including the anastomotic site with the adenocarcinoma, combined with a resection of the ileum for strong adhesion. The patient was discharged from our hospital 42 days after the operation.
Gross appearance of the resected rectum showed a defect of the rectal mucosa with a smooth edge and a mucosal bulge located at the anastomotic site (Fig. ). Cut surfaces demonstrated a submucosal tumor mainly occupying the proper muscle layer under the defect (Fig. ). Microscopically, the submucosal tumor comprised an adenocarcinoma and a bone lesion at the anastomotic site (Fig. ). The surface of the tumor was covered with granulation tissue (Fig. ). The bone lesion not only included the carcinomatous glands but also normal glands in the bone tissue (Fig. ). In addition, we identified the incorporation of the normal mucosa in the submucosal fibrosis at the anastomotic site (Fig. f). |
pmc-6125373-1 | A 65-year old Caucasian woman with mild diabetes since 4 years, migraine and family history negative for neuromuscular diseases (Figure ), had a few episodes of loss of consciousness and fall, sometimes associated with urinary incontinence. A CT scan showed cerebral atrophy and an EEG slowing in the theta frequency range and left temporal spike activity. Based on the suspicion that those episodes could be epileptic, she was given a daily dose of 800 mg VPA. Within 3 months of treatment, the patient had a dramatic worsening of her clinical status, becoming bedridden and lethargic.
On admission clinical examination showed a short and stocky woman (height 138 cm, weight 70 kg) who appeared drowsy, but yet oriented in space and time. She could not walk nor stand unaided. Neurological examination showed vertical gaze palsy, intact function of the other cranial nerves, including normal fundus oculi, diffuse lower limb weakness (MRC score 3), and brisk tendon reflexes, without sensory, extrapyramidal and cerebellar involvement. Blood VPA was 61.9 mcg/ml (recommended therapeutic range 50–100), blood ammonia 45 μmol/l (n.v. 11–35), and serum lactate level at rest 8.6 mmol/l (n.v. < 2.2). There was also presence of organic aciduria with intermediates of Krebs cycle in the urine. Abdomen ultrasound imaging showed moderate fatty liver and no other relevant findings. The EEG showed slow activity in the lower alpha range (7.5–9/sec), mixed to theta and delta activity over the left fronto-temporal and occipital regions (Figure ). Brain MRI with MR-spectroscopy (MRS) showed diffuse cortico–subcortical atrophy, more marked in the fronto-temporal region. There were large confluent areas of white matter (WM) hyperintensity in T1 and T2-weighted images at level of the semioval centers and the periventricular region bilaterally, with extension in the capsula externa and sparing of the juxtacortical “U” fibers (Figures ). MRS showed a marked reduction of the NAA spectrum in the basal ganglia and in the WM, with a double spike at 1.3 ppm compatible with a peak of lactate (not shown).
We decided to titrate and then dismiss VPA therapy. During the following 2 weeks the patient had a significant improvement: she appeared alert and oriented, could walk unaided and came back able to perform daily activities independently. Neurological examination showed significant improvement of the lower limbs muscle strength (MRC score 4++). At a 12 month follow-up her clinical condition appeared unchanged. She underwent a muscle biopsy that evidenced some nonspecific age-related alterations as one necrotic fiber and a variability of morphology with some hypotrophic and angulated fibers and some evidence of mitochondrial dysfunction. In particular, 20% of the fibers were ragged-red at the Gomori trichrome stain with few cytochrome c oxidase negative (COX) fibers and slightly reduced activity of succinate dehydrogenase (SDH) (Figure ). The contemporary alteration of COX and SDH activity at histochemistry suggested an oxidative metabolism dysfunction. Subsequently, the spectrophotometric determination of respiratory chain enzyme activities in muscle homogenate showed multiple complex enzyme deficiencies. In particular, the activities of NADH-cytochrome c oxidoreductate (complexes I+III), succinate cytochrome c oxidoreductase (complexes II+III) and COX (complex IV) were 27, 20, and 23% of normal control values, respectively, when enzyme complexes were corrected for the activity of citrate synthase, a mitochondrial matrix enzyme used as an index of total mitochondrial mass (Table ).
Sequencing of the whole mitochondrial DNA in peripheral blood and skeletal muscle assigned the patient to mitochondrial haplogroup X2b and detected the homoplasmic m.8393C>T/p.Pro10Ser variant in MT-ATP8. Large scale mitochondrial deletions were appropriately ruled out. The p.Pro10Ser variant, of uncertain pathogenic significance () but already associated with VPA-induced toxic encephalopathy (1), was also homoplasmic in blood from six healthy relatives (Figure ). Western blot analyses in muscle homogenate from the patient did not reveal any reduction in the expression of respiratory chain complex subunits compared to controls (Supplementary Figure ) whereas ATP levels determined in cultured skin fibroblasts () showed reduced mitochondrial ATP synthesis and increased glycolytic ATP in the proposita, but not in her healthy daughter (III-02), compared to controls (Supplementary Figure ), suggesting an impaired ATP production machinery. To investigate if additional variants in nuclear DNA-encoded mitochondrial gene could contribute to the clinical phenotype, we analyzed in blood DNA from the proposita the coding regions of 1172 nuclear genes known to be associated with mitochondrial disorders (Mito-chip, see ) but we failed to detect rare predictably pathogenic variants of clinical significance. Supplementary Table lists rare (MAF < 0.01) variants of uncertain significance identified in the patient. |
pmc-6125864-1 | A 20-year-old Caucasian woman presented to our institution with decreased vision in the right eye (RE) with a 4-month evolution. The patient’s vital signs were within normal limits, and no abnormalities were noticed upon physical and neurological examination. Similarly, her past medical history was unremarkable. Her best corrected visual acuity (BCVA) was 50 ETDRS (Early Treatment Diabetic Retinopathy Study) letters in the RE and 84 ETDRS letters in the left eye. Her intraocular pressure (IOP) was normal in both eyes, and the result of her anterior segment examination was unremarkable. Upon ophthalmoscopic examination, a red-colored globular lesion of 3 disk diameters (DDs) with prominent feeder vessels was noticed in the superior temporal region of the retina in the RE (Fig. ). The fellow eye was normal on fundus examination, and no other lesions were found in the posterior pole or periphery. Optical coherence tomography (OCT) was carried out using the DRI OCT Triton™ SS-OCT device (Topcon Medical, Tokyo, Japan).
A structural OCT B-scan of the RE showed a diffuse cystoid macular edema (central macular thickness of 450 μm) (Fig. ). The en face scan enabled assessment of the extent of the cystoid edema, which involved the posterior pole and expanded outside the vascular arcades (Fig. ).
The patient’s family history was collected, and it was discovered that the patient’s mother had died of pulmonary edema during pregnancy at the age of 40. A genetic test was carried out, which showed a variant in the VHL gene: c.335A>G(p.Y112C). In our patient, this variant was in the heterozygous state. On the basis of genetic findings and considering the presence of RHB, the diagnosis of VHL disease was made. A systemic study was conducted to search for other organs with lesions. Results of renal ultrasonography and magnetic resonance imaging of the brain were both negative for visceral lesions.
The patient received an intravitreal injection of ranibizumab and was then followed every month. Forty days after the injection, an OCT B-scan and an OCT en face scan revealed a reduction in RE macular edema (Fig. ). The patient’s BCVA was 50 ETDRS letters in the RE. Considering the persistence of cystic spaces, an intravitreal injection of slow-release dexamethasone was considered to reduce macular edema in preparation for cryotherapy. At 60 days following ranibizumab administration, a slow-release intravitreal dexamethasone implant (IDI) was injected. A structural OCT B-scan performed 1 week after IDI showed the almost complete absence of cystic spaces in the subfoveal and perifoveal areas (Fig. b′) with complete restoration of the retinal profile (Fig. a′). Inconsistent with the improvement in retinal morphology, the patient complained of visual impairment and recurring headache. BCVA was found to be 42 ETDRS letters in the RE. No changes IOP values were observed during the follow-up examinations.
Twenty days after IDI, the patient’s RHB was treated with a combination of laser photocoagulation and a triple freeze-thaw technique of transconjunctival cryotherapy. Although the patient’s retinal profile seemed to have been restored, OCT images obtained 20 days after cryotherapy was performed (Fig. ) showed increased exudation causing a massive and wide serous retinal detachment. The patient was then followed every month for 6 months, and, considering the persistence of the exudative retinal detachment and having ruled out the presence of a retinal break, she is currently under evaluation for pars plana vitrectomy (possibly associated with lens extraction and/or scleral buckling) and endovitreal tumor treatment. |
pmc-6125870-1 | A esophageal cancer patient who was diagnosed as S. haliotis pulmonary inflammation.
A 68-year-old male patient was admitted to people’s hospital of Liaocheng city, China, on July 24, 2016, because of “hematemesis for 4 hours”. He had been diagnosed with the operation of esophageal cancer for more than 2 years. His admitted physical examinations were body temperature of 36.3 °C, pulse rate 92 beats/min, breathing of 22 times/min and blood pressure 135/80 mmHg. Nonpalpable enlargement of bilateral neck and supraclavicular lymph nodes, trachea in the middle, pectoral symmetry, visible scars at right chest, clear percussion sound at double lung, auscultation of coarse breath sound, no dry and wet rales, regular rhythm, percussion no pain of the kidney area, negative for shifting dullness and bowel sounds of 3 times/min. His admission diagnosis was esophageal cancer after operation and hypertension. On admission, the auxiliary examinations were performed to determine the source of hematemesis. The painless gastroscopy was carried out, but no obvious abnormalities was observed. The painless bronchoscopic examination revealed posterior basal segment of left lower lobe hemorrhage. Brushing pathology indicated no obvious tumor cells. Thoracic and abdominal enhanced computed tomography scan showed that he had esophageal surgery, bronchitis and emphysema, middle lobe of right lung nodules, right upper lobe and left lower lobe interstitial lesions and the lower lobe of the left lung inflammation. He was given medicine (3 g of cefoperazone/sulbactam was administrated twice a day for 6 days) and therapy of anticancer, anti-inflammatory, rehydration and hemostasis. After six days’ treatment, his symptoms improved and the patient was discharged from the hospital.
The bronchoalveolar lavage fluid (BALF) was collected when he received painless bronchoscopic examination and the cell number was over 104 cfu/ml. Sample was streak-inoculated on blood agar medium for bacterial culture. Strains of different phenotypic features at blood plates were isolated and identified as S. algae, Escherichia coli and Klebsiella pneumoniae by VITEK 2 system using the ID-GN card (boiMérieux). Since only two Shewanella species, S. putrefaciens and S. algae, were registered in the database of VITEK 2 system, the 16S rRNA gene sequence was amplified by a PCR described previously []. The PCR product was sequenced and the nucleotide sequence had been deposited at GenBank, under the accession number of MF589233. BLAST analysis of 16S rRNA gene sequence at GenBank showed a similarity of 99.0% with type strain of S. haliotis DW01 (accession numbers NR_117770.1). Further phylogenetic analysis with all type sequences of Shewanella species available in the GenBank database, confirmed the strain was identified as species of S. haliotis (LC2016–1 in Fig. ).
To further confirm the bacterial community composition and richness of the BALF, sample was subjected to the 16S rRNA amplicon sequencing [, ]. The result indicated the bacterial community composition included genera of Shewanella (88.34%), Escherichia (11.11%) and Streptococcus (0.38%), et al., whereas the majority of genus was Shewanella.
Antibiotic susceptibility testing was performed by microdilution method on Mueller-Hinton broth. The strain was susceptible to piperacillin/tazobactam (minimal inhibitory concentration, MIC: 8 μg/ml), ceftazidime (1 μg/ml), cefepime (1 μg/ml), amikacin (2 μg/ml), gentamicin (1 μg/ml), imipenem (4 μg/ml), meropenem (4 μg/ml), but was resistant to ciprofloxacin (8 μg/ml) and levofloxacin (8 μg/ml). |
pmc-6125870-2 | A gastric cancer patient who was diagnosed as S. algae bacteremia.
A 56-year-old man was admitted to people’s hospital of Liaocheng city, China, on 6, Oct. 2016, because of “discomfort of upper abdominal pain for 1 month”. His admitted physical examination included body temperature of 36.1 degrees, pulse rate of 72 beats/min, breathing 18 times/min and blood pressure 140/90 mmHg. Detection of nonpalpable enlargement of bilateral neck and supraclavicular lymph nodes, flat abdomen, no gastrointestinal or peristaltic waves were observed. Soft abdominal muscles, mild tenderness in the upper abdomen and no obvious rebound pain were reported. His liver and spleen did not touch under the rib and no palpable mass was discovered. Negative for shifting dullness, normal bowel sounds and no abnormal of rectal examination were detected. The gastroscope suggested visible ulcer lesions at the cardiac involving gastric fundus and gastric body. The pathological results indicated adenocarcinoma. His admission diagnoses were gastric cancer and hypertension.
On admission, the auxiliary examination were carried out on Oct. 9, 2016. Laparoscopy indicated he was in the late stage tumors without radical resection. He then received intravenous and intraperitoneal chemotherapy, followed by severe bone marrow suppression with blood cells and platelets significantly lower than normal. He was given further treatment of anti infection, nutritional support, rehydration, stimulating granulopoiesis and symptomatic treatment. On Oct. 26, 2016, patients had shortness of breath, heart rate and other symptoms with lung breath sounds rough, and no rales, limbs cold. He was considered the existence of septic shock. He was given non-invasive mechanical ventilation and fluid expansion, colloid, blood transfusion products, anti infection (1 g of imipenem was administrated every 8 h for 7 days), maintain circulation, acid suppression, liver protection, nutritional support, maintenance of water and electrolyte acid-base balance, monitoring blood pressure, heart rate, respiratory function, hour urine volume and bleeding. Patient had severe infection, and the presence of multiple organ dysfunction syndrome (breathing, circulation, gastrointestinal, blood and kidney). Patient and his family members required automatic discharge for hospice care. His discharge diagnoses were multiple organ dysfunction syndrome (respiratory, circulatory, gastrointestinal, blood and kidney), gastric cancer and hypertension.
After appearing septic shock, his blood culture was sampled to separate the bacteria. The microbial growth was detected in both anaerobic and aerobic bottles and the positive reported time were 8.1 and 11.9 h, respectively. Both bottles yielded an uniform Gram-negative bacillus. After 24 h incubation, haemolytic, oxidase-positive yellow colonies grew on blood agar. The strain was identified as S. putrefaciens by VITEK 2 system using the ID-GN card (boiMérieux). The 16S rRNA gene sequence of the strain had been deposited at GenBank (accession number: MF589234). BLAST analysis at GenBank showed a similarity of 100.0% with S. upenei strain VITVAGJ (accession numbers KP090164.1). Further phylogenetic analysis with all type sequences of Shewanella species available in the GenBank database, confirmed the strain belonged to species of S. upenei (LC2016–5 in Fig. ). On the day of blood sampling, his peritoneal drainage fluid was also collected and cultured using the same identification methods, and the results of bacterial identification and drug sensitivity were consistent with that of blood.
Antibiotic susceptibility testing was performed by microdilution method on Mueller-Hinton broth. The strain was susceptible to aztreonam (1 μg/ml), ceftazidime (1 μg/ml), cefepime (1 μg/ml), amikacin (2 μg/ml), gentamicin (1 μg/ml) and levofloxacin (1 μg/ml), but was intermediate to imipenem (8 μg/ml), piperacillin/tazobactam (64 μg/ml) and ciprofloxacin (2 μg/ml). |
pmc-6125953-1 | A 14-year-old Chinese Malaysian boy presented to University Malaya Medical Centre, Kuala Lumpur in September 2013 with history of recurrent pneumonia, poor growth and steatorrhoea since childhood. He had finger clubbing and bronchiectasis. Later, he was diagnosed with CF and Pseudomonas aeruginosa was isolated from his sputum. He received 3 weeks of intravenous ceftazidime (50 mg/kg/dose, QDS) and gentamicin (5 mg/kg/dose, OD). He was discharged with azithromycin (5 mg/kg EOD), nebulised gentamicin (80 mg BD) amongst other CF-related medications. In November 2013, he was readmitted with a pulmonary exacerbation and his sputum sample grew methicillin-resistant Staphylococcus aureus (MRSA) and he received intravenous vancomycin, oral rifampicin (300 mg BD) and sodium fusidate (500 mg TDS) with significant clinical improvement. During a follow-up visit in December 2013, he had a productive cough but was apyrexic. He was empirically treated with oral ciprofloxacin (750 mg BD) and the sputum sample later isolated B.pseudomallei. As he clinically improved, the treatment regimen remained unchanged. Subsequently, the repeat sputum samples were negative for B.pseudomallei and he continued to remain active with good exercise tolerance and relatively stable lung function. It is noteworthy that he had been residing in an urban area of non-endemicity for melioidosis and there were no other known risk factors identified.
In August 2014, he was admitted with another pulmonary exacerbation and his cultured sputum grew B.pseudomallei and Pseudomonas spp. His chest radiograph showed diffused interstitial changes with bronchiectasis throughout both lungs with minimal pleural effusions. He received 2 weeks of intravenous ceftazidime (2 g; 6hourly) and amikacin (720 mg; 15 mg/kg/OD). Upon completion of antibiotics, he remained afebrile and the chest auscultatory findings improved. He was discharged with 6 months of oral doxycycline, and co-trimoxazole to treat the B.pseudomallei and 3 months of nebulized amikacin for chronic P.aeruginosa. He still continued on his alternate day of azithromycin (250 mg).
A detailed travel history revealed that in June 2014, he visited recreational parks in Sabah, Malaysia. During the visit, he went jungle trekking, snorkeling and dipped in a hot-water spring. It is noteworthy that melioidosis is endemic in Sabah, one of the two East Malaysian states on the island of Borneo, where B.pseudomallei prominently occurs in soil and water. Later then, he was admitted 3 monthly for antibiotic tuning and his sputum culture had no specific bacterial growth.
In August 2015, there was a decline in his lung function tests with deterioriorating cough. A bronchoscopy was performed and Burkholderia cepacia was isolated from his bronchoalveoloar lavage specimen, while acid-fast bacillus (AFB) smear was weakly positive. Initially, the patient was treated with intravenous imipenem and ceftazidime for 3 weeks but had recurrence of fever. However, the sputum AFB smears remained positive although the suspected nontuberculous mycobacterium could not be isolated despite various culturing techniques. Therefore, the antibiotics were changed to intravenous meropenem, doxycycline, amikacin and oral clarithromycin to treat both the B.cepacia and the suspected nontuberculous mycobacterium.
Upon discharge, he had been continuing with amoxicillin-clavulanate and doxycycline for 6 months, which helped with weight gain and secretion reduction. Repeat AFB smear remained negative for the subsequent 5 months. However, in January 2016, further decline in his lung function was observed with worsening respiratory symptoms. A chest computed tomography showed worsening bronchiectasis, tree in bud appearance in the lung peripheries, patchy consolidation and several enlarged lymph nodes at the right paratracheal region (Fig. ). His sputum sample grew P.aeruginosa and was also strongly positive for AFB. Intravenous meropenem and ceftazidime (for P.aeruginosa) and combination therapy of rifampicin, ethambutol, azithromycin and nebulized amikacin (for nontuberculous mycobacterium) was started. He improved clinically and was discharged with the above oral medications for 6 months.
B.pseudomallei was isolated once again in April 2016 and he was treated with intravenous amoxicillin-clavulanate and ceftazidime for 3 weeks. He was then discharged with 6 months of oral amoxicillin-clavulanate. However, in May 2016, his antibiotics were changed to levofloxacin (750 mg) and clarithromycin (500 mg). Following that, for the next 8 months, his sputum sample continued to grow B.pseudomallei but was negative for AFB. Despite many admissions for intravenous antibiotics against B.pseudomallei, the patient passed away from end stage respiratory failure in February 2017. Bacteriological reports were reviewed, and over the 3 years, the patient had several infective exacerbations and his sputum samples grew Gram-negative organisms that were later identified to be B.pseudomallei, Pseudomonas spp., P.aeruginosa, or B.cepacia (Table ).
All the isolates were found to have different susceptibility patterns (resistant to co-trimoxazole; intermediate to doxycycline and susceptible to all other antibiotics). The B.pseudomallei isolated in 2013, 2014 and 2016 (UMC083, UMC 082 and UMC114, respectively), were also further confirmed as B.pseudomallei using API 20NE (Biomerieux, France), Ashdown agar and also an in-house polymerase chain reaction (PCR) using specific primers []. However, we were not able to obtain the B.pseudomallei isolated in 2017.
The isolates were characterized by multilocus sequence typing (MLST), a method of molecular subtyping that compares sequences of seven housekeeping genes [], and repetitive-element PCR (rep-PCR). It appeared that these isolates were of two different sequence type (ST); ST51 (UMC083 and UMC114), which is a common ST found widely in Malaysia, Thailand, Singapore, Hong Kong and China, and ST1644, (UMC082) a new ST. The STs were deposited in the B.pseudomallei MLST database (). |
pmc-6125993-1 | We report a 77-year-old Caucasian female who had presented to nephrology clinic with a history of multiple sclerosis in remission who was noted to have progressive weakness for 2 months prior to presentation. Suspicion for a multiple sclerosis flare was low since her electrolytes were grossly abnormal with a serum calcium of 13.7 mg/dL and a serum creatinine of 2 mg/dL on June 23, 2017, increased from baseline of 8 – 9 mg/dL (calcium) and 0.9 – 1.1 mg/dL (creatinine). Ionized calcium was measured at 1.54 mmol/L (reference range 1.09 – 1.29 mmol/L), confirming the hypercalcemia noted on chemistry. Patient had initially been taking cholecalciferol 2,000 units PO daily for osteoporosis prophylaxis which were stopped, but this failed to improve the serum calcium. Parathyroid hormone (PTH) was appropriately suppressed at low normal 18 – 21 pg/mL (reference range 11 – 51 pg/mL), PTH-related peptide was in range at 17 pg/mL (reference range 14 – 27 pg/mL) which was not consistent with hypercalcemia of malignancy. The patient had normal sodium and alkaline phosphatase values. Urinalysis showed only 1+ proteinuria and was otherwise normal, and the kidney ultrasound demonstrated normal kidney structure. 25-hydroxy vitamin D level was 28 – 37 ng/mL (reference range: 20 – 50 ng/mL), but 1,25-dihydroxy vitamin D levels remained elevated despite stopping any supplements and remained elevated for nearly 2 months. 1,25-dihydroxy vitamin D peak level was 158 pg/mL (reference range: 19.9 – 79.3 pg/mL) and remained elevated between 100 and 113 pg/mL despite stopping vitamin D supplements. Urine protein electrophoresis and serum electrophoresis were negative or an M-spike, immunofixation was only positive in serum with IgG-κ monoclonal being found. κ- and λ-light chains were only slightly skewed towards IgG-κ > IgG-λ with a ratio of 2.32, ruling out monoclonal gammopathy as the etiology for the hypercalcemia.
The patient’s hypercalcemia continued to cause acute kidney injury, her calcium reached 12.6 mg/dL, she was hospitalized where she was given IV fluids, furosemide, and pamidronate. A high resolution CT scan did not show any lymphadenopathy or pulmonary pathology (), and angiotensin-converting enzyme levels were elevated at 100 U/L and 102 U/L for 2 draws. After the aforementioned treatment, her serum calcium decreased to 10.5 mg/dL.
When her serum calcium increased to 11.8 mg/dL, she was given denosumab 120 mg formulation in the interim leading to the return of serum calcium to 10.5 mg/dL. Since infectious causes of granulomatous diseases, such as tuberculosis and fungal infections, were in the differential diagnosis corticosteroids were not given empirically. While the high level of angiotensin-converting enzyme suggested possible sarcoidosis, we considered the low specificity of the test to demand more definitive tissue diagnosis could be obtained. Thus, corticosteroids were deferred until definite diagnosis, and denosumab was prescribed in the interim to control hypercalcemia.
See for graphs of serum calcium, PTH, 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D, angiotensin-converting enzyme level, and serum creatinine levels. Mycobacterial serologies, coccidiomycosis, and other fungal serologies were negative as well.
It was during this time that granulomatous disease, specifically sarcoidosis was suspected. She underwent PET scan with findings of upper lobe predominant peri-bronchial wall thickening, diffuse lymphadenopathy and flourodeoxyglucose (FDG) uptake throughout pulmonary parenchyma. This was suggestive of a granulomatous process such as sarcoidosis. No other focus of FDG uptake in a pattern that suggests malignancy was found, and no splenic involvement was seen. See for PET scan image and findings.
When the patient’s creatinine increased to 2.58 mg/dL with a serum calcium of 11 mg/dL, the patient was admitted for definitive diagnostic procedures. Bone marrow biopsy and a transbronchial lymph node biopsy were obtained. The patient’s serum calcium and serum creatinine normalized with hydration and subcutaneous calcitonin injection. Biopsy results showed diffuse non-necrotizing/non-caseating granulomata in lung and bone marrow confirming diagnosis of systemic sarcoidosis. Cultures from lung biopsy were negative for mycobacteria, fungal elements, or bacteria. The sarcoidosis staging was rated at stage 0 according to lung imaging, but with a high enough burden of disease to cause significant hypercalcemia. Please see for details of biopsy findings and bone marrow biopsy results. The patient started 20 mg of prednisone after diagnosis with improvement of hypercalcemia down to serum calcium of 10.2 mg/dL. She is receiving 3 times weekly hydration with IV normal saline to help prevent dehydration which helped decrease serum creatinine to 1.58 mg/dL. The patient was not on TNFi (tumor necrosis factor) to suggest secondary sarcoidosis. Her multiple sclerosis was stable as well. She was started on plaquenil for maintenance treatment of the diagnosed sarcoidosis. |
pmc-6125994-1 | A 61-year-old man presented with pain, redness, floaters and decreased vision in his right eye for two days. It was diagnosed as anterior uveitis at a local clinic and treated with prednisolone acetate eye drops combined with intravenous drip of dexamethasone and cephalosporin for seven days. Two weeks later, the patient’s visual acuity decreased to light perception, so he was referred to us eighteen days after his initial onset of symptoms. The patient had no previous history of systemic diseases or infectious diseases, no trauma or surgery before, no chronic medication used. He had a history of heavy drinking and chronic peptic discomfort, and he had been diagnosed suffering from peptic ulcer by agastroscopytwo weeks prior to the onset of symptoms. He had loss of appetite after abstinence from alcohol and reduced 15 kg of weight during the previous one month.
At presentation, vision was light perception in the right eye and 6/6 in the left. The slit-lamp examination of the right eye revealed mild injection, anterior chamber cells of 2+ with a hypopyon of 1.4 mm, pupillary hypopyon, posterior iris synechia, and fibrinous exudates covering the anterior lens capsule (Fig. ). Fundus of the right eye was invisible due to the vitreous opacity and the left eye was normal. Intraocular pressure was normal in both the eyes. The color ultrasound examination revealed dense vitreous opacities and a avascular homogeneous hyperechoic mass (Fig. ).
The vital parameters were in normal range, with the blood pressure of 132/80 mmHg, pulse 76/min and a temperature of 36.7° Celsius. Physical examination did not show any abnormalities. Systemic investigations including blood routine examination, liver and renal function tests, computed tomography scan of the lung and abdominal were all unremarkable. Serologic tests that included human immunodeficiency virus antibody, antibodies for toxoplasma, varicella zoster virus, herpes simplex virus and the treponemal antibody-absorption test yielded negative results. Laboratory result for fasting blood glucose was 9.07 mmol/l (normal range: 3.88~ 6.1). The patient was diagnosed as diabetes mellitus after many blood glucose tests and was treated with Metformin. No specific site of systemic infection was found. Presumptive diagnosis of right EE was made, but intraocular lymphoma could not be ruled out.
Vitreous and anterior chamber taps of the right eye were performed, aqueous and vitreous aspirations were sent for cultures and histopathology examination. The patient was treated with intravitreal injection of vancomycin 1 mg/0.1 ml and ceftazidime 2 mg/0.1 ml, topical levofloxacin 0.5% and prednisolone 1% acetate eye drops six times a day, atropine 1%ointment at night in the right eye, concurrent with intravenous drip of cefoperazone.
Three days after the intravitreal injection, the results of vitreous samples cultures and histopathology examination were all negative. The anterior chamber inflammation improved, and fundus of the right eye was still invisible. B-scan ultrasound showed increased vitreous debris and extensive thickening of the retina and choroid layer. Therefore, a pars plana vitrectomy (PPV) combined with phacoemulsification was performed. After a complete vitrectomy, a white elevated fluffy mass with the overlying retinal whitening and necrosis was revealed in superior periphery (Fig. ). In addition to this, extensive retinal hemorrhages and five adjacent subretinal whitish masses with exudative retinal detachment were observed in the posterior pole and inferior quadrants which were suggestive of extensive subretinal abscess with intense overlying retinal inflammation (Fig. ). Intraoperatively, we carefully cleared the white fluffy mass in superior and peripheral vitreous without retinal break formation. A white fluffy cotton-like substance was excised from the superior mass (Fig. ) and finally left a 4-disc diameter retinal defect (Fig. ). The vitreous and cotton-like substance were sent for culture, histopathology examination, and polymerase chain reaction (PCR) testing. Retinotomy and aspiration of extensive subretinal abscess in the posterior pole and inferior were not performed. Laser photocoagulation around the retinal defect site and gas or oil intraocular tamponade were not performed either. No intravitreal or intravenous antibiotics were used for we were not sure if the infection arose from fungal, bacterial, mycobacterial or a different aetiology. Post-operative administration remained topical levofloxacin 0.5%, prednisolone 1% acetate eye drops six times a day and atropine 1% ointment once a day.
On post-operative day 1, slit-lamp examination showed anterior segment moderate inflammatory reaction and no posterior segment view because of vitreous opacities. B-scan ultrasound of the right eye showed vitreous opacities and an extensive retinal detachment with sub-retinal exudates (Fig. ). On post-operative day 4, the inflammatory reaction subsided significantly and the media started clearing. A blurry fundus was observed. B-scan ultrasound showed slight vitreous opacities and shallow retinal detachment (Fig. ). The result of vitreous samples PCR was positive for Klebsiella pneumonia (KP). The results of cultures and histopathological examination were again negative. Clinical examination along with PCR testing confirmed the diagnosis of EE caused by KP. An intravitreal injection of ceftazidime 2 mg/0.1 ml on the right eye was performed. On post-operative day 9, the anterior chamber and vitreous cavity were clear, the retina reattached with lots of yellowish subretinal precipitates and a scar at the superior region (Fig. ). B-scan ultrasound showed retina reattached except localized shallow retinal detachment (Fig. ). Corrected visual acuity improved to hand motions and intraocular pressure was normal. Intravitreal injection of ceftazidime 2 mg/0.1 ml was repeated in the right eye. The patient was discharged for follow-up as an outpatient with levofloxacin 0.5% and prednisolone 1% acetate eye drops administered topically for one week. He was in a stable condition at subsequent visit two months later. Fundus and B-scan ultrasound examination revealed the retina remained attached with some yellowish subretinal precipitates, a large fibrotic scar superiorly, an epiretinal membrane presented in the posterior pole (Fig. ). At eight months, his eye remained quiescent with a corrected visual acuity of hand motions. |
pmc-6126002-1 | A 55-year-old woman suddenly became aware of speech difficulty and left arm numbness at 11:00 pm while talking on the telephone with her daughter. She was taken to our hospital by ambulance. She was diagnosed with RA 6 months earlier, and she had been treated with methotrexate at a dose of 10 mg daily. She had a history of herpes simplex encephalitis from 30 years earlier. Her blood pressure was 155/80 mmHg, pulse rate was 80/min and regular, and temperature was 36.8 °C. ECG was normal. Her Glasgow coma scale was E4 V4 M6, and neurological examination demonstrated dysarthria, left hemiparesis, left-sided sensory impairment, and left unilateral spatial neglect. The National Institutes of Health Stroke Scale (NIHSS) score was 5. Head computed tomography (CT) showed no obvious lesions except effacement of the cortical sulci in the right parietal lobe, and the Alberta Stroke Program Early CT Score (ASPECTS), a 10-point quantitative topographic CT scan score, was 8. No arterial occlusion or stenosis was seen on CT angiography (Fig. ). Blood tests showed a platelet count of 274 × 103/μl, prothrombin time International Normalized Ratio (PT-INR) of 1.07, and activated partial thromboplastin time (APTT) of 25.6 s (APTT-control 31.0 s). She was diagnosed with acute embolic stroke in the right parietal lobe, and there was no contraindication to intravenous thrombolytic therapy. At 4 h 6 min after onset, intravenous administration of rt-PA was started in accordance with the Japanese guideline (alteplase, 0.6 mg/kg) [, ], with an intravenous drip infusion of 30 mg of edaravone, a free radical scavenger, over a period of 30 min. Head magnetic resonance imaging (MRI) was performed at 1 h, 30 min after starting the thrombolytic therapy (Fig. ). Diffusion-weighted imaging (DWI) demonstrated a linear high-intensity lesion in the right temporoparietal cortex. The lesion was demonstrated to be a hypodense linear lesion on the apparent diffusion coefficient (ADC) map image. This cortical lesion was seen as a high-intensity lesion on fluid-attenuated inversion recovery (FLAIR) imaging. These MRI findings were not compatible with acute ischemic stroke. Her neurological deficits improved rapidly (NIHSS score: 5 on admission, 1 at 24 h after thrombolytic therapy).
Contrast-enhanced head MRI performed on hospital day 3 found that the high signals on DWI had disappeared. However, the FLAIR image showed ribbon-like high signals in the cerebral cortex, and no contrast effect was observed (Fig. ). In subsequent additional tests, rheumatoid factor (RF) was 85 IU/L and anti-cyclic citrullinated peptide (CCP) antibody was elevated at 223.7 U/mL, while myeloperoxidase-anti-neutrophil cytoplasmic antibodies (MPO-ANCA) and proteinase-3-anti-neutrophil cytoplasmic antibodies (PR3-ANCA) were negative. Lumbar puncture showed a cell count of 68/μL (monocytes 14, polynuclear cells 54), protein 40 mg/dL, and glucose 52 mg/dL. Single photon emission computed tomography (SPECT) performed on day 6 showed decreased accumulation in the right temporoparietal region. Spinal fluid testing performed on day 10 showed an elevated interleukin-6 (IL-6) of 271 pg/mL, but anti-CCP antibody was normal at 3.7 U/mL. Because of the elevated cerebrospinal fluid cell count and the patient’s history of herpes encephalitis, she was temporarily treated with a continuous intravenous infusion of acyclovir 1500 mg/day until the polymerase chain reaction test was confirmed to be negative. The patient was finally diagnosed with RMSA. On day 16, continuous infusion of methylprednisolone 1000 mg daily was started for 3 days, and it was repeated on day 28. Her symptoms then gradually resolved, and the high signal on the FLAIR image also disappeared. The patient was discharged on day 44 with only a slight attention deficit on neurological examination. |
pmc-6126020-1 | Our patient was a 47 year old female with a history of ulcerative colitis, Sjogren’s syndrome, migraines, and fibromyalgia who presented with a 6 month history of left lower extremity paresthesia followed by a 2 month history of progressive headaches, imbalance, ataxia, nausea, vomiting, and diplopia. Neurologic examination revealed severe gait ataxia requiring assistance to stand or walk and nystagmus with lateral gaze. MRI revealed a 3.0 cm heterogeneously enhancing mixed cystic and solid mass centered upon the cerebellar vermis with mild surrounding vasogenic edema and abnormal thickened enhancement of the bilateral vestibular nerves, left facial nerve, and right trigeminal nerve (Fig. ).
The patient was promptly started on steroids, admitted to the hospital, and underwent a midline suboccipital craniotomy for debulking of the large intracerebellar tumor. Upon entering the cystic cavity, grossly purulent material without hemorrhage was noted. Gram stain and cultures were negative for infection. A subtotal resection was achieved and final pathology rendered the diagnosis of primary CNS histiocytic sarcoma (see Fig. ). The H&E section (Fig. ) revealed sheets of large neoplastic cells with marked cytological atypia, brisk mitosis with occasional multilobated nuclei, and focal necrosis. Extensive immunohistochemical studies (Fig. ) showed the neoplastic cells positive for CD163, CD68, CD45, and Vimentin; negative for CD20, CD3, CD30, s-100, CD1a, CD21, CD23, pancytokeratin, MPO, CD61, CD123, GFAP, and BRAF. Further immunostains for PD-L1 with two different antibody clones (22C3 and 28–8) were also performed and showed more than 50% of the tumor cells were positive with membrane stain (Fig. ).
Post-operative MRI showed a midline posterior occipital craniotomy with subtotal resection of tumor and continued bilateral-enhancement along multiple cranial nerves, concerning for leptomeningeal spread (Fig. ).
A staging PET scan was performed two weeks following surgery suggesting diffuse leptomeningeal spread. A complete spinal MRI confirmed diffuse leptomeningeal spread in the lower thoracic and lumbar spine as well as cauda equina involvement. Due to the convincing evidence on MRI, a CSF analysis was deferred. Standard lab work was within limits, including LDH (Fig. ).
Three weeks following surgery, due to progressive lower back pain, she initiated radiation therapy including whole brain radiotherapy (30.6 Gy in 17 fractions) followed by a posterior fossa boost (5.4 Gy in 3 fractions) and a gross tumor boost (9 Gy in 5 fractions), for a total dose of 45 Gy in 25 fractions to gross disease with simultaneous radiation therapy to the lower thoracic and lumbar spine, receiving 40 Gy in 20 fractions, encompassing the areas of leptomeningeal disease in the spine and cauda equina. Full craniospinal radiotherapy was not performed to limit profound cytopenias that may have prevented further cytotoxic chemotherapy.
Interval follow up MRI showed a partial response with persistent posterior fossa disease but near complete resolution of previous leptomeningeal enhancement. Our plan was to initiate chemotherapy with a primary CNS lymphoma regimen with high CNS penetrating therapeutic agents including high-dose methotrexate, high-dose Ara-C, and thiotepa followed by high-dose chemotherapy with BCNU and thiotepa rescued by autologous stem cell transplantation. The patient was started on high dose intravenous methotrexate (HD-MTX) therapy, but received only one cycle secondary to patient intolerance.
A CT of the chest approximately two weeks after initiation of HD-MTX therapy for left sided rib pain showed new pulmonary nodules and a left sided pleural effusion, suspicious for metastatic disease. Thoracentesis revealed findings consistent with a malignant pleural effusion. The patient was initiated on cladribine (Leustatin).
Within two weeks after the completion of this infusion, the patient developed headaches, somnolence, fever, and nuchal rigidity. Malignant meningitis was suspected and the patient was started on IV antibiotics. Lumbar puncture was recommended but the patient declined. Her mental status significantly improved following antibiotic treatment. Brain MRI showed continued response of the cerebellar residual disease and no new intra-cranial lesions, but an MRI of the cervical spine showed new lesions consistent with metastatic disease in the untreated cervical spinal cord and thoracic vertebrae, including intramedullary involvement. She underwent further radiation therapy targeting C4-C6 and T1-T7 (20 Gy in 5 fractions). The patient rapidly showed improvement in symptoms.
Genomic sequencing of her tumor showed a novel mutation in the platelet-derived growth factor receptor A (p.V608I) and therefore, she was started on Dasatinib, a tyrosine kinase inhibitor (TKI) with known CNS penetration []. Unfortunately, this medication was poorly tolerated because of nausea, diarrhea, and acute pancreatitis so it was discontinued after one week.
The patient was readmitted to the hospital for continued decline in functional status, weakness, and failure to thrive. CT images of the chest, abdomen, and pelvis showed progressive bilateral pulmonary nodules. An MRI of the spine showed persistent but significantly improved leptomeningeal enhancement. Due to progression of symptoms, worsening systemic disease despite control of CNS disease, and limited systemic options available, the patient chose to enroll in hospice. The patient expired four weeks later, eight months after initial diagnosis. |
pmc-6126034-1 | A 9-day-old Caucasian boy was referred to our department of ophthalmology for bilateral buphtalmia and corneal haze. He was born at term, by spontaneous delivery, of non-consanguineous parents, with no significant personal or family medical history, except a keratoconus in his older brother.
Clinical examination showed no dysmorphic facies, but bilateral megalocornea and buphtalmia, associated with photophobia. Right eye (OD) examination revealed nasal corneal clouding, deep anterior chamber and normal crystalline lens. Funduscopic examination confirmed optic disc cup (cup-to-disc ratio: 0.4) without any vitreous or retinal hemorrhages. Left eye (OS) examination disclosed an epiphora, associated with major corneal edema, deep anterior chamber and normal crystalline lens. Funduscopic examination showed optic disc cup (cup-to-disc ratio: 0.7). Detailed examination under inhalational anesthesia was performed urgently and demonstrated corneal asymmetry up to 1.5 mm (horizontal corneal diameter: 11.5 mm OD and 13 mm OS) and increased axial length in the left eye (axial length: 18.5 mm OD and 19.21 mm OS). The pachymetry showed central corneal thickness of 863 μm OD and 927 μm OS. The IOP (measured with Perkins MK2 tonometer, Haag-Streit, UK) was 22 mmHg OD and 26 mmHg OS. Gonioscopy showed an open angle with normal trabecular meshwork pigmentation in both eyes. Findings included the absence of angle recess and flat iris insertion. There was no peripheral anterior synechiae or embryotoxon (Table ).
A non-penetrating deep sclerectomy with trabeculotomy was firstly performed in the left eye under general anesthesia.
The surgical procedure started with a corneal traction suture temporally and nasally. This is followed by a conjunctival incision and localized tenectomy in the superior quadrant. A pentagonal scleral flap was created of 5 × 4 mm, half the scleral thickness, and dissection was carried forward 2 mm into clear cornea. We used mitomycin C, 0.4 mg/ml for two minutes, followed by careful irrigation. After this, a deep triangular scleral flap was marked, 4 × 4 × 2 mm, and dissection was performed forward until the level of Descemet’s membrane. The inner wall of Schlemm’s canal and the juxtacanalicular trabeculum were peeled off using toothed forceps (25-gauge Eckardt End-gripping Forceps, Dutch Ophthalmic, USA) without perforation of the trabeculodescemetic membrane. Then, a trabeculotomy was made, using the trabeculotome handpiece (Bausch & Lomb E0421 Harms Trabeculotome Set 1.8″ Left Right Ophthalmic, USA). The two third of the trabeculotome length were introduced into Schlemm’s canal to treat, nasally and temporally, an average of 70 degrees of the angle. A space maintainer (cylindrical collagen implant; Aquaflow®, Staar Surgical, Monrovia, CA, USA) was inserted in the scleral bed to prevent collapse of the superficial flap and secured with a single 10/0 Ethilon suture. Closure of the scleral flap and the conjunctiva was done by 10/0 Ethilon sutures and 10/0 Vicryl reabsorbable sutures respectively. The procedure was completed by subconjunctival injection of betamethasone (0,1 ml).
The same surgical protocol was performed in the right eye one week after. Postoperative treatment included antibiotic (tobramycin) and steroid (dexamethasone) eye drops, 6 times a day, during one week, followed by gradual reduction of the steroids over a period of 8 weeks and reduction of antibiotic dose.
One week postoperatively, the IOP was 11 mmHg OD and 7 mmHg OS. The anterior chamber and the bleb were well-formed in both eyes (Table ). Fundoscopy exhibited a well-circumscribed, crab claw-shaped hemorrhage, corresponding to a pre-macular subhyaloid hemorrhage in the right eye, resulting in an artificially decrease of the OD axial length (Fig. ). Fundus examination of the left eye was unremarkable. Complete blood coagulation analysis was performed and revealed no significant anomaly, excepted moderate polycythemia (hemoglobin: 22.8 g/dL). The patient had no incident of coughing or sneezing postoperatively. A suspected diagnosis of decompression retinopathy was proposed. Close observation was firstly decided. Three weeks after initial surgery, as there was no improvement in subhyaloid hemorrhage, pars plana vitrectomy (25-gauge Stellaris PC System, Bausch & Lomb, Rochester, NY, USA) of the right eye was performed, allowing a complete resolution without any recurrence.
Three years after initial surgery, the IOP remained controlled in the normal range for both eyes, with reversal of optic disc cupping (c/d 0.1 OD and c/d 0.1 OS). A relevant finding was the onset of high myopia in the OD requiring refractive correction (Table ). |
pmc-6126040-1 | A 48-year-old female patient underwent her first work-up for possible liver disease 30 years ago. Based on findings of chronic active hepatitis in liver biopsy, autoimmune hepatitis was suspected, and treatment with prednisolone and azathioprine initiated. Seven years later, an endoscopic retrograde cholangiopancreatography (ERCP) showed a stricture in the common bile duct which was interpreted as possible extrahepatic PSC or tentatively an inborn anomaly of the common bile duct. After 20 years with fluctuating transaminases between 100 and 300 U/L and no recorded major clinical events, she developed general edema and thoracic spider nevi. A computed tomography (CT) scan revealed liver cirrhosis and portal hypertension with massive ascites. After an initial response to symptomatic treatment, she soon developed uncompensated liver failure with severe hepatic encephalopathy and was transferred to the national transplant unit for work-up and listing for liver transplantation. A few days later, an ABO-identical donor liver was available and LTX was performed with a duct-to-duct biliary anastomosis. The histopathological examination of the liver explant revealed cirrhosis and pathological changes typical for underlying PSC. Cholangiocarcinoma in situ was found in the common hepatic duct, the cystic duct, and the common bile duct, involving the resection margin. It was decided that the patient should be controlled with ERC with brush cytology from the duct-to-duct anastomosis after 6 months due to the histopathological findings. The brush cytology showed mild to moderate epithelial dysplasia in the common bile duct. After discussion in the multidisciplinary team, a pancreaticoduodenectomy (Whipple procedure) was decided due to the risk of development of cholangiocarcinoma. Ten months after LTX, the procedure was performed. Because of a possible increased risk of anastomotic leak due to immunosuppression, an enteropancreatic anastomosis was avoided and the pancreatic duct was occluded. The surgical specimen showed intestinal metaplasia in the common bile duct, but no dysplasia or carcinoma. She was then followed according to standard post-liver transplantation follow-up regimen. The patient developed insulin-dependent diabetes mellitus and received tuberculostatic treatment due to disseminated tuberculosis (pulmonary and meningeal), but the graft function remained good. At the 5-year post-transplantation control, recurrent PSC in the graft was diagnosed on liver biopsy. In addition, a 10 × 4 cm multicystic mass in the lower right abdominal quadrant was described on the routine abdominal ultrasound (US) exam. Upon reassessment, a CT scan of the abdomen performed before the Whipple procedure also showed a 10 × 5 cm multicystic mass in the same region. The lesion was asymptomatic, and based on imaging, the lesion was considered to be a benign gynecological cyst. Consequently, no further investigations were performed to establish the exact etiology. At 10 years of follow-up, the patient reported increasing abdominal distension, anorexia, weight loss, and fatigue for the past 6 to 8 months. Clinical examination revealed extensive sarcopenia, multiple spider nevi, and tense ascites. Biochemical tests showed an iron deficiency anemia with Hgb of 9.0 g/dL, moderately elevated liver function tests, inflammatory markers, and carcinoembryonic antigen (CEA). Imaging, including liver and abdominal US, abdominal and thoracic CT, CT enterography, and positron emission tomography (PET)-CT unveiled liver graft fibrosis/cirrhosis with features of portal hypertension, massive low-attenuating heterogeneous ascites, a focal wall thickening in the middle part of the jejunum, multiple focal lesions in both lungs, a focal lesion in the thyroid gland, and the previously described cystic mass in the lower right abdominal quadrant. Diagnostic abdominal paracentesis revealed thick gelatinous ascites, which was culture negative. The ascites was rich in mucin, but without neoplastic cells on repeated cytology examinations. The provisional primary diagnosis of graft fibrosis-related portal hypertension with ascites could not be supported. Further extensive diagnostic work-up did not confirm tentative diagnoses such as gastrointestinal tuberculosis, sarcoidosis, mucinous tumors of the ovaries, or other causes of peritoneal carcinomatosis. Bearing in mind the differential diagnosis of PMP as a rare, but relevant tentative cause of mucinous ascites, re-evaluation of the contrast-enhanced CT scan raised the suspicion of PMP and that the cystic lesion actually represented a mucinous cystadenoma of the appendix (Fig. ).
The multidisciplinary team initially turned down cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for the patient due to concerns of the magnitude of the disease with the risk of harming the graft during the procedure. However, after a renewed assessment, the patient was accepted for explorative laparotomy and potentially CRS-HIPEC. Perioperatively, the peritoneal cancer index (PCI) was estimated to 28 of 39 and it was found that CRS-HIPEC was technically doable and meaningful. The operation time was approximately 11 h. Surgery included removal of considerable amounts of mucinous masses, extensive peritonectomy including the right hemidiaphragm, part of the left hemidiaphragm and the pelvis, omentectomy, hysterectomy, bilateral salpingo-oophorectomy, ileocaecal resection, splenectomy, and removal of the umbilicus. Minimal mucinous masses in relation to the piggyback anastomosis to the inferior caval vein were left due to safety reasons. HIPEC was then performed with mitomycin C for 90 min. The histopathological examination showed perforated low-grade appendiceal mucinous neoplasm and wide-spread mucin without viable tumor cells in all abdominal specimens, compatible with PMP. Forty-two days after surgery, the patient was readmitted with urinary tract infection, anemia, high glucose levels, reversible kidney failure, weight loss, and malnutrition. She recovered on antibiotics and supportive treatment and received follow-up by nutritionists after discharge. Two months after surgery, she had started regaining weight and transplant control displayed satisfactory graft circulation and function (Fig. ). |
pmc-6126067-1 | An 88-year-old man, BMI 24, presented to the clinic with complaints of pain and a cracking sensation in his right hip, nine years post primary right THA. His previous medical history was significant for coronary artery disease, myocardial infarction, hypertension, chronic kidney disease, and gastroesophageal reflux disease. His medications included aspirin, metoprolol, ramipril, simvastatin, and ranitidine.
During the initial procedure, the primary components utilized an Accolade #3 stem with a 127-degree neck-shaft angle and +5 36 mm L-fit head. Postoperative course for this patient was uncomplicated. After routine follow-up, at the one-year postoperative mark, the patient was subsequently lost to follow-up. Nine years after the index procedure, the patient returned to the clinic complaining of pain and “cracking” in the right hip for approximately six months. The patient denied any history of injury as well as any subjective infectious symptoms. Radiographic images of the right hip showed an apparent trunnion fracture with significant asymmetric wear of the polyethylene liner within the acetabular component ().
Preoperative bloodwork revealed normal leukocytes and normal-range C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Thus, the patient was consented for revision THA for a presumed trunnion fracture.
Intraoperative assessment revealed marked heterotopic ossification along the greater trochanter of the right femur, extending into the gluteus maximus, which was excised and debrided thoroughly. Though the femoral head was intact and showed no gross signs of wear (), there was complete dissociation from the femoral stem. There were also significant signs of metallosis with metal-stained debris and granulation tissue (), which extended deep to the margins surrounding the acetabular shell. Interestingly, the femoral stem demonstrated significant medial trunnion wear (see Figures and ), though no true trunnion fracture was noted, contrary to the initial preoperative radiographic assessment. Stem removal was facilitated by an extended trochanteric osteotomy, and definitive reconstruction was performed with a long cementless femoral stem and Luque wire fixation of the osteotomy. Intraoperative assessment demonstrated a stable final construct (Figures and ). The patient had an uneventful postoperative recovery and at the time of the 6-week follow-up had completed his outpatient rehab protocol with excellent effect. |
pmc-6126070-1 | A 76-year-old man was electively admitted for intervention and management of severe symptomatic aortic stenosis resulting in worsening New York Heart Association Class III cardiac failure. His medical history included stage III chronic kidney disease, type 2 diabetes mellitus, hypertension, and prior coronary artery bypass grafting. Coronary angiography demonstrated a patent left internal mammary artery graft to the left anterior descending coronary artery and a saphenous vein graft to the dominant distal left circumflex artery with a severe stenosis distal to the surgical anastomosis.
Transthoracic echocardiography was performed and showed a thickened and calcified aortic valve with reduced cusp excursion, mild concentric left ventricular hypertrophy with normal left ventricular cavity size, and systolic function. The left atrium was severely dilated. Left ventricular ejection fraction was above 55%. Valve area was estimated at 0.8 cm2, with a measured mean gradient of 44 mmHg.
A cardiac conference was held to discuss intervention for his severe aortic stenosis. TAVI was chosen in preference to a redo sternotomy in the setting of the Society of Thoracic Surgeons score of 5.8% (intermediate risk cardiac surgery), stable coronary artery disease, and in accordance with the patient's preference.
The preoperative electrocardiogram (ECG) showed sinus rhythm with a narrow QRS complex (). Using a right femoral approach, a CoreValve Evolut R 29 mm (Medtronic, Minneapolis, Minnesota) transcatheter aortic valve was deployed after balloon aortic valvuloplasty with an 18 mm Cristal balloon. TAVI was uneventful. Postdilatation was performed using a 23 mm Cristal balloon due to moderate paravalvular aortic regurgitation around the left coronary cusp seen on a postprocedure transoesophageal echocardiogram. At the time of TAVI, the patient developed LBBB (average QRS duration of 180 ms) with a prolonged PR interval of 240 ms (). Within the first 24 hours post-TAVI, he also had episodes of high-grade AV block.
A dual-lead Boston Scientific Accolade™ Extended Life DR Pacemaker was implanted via the left cephalic vein (). The HV interval was mildly prolonged at 60 ms. Proximal His capture (selective) threshold was less than 1 V without recruitment of the left bundle branch; RV myocardial capture threshold was 1.5 V at 1 ms; correction of LBBB—due to the presumed capture of distal His bundle and recruitment of the left bundle branch—occurred at 4.5-5 V at 1 ms. A Medtronic 5076 lead was then placed in the right atrial appendage with a threshold less than 1 V. The device was programmed DDD 50. The paced QRS duration on 12 lead ECG was 125 ms consistent with nonselective HBP (para-Hisian morphology) (). At 1 month, 12 lead electrocardiogram tracing showed continued correction of LBBB at 5 V @ 1 ms. |
pmc-6126075-1 | A 49-year-old man sustained a tibial shaft spiral fracture (AO/OTA classification 42-A2) with a fibular fracture (). He had no previous medical history. The fracture was treated initially at another hospital with a reamed statically locked intramedullary nail (). He noted increased external rotation of the affected leg immediately after the surgery. The tibial fracture united after a year (), but he still complained of the asymmetry of his legs, difficulty walking and running, and inability to ride a bicycle. Computed tomography (CT) of both tibias showed 24° of increased external rotation of the affected leg (Figures , ). Because it was a symptomatic rotational deformity, we decided to perform corrective osteotomy in a minimally invasive fashion.
The surgical procedure consisted of, first, a 1 cm skin incision at the original fracture site. Multiple efforts were then made to drill around the nail in a radial manner (leaving the nail in place) while using a 3.0 mm Kirschner wire to prepare a percutaneous osteotomy line. Osteotomy for the affected tibia was performed percutaneously using an osteotome on the prepared osteotomy line while retaining the intramedullary nail (). Fibular osteotomy was also done at the same level. Next, two 3.0 mm Kirschner wires, which created a 24° rotational angle in the axial plane between the bone fragments, were inserted as guides for correction (). The distal locking screws were then removed. After matching the two Kirschner wires in a straight line, correct rotation was confirmed (). We assessed the rotational correction intraoperatively to evaluate both sides of the thigh-foot angle [, ]. Finally, the distal three locking screws were inserted into holes different from the original hole (). At 1 year postoperatively, the patient obtained bony union and has returned to his preinjury activities with no symptoms. The implant was removed 1 year postoperatively on the patient's demand. The appropriate correction of the rotational deformity was confirmed on a CT scan (). Postoperative follow-up was continued until 5 years after the corrective osteotomy (). The patient was still free from any symptoms and had full range of hip, knee, and ankle motion. |
pmc-6126077-1 | A 19-year-old young male patient presented to our clinic with sudden vision loss in his right eye 2 weeks after push-up and sit-up exercise. He was admitted to another centre before; he was told that he had haemorrhage in his eye and was advised only follow-up. He had no history of trauma, ocular, or systemic disease. His examination showed that his best corrected visual acuity (BCVA) was counting fingers from 1 meter distance in the right eye, 20/20 in the left eye. Anterior segment examination and intraocular pressure findings were unremarkable. Fundus examination of his right eye showed a well-circumscribed, elevated, and around 4 disc diameter (DD) premacular haemorrhage that extended from the upper vascular arcuate to the fovea. Colour fundus photography and fundus fluorescein angiography were performed. Spectral-domain optical coherence tomography (SD-OCT) revealed dome-shaped elevated lesion with a hyperreflective surface and hyporeflective area underneath (). It was suspected to be the combination of subhyaloid haemorrhage with wider localization and sub-ILM haemorrhage localized only in the fovea. Complete blood counts and biochemical and clotting parameter were ordered for Valsalva retinopathy and other causes of premacular haemorrhage for the differential diagnosis. Internal diseases clinic was consulted. After all the other evaluations, he was diagnosed with Valsalva retinopathy. Treatment options were explained to the patient. He preferred laser treatment.
Nd:YAG laser (VISULAS YAG III, Carl Zeiss Meditec AG, Jena, Germany) and Ocular Abraham Capsulotomy YAG Laser Lens were performed with a posterior approach. The initial energy of laser exposures was 1.9 mJ and then it was gradually increased until it was observed that a rapid stream of blood was trapped into the vitreous cavity. Laser energy was carefully shot onto the anterior surface and inferior margin of the haemorrhage away from the fovea and two openings were made.
At the first hour after the procedure, haemorrhage was resolved considerably (). During his follow-up 2 days later, the laser shot sites could be clearly observed and there were only peripherally localized sub-ILM haemorrhage sites. Although his fundus findings were observed to be resolved totally during his control at week 1, BCVA was counting fingers from 3 meter. SD-OCT revealed full-thickness macular hole (). He did not have a marked vision acuity at month 3 and his macular hole findings persisted (). At month 6, BCVA was 20/50, and his fundus examination showed that laser coagulation sites disappeared. SD-OCT revealed the macular hole was spontaneously closed and the normal foveal contour was reformed (). At month 12, the fundus examination and SD-OCT findings were stable, the final visual acuity was 20/32. |
pmc-6126084-1 | An 81-year-old male presented to the clinic with yellowish discoloration of skin and urine for 2 weeks. He denied any fever, abdominal pain, nausea, vomiting, melena, hematochezia, or acholic stools. Past medical history was significant for hypertension, hyperlipidemia, diabetes mellitus type II, coronary artery disease, and chronic kidney disease stage IV. He reported recent loss of appetite but denied any significant weight changes. Ultrasound ordered by primary care physician showed intra- and extra-hepatic biliary dilation with distension of gall bladder without cholelithiasis. He was sent to the emergency department (ED) for further evaluation.
On examination, blood pressure was 133/60 mmHg, heart rate was 75 beats per minute, respiratory rate was 23 breaths per minute, temperature was 97.7°F, and oxygen saturation was 98% in room air. He had mild icteric sclera, and chronic venous stasis changes in bilateral lower extremities were noted. Bowel sounds were normal, and no hepatosplenomegaly or abdominal tenderness was noted on exam.
Laboratory investigations showed a hemoglobin count of 11 g/dl, white blood cell count of (WBC) 3800 cell/mm3, and platelet count of 214,000/mm3. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were elevated at 326 and 321 IU/L, respectively. Total bilirubin was 3.1 mg/dl with direct bilirubin of 1.8 mg/dl. Alkaline phosphatase (ALP) was 1,219 IU/L with lipase 250 IU/L. Renal function tests were at baseline at 1.72 mg/dl (baseline 1.7–1.9 mg/dl). Recent upper and lower endoscopy (1 month earlier) did not show significant abnormalities, except for mild antral gastropathy. A computed tomography (CT) scan of abdomen and pelvis revealed stable pelvic adenopathy with largest lymph node measuring 4.4 × 1.7 cm (which was noted on the earlier CT scan as well). The pancreatic tissue and abdominal vessels appeared normal. With concern for underlying malignancy, a lymph node biopsy was performed. Endoscopic retrograde of cholangiopancreatography revealed distal common bile duct stricture of 3 cm without obstruction, for which a biliary stent was placed. No pancreatic lesions were observed, and biliary brushings were negative for malignancy.
The patient returned to the ED two months later; this time with a fever (102°F), nausea, and right upper quadrant pain for 2 days. Complete blood counts revealed elevated white cell count of 18,700/mm3. AST, ALT, and bilirubin levels were within normal limits, and ALP was elevated at 127 IU/L. The CT scan of abdomen revealed intrahepatic biliary ductal dilatation and gall bladder wall thickening with pericholecystic inflammatory stranding with normal pancreas (). He was started on broad-spectrum antibiotics with piperacillin-tazobactam. Urgent surgical decompression with percutaneous drain placement was performed for stent blockage (with re-stent placement) and bile duct stricture from unknown etiology.
Meanwhile, histopathology from the earlier right iliac lymph node biopsy revealed sinus histiocytic aggregates interlaced with lymphocytes and plasma cells (), majority of cellular constituents being plasma cells, characterized by oval cellular contours and eccentrically located nuclei (); this was confirmed by diffuse immunoreactivity for CD138 (). Chromogenic in situ hybridization for kappa light chain () and lambda light chain () showed a mixture of kappa and lambda-bearing cells (approximate kappa to lambda ratio of 3 : 1); this finding suggested that the plasma cells were reactive in nature, arguing against the possibility of a plasma cell neoplasm. In situ hybridization for EBV-encoded RNA (EBER) was interpreted as negative.
As there was no evidence to suggest a lymphoma or a plasma cell neoplasm, a diagnosis of IgG-related disease was considered. Additional immunohistochemistry showed that the plasma cells present expressed predominantly IgG (); of these, the majority (over 60%) were reactive for IgG4 (). Serum protein electrophoresis and immunofixation showed polyclonal increase in IgG with no monoclonal proteins. Serum immunoglobulin (Ig) G levels were high (3390 mg/dl) with normal IgA and IgM. IgG subclasses were also high with IgG1 of 1800, IgG2 975, IgG3 324, and IgG4 729 mg/dl.
A diagnosis of IgG4-related sclerosing cholangitis was made, and he was started on prednisone 40 mg daily for 6 weeks. A follow-up CT scan of abdomen after a month revealed significant reduction in the size of his pelvic lymph nodes with largest lymph node measuring 1.8 × 0.7 cm (). Endoscopic retrograde cholangiography (ERC) performed revealed resolution of stricture (). The biliary stent was removed following resolution of the stricture. He remains on prednisone 20 mg daily with close rheumatology follow-up. Rituximab therapy is being considered as a steroid-sparing agent. |
pmc-6126086-1 | A 56-year-old healthy man presented to the emergency department in the summer season with three days of fatigue and bilateral thigh pain. He was born in Puerto Rico but resided in the Northeast Region of the US, where he worked as a chef in a major metropolitan city. He had no sick contacts, recent travel, or alcohol or drug use.
Laboratory data on presentation demonstrated a creatinine (Cr) of 1.73 mg/dL, creatinine kinase (CK) of 3494 U/L and platelet count of 68x103/μL with initially normal liver function tests (LFTs). The patient was admitted for treatment of acute kidney injury from presumed rhabdomyolysis of unclear cause but subsequently developed low-grade fevers, leukocytosis, and worsening thrombocytopenia over the following days. His Cr worsened despite hydration and conservative management for which the patient underwent a renal biopsy on hospital day 4, with findings of acute tubular necrosis, interstitial hemorrhage, and capillaritis.
In addition to worsening renal function, he had an impressively rapid rise in his total and direct bilirubin with development of clinical jaundice over the subsequent days with laboratory values on hospital day 8 as follows: Cr of 4, total bilirubin of 41 mg/dL, and direct bilirubin of 38 mg/dL (). The GI consult service became involved in his care and on physical examination noted no evidence of chronic liver disease other than jaundice. The patient had no abdominal tenderness, hepatosplenomegaly, or asterixis. The bilirubin values were out of proportion to his other liver tests such as INR and albumin, which remained within normal values and AST/ALT and alkaline phosphatase values wavered between mildly elevated (<2 times the upper limit of normal) and normal values. Based on the kidney biopsy results and significant hyperbilirubinemia, testing was done for bacteremia, influenza, tuberculosis, HIV, tick-borne diseases, Hantavirus infection, acute viral hepatitis (A, B, C, E, CMV, EBV, and VZV) and vasculitis, which were all negative or normal.
An abdominal ultrasound and MRI liver protocol/MCRP showed a normal hepatobiliary system. Given his impressive rise in bilirubin out of proportion to other LFTs in combination with renal failure and rhabdomyolysis, the GI service recommended antibody testing for leptospirosis, for which serum IgM antibodies were checked on hospital day 5. The following day, he was started on empiric doxycycline in liaison with infectious disease consultation at 100 mg intravenously twice daily. In the interim, a liver biopsy was done showing liver parenchyma with marked canalicular and intracellular cholestasis, accentuated in perivenular zone, and rare foci of bile duct injury and ductular proliferation. There was no evidence of significant steatosis, fibrosis or intracellular iron deposition with trichrome, reticulin, PAS-D, and iron stains being unrevealing.
On hospital day 10, the Leptospira IgM returned positive, consistent with the diagnosis of icteric leptospirosis. He was continued on doxycycline 100 mg twice daily with subsequent normalization of leukocyte and platelet counts (). In view of the positive Leptospira IgM antibody results, the liver tissue obtained from biopsy was reevaluated for spirochete organisms with special staining; however no organisms were found.
The patient completed a 10-day course of doxycycline but unfortunately suffered from bile cast nephropathy from severe hyperbilirubinemia with continued rise in Cr (), for which he was treated with cholestyramine and ursodiol. His liver function tests and kidney laboratory results began to improve thereafter, and he was discharged on hospital day 26. At six-week follow-up, his renal function improved (Cr of 1.4 mg/dL) and his LFTs had normalized. It was later discovered that the restaurant where the patient had been working had a rodent infestation, which were the most likely source of his infection. |
pmc-6126097-1 | A 49-year-old male patient was referred to our clinic with a prediagnosis of retinal vascular occlusion. In his medical history, he reported developing low vision after a traffic accident in childhood, having laser treatment in both eyes at 12 years of age and again 1 month earlier, and undergoing bilateral laser-assisted in situ keratomileusis in 2002. His medical and family histories were otherwise unremarkable. Following fundus examination and FFA, he was questioned again about his birth and he stated that he had been born full term by normal delivery. On ophthalmologic examination, his visual acuity was 0.4 in the right eye and 0.3 in the right eye, with mild cortical lens opacities. Fundus photography showed straightening of the temporal retinal vascular arcades and temporal dragging of the macula in both eyes ().
Previously applied laser spots with corresponding preretinal fibrosis were observed in the temporal periphery. Although the nonperfused areas in the temporal retina had been partially laser treated, FFA revealed leakage due to persistent retinal NVE in the right eye ().
Optical coherence tomography revealed disrupted macular contour associated with epiretinal membrane in the right macula and minimal perifoveal thinning in the left macula ().
Suspecting FEVR, the patient’s family members were invited for ophthalmologic examination. The patient’s father had normal ocular findings, while his brother showed straightening of the temporal vascular arcades in both eyes and excessive vascular branching and nonperfusing cord vessels in the peripheral vasculature, as well as temporal avascular areas ().
His brother was also not born prematurely. FFA was not performed for his brother because he did not return for the procedure. FFA in the patient’s father was within normal limits. Based on the brother’s findings and the revised Pendergast and Trese classification, the patient was diagnosed with stage 2A FEVR and his brother was diagnosed with stage 1A FEVR (). The patient’s other family members did not appear for examination. Additional laser therapy to the nonperfused areas was recommended due to persistent NVE. When obtaining his family history, it was learned that his parents were second-degree cousins. |
pmc-6126100-1 | A 53-year-old woman presented with complaints of visual deterioration in the right eye. Her anamnesis revealed no ocular or systemic diseases except a mild influenza-like illness a week earlier. Her best corrected visual acuity (BCVA) was 0.5 in the right and 1.0 in the left eye. Anterior segment examination and intraocular pressure was within normal range in both eyes. Fundoscopic examination of the right eye revealed splinter hemorrhages, optic nerve head hemorrhage, and cotton wool spots in the superior arcuate region, and the patient was diagnosed with papillophlebitis (). Fundus fluorescein angiography revealed no ischemic areas; however, there was hypofluorescence in the areas corresponding to hemorrhages, and hyperfluorescence in the optic nerve head (). Optical coherence tomography revealed macular edema and intraretinal edema and hyperreflective spots in the nasal fovea corresponding to the areas affected by the occlusion (). Laboratory and radiological tests were requested to determine the etiology of the papillophlebitis. One week after onset of these complaints, the patient began to experience numbness, pain, and tingling sensation in both lower legs. Motor weakness became progressively severe in both extremities and she was admitted to the neurology clinic for advanced examination and treatment. No abnormalities were detected in magnetic resonance imaging of the brain and spinal cord. Complete blood count, electrolytes and blood chemistry and urinalysis were normal. Coagulation tests, including serum levels of homocysteine, protein C and S, partial thromboplastin time, and prothrombin time were normal. Erythrocyte sedimentation rate and anticardiolipin G and M were within normal range. Lumbar puncture revealed no pathology. She was diagnosed with GBS and treated with intravenous immunoglobulin (IVIg) therapy. Her symptoms improved in the following 3 months. During follow-up, her BCVA in the right eye returned to 1.0 without any treatment for ocular findings (). |
pmc-6126102-1 | A 26-year-old female patient presented to our clinic with blurred vision in both eyes for 2 weeks. She reported no history of any major illness, but had complaints of fever, sweating, exhaustion, joint pain, and headache starting 2 months earlier. Upon presentation to another center for these complaints, chest x-ray revealed hilar fullness and a thoracic computed tomography (CT) scan was performed. Thoracic CT revealed bilateral hilar lymphadenopathy, and the patient was referred to our hospital for further diagnosis and treatment, where she underwent endobronchial ultrasound-assisted lymph node biopsy in our pulmonary diseases unit. Histopathological examination revealed granulomatous structures, lymphocytes, and sporadic bronchial epithelial cells.
The patient was not under treatment when she presented to our clinic. Physically, she exhibited somnolence and clouding of consciousness. Her visual acuity was 20/25 in the right eye and 20/20 vision in the left eye. Granulomatous keratic precipitates and +1 Tyndall effect were detected in both eyes in anterior segment examination. In both eyes, +1 vitritis was observed in the anterior vitreous.
On fundus examination, the optic discs of both eyes were edematous and hyperemic. In the right eye, a soft exudate was observed inferior to the optic disc and the lower half of the macula was ischemic (). The patient was started on topical treatment with 1% prednisolone acetate 4 times daily and 0.5% tropicamide 3 times daily.
Neurology consultation was requested due to the patient’s complaints of intense headaches and the presence of bilateral optic disc involvement. However, no pathology was detected on neuromuscular examination. Cranial imaging and a lumbar puncture were performed. Diffusion magnetic resonance imaging (MRI) revealed extending nodular enhancements within and adjacent to the optic chiasm, at the basal cisternal level, and in the leptomeningeal layers in the posterior fossa. Thoracic and cervical MRI revealed leptomeningeal enhancement adjacent to the entire spinal cord. Cranial MR venography was normal.
Laboratory tests revealed low hemoglobin (10.7 g/dL; normal: 12-17), high sedimentation rate (57 mm/h; normal: 6-12), elevated CRP (9.4 mg/dL; normal: 0-3.5), and high urinary calcium (324 mg/24 hours; normal: 0-250). Anticardiolipin antibodies and lupus anticoagulants were negative. Cerebrospinal fluid (CSF) analysis showed high protein (145 mg/dL; normal: 15-45) and normal glucose (47 mg/dL; normal: 40-70), cell count in the cytological specimen was high (8500 cells/mL; normal: 0-10), and CSF pressure was normal (12 cm H2O; normal: 8-18). CSF tuberculosis culture and acid-fast bacilli staining was negative. Based on the laboratory values, lymph node biopsy, and imaging findings, the patient was diagnosed with neurosarcoidosis-associated optic neuropathy and treatment was initiated with intravenous 1 g methylprednisolone for 3 days followed by oral methylprednisolone at 1 mg/kg/day. The macular ischemia initially observed in the right eye regressed within 1 week. The patient’s general condition improved significantly with treatment and fundus fluorescein angiography (FFA) was performed. In both eyes, hyperfluorescence beginning in the early phase and increasing in the late phase was observed in the optic discs () and a hyperfluorescent spot that increased in intensity in the late phase was observed on the vessel passing superiorly over the left fovea (). Hyperfluorescent leakage that increased toward the late phase was observed in the lower peripheral retinal vessels of both eyes ().
Although systemic steroid therapy was reduced, it was decided to initiate systemic immunosuppressive therapy; oral methotrexate 15 mg/week and folic acid 5 mg/day were added to her treatment. Her vision was 20/20 in both eyes after 3 months of treatment. Anterior segment examination was normal. Fundus examination showed regression of the optic disc edema (). Follow-up diffusion MRI revealed that the extending nodular enhancements within and adjacent to the optic chiasm at the basal cisternal level and in the leptomeningeal layers in the posterior fossa had disappeared. In addition, thoracic and cervical MRI showed that the leptomeningeal enhancements along the spinal cord had completely resolved and the hilar lymphadenopathy had disappeared.
The patient had no systemic or ophthalmological recurrence while under oral 15 mg/week methotrexate and 5 mg/day folic acid therapy or during the 15-month follow-up period. No side effects related to systemic immunosuppressive therapy were observed. |
pmc-6126105-1 | The blind and painful right eye of a 38-year-old man was eviscerated in September 2016. The patient stated that his right eye had been blind since early childhood due to a unilateral congenital anomaly complicated by secondary glaucoma. He received the diagnosis of SO in January 2017 after he experienced visual loss in his only seeing (left) eye. At the time of diagnosis, the patient was admitted to the hospital and meticulously investigated for possible infectious and noninfectious causes to rule out other uveitic entities, but without any positive findings. At that time, his best-corrected visual acuity was 6/10. Slit-lamp examination yielded some vitreous cells in the left eye. Fundoscopy showed a few scattered pigmented chorioretinal scars and discrete yellowish round choroidal lesions throughout the left fundus (). Fluorescein angiogram delineated the active lesions as early hypofluorescent () with late staining. Left macular contour was normal on optical coherence tomography (OCT) examination (). He was started on oral prednisolone (64 mg) for 2 weeks with gradual tapering of 8 mg per week. Despite initial visual improvement, he experienced another episode of visual decline while taking 32 mg of prednisolone. His best-corrected visual acuity decreased to 2/10 and he had grade 4 vitreous haze according to the Miami grading. Fundus examination showed marked yellowish-white discoloration of the macula with some evidence of intraretinal hemorrhage ( and ). He was hospitalized and treated with pulse methylprednisolone 1 g (250 mg 4 times daily) for 3 days. Following pulse therapy, 64 mg oral prednisolone and 150 mg (50 mg 3 times daily) azathioprine were co-administered. Two weeks after the completion of pulse therapy, his visual acuity was still 2/10 despite a significant reduction in vitreous haze. Fluorescein angiogram and OCT demonstrated type 2 choroidal neovascularization (). Five intravitreal 2 mg aflibercept injections were given within a period of 8 months. His final visual acuity was 6/10 with a stable-looking macula ( and ) and he was continued on a treatment regimen of 150 mg azathioprine and 8 mg prednisolone daily. |
pmc-6126108-1 | A 27-month-old boy was referred for a second opinion regarding polyuria and polydipsia of sudden onset four months prior to presentation. He drank between 3 and 4 L of water per day and had frequent heavy wet diapers, decreased appetite, and a 1-pound weight loss. He had no prior episodes of dehydration or any preceding or intercurrent illnesses. He had no prior medical history, met normal developmental milestones, and was not taking any prescribed or over-the-counter medications. There was no family history of diabetes insipidus. Social history was remarkable for the mother returning to work prior to the onset of symptoms.
Prior evaluation was significant for normal serum sodium, glucose, blood urea nitrogen (BUN), creatinine, adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), thyroxine level, insulin-like growth factor (IGF), cortisol, erythrocyte sedimentation rate (ESR), and prolactin. The random arginine vasopressin (AVP) level was 1.4 pg/mL (normal range 1–13.3 pg/mL) with a random urine osmolality of 285 mOsm/kg. A head MRI did not reveal any pituitary or other intracranial pathologies. A renal ultrasound showed a right kidney with a duplicated collecting system with mild prominence of the lower pole of the renal pelvis. An informal water deprivation test was conducted at home, and parents were instructed to limit water intake at home overnight and to return for laboratory evaluation in the morning. Urine osmolality was 683 mOsm/kg after 12 hours of water deprivation. However, mother stated that, at the end of the water deprivation, she had to give him water to stimulate diuresis. No serum osmolality or sodium levels were collected. He was diagnosed with partial DI and started on oral desmopressin (DDAVP). The dose of DDAVP was titrated up to 0.2 mg twice daily for effect, his polyuria and polydipsia resolved, his appetite improved, and he began to gain weight.
Vital signs were normal, with weight-for-age at the 45th percentile, height-for-age at the 57th percentile, and body surface area 0.57. Physical exam was remarkable only for a tired-appearing toddler. Chemistries performed were remarkable for serum sodium of 121 mEq/L. DDAVP was discontinued, and the serum sodium normalized to 138 mEq/L 24 hours later.
He was admitted to the hospital for a water deprivation test. After eight hours of observed water deprivation, urine osmolality increased from 270 mOsm/kg to 753 mOsm/kg. During this observed period, urine output was 4 ml/kg/hour and total weight loss was 160 grams. Serum sodium was 139 mEq/L and 140 mEq/L and serum osmolality was 298 mOsm/kg and 294 mOsm/kg, before and after water deprivation, respectively. He was discharged home with fluid restriction to 1.5 L/day. Since discharge from the hospital, parents were able to reduce his water intake with resolution of polyuria. However, he continued to ask for water to help him fall asleep at night. Retrospectively, his mother suspects that water drinking was his method for self-comfort following her return to work. |
pmc-6126109-1 | The case is of a 72-year-old female, chronic smoker patient with a 3 pack-years until 20 years ago, with a personal history of hypertension, obesity, dyslipidemia, breast nodules, and transverse myelitis with motor sequelae. She has been hospitalized 6 years ago for community-acquired pneumonia.
She consulted for several months of asthenia, adynamia, hyporexia, and subjective weight loss. Associated with this, she had 10 days of fever, malaise, myalgias, non-palpable purpura on the lower limbs (), mild dyspnea, and intermittent cough without hemoptysis.
She had dry symptoms (xerostomia and xerophthalmia) initiating a study for primary SS during hospitalization. She had a positive Schirmer tear test, antinuclear antibodies 1:160 with a speckled pattern, positive anti-Ro/SSA, and anti-La/SSB, as well as positive rheumatoid factor and mild C3 hypocomplementemia. The diagnosis of SS was confirmed with a minor salivary gland biopsy that reported chronic sialadenitis with Chisholm-Mason grade of 4.
Her physical examination did not present hemodynamic instability; she was afebrile with a few bibasilar rhonchi without respiratory difficulty. She had urinary incontinence, nonpalpable purpuric lesions on the lower limbs, and decreased distal muscular strength, partially limiting the gait. During her stay, she presented respiratory and metabolic acidosis with a blood urea nitrogen/creatinine ratio> 20 that was corrected with supplemental oxygen and intravenous fluids. Her exams were performed, including a complete blood count, complete liver function tests, serum electrolytes, and acute phase reactants, which were found in normal ranges. She also had negative hepatitis C virus (HCV) antibody test and nonreactive tests for human immunodeficiency virus (HIV) and syphilis. The serum protein electrophoresis: mild broad-based peak in the gamma region (<3 g/dL) and skin biopsy reported capillaritis with no histological signs of malignancy.
The possible associated pathologies in SS, like non-Hodgkin lymphoma, mainly of mucosa-associated lymphoid tissue (MALT) type, ANCA-associated vasculitis, and cryoglobulinemic vasculitis were ruled out.
In this context, due to pulmonary nodular involvement evidenced in the non-contrast computed tomography (CT) scan of the chest, an HRCT was requested (Figures and ) which showed multiple generalized, noncalcified nodular lesions, some with cavitations, and the presence of focal areas of ground-glass opacity associated with suggestive basal predominance subpleural cysts that are suggestive of lymphocytic pneumonia. The CT-guided lung biopsy was considered to clarify its etiology as there were no findings of neoplastic foci in the extension studies (non-contrast head CT scan, non-contrast abdominal CT scan, transthoracic echocardiography, mammography, and upper digestive endoscopy).
Fiberoptic bronchoscopy did not report any anatomical abnormalities or evident lesions in the pharynx, hypopharynx, larynx, main bronchus, interlobar bronchus, lobular bronchus, or segmental bronchus. In the left main bronchus, there were scarce and diffuse mucohemorrhagic secretions in the bronchial tree, predominating in the bronchus for the upper left lobe, with no evidence of apparent active bleeding. Microorganisms were not isolated in bronchoalveolar lavage. Bronchial brushing showed a benign cytological pattern, acute inflammation, and negative special staining for mycobacteria and fungi.
Subsequently, video-assisted thoracoscopy (VATS) was performed with pulmonary biopsy. The biopsy of the upper lobe and lingula of the left lung had as findings distortion of the parenchyma architecture, pleural thickening with the presence of anthracite pigment, and alveolar septa thickened with inflammatory infiltration of lymphocyte predominance. Presence of inflammatory infiltration of peribronchiolar lymphocyte predominance in some lymphoid nodules is shown in . There was formation of nodules with dense amorphous eosinophilic material, in the middle of which there are lymphoplasmacytic inflammatory cells. In addition, with positive CD3: immunohistochemical markers for reactive T lymphocytes, CD20: for reactive B lymphocytes, and CD38: for plasma cells and kappa and lambda positivity, similar areas of nodular formation were found with amyloid deposition using special staining for crystal violet () and Congo red ().
With these findings, the diagnosis of nodular pulmonary amyloidosis and non-specific interstitial pneumonia (NSIP) was made. Both pathologies were explained by the SS. Inpatient immunosuppressive treatment was with cyclophosphamide 800 mg IV single dose and methylprednisolone 150 mg IV single dose; subsequently, on an outpatient basis, prednisolone 50 mg PO qd was administered for one month with gradual reduction. |
pmc-6126179-1 | The first case describes a 48-year-old female who had an established diagnosis of heterozygous FVL with a positive family history and was diagnosed with left breast cancer in October 2010. She presented to our institution in November 2013 with painful capsular contracture from prior implant-based reconstruction and a desire for bilateral autologous reconstruction. After detailed counseling regarding her operative risks, she underwent bilateral implant removal, capsulectomy and bilateral sensate DIEP flaps. There were no significant perioperative adverse events. The patient received 3000 IU of intravenous unfractionated heparin (UFH) after both sets of anastomoses were performed. At her 2-year follow-up at our institution in early 2016, the patient was in good health with her flaps sensate and well-perfused (Fig. ). |
pmc-6126179-2 | The second case involved a 49-year-old female who was diagnosed with infiltrating ductal carcinoma in 2010. After initial lumpectomy and subsequent chemoradiation, she presented in 2016 expressing desire for mastectomy of the left breast with autologous breast reconstruction. Her history was significant for heterozygous FVL and a previous lower extremity deep venous thrombosis which required 2 years of warfarin therapy. She underwent left completion mastectomy with neurotized DIEP flap reconstruction. There was clotting noted intraoperatively prior to performing the anastomosis, and the decision was made to irrigate the vessels with tissue plasminogen activator solution. The patient was given an intravenous dose of 3000 units of UFH. At her 1-year follow-up in August 2017, her flaps and abdominal scar were inconspicuous and the patient was awaiting her symmetry breast revision procedures (Fig. ).
All lab values of both patients are displayed in Table and their medications in Table . The TEG® 5000 Thromboelastograph® Hemostasis System (Haemonectics Corporation, Braintree, MA) was the device performing all TEG tests. Additionally, the thrombocyte count, prothrombin time (PT) and activated partial thromboplastin time (aPTT) were obtained. |
pmc-6126703-1 | A 42-year-old female with a history of morbid obesity and tricuspid valve endocarditis with mechanical TV replacement, who had stopped taking Coumadin for one week, presented with worsening dyspnea, facial cyanosis, marked lower extremity edema, and increased abdominal girth. Transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) revealed significant tricuspid valve thrombosis with severely immobile leaflets and severe pulmonary hypertension (Figures -).
She was initially started on a high-intensity heparin infusion with 8000U bolus followed by 1800U per hour infusion. She was brought to the interventional laboratory where a 7-French triple-lumen central venous catheter was advanced to the right atrium via the right internal jugular vein under fluoroscopic guidance. A bolus of 2 mg of alteplase (tPA) was delivered followed by a continuous infusion of 1 mg/hour for 24 hours. Fluoroscopy revealed a tricuspid valve with severely reduced mobility (Figure ).
The gradient across the tricuspid valve was above 20 mmHg and right atrial pressure was elevated at 22 mmHg. Repeat gradients were assessed 24 hours later, and TV gradient remained elevated above 20 mmHg, with severely elevated central venous pressure, and markedly reduced cardiac index. The patient underwent redo sternotomy with redo tricuspid valve replacement with a porcine bioprosthesis. Her postoperative course was uneventful. She was started on coumadin and bridged with heparin infusion and was discharged home with INR 2.6. |
pmc-6126704-1 | A 79-year-old Hispanic male with a history of hypertension, schizoaffective disorder, benign prostatic hypertrophy, and chronic renal insufficiency was admitted for evaluation of a wide complex tachycardia found on his outpatient 24-hour Holter monitor done to evaluate his complaint of frequent palpitations. The patient acknowledged that he had palpitations for several years and that he was always nervous. He also stated that this “nervousness runs in the family”. There was no associated weight loss, unusual hair loss, or visual changes. He also denied any neck mass/goiter, diarrhea, or abdominal skin rash/thickening but stated that his hand always “shakes”. He denied any chest pain or shortness of breath, either at rest or with exertion. He also denied any orthopnea or paroxysmal nocturnal dyspnea but had complained of chronic leg swelling with no recent change. Exercise tolerance remained very good and unchanged.
On admission, an endocrinology consult was requested for evaluation of persistently elevated TT4 and FT4 levels. His vital signs were stable and physical exam revealed a mildly anxious elderly male with coarse tremors of the hands on extension. The rest of the examination was unremarkable. A sonogram of the thyroid gland showed bilateral prominent lobes, the left greater than the right. A thyroid iodine (I)-123 uptake scan was 19.4% (normal level: 15 - 40%). It also showed a mildly enlarged but non-palpable lower pole of the thyroid lobe with homogenous activity throughout the gland. Thyroid function tests (TFTs) done using routine automated direct one-step/two-step immunoassays showed normal TSH levels of 1.22 and 0.78, respectively (normal level: 0.34 - 5.6 mU/mL). T3 levels were normal at 98.4 and 125.3 ng/dL (normal level: 87 - 178 ng/dL). However, TT4 and FT4 levels were elevated. FT4 levels were 2.25 and 2.34 ng/dL (normal level: 0.58 - 1.64); and TT4 levels were 17.58 and 18.69 (normal level: 6.09 - 12.2). Free T3 by equilibrium dialysis was 402 ng/dL (normal level: 230 - 420) and an alpha subunit for pituitary hormone was less than 0.3 ng/ml (normal level: < 1.0). Free T4 by equilibrium dialysis was normal at 2.1 ng/dl (normal level: 0.8 - 2.7).
Cardiac workup, including echocardiogram, cardiac enzymes, stress test, and telemetry monitoring, was unremarkable. He was treated with a beta-blocker and discharged after being assured that his thyroid condition was benign. |
pmc-6126705-1 | A 49-year-old woman presented to our neurology clinic with complaints of pain and weakness in her upper-right and lower-left extremities, lower back pain, and numbness in her lower extremities for many years. For the past couple of months, the pain in her lower back, left hip, and lower extremities (including feet) has gotten worse. The pain increased at night, was exacerbated while standing or sitting, and was accompanied by numbness in her left lateral thigh. The rest of her medical history was unremarkable. The nerve conduction studies showed mild but painful sensory axonal neuropathy with superimposed mild bilateral sensory carpal tunnel syndrome. During the needle EMG using a 50 mm * 25 gauge needle, she complained of a significant amount of discomfort when her right cervical paraspinal muscles were punctured; however, she did not exhibit any other symptoms. After the EMG study, her blood pressure was 156/103 mmHg, with a pulse rate of 90/min (right radial, sitting), then it was 154/101 mmHg with a pulse rate of 97/min. She was given the appropriate treatment, which included blood tests to eliminate correctable causes of neuropathy, vitamin B12, exercise, and appropriate medications.
After leaving the clinic symptom-free, she returned 30 minutes later, with complaints of right-sided pleuritic chest pain and the coughing up of some mucus. Upon physical examination, she had a tender right pectoralis major muscle, equal breath sounds bilaterally, a normal cardiac examination, a blood pressure of 130/80 mmHg, and a pulse of 100/min (right brachial, sitting). She was immediately sent to the emergency room for a workup, including a chest X-ray, which disclosed a 15% right-sided pneumothorax. This was most likely due to the needle EMG puncture of her right cervical paraspinal muscles. The patient was admitted overnight for non-rebreathing oxygen treatment. Once her symptoms were resolved, she was discharged with a follow-up to ensure that her pneumothorax had resolved. |
pmc-6126779-1 | A 50-year-old male who is an established patient of ours underwent preoperative evaluation in August 2013, which revealed an abnormality not present in the imaging taken in 2011. His chest X-ray revealed a prominence in right hilum and a density along the right pleura towards the right upper lobe. Later, the patient underwent noncontrast computed tomography (CT) of the chest depicting pleural-based mass measuring 3.3 cm x 3.7 cm in the right upper lobe (Figure ). Biopsy performed a few weeks after imaging showed adenocarcinoma,
poorly differentiated with a solid and single cell pattern. Molecular genetics was positive for thyroid transcription factor-1 (TTF-1), which is found in type II pneumocytes and Clara cells. Evidence suggests that TTF-1 expression is associated with better overall survival []. A full body positron emission tomography (PET) revealed a hypermetabolic spiculated 4.4 cm x 3.2 cm mass in the right upper lobe of the patient (Figure ). Also, a pathologic hypermetabolic right suprahilar lymph node measuring 1.8 cm x 2.4 cm. was noted. The standardized uptake values (SUVs) were 12 and 5.8, respectively. On November 25, 2013, the patient underwent right upper lobe lobectomy and frozen section determined tumor, node and metastases (TNM) classification to be T3, N1, and Mx.
After resection, the patient began concurrent chemo-radiotherapy with cisplatin and pemetrexed on January 15, 2014. He declined further chemotherapy treatments after the second treatment session citing intolerable side effects such as nausea, vomiting, fatigue, and malaise. However, he completed the radiation regimen, which lasted for a total of six weeks.
In subsequent weeks and months, the patient faced numerous challenges including several admissions for pneumonia, fluid overload, and bronchospasms. Later, he was admitted for pulmonary embolism, which led to the addition of rivaroxaban for life and placement of an inferior vena cava (IVC) filter. The patient has a history of permanent tracheostomy for chronic hypercapnic respiratory failure in 2006 along with a radical prostatectomy due to a Gleason 7 prostate carcinoma in 2008. Subsequently, after many positive antidotal cases in our practice utilizing LDN, a decision was made to try and start the patient on this complementary therapy. Therefore, he was started on LDN 4.5 mg HS on July 23, 2014. Imaging performed following LDN has been unremarkable. More specifically, a PET scan performed on October 27, 2017, and computed tomography (CT) of chest/abdomen/pelvis with contrast performed on April 25, 2018, have been negative for evidence of any recurrence. The patient is currently on rivaroxaban, amlodipine, atorvastatin, clonidine, insulin lispro, insulin glargine, losartan, metoprolol, prednisone, montelukast, diltiazem, and LDN. |
pmc-6126787-1 | A 75-year-old man presented for his semiannual total body skin evaluation. His past medical history was significant for diverticulitis of 27 years duration. Three months earlier, the treatment of his abdominal pain had necessitated a sigmoid resection—with a concurrent appendectomy—and an end colostomy with mucous fistula.
He also has anxiety (for which he takes alprazolam, as needed) and mitral valve prolapse (for which he takes diltiazem daily). In addition to his recent operation, his prior surgery includes the repair of an anal fistula with a rectal advancement flap.
His history of skin disease includes a basal cell carcinoma on the right side of his neck that was excised five years ago and actinic keratoses on sun-exposed skin that have been treated with cryotherapy. He developed psoriasis as a middle-aged adult; his psoriasis is limited to less than 5% of his body surface area; individual plaques were treated initially with clobetasol propionate 0.05% cream or solution followed by triamcinolone 0.1% cream, each applied twice daily for three to five days. He also had a history of allergic contact dermatitis to bandaid adhesive and congenital idiopathic leukonychia that has been present since early childhood.
Cutaneous examination showed eight keratotic plaques on the sun-exposed areas of his face, arms, and legs; the actinic keratoses were treated with liquid nitrogen cryotherapy. Psoriasis lesions were also present, appearing as small, red scaly plaques on the chest, arms, and legs. There were no nail plate changes of psoriasis.
Evaluation of his fingernails and toenails confirmed the presence of leukonychia; all of the nail plates on his fingers and toes showed diffuse whitening (Figure ). His thumbnails also demonstrateed alternating horizontal bands of white and red beginning at the proximal nail fold and extending to the tip of the nail plate: the nail flag sign (Figure ). In addition, the surfaces of both thumbnail plates had longitudinal striations. |
pmc-6126788-1 | A 48-year-old female patient visited the emergency room (ER) due to left buttock pain after she slipped down on her way to the bathroom. The accident occurred just before she visited the ER, while the left buttock pain started two weeks ago. The patient denied for any remarkable medical history except for being a hepatitis B virus carrier. According to the ER records, she had a generalized fever up to 37.8°C and had tenderness, swelling on her left buttock and proximal area of the posterior thigh. The blood laboratory test showed elevated C-reactive protein (CRP) level (4.08 mg/dl) without leucocytosis (WBC: 6930/μl). The liver enzyme values were mildly elevated such that serum glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) were 68 and 45, respectively. The plain radiography showed no evidence of fracture around her hip joint. The emergency medicine physician had a clinical impression of early stage cellulitis or contusion of hip and she was discharged from ER after prescribing empirical antibiotics and nonsteroidal anti-inflammatory medications.
A week later, she visited the orthopedic outpatient department with aggravated pain and weakness on her left lower extremity. The vital signs were unremarkable. On physical examination, she had a left foot drop and was unable to dorsiflex or plantar-flex her left ankle. Extension of the great toe was also impossible. Hypoesthesia was detected on L4, 5, S1 dermatomes. Deep tendon reflexes on patellar and Achilles tendon were normal and symmetrical. A patchy erythematous rash with sharp pain existed on the left buttock and posterior thigh without any sign of vesicle formation. The blood laboratory test showed mildly elevated CRP (2.03 mg/dl) and normal procalcitonin (0.05 ng/ml) levels. Due to the aggravated sciatica and left lower limb weakness, the lumbosacral magnetic resonance imaging (MRI) was urgently performed under suspicion of a spinal lesion. The MRI revealed mild bulging disc with bilateral facet arthritis at L4-5 level; however, it was not thought to be the direct cause of the symptoms. The result of electromyography and nerve conduction velocity (EMG-NCV) tests showed severe left sciatic neuropathy that no motor nerve responses from the left peroneal nerve and reduced compound muscle action potential on tibial nerve were found. Pelvis MRI with contrast enhancement revealed asymmetrical diffuse swelling of the left sciatic and femoral nerve, which suggested neuritis (Figure ).
A more detailed investigation on her past medical history revealed that she had been treated for herpes zoster infection of the left buttock three years ago. A thorough systematic review was done again; however, she had no comorbidity or medication history that can cause immunosuppression. The putative diagnosis of herpes zoster was confirmed by detecting VZV DNA from her blood sample using the polymerase chain reaction test. The patient was treated with famciclovir 500 mg every eight hours and 20 mg/day of prednisolone for two weeks and changed to oral pregabalin 75 mg every 12 hours thereafter. After 12 weeks of an inpatient rehabilitation admission, she had a partial neurological recovery and could walk with a foot drop splint. The manual muscle test showed that muscular strength of her left ankle dorsi-flexor, plantar-flexor and great toe extensor improved to grades II, III, and III, respectively. The hypoesthesia of S1 dermatome was completely recovered, while L4, L5 dermatomes showed 50% improvement. Also, the skin rash and pain around it was completely alleviated. Follow-up pelvis MRI taken at 10 weeks after the treatment showed markedly diminished swelling of the left sciatic and femoral nerve (Figure ). |
pmc-6127073-1 | A 68-year-old man was referred to our hospital with diagnosis of rectal tumor. Medical history notably included diabetes mellitus, but family and social history were unremarkable. Colonoscopy identified a two-thirds circumferential type 2 tumor in the rectum, about 5 cm from the anal verge (Fig. a). Biopsy of the tumor revealed well differentiated tubular adenocarcinoma and papillary adenocarcinoma with enteroblastic differentiation which was characterized by clear cytoplasm and regarded as one of the histological features in AFP-producing cancer (Fig. ). Laboratory evaluation showed fasting blood glucose and HbA1c levels were elevated at 152 mg/dl (normal range 73–109 mg/dl) and 13.7% (normal range 4.9–6.0%), respectively. Serum tumor marker levels were increased to 8.8 ng/ml in CEA (normal range ≤ 5.0 ng/ml) and 28.3 ng/ml in AFP (normal range ≤ 7.0 ng/ml). Two-thirds circumferential thickening of the wall over 4 cm in the lower rectum, and a pararectal lymph node swelling about 8 mm in diameter was revealed by enhanced abdominal computed tomography (CT) and pelvic magnetic resonance imaging (MRI) (Fig. a). The tumor was classified as stage IIIB (T3N1M0). To improve the local control rate and the survival rate, preoperative radiation therapy (total dose of 45 Gy/25 fractions) with capecitabine (1,650 mg/m2/day) was performed. Effective tumor reduction was observed on colonoscopy, CT, and MRI after 5 weeks of the above treatment. A swelled pararectal lymph node also showed a significant decrease of its size from 8 to 3 mm in diameter (Fig. , ). In addition, serum tumor marker levels decreased to normal range: CEA, 2.0 ng/ml; AFP, 3.7 ng/ml. At 7 weeks, low anterior resection with temporary diverting ileostomy was performed. Histopathologically, residual poorly differentiated, non-solid type adenocarcinoma was present, although most of the tumor comprised fibrous scar tissue. There was no lymph node metastasis, and pathological diagnosis was stage I (T2N0M0). Histological evaluation of the treatment with chemoradiotherapy was assessed to be grade 2 according to the Japanese Classification of Colorectal Carcinoma []. Immunohistochemical studies yielded positive results for AFP, Sal-like protein 4 (SALL4), and glypican3 (GPC3) (Figs. , ). The postoperative course was uneventful. Four weeks after the operation, serum tumor marker levels had decreased to 1.2 ng/ml in CEA and 1.6 ng/ml in AFP. The patient received adjuvant chemotherapy with capecitabine and oxaliplatin (CAPOX) for 3 months in consideration of high recurrence rate in AFP-producing cancer. After completing this regimen, we checked no signs of recurrence. To date, he has not developed any recurrence for 6 months after the operation.
AFP is a serum glycoprotein frequently detected in patients with hepatocellular carcinoma and yolk sac tumors [–]. Its production has also been reported in malignant tumors of various organs, such as the bile duct, the pancreas, and particularly the stomach [, ]. AFP-producing colorectal cancer, however, is extremely rare. AFP-producing gastric cancers are associated with aggressive clinical behavior and poorer prognosis compared to AFP-negative gastric cancer because of a significantly higher incidence of vascular invasion, lymph node metastasis, and liver metastasis [, , ]. As for AFP-producing colorectal cancers, a similar tendency has been observed in previous reports and their reviews of up to 12 patients [–]. Patients with AFP-producing colorectal cancer underwent several treatments, including surgery and chemotherapy according to conventional colorectal cancer treatment. There are no confirmed treatment strategies, however, and about half of the patients died within a year of therapeutic intervention. The present case was of rectal cancer classified as stage IIIB (T3N1M0), so we elected to perform the preoperative chemoradiotherapy that is recommended for cases clinically diagnosed as deeper than T3 or node-positive rectal cancer. The aim was to improve the local control rate and the survival rate [–]. As of chemotherapy regimen for preoperative chemoradiotherapy, we chose capecitabine alone according to the papers describing that preoperative radiation therapy with capecitabine was as effective as with intravenous infusional fluorouracil, but the addition of oxaliplatin did not improve surgical and oncological outcomes [, ].
Although there are no reports of AFP-producing rectal cancer treated with radiation therapy, several reports in hepatocellular carcinoma and a few reports in yolk sac tumor have shown its effectiveness [–]. In our case, effective tumor reduction was observed and serum tumor marker levels decreased to normal range by this treatment. After 7 weeks of the above treatment, the operation was performed. Although pathological findings showed R0 resection, immunohistochemical studies revealed AFP production. The tumor was therefore diagnosed as AFP-producing adenocarcinoma. Immunohistochemical studies also yielded positive results for SALL4 and GPC3; known novel oncofetal proteins expressed in germ cell tumors. SALL4 and GPC3 are also highly expressed in AFP-producing gastric cancers [], but there are no reports on their expression in AFP-producing colorectal cancers. In this case, as with AFP-producing gastric cancers, fetal differentiation may be induced, and immunohistochemical studies showed positive results for these oncofetal proteins. SALL4 expression in colorectal cancer is reportedly associated with lymph node metastasis and poor prognosis []. Although our case was pathologic stage I which was not normally needed for adjuvant chemotherapy in AFP-negative colorectal cancer, he was deemed to have a high probability of recurrence, and hence, adjuvant chemotherapy was performed. As effective therapies against AFP-producing colorectal cancer have not been established, regimen is performed according to various guidelines and personal experiences. Our patient received CAPOX treatment for 3 months according to the latest guidelines, and the report showing 3 months of therapy with CAPOX was as effective as 6 months in patients with stage III colon cancer even among those with high-risk factors [, ]. |
pmc-6127469-1 | A 24-year-old gravida-3-para-2 at 24 weeks’ gestation was referred to our department for TTTS. Her physical and gynecologic examinations were usual. Fetal examination revealed a diamniotic MC twin pregnancy. The recipient twin was diagnosed as having polyhydramnios and the donor twin had oligohydramnios. The diagnosis of stage 3 TTTS was made on the basis of Quintero Staging system. A negative ductus venosus A-wave was observed in the recipient twin. The deepest vertical pocket was 140 mm for the recipient and 5 mm for the donor twin. The complications and prognosis of TTTS and risks of placental laser surgery were discussed with the family and the patient opted for placental laser surgery. The patient underwent placental laser surgery under local anaesthesia in operating room. On the day of the operation, 100 mg indomethacin was administered due to regular uterine contractions as rectal suppository once a day. Indomethacin administration was continued until postoperative day 2 and the contractions disappeared. On postoperative day 3, an ultrasound examination revealed pleural effusion, ascites, increased nuchal thickness, oligohydramnios, tricuspid regurgitation, and negative ductus venosus A-wave in the donor twin and normal Doppler findings in the recipient twin. A detailed examination of the ductus arteriosus showed ductal narrowing with a transverse diameter of 1.49 mm (<5th percentile) ()(. There was no turbulent flow or aliasing in the ductus arteriosus region and systolic and diastolic velocities were 69 and 6 cm/s, respectively. Although Doppler criteria of ductal constriction were not observed, hydrops was prominent. The indomethacin treatment was stopped. The direction of ductus venosus flow turned to positive on the next day and further examination revealed a 50% increase in the transverse diameter of the ductus arteriosus, and the ductal arch returned to its normal shape (). The tricuspid regurgitation and ascites, and pleural effusion disappeared completely on postoperative days 5 and day 7, respectively. The patient was discharged on tenth day postoperatively. Her antenatal visits were uneventful until delivery. The patient underwent a cesarean section for breech-vertex presentation at 35 weeks’ gestation. Male infants weighing 2200 and 2100 g were delivered. |
pmc-6127469-2 | A 25-year-old gravida-2-para-1 at 20 weeks’ gestation was referred to our department for TTTs. The patient reported abdominal bloating. The diagnosis of TTTs stage 2 was made on the basis of Quintero staging. The deepest vertical pocket was 154 mm for the recipient and 10 mm for the donor twin. The estimated foetal weight (EFW) was less than 10th centile for donor twin. Placental laser surgery was performed after preoperative counselling. Postoperatively, a single-dose 100 mg indomethacin suppository was inserted into the rectum to prevent uterine contractions. On the next day (postoperative day 1), constriction of the ductus arteriosus and tricuspid regurgitation were observed in the donor twin. There was a marked ductal narrowing (). The peak systolic velocity was 149 cm/s (). On postoperative day 3, the transverse diameter of the ductus arteriosus and peak systolic velocity returned to normal (). On postoperative day 5, the tricuspid regurgitation had disappeared and the patient was discharged. On the next day, the patient was admitted to the hospital due to regular contractions and cervical opening and she delivered at 21 weeks and 3 days’ gestation. |
pmc-6127471-1 | A 64-year-old woman, gravida 2, para 2, presented with pelvic pain, which she had had for approximately four months. She underwent a ventro-suspension 25 years ago for uterine prolapse. However, a re-operation for uterine prolapse consisting of laparoscopy-assisted vaginal hysterectomy was performed 3 years ago. During this procedure, the uterus was separated from bilateral cornual regions and adnexae were left. The result of a pathologic evaluation was reported as benign for the uterus corpus material but wide cervical intraepithelial grade 3 neoplasia signs for the cervix were reported. A physical examination revealed a pelvic mass fixed to the left anterolateral abdominal wall. Abdominal magnetic resonance imaging revealed a huge mass in the pelvic cavity backward the bladder with irregular borders. The tumor markers were carbohydrate antigen (CA)-125; 269.7 kU/L (reference value; 0-35 kU/L). She underwent a debulking operation with bilateral salpingoopherectomy and total omentectomy, bilateral pelvic and paraaortic lymph node dissection, appendectomy, and aspiration for cytologic evaluation. The left ovarian mass had invaded the abdominal wall and resection of the fascia and part of the rectus abdominis muscle was needed; a polypropylene mesh was used to close the abdominal wall. There was no visible tumor after surgery. The tumor was characterized by a proliferation of small, round, primitive cells with a diffuse growth pattern. The cells had scant cytoplasm, irregularly-shaped and hyper-chromatic nuclei with coarse chromatin and a brisk mitotic rate. In some areas there were perivascular pseudorosette-like structures. The histology showed round cells with hyper chromatic nuclei and pleomorphisms, eosinophilic cytoplasm, very frequent mitosis, apoptosis, and focal necrosis. The tumor showed diffuse, strong, cytoplasmic and membranous CD56, nuclear Fli-1 positivity. Multifocal staining for neuron specific enolase (NSE) and mesothelin and focal high molecular weight (HMW)+low molecular weight cytokeratin (CK), epithelial membrane antigen (EMA), synaptophysin (SYNP), WT1 positivity was detected (, ). The tumor cells were also positive for p53. CD99, chromogranin A, CD45, inhibin, calretinin, CA-125, ER, PR, CK7, CK20, Moc31, Tag72, myogenin, S100, and destine were negative. The surgical specimens of one ovary, appendix, and omentum were interpreted as Ewing sarcoma/PNET after immunohistologic and histologic studies. The patient was referred to the medical oncology department and chemotherapy consisting of vincristine, cyclophosphamide, and cisplatin was started. Radiotherapy was not applied. The CA-125 value was 84.4 U/mL before her first chemotherapy. The patient completed six chemotherapies after surgery. There was no evidence of disease after 7 months of follow-up. |
pmc-6127896-1 | A 55-year-old Malagasy man, a doctor, a non-smoker of tobacco, with no significant past medical history, presented with bullous and erosive skin lesions involving his trunk and scalp for the past 2 months. No toxic exposure was noted. He had a family history of cancer; his mother and sister presented breast cancer and multiple myeloma, respectively, the diagnosis of which were delayed. He had no personal or family history of any autoimmune disease. No medication was prescribed prior to diagnosis. A physical examination revealed multiple crusted erosions intermixed with erythematosus patches over his scalp (Fig. ), trunk (Fig. ), and his back (Fig. ). He had no mucous membrane involvement. General physical and systemic examinations were normal.
A complete blood count revealed microcytosis without anemia with mean corpuscular volume (MCV) of 76 fl and hemoglobin of 15.7 g/dL; his white cell count and platelet count were normal. Alanine and aspartate aminotransferase were normal (28 U/L and 25 U/L, respectively) but serum creatinine was high (121 umol/l; normal range: 53–115 umol/L). Other laboratory tests including corrected calcium level, phosphoremia, lactate dehydrogenase, and urine analysis were normal. His HIV status was negative.
A skin biopsy showed suprabasal blisters containing eosinophils and acantholytic keratinocytes. Direct immunofluorescence of perilesional skin revealed immunoglobulin G (IgG) deposition in the intercellular spaces in the epidermis. In an enzyme-linked immunosorbent assay (ELISA), his serum autoantibody index against desmoglein-1 and 3 was found to be 112 RU/mL and 34 RU/mL (normal range, < 20 RU/mL), respectively. Serum immunoelectrophoresis showed a monoclonal gammopathy with a markedly elevated IgG level (2880 mg/dL) in association with a lambda free light chain. Urine analysis was negative for Bence-Jones protein and beta2-microglobulin was 2.4 mg/L. Bone marrow aspirate showed 6% plasma cell infiltration. Further investigations, including creatinine blood test and whole body radiographic examinations, showed that he had clinical stage I multiple myeloma of the IgG-λ type.
At first, the skin lesions regressed significantly after topical applications of corticosteroid ointment and no specific therapy for myeloma was conducted. Three months later, the dermal affliction occurred again so systemic administration of prednisolone (1 mg/kg per day) was started. Six months later, bone tomography revealed vertebral compression fractures of the thoracic and lumbar spine that correlated with our patient’s back pain topographically. However, his IgG level decreased (1080 mg/dL). Anti-myeloma treatment including melphalan and prednisone was started, which resulted in a rapid decline of monoclonal IgG concentration immediately. Skin and hematologic remission were maintained for 12 months. |
pmc-6127913-1 | The patient is a 72-year-old man with histologically confirmed moderately differentiated intrahepatic cholangiocarcinoma (Fig. ). He was diagnosed in October 2015 with the following symptoms: moderate weight loss, pain in the right hypochondrium, loss of appetite and asthenia, with a Karnofsky scale index of 70%. MRI image at the time of diagnosis is shown on Fig. a. The tumor was not surgically removed because of advanced stage, multiple intrahepatic nodules and lung metastases.
Four courses of chemotherapy (2 courses Gemcitabine in combination with Capecitabine and subsequent 2 courses Gemcitabine in combination with Cisplatin) were administered till May 2016. The treatment was poorly effective, and the tumor increased in size according to MRI (Fig. b); additional metastatic nodules appeared in the left and the right lobes with the spread to the bile duct, holedoch and into the gallbladder. Serum gamma glutamyltranspeptidase (GGT) level, which is associated with poor prognosis and tumor aggressiveness [, ], was significantly increased, when compared to pre-treatment levels (Fig. ). Karnofsky scale index decreased to 60%. As the patient did not respond to the best clinical practice treatment, we decided to switch the medication and considered TKI inhibitors as further treatment option. Taking into account available data on differential response of CCA patients to TKIs we performed advanced molecular analysis of the tumor to support our choice and identify the most effective drug.
We profiled gene expression in formalin-fixed, paraffin-embedded (FFPE) patient’s tumor biopsy sample, obtained at the time of the first CCA diagnosis. Briefly total RNA was extracted using Ambion’s RecoverAll™ Total Nucleic Acid Isolation. Complete Whole Transcriptome Amplification WTA2 Kit (Sigma) was used for reverse transcription and library amplification. Hybridization was performed according to CustomArray ElectraSense™ Hybridization and Detection protocol. Hybridization efficiency was detected electrochemically using CustomArray ElectraSense™ Detection Kit and ElectraSense™ 4X2K/12K Reader.
We next used bioinformatical software Oncobox to analyze gene expression data and to identify molecular pathways differentially regulated in the patient’s tumor sample []. Based on the abundance of gene transcripts for the molecular targets of anticancer drugs, Oncobox also makes it possible to generate a rating of target drugs potentially effective for the individual patients [, ]. Particularly, this analysis revealed that the ERK and Ras molecular signaling pathways were highly activated in the CCA patient’s tumor biopsy (Fig. ), the predicted rating of the most effective target drugs is shown in Table . Regorafenib, a multi-tyrosine kinase inhibitor was on the top position of the rating. However, there were no published studies of Regorafenib efficacy and tolerability in CCA. At the same time, several case reports demonstrated efficiency of TKI target drug Sorafenib for CCA treatment [–]. We, therefore, decided to use Sorafenib as the next line therapy and it was prescribed to the patient (800 mg daily) in May 2016. Treatment with Sorafenib coincided with the decrease of serum GGT level. MRI analysis in October 2016 revealed moderate tumor growth, corresponding to disease stabilization (Fig. c). However, additional nodules occurred slightly below the xiphoid process in the diaphragm area. Therefore, disease progressed according to RECIST criteria. And, importantly, after Sorafenib treatment, the patient did not complain of pain in the right hypochondrium. Before Sorafenib treatment the patient received Tramadol (100 mg im once a day) and Fentanyl (75 µg/h, Duragesic transdermal tape). After 1 month of treatment with Sorafenib the pain medication was switched to Ketoral (30 mg im twice a day). Considering all the above-mentioned facts it was decided to continue Sorafenib treatment. MRI performed in January 2017 revealed progression of tumor growth and additional nodule in the left lung (Fig. d). In addition, the following side effects occurred: redness, swelling, pain on the palms of the hands and soles of the feet. GGT level increased up to 319 U/L in December 2016.
The treatment regimen was next changed to Pazopanib, another TKI drug recommended based on the Oncobox rating. Sunitinib was not chosen because we attempted to eliminate the hand-foot syndrome, which occurred during Sorafenib administration. In the previous studies, Sunitinib treatment of CCA patients induced hand-foot syndrome in 43% of patients []. On the other hand, recent clinical trial of Pazopanib in combination with Trametinib in CCA did not report hand-foot syndrome as a side effect []. Pazopanib administration (800 mg daily) started since January 2017. The control MRI in July 2017 revealed progression in the lung nodes and 20% increase in sum of diameters of target lesions, which is a borderline between stabilization and progression according to RECIST (Fig. e). However, the change of treatment regimen resulted in elimination of Sorafenib side effects and general improvement of life quality. In addition, start of Pazopanib treatment coincided with a start of a trend towards decrease of serum GGT level (Fig. ). As for October 2017 (2 years after initial diagnosis), the patient was alive and physically active, with Karnofsky scale 80%. Our patient passed away due to the liver failure in November 2017. |
pmc-6127953-1 | A 7-day-old male Red Holstein–Friesian calf (No. 1) and a 28-day-old male Holstein–Friesian calf (No. 2) underwent respectively hot iron disbudding and sham disbudding in the context of a cross-controlled prospective clinical trial (ethical approval by Cantonal authority 2014_52_FR) investigating acute and chronic pain after disbudding. The procedure was standardized as following: after sedation with IM xylazine (0.1 mg/kg) an intravenous catheter was placed in a jugular vein and bilateral cornual nerve anesthesia (lidocaine 2%, 200 mg in total) was provided. In order to record physiologic nociceptive changes, heart rate (HR), respiratory rate (RR) and invasive blood pressure (IBP) were monitored during the procedure and hourly for the following 8 h. Prior to disbudding, an arterial cannula was placed in a caudal auricular artery and connected with the arterial monitor line previously filled with heparinized saline (100 IU/mL) from a fluid bag under 250 mmHg pressure. The bag was hanging vertically and only after verification that all parts were primed with fluids, the tubing system was connected to the arterial cannula. After zeroing the system at the height of the heart, to assess that the amount of damping was appropriate, the inline flushing device adjacent to the pressure transducer (Codan System DPT-6000, Codan Medical AG, Switzerland) was rapidly squeezed and released (fast flush test).
Baseline IBP was 110/64/80 mmHg (SAP/DAP/MAP) and HR 79 beats per minute (bpm). Few seconds following the arterial flushing, IBP increased moderately (149/103/118 mmHg), and peak values were reached within 1 min (238/161/190 mmHg). During the hypertensive phase, HR first decreased slightly (68 bpm) and then increased up to 141 bpm. A short hyperpnoea (60 breaths per minute) was noticed. Concomitantly, the calf showed mild excitation, vocalization and purposeless movements, horizontal nystagmus and finally sensory depression. Over the following 10 min IBP decreased progressively to 166/126/141 and HR to 98. Disbudding was performed as foreseen. One hour later, sensory depression ameliorated and IBP returned to the baseline level. In the following 2 h a clinical improvement was observed, the calf could stand, yet it was reluctant to move. Four hours later, the calf could stand but right hemiparesis and severe ataxia were noticed and clear proprioceptive deficits on the right forelimb appeared. However, at that time, IBP, HR, RR remained in the baseline range. Neurologic examination revealed bilateral deficits of the V, VII and VIII cranial nerves. Sensory depression worsened progressively. An arterial blood sample taken 9 h after disbudding indicated mild hypoxemia (PaO2 = 78 mmHg with 0.2 FiO2), with normocapnia. Moderate hyperglycemia (6.6 mmol/L) was also present. When milk was offered, gag reflex was absent. Despite fluid and oxygen-supportive therapy during the night, the calf’ clinical conditions progressively worsened; the following morning, he was severely hemiparetic, stuporous and unable to drink. Blood gas and electrolyte analysis was unremarkable. Bilateral periocular edema and increased tension of the eye globe and opacity of the anterior chamber was noticed in the left eye (Fig. ). Menace response was bilaterally absent. Euthanasia was performed for ethical reasons.
Necropsy revealed a mild, diffuse, acute anterior uveitis with occlusion of the filtration angle and glaucoma in the left eye. Multifocal petechiae were noticed on the skin. In both lungs, a severe alveolar edema was present with neutrophilic infiltration of terminal bronchioli and surrounding alveoli, interpreted as a mild acute bronchopneumonia. Multifocal perivascular edema was noticed in the heart. The brain was macroscopically normal, but the histological examination revealed bilateral, well demarcated, infarct-like areas of necrosis in the brainstem, which were most conspicuous ventrolaterally to the hypoglossal nuclei (Fig. ). These areas were characterized by edema, axonal swelling, neuronal eosinophilia and loosening of parenchyma with cavity formation. Small vessels within these areas had ill-defined and hypereosinophilic walls with necrotic endothelial cells (vessel wall necrosis) and contained degenerated neutrophils. Additionally, small infarcted areas were observed in the cerebellar vermis and in the cortex. Infarcts were associated with the presence of fibrin thrombi in small-sized vessels and capillaries and perivascular microhaemorrhages. These findings were interpreted as suggestive of disseminated intravascular coagulation (DIC).
Despite that, no entry of air bubbles into the arterial cannula was noticed; we suspected retrospectively a retrograde cerebral arterial embolism as air was noticed in the distal part of the tubing system.
After successful placement of the arterial line, the tubing system was filled with the inline flushing device adjacent to the transducer and carefully checked for the presence of air bubbles. Baseline rectal temperature was 38.8 °C. IBP was 115/58/78 mmHg and HR 109 bpm. Thereafter, a fast-flush test was performed, and some bubbles were noticed entering the arterial cannula under high pressure. The investigators (DC and AM) recognized later on that there was a partial disconnection of the luer-lock connector between the flushing system and the transducer. We hypothesized therefore the same mechanism for calf 1 (Fig. ). Few seconds after the inadvertent bubbles injection, the calf laid in lateral recumbency, showed excitation, hyperextension of the forelimbs, horizontal nystagmus and V and VII cranial nerve deficit. IBP pressure increased over 1 min up to 158/102/120 mmHg and concomitantly HR increased up to 128 bpm. The calf was repositioned in sternal recumbency, furosemide, 1 mg/kg, was injected IV and oxygen was provided. As the blood pressure increased further to 170/116/134, a second bolus of furosemide was injected (1 mg/kg IV). Over the next 2 min, IBP decreased to 153/92/112. HR decreased to 100 bpm and neurologic symptoms ceased. Sham disbudding was performed 1 min later when IBP was 138/74/95 mmHg and HR 98. One hour after disbudding, the calf was calm and still lying in sternal recumbency, but interactive. When encouraged, he could stand up without showing paresis. Blood pressure (115/60/80 mmHg) and HR (115 bpm) approached the baseline values. Slight hyperthermia (39.2 °C) was recorded. Respiratory rate remained in the normal range. No abnormalities were noticed in the following hours apart from slight hyperthermia (maximal peak 6 h later 39.6 °C). Behaviour and motor functions were deemed normal throughout the day; 8 h after disbudding, the calf showed normal temperature (38.8 °C) and normal appetite and it was reintroduced in the herd. The calf was observed for the following 3 months and it did not show either behavioral or neurological alterations. |
pmc-6128017-1 | In a 71-year-old, female patient with GCA, MRI showed vasculitis of the abdominal aorta and both common iliac arteries. Response to methotrexate alone or combined with leflunomide, and cyclophosphamide was inadequate, upon which TCZ-IV was commenced. After two initial intravenous applications, TCZ was switched to TCZ-SC. Prednisolone was tapered to 5 mg within 4 months without symptoms indicating relapse. The patient relapsed after seven months, with cervical tenderness, signs of aortitis on MRI and vessel wall thickening of the carotid arteries (daily prednisolone dose at relapse: 5 mg). TCZ-SC was switched back to TCZ-IV, and prednisolone dose was increased to 30 mg with consecutive tapering. 3 months later, under 10 mg of prednisolone, wall thickening of the carotid arteries and of the aorta markedly decreased in CDU, and MRI respectively. The patient was free of clinical symptoms and remained in remission for 9 months (prednisolone dose 5 mg), until tocilizumab was stopped in preparation of valve surgery for progressive aortic regurgitation. 4 weeks after surgery, tocilizumab was restarted and prednisolone dose increased to 20 mg due to relapse (aortic histology, CRP). |
pmc-6128017-2 | In a 47-year-old, female patient with GCA and anterior ischemic optical neuropathy, MRI and CDU showed halo and increased wall thickness of both ACC. Steroid-sparing treatment with methotrexate, leflunomide, and azathioprine had to be stopped due to toxicity. Intravenous cyclophosphamide (cumulative dose: 8000 mg) was ineffective. Therefore, TCZ-SC was started. Within 6 months prednisolone could be reduced to 5 mg, and CDU aspect became normal. After 10 months of TCZ-SC treatment, the patient relapsed with severe cervical tenderness responsive to prednisolone (daily prednisolone dose before pulse 5 mg). Therefore, TCZ-SC was switched to TCZ-IV. After a further follow up of 24 months, the patient is still in remission after tapering prednisolone to 3 mg with normal CDU. |
pmc-6128017-3 | In a 21-year-old, female patient with TAK, CDU showed vessel wall thickening of both ACC, occluding the right one, of both internal and external carotid arteries, the left subclavian artery with occlusion, and the left vertebral artery with occlusion. She relapsed after 2 months of treatment with methotrexate and prednisolone, wherefore TCZ-SC was added and prednisolone increased from 15 to 100 mg. While tapering prednisolone in the following 4 months, the patient suffered two minor and one major relapse (severe cervical tenderness and progressive wall thickening in CDU), treated by prednisolone pulses. Prednisolone was increased from 15 mg to 100 mg and TCZ-SC was switched to TCZ-IV. Since the switch, no further relapse occurred during follow up of 20 months, and prednisolone could be tapered to 4 mg. |
pmc-6128371-1 | A 78-year-old male with multiple comorbidities, including hypertension, hyperlipidemia, and type II diabetes mellitus, presented to our emergency setting with complaints of recurrent bouts of abdominal pain and fluctuating fevers for the previous two weeks. The patient reported that the pain is a new manifestation of a previously dull aching pain that had waxed and waned over the last decade. His description alluded to a pain that was sharp and intermittent with localization in the right upper quadrant. He could not attribute the intermittent nature of his predicament to any aggravating or relieving influences. The pain was associated with fluctuating low-grade fevers (99°F-100°F), anorexia, and an associated 13-pound weight loss, which culminated in a visit to our clinical setup.
Further interrogation disclosed that the patient underwent a laparoscopic cholecystectomy in 2003. The ensuing year was relatively pain-free but was followed by recurrent bouts of right upper quadrant pain, albeit less upsetting than his current presentation. He was subsequently diagnosed in 2005 with gallstone spillage. The patient chose conservative treatment for his abdominal pain, rather than invasive interventions, which included the administration of acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs). This treatment modality was sufficient for the duration of a decade. He presented to another medical facility with similar complaints of fever and abdominal pain in 2016. A computed tomography (CT) scan of his abdomen disclosed the presence of a necrotic phlegmon, which was subjected to aspiration. Its composition included a combination of fibrous material, granulation tissue, and inflammatory infiltrate. The aspiration provided considerable relief of symptoms and he was discharged on a gabapentin prescription that was well-tolerated and produced sustained amelioration of his pain, with only occasional wavering with respect to his baseline.
The initial assessment showed an elderly gentleman, who was alert and well-orientated but under considerable distress due to the abdominal pain and accompanying chills. He had a fever of 104°F, a heart rate of 120 beats per minute, a blood pressure of 95/70 mm Hg, and a respiratory rate of 19 per minute. An abdominal exam revealed a non-protuberant, soft, and tender abdomen with marked sensitivity in the right upper quadrant. He had perceptible bowel sounds, an absence of dullness on percussion, and a clear rectal vault. Pertinent initial laboratory investigations included an elevated white blood cell (WBC) count of 16,900/µL, C-reactive protein (CRP) of 6.5 mg/dL, and a random blood glucose (RBG) of 280 mg/dL. The patient subsequently underwent a whole body CT scan, which revealed a large 19-cm sub-diaphragmatic, right retroperitoneal abscess, which was inferior and posterior to the right hepatic lobe (Figure ).
In lieu of these findings, the patient was admitted and started on a combination of intravenous fluids, intravenous (IV) vancomycin and piperacillin-tazobactam due to an underlying suspicion of sepsis secondary to a hepatic and/or perihepatic liver abscess caused by a lack of gallstone retrieval following his cholecystectomy. He was subsequently subjected to a percutaneous CT-guided drain placement, which allowed for the evacuation of approximately 700 mL of grossly purulent material and provided prompt pain relief. The fluid sample was sent for a gram stain, culture, and a bilirubin assay. The gram stain of the abscess fluid revealed branching gram-positive rods concerning for Actinomyces, Nocardia, and Streptomyces; therefore, the patient remained on IV vancomycin and piperacillin-tazobactam, with the addition of trimethoprim-sulfamethoxazole (TMP-SMX) to the antibiotic regimen. Remarkably, the culture growth was positive for Propionibacterium and ampicillin-sulbactam was added to the list of antibiotics. Two days later, the patient was shifted to the intensive care unit (ICU) following unrelenting fever and persistent tachycardia, even after his abdominal drain placement was supplemented with vigorous antibiotic and antipyretic therapy. His ICU stay was complicated by episodes of dyspnea, tachypnea, and pleuritic chest pain, while a chest auscultation unveiled a decrease in breath sounds at the right basal region. A repeat CT scan confirmed the reduction in the size of the abscess and showed a new right-sided pleural effusion, which explained the patient’s breathing difficulties (Figure ).
The patient underwent an ultrasound-guided chest tube placement, which evacuated 10 mL of purulent fluid, followed by two doses of lytic therapy with tissue plasminogen activator (tPA) via the catheter. The following morning, he described an aggravation in his pleuritic chest pain, and an episode of shortness of breath, whereby, the oxygen saturation dipped to 90%. A new chest CT scan was ordered, which showed an interval increase in the right basilar opacity with a moderately sized pleural effusion (Figure ).
He was subsequently upgraded to a larger catheter via a CT-guided approach that evacuated a total of 900 mL of purulosanguinos fluid. The patient tolerated subsequent lytic therapies well and showed vast clinical improvement following this procedure, with a reduction in dyspnea, pleuritic chest pain, and fever, as well as a down-trending of his inflammatory markers.
A repeat CT scan was performed on the 10th day of admission, which revealed a near-complete resolution of his right-sided pleural effusion, and a decrease in his right-sided retrohepatic intrabdominal abscess (Figure ).
The chest drain was removed and the patient was subsequently discharged with a transhepatic drainage catheter, daily intravenous ampicillin-sulbactam, and acetaminophen, as needed for pain control. The patient was shifted to oral amoxicillin-clavulanate a month after the resolution of his pain, fever, and stabilization of inflammatory markers. The transhepatic percutaneous drain was left in place in order to allow for the formation of a chronic drainage tract, with hopes of localizing the perpetrating gallstones at its base.
Two months after discharge, the patient underwent a procedure for upsizing the drain in order to accommodate for a choledochoscope into the abscess cavity and the maturing sinus tract. He subsequently underwent an abscess cavity endoscopy, whereby a catheter and scope were advanced into the cavity for exploration. An abscess catheter study was performed through the existing catheter and showed no filling defects, after which the catheter was removed and an endoscope was inserted for direct visualization of the main cavity, as well as the two “fingers” branching out of the abscess cavity. Two small stones were expelled after flushing the main cavity multiple times. Following the expulsion of the gallstones, a replacement catheter was advanced into the cavity and a second catheter study was performed to rule out the possibility of any other stones. The patient tolerated this intervention well and had no further drainage from the intra-abdominal drain.
Following a lack of drain output and resolution of symptoms after his last endoscopic procedure a month ago, the patient's intra-abdominal drain was removed. The patient is currently stable and is being followed as an outpatient to date. |
pmc-6128586-1 | A previously healthy 24-year-old male presented to the emergency department with a head injury after falling 15 feet, and he was admitted with a diagnosis of a TBI to his right lateral frontal lobe. He was monitored for four days in the neurology intensive care unit and then discharged after improvement in symptoms. Three weeks from the initial injury the patient was brought into the emergency department by his family with symptoms like insomnia, atypical aggression, psychosis, and impulsive behavior. Upon arrival in the emergency department, the patient admitted to new onset suicidal and homicidal ideations with a plan to shoot himself and the (illusory) “friend who murdered his family and robbed his home” with a loaded gun in his possession. He admitted that two days prior to re-admission, he had become frustrated upon return to work, had not slept for 26 hours, and began damaging items around his house. He admitted to increased aggression, hallucinations, and paranoid ideations.
The patient, accompanied by his mother, denied any previous family or personal psychiatric history. His mother stated his personality had become increasingly impulsive and aggressive since his previous discharge from the hospital. The patient complained of worsening auditory and visual hallucinations, insomnia, headache, and visual floaters. The patient denied nausea, emesis, weakness, gait difficulty, and focal motor defects.
The patient had an unremarkable past medical history. Hypertension was diagnosed during his initial admission and he was started on lisinopril for management. Social history included intermittent alcohol and occasional marijuana use. He denied any tobacco or other illicit drug use. He lived with his parents, was in a monogamous relationship with his girlfriend, and worked in the construction field.
Upon this admission three weeks postinjury, the patient presented with a blood pressure of 152/92 mmHg and a heart rate of 105 beats/minute. He was alert, oriented, anxious, and agitated. His five-digit forward recall was 4/5, and he was able to spell the word “WORLD” backwards and forward. The patient spoke with a normal rate and volume and without aphasia. Speech was coherent and goal-directed. Mood was anxious and affect-constricted. He had paranoid ideations with auditory and visual hallucinations. His heart had a regular rhythm without clicks or murmurs. Lungs were clear to auscultation bilaterally, and he had a soft and nontender abdomen with normoactive bowel sounds. Neurological examination revealed cranial nerves II-XII were intact bilaterally. Patient had 5/5 strength bilaterally without pronator drift. No pathological reflexes were noted.
Upon chart review, a two-week routine follow-up CT after his initial injury revealed increasing cerebral edema on the right parietal lobe with no increasing mass effect or midline shift (Figure ). It also noted a nondisplaced fracture of the right temporoparietal region that was not commented on prior imaging.
On day one of this admission, three weeks postinjury, the patient’s electroencephalography was unremarkable, and an MRI showed several acute/subacute cerebral contusions within the right frontotemporal region; with progression of the temporal lobe contusion (Figure ). It showed mild associated perifocal edema without significant mass effect or midline shift. Four days later, a second MRI of the brain showed no significant changes. A third brain MRI was taken after the patient accomplished a full night’s rest and psychotic symptoms had resolved (Figure ). This MRI showed a persistent dominant focus in the right temporal region that was well demarcated and stable in size. It showed resolving white matter edema and improving post-traumatic foci of altered signal intensity when compared with prior imaging.
A multi-disciplinary team was consulted which included a hospitalist, neurologist, neurosurgeon, psychiatrist, occupational therapist, physical therapist, and speech therapist. Upon this admission, the patient suffered from fluctuating auditory and visual hallucinations, anxiety, headaches, and agitation. He was started on dexamethasone, valproic acid and lorazepam, which did not alleviate his psychosis. Throughout the hospital admission, the patient reported some insight and memory to these symptoms; yet, he reported being unable to control them. Although he could recall all the events, at times he was unable to differentiate between reality and the hallucinations. Throughout the next week, a new medication was incorporated into his regimen daily to help induce sleep. These medications included high-dose trials of zolpidem, hydroxyzine, quetiapine, and olanzapine. The patient was finally able to accomplish rest with the combination of 20 mg intramuscular (IM) ziprasidone and 2 mg IM lorazepam on the seventh evening. After one night of sleep the patient was alert, oriented, cooperative with normal mood and affect. The following morning postsleep, his hallucinations and psychosis ceased completely. A few days later he was discharged to his home under family supervision with scheduled outpatient TBI rehabilitation to follow. |
pmc-6128587-1 | A woman in her late 30s, with a history of SLE characterized by positive anti-nuclear antibodies, anti-Smith antibodies (1:160), anti-double-stranded deoxyribonucleic acid (anti-dsDNA) antibodies (> 1:640), anti-ribonucleoprotein (anti-RNP) antibodies, lupus anticoagulant, immunoglobulin M (IgM) anti-cardiolipin antibodies (27, normal: 0 - 12 U/ml), hypocomplementemia (C3 < 40, normal: 90 - 165 mg/dl; C4 < 8, normal: 10 - 40 mg/dl), rheumatoid factor of 50 IU/mL (negative: < 13.9), elevated erythrocyte sedimentation rate (ESR), arthritis, lymphopenia, and thrombocytopenia, presented to our clinic with new proteinuria (spot urine protein/creatinine ratio 1,059 mg/g) and a normal creatinine (0.6 mg/dl). Evaluation for antibodies of perinuclear (p)-ANCA, cytoplasmic (c)-ANCA, and atypical p-ANCA were all negative. She underwent a renal biopsy that demonstrated focal, mild necrotizing crescentic glomerulonephritis. Glomerular staining showed non-specific 1+ linear staining of the glomerular basement membrane and rare 1+ granular mesangial staining for IgG, IgM, and kappa but with negative staining for immunoglobulin A (IgA), C3, C1q, and lambda. Taken together, this renal biopsy was summarized as a pauci-immune focal necrotizing/extracapillary proliferative glomerulonephritis. The patient was treated with rituximab, mycophenolate mofetil (3g daily), and prednisone but continued to demonstrate proteinuria with 0.73 g/24 hours, creatinine of 0.7 mg/dl, and no hematuria. She underwent a second renal biopsy (at a time when serologies demonstrated low C3 at 77 mg/dl and positive anti-dsDNA antibodies), which resembled class II lupus nephritis with limited subcapsular glomerular sample with deposits staining for IgG, IgM, kappa light chain, and C3, along capillary loops and peripheral mesangium with sparse deposits on electron microscopy. Given the concerns for steroid side effects, a change in insurance, and the lack of follow-ups, she was maintained on mycophenolate mofetil, 3g daily, and a low dose of prednisone, 5 mg, along with lisinopril. However, she continued to experience prolonged morning joint stiffness and her hand MRI demonstrated synovitis. Adding methotrexate led to significant improvement in her arthritis. By 23 months after the initial renal biopsy, she continued to have proteinuria, intermittently low C3, and positive anti-dsDNA antibodies and underwent a third renal biopsy. This biopsy, similar to the first sample, demonstrated a pauci-immune focal proliferative segmental crescentic/necrotizing lesion in 30% of the glomeruli. On repeat serologic testing, her c-ANCAs, p-ANCAs, and atypical ANCAs were still negative. |
pmc-6128598-1 | A 71-year-old female with the history of HTLV-1 infection for 20 years, congestive heart failure, coronary artery disease, hypertension, diabetes type-2, peripheral vascular disease, chronic neck and back pain, nonambulatory for a year admitted to the medical service as dehydration and acute kidney injury. Neurology was consulted for worsening weakness and pain in the legs with paresthesia as well as evaluation for HTLV-1 myelopathy with pain, stiffness and gait problems. Neurological examination showed flat, mask-like face with a positive glabellar reflex. She was noted to have decreased power bilaterally in upper and lower extremities with brisk reflexes and hypertonia. Motor examination of upper extremities showed a strength of 4 x 5 with brisk reflexes and also noted to have resting as well as intention tremor. Lower extremity muscle power was 2 x 5 with brisk reflexes and bilateral clonus and bilaterally upgoing toes. Sensory examination was normal with generalized diffuse rigidity. Her workup included computed tomography (CT) scan of the brain showing bilateral basal ganglia calcifications and mild cortical atrophy, magnetic resonance imaging (MRI) brain T2W image demonstrating low signal intensity from iron accumulation in the red nucleus, and substantia nigra and atrophy of the cerebral cortex and superior vermis of the cerebellum (Figure ). MRI C-spine, MRI of the thoracolumbar spine and magnetic resonance angiogram (MRA) were unremarkable. Serum HTLV-1 antibody was positive by enzyme immunoassay (EIA) and glutamic acid decarboxylase (GAD65) antibody was also positive at 8 IU/ml by enzyme-linked immunosorbent assay (ELISA). The clinical evaluation was suggestive of HTLV-1 related myelopathy with parkinsonism and patient was started on a trial of baclofen and Sinemet® (carbidopa-levodopa). |
pmc-6128601-1 | A 31-year-old Asian American female with past medical history of chewing of betel leaf with betel nuts and non-smoker, who immigrated to the USA from Burma four years previously, was referred to the Digestive Health Center at the University of Virginia for evaluation of elevated transaminases discovered upon routine testing. She reported no previous history of liver test abnormality or liver disease. She was not using any hepatotoxic prescription or over the counter medications or supplements and reported rare consumption of alcohol. Besides, she had no family history of liver disease, hepatocellular carcinoma, autoimmune disorders or diabetes mellitus.
The physical examination was significant for obesity with weight 66 kg, height 146 cm, body mass index (BMI) 31, hepatomegaly, nonpalpable spleen, and lack of stigmata of chronic liver disease. Extensive laboratory workup revealed normal complete blood count, renal function, serum electrolytes, iron studies, serum immunoglobulin levels, and ceruloplasmin. Also, hepatitis B and C serologic tests and autoimmune markers were negative. Fasting lipid profile revealed dyslipidemia (total cholesterol 260 mg/dL, triglycerides 267 mg/dL, high density lipoprotein 45 mg/dL, and low density lipoprotein 170 mg/dL). Fasting blood glucose was 165 mg/dL with simultaneous fasting insulin level of 4.8 mill international units/liter and a homeostasis model assessment of insulin resistance score of 2.9, thus has insulin resistance. Hemoglobin (Hgb) A1c level at this time was 6.8% which was higher than previous values from eight months prior (6.1%), 16 months prior (6.1%) and 39 months prior (4.8%).
Ultrasonographic evaluation of the abdomen revealed hepatomegaly, hyperechogenic liver indicative of severe hepatic steatosis, an ill-defined liver mass, and standard spleen size. Magnetic resonance examination defined the liver mass as hemangioma in addition to hepatomegaly and severe hepatic steatosis. Ultrasound-guided liver biopsy (sample size of 3.5 cm) showed severe macrosteatosis with mild lobular and periportal inflammation associated with focal hepatocyte damage (Figure , Panel A). Trichrome staining revealed focal portal, periportal and perisinusoidal fibrosis consistent with stage II (Figure , Panel B) with a NASH activity score (NAS) of 7. The patient was instructed to exercise routinely and follow a healthy diet. She was seen in follow-up for three months at which time her weight was unchanged. Physical examination revealed dark brownish red pigment on the teeth, tongue, and oral mucosa. Upon questioning the patient about this finding, she admitted to chewing betel on an average of 10 times per day for the last eight years. The patient reported an associated weight gain of around 16 kg from her baseline weight maintained for many years at 50 kg (BMI 23.5). This significant weight gain could not be reversed despite daily physically demanding work and following a healthy diet recommended by her primary care physician. |
pmc-6128602-1 | A 59-year-old male with no significant past medical history presented to the emergency department (ED) with a sudden onset of chest pain and shortness of breath that had begun while he was eating dinner. The physical examination was unremarkable, including the chest examination, except that the patient remained quite anxious. A blood sample analysis was within the normal range, including troponin. The electrocardiogram (EKG) was unremarkable. A plain chest radiograph did not show any abnormality. A computed tomography (CT) scan of the neck revealed a 2.5-cm long rectangular prism-type bone, horizontally lodged in the esophagus at the level of the aortic arch (cervical vertebra 7-thoracic vertebra 1, as shown in Figure ). Because the patient was symptomatic and the CT neck scan showed the presence of a sharp, pointed bone, esophagogastroduodenoscopy (EGD) was performed under general anesthesia, which involved the retrieval of a piece of bone from the upper esophagus just below the upper esophageal sphincter (Figure ). The foreign body was removed with the help of queen retrievers (Figure ). The patient did well after the removal of the foreign body and did not suffer a recurrence of the prior chest pain. He was discharged home on proton pump inhibitors. |
pmc-6128997-1 | A 63-year-old Caucasian man, a dentist, was referred by another professional with an epiretinal membrane and cataract in his left eye. His medical history revealed he had hypertension for the past 6 years under treatment. He had no relevant history of eye problems. His visual acuity test was 20/30 in his left eye. An ophthalmologic examination of his left eye revealed a nuclear cataract ++, epiretinal membrane with microfolds, and macular edema confirmed by a macular optical coherence tomography (OCT) scan. Phacovitrectomy was performed in his left eye under general anesthesia. On postoperative day 1, he did not experience pain and his visual acuity was 20/50. The findings included: a corneal edema, well-positioned intraocular lens, and Tyndall +. A fundoscopy showed an attached retina. On postoperative day 7, he did not experience pain and visual acuity was 20/20. The pseudophakia was unremarkable and an attached retina, without an epiretinal membrane, was observed on the fundoscopy. On postoperative day 20 he was admitted to an emergency ward due to severe eye pain that woke him up in the middle of the night. He described it as a severe, paroxysmal, lancinating facial pain and rated it as a 10/10 lasting 10 to 30 seconds. It radiated to the distribution of the first division of the right trigeminal nerve. He denied contralateral pain. On physical examination, he was neurologically intact. No family history of neurological problems was found. His visual acuity was 20/20. Pseudophakia and nasal choroidal detachment were observed. After consultation with specialists from the anesthesia and neurology departments, he was diagnosed as having TN with ophthalmic branch involvement. A complete blood count (CBC) test and liver function test were ordered and the results were unremarkable. Normal findings on both CT and MRI were reported. Treatment with tramadol and morphine was started. A good response to medical treatment was observed. He had some episodes of TN during the first 2 months. After 1 year of follow-up, he did not have any more episodes of TN. |
pmc-6128997-2 | A 38-year-old Caucasian man, a mechanic, presented at the Ophthalmology unit of Sanatorio Mapaci with a perforating wound in his right eye. He had no relevant past medical/family history or eye problems. Visual acuity was hand motion in his right eye. Slit lamp biomicroscopy showed a penetrating wound in the cornea between hours 3 and 7, anfractuous injury, iris prolapse, and grade IV hyphema. There was no visualization of the posterior segment structures. Primary closure of the cornea with removal of the necrotic iris was performed on the same day under general anesthesia without a nerve block. On postoperative day 1 he did not experience pain and his visual acuity was light projection; IOP was 6 mmHg. The corneal wound was sealed with seven stitches (10/00 nylon sutures), Seidel test was negative, and hyphema was grade IV. He made good progress during the following days. On postoperative day 6 he was admitted to an emergency room due to severe pain in the right side of his face activated by numerous facial stimuli. He described it as disabling lacerating pain and rated it as a 10/10. A neurological examination was unremarkable. On a visual acuity test, he was able to count fingers at 10 cm. Slit lamp biomicroscopy showed a sealed corneal wound and grade III hyphema; IOP was 16 mmHg. He was referred to a medical clinic and underwent anesthesiology, where he was diagnosed as having TN. Blood tests including CBC and liver function test were normal. Normal findings in both CT and MRI were reported.
Treatment with tramadol, pregabalin, and B12 complex was started; during the first 2 months of medication he lost 9 kg (20 pounds) from not eating for fear of exacerbating the pain. Chlorpromazine and carbamazepine were added and his course evolved with sporadic pain. |
pmc-6128997-3 | A 52-year-old Caucasian man, a construction worker, was referred 15 days after suffering a blunt trauma to his right eye. His visual acuity was no light perception. An ophthalmologic examination revealed a clear cornea, traumatic mydriasis, aphakia, and Tyndall +++. The findings included: intraocular pressure (IOP), 40 mmHg; a pale optic disc with well-defined edges; temporal retinal necrosis; and an intumescent crystalline lens at hour 6. Vitrectomy was performed to remove the crystalline lens. On postoperative day 1, he did not experience pain. The findings included: visual acuity; no light perception; traumatic mydriasis; aphakia; Tyndall ++; IOP, 12 mmHg; and temporal retinal necrosis. On postoperative day 7, he was admitted to an emergency room with severe and excruciating pain in the right side of his face, predominantly in his right eye. After consultation with specialists from the anesthesia and neurology departments, he was diagnosed as having TN, with ophthalmic branch involvement. Blood tests were unremarkable. Normal findings on both CT and MRI were reported. He reported that Valsalva’s maneuver triggered pain. Treatment with tramadol, pregabalin, and B12 complex was started. A good response to medical treatment was observed. |
pmc-6128999-1 | The proband was a preterm newborn boy, the first child of non-consanguineous parents, born at 31 weeks gestation to a 44-year old father and a 43-year old mother by cesarean section. At birth, the child weighed 1,480 g, measured 44 cm in crown-to-heel length, and exhibited multiple congenital anomalies. The newborn was transferred to the Intensive Care Units (ICU) immediately after birth. His general health condition deteriorated progressively, leading to his death at 105th days after birth. The newborn had brain malformation, including ventriculomegaly and corpus callosum dysgenesis, cleft lip and palate, retrognathism, hypertelorism, clenched hands with overlapping fingers, and hypotonia. Additionally, he revealed mild heart septal hypertrophy, ambiguous genitalia, enlarged kidneys without corticomedullary differentiation, and gallbladder with tiny cystic formations (Fig. ). His mother had three miscarriages from previous marriages and one miscarriage with her current husband. The remaining of his family history was otherwise unremarkable.
Both parents signed a written informed consent and the mother signed as the legal representative for the child. Peripheral blood was obtained to isolate genomic DNA for CMA using Qiagen QIAamp® DNA Mini kit (Hilden, Germany). Karyotyping was performed in a private laboratory through conventional cell culture, harvesting, and GTG banding with a > 550 bands resolution following standard procedures []. Chromosome analyses were done using Zeiss Axio Scope (Jena, Germany) and the software IKAROS® (Metasystems Corporation, Altlussheim, Germany). All laboratory procedures were carried out following international standardized protocols and consensual criteria of quality.
The CMA was carried out on proband and his biological parents using the GeneChip® CytoScanHD™ (Affymetrix, Santa Clara, USA) following the manufacturer’s recommendations without modifications. Chromosomal analyses were done using the Chromosome Analysis Suite (ChAS®) software (Affymetrix, Santa Clara, USA) and the CNVs found in the patient were analyzed in comparison with public databases, including Database of Genomic Variants (DGV), Database of Chromosomal Imbalance and Phenotype in Humans using Ensemble Resources (DECIPHER), and CytoScanHD™ Array Database. Furthermore, CNVs were classified according to their nature, based on [, ].
The proband showed a male karyotype with a large submetacentric SMC in 90% of the analyzed metaphases after counting 50 metaphase spreads. His karyotype was 47,XY,+mar[45]/46,XY[5], suggesting 10% mosaicism. The parental karyotypes and CMA results had no visible numerical or structural alterations. The proband’s CMA revealed the marker chromosome corresponded to a de novo 70.77 Mb gain at arr[GRCh37] 9p24.3q21.11(203,861_70,974,662)× 4[0.3] dn with 30% mosaicism, encompassing 286 genes, including 152 OMIM morbid genes (Fig. ). |
pmc-6129296-1 | A 76-year-old Korean man presented with upper back pain for 2 months and motor weakness in both lower extremities for 2 days. A chest radiograph and computed tomography (CT) performed at another institution showed a pleural mass in the upper lobe of his right lung. He was referred to our hospital for evaluation of the pleural mass and paraplegia. He had been treated with medication for 4 years for type 2 diabetes mellitus and primary hypertension. He did not have a family history of malignant disease. On chest examination, he had tenderness at the level of the fifth rib on the right side. On neurologic examination, he showed paraplegia with numbness and a sensory deficit below the T5 dermatome.
Laboratory findings showed an elevated C-reactive protein level of 6.84 mg/dL (normal range, 0.0–0.3 mg/dL), blood urea nitrogen of 25 mg/dL (normal range, 7.8–22.0 mg/dL), and a serum creatinine of 1.5 mg/dL (normal range, 0.6–1.4 mg/dL). Urine analysis showed 4+ blood, with many red blood cells and 0–1 white blood cells/high-power field (Table ).
A chest radiograph showed a large homogenous opacity in the right superior mediastinum. Contrast-enhanced chest CT showed a 7.3 cm × 4.4 cm × 7.7 cm heterogeneous pleural mass involving the right fifth rib and vertebral body (Fig. ).
Contrast-enhanced abdominopelvic CT showed a mass infiltrating the right renal hilum without vascular occlusion or hydronephrosis (Fig. ). Spine CT and enhanced magnetic resonance imaging (MRI) showed a large pleural mass in the right paravertebral area at the level of T3 to T6 (Fig. , ). CT-guided percutaneous needle biopsy of the pleural mass was performed.
Histological findings on hematoxylin and eosin (H&E) staining showed proliferation of spindle cells with infiltration of lymphocytes and plasma cells (Fig. ). Immunohistochemistry showed neoplastic cells positive for CD68, focally positive for smooth muscle actin (SMA), and negative for cytokeratin and desmin (Fig. ). IMT was diagnosed based on the histological examination.
As the tumor could not be completely resected, treatment with glucocorticoids (methylprednisolone 1 mg/kg) and radiotherapy (5 days/week for 3 weeks at 3 Gy/fraction, 45 Gy/15 days) was started. After 1 month, laboratory findings were unremarkable. Hematuria, which is thought to be caused by kidney metastasis of IMT improved after treatment (Table ). Chest CT showed reduction in the size of the pleural mass (6.0 cm × 1.8 cm × 5.3 cm) and abdominopelvic CT showed decreased infiltration around the right renal pelvis (Fig. ). The summed-up diameters of both target lesions decreased from 121 mm to 91 mm, that is, a 24.8% reduction of baseline diameter. According to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria it could be defined as stable disease. He was discharged on orally administered glucocorticoids and showed improvement in symptoms on follow-up 1 month after hospital discharge. Since then, however, he has not attended a follow-up visit. |
pmc-6129320-1 | Index patient is a 28-year-old gravida 1 para 0 at 12 weeks and 3 days gestational age by the last menstrual period who presented for routine first trimester aneuploidy screening. During nuchal translucency ultrasound, pregnancy noted to be located within the cervix, specifically, 8mm from the external cervical os (). Fetal heart rate was 168 at this time and there were no notable fetal anomalies. Patient denied vaginal bleeding or pain. She denied any history of gynecologic surgery. Findings were subsequently confirmed by magnetic resonance imaging (MRI) (). The MRI showed a 6.5 x 4 x 5cm amniotic sac with embryo located within the cervix. Sterile speculum exam revealed no visible pregnancy tissue from os but enlarged and edematous cervix. HCG was 68,350 mU/mL at this time.
Given the proximity to cervical vasculature, the risk of life-threatening hemorrhage was very high. A multidisciplinary team including Reproductive Endocrinology, Maternal-Fetal Medicine, Gynecologic Oncology, and Interventional Radiology reviewed the case. At 12 weeks and 6 days gestational age, the patient was admitted to Special Delivery Unit (SDU) at the Cleveland Clinic.
Uterine artery embolization (UAE) under conscious sedation was performed with Gelfoam suspension in contrast until each uterine artery was embolized to stasis and confirmed by angiogram. Procedure was well tolerated and fetal heart rate was monitored before and after the procedure, per institutional policy. Initially the fetal heart rate was low and then not present after the procedure. Patient was then given weight-adjusted intramuscular methotrexate. On day 4 after MTX injection, patient remained asymptomatic with HCG of 19,795 mU/mL. Day 7 after MTX injection, HCG was 14,765 mU/mL. Patient was discharged on hospital day 11.
On postoperative day #14 after UAE, patient represented. Patient was febrile, with nausea/vomiting and with profuse vaginal bleeding. HCG at this time continued to show downtrend at 3360 mU/mL. Patient was taken to the operating room for dilation and curettage (D&C). Uncomplicated ultrasound-guided suction and sharp D&C were performed. Postoperatively, patient was febrile and tachycardic with evidence of pulmonary edema and acute vaginal blood loss. Patient was transferred to the intensive care unit for severe sepsis and acute kidney injury. Sepsis treated aggressively with vancomycin, clindamycin, and piperacillin-tazobactam and furosemide diuresis with clinical improvement. Antibiotics narrowed to renal-dosed piperacillin-tazobactam and then ampicillin-sulbactam. Patient was discharged in stable condition with IV antibiotic regimen. Patient was seen 2 weeks after discharge; kidney injury had resolved as well as vaginal bleeding; HCG was negative. |
pmc-6129327-1 | A 78-year-old woman with a long-standing history of anti-centromere antibody positive systemic sclerosis with limited skin involvement (CREST syndrome) initially presented to emergency room (ER) for a one-day history of hematemesis and mild abdominal pain. Her medical history was remarkable for peripheral artery disease and duodenal arteriovenous malformation. At presentation, her vital signs were within normal limits and her physical examination revealed mild periumbilical tenderness and decreased bowel sounds without significant signs of peritonitis. Laboratory studies revealed a WBC count of 29X10 ∧3/μl and a hemoglobin of 4.7 g/L which acutely declined compared with her baseline hemoglobin of 9.5 g/L. Renal/liver function tests were within normal limits. Elevated venous lactate level was noted. Patient received intravenous fluid resuscitation and empirical piperacillin/tazobactam as well as 2 units of red blood cells transfusion in ER. A subsequent computed tomography (CT) scan of the abdomen that showed significantly dilated colon and pneumatosis intestinalis (). No surgical intervention was deemed necessary per general surgery consultation, considering that the pneumatosis intestinalis was stable compared to the previous CT findings two years ago and the absence of acute peritonitis sign. Patient was then admitted to ICU for close monitoring and management of acute on chronic anemia from GI bleeding. Urgent esophagogastroduodenoscopy (EGD) only identified Barrett's-type esophageal mucosa, erosive gastritis without actively bleeding lesion. Patient was discharged home on the 4th day of hospitalization after tolerating liquid food. However, she was brought back to ER for severe lower abdominal pain just a few hours after discharge. The abdominal pain was sharp, constant, and nonradiating. No melena or hematochezia was reported. On examination, absent bowel sounds and abdominal distention without rebound tenderness or guarding were noted. Her laboratory evaluation was significant for leukocytosis and hypokalemia. Repeated CT scan of abdomen/pelvis showed distended small and large bowel loops, portal venous gas, and pneumatosis within the jejunum and colon (). Clinical diagnosis of bowel perforation was made, for which patient underwent emergent exploratory laparotomy. Patchy necrosis throughout the large intestine and a perforated lesion in the ascending colon were identified during the operation. Subtotal colectomy, omentectomy, and end ileostomy were performed. Pathological findings were consistent with colonic perforation with transmural ischemic necrosis and fibrosis (). CT angiography and conventional angiogram were performed to determine the culprit artery for bowel ischemia and identified a noncritical stenosis in superior mesenteric artery (). Patient was then transferred to ICU for postoperative care. Patient's recovery was complicated with ventilation dependent respiratory failure and another episode of bowel perforation. Given her advanced age, comorbidities, and poor prognosis, end-of-life care was discussed with family members, and they decided to initiate comfort care after a prolonged hospital stay. |
pmc-6129342-1 | A 26-year-old African-American gentleman presents to the emergency department with pressure-like retrosternal chest pain that occurred one hour after he completed a workout. His pain subsided after ingestion of an antacid. He has no known medical history and takes no medications. He is a current smoker with a pack-year index of 22. He smokes marijuana but denies other illicit drug use. Both his father and grandfather had hypertension, diabetes, and peripheral arterial disease requiring limb amputation, but there was no known family history of coronary artery disease.
EKG revealed a right bundle branch block with no ST segment or T wave changes indicating ischemia. Initial troponin level was elevated at 8 ng/ml (normal range: <0.03 ng/ml). The patient refused to be admitted for further evaluation and left the hospital against medical advice. He returned a week later, with no symptoms, only to complete the evaluation of his prior episode of chest pain. Echocardiography revealed akinesis in the basal and inferior walls with an ejection fraction of 50%. Coronary angiography revealed moderately to severely dilated aneurysms in the proximal segments of the left anterior descending, left circumflex, and right coronary arteries without flow-limiting lesions ().
The patient had no recollection of any febrile childhood illness that would be consistent with childhood Kawasaki disease. He was discharged on dual antiplatelet therapy and a high-intensity statin, as well as metformin for a new diagnosis of prediabetes. |
pmc-6129343-1 | An 80-year-old woman was accompanied by her son at the emergency department (ED) of our hospital because of progressive altered mental status and persistent high fever in the previous 48 hours. The patient had medical history of depression in treatment with bromazepam and olanzapine. At the ED evaluation, patient was conscious and alert with stable respiratory and hemodynamic conditions and fever (39°C) and mild abdominal pain without defensive reaction. Laboratory tests showed only an increased C-reactive protein (6,1 mg/dl). Abdomen ultrasound showed signs of previous cholecystectomy and a slight dilatation of biliary tree. Two hours later, the patient became progressively drowsy, cyanotic, and mottled on chest and lower extremities despite stable hemodynamic parameters. Arterial blood gas analysis (ABG) revealed mild hypoxia and hypocapnia. Blood and urine samples were collected for microbiological cultures before starting empiric therapy with piperacillin-tazobactam (loading doses 4, 5 g, and 18 g/day continuous infusion). Patient underwent chest and abdomen computed tomography (CT) that showed extended ground-glass area in basal lobes bilaterally () and hypoperfusion in liver, spleen, and kidneys and dilatation of intra- and extrahepatic biliary tree.
At the end of CT scan, the patient was transferred to the Intensive Care Unit (ICU) because of severe respiratory failure. At ICU, admission patient was unconscious (Glasgow Coma Scale (GCS) 3/15), hypoxic (SpO2 88% with FiO2 60%), and hypotensive (100/50 mmHg). At physical examination, we observed petechiae and purpura on her trunk and her skin was grayish and mottled (). ABG analysis showed a severe metabolic acidosis with lactate 16 mM. The patient became extremely hypotensive and after aggressive fluid resuscitation (40 ml/kg crystalloides) we started norepinephrine (up to 0,2 mcg/Kg/min). Hemodynamic measurements by pulmonary artery catheter revealed a low cardiac Index (CI) (1,3 L/min/m2). Echocardiography showed a severe depression of left ventricle ejection fraction without segmental akinesia and, thus, we started dobutamine infusion that after 2 hours was switched to levosimendan because of severe tachycardia without CI improving. At ICU admission, the patient showed severe leukopenia (610/mmc), thrombocytopenia (8000/mmc), and low levels of immunoglobulins (IgG 392 mg/dl, IgA 111 mg/dl and IgM 16 mg/dl); aPTT was undeterminable and INR was prolonged (2,79). Renal and hepatic functional indexes worsened compared to ED first evaluation with a total SOFA score of 22; troponin was high (847 ng/l) as well as procalcitonin (115 ng/ml). The severe hypotension and hyperlactatemia (17 mM) refractory to vasopressors, steroids, and inotropes led us to initiate blood purification (Cytosorb, CytoSorbents Europe GmbH, Germany) as rescue therapy 8 hours after admission. Despite aggressive therapies, cardiac arrest unresponsive to resuscitation maneuvers occurred 4 hours later.
During an extended interview with patient's family members some hours after ICU admission, an important anamnestic element was revealed: 3 days before hospital admission the patient was bitten by a dog, getting a small lesion on the fourth finger of the right hand. Two days after patient's death, the microbiological laboratory reported a blood culture positive for C. canimorsus sensitive to any tested antibiotic class. No other microorganisms were identified in the samples evaluated (rectal swab, skin lesions swab, bronchial secretion, urine, Legionella and Streptococcus pneumoniae antigens, CMV-DNA, and B-D-glucan). |
pmc-6129347-1 | A 20-year-old male with no past medical history presented with acute hypoxic respiratory failure requiring intubation. CT scans revealed a 9.1 × 7.3 cm mediastinal mass encasing the aortic arch with extension into the lower neck resulting in tracheal deviation. Laboratory evaluation demonstrated a white blood cell count of 2.5 × 109/L with 78% blasts on differential, hemoglobin 7.1 g/dL, and platelets 51 × 109/L. Bone marrow evaluation revealed a hypercellular marrow with 98% blasts by morphology. By flow cytometry, blasts expressed CD34, CD117, CD33, CD38, CD56, and CD7 and lacked expression of myeloperoxidase (MPO) and monocytic markers. A subset of blasts expressed low levels of cytoplasmic CD3 although subsequent assessment by immunohistochemistry for CD3 was negative. The blasts were negative for CD2, CD4, CD5, CD8, CD19, and cCD79a. Cytogenetic analysis revealed 10 metaphases with a complex karyotype including rearrangement of chromosome 4, loss of chromosomes 12 and 13, and a rearrangement between chromosome 13 and 1-2 unidentified markers. Molecular testing was positive for a FLT3-ITD mutation. A fine needle aspiration of the mediastinal mass demonstrated acute leukemia with an immunophenotype similar to that of the bone. T-cell gene rearrangement analysis by PCR on the mediastinal biopsy showed no evidence of clonal T-cell gene rearrangement. While it was difficult to assign a definite lineage for this acute leukemia, diagnostic considerations included acute myeloid leukemia (AML), T-ALL, and mixed phenotype acute leukemia T/myeloid (MPAL). To meet criteria for MPAL T/myeloid, blasts must express lineage-defining markers for both T and myeloid lineages []. This acute leukemia lacked MPO as well as monocytic markers and therefore did not meet criteria for the myeloid component of MPAL T/myeloid. While flow cytometry demonstrated weak cytoplasmic CD3 on the blasts suggestive of T-lineage differentiation, this could not be confirmed by immunohistochemical stains. Additionally, the blasts lacked expression of CD2, CD4, CD5, CD8, and CD1a. Therefore, a diagnosis of AML, NOS was initially favored.
The patient was induced with daunorubicin in combination with high-dose cytarabine and achieved complete remission (CR). He was consolidated with 2 cycles of high-dose cytarabine and in light of the FLT3-ITD mutation, sorafenib was added. Because his leukemia was considered “poor-risk” given the extramedullary disease at presentation, complex karyotype, and FLT3-ITD mutation, he underwent a 7/10 haploidentical allogeneic hematopoietic cell transplant (alloHCT) from his father in first remission. Conditioning included fludarabine, cyclophosphamide, and low-dose total body irradiation as per the standard Hopkins regimen []. Prior to alloHCT, multiparameter flow cytometry from the University of Washington showed no evidence of measurable residual disease (MRD). Posttransplant immunosuppression consisted of cyclophosphamide, tacrolimus, and mycophenolate mofetil. A bone marrow biopsy and restaging PET CT at approximately day +60 confirmed an ongoing CR and 100% donor chimerism in the CD3, CD14/15, and CD19 compartments. For posttransplant maintenance, he received 6 cycles azacitidine (given daily for 5 days at 32 mg/m2 in 28-day cycles)—initiated at approximately day +100—followed by maintenance sorafenib 200 mg twice daily. His tacrolimus was discontinued at approximately 6 months posttransplant with no evidence at any point of either acute or chronic graft-versus-host disease (GVHD).
At 13 months posttransplant, he developed progressive neutropenia. Bone marrow evaluation revealed relapsed leukemia with 42% blasts expressing a slightly different immunophenotype than that of his original disease (CD117-negative and CD5-positive). Immunohistochemical stains on the core biopsy demonstrated that blasts were positive for CD34, TdT, CD5, and CD7, with a small subset that was weakly positive for CD3. Cytogenetic studies demonstrated a complex karyotype similar to that of his original leukemia. FLT3-ITD PCR was negative but extended mutational testing—not previously performed—revealed mutations in FBXW7, NOTCH1, and EZH2, all of which are recurrently mutated in T-ALL []. Additionally, bone marrow chimerism studies showed for the first time a decline in CD3 donor chimerism from 100% to 91%.
Based on emerging data to support the use of venetoclax in T-ALL, he began salvage therapy with venetoclax (given daily, initially at 800 mg then dose reduced to 400 mg due to the interaction with his azole for fungal prophylaxis) in combination with decitabine (given daily for 5 days at 20 mg/m2 in 28-day cycles). After 2 cycles, his peripheral blood counts had normalized, formal CR criteria were met, and a restaging bone marrow evaluation demonstrated no morphologic evidence of residual leukemia. MRD assessment—again performed via multiparameter flow cytometry at the University of Washington—also showed no evidence of persistent disease. CD3 chimerism in the bone marrow was restored to 100% donor.
In light of the lymphoid origin of his relapsed leukemia, next generation sequencing (NGS) was performed (ClonoSEQ, Adaptive Biosciences) on his relapse specimen, identifying a dominant T-cell receptor (TCR) clone comprising 8.249% of total nucleated cells. We retrospectively also assessed his original diagnostic bone marrow specimen and found that the same TCR clone was present in 11% of total nucleated cells. MRD assessment from a bone marrow specimen after 2 cycles of venetoclax and decitabine—also via ClonoSEQ—showed no detectable residual leukemia at a sensitivity of 1 leukemic cell per 106 cells. He received a total of 5 cycles of decitabine and venetoclax, with intermittent dose interruptions of venetoclax due to neutropenia. He remained MRD negative via multiparameter flow cytometry and ClonoSEQ and subsequently underwent a second haploidentical alloHCT with fludarabine, cyclophosphamide, and low-dose TBI conditioning. Decitabine and venetoclax were discontinued shortly prior to the second haploidentical alloHCT. He achieved full donor chimerism at day +18 posttransplant and continues in follow-up. |
pmc-6129358-1 | A previously healthy 3.5-year-old male was referred to our department because of a five-day history of weakness and pallor. Two weeks before, a three-day history of diarrhea was mentioned. The past medical history is unremarkable, and no family history of hematological problems or autoimmune disorders was reported.
Physical examination revealed jaundice, pallor, and splenomegaly. The boy's heart rate was 125 beats/min, and a 2/6 systolic heart murmur was present. The initial laboratory investigation showed: hemoglobin 5.1 g/dL, absolute reticulocyte count 220 × 103/μL, mean corpuscular volume 75 fl, white blood cells 9.3 × 109/L, and platelets 255 × 109/L. The peripheral blood film showed polychromasia and spherocytes without schistocytes. Serum lactate dehydrogenase levels were 1540 U/L, total bilirubin 3.8 mg/dl, and indirect bilirubin 0.9 mg/dl. The renal and liver function tests showed calcium and phosphate were normal. Urine examination was negative for hemoglobin and myoglobin. The direct antiglobulin test (DAT) was strongly positive for IgG autoantibodies with no fixation of the complement. The results of antinuclear antibody and anti-deoxyribonucleic acid were negative. Serum C3 and C4 as well as IgG, IgM, and IgA levels were normal. Serology for cytomegalovirus, Epstein–Barr virus, Mycoplasma pneumonia, and human immunodeficiency virus were negative. Based on the symptoms, the clinical findings and the laboratory tests the warm type of AIHA was established.
Erythrocyte transfusion was firstly administered because of the severe anemia in order to avoid cardiovascular compromise. Intravenous methylprednisolone was also initiated at a dose of 3 mg/kg/day for the first 72 hours with excellent hematological response. When the boy was clinically stable, oral prednisolone at a dose of 2 mg/kg/day was then used for 4 weeks followed by a slow taper during the following 5 months. At that time, prednisolone was discontinued, and a relapse occurred after an upper respiratory infection as shown in .
For this reason, prednisolone was restarted at 2 mg/kg/day with a good hematological response. Due to the steroids side effects, the dose of prednisolone was slightly reduced two weeks later and a hematological deterioration occurred. After that, the dose was increased again to 2 mg/kg for 1-month period. The expected side effects, such as blood pressure above the 95th percentile, bilateral posterior subcapsular cataract, facial edema, and hairy back, were quite evident, and it was decided to slowly discontinue prednisolone and to administer azathioprine at a dose of 2 mg/kg/day.
Azathioprine was given for 4 months with a slight hematological deterioration despite the increase up to 3 mg/kg/day, as shown in , while the boy suffered from mumps, possibly due to the underlying immunosuppression. At this point, rituximab was initiated after informed written consent. The agent was given in 4 weekly doses at a dose of 375 mg/m2, with no infusion-related side effects. Stable response was noticed 2 months after initiation of rituximab (). Immunoglobulin levels remained normal without the need for replacement therapy with intravenous immunoglobulin (IVIG). The DAT became negative 12 months later. The boy remains disease-free without relapses, 3 years after the first presentation. |
pmc-6129367-1 | We present the case of a twelve-year-old girl originally from the Faroe Islands with compound heterozygotic MKD (p.V377I/c.417insC), who first presented with symptomatic periodic fever attacks from the age of 3 months. These presented as recurrent episodes of fever (39–41°C) without infectious cause, occurring once or twice monthly, associated with rigors, pallor, fatigue, lymphadenopathy (inguinal, axillary, and intra-abdominal), abdominal pain, oral ulceration, and arthralgia/myalgia of the lower limbs. Attacks lasted between 3 and 7 days and were accompanied by very high acute phase responses (C reactive protein [CRP] typically greater than 100 mg/L). Attacks were also triggered by vaccinations. Her past medical history included an episode of Stevens–Johnson syndrome in response to penicillin at the age of three years and appendectomy aged 7 years of a normal appendix. She was referred to us in London at the age of 12 years. At that time, she was receiving the anti-TNFα agent etanercept, which she had been on for the previous 34 months. She had at best only partial response to etanercept in terms of attack severity and duration, but was still missing 100 days per year of school because of attacks which occurred twice a month, lasting for 3 days. In addition, despite etanercept, her inflammatory markers remained significantly raised between attacks: CRP 82 mg/L (reference range [RR] < 10); serum amyloid A (SAA) 1310 mg/L (RR < 10), indicative of severe systemic inflammation in-between attacks and significant risk of reactive AA amyloidosis. Anakinra (2 mg/kg/day; recombinant interleukin-1 receptor antagonist) had also been tried previously, but was complicated both by a severe skin rash and also by the worst disease flare she had ever experienced; hence after four weeks, this was discontinued. Following a six-week washout period from the etanercept (during which she suffered one severe attack), in December 2015 she started intravenous tocilizumab 8 mg/kg every 2 weeks.
After one dose of tocilizumab, her CRP and ESR both rapidly normalised (). She had one minor attack with minor, short-lived fleeting rash, but no fever after the first dose. Since normalisation of CRP is a well-known effect of tocilizumab and may occur without necessarily any true improvement in clinical disease activity, we also prospectively used a physician global assessment of disease activity using a 0 to 10 scale, 0 indicating no disease activity and 10 indicating severe disease activity (), and change in haemoglobin, white cell count, and platelets () as adjunctive laboratory indicators of successful treatment. In addition, the patient reported significant improvement even after a single dose of tocilizumab, with improved energy levels, reduction in pain, and improvement in oral ulceration. She was also able to return to full-time school.
This excellent clinical and serological response has been sustained for more than 24 months. There have been no reported adverse events. The patient was switched to weekly subcutaneous tocilizumab at 162 mg in June 2016 for ease of administration and reduction in hospital attendances. A year since that change, the patient has had several short-lived flares lasting 1–3 days associated with fever, adenitis, and mouth blistering, but she has not required prednisolone as before and overall expressed a preference for the subcutaneous route as it was associated with improved quality of life despite the breakthrough fever attacks. |
pmc-6129369-1 | A 29-year-old G0P0 South Asian female was brought into the ED via ambulance following an MVA at freeway speeds involving multiple vehicles. The crash resulted in the deployment of the airbags and a subsequent loss of consciousness in the patient lasting less than one hour. Blood pressure was 89/40 on scene and improved to 117/95 en route to the ED. Upon arrival to the ED, the patient complained of 10/10 pain in the abdomen and left hip. Triage vitals were as follows: blood pressure 96/58, heart rate 85 beats/minute, respiratory rate 19 breaths/minute, and Glasgow coma scale 15/15. The patient arrived with a cervical collar and backboard in place and was noted to have a positive seat belt sign. A focused assessment with sonography for trauma (FAST) exam was positive in the right upper quadrant (). Leiomyomata uteri were incidentally noticed on ultrasound (Figures and ). A pelvic X-ray showed no acute fracture or traumatic malalignment. Hemoglobin was 10.7 grams/deciliter (reference range 12-16 grams/deciliter). The patient was subsequently taken to the operating room where a midline laparotomy was performed with an immediate upwelling of blood. The abdomen was packed in all four quadrants to control bleeding and stabilize blood pressure. Upon unpacking and inspection of the upper quadrants, no damage was observed to the mesentery, colon, liver, or spleen. Inspection of the lower quadrants revealed a free-floating mass of tissue later identified as a leiomyoma (). In addition, the uterus was noted to be bleeding from a 5 cm fundal laceration. The uterus appeared fibroid in character, and a 3 cm subserosal leiomyoma was seen extending into the laceration. The gynecologic team was consulted and proceeded to inject 20 units of vasopressin in 60 cc dilution into the uterus. This was followed by a myomectomy of the subserosal leiomyoma and closure of the uterine laceration. The abdominal incision was then closed, with a total estimated blood loss of 1000 mL. The patient was administered 2 units each of red blood cells and fresh frozen plasma, as well as 1.3L of crystalloid intraoperatively. Hemoglobin on post op day 1 downtrended to 6.5, at which point a third unit of red blood cells was given. On post op day 2, the patient developed intractable nausea, after which a nasogastric tube was inserted and 1 liter of green bilious output was achieved. The patient was stabilized and transferred to an outside hospital on post op day 3 for further recovery. |
pmc-6129370-1 | Case 1. A 5-year-old boy (height: 108 cml weight: 16.5 kg) who had sandwich 4 hours ago was brought to the operating rooms for removal of a coin that he has ingested 3 hours prior to presentation. A gastroscopy was performed under general anesthesia and the foreign body was successfully retrieved. Interestingly, no food residues were observed in the stomach (). |
pmc-6129370-2 | Case 2. A 4-year-old girl (Height: 100.5 cm; weight: 15 kg) who had cereal 3 hours prior to presentation underwent a gastroscopy for the removal of a pebble that is the size of 1 euro coin that she has ingested 4 hours prior to presentation. After ingestion, the patient was directly admitted to the emergency room. The foreign body was successfully retrieved and again the patient had no food in her stomach with only gastric secretions. |
pmc-6129370-3 | Case 3. A 3.5-year-old girl (height: 105 cm; weight: 15.5 Kg) had a gastroscopy to remove a metal coin that she has ingested 4 hours prior to the procedure. The mother also reports that the girl had a cup of cereals an hour before ingesting the coin. Again, the girl was found to have only gastric secretions with no food and the coin was successfully retrieved (). |
pmc-6129671-1 | A 10 year-old girl presented with the complaint of palpitation to a cardiologist. She had normal physical examination and laboratory tests, except tachycardia (heart rate = 130 per minute) and low TSH levels (0.005) with normal T3 (9.46) and T4 (145). She was referred to endocrinologist for possible hyperthyroidism evaluation. The thyroid gland was normal size, with no nodularity. She was diagnosed with possible thyrotoxicosis, but due to the normal physical examination, she underwent thyroid scan to rule out possible thyroiditis, which did not show any uptake in the thyroid gland, while there was an increased uptake in the right ovary (). Pelvic trans-abdominal sonography showed a heterogeneous complex solid mass of 113 × 112 × 100 mm with volume of 670 cc in the right ovary with no ascites. The patient had no complaint of abdominal pain or pelvic pain or abnormal uterine bleeding.
She was treated with methimazole 10 mg daily and propranolol 40 mg daily and were candidate for surgery after being euthyroid. The patient was referred to a gynecologist with the possible diagnosis of struma ovarii for further evaluation. She underwent right oophorectomy with the presumption of teratoma combined with thyroid-stimulating hormone (TSH)-suppressive therapy following treatment with I131. Total thyroidectomy was performed to permit evaluation for metastatic disease and monitoring for recurrence by thyroglobulin levels. The pathology report of the ovary mass indicated teratocarcinoma with 60% well-differentiated follicular thyroid carcinoma and 40% well differentiated follicular-variant with tumor necrosis, microscopic capsular invasion and peritumoral lymphovascular invasion, considering stage IC of PTC () and the thyroid gland did not show pathologic features of PTC.
Further evaluation with whole body scan with Iodine 123 (I123) showed metastasis to lymph nodes. She had high levels of thyroglobulin and received iodine therapy (150 mCi) twice. In the follow-up whole body scan, there was no trace of iodine uptake and the patient was symptom free.
The patient is now under treatment with levothyroxine 0.1 mg daily. Following 8 months after surgery and iodine therapy, she is totally symptom free. |
pmc-6129673-1 | A 74-year-old obese male was presented to ED (Emergency Department) with abdominal pain, distension, vomiting and diarrhea for 5 days. His past medical history is significant for hypertension and CVA (Cerebrovascular accident) 3 years before admission. He had a Colonic polyp removed 5 years ago. In addition, He had a history of gallstones removed 10 years ago. He was on Atenolol. Captopril and, Aspirin. On examination, the patient had generalized weakness of the left side of his body due to previous CVA.
There was a tender irreducible swelling in the right inguinal region, covered by normal skin. Since the patient had a history of stroke years ago, it was not possible to ask him about duration of the swelling, pain at the site, or to cough to evaluate the swelling more. The vital signs were within normal. Bowel sounds were sluggish. Digital rectal examination showed nothing of significance.
Lab results showed Blood Urea: 11.8 mmol/L, Serum Creatinine: 116.96 μmol/L, Serum Potassium: 5.5 mmol/L, Blood Sugar: 10.3 mmol/L, WBC Count: 14.2 × 103/mm3, Hemoglobin: 12.4 g/dL, Platelets: 312 × 103/mm3.
On Abdominal ultrasound, the gallbladder wasn’t visualized, but a cystic like lesion in the right inguinal region mostly representing a bowel loop was seen. The tentative diagnosis for this case was strangulated right inguinal hernia causing intestinal obstruction. Consent was taken from the patient’s next of kin and the right inguinal region was explored. A sliding direct Ogilvie inguinal hernia was discovered. There was a well circumscribed soft mass of a narrow neck, protruding from the posterior wall of the hernia that looks like a foreign body (). On exploration, the mass was the balloon of a Foley's catheter in the sliding part of the bladder within the inguinal hernia, and the urinary bladder was part of the posterior wall of the inguinal canal (). The direct sliding Ogilvie inguinal hernia was repaired, and Explorative laparotomy was done to deal with the cause of intestinal obstruction through a mid-line incision. Upon exploration, a superior mesenteric artery occlusion was noticed causing strangulation of all small bowel (excluding first 100 cm of jejunum), all right colon and most of transverse colon. Resection of all gangrenous bowel was done, with end to end jejuno-colonic anastomosis. The patient’s case deteriorated over the next few days until he died on the 5th day post operation due to cardiac issue. |
pmc-6129795-1 | A 68-year-old woman with past medical history of hypertension, chronic kidney disease stage 3, hyperlipidemia, and hereditary hemorrhagic telangiectasia (HHT) presented to the emergency department with sudden onset of shortness of breath. She also reported chest pain, orthopnea, and paroxysmal nocturnal dyspnea. Review of systems was otherwise unremarkable. Her HHT was previously managed by regular blood transfusions and epsilon-aminocaproic acid. Because of the need for frequent blood transfusion due to persistent epistaxis and gastrointestinal bleeding, she was started on bevacizumab infusion at 15 mg/kg/dose (1150 mg total) by her haematologist a month prior to presentation. Initial vital signs on presentation revealed respiratory rate of 25/min, oxygen saturation of 65% on ambient air, blood pressure of 138/83 mmHg, and pulse rate of 92/min. Physical examination revealed respiratory distress with diffuse wheeze, jugular venous distention, and trace pedal edema. Laboratory tests revealed markedly elevated brain natriuretic peptide (BNP) of 1697 pg/ml (normal 0–100 pg/ml) with initial troponin of 0.05 ng/ml (normal < 0.04 ng/ml). Chest X-ray revealed pulmonary vascular congestion and interstitial edema with mild cardiomegaly. She was immediately placed on noninvasive ventilation and started on intravenous furosemide with quick symptomatic improvement. Transthoracic echocardiogram (TTE) showed ejection fraction of 30% and global hypokinesia (please see Supplementary Materials ()). Of note, TTE done three years prior to index presentation showed ejection fraction of 56%. She does not drink alcohol, and her thyroid function and sedimentation rate were normal making other etiologies of acute systolic heart failure such as thyroid disorder, alcoholic, or inflammatory cardiomyopathy less likely.
She refused to wear LifeVest and was placed on guideline-directed medical therapy including beta-blocker, angiotensin-converting enzyme inhibitor (ACEi), and aldosterone antagonist along with an oral diuretic. The patient progressively improved and was discharged three days later and scheduled for follow-up with cardiology for outpatient right and left heart catheterization. Two weeks later, she developed another episode of flash pulmonary edema deemed to be due to medication noncompliance. On this occasion, she underwent left and right heart catheterization which revealed widely patent coronary vessels (), elevated pulmonary capillary wedge pressure, and elevated left ventricular end-diastolic pressure. She continued to have her monthly bevacizumab infusions with her haematologist as this was not thought to be the cause of her cardiomyopathy at the time. Three months later, she developed sudden onset of chest pain and shortness of breath at home and went into ventricular fibrillation-related cardiac arrest. She underwent prolonged cardiopulmonary resuscitation but eventually had return of spontaneous circulation. She was intubated and admitted to the medical intensive care unit and underwent therapeutic hypothermia. Repeat TTE showed ejection fraction of 34%. She quietly passed away 3 days later. |
pmc-6129844-1 | A 23-year-old male presented to the emergency department with one-day history of right-sided pleuritic chest pain, haemoptysis, and fever. He had no history of a recent travel or contact with sick individuals. The patient had no significant medical background, and he was not taking any regular medication.
On admission, blood pressure was 140/60 mmHg, heart rate 89/min, body temperature 40°C, respiratory rates 20 breaths/min, and oxygen saturation 98% in room air. Physical examination revealed rales and bronchial breathing in the right infrascapular region. There was no clinical evidence of meningitis.
Laboratory analysis showed the following results: haemoglobin level 146 g/L (normal 140–175), platelets count 373 × 109/L (normal),white blood cell counts 19.6 × 109/L (normal 3.5–10.0) (90% neutrophils and 10% lymphocytes), sodium 140 mmol/L (normal 135–145), potassium 3.6 mmol/L (normal 3.5–4.5), urea 3.7 mmol/L (normal 2.5–7.0), creatinine 104 µmol/L (normal 50–100), eGFR 87 ml/min/1.7 m2 (normal > 90), C-reactive protein at 58.5 mg/L (normal < 3), and an unremarkable liver function test. Chest X-ray demonstrated right lower lobe consolidation. With the history of haemoptysis and pleuritic chest pain, computed tomography pulmonary angiogram (CTPA) was performed, and it did not show pulmonary embolism (PE).
Sputum culture was found to be positive for oropharyngeal Candida species. However, a day later, N. meningitidis grew in one blood culture bottle, and it was sensitive to penicillin and ceftriaxone. Using polymerase chain reaction (PCR), we have identified N. meningitidis serogroup Y. Subsequently, two repeat sets of blood cultures, after initiation of antibiotics, were sent and reported negative. Additional results included undetectable urinary Streptococcus and Legionella pneumophila serogroup 1 antigens and a negative HIV serology test.
The patient was started on 2 g of IV ceftriaxone and 100 mg of doxycycline as per the hospital guidelines for the management of community-acquired pneumonia. However, doxycycline was discontinued after day 1 after the blood culture result. In total, the patient received 4 days of IV ceftriaxone followed by 3 days of oral amoxicillin (1 gm,TDS). The Centers for Disease Control and Prevention was contacted to arrange chemoprophylaxis for the patient's contacts.
On day 4, the patient was discharged from the hospital and was reviewed at an outpatient clinic two weeks later. He showed a complete resolution of his symptoms. |
pmc-6130057-1 | A 46-year-old man with a recent diagnosis of hiatal hernia was admitted to the Respiratory Diseases Unit of the University Hospital of Modena, Italy for several dramatic episodes of hemoptysis during the previous 30 days, severe anemia (6,9 g/dl) and initial signs of hemodynamic instability (shock index = 1,4). The past medical history revealed that the patient had undergone cardiac surgery for aortic coarctation at the age of 18 without complications neither during the immediate post-operative course nor in the following 20 years follow up period. He was referred to the Respiratory Intensive Care Unit of our Department where blood transfusion was immediately started. A chest X-ray was performed but no significant abnormalities were detected. Thus he underwent urgent digestive endoscopy that revealed a grade B esophagitis according to Los Angeles classification [] without any evidence of recent bleeding. Fiber bronchoscopy was then immediately conducted showing limited traces of blood in the bronchial tract afferent to the left upper lobe while no sings of active bleeding was found (Fig. ). He eventually underwent a contrast-enhanced CT scan of the chest that showed an aneurysmal dilatation of the descending thoracic aorta (Fig. ) communicating with the left upper bronchus, whose upper posterior hemorrhagic leak determined initial left upper lobe compression and ground-glass opacities with scissural delimitation (Fig. ). Given the evidence of a communication between aortic aneurism and lung parenchyma or either the tracheobronchial tree the patient was referred to the Cardiac Intensive Care Unit. Thoracic endovascular aortic repair (TEVAR) was preferred rather than a more invasive open surgical approach due to the persistent hemodynamic instability of the patient. Aortobronchial fistula was thus successfully treated with endovascular stent-graft without complications. The patient survived the intervention with uneventful postoperative course and good recovery in less than 30 days. Strict follow up was then started. |
pmc-6130071-1 | A 34-year-old woman (gravida 4, para 1, abort 3) presented to our clinic for pelvic pain and enlarged ovaries at PUMCH (Peking Union Medical College Hospital) with a 5-day history of left lower quadrant abdominal pain. The pain was atypical, without nausea, vomiting, dysuria, or diarrhea. Her last menstrual period was 2 weeks prior to presentation. There were palpable, cystic, solid masses on both sides in the lower quadrant. Laboratory tests revealed a white blood cell count of 22.9 × 109/L, granulocyte rate of 80.6%, and a normal β-human chorionic gonadotropin (β-hCG) level. She had a transient fever of 37.9 °C; therefore, antibiotics was administered for 4 days. When she came to our hospital, pelvic pain was relieved. Ultrasound imaging and computed tomography (Fig. ) revealed that both the ovaries were enlarged (≥10 cm) with multiple follicles inside. Serum hormone levels were normal: follicle-stimulating hormone (FSH), 2.38 IU/L; E2, 46.85 pg/mL; progesterone (P), 0.35 ng/mL; testosterone (T), 0.54 ng/mL; luteinizing hormone (LH), < 0.2 IU/L; prolactin (PRL), 7.44 ng/mL.Dehydroepiandrosterone (DHEA), 497.5 μg/dL and 24-h urinary-free cortisol (UFC), 165.24 μg were slightly higher than normal. Adrenal ultrasound, serum thyroid-stimulating hormone (TSH)/free thyroxine (FT4), thyroxine (T4) and hypothalamic-pituitary magnetic resonance imaging revealed no abnormality. The concentration of tumor marker CA125 was 365.7 U/mL; therefore, a malignant tumor could not be excluded.
Before presentation, she was diagnosed with PCOS and underwent several attempts of ovulation induction and intrauterine insemination. After these failed, she underwent IVF with Marvelon (N.V. Organon, Oss, The Netherlands) and GnRHa stimulation. A combined estrogen and progesterone pill (Marvelon; N.V. Organon) was administered from day 5 of the previous cycle, and 1.2 mg triptorelin embonate (Diphereline; Ipsen Pharma Biotech, France) was injected intramuscularly on day 16 of taking Marvelon. Stimulation with recombinant follicle-stimulating hormone (Puregon; N.V.Organon) was started subcutaneously after 16 days’ down-regulation. Human chorionic gonadotropin (HCG) 5,000 IU was injected when the maxium follicle diameter reached 20 mm. The IVF procedure was performed at another center; therefore, details of estrogen and follicle development could not be traced. Transvaginal oocyte retrieval was uneventful and yielded 24 mature oocytes. Two blastocysts were transferred 4 days later. The patient had severe OHSS 10 days after oocyte retrieval, for which paracentesis was performed three times, with an average of 1,500 mL abdominal effusion drained each time. She was also suspected to have vein thrombosis of the right lower limbs. The patient became pregnant, and the follow-up was performed at another center. Throughout her perinatal examinations, both the ovaries did not become smaller. The patient delivered a healthy newborn via cesarean at term, a biopsy of the enlarged ovary was performed with benign pathology. No intervention was performed due to the expectation that the hyperstimulated ovaries would shrink during the postpartum period, at the same time she was concerned about the side-effects of those medicines in lactation. Her menstrual period resumed 14 months after delivery, and the child was weaned from breastfeeding at 24 months. However, the size of both the ovaries were still not reduced by then. Three months of oral contraceptives (Marvelon; N.V. Organon) were prescribed.
After admission, she underwent laparoscopic surgery to determine the cause of the persistent enlarged ovaries as well as pain. During laparoscopy, we found a large, torsed, congestive left ovary and a torsed, congestive, ipsilateral fallopian tube. The contralateral adnexa were enlarged but had a normal color. Both ovaries measured approximately 10 × 12 cm, kiss-forming, were closely stuck together. There were minimal ascites in the abdominal cavity. The omentum majus was adhered to and laid over the left ovary. Laparoscopic detorsion followed by left ovary biopsy and bilateral ovarian acupuncture were performed (Fig. ). Histopathological examination (Fig. ) revealed localized congestion and necrosis of the ovary that underwent biopsy, with no associated lesions. Ovary puncture liquid showed elevated E2 (2,078 pg/mL) and decreased FSH (0.3 IU/L) and LH (< 0.2 IU/L). The postoperative course was uneventful.
The patient was discharged the following week and received GnRHa 3.75 mg for 3 months. The ovaries shrank somewhat during the first month (left ovary, 5.8 × 5.1 cm; right ovary, 9.3 × 6.3 cm). Four months after surgery, she underwent an ultrasound scan that found slightly enlarged ovaries with multiple follicles (left ovary, 6.5 × 4.7 cm; right ovary, 4.1 × 3.0 cm). She did not feel any discomfort; therefore, she was advised to return 6 months later with no further treatment. |
pmc-6130082-1 | A 35-year-old Thai man was diagnosed as having CML in the chronic phase in February 2016 during his annual checkup at a primary hospital; the diagnosis was confirmed with a cytogenetic study, which demonstrated 46,XY,t(9;22) [] and was positive for the BCR-ABL fusion gene. He was therefore referred to our hospital in July 2016 to receive definitive treatment of 400 mg/day of imatinib. After receiving imatinib, his treatment response was monitored by a real-time quantitative polymerase chain reaction (RQ-PCR) for the BCR-ABL gene using the international scale (IS) method. The results showed an optimal response was achieved at 3 and 6 months, according to the 2013 European LeukemiaNet recommendations, with RQ-PCRs for the BCR-ABL gene (IS unit) of 1.527% and 0.896%, respectively []. During the treatment, he showed good compliance, and he did not use any herbs or other medications. He denied a family history with hematologic malignancies and he had no psychological problems.
In February 2017, however, he was admitted to our hospital with fever and severe pain in both knees and ankles of 5 days’ duration. A physical examination showed symmetrical oligoarthritis in his knees and ankles. A complete blood count (CBC) revealed hemoglobin (Hb) of 6.5 g/dL, hematocrit (Hct) of 20.3%, a WBC count of 16.9 × 109/L (49% neutrophils, 42% lymphocytes, 1% monocytes, 1% basophils, and 7% myeloblasts), and a platelet count of 16 × 109/L. A synovial fluid analysis of his right knee showed a clear, colorless fluid with an absence of crystals and a WBC count of 180 cells/L, with 65% neutrophils, 32% lymphocytes, and 3% blasts. A synovial fluid culture and hemoculture yielded no growth. A bone scintigraphy revealed: a symmetrical blood flow to both ankles; a symmetrical soft-tissue uptake at the knees and ankles, with a prominent early bone uptake; and a symmetrical increased uptake at the mandible, bilateral proximal humeri, both elbows, both forearms, the bilateral femoral heads, the trochanteric region of both femora, the left femoral shaft, the distal femora, the proximal tibiae, the bilateral tibial shafts, and both distal tibiae, all of which favored a bone marrow expansion which might have been related to a leukemic infiltration (Fig. ). The real-time quantitative-polymerase chain reaction (RQ-PCR) for BCR-ABL/ABL (IS unit) had increased to 21.26%. Testing for mutations in the BCR-ABL gene showed a negative result. A bone marrow aspiration revealed 10% myeloblasts. CML blast phase was established due to the highly suspicious evidence of extramedullary blasts at multiple bones and joints. Induction therapy with a 7 + 3 induction regimen (200 mg of cytarabine administered intravenously on days 1–7, plus 15 mg of idarubicin administered intravenously on days 1–3) was prescribed in conjunction with 600 mg of imatinib once daily before switching to 140 mg of dasatinib. His clinical symptoms, including joint pain and fever, improved, and he achieved a complete hematological remission, confirmed by a bone marrow study, 4 weeks after the induction therapy. Unfortunately, he developed dyspnea on exertion after dasatinib treatment for a month, and pleural effusion with pulmonary hypertension were suspected from the dasatinib. We therefore decided to permanently stop administering the medication.
A month later, in November 2017, he presented to our hospital with severe headaches of 1 week’s duration, a low-grade fever, nausea, vomiting, and polyuria. A physical examination revealed hepatosplenomegaly without an abnormal neurological finding. A CBC revealed Hb of 12.8 g/dL, Hct of 39.1%, a WBC count of 20.8 × 109/L (87.1% neutrophils, 9.1% lymphocytes, 2.6% monocytes, 0.7% eosinophils, 0.5% basophils, and no blasts), and a platelet count of 282 × 109/L. A computed tomography (CT) scan of his brain (non-contrast) showed several osteolytic lesions with soft tissue formation at the skull, skull base, and mandible, without intracranial lesions (Fig. ). A film bone survey demonstrated moth-eaten osteolytic bony destruction scattered diffusely on the pelvic bone, skull, spine, and both femurs (Fig. ). His laboratory chemistry revealed serum blood urea nitrogen (BUN) of 64.8 mg/dL, creatinine (Cr) of 4.1 mg/dL, albumin of 4 g/dL, globulin of 4.3 g/dL, total calcium of 17.8 mg/dL, serum parathyroid hormone (PTH) of 9.82 pg/mL (normal 15–65 pg/mL), 25-hydroxyvitamin D of 50.64 ng/mL (normal ≥ 30 ng/mL), and uric acid of 17.4 mg/dL; all other laboratory results were normal. The serum 1,25-dihydroxyvitamin D and PTH-related protein (PTHrP) levels were not available as the relevant tests were not routinely provided by our hospital at that time. A bone marrow aspiration showed multiple stages of the myeloid series with 7% myeloblasts. He was treated with intravenously administered hydration (200 mL/hour of 0.9% normal saline), calcitonin (300 μg administered intravenously every 6 hours for 3 days), and imatinib (600 mg/day). However, as there was a minimal response in his high serum calcium level, we decided to add 20 mg/day of intravenously administered dexamethasone on day 8 of admission. His severe headache symptom improved gradually, and the serum calcium level decreased dramatically to the normal range within a few days. He was then discharged with a serum calcium level of 7.6 mg/dL on day 15 of admission. His hypercalcemic treatment and outcomes are illustrated at Fig. . After that, he was lost to follow-up and died a few weeks after discharge at his home with unknown cause of death. A timeline table of our patient is provided in Additional file . |
pmc-6130085-1 | A 61-year-old female with medical history of hypertension, diabetes mellitus type 2, and chronic kidney disease stage V was transferred to our institution from an outside hospital for further evaluation and definitive management of a migrated intracardiac stent.
She initially presented to the outside facility with progressive dyspnea on exertion, orthopnea, and bilateral lower extremity edema. She was initially diagnosed with acute heart failure and pneumonia and treated with diuretics and antibiotics. Subsequently, a transthoracic echocardiogram was performed, which revealed a foreign body within the right ventricle. On transfer to our facility, a transesophageal echocardiogram revealed a long stent straddling the tricuspid valve from the right atrium with the other end lodged in the trabeculation of the right ventricle with severe tricuspid regurgitation ().
On further investigation, we learned that the patient had undergone peripheral endovascular intervention for May-Thurner syndrome with placement of a self-expanding Nitinol Protege (14 mm × 60 mm) stent to the left iliac vein 6 months prior to presentation.
A percutaneous endovascular approach with a 35- mm Medtronic-Covidien Amplatzer Gooseneck Snare was initially attempted to retrieve the migrated stent. However, the snared proximal segment fractured, leaving behind 2 stent fragments. After ensuring there was no myocardial perforation or pericardial effusion with intracardiac ultrasound, the patient was referred for surgical extraction via median sternotomy with use of cardiopulmonary bypass.
During the operative procedure, the stent was found to be densely adherent to the tricuspid leaflets and the subvalvular apparatus, with majority of the primary chords to the anterior and posterior leaflets ruptured (). After successful extraction of the stent and native tricuspid valve, she underwent valve replacement with a 29-mm Carpentier-Edwards bioprosthetic valve. Her postoperative course was complicated by hemopericardium secondary to anticoagulation resulting in cardiac tamponade that was drained percutaneously, and small thromboembolic cerebellar stroke from atrial fibrillation. She was discharged to an inpatient rehabilitation facility and did well on 8-month follow-up. |
pmc-6130086-1 | Patient: A 76-year-old woman.
Chief complaint: To improve asthma management before undergoing neck surgery.
Past medical history: Diabetes, hypertension, pollen allergy.
Tobacco use: No.
Current medication (antiasthmatic drugs): Symbicort® Turbuhaler® (Symbicort), 2 inhalations twice daily up to a total of 8 inhalations per day (SMART); montelukast tablets 10 mg/day; theophylline sustained-release tablets 400 mg/day; ketotifen capsules 2 mg/day; salbutamol inhalation 0.5%, 0.5 mL/asthma attack; and prednisolone tablets 5 mg, to be taken at the patient’s discretion at the time of an attack.
Respiratory function test: Forced vital capacity, 2.74 L (129.2%); forced expiratory volume for 1 s (FEV1), 1.09 L (76.8%); FEV1, 39.8%, with findings of obstructive ventilatory defect.
Current medical history: Adult-onset asthma. Despite undergoing Step 4–5 (Global Initiative for Asthma 2017 [GINA2017]) therapy as a long-term management approach, wheezing persisted, and she had been admitted to a nearby hospital once every 2 years or so due to asthma attacks triggered by irregular weather conditions.
She was referred by a nearby otolaryngologic clinic to the Department of Otorhinolaryngology in our hospital for thorough examination of hoarseness lasting for 1–2 years. Examination findings revealed thyroid cancer with tracheal infiltration for which radical surgery was indicated. However, because wheezing increases surgical risk, she was referred to the Department of Internal Medicine for preoperative control of intractable wheezing. Consistent with her complaint of constant wheezing, initial examination revealed expiratory wheezing at rest.
To improve asthma management during a 4-week period before surgery, we prescribed Spiriva® Respimat® (Spiriva Respimat) 2.5 μg (two inhalations once daily) and subcutaneous injections of 300 mg anti-IgE antibody omalizumab every 2 weeks (determined based on the level of serum IgE [159 IU/mL IgE specific to Aspergillus fumigatus] and body weight [50.9 kg]).
Owing to these additions, wheezing disappeared after 1 week, and so the patient was able to undergo right thyroid lobectomy with tracheoesophageal resection as scheduled.
Considering that it would be difficult for the patient to use the inhalation powder Symbicort because of a permanent tracheostomy postoperatively, we switched from Symbicort to nebulized budesonide 2000 μg/day and a tulobuterol patch (2 mg). Spiriva Respimat and omalizumab were continued after surgery.
Approximately 3 weeks after surgery, the patient began to develop respiratory distress and wheezing early in the morning. According to the patient, these attacks would have been managed quickly as small attacks by additional inhalations of Symbicort, suggesting that the nebulized SABA that she had been taking postoperatively was not sufficiently effective. Because these symptoms used to be well managed when Symbicort was used, we considered switching back to Symbicort from nebulized budesonide and the tulobuterol patch. In Japan, however, Symbicort is available in only a DPI formulation, Turbuhaler®. In order to maximize the beneficial effects of Symbicort Turbuhaler, inspiratory flow rates need to exceed a certain level, but our patient would likely have had insufficient inspiratory flow rate due to the tracheostomy, and would thus need a device that does not require a high inspiratory flow rate, such as a pressurized metered-dose inhaler (pMDI). Adoair® and Flutiform® aerosols are commercially available pMDIs in Japan and contain ICS/LABA. Flutiform® aerosol was considered the most likely candidate because it contains the same LABA (formoterol), but not ICS, as in Symbicort, but Flutiform may leak out from the tracheostomy after being sprayed intraorally. Because the patient had previously been undergoing SMART with additional inhalations of Symbicort for acute exacerbations, it would be best to use Symbicort if possible. There seems to be no difference in the degree of distribution to the respiratory tract whether a tracheostomy is present or not if the patient is able to close the tracheostomy using his or her hand. However, the drug distribution in the respiratory tract is unknown when a patient with a tracheostomy uses an inhaled drug. Since the diameter of the tracheostomy is about 1 to 2 cm, the dead space can potentially be ignored. When the effect was found to be inadequate, we considered a change to Flutiform®, which has similar components in a different device (pMDI), because the tracheostomy was just under the skin in this patient.
Two types of devices are used to measure inspiratory flow rate: the whistle-type Turbutester (accessory for the Turbuhaler®) and the In-Check Dial®, an inspiratory flow measurement device. The Turbutester generates an audible whistling sound during inhalation, signifying that the patient has an adequate inspiratory flow rate to use Symbicort. The In-Check Dial, when used with an adapter tailored to conventional inhalers, functions as an inspiratory flow measurement device and expresses inspiratory flow rates in L/min. Our patient had an inspiratory flow rate barely sufficient to generate a whistling sound from the Turbutester during inhalation while simultaneously closing the tracheostomy with her hands. So, to select the best inspiratory flow rate, she was instructed to measure the rate three times using the In-Check Dial®, the Turbuhaler®, and the special adaptor while closing tracheostomy. The results were 40, 43, and 43 L/min. Several inspiratory flow rates have been suggested to be required to exert the beneficial effect of Turbuhaler®, but the consensus is that inspiratory flow rates above 30 L/min are sufficient to use Turbuhaler® [, ]. These findings, together with the findings from the Turbutester, suggest that the present patient could benefit from these devices.
Based on these findings, nebulized budesonide 2000 μg and tulobuterol patch 2 mg were switched to 2 inhalations of Symbicort twice daily up to a total of 8 inhalations/day (SMART). The antiasthmatic drugs Spiriva Respimat and anti-IgE antibody, which had been added before surgery, were continued. The patient’s symptoms improved quickly over the course of 2 days after starting 2 inhalations of Symbicort in the morning and evening plus additional inhalations as needed (usually 1 inhalation in the evening). Owing to stabilized asthma symptoms, she was discharged on the third day after switching drugs (Fig. ). |
pmc-6130588-1 | A 49-year-old female patient presented with complaints of worsening right knee pain since two years ago. The patient had pain when she walks, goes up the stairs, sits and gets up. The symptoms sustained even after three months of non-operative treatment. On physical examination, she had a full range of motion and had pain and tenderness on both lateral and medial joint line with positive McMurray test. No pain was observed during patellar grind and compression test. Mild to moderate degree of swelling and effusion were observed without significant instability. Plain radiographic examination showed Kellgren-Lawrence grade 2 medial compartment tibiofemoral osteoarthritis. Mechanical hip-knee-ankle axes were varus 6.5° in right knee and neutral in left knee. Posterior tibial slope angle was 4.2° and the Insall-Salvati ratio was 1.13 in right knee. Right knee magnetic resonance imaging (MRI) revealed a horizontal tear of the medial meniscus with grade 3 chondromalacia of medial femoral condyle and grade 2 chondromalacia of medial tibial condyle. Also, complex tear with extrusion of the lateral meniscus was observed with intact lateral femoral and tibial condyles. The patellofemoral joint had grade 2 chondromalacia (Figure ).
The International Knee Documentation Committee (IKDC) score and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score of the patient were 52 and 48, respectively. To address both medial compartment arthrosis and lateral meniscus tear, we planned to perform simultaneous medial open wedge HTO and lateral MAT after consulting with the patient. Knee arthroscopy was performed first, and the torn lateral meniscus was removed to within 1-2 mm of the peripheral rim, and a bleeding bed was made using a shaver. Biplanar medial open wedge HTO was performed under fluoroscopic control. Fixation of osteotomy was performed using an anatomical locking plate. After plate fixation, 5 cc of beta-tricalcium phosphate (Ca3(PO4)2) was injected into the osteotomy gap. To secure enough space for bony bridge fixation for lateral meniscal allograft in proximal tibia area, the osteotomy site and proximal screw position were made about 1.5 cm below the routine position (Figure ).
The lateral meniscus allograft was transplanted using the keyhole technique. A keyhole slot parallel to the posterior tibial slope was made just under the lateral tibial spine. After the graft was introduced into the joint through the anterior mini-arthrotomy site, inside-out meniscal suture fixations were performed at 5 mm intervals. Bony union of osteotomy site was achieved without any complication. Radiographic measurements at postoperative one-year follow-up showed valgus 2.7° of mechanical hip-knee-ankle axis, 4.9° of posterior tibial slope, and 1.07 of Insall-Salvati Ratio. Intact lateral meniscus allograft and lateral tibiofemoral cartilage were confirmed by the follow-up knee MRI taken at postoperative three months and second-look arthroscopic examination performed at postoperative 12 months (Figure ). Clinically, the patient had full knee range of motion and the improved IKDC and WOMAC scores of 95 and 12, respectively. |
pmc-6130589-1 | A 59-year-old man had undergone prostate needle biopsy after a high prostate specific antigen (PSA) level (218.5 ng/mL) observed at the age of 54 years and he was diagnosed with adenocarcinoma of the prostate (Gleason score 4＋5). He underwent pelvic magnetic resonance imaging (MRI) and bone scintigraphy at our hospital. The MRI showed the mass in the right peripheral zone as a low signal intensity on the T2-weighted image and as an abnormal signal intensity on the diffusion-weighted image, reflecting prostate cancer. Bone metastases of the right rib and L2 vertebra were clarified. Therefore, clinical stage was T2aN0M1. He was treated with radiation therapy and androgen deprivation therapy (ADT) including bicalutamide and goserelin and his PSA dropped to 0.053 ng/mL. At the age of 56 years, his PSA was found to be elevated (1.15) and ADT with flutamide, estramustine phosphate, enzalutamide, and abiraterone was restarted. At the age of 58 years, the disease became refractory to hormonal treatment (PSA recurrence: 24.9 ng/mL), and the patient started chemotherapy with docetaxel for six cycles. However, both symptomatic and biochemical progression (PSA: 33.7 ng/mL) appeared. We confirmed multiple bone metastases without lymph node metastases or visceral metastases by carrying out baseline 11C-choline PET/CT and started Ra-223. He completed all the six cycles without any interruption and with no adverse events. Before each treatment, laboratory evaluation was performed to assess hematological parameters as well as PSA. After treatment cycles 3 and 6, 11C-choline PET/CT imaging studies were performed to evaluate and predict treatment response of Ra-223 on imaging.
Baseline 11C-choline PET/CT showed multiple areas of increased focal activity in multiple cervical, thoracic and lumbar vertebrae as well as in both ribs, right ileum, and left ischium (Figures -). Second 11C-choline PET/CT after three cycles showed the increasing tumor activity in the existing lesions and the new uptake spots of thoracic spine, both ribs, and left ileum (Figures -). Third 11C-choline PET/CT after six cycles showed the increasing tumor activity in the existing lesions and the new uptake spots of thoracic spine, sacrum, right rib, and right ileum (Figures -).
The patient’s serum alkaline phosphatase (ALP) level was 226 U/L at baseline, 191 U/L after one cycle, 208 U/L after two cycles, 235 U/L after three cycles, 206 U/L after four cycles, 200 U /L after five cycles, and 262 U/L after six cycles, respectively. His serum PSA level was 33.7 ng/mL at baseline, 54.1 ng/mL after one cycle, 79.4 ng/mL after two cycles, 85.6 ng/mL after three cycles, 120 ng/mL after four cycles, 175 ng/mL after five cycles, and 267 ng/mL after six cycles, respectively. During Ra-223 therapy, his serum ALP did not dramatically change with minor increase and decrease and PSA gradually increased. After the completion of Ra-223 therapy, he started a new chemotherapy with cabazitaxel. |
pmc-6130590-1 | A 60-year-old female presented with three days of diarrhea and diffuse abdominal discomfort. She reported having five to six bowel movements for two days followed by an additional 15 bowel movements prior to admission. She described that her bowel movements were watery and yellow in appearance. The patient also complained of generalized myalgias and subjective fevers intermittently. She denied any hematochezia, melena, or recent weight loss.
She was hospitalized three weeks prior to this admission with similar symptoms. During that time, she was found to have mild colitis and workup including gastrointestinal (GI) polymerase chain reaction (PCR), stool ova and parasites, Clostridium difficile (C.diff) testing by PCR were all negative. The patient was started on a 10-day course of ciprofloxacin and flagyl. The patient stated that diarrhea resolved with the antibiotics, but restarted two days after completion.
During admission, the patient was started on intravenous (IV) fluids and stool samples were collected and sent to the lab. Stool PCR, C.diff, cultures and ova/parasite testing all again came back negative for the second time. Subsequently, a colonoscopy was performed that revealed a solitary five-millimeter ulcer in the cecum (Figure ). Biopsies were taken with cold forceps and histopathological analysis confirmed lamina propria histiocytosis with intracellular microorganisms consistent with histoplasmosis (Figure ). Grocott’s methenamine silver stain and Period acid-Schiff stain were both positive, further confirming the diagnosis of histoplasmosis (Figures -). Subsequently, the patient tested positive for HIV with a CD4 count of 59 and viral load of 140,000. The patient was started on IV amphotericin B with acetaminophen and diphenhydramine premedication. She was also started on a combination of abacavir, dolutegravir and lamivudine daily for HIV infection, sulfamethoxazole/trimethoprim for pneumocystis jiroveci prophylaxis and nystatin for oral thrush. She continued to improve clinically in the hospital and was then discharged home on IV infusion to receive the last three days of amphotericin B to complete a total of 14 days. The patient was then switched to oral itraconazole and scheduled to follow up with an infectious disease specialist. |
pmc-6130742-1 | Mr C was a single man in his 60s. He had served in the UK military police during the Northern Ireland peacekeeping operations in the 1960s. During his service he attended the aftermath of an explosion that had killed several civilians, including a child. Afterwards he experienced an intrusive fragmented image of the scene in his right peripheral field of vision. At assessment he reported experiencing the image every day but avoided focusing on it. He had not spoken about the event to anyone in his life prior to the start of therapy. He identified that his mood state fluctuated between detachment and feeling overwhelmed by anxiety symptoms when confronted by a reminder of the event (e.g. a news item about Northern Ireland). This could lead him to dissociate and therefore he avoided such triggers. He also experienced periods of depression and had previously used alcohol to cope with his difficulties. His avoidance of the trauma memory maintained his PTSD symptoms (). He reported he had not received any previous psychological therapy.
Mr C presented as avoidant of engaging in TF-CBT, and utilized several therapy sessions to discuss his concerns. He identified the appraisal as ‘I won’t be able to cope’. Mr C attempted to use multiple grounding strategies in the therapy room, combining olfactory strategies with standing up and holding an object; however, he either presented as matter of fact and detached from any emotion or unable to tolerate ‘in vivo’ reliving that involved closing his eyes, claiming he felt overwhelmed by physical panic symptoms and he began to dissociate. In both reliving sessions he could not gain access to his peri-traumatic cognitions. |
pmc-6130742-2 | Mr P was a married man in his 40s with one child. He had served in the UK army and was deployed to the Bosnian conflict in the mid-1990s. During his deployment he was stationed at a morgue that had been set up to aid the identification of bodies recovered from a mass burial site. He described how the morgue contained a large number of bodies in various states of decomposition, with varying degrees of physical trauma. He reported re-experiencing fragmented intrusive images of the morgue and daily emotionally distressing nightmares of which he could not recall the content. He experienced high levels of anxiety that triggered his dissociative symptoms. These appeared to function as a coping strategy to avoid distressing emotions connected to his memory of the morgue. Other avoidance symptoms included feeling detached from people around him and feeling emotionally numb. Mr P avoided family occasions and busy places which could trigger his hyper-arousal symptoms and had never spoken to anyone about his experiences. He reported coping historically through the use of alcohol to block out his emotions. His avoidance behaviours had maintained his PTSD symptoms.
At the start of therapy sessions, Mr P was reluctant to talk about his past experiences stating he only felt able to discuss vague details about his intrusive memories. Mr P attempted to use physical objects such as stones and leaves, or his e-cigarette, as grounding strategies in the clinic room. However, he also reported feeling unable to tolerate any emotions connected to the events and found it difficult to identify peri-traumatic cognitions. Mr P appeared to experience intrusions of one particular fragmented image and could not recall any other contextual information from before or after this moment.
In both cases Mr C and Mr P experienced difficulties in engaging with traditional methods of imaginal reliving and prolonged exposure, due to high levels of avoidance and low thresholds for dissociation, and subsequently had difficulties accessing their cognitions for updating. For both clients the prior use of multiple grounding methods in the therapy room were unsuccessful. They experienced their traumatic memories as fragmented images with a sense of ‘nowness’ (), which indicated a distinct lack of contextualization.
An adaptive approach was then trialled to address these hindering factors. This involved three stages: (1) walking the client through the imaginal scene outdoors to address dissociation, (2) viewing the imaginal scene from multiple perspectives to facilitate contextualization of the memory and (3) identifying and reappraising the cognitions with frequently used approaches in trauma-focused therapy. |
pmc-6131093-1 | A 56-year-old male patient was presented to the emergency department, one day following a road traffic accident. Full history was obtained and thorough neurological examination was done, the patients Glasgow coma score was 13/15, he had right otorrhea, ecchymosis of both eyes, the right pupil was dilated fixed, and the left one was regular and reactive to light. Patient had history of old orthopedic instrumentation, 30 years ago.
CT (computed tomography) scan was obtained, which revealed pneumocephalus, and an incidental finding of a right frontal intra-axial mass with aggressive perilesional edema. Patient received conservative management, including dehydrating measures, antibiotics, and prophylactic antiepileptic. Complete investigations showed fracture maxilla and mandible.
Two days after admission, patient regained consciousness and re-evaluation showed right sixth nerve palsy, right optic atrophy, and anosmia. We recommended magnetic resonance imaging (MRI) brain with contrast, but it was not possible due to the old fracture and instrumentation, so a CT scan with contrast was done, as shown in
, and revealed an intra-axial mass with perilesional edema, and a cystic component. Our differential diagnosis was a high-grade glioma, an abscess, or metastatic deposits. Metastatic workup including CT chest, pelvi-abdominal ultrasonography, and tumor markers including PSA,
α
-feto protein were all negative.
Expecting the mass to be intra-axial a right frontal craniotomy with trans-cortical approach was decided. Intraoperatively, palpation of the brain surface revealed no underlying cystic lesion, neither did aspiration, using a brain needle came up with any fluid. We proceeded with the transcortical approach, where a well-defined basal intraparenchymal mass appeared. The mass was reddish, soft in consistency, and was excised completely at the end of the procedure. Postoperative CT scan is shown in
.
We were not able to identify neither optic nerves, nor the olfactory, at the end of our transcortical approach.
Histopathological examination showed benign spindle-shaped cells, with elongated nuclei and fibrillary cytoplasm (Antoni-A pattern), and less cellular, loosely textured tumor areas,
.
Postoperatively, the patient was fully conscious, with improvement of his right sixth nerve palsy, but no improvement occurred in his smell, or right optic atrophy, right sixth nerve palsy, and anosmia. |
pmc-6131193-1 | A 17-year-old male with Marfan's syndrome and a family history of Marfan's and aortic dissection in one parent, was diagnosed with a dilated aortic root (sinuses of Valsalva 47 mm) with trivial aortic regurgitation. He took candesartan 8 mg every morning including the day of surgery. He underwent a valve-sparing aortic root replacement. Maintenance of normotension during cardiopulmonary bypass required the administration of noradrenaline. Postoperatively he developed severe vasoplegia with a rise in serum lactate to 8.1 mmol/L that responded to treatment with noradrenaline. He did not have any other organ dysfunction and was extubated after 12 h. He required vasoconstrictor therapy for 53 h. He made an uneventful recovery thereafter and was discharged home on postoperative day 8. |
pmc-6131193-2 | A 14-year-old male with Marfan's syndrome and progressive aortic root dilatation (sinuses of Valsalva 47 mm), moderate mitral regurgitation and significant pectus carinatum, underwent a valve sparing aortic root replacement, aortic valve repair, mitral valve repair and concomitant Ravitch procedure. He took candesartan 4 mg twice a day including the night prior to surgery. Maintenance of normotension during cardiopulmonary bypass required the administration of noradrenaline. Shortly after transfer to the intensive care unit he developed profound hypotension despite fluid boluses and increasing vasopressor doses and required a brief period (2 min) of cardiopulmonary resuscitation. His inotrope requirement included adrenaline up to 0.1 mcg/kg/min, noradrenaline up to 0.08 mcg/kg/min, dopamine up to 10 mcg/kg/min, and vasopressin up to 0.6mU/kg/min. His serum lactate postoperatively increased to 9.7 mmol/l before normalizing over 24 h. There was no evidence of other organ dysfunction. He required vasoconstrictor therapy for 106 h and mechanical ventilation for 72 h after which time he made an uneventful recovery. The clinical parameters and the vasoactive medications used have been summarized in Table .
Both patients had gas induction for anesthesia and maintenance using Sevoflurane (Case 1: 1.7% and case 2: 2.9%). Both had a combination of antegrade-retrograde intermittent cold blood cardioplegia instituted and the cardiopulmonary bypass was maintained at normothermia. At the end of the procedure both patients underwent modified ultrafiltration and were transferred to the intensive care unit with a positive fluid balance of 140 and 790 ml respectively. |
pmc-6131512-1 | A 57-year-old male patient, with no personal or family history of liver disease or alcohol addiction, was admitted for acute hepatitis with cholestasis and cytolysis. Three weeks before, he had started consuming an aqueous extract of “lian-sepent”, a traditional medicine corresponding to T. crispa according to local ethnobotanists. This herbal remedy was supposed to detoxify his liver. It consisted of a piece of T. crispa stem put into a bottle of water and drunk regularly over the next two days. Two weeks later, the patient prepared a similar aqueous extract of T. crispa and consumed it over two days. Following his last intake, the patient felt fever and asthenia for one week and went to the emergency room after occurrence of dark urine. On admission, he suffered from jaundice, was not overweight, and had normal vital signs. Biological tests revealed evidence of hepatocellular damage (ALT 1923 U/L; AST 873 U/L) and cholestasis (γGT 155 U/L). Abdominal ultrasonography was normal with no hepatomegaly or lithiasis. The results of laboratory testing disclosed no serological arguments for viral hepatitis (hepatitis A virus, hepatitis B virus, hepatitis C virus, cytomegalovirus, Epstein-Barr virus and varicella zoster virus). The patient was discharged two weeks after admission and evolution was marked by the regression of jaundice and progressive decrease in liver function tests without any specific treatment (Table ). |
pmc-6131554-1 | A 76-year-old man with severe chronic obstructive pulmonary disease (COPD) presented with a feeling of fatigue, weight loss, and reduced physical activities. He was diagnosed with COPD at the age of 69 years and had retired from work the following year. His smoking history included 40 cigarettes per day between the age of 14 and 69 years; his airflow limitation was classified as severe by the Global initiative for Chronic Obstructive Lung Disease; and a chest computed tomography (CT) scan showed severe emphysema. He had started long-term oxygen therapy at the age of 72 years and is currently inhaling 3 L/min of oxygen. Medical and family histories were otherwise unremarkable. Cardiac ultrasound excluded comorbid congestive heart failure or pulmonary hypertension, and CT pulmonary arteriography also excluded chronic pulmonary thromboembolism. As the patient had a history of acute exacerbations of COPD more than twice a year with extreme respiratory symptoms, he was prescribed a combination of inhaled long-acting antimuscarinic antagonist, long-acting beta2-agonist, corticosteroid, and oral carbocysteine, ambroxol, and theophylline. He reported symptoms of dyspnea on exertion, depression and anxiety, and a decrease in physical activity. He also experienced anorexia with a weight loss of more than 5 kg in a year, and no other possible causes of weight loss, such as tuberculosis and malignant tumor, were observed. Therefore, in addition to respiratory pharmacotherapy, we prescribed an antianxiety drug and provided nutritional supplement therapy, patient education, and pulmonary rehabilitation. However, the patient's mental and physical symptoms did not improve after 4 months. Furthermore, he exhibited deterioration in activities of daily living as well as physical and mental weakness; hospital visits were difficult and therefore, he considered home care. Persistent weight loss, poor endurance and energy, and low physical activity levels led to the diagnosis of physical frailty according to Fried's criteria (). This vulnerability was supported by assessments using the Kihon Checklist (KCL) (), the COPD Assessment Test (CAT) (), and the Hospital Anxiety and Depression Scale (HADS) (), all of which revealed high scores indicating inferior status. The KCL is a tool designed by a study group from the Japanese Ministry of Health, Labor and Welfare and comprises 25 items divided into seven categories: physical strength, nutritional status, oral function, socialization, memory, mood, and lifestyle. The KCL scores range from 0 (no frailty) to 25 (severe frailty); a previous study classified the patients' frailty status as non-frail (0–3), prefrail (4–7), and frail (8–25) (). The CAT is a reliable tool that comprises eight items that assess the various COPD symptoms and is widely used in clinical practice. The CAT scores range from 0 to 40, with a score of 0 indicating no impairment. The HADS is also widely used to measure the level of anxiety and depression and comprises 14 items: 7 associated with anxiety (HADS-A) and 7 associated with depression (HADS-D). The HADS-A and HADS-D scores ranged from 0 to 21, and are in the range 8–10 for doubtful cases and ≥11 for definite cases. For the present case, we continued the pharmacological treatment, nutritional supplement therapy, patient education, and pulmonary rehabilitation and included 2.5 g of Ninjin'yoeito to be taken 3 times a day before meals.
After administration of Ninjin'yoeito, physical examination and blood tests such as electrolytes, liver function tests, and renal function test were performed to evaluate the side effects of Ninjin'yoeito administration. However, no side effects were detected. A significant improvement in symptoms, including increased appetite and alleviation of mood disorders and weight loss, was observed 1 month after initiating Ninjin'yoeito administration. Body weight and muscle mass continued to increase, and after 6 months of Ninjin'yoeito administration, the body weight increased by 8 kg compared with that prior to Ninjin'yoeito administration. Body composition assessed using bioelectrical impedance (InBody 720; Biospace, Tokyo, Japan) showed increasing muscle mass and no change in the body fat percentage (Figure ). The patient's KCL, CAT, and HADS scores increased over time (Figure ), and his status improved from frailty to non-frailty. Written informed consent was obtained from the participant for the publication of this case report. |
pmc-6131676-1 | A 9-year-old boy presented to our hospital with a history of recurrent neck abscesses since 8 years of age. He had received antibiotics and had undergone drainage of the abscesses in other hospitals. He was admitted to our hospital after control of inflammation. Barium esophagography showed a PSF on the left side (Fig. ). Oral contrast coronal computed tomography (CT) showed an air- and barium-containing fistula (Fig. ). He underwent open neck surgery for definitive treatment of the PSF. He quickly recovered, and he was discharged from the hospital 7 days after the surgery. However, 2 weeks later, he visited our hospital again because of a neck abscess. He received antibiotics and underwent drainage. Barium esophagography revealed fistula recurrence at the same location (Fig. ). As reoperation with the cervical approach was expected to be difficult owing to possible severe adhesions, MLS was planned. Although the internal orifice was detected easily (Fig. ), the fistula was found to be wider and deeper than expected after resection of the fragile layer associated with inflammation (Fig. ). The fistula was resected piecemeal because it could not be easily inverted and peeled off. The entire mucosal remnant was macroscopically removed. Although suturing was difficult because of the wide internal orifice, the procedure was completed uneventfully (Fig. , ). Barium esophagography was performed on the seventh postoperative day, and no issues were noted. He had an uneventful recovery, and he was discharged 10 days after the surgery. No recurrence was observed during an 18-month follow-up. |
pmc-6131676-2 | A 10-year-old girl presented to our hospital with a history of recurrent left-sided neck swelling since 6 years of age. After control of inflammation, barium esophagography was performed, and it showed a PSF on the left side. CT showed an air- and barium-containing fistula. MLS was performed as first-line treatment. The fistula was narrow, and its tissue was not fragile (Fig. ). Therefore, we made the incision as small as possible (Fig. , ), and the operation was completed uneventfully (Fig. ). Barium esophagography was performed on the fifth postoperative day, and no leakage was noted. Free oral intake was started on the same day. She had an uneventful recovery, and she was discharged 7 days after the surgery. No recurrence was observed during a 10-month follow-up. |
pmc-6131731-1 | A 17-year-old man with no known past medical history, presented with 6 months of blurry vision in both eyes. He had no other ocular, medical, or surgical history.
Baseline visual acuity (VA) was 20/20 in the right eye (RE) and 20/63 in the left eye (LE). His intraocular pressure was normal (17/16 mmHg). Slit lamp examination revealed normal anterior structures and no anterior segment inflammation. A subclinical keratoconus was described in the topography study. 1+ cells in the vitreous (graded on a scale of 0+ to 4+), snowballs and snow banking in the inferior pars plana as well as peripheral vasculitis were observed in both eyes (BE) on dilated fundus examination.
Serological tests for HIV, Toxoplasma gondii, Borrelia burgdorferi or Treponema pallidum were negative, as well as for antinuclear (ANA) and antineutrophil cytoplasmatic (ANCA) antibodies.
He was diagnosed with bilateral pars planitis. Optical coherence tomography (OCT) showed cystoid macular edema in the LE, so that sub-tenon injection of triamcinolone was performed in order to control inflammation, which was slowly reduced.
Subsequent follow-up visits showed improvement in vision to 20/25 in the LE, resolving progressively the inflammation of the posterior pole although 0.5+ cells were observed in the vitreous cavity. Then, no additional therapy was needed. Nonetheless, the patient complained of loss of visual field in his LE.
In-depth fundus examination showed a mild, diffuse, granular appearance of the retinal pigment epithelium (RPE) throughout the LE. Progressive, intraretinal bone crepuscule pigmentation developed during the following three months (Fig. ). The RE showed no retinal pigmentation. Humphrey perimetry confirmed peripheric constriction of the visual field in the LE and no scotomas in the RE.
An electroretinogram (ERG) showed subnormal response only in the LE. The diagnosis of unilateral RP-like appearance was made. |
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