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pmc-6411848-1 | The 3rd patient of the family (IV:4) is a 10 years old boy who has had similar clinical course and manifestations as his two older cousins. Presently, his height is 111 cm (Z-score -3.7) and weight 33 kg (Z-score -0.4). Delayed milestones and multiple compression fractures were apparent at the age of 9 months. His first femoral fracture occurred at the age of 18 months and generalized osteopenia was observed; multiple other fractures have occurred thereafter. Physical evaluation revealed a low posterior hairline, short and webbed neck, low set ears, shield chest, long fingers and toes. Sclerae and teeth were normal. Radiographs revealed moderate thoracic kyphosis and platyspondyly. He started intravenous pamidronate treatment at the age of 3 years which improved the compression fractures but did not completely prevent new fractures. Along with skeletal problems he was also diagnosed with hearing loss and visual impairment at the age of 5 years. He was operated on for bilateral cataract. Learning difficulties were observed since early childhood. Blood biochemistry for calcium, alkaline phosphatase, creatinine and 25-OH-vitamin D was normal. |
pmc-6412033-1 | A 62-year-old man of Bangladeshi origin was brought to the emergency department with lethargy and fever. Over the previous 2 weeks, he had developed a productive cough and weight loss. His past medical history included ulcerative colitis (diagnosed in 1999), which was quiescent on surveillance colonoscopy 2 days prior to admission. A suspicious rectal lesion was, however, biopsied. He had coronary artery bypass grafting in 1999, type 2 diabetes, hypertension, hyperlipidaemia and chronic hepatitis B. His medication included prednisolone, 10 mg daily (which he had been taking for 15 years), azathioprine 150 mg daily, Asacol (mesalazine) 2 mg daily, tenofovir and allopurinol 100 mg daily. His family acknowledged he had been taking prednisolone at greater than the prescribed dose for approximately 2 months prior to admission.
The patient was born in Sylhet, Bangladesh, and had moved to the UK aged 14. 6 months previous to the admission, he had travelled back to Sylhet for a 1 month family visit. He had not been unwell during the trip or until presentation. There was no unusual exposure history. There was no other significant or relevant travel history during his lifetime.
On examination he had a temperature of 34.8 °C, a non-tender erythematous left calf overlying a saphenous vein harvest site. His haemoglobin was 116 g l−1, white cell count 6.2x109 per litre and C-reactive protein 138 mg l−1. Initial management included empirical intravenous flucloxacillin 1 g four times daily for presumed cellulitis. A lower limb ultrasound excluded deep vein thromboses, and a computed tomography scan of chest, abdomen and pelvis demonstrated a rectal mass and a right basal pneumonia. Antibiotics were changed to intravenous benzylpenicillin 1.2 g four times daily and oral clarithromycin 500 mg twice daily.
Over the initial week, his condition deteriorated with fever to 40 °C, rising C-reactive protein and erythema spreading up the left leg to the scrotum, abdomen, left flank and right leg. The skin became tender and warm to touch. Dermatologists reviewed the skin on day 6 (). A differential diagnosis of multifocal cellulitis, panniculitis or migratory thrombophlebitis, in the context of possible malignancy was made. The patient developed a tender, swollen right testicle. An ultrasound showed epididymo-orchitis. Empirical treatment with oral ciprofloxacin 500 mg twice daily and oral doxycycline 100 mg twice daily was added.
The infectious diseases team suggested changing the benzylpenicillin to intravenous ceftriaxone 2 g daily, and adding oral linezolid 600 mg twice daily and intravenous amikacin 1.2 g once daily. Vasculitic, auto-immune and sexual health (HIV, chlamydia, gonorrhoea) screens and mycoplasma serology were negative. A trans-thoracic echocardiogram showed no signs of endocarditis. Blood cultures were negative.
On day 12, the patient was transferred to critical care for ventilation and noradrenaline (dose titrated to blood pressure within the standard critical care range of 6–13 µg min−1) for septic shock, considered secondary to cellulitis. He remained febrile at 40 °C and had developed a coagulopathy and bloody diarrhoea. His antibiotics were changed to meropenem 1 g three times daily and linezolid 600 mg twice daily. Plastic surgeons and urologists did not suspect necrotizing fasciitis.
The erythema spread to his flanks. No papules, nodules or umbilicated lesions were noted. In view of the diagnostic uncertainty, a skin biopsy was performed on day 15. A rectal biopsy showed CMV inclusion bodies and the plasma CMV DNA viral load was 15 304 copies ml−1. Intravenous ganciclovir 375 mg twice daily was initiated on day 19 to treat suspected disseminated CMV disease with evidence of colitis, epididymo-orchitis and panniculitis. CMV DNA was detected in skin, urine and throat samples.
Due to worsening leucopenia and thrombocytopenia, the ganciclovir was changed to foscarnet 4.5 g three times daily. Fluconazole 400 mg daily was added empirically on day 27 given the lack of clinical improvement, due to the presence of Candida albicans in the urine on day 24. The skin biopsy was reported on day 28 as showing septal/lobar panniculitis. To exclude necrotizing fasciitis, a scrotal incision was performed, which was sterile. Examination of the rectum showed no inflammation.
The fluconazole was switched to micafungin 100 mg daily on day 31, due to the growth of Candida glabrata from urine culture on day 30. Following a methenamine silver stain, the histopathologists reported the first skin biopsy as showing small, round yeasts of 3–5 microns within well-circumscribed areas of inflammation in the dermis and subcutaneous fat (). A skin biopsy was repeated the same day with samples sent for microbiological and fungal culture and molecular testing. On day 34, the pan-fungal PCR confirmed DNA from H. capsulatum. The micafungin was changed to AmBisome (amphotericin B) 320 mg daily.
A bone marrow biopsy was performed on day 33, which showed pancytopenia with increased macrophage activity, without evidence of malignancy, acid-fast bacilli or fungi. Ferritin and triglyceride levels were raised (47 798 µg l−1 and 2.45 mmol l−1, respectively) supporting a diagnosis of HLH. Immunosuppression was considered, but due to the patient's extremely poor clinical condition was not given. The bone marrow culture subsequently grew H. capsulatum. The patient continued to deteriorate and died on day 36 of admission. |
pmc-6412036-1 | A 27-year-old female with acute gastroenteritis was admitted to Kasturba Hospital, Manipal, India. She was suffering from lupus nephritis class IV and on a NIH (National Institute of Health) protocol for 6 months. The patient was on a treatment regime with four cycles of cyclophosphamide (700 mg for 2 weeks) and she was due to receive the fifth pulse of cyclophosphamide. On admission, she had complaints of loose stools, vomiting, abdominal pain and fever for 1 day. Stools passed were watery with no mucus and blood. She had a history of oral candidiasis, upper respiratory tract infection and leucopenia. |
pmc-6412971-1 | A 64-year-old man with three-month history of increasing right-sided neck lump was reviewed at the local tuberculosis control centre for suspected tuberculosis. Three weeks prior, he underwent an ultrasound-guided fine-needle aspiration (FNA) of the lesion arranged by his general practitioner, which yielded 20 mL of purulent material. Computed tomography (CT) scan of his neck and thorax (Fig. A–C) revealed an enhancing mass measuring 85 mm × 44 mm × 57 mm within the lower neck and supraclavicular fossa and multiple parenchymal nodules over bilateral upper lobes. The patient denied any fever, night sweats, or weight loss. Except for a mild chronic cough, systemic review was unremarkable. There was no prior history of diabetes mellitus, recent travel, or history of trauma/open wounds on his neck. He had a 10-year history of rheumatoid arthritis, which was controlled with leflunomide 10 mg daily and methotrexate 20 mg weekly. He is an active smoker of 20 pack-years. He worked as a foundry metal machine operator all his life. Clinically, the patient was afebrile, normotensive, and appeared well. The right cervical mass was firm, non-tender, and with no overlying skin changes. A small sinus just above the supraclavicular fossa oozing greenish creamy fluid was seen. This spontaneous discharge had developed two weeks after FNA. Basic blood tests were normal; white cell count 6.09 × 109/L, haemoglobin 131 g/L, platelet 243 × 109/L, C-reactive protein 4.9 mg/L, Na 137 mmol/L, K 4.7 mmol/L, Ur 8.2 mmol/L, Cr 103 μmol/L, albumin 39 g/L, haemoglobin A1c 5.5%, and human immunodeficiency virus screening test negative. The FNA specimen was acid-fast bacilli (AFB) smear 2+ and GeneXpert MTB/RIF molecular assay was negative for Mycobacterium tuberculosis complex. M. paraffinicum was identified based on 99% homology with 16S rRNA gene sequence information. The minimum inhibitory concentrations (MIC) of antibiotics were as follows: clarithromycin MIC: 8.0 μg/mL; rifabutin MIC: 1.0 μg/mL; ethambutol MIC: 16.0 μg/mL; isoniazid MIC: >8.0 μg/mL; moxifloxacin MIC: 4.0 μg/mL; rifampin MIC: >8.0 μg/mL; trimethoprim/sulfamethoxazole MIC: >8/152 μg/mL; amikacin MIC: 16.0 μg/mL; linezolid MIC: 32.0 μg/mL; ciprofloxacin MIC: 8.0 μg/mL; and streptomycin MIC: 16.0 μg/mL. Two out of three sputa were AFB smear positive, but cultures failed to yield any viable organism. Cytology showed no malignant cells but numerous macrophages and neutrophils. Spontaneous discharge of the neck lump persisted over a two-month period and was managed with regular wound care. A multidisciplinary decision was initially made to treat residual disease with rifabutin, clarithromycin, and moxifloxacin. However, he went on to recover with a completely healed sinus before any drug therapy was started. Follow-up CT scans at six and 12 months (Fig. A–C) confirmed resolution of the neck mass and stable pulmonary changes. His lung function tests on follow-up showed only mild obstruction of forced expiratory volume in 1 s 2.30 L (79%) and normal diffusion capacity. Plans for further treatment were held off. He has since remained well and is maintained on close monitoring. |
pmc-6413355-1 | A 69-year-old white male with history of hypertension, noninsulin-dependent diabetes, chronic kidney disease stage 3, hyperlipidemia, coronary artery disease, and congestive heart failure was brought to hospital with complaints of generalized malaise, muscle weakness with pain in both his lower extremities, and inability to ambulate for last 4-5 days. He had developed these symptoms within 2 days of starting sitagliptin (Januvia 100 mg) therapy. His other medications included simvastatin, amlodipine, carvedilol, clopidogrel, gabapentin, glipizide, hydrochlorothiazide, metformin, quinapril, and ezetimibe. He gave history of similar weakness when he was started on sitagliptin therapy few months ago, so he discontinued it by himself. His primary care physician however restarted it again at recent follow-up, when the patient refused insulin therapy.
In the emergency department, the patient was hypotensive with a blood pressure of 90/60 mm Hg with a pulse of 70 bpm. On examination, he had marked proximal muscle weakness of bilateral lower extremities. There was mild tenderness to palpation of both thighs. The rest of physical examination was unremarkable. Laboratory data revealed serum creatinine of 9.1 mg/dL with blood urea nitrogen of 130 mg/dL. 3 months prior to presentation, the patient's serum creatinine was 1.2 mg/dL with urinalysis showing 1+ proteinuria and an estimated glomerular filtration rate of 62 ml/min/1.73 m2. Creatine kinase (CK) level came back significantly elevated at 43,900 U/L. Potential causes of rhabdomyolysis like trauma, seizures, hypophosphatemia, drug and alcohol abuse, hypothyroidism, and vitamin D deficiency were ruled out. He had been on a stable dose of simvastatin 80 mg daily for more than 10 years. Intravenous hydration with bicarbonate therapy was initiated; however, the patient was noted to be oliguric and required initiation of hemodialysis therapy. AKI was presumed to be due to rhabdomyolysis-induced acute tubular necrosis and so kidney biopsy was not performed. Both sitagliptin and simvastatin were promptly discontinued. Rhabdomyolysis gradually improved; however, our patient remained oliguric and dialysis-dependent at the time of discharge at 2 weeks. The patient recovered his kidney function and was taken off hemodialysis after 2 months following his discharge. |
pmc-6413360-1 | A 15-year-old Syrian female was admitted to the hospital on November 2016 with a one-day complaint of sudden onset of numbness in the left lower and upper limbs, followed by weakness in the same areas, right mouth angle deviation, and loss of sphincters' control. She did not experience headache, nausea, vomiting, convulsions, or coma.
Eight months earlier, she developed massive rectal bleeding, colonoscopy was performed, and the patient was diagnosed with ulcerative colitis (UC). She was treated with mesalazine 1 gram three times daily, azathioprine 50 milligram daily, prednisolone 40 milligram daily, and cefuroxime 500 milligram tab twice daily for a week.
She has no history of smoking, alcohol abuse, or illicit drug use. She did not report any suspected allergies and she has no other history of hypertension, diabetes mellitus, cardiac, rheumatological, or hematological disease.
On examination, her vital signs are blood pressure 100/60 mmhg, Pulse 110/minute, respiratory rate 36/minute, and temperature 37.5°C. General examination revealed conjunctival pallor and pitting edema in the left lower limb and purple stretch marks extends on the whole lower limbs till the sacrum.
On neurological examination, there was no impaired consciousness and the patient was awake and alert. Cranial nerves exam was only significant for left facial nerve palsy. Motor examination showed 5/5 strength in the right upper and lower limbs, 3/5 left upper limb, and 0/5 left lower limb; there was also hypotonia on the left limbs and normal tone on the right limbs without any atrophy. Reflexes examinations scored 2/4 for the right limbs (normal) and 1/4 for the left limbs (hyporeflexia). Right toes showed planter flexion and absence of the flexion for the left toes. No cerebellar abnormalities were noted in the right side; cerebellar exam was not performed on the left side due to limbs weakness. She scored 10 on National Institutes of Health Stroke Scale (NIHSS). Sensory examination revealed loss superficial and deep sensations on the left side and normal sensations on the right side. Other systematic examinations, including cardiac, respiratory, and gastrointestinal systems, were all normal.
Investigations including blood tests showed evidence of pancytopenia (hemoglobin 4.4 g/dL, platelets: 66 x1000/mm3 dropped to 3 x1000/mm3 after in two days of admission, WBCs: 1.4 x1000/mm3 with 35% neutrocytes, 61% lymphocytes, 3% monocytes, and 1% eosinophils); urinalysis values were within normal ranges. Thrombophilic and immunological screening including homocysteine, factor V Leiden, protein C, protein S, antithrombin, lupus anticoagulant factor, and antiphospholipid antibodies were all insignificant.
An emergency computerized tomography (CT) scan () showed small hypodensity foci situated in the cortical and subcortical area in right partial lobe. Magnetic resonance imaging (MRI) () showed cortical and subcortical areas in the right temporoparietal fossa with high signal on T2 and FALIR studies. T1 study showed isointense foci in the cortical and subcortical area in the posterior part of the parietal lobe extending deeply through the posterior horn of the right lateral ventricle. Based on these findings, the accident is complicated with focal infarction around the M2-M3 segments of the right middle cerebral artery. Aspirin 162mg was given upon these findings and the prednisolone treatment was continued.
Cardiac echocardiogram and carotid arteries Doppler ultrasound study were both normal. The patient did not complain of any symptoms related to her UC when she had the CVA, which indicates that the UC was not in active stage.
On December 2016, the patient was able to walk and her neurological examination dramatically improved (NIHSS: 0); she was then discharged and referred to physical therapy. On January 2017, the patient suffered from overt rectal bleeding, she was admitted again to the hospital, and proctocolectomy was performed.
A written informed consent was obtained from the patient before writing this report, Syrian Private University and Damascus Hospital Ethical Committee approved the report, and both are available upon request. |
pmc-6413368-1 | A 60-year-old male had incidentally discovered bilateral renal masses identified on computed tomography (CT) imaging. Robotic assisted partial nephrectomy of the right renal lesion was completed on a 4-centimeter Furman Grade 2, pT1a clear cell RCC with negative surgical margins. Due to the posterior location of the 2-centimeter mass on the left kidney (), the patient opted for percutaneous cryoablation of the mass 4 months following the right robotic partial nephrectomy (). Follow-up cross-sectional imaging revealed no evidence of cancer recurrence in either kidney over a 2-year period (). A new contrast-enhancing lesion was noted in the perinephric fat of the left kidney 2 years following therapy (). Magnetic resonance imaging (MRI) scans also demonstrated a 2-centimeter enhancing and restricting ill-defined soft tissue focus in the left kidney region where previous cryoablation was performed. Biopsy was foregone due to the new rapid development, consistency, and location of the lesion. The patient underwent open subcostal partial nephrectomy with complete perinephric fat removal (). Surgical pathology revealed the resected renal mass to contain organized tumefactive fat necrosis with multinucleate GC reaction () without evidence of clear cell RCC recurrence (Figures and ). Immunohistochemistry studies (Figures and ) demonstrated an inflammatory reaction characterized by abundant histiocytes and multinucleate giant cells that were positive for CD68 (KP1). Cytokeratin AE1/AE3 and PAX-8 immunohistochemistry were both negative (Figures and ). The patient is 2 years removed from surgery without cancer or disease recurrence. |
pmc-6413388-1 | The patient was a 37-year-old married Japanese woman. She was referred to the Department of Psychiatry at the Toho University Omori Medical Center, Tokyo, to receive care for a severe postpartum depressed mood and intense suicidal ideations. The participants provided written informed consent prior to enrollment in this case report.
She had no previously documented psychiatric history and no documented family history of psychiatric or perinatal illness. She had been brought up in an urban environment since childhood. She had a good relationship with her parents and did not experience any abuse or maltreatment. Her character was honest, diligent, and orderly, and she had an especially strong sense of responsibility. After graduating from university, she worked as an assistant curator in a museum. At the age of 34 years, she met and married her husband, who was an engineer. They were not eager for her to become pregnant. Although she and her husband moved to the countryside because of his work, she decided to continue her job because, despite a 3-hour commute, she found her work to be very fulfilling.
At the age of 36 years, she became pregnant. She quit her job to become a housewife and became bored with her daily life; she also felt that living in the countryside was inconvenient. Her husband was busy with work and left all the pregnancy preparations to her, which caused her to feel frustrated. She started feeling very anxious about her primiparity and child-care, and she moved to her parents' house to receive their support. During her 39th week of pregnancy, she had a forceps delivery because of a birth canal infection. The delivered boy was 3150 grams and had no deformities of any kind. However, she could not hold her child immediately after childbirth because she was receiving treatment for her infection. She appeared to lack affection towards her baby because she could not remember how she felt when she eventually held her baby for the first time.
It was difficult for her to control her baby when he cried, and she felt fatigued and anxious. He was very demanding for his mother's breast milk, and she continued to feed him because of a feeling of responsibility. A month after the delivery, depressive symptoms (depressed mood, abnormal fear, and insomnia) appeared and gradually worsened. She felt a strong sense of distress while she was with her baby and was confused as to how to care for him. She had difficulty asking for help because she felt that she should do everything on her own. She began to regret having given birth because it had led to her present circumstances. Her husband was still unable to provide her with either emotional or physical support, but her mother continued to help her care for her baby. The patient's lack of affection worsened and was accompanied by other depressive symptoms, such as poor concentration, indecisiveness, and reduced energy. The patient began to worsen daily and began to have difficulty taking care of both herself and her baby.
Three months after the birth, she visited a psychiatric outpatient clinic and was diagnosed as having postpartum depression and bonding disorder. Her Temperament and Character Inventory (TCI) scores were as follows: Novelty Seeking (NS): −1.78; Harm Avoidance (HA): 2.52; Reward Dependence (RD): −2.09; Persistence (PS): 1.78; Self-directedness (SD): −2.1; Cooperativeness (CO): −1.35; and Self-transcendence (ST): −0.54. Her temperament was judged as logical and obsessive-compulsive, and her character was judged as melancholic and schizoid.
Treatment with an antidepressant (sertraline, 25 mg/day) and psychotherapy was started, but her depressive symptoms worsened. Because of strong nausea, the treatment with sertraline was discontinued and treatment with mirtazapine (15 mg/day) and olanzapine (initial dose, 2.5 mg/day) was started. Finally, she was admitted to the Department of Psychiatry at the Toho University Omori Medical Center.
On admission, her Hamilton Rating Scale for Depression (HRSD) score was 35. She was characterized as having a depressive mood most of the day, markedly diminished interest and pleasure, insomnia, psychomotor agitation, loss of energy, feelings of worthlessness, indecisiveness, suicidal ideation, and a suspicious attitude. We diagnosed her as having peripartum-onset major depression, and we gradually increased the dosage of mirtazapine up to 45 mg daily and that of olanzapine up to 10 mg daily, with poor results. Therefore, nortriptyline was prescribed along with these drugs. After the dosage of nortriptyline was increased to 100 mg, her depressed mood and indecisiveness began to improve at around day 45 of her hospitalization. She was allowed to stay overnight at her house, with her child, on day 53. However, her depressed mood and anxiety were suddenly exacerbated when she returned to the hospital. Hence, we started a series of electroconvulsive therapy (ECT) treatments beginning on day 72 and her depressive state improved somewhat.
She made comments such as “Even though I should have been happy to have been with my child, it did not go so well emotionally” and “I'm convinced that I'm incurable.” Her score on the Mother to Infant Bonding Scale (MIBS), which is a 10-item self-reported instrument, was 12, indicating a severe bonding disorder []. We focused on the bonding disorder and provided Kangaroo Care during family sessions. We started providing Kangaroo Care with her baby for two hours in a private room of the ward while her husband was present. During the Kangaroo Care session, we facilitated skin-to-skin contact and educated her regarding parenting behavior in cooperation with the ward nurses. Two sessions were provided, and similar follow-up care was subsequently provided by midwives. She learned to recognize her baby's gestures, facial expressions, and emotions. She was transfixed and embarrassed when the baby was crying, and she barely smiled at the baby during the first session. To allow the patient to gain self-confidence, we first had the patient hold her baby while he was in a good mood. We repeatedly showed her how to cope with the baby's discomfort in a concrete manner and told her that her baby was very cute to improve her capacity to verbalize her emotions. Her husband was encouraged to send her photos and movies of her child taken at home every day based on the policy of imaginary exposure. After this intervention, her awareness of her child's feelings and her ability to provide flexible care for her baby improved.
The patient began to experience tender feelings towards her child and her anxiety decreased (HRSD = 7). She tried staying at home overnight, and her depression and bonding problem did not worsen. On day 114, she was discharged from the hospital. She was taking maintenance doses of 100 mg of nortriptyline, 30 mg of mirtazapine, and 5 mg of olanzapine per day at the time of her discharge. We continued outpatient treatment and supported her in caring for her child. In addition, we liaised with midwives, public health nurses, and home visit nurses regarding her care and ideal environment after discharge. At 9 months after her discharge, her MIBS score was 5 (). A tendency towards an improvement in her bonding disorder was seen, and her depression remained in remission (HRSD = 6). |
pmc-6413389-1 | This case concerns a 50-year-old female. Past medical history was significant for ulcerative colitis, hypertension, hypothyroidism, and a left deep vein thrombosis. She had a history of intermittent night sweats for 3-4 months before presentation. Her ulcerative colitis had flared up about 6 months before presentation to hospital and was treated with prednisone 5 mg daily. This flared again 2 weeks before presentation, so prednisone was restarted, and the day before presentation she underwent colonoscopy. She was on drugs to treat hypertension (ramipril), elevated cholesterol (rosuvastatin), hypothyroidism (levothyroxine), and ulcerative colitis (mesalazine and prednisone 5 mg daily for the recent flare up). She had not been treated with anti-TNF biologics. For her presenting complaint, there was a one-day history of continuous dull headache increasing in severity by evening. The patient then developed slurred speech, unsteady gait, and progressive right-sided weakness. She was seen at a local hospital, where her blood pressure was recorded as 177/95, pulse 90/min, and temperature 35.9°C. Her left pupil was 3 mm in diameter and sluggishly reactive to light, while the right pupil was fixed. Her right side was not moving spontaneously, and a right-sided stroke was diagnosed. While in hospital, there was a sudden reduction in the level of consciousness and a “grand mal” seizure lasting for 2 minutes. While in the local hospital, a CT brain scan showed hemorrhage into the left basal ganglia and left temporal lobe with ventricular extension. Just one CT brain scan was carried out owing to the rapidity of events. The next day, she was transferred to a tertiary care hospital where MRI scan gradient echo mapping highlighted the extent of the hematoma in the left basal ganglia (). MRA (magnetic resonance angiography) of the circle of Willis demonstrated normal intracranial vessels without focal stenosis or aneurysmal dilatation. There were no vascular malformations. MRV (magnetic resonance venography) demonstrated normal venous sinuses as well as normal deep veins, ruling out widespread cerebral venous thrombosis as the primary diagnosis. The preferred clinical diagnosis was acute hemorrhagic leucoencephalitis, with viral encephalitis and cerebral vasculitis in the differential. On further examination, there was extensor posturing in the left arm and no movement of the right arm. Pupils were asymmetric (right 5 mm, left 3 mm) and fixed. There was no corneal or doll's eye reflex and no facial asymmetry. Tone and bulk were normal, with no fasciculations. Plantars were unresponsive, with absent knee jerks, but other reflexes were 1+ to 2+ in strength. Blood work during the admission showed an elevated white cell count (17.0 × 109/L, normal range 4–11 × 109/L), with increased lymphocytes and neutrophils), normal platelet count (184 × 103/µl, normal range 150–400 × 103/µl), slightly elevated rheumatoid factor (22.5 IU/ml, normal < 15 IU/ml), and markedly elevated C reactive protein (287 mg/ml, normal < 3 mg/ml). A serological screen for autoantibodies was also carried out. The patient was screened for antinuclear antibodies used to diagnose a number of systemic autoimmune rheumatic diseases such as systemic lupus erythematosus, systemic sclerosis, Sjögren's syndrome, mixed connective tissue disease, and idiopathic inflammatory myopathies. The screen measured antibodies against double-stranded DNA, chromatin, ribosomal P, SS-A/Ro, SS-B/La, centromere B, SM, Sm/RNP, Scl-70, and Jo-1, and was negative. In addition, the patient was screened for antiglomerular basement membrane (GBM) antibodies (which defines anti-GBM disease, a small vessel vasculitis of kidneys and lungs), antimyeloperoxidase, and antiproteinase antibodies (which are also elevated in systemic vasculitides), all of which were found to be negative. The patient was not screened for antibodies against antineutrophil cytoplasmic antibodies (ANCAs) or antiphospholipid antibodies. Blood, urine, and sputum cultures were negative. The patient was started on pulse dose steroids for likely vasculitis, but her clinical status rapidly declined, and she died 2 days after presentation.
A full autopsy was performed. Continuous mucosal thickening and flattening was noted in the colon, predominantly on the left side, while the esophagus, stomach, duodenum, and ileum had a normal appearance. There was no intestinal hemorrhage, obstruction, or perforation. Microscopic examination of sections from the left colon showed mucosal ulcers with inflammatory exudates. Inflammatory cells including lymphocytes and eosinophils infiltrated the mucosa and submucosa, without vasculitis. There was no inflammation in the muscularis propria or serosa and no evidence of malignancy. These findings were interpreted as “consistent with ulcerative colitis” by the examining anatomic pathologist. When first removed at autopsy, the brain weighed 1400 g before fixation. The fixed brain showed diffuse hemispheric edema and an area of disruption over the left temporal lobe measuring 4.5 × 1.0 cm. There was left-sided uncal herniation, but no tonsillar herniation. Coronal sections through the cerebral hemispheres showed extensive hemorrhage and disruption in the left middle temporal gyrus and inferior portions of the left striatum and pulvinar. There was a discrete hematoma in the left superior frontal gyrus and hemorrhage in the right median frontal cortex and in white matter adjacent to the right orbitofrontal surface (). There was extensive right-sided hemorrhage in the brainstem, involving the crus and dorsal pons with extension into the fourth ventricle. Hematoxylin and eosin/luxol fast blue stained sections showed extensive acute hemorrhage with infarction (). Changes were noted in both grey and white matter. There was a striking vasculopathy. Vessels showed invasion by leucocytes () as well as fibrinoid necrosis of the wall (). Invading leucocytes were rarely positive for the lymphocyte marker CD3 or the macrophage-microglia marker CD68 but more often positive for the general white blood cell marker Leucocyte Common Antigen (LCA/CD45) consistent with neutrophils (). Some vessels contained luminal thrombus (). There were no perivascular sleeves of demyelination. Detailed measurements were made on 173 involved vessels, of which 88 were in grey matter (cortex, putamen, or brainstem nuclei) and 85 in white matter. The mean diameter (for all vessels) was 66.7 ± 3.9 µm (mean ± standard error of the mean). The ratio of wall thickness to diameter is plotted as a function of vessel diameter in . The mean ratio was 0.18 ± 0.01. Most vessels were under 100 µm in diameter which would correspond either to venules or small veins on the venous side or to arterioles or small arteries. However, the ratio of wall thickness to diameter is smaller for venous vessels than arterial ones. It is closer to 0.1 for venous vessels but around 0.5 for arterial vessels []. This indicates that most of the involved vessels were venous. The findings point to an acute cerebral vasculitis, predominantly involving invasion of venous vessels by neutrophils. |
pmc-6413394-1 | A 55-year-old male with multiple myeloma on his eighth cycle of chemotherapy with bortezomib, lenalidomide (recently decreased to 10 mg po daily from 25 mg po daily), and dexamethasone presented with a two-week history of worsening blurriness and floaters in his right eye. An outside provider noted panuveitis and retinal whitening on examination. Anterior chamber paracentesis was negative for CMV, HSV-1, HSV-2, VZV, and Toxoplasmosis. Oral valacyclovir and topical steroids and cycloplegics were started for presumed acute retinal necrosis, and the patient was referred to our institution for further diagnostic work-up and management. Of note, recent serum laboratory values revealed a normal white blood cell count (9.41 k/µL; range 4.5–11 k/µL) and neutrophilic profile (71.0%; range 39–69%) with negative CMV antigen and aerobic blood culture; lambda light chain immunoglobulins were significantly elevated (67.29 mg/L, range 5.7–26.3 mg/L) and alpha-2 globulin proteins were abnormally high on serum electrophoresis (0.93 g/dL, range 0.58–0.84 g/dL) as expected given his disease.
Best-corrected visual acuity (BCVA) was 20/60 in the right eye, 20/20 in the left. Pupils and intraocular pressures were normal. Slit lamp examination of the right eye revealed mild anterior chamber flare without cell, mild cataract, and 3+ cell in the anterior vitreous. Dilated funduscopic examination revealed vitreous haze, diffuse vascular sheathing, and a poorly-defined area of inferotemporal retinal whitening without associated hemorrhage (). The left eye was normal. Spectral-domain optical coherence tomography of the right eye showed no significant abnormalities aside from overlying hyperreflective vitreous debris (). Fluorescein angiography demonstrated irregular vascular filling and blockage from vitreous debris ().
Given the previous negative anterior chamber tap, worsening clinical exam, and high suspicion for infectious retinitis, the decision was made to proceed with a diagnostic vitrectomy. Diluted and undiluted vitreous biopsy were obtained via a 23-gauge pars plana vitrectomy. Intraoperatively, extensive retinal whitening and granular necrosis were observed along with diffuse vascular sheathing and perivascular inflammatory aggregates (). Endolaser was placed 360 degrees prophylactically. The vitreous biopsy was sent for gram stain, cytology (to rule out malignant infiltration), fungal culture, Toxoplasmosis, AFB, VZV, EBV, CMV, HSV-1, HSV-2, and RPR testing.
On postoperative day 2, the vitreous PCR returned positive for CMV; all other tests were negative. The patient was switched from oral valacyclovir to valganciclovir 900 mg po twice daily. By postoperative day 3, the patient's visual acuity declined to 20/200 and there was an increase in anterior chamber cell. Hence, intravitreal foscarnet (2.4 mg/0.1 cc) was injected. At the postoperative week 1 visit, visual acuity had not improved, but the area of retinitis appeared less active (). Repeat intravitreal foscarnet was given. Improvement continued over the first month with complete resolution of the patient's uveitis, vasculitis, and retinitis. By postoperative month 2, BCVA had improved to 20/63 without evidence of active disease. Five months after the vitreous biopsy, the patient remained without signs of intraocular infection with BCVA 20/50, mostly limited by cataract. Following cataract extraction one year later, his visual acuity was 20/25 with stable fundus findings (). |
pmc-6413403-1 | A 35-year-old woman presented to the emergency department (ED) complaining of sudden-onset, persistent, moderately severe, left-sided headache with focal left visual field defect followed by right limb clumsiness three hours priorly. She was diagnosed with SLE 11 years previously after developing nephritis, intermittent arthritis, thrombocytopenia, and chronic leg ulcers. She was lupus anticoagulant positive. Treated with monthly cyclophosphamide pulse therapy followed by trimonthly injections for the first two and a half years, she remained free of flares on daily maintenance therapy (azathioprine, 50 mg; hydroxychloroquine, 200 mg; prednisolone, 5 mg (0.05 mg/kg/day); and aspirin, 100 mg).
Neurological exam revealed right homonymous hemianopsia without facial palsy but with right-sided hyperesthesia and dysmetria. Brain computed tomography (CT) and magnetic resonance angiography showed acute cerebral infarction in the left posterior cerebral artery territory involving the thalamus and occipital lobe complicated by minimal left temporo-occipital subarachnoid hemorrhage. She was weakly positive for lupus anticoagulant and borderline positive for anticardiolipin antibodies.
Her symptoms gradually improved, but she developed sudden-onset, severe epigastric pain with tachycardia, hypotension, and altered level of consciousness two weeks after hospitalization. Her hemoglobin dropped from 114 to 88 g/L, and abdominal CT angiography (CTA) showed a massive subcapsular hematoma with contrast extravasation in the left lateral segment of the liver (). Emergent angiography showed diffuse hepatic artery aneurysms bilaterally over the liver parenchyma with contrast extravasation from a left hepatic subcapsular hematoma (). Diagnosed with hepatic aneurysm rupture, embolization of left proximal hepatic artery with Gelfoam cubes was performed. However, her tachycardia persisted, and her hemoglobin was 66 g/L the next day. Follow-up CTA showed a new hematoma over liver segment 7/8. A second superselective TAE with Gelfoam cubes was performed via branches of right hepatic artery after which her vital signs stabilized. Concerned that antiphospholipid antibodies were responsible for the vascular events, rituximab was administered (500 mg in two consecutive doses two weeks apart). Follow-up abdominal CTA three months later showed resolution of the hepatic aneurysms (). |
pmc-6413405-1 | A 59-year-old woman was diagnosed with schizophrenia at 17 years of age and had been taking antipsychotic drugs since the diagnosis. She had no history of alcohol consumption or drug abuse. At age 57, she was admitted to another mental hospital after entering a catatonic state that was resistant to several antipsychotic drugs and benzodiazepines. She experienced delusions, hallucinations, grossly disorganized and catatonic behavior, and negative symptoms lasting more than 6 months. She showed no symptoms of organ disease on blood tests, neurological tests, or magnetic resonance imaging (MRI) of the head. Thus, we diagnosed her with schizophrenia based on the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5). At her one-year follow-up after ECT, she had no symptoms indicating organ disease, and her diagnosis remained the same. In addition, she exhibited stupor, catalepsy, waxy flexibility, negativism, mannerism, stereotypy, agitation not influenced by external stimuli, and echolalia. Thus, we diagnosed her with catatonia per the DSM-5. No EEG and CSF analysis had been performed. Therefore autoimmune NMDA-R-encephalitis and potentially associated viral infections (e.g., Herpes; Influenza) had not been sufficiently ruled out.
She had been taking 9 mg of risperidone daily for 2 years for her severe symptoms without exothermic reactions or increased creatine phosphokinase (CPK); thus, she continued taking risperidone for her severe symptoms. Clozapine could not be administered because her white blood cell count was too low. No other symptoms of cytopenia, infection, or blood disorders were observed. She had no symptoms of organ disease. We suspected that the antipsychotic drugs were affecting her blood cell counts, but we determined that the cell counts were not clinically significant. Her white blood cell counts did not change, even after receiving ECT.
In addition, she had been taking 1.2 g magnesium oxide and 36 mg sennoside daily for constipation for many years during and after ECT. Her laxative remained unchanged. We did not exclude organ digestive diseases using advanced methods such as endoscopy. Instead, we judged clinically that her constipation were due to adverse effects from the drugs and her lifestyle habits. She had no intestinal obstruction or diseases that caused outright autonomic nervous abnormalities.
The patient's feces were sampled 1 month after admission (on the day before administering ECT) and 2 days after the final ECT session. The feces were collected promptly after defecation and stored at below -20°C until analysis. The bacterial composition of the gut microbiota was analyzed using the terminal restriction fragment length polymorphism method (Techno Suruga Labo Co. Ltd., Shizuoka, Japan). Her psychiatric symptoms were also evaluated using the Brief Psychiatric Rating Scale (BPRS) and the Bush-Francis Catatonia Rating Scale (BFCRS) []. We assumed that she lacked the capacity to provide informed consent; therefore, her father provided written informed consent for both publishing and this protocols approved by the Ethics Committee of Shimane University Hospital (no. 20160727-1).
We performed 14 ECT sessions (three times per week) in accordance with the revised edition of the Electrical Convulsion Therapy (ECT) Recommendation of the Department of Neuropsychiatry of Japan, which was created by translating the American Psychological Association (APA) treatment guidelines. The number of ECT sessions was reevaluated at the 10th session and continued. We used thiopental or ketamine as an anesthetic and stopped her breakfast on the morning of the ECT. After ECT, her BPRS score decreased from 83 to 65, and her BFCRS score decreased from 51 to 28. In addition, her gut microbiota differed before and after ECT. Clostridium decreased from 86.5% to 72.5%, while Lactobacillus increased from 1.2% to 5.5%, and Bacteroides increased from 9.1% to 31.5%. |
pmc-6413441-1 | We present a case of a 53-year-old male, a professional chef, with a personal history for allergic rhino-conjunctivitis. He began showing initial signs of AD in 2015, with involvement of the face, neckline, trunk and forearms. The allergological work-up was positive for pollens, foods, latex. Due to a severe exacerbation of dermatitis, the patient was referred to our attention on January 2017. The patient had been prescribed oral steroids at an average daily dose of 8–12 mg of 6-methyl prednisolone, raised during flare-ups, in addition to anti-histamines (cetirizine 10 mg/day), to no avail. At this time he presented with a sub-erythrodermic state and a SCORing Atopic Dermatitis (SCORAD) of 59.3. In vitro testing (ImmunoCAP Thermofisher, Upssala, Sweden) found IgE serum levels of 433 kU/L, and specific IgEs positive for pollens [Grass pollens (21 kUA/L); Olive tree (6.1 kUA/L); Cypress tree (4.4 kUA/L); Parietaria officinalis (6.04 kUA/L)]; Dermatophagoides pteronyssinus (27.8 kUA/L); and foods [hazelnuts (26.3 kUA/L); peanuts (18.4 kUA/L); wheat (6.4 kUA/L); tomato (31.4 kUA/L); onion (53.3 kUA/L); apple (51.2 kUA/L)]. In vitro testing for molecular allergens was positive for Prup3 (72.7 kUA/L) and Betv2 (8.6 kUA/L). Peripheral blood eosinophil count was 2.8% (260 cells/mmc). Daily episodes of diarrhoea was referred despite the diet restrictions. Frequent severe exacerbations occurred due to the exposure to cooking vapour during the work activity. No history of anaphylactic reactions was referred. Given the absence of previous acute hypersensitivity reactions to foods, but taking into account the high levels of Prup3, and specific food IgEs, the patient followed a pseudo-allergen free diet and exclusion of grains and tomatoes for 6 months. To induce a rapid improvement of symptoms, three consecutive days of treatment with 80 mg of 6-methyl prednisolone i.v. were administered, progressively tapered over the course of 3 weeks to a minimal daily dose of 8 mg. However, a rapid relapse of the skin legsions, and severe pruritus was observed. Considering the lack of response, treatment with Cyclosporine A (CoA) 3 mg/kg body weight (kg 75) was started. The patient was advised to implement strict environmental, hygiene, and diet restrictions based on the test results. After 3 months the patient found no significant improvement, with a SCORAD of 42.49. Due to severe clinical presentation, the weak response to conventional therapy and CoA, an off-label treatment with Omalizumab 600 mg every 4 weeks based on patient weight and total IgE value was proposed, after obtaining written informed consent from the patient and the local Ethical Committee approval. Unexpectedly, clinical results were observed after just about 2 months of treatment as confirmed by a SCORAD of 1, and a clear improvement of QoL (Fig. ). Also, gastrointestinal symptoms disappeared after 3 weeks from the beginning of treatment. Steroid dose was progressively tapered to 2 mg of 6-methyl prednisolone in anticipation of complete suspension, and a gradual reduction of CoA until a stable maintenance dose of 1 mg/kg/day was reached. The patient has since returned to work as a chef without complications, and has begun eating grains again with no gastro-intestinal problems nor relapse of dermatitis, but only occasional mild pruritus (just one occurrence). After 1 year of Omalizumab treatment, the patient maintains a good control for both skin and gastrointestinal symptoms (Fig. ). |
pmc-6413449-1 | A 58-year-old female presented with 40-pound weight loss over several months with new lower extremity edema, dyspnea on exertion, and flank pain. A CT scan revealed a 12.2 cm × 8.1 cm left renal mass with regional adenopathy and a bulky thrombus extending cephalad within the inferior vena cava (IVC) to the junction of the IVC and right atrium with occlusion and distension of the IVC with maximum thrombus diameter of 49 mm (Fig. a). Upon contrast administration, the thrombus showed strong uniform enhancement, confirming suspicion of tumor thrombus. No bland thrombus was identified, so anticoagulation was not initiated. A transthoracic echocardiogram revealed no tumor within the right atrium. Serum hemoglobin was 7.8 g/dL, corrected calcium level was 9.8 mg/dL, absolute neutrophil count was 9.88 × 109/L and platelet count was 474,000/uL. She underwent a CT of the chest and MRI of the brain without evidence of metastasis. A core needle biopsy of the renal mass showed clear cell renal cell carcinoma, WHO/ISUP grade 3 with focal grade 4 and with no identified sarcomatoid elements.
Her Eastern Cooperative Oncology Group (ECOG) performance status was 3, so she was deemed not a surgical candidate. Given her IMDC poor-risk classification, she was offered systemic immunotherapy with the possibility of consolidative surgery if she had a radiographic response. She received 4 cycles of nivolumab and ipilimumab and her re-staging CT revealed stable locoregional adenopathy; the renal mass slightly decreased to 9.1 cm in diameter. The thrombus, however, had regressed from the cavo-atrial junction to the suprahepatic IVC with a marked decrease in diameter so that it no longer obliterated the IVC (Fig. b). She then received 4 cycles of nivolumab monotherapy dosed 480 mg every 4 weeks. She had marked improvement in her ECOG performance status to 1 and resolution of lower extremity edema and dyspnea. A second follow up CT re-demonstrated the regressed and non-enhancing tumor thrombus, with persistence of the primary renal mass, which measured 10.4 cm.
She subsequently underwent a left radical nephrectomy and IVC thrombectomy through a chevron incision. There were dense adhesions near the renal hilum and bulky lymphadenopathy which required en-bloc ligation of the hilum. Hilar and para-aortic lymph node sampling was performed. The tumor thrombus remnant was estimated to be 5 mm in diameter. After obtaining proximal and distal vascular control, the vena cava was entered at the renal vein ostium. A long, thin, firm, intravascular thrombus was encountered, which was densely adherent to the endothelium without a discernable surgical plane It was deemed unable to be extracted without resection of a substantial portion of the sub-diaphragmatic vena cava. Samples were sent to pathology. The renal vein and vena cava cuff were resected and reconstructed with running non-absorbable suture. Her post-operative course was uneventful. All systemic therapy was discontinued after surgery and she remains without evidence of disease longer than 1 year after her original diagnosis.
Final pathologic analysis revealed a 6.3 cm ISUP Grade III clear cell renal cell carcinoma with focal rhabdoid features (5%) and sinus fat invasion of the left kidney. The primary tumor demonstrated areas of necrosis as well as a dense neutrophilic infiltration alongside viable tumor without evidence of treatment response (Fig. ). The resected residual renal vein thrombus was characterized by hemosiderin-laden macrophages and other signs of treatment effect, but no viable tumor was present within the IVC cuff or main renal vein. There was viable tumor thrombus present within segmental renal veins of the renal sinus. The 13 sampled regional lymph nodes had no evidence of carcinoma or treatment effect to suggest any previous malignant infiltration.
PD-L1 immunohistochemistry on the renal tumor showed absence of staining in most of the tumor. Subsequently, multichannel immunofluorescence for Pan CK, CD8, PD-L1, FoxP3, Batf3, and DAPI was performed on the residual renal tumor and remaining segmental renal vein tumor using the PerkinElmer Vectra Polaris system (Fig. ). The primary renal tumor appeared to be immune-excluded and lacked infiltration of CD8+ T cells or Batf3+ dendritic cells. In contrast, within the residual segmental renal vein tumor thrombus, we observed a marked infiltration of CD8+ T cells, FoxP3+ regulatory T cells, and Batf3+dendritic cells. The non-inflamed renal tumor lacked PD-L1 expression whereas the tumor thrombus remnant showed interspersed strongly positive PD-L1 expressing cells in stromal areas (Fig. b). |
pmc-6413452-1 | Our patient was a 67-year-old white woman with no relevant medical history. She was on no medication at time of admission. She did not smoke tobacco and consumed no alcohol. She was retired at time of admission and worked as a librarian before. She was married and had two children, both healthy. Her mother was 88-years old and still alive; her father died at the age of 94, cause not known. None of them had malignancies in their past. At time of admission she felt perfectly normal, had no B-symptoms, no bleedings, and no signs of infections. She was 152 cm in height and weighed 72 kg, with a body surface area of 1.7 m2. Her temperature was 36.7 °C (98 °F), blood pressure 128/79 mmHg, and pulse 73 beats per minute. No cardiac, respiratory, gastrointestinal, urological, dental, or neurological anomalies were detected at physical examination. The reason for her admission at our Hematology department was a routine blood analysis, performed before undergoing knee surgery, which showed leukopenia (Fig. ). A bone marrow examination was performed, revealing an underlying AML (Table and Fig. ).
Induction therapy with cytarabine (200 mg/m2, continuous infusion over 24 hours, on days 1–7) and idarubicin (12 mg/m2, once daily, infusion over 1 hour, on days 1–3) was initiated, and given her neutropenic condition from the start, she stayed in protective isolation at the Hematology department. She received levofloxacin 500 mg once daily for intestinal decontamination and infectious prophylaxis. Since no complications occurred, the second induction was initiated with cytarabine (1000 mg/m2, twice daily, infusion over 3 hours, on days 1–3) and idarubicin (12 mg/m2, once daily, infusion over 1 hour, on days 3–5). After this therapy, she developed general weakness and diarrhea. At day 35 after the first induction, she developed neutropenic fever for which ceftazidime (2000 mg intravenously every 8 hours, continuous infusion over 8 hours) and Colimycin (colistimethate sodium; 2 × 106 international units intravenously every 6 hours) were started, guided by the presence of a resistant Pseudomonas aeruginosa strain in the fecal cultures. Two days later she started vomiting and reported headaches and photophobia. Analysis of her cerebrospinal fluid (CSF) was compatible with bacterial meningitis (Table ). She was transferred to our intensive care unit receiving empirical antibiotic therapy with ceftazidime, Colimycin (colistimethate sodium), amoxicillin (2000 mg intravenously every 4 hours), and vancomycin (loading dose 1400 mg intravenously over 2 hours, maintenance dose 2500 mg intravenously over 24 hours); although the plasma concentration of this last one only reached therapeutic levels after 2 days. Gram staining on the CSF showed Gram-positive cocci, which were presumed to represent Staphylococci at first. However, cultures identified Rothia mucilaginosa as the responsible pathogen and after 2 days of empirical therapy, antibiotics were switched to amoxicillin (2000 mg intravenously every 4 hours) and rifampicin (600 mg intravenously every 12 hours) bi-therapy based on an antibiogram (Fig. ) and the (limited) available literature [, , , ]. Blood cultures remained negative. She was stable for 1 week until she developed significant lethargy and anisocoria. Hydrocephalus was diagnosed with computed tomography (CT) imaging for which external ventricular drainage was provided. Because of a non-communicating hydrocephalus due to ventriculitis, a second drainage was performed. In spite of this, our patient developed bilateral mydriasis without reactivity to light and increasing edema on brain CT, leading to the placement of two more external ventriculostomies in the temporal horns (Fig. ). Despite these neurosurgical interventions and medical therapy with hypertonic salt and mannitol, intracranial pressure continued to rise, resulting in progressive brain edema and transtentorial herniation. In consultation with her family, further therapy was discontinued and she died on day 49 after the first induction chemotherapy. An autopsy was considered, but, given the clear medical context, this would not have led to other conclusions (Additional file ). |
pmc-6413457-1 | A 69-year-old Japanese woman was referred to our department in August 2015, complaining of swelling in the right preauricular region. She had shown a mass lesion of the right lung on a chest x-ray and was referred to the university hospital. Fluorodeoxyglucose-positron emission tomography (FDG-PET) examination showed accumulation indicative of a pulmonary lesion and a temporomandibular joint lesion. The temporomandibular joint lesion had been enlarging but was otherwise asymptomatic. Her medical history included treatment for pulmonary tuberculosis at the age of 13 and surgery to remove breast cancer at the age of 53.
On examination, a tender mass in the right preauricular region was palpable. The chin of the mandible was deviated to the right side during mouth opening (mandibular maximum mouth opening, 41 mm). Facial nerve function and mandibular nerve were intact. There was no indication of cervical lymphadenopathy.
A panoramic radiographic examination showed resorption of the right mandibular condyle to the ramus (Fig. ). Computed tomography (CT) showed destruction of the right mandibular condyle and a large mass lesion with enhanced margin in the masticator space; a cystic lesion was present inside the tumor mass. Three-dimensional CT was useful to understand the bone resorption findings of the mandibular condyle. There was no finding of metastatic cervical lymph node (Fig. ). T1-weighted magnetic resonance imaging showed an enhanced mass lesion in the right masticator space. Because some portions of the mass lesion showed high intensity in T2-weighted images, cystic lesions were suspected to exhibit changes of blood flow or retention of high-protein liquid. Tumor development was not observed in the articular disk of the temporomandibular joint (Fig. ). FDG-PET revealed abnormal FDG uptake in the right submandibular condyle and masticator space.
A malignant tumor was suspected after analysis by various modalities. Therefore, we performed an incisional biopsy via preauricular incision. Histopathologically, the tumor was largely composed of proliferative, atypical, spindle-shaped cells. Some tumor cells showed increasing mitotic change and extreme atypia (Fig. ). The histopathological findings of biopsy suggested spindle-cell sarcoma. Tumor resection was performed with the patient under general anesthesia via a combined preauricular and transmandibular approach to the masticator space and infratemporal fossa.
After preauricular temporomandibular incision, the superficial temporal fascia and temporal fascia were elevated. The facial nerve (temporal and zygomatic branches) was protected by the fascia (Fig. a).
The facial nerve trunk was identified, and its branch was traced according to the conventional method.
A midline lip-splitting incision was connected to the submandibular incision and accessed the anterior mandibular ramus. The lip-split incision traversed to the periosteum of the mandible; the periosteum dissector was used to elevate the soft tissues of the mandible, and the lateral mandible was exposed. The branch of the facial nerve was traced continuously with the skin flap, and the masseter muscle and deep parotid gland were dissected on the tumor side (Fig. c). The mandible was resected to within ≥ 20 mm from the primary tumor on the anterior of the mandibular ramus. The masseter muscle was divided at the lower edge of the zygomatic arch; further, the temporal muscle was divided horizontally at the height of the zygomatic arch to reach the side of the temporal bone. Excision was performed on the temporal bone to the base of the pterygoid process, and an osteotomy was performed continuously from the maxilla to the pterygoid process. Osteotomy was performed via ultrasonic scalpel. Then, deep excision was performed on the skull base until the foramen ovale was reached. The mandibular branch (VIII) of the trigeminal nerve was resected at the foramen ovale, and bone wax was used to fill the foramen ovale when hemostasis was achieved. The tumor was excised in bulk with the surrounding tissue (Fig. d). Especially, the glenoid fossa was close to the primary tumor site; however, it was excised including the joint disc, and the glenoid and infratemporal fossa were excised, including the periosteum of the skull base. For that reason, the margin was considered complete, and we did not perform the histopathological evaluation intraoperatively.
The surgical defect was reconstructed with a free vascularized fibula with skin paddle (Fig. e). The occlusion was performed with intermaxillary wire fixation for 1 week postoperatively. There were no abnormal findings during the postoperative course with complete healing. Right-sided facial nerve dysfunction appeared immediately after surgery.
The resected specimen exhibited nearly identical histological findings as observed in the biopsy. Because it involved a periosteal reaction corresponding partially to Codman’s triangle, the tumor was thought to have derived from bone (Fig. ). Immunohistochemical analysis showed positive staining for vimentin, MIB-1 index (40–80%), desmin, α-smooth muscle actin, Bcl-2, neuron-specific enolase, and S-100; it showed negative staining for AE1/AE3, caldesmon, and CD34. Thus, the final diagnosis was osteosarcoma (fibroblastic). The resection margin was negative for tumor. After excision of the mandibular tumor, excision of lung cancer was performed under thoracoscopy by a respiratory surgeon in our hospital. Although we recommended adjuvant treatment after surgery, the patient refused this treatment.
There has been no evidence of local recurrence or distant metastasis through 30 months of follow-up. The chin of the mandible deviates to the right side during opening (maximum mouth opening, 40 mm). Centric occlusion has not changed. Facial nerve dysfunction gradually improved and became mild according to House-Brackmann Scale evaluation (Figs. and ). |
pmc-6413671-1 | A 36 year-old right handed man with intractable right temporal lobe epilepsy of unknown etiology since the age of nine was enrolled into the study. His seizure semiology consisted of psychic aura followed by auditory aura with impaired awareness, and rare secondarily generalization. The last generalized convulsion had occurred 4 years before the admission. He had co-morbid depression. Previous antiepileptic drugs (AEDs) were carbamazepine, phenytoin, valproic acid and zonisamide. At admission for presurgical evaluation he was on oxcarbazepine 1,800 mg/day. Physical and neurological examinations were normal. Brain MRI was normal and the interictal PET scan showed bilateral mesial temporal hypometabolism, more pronounced on the right. Interictal recordings showed right temporal sharp waves (maximum at T8>F8). Retrospective review of older (non-study) VEEG records revealed a near-SUDEP incident (not included in the above analysis). The patient had 4 seizures during that admission. The first one, was a brief (<10 s duration auditory aura). The second and third seizures, were brief auras with rapid secondarily generalization, one arising from wakefulness and the other one arising from sleep. No comment about presence of ICA could be made on those seizures due to lack of plethysmography and rapid secondary generalization. No PCCA was noted in any of the GCS and regular breathing resumed immediately after clinical seizure end. These GCS occurred within 12 h of the fourth and last seizure. This was an apneic seizure with impaired awareness, and respiratory arrest lasting for 285 s, as evidenced by video analysis and oxygen desaturation. After a period of several shallow breaths, breathing finally resumed normally 311 s after seizure onset. Ictal EEG showed rhythmic alpha activity arising over the right antero-mesial temporal lobe with bilateral spread. No alteration in heart rhythm was noted apart from tachycardia. The patient was repositioned, oxygen administered, and ventilated with a face mask. He later underwent invasive evaluation, had further seizures without apnea, and a right temporal lobectomy in 2016 which resulted in seizure freedom (Engel Class 1, [>2 years]) . |
pmc-6413671-2 | A 15 year-old right handed girl with epilepsy since age 5 years was admitted for evaluation. She was not an enrolled study patient. Seizures occurred once or twice a month and lasted up to two with whole body sensory aura (tingling) followed by oral automatisms with impaired awareness. This was rarely followed by secondary generalized convulsions lasting 1–2 min. On several occasions, paramedics were summoned as an emergency because of cyanosis and unresponsiveness after generalized convulsions. On admission she was on lamotrigine 200 mg/day and levetiracetam 3,000 mg/day, having previously failed multiple other AEDS. She had no epilepsy risk factors and no family history of epilepsy. Her physical and neurological examinations were normal. Epilepsy protocol MRI brain scans were normal on two occasions. Inter-ictal brain FDG-PET showed focal hypometabolism in the anterior left temporal lobe tip. Non–invasive VEEG monitoring showed left temporal sharp waves, maximum at F7/T7/FT9. Four habitual clinical seizures were recorded without secondarily generalization. EEG onsets were left hemispheric but not further localizable.
She underwent invasive EEG monitoring for better localization of the epileptogenic zone. A left subdural grid (8 × 6) was implanted along with strips covering the left orbitofrontal, superior temporal, inferior temporal regions, as well as left anterior-anterior, anterior-middle and anterior-posterior temporal, left middle temporal, left middle-middle, and middle-posterior. A left anterior temporal seizure was recorded, with typical automatisms and impaired awareness, right face clonic movements, and a secondary generalized tonic clonic seizure. After clinical seizure end, the patient was immediately apneic (as evidenced by video analysis, cyanosis, and severe O2 desaturation) for 126 s, followed by an isolated breath. A second period of apnea/hypopnea was then seen until regular breathing pattern resumed a total of 187 s after clinical seizure end. EEG seizure discharges were seen up to 25 s after clinical seizure end. Thirty nine seconds after clinical seizure end, there was concurrent progressive bradycardia followed by 10 s of asystole. Cardiac rhythm resumed, with a pattern of bradycardia and normal sinus rhythm, for 75 s, after which EKG signal was lost, but pulse artifact was evident on EEG. EEG suppression duration (all invasive electrodes), was ~254 s. During the episode, there was repeated tactile nursing intervention. Further, her head was re-positioned and O2 administered. No active resuscitation measures were performed. Due to continuing seizures, the patient underwent responsive neurostimulation (RNS® System) and was temporarily seizure free for 3 years, until recent recurrence of focal seizures at last follow up . |
pmc-6414181-1 | A 50-year-old woman with no significant prior medical history presented with a six-month history of a rapidly enlarging left-sided breast mass that, in recent weeks, had become increasingly painful and ulcerative in nature. She had initially felt a small lump in her breast but chose not to have it evaluated by a physician until the pain from the mass became intolerable. On presentation, she was tachycardic and mildly tachypneic with a low-grade fever. The breast mass had evidence of extensive necrosis with active drainage of blood and pus. The patient was unable to ambulate due to the weight of the tumor and the accompanying back pain. Laboratory testing revealed lactic acid levels of 13 mmol/L (normal <1.70) and a white cell count of 21.9 K/uL (normal range: 4.1-10.8). Computerized tomography (CT) imaging showed extensive primary tumor burden that crossed the midline and measured 25.3 x 21.2 x 15.5 cm, as well as an additional smaller tumor in the right breast (Figure ). Pulmonary, osseous, and nodal metastases were also noted. Tissue biopsy revealed triple negative, poorly differentiated, spindle cell carcinoma with immunochemistry positive for cytokeratin (CK) AE1/3, CK 5/6, CK 14, and tumor protein p63. Treatment was initially focused on supportive care that included broad-spectrum antibiotics to cover any soft tissue infection that may have been contributing to the patient’s metabolic derangement. Chemotherapeutic and surgical interventions were deemed futile due to the advanced stage of the disease. It was determined that radiation therapy could be of palliative benefit and thus, the patient underwent appropriate simulation and a single treatment to the affected site, with additional treatments planned for future. The patient’s hospital course was further complicated by persistent hypoglycemia that began on day three after admission. Despite being maintained on a continuous infusion of 5% dextrose in normal saline, the patient’s blood glucose would recurrently drop as low as 42 mg/dl (normal range: 70-110), requiring intermittent oral glucose administration and a change in intravenous fluids to 10% dextrose in water. An extensive endocrine workup, which included checking serum levels of insulin, proinsulin, insulin-like growth factor 1, c-peptide, adrenocorticotropic hormone, and cortisol, revealed no significant abnormalities. The patient continued to decline with a worsening of her metabolic acidosis and an increasing need for respiratory support. After a detailed meeting, the family decided to pursue comfort measures. The patient passed away 11 days after initial presentation. |
pmc-6414183-1 | A 58-year-old female presented to our emergency room with worsening left upper quadrant abdominal pain radiating to her left shoulder the day after outpatient colonoscopy. A CT scan of the abdomen and pelvis revealed a grade III splenic injury with no obvious active extravasation (Figure ).
She was admitted to our intensive care unit and her initial hemoglobin (9 grams per deciliter) dropped gradually to 7.4 grams per deciliter over 24 hours. Angiography revealed a subcapsular blush (Figure ). Splenic artery embolization, with interlocking coils, was performed (Figure ). The patient did well with no further drop in her hemoglobin and was discharged from the hospital the following day. |
pmc-6414186-1 | A 46-year-old Caucasian female with a significant past medical history for cervical cancer, anticardiolipin antibody syndrome, peripheral artery disease, hyperlipidemia, anxiety, and depression presented to the Medical Center in Bowling Green, Kentucky due to a recent ultrasound that showed elevated pressures of a femoropopliteal bypass graft in her right lower extremity. On angiography of her right lower extremity, she was found to have high-grade stenosis in the upper portions of her bypass along with a diseased popliteal artery with tandem stenotic lesions. The patient then underwent an AngioJet thrombectomy of the right femoropopliteal bypass which began thrombosing immediately afterwards.
The patient was admitted to the hospital for post-operative recovery and the on-call internal medicine physician took the patient onto their service, at which point a complete history was taken and a physical exam was performed. The patient was found to be morbidly obese (body mass index 42.5), well developed, well-nourished patient in no acute distress, with a normal respiratory and cardiac exam. The patient was found to have tenderness along the anterior of the right lower extremity, and mild inflammation along the lateral portion of the left foot. The left lower extremity pulse was slightly weaker than the right.
A lower extremity angiography was performed on this patient prior to the AngioJet thrombectomy which revealed damage to the distal left lower extremity caused by the patient’s TAO. The posterior tibial artery is shown to have developed a tortuous, corkscrew-like path through the left foot, an anatomical feature associated with TAO (Figure ). Vessels contributing to the left calcaneal anastamosis along with the lateral plantary artery were shown to be obliterated from this patient’s TAO (Figure ). The angiography also shows arterial occlusions where the calcaneal anastamosis vessels and lateral plantar artery typically branch off of the posterior tibial artery (Figure ).
The patient currently works from a home office. She claims to have smoked a pack to a pack and a half of cigarettes daily since her early teens, giving her a thirty to fifty pack-year history. The patient admits to consuming alcohol three to four times per month. The patient denies any illicit drug use. |
pmc-6414190-1 | A 37-year-old Caucasian female with a past medical history significant for spina bifida complicated by paraplegia and neurogenic bladder, kyphoscoliosis with multiple spine surgeries, hypertension, sinus tachycardia, depression, and multiple episodes of right lower leg cellulitis presented as a transfer to our tertiary medical center for further management of a left popliteal artery occlusion and right lower extremity cellulitis. Her daily medications were trazodone, Celexa, tolterodine, propranolol, Wellbutrin, and hydrochlorothiazide.
On physical examination, she was calm, cooperative, and in no acute distress. She weighed 65 kg and was 134 cm tall. Her blood pressure was 119/85 mm Hg, heart rate 101 per minute, temperature 98.8°F, respiratory rate 18 per minute, and arterial oxygen saturation of 96% on 2 liters nasal cannula. Head and neck examination was normal, and she had moist oral mucosa with no oral thrush or ulcers noted. There were no abnormal lung or heart sounds. The abdomen was soft, non-distended, non-tender with no rebound or guarding, and normal bowel sounds. Physical examination revealed kyphoscoliosis of the back, underdeveloped paraplegic lower extremities with bilateral sensory loss, and intact distal pulses in the left foot with warm pink toes. The right lower leg and foot were swollen, erythematous, and non-tender with bullae of serosanguinous fluid. Her laboratory tests were normal, except for hypokalemia, with a potassium level of 2.4 mmol/L and lactic acid of 1.6 mmol/L.
The vascular surgery team was consulted. She was started on a heparin drip for left popliteal artery thromboembolism and the recommendation was made for transthoracic echocardiography (TTE) and antiphospholipid syndrome screening.
The TTE showed a cardiac mass in the right atrium extending into the inferior vena cava (IVC) (Figure ). For further identification of the mass, cardiac magnetic resonance imaging (MRI) was done which showed a normal left ventricular ejection fraction of 57%, right ventricular dilatation with moderately reduced systolic function of 36%, and a mass-like structure projecting over the right atrium with the appearance most suspicious for a diaphragmatic caval foramen herniation of liver parenchyma encroaching on the right atrium (Figure ). A sulfur colloid nuclear single-photon emission computed tomography (SPECT) study also confirmed this finding (Figure ). She continued inpatient treatment with anticoagulation and antibiotics during which she was seen by cardiology who recommended outpatient follow-up with cardiothoracic surgery for evaluation for potential surgical excision of the right atrial mass that was found to be herniated liver tissue. |
pmc-6414191-1 | A 13-year-old phototype III female patient presented to our institution with a congenital nevus on her left lumbosacral region with a large diameter of 8 cm. At the time of the consultation, it had been one year since the appearance of a rapidly growing exophytic lesion on this congenital nevus, which exhibited color changes, edge irregularity, bleeding, and occasional pain. The physical examination of this patient revealed a 6 x 4-cm erythematous tumor with active bleeding on top of an 8.5 x 3-cm dark brown plate (Figure ).
The total body photography and digital dermoscopy (FotoFinder Systems, Inc., Columbia, MD, USA) documented more than 20 additional melanocytic lesions. A biopsy of the lumbosacral lesion was obtained, and the histopathological results showed a superficial spreading malignant epithelioid melanoma. The fluorescence in situ hybridization (FISH) results for the RREB1, MYB, and CCND1 genes (common molecular alterations in malignant melanomas) were positive for the tissue obtained from the new exophytic lesion and negative for the congenital nevus tissue (Figure ).
This patient underwent a wide local excision, sentinel lymph node biopsy, and flap reconstruction. The pathological results were as follows: a Breslow’s tumor thickness of 13 mm, Clark Level V, extensive ulceration, mitoses of 10/mm2, negative margins, and sentinel lymph nodes with extensive metastatic involvement. A lymphadenectomy was also performed, and 20 lymph nodes were obtained, six of which were positive. Based on the above-mentioned results, this patient was diagnosed with a stage IIID melanoma or clinicopathologically, T4bN3aM0, according to the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, 8th edition. The polymerase chain reaction (PCR) showed no BRAF mutations. She was given interferon-α-2b as an adjuvant treatment, but it caused toxicity during the first week of the induction phase, with a grade 3 transaminase elevation. At that point, the treatment was withheld, and the patient was voluntarily lost to follow-up for four months. When she returned for treatment, the interferon was resumed at the maintenance phase for two additional months of treatment. Then, she presented to the emergency room with a rapidly growing mass in her right breast. A biopsy was obtained, which confirmed the diagnosis of metastatic melanoma. Positron emission tomography-computed tomography (PET-CT) was used to identify the mass, and it had completely replaced the breast tissue with a standardized uptake value of 12 (Figure ). There was no evidence of metastases in any other site.
A metastasectomy was performed (right mastectomy plus axillary lymph node dissection), and an 11-cm tumor was obtained with a 1-mm margin. Three of the 28 lymph nodes that were removed were positive for metastatic involvement. Postmetastasectomy, with no approved active therapy, this patient was closely monitored. The subsequent tomographies (less than two months after surgery) showed multiple metastatic bilateral pulmonary nodules and right axillary matted lymph nodes. This conglomerate was noticeably painful, and so radiotherapy was administered with a palliative intention (total dose of 30 Gy).
In a multidisciplinary meeting, with the Ethics Committee’s approval, systemic nivolumab therapy was chosen as a palliative treatment, based on the extrapolation of evidence from adult cases. This patient tolerated the treatment well; however, after two cycles, she exhibited gastrointestinal bleeding. An upper endoscopic evaluation showed a 6-cm gastric exophytic mass, and a biopsy confirmed the diagnosis of metastatic melanoma. This patient was reassessed, and an explosive progression of the disease was found, with a 50% growth in her lung lesions and the appearance of new hepatic, retroperitoneal, and mediastinal masses of up to 4 cm. Some of these were adjacent to the right atrium, descending aorta, and left ventricle. Additionally, metastatic lesions had developed in the central nervous system (infundibulum and pituitary gland) and an 8.5-cm ulcerated mass reappeared on the thoracic wall at the location of the previous mastectomy (Figure ).
We considered this as hyper-progression, and a second line with carboplatin and paclitaxel was proposed. Whole brain palliative radiotherapy was carried out, and gastrointestinal bleeding became difficult to control, with chemotherapy having little effect. Hence, we offered palliative radiation to the gastric mass and chest wall mass to alleviate symptoms, with limited response. Her performance quickly deteriorated over the next few weeks, until treatment was suspended. The patient was offered the best support care possible before she passed away. |
pmc-6414192-1 | A 66-year-old physician was treated for a prostate-specific antigen recurrence of prostate cancer with radiation and six months of androgen depletion therapy with leuprolide (Eligard®, Tolmar Pharmaceuticals, Illinois, US) and bicalutamide (Casodex®, AstraZeneca Pharmaceuticals, Maryland, United States) starting October 11, 2017. He finished radiation on February 5, 2018. During this time, he developed significant myopathy with a decline in his marathon times, as reported in one other highly trained athlete []. He had pulmonary function tests (PFTs) done on July 5, 2018, showing forced expiratory volume (FEV1) at 61% of the normal, total lung capacity (TLC) at 65% of predicted, and diffusing capacity of the lungs for carbon monoxide (DLCO) at 75% of predicted. The workup for interstitial lung disease and neuromuscular causes of restrictive lung disease were negative. He was started on 40 mg of prednisone for a week, then 30 mg for three additional weeks to treat possible bronchiolitis. His muscle weakness worsened, so the prednisone was tapered to zero over three weeks beginning August 2, 2018. At the end of this taper, he developed substantial tendinitis, arthritis, and a small left knee effusion where he had existing chondrocalcinosis []. The rheumatologic workup was negative except for an increased sedimentation rate, up from eight to 29. To combat the near-crippling inflammation and arthritis, he began the intake of turmeric extract on September 13, 2018, with about six 538 mg turmeric extract capsules a day []. Doses up to 12 grams per day have been reported to be safe and well-tolerated [].
Prior to starting radiation and androgen deprivation therapy, his hemoglobin was normal at 14.0 g/dL. He was an active red cell donor, having given over 100 units in the past 20 years, with low iron reserves [] requiring iron supplements after prostatectomy in April 2016, when his hemoglobin fell to 9.8 g/dL. During and after radiation and androgen deprivation, his hemoglobin remained above 13.0 g/dL. During the period of respiratory dysfunction in July, his hemoglobin was found to be 11-12, so workup was begun. His ferritin and iron were both low, so he began iron supplementation with “Gentle Iron” (Nature's Bounty, New York, United States), containing 28 mg of elemental iron twice a day. Despite the supplements, his iron and ferritin continued to drop. Stool Hemoccult™ was negative. Upper and lower endoscopies in November were both completely normal. After the negative endoscopies, he reviewed the literature on a possible turmeric-related iron deficiency and stopped the turmeric. Within two weeks, his iron, ferritin, and hemoglobin were rising while taking the same iron supplement, with no changes in his medical regimen (Figures -). His tendinitis and arthritis mildly worsened and then stabilized, and his lung function improved. |
pmc-6414193-1 | A 56-year-old male presented to a hospital in Togo, West Africa, with a long-standing swelling on the left lower leg, which progressively increased in size over time. He had a wide local excision done following a confirmatory biopsy for dermatofibrosarcoma protuberans (DFSP). No adjuvant therapy was recommended on account of clear surgical margins and the absence of distant metastases. The lesion recurred after two years and re-excision was performed. A second recurrence occurred in a year, which involved the knee joint, necessitating a transfemoral amputation. The surgical margin was clear and there was no evidence of distance metastases. He was rehabilitated and started walking with a prosthetic limb.
Two years after the second recurrence, the disease recurred in the left lower limb stump. At this point, a re-biopsy was done and DFSP was confirmed (Figure ). There was no fibrosarcomatous transformation. Immunohistochemistry was positive for CD34 (Figure ), focally positive for actin, and negative for desmin and S100 protein. Metastatic workup, consisting of chest X-ray and abdominal ultrasound, was negative. He commenced imatinib mesylate at a recommended dose of 400 mg twice daily. The recurrent lesion on the left lower limb stump gradually progressed in size after five months of imatinib mesylate treatment, and he eventually developed multiple lesions on the posterior torso.
He was then referred to the National Radiotherapy Oncology and Nuclear Medicine Centre, Korle-Bu Teaching Hospital in Accra. Physical examination showed a 15 x 12 cm mobile mass on the left lower limb stump and two palpable, firm, and fixed lesions on the posterior torso; the largest measuring 9 x 7 cm in size. There was no other clinical or radiological evidence of distance metastases. The decision was made to treat him with palliative radiotherapy to relieve pain in the left lower limb stump and to enable him to use the prosthetic limb.
Six months after stopping imatinib mesylate, he received conformal radiotherapy with Cobalt-60 to the left lower limb stump; 40 Gy in 20 fractions, five fractions a week, which he tolerated very well. On a regular five months post-radiotherapy follow-up, there was no palpable or visible lesion on the left lower limb stump or the posterior torso. At 12 months post last follow-up and 17-month post palliative radiotherapy, there was no clinical or radiological evidence of local or distant metastases. |
pmc-6414194-1 | An 87-year-old female came to consult for swelling in the right lumbar area. The patient's past medical history was positive for a carotid aneurysm embolization, left hip prosthesis insertion, and multiple arthroses. A smooth, reducible, and slightly tender right lumbar mass approximately 4 x 3 cm was evident and a transmitted impulse could be felt during a cough. The lumbar swelling was reduced in the prone position. The suspicion for a Grynfeltt's hernia was confirmed by lumbar ultrasound (US) with evidence of herniation of a small intestinal loop through a 10 mm abdominal defect with a diameter increase to 15 mm during deep breathing. The patient was submitted to surgery under local anaesthesia. An open approach was performed. A lumbar transverse incision and a dissection of subcutaneous fat and the latissimus dorsi muscle fibres were performed in order to access the hernia sac (Figure ). After reduction of the herniated mass, a direct suture was applied on the transversalis fascia. Reconstruction was performed with a polypropylene mesh with a circumferential overlapping of 3 cm in the extraperitoneal position. The mesh was fixed to the abdominal wall with interrupted non-absorbable monofilament sutures. The fibres of the latissimus dorsi muscle were approximated with loose absorbable sutures and the skin was closed with intradermal sutures. No drain was positioned. The postoperative course was regular. She was discharged on the third postoperative day in optimal clinical condition. Her 12-month follow-up examination was uneventful. |
pmc-6414296-1 | A 67-year-old man presented to the clinic for follow-up of celiac disease and microscopic colitis diagnosed five years prior. He complained of six to seven large, loose bowel movements daily starting 10 months prior to this visit. His symptoms began soon after a prior admission for acute coronary syndrome requiring percutaneous coronary artery intervention. Review of systems was negative for dark stools, hematochezia, and abdominal pain. He denied any upper gastrointestinal symptoms, and he was adherent to a strict gluten-free diet. His last upper and lower endoscopies were five years prior to presentation, both of which were normal examinations. Biopsies were consistent with celiac disease and microscopic (lymphocytic) colitis.
The patient was started on aspirin and ticagrelor after his coronary artery stent placement 10 months prior. Additionally, he was on lisinopril and atorvastatin.
Physical examination was unremarkable. Laboratory workup, including a complete blood count (CBC) and comprehensive metabolic panel (CMP), was also unremarkable. Further testing revealed a negative Clostridium difficile polymerase chain reaction (PCR), negative stool studies for Giardia, and a negative enzyme-linked immunosorbent assay (ELISA) test for immunoglobulin A (IgA) tissue transglutaminase antibodies. The patient continued to have diarrhea despite multiple trials of different interventions, including budesonide, cholestyramine, atropine/diphenoxylate, and bismuth. Subsequently, a course of rifaximin for possible small intestinal bacterial overgrowth was tried, which yielded no change in symptoms.
The possibility of ticagrelor being the offending agent was considered, as the onset of diarrhea corresponded with the time of initiation of treatment. The patient’s ticagrelor medication was replaced with clopidogrel, and his diarrhea completely resolved within one week. The patient had no complaints at his one-month follow-up visit, and he reported one to two well-formed stools per day. |
pmc-6414298-1 | A 67-year-old, 115.3 kg, 157-cm female patient with papillary serous adenocarcinoma of the uterine adnexa and uterine masses was brought to the operating room for an exam under anesthesia, exploratory laparotomy, total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, debulking, and lymph node dissection. Her medical history included hypertension, hemorrhoids, morbid obesity (body mass index (BMI) 46.8), and a pulmonary embolism three months prior to surgery. Enoxaparin sodium was stopped two days prior to surgery. The patient’s functional capacity was moderate to excellent at greater than or equal to four metabolic equivalents (METS). She reported completion of all household chores, cycled three to five miles daily and was capable of climbing two flights of stairs. She reported no history of anesthetic complications and no family history of anesthetic complications. Her surgical history included one previous colonoscopy, for which she received deep sedation.
The patient's home medications included prochlorperazine 10 mg as needed after chemotherapy, dexamethasone 4 mg for three days only after chemotherapy, rivaroxaban 20 mg daily, and enoxaparin 120 mg/0.8 mL solution subcutaneous (held two days prior to surgery). In addition, hydrochlorothiazide-valsartan 12.5-320 mg was taken by the patient daily for control of essential hypertension. A non-smoker, the patient reported one alcoholic beverage an average of four times per month. Her medication allergies consisted of benazepril (tachycardia), ezetimibe (myalgias), simvastatin (myalgias), and triamterene (myalgias).
Premedication for anxiolysis was accomplished with 2 mg midazolam. In the operating room, standard anesthesia monitors were applied, including non-invasive blood pressure measurement, electrocardiogram, peripheral oxygen saturation, and a temperature-sensing Foley catheter. Her baseline vital signs were a temperature of 36.94 degrees Celsius, blood pressure 138/80 mm Hg, heart rate 81 beats/min, and oxygen saturation (SaO2) 99%. Induction of general anesthesia proceeded with the administration of 180 mg of 1% propofol, 70 mg lidocaine, and 50 mcg fentanyl after preoxygenation with 100% oxygen. Tracheal intubation was facilitated with the administration of 40 mg rocuronium. A 7.0 mm cuffed oral endotracheal tube was placed with one attempt and then secured at 22 cm. The maintenance of anesthesia with sevoflurane was initiated and the patient received 10 mg of intravenous (IV) dexamethasone after the start of surgery. Mechanical ventilation with volume control was selected with 6 mL/kg and a fraction of inspired oxygen (FiO2) of 0.5. A second 18 g IV was started in the left hand and an arterial line was placed in the right radial artery with one attempt.
At the conclusion of the surgery, 400 mg IV sugammadex (3.74 mg/kg) was given as reversal for the neuromuscular blockade (the train-of-four was 0/4). Within 60 seconds, her blood pressure dropped to 58/39 mm Hg, heart rate remained stable at 80, and SpO2 dropped to 94%. Phenylephrine was titrated in 0.2 mg doses for a total of 1 mg. Intravenous fluids were administered liberally and the surgical team notified of intractable hypotension. Ischemic changes were observed in electrocardiogram (ECG) leads II and V at the same time that the heart rate began to increase. Given the presentation of symptoms in close proximity to the administration of sugammadex, the possibility of anaphylaxis was considered. At this time, 150 mcg IV epinephrine was given followed an additional dose of 100 mcg. Vasopressin two units IV was then administered to restore the blood pressure to baseline in the setting of epinephrine-induced tachycardia. Auscultation revealed clear breath sounds and there was no increase in airway pressures noted. However, a maculopapular rash was noted over the upper thorax. Greater attention was given to the possibility of anaphylaxis at this point and diphenhydramine 50 mg and famotidine 20 mg were administered. A serum tryptase level was sent to the laboratory to assist with determining the cause of the patient's symptoms. After her condition was stabilized, the patient was successfully extubated and transferred to the recovery room. A 12-lead electrocardiogram showed sinus tachycardia and a prolongation of the corrected QT (QTc) interval (Figure ).
Cardiology was consulted and the patient was observed in the intensive care unit overnight as a precaution. Dermatological manifestations resolved within a few hours. Serum tryptase from the time of the episode returned at 62 ng/mL (normal < 11.4 ng/mL), which effectively confirms that the cause of this patient's symptoms was consistent with an anaphylactic reaction. She was discharged home on postoperative Day 4 with a recommendation for follow-up with her primary care physician. |
pmc-6414299-1 | A 32-year-old female goalkeeper developed severe abdominal pain and vomiting after a collision during a soccer game. At presentation, she was haemodynamically stable, with generalised abdominal tenderness and signs of peritoneal irritation. Investigations showed hyperamylasaemia (more than 1000 iu/L), leucocytosis and metabolic acidosis. Computed tomography (CT) demonstrated a major parenchymal injury of the proximal pancreas (Figure ).
She was transferred to a tertiary hepatobiliary centre for further treatment. At laparotomy, transection of the neck of pancreas was seen with a small laceration of the body and no ductal injury. The duodenum was intact and viable. Intra-operative peritoneal fluid amylase was 381 iu/L, compared with serum amylase 311 iu/L, also suggesting no significant pancreatic duct (PD) injury. After thorough lavage, three large closed suction drains were placed adjacent to the pancreas and in the subhepatic and subphrenic spaces (Figure ).
On post-operative day one, the drain output was over 500 mls/day and drain fluid amylase was 10484 iu/L, confirming PD leak. This high output pancreatic fistula persisted. The patient was managed conservatively, with parenteral then nasojejunal feeding. Four weeks post-injury, she was suitable for discharge home with the nasojejunal tube and lesser sac drain in situ. An endoscopic retrograde cholangiopancreatography (ERCP) with pancreatic stent insertion was planned in a further four weeks. The patient was reviewed weekly as an outpatient and remained well in the interim period. She was admitted the day before her scheduled ERCP (eight weeks following injury), with sudden onset abdominal pain and bile in the drain, with no signs of generalised peritonitis. CT confirmed that the drain had eroded into the second part of the duodenum (Figure ).
Tubogram demonstrated free flow of contrast into the small bowel (Figure ).
Her abdominal pain settled and she remained well, so the patient was managed conservatively. After three weeks, the drain was removed without complication. |
pmc-6414426-1 | We present a previously healthy 17 year old female who initially complained of migraines resistant to ibuprofen and imitrex. Symptoms progressed over the next 3–4 months to nasal congestion and she became unable to breathe through the left nostril. She saw a dental surgeon for trismus due to concern of a dental infection and was prescribed antibiotics (Amoxicillin) with no relief. Her symptoms progressed over another 3 months to unexplained weight loss, headaches, loss of hearing, frequent bloody nose, tooth pain, and hoarseness. Approximately 9 months after her initial symptoms, she eventually was seen by ENT and a rigid nasal endoscopy was performed which demonstrated a polypoid mass along the floor of the left nasal cavity. MRI with and without gadolinium contrast performed on a 3-T Siemens Skyra showed a large mass in the posterior left nasal cavity and nasopharynx invading the left maxillary sinus, nasal septum, left pterygopalatine fossa, left masticator and pharyngeal spaces and left longus colli muscle causing narrowing of the nasal airway and nasopharynx as well as a unilateral mastoid effusion (, top row). The top differential considerations included adenoidal benign lymphoid hyperplasia, nasopharyngeal non-Hodgkin and Hodgkin lymphoma, juvenile angiofibroma, nasopharyngeal rhabdomyosarcoma, and nasopharyngeal carcinoma. Subsequent biopsy of the mass was consistent with non-keratinizing nasopharyngeal carcinoma (). She then presented for an 18F-FDG PET/CT study performed on a Philips Gemini Time of Flight system imaged from the top of the skull to the feet (FDG dose 6.8 mCi). The scan demonstrated an intense FDG avid mass in the left nasopharynx and nasal cavity extending to the left maxillary sinus (SUV max 10.8) and a metastatic left cervical lymph node (SUV max 6.9) with no distant metastasis (, bottom row). EBV panel and PCR were both strongly positive (see Discussion section). According to the TNM classification, the tumor was classified as T3 (tumor has grown into the sinuses and/or bones nearby), N2 (spread to nearby lymph nodes no larger than 6 cm), and M0 (no distant metastasis), stratifying her to stage III disease. She has recently completed neoadjuvant chemotherapy (cisplatin and 5-fluorouracil) and radiation therapy and currently under strict follow-up. This retrospective study was approved by the Institutional Review Board and the informed consent was obtained. |
pmc-6415281-1 | A 26-year-old male patient, who is asthmatic and being treated with montelukast, presented with recurrent respiratory tract infections and repeated episodes of haemoptysis.
There was no evident lesion more than a small depression in the mucosa, but no connecting duct was revealed in the bronchoscopy. The CT scan showed a right paratracheal well-defined air image immediately above the thoracic inlet (). It was 15 mm in size and had a close relation with the posterior right trachea wall at the level of C6. There was no fluid inside the cavity and no sign of inflammation.
Due to the persistence of the symptoms, we decided to perform surgery to resect the tracheal diverticulum. We made a lower transversal anterior cervical incision, exposed the trachea, and carefully identified the cyst on the right side. The lesion was identified behind the trachea-oesophageal groove connected with the trachea (). The laryngeal recurrent nerve was extremely adhered to the cyst but was freed. A complete resection was performed and then sutured with absorbable thread in the posterior membrane. The patient was discharged 72 hours after surgery with minor dysphonia. In the follow-up, two months after surgery, the patient was asymptomatic. |
pmc-6415282-1 | A 56-year-old male patient, whose plasmacytoma was enucleated 3 years ago from the medial side of the left mandible, was referred to our clinic due to his complaints of persistent orocutaneous fistula (Figures –). Past medical history revealed that the patient was operated three times to close the orocutaneous fistula by local flaps; however, none of these operations were successful. CT images of the patient demonstrated that the medial side of the left mandible was missing and there was a 3 × 2 cm diameter defect located between the left side of the mouth floor and the basis of the left mandible neighboring the left submandibular gland. The main reason of the failed attempts to close the fistula was considered to be the ineffective management of dead space surrounding the fistula. Consequently, it was decided to use the submandibular gland as a pedicled flap to fill the defect and support the oral and the cutaneous flaps.
Under general anesthesia, the fistula was excised initially and the oral and the cutaneous healthy soft tissues were prepared. At the extraoral site, the incision was extended to the posterior and anterior directions, following the previous incision lines. In the subplatysmal plane, the superficial layer of the neck fascia was dissected to reach the base of the mandible. After the dissection of the fascia, the submandibular gland and the base of the mandible were exposed, the soft tissues surrounding the submandibular gland were dissected, and the gland was mobilized by protecting the arteriovenous supply and the duct. At the oral site, the margins of the wound were released by blunt dissection and were closed by mattress sutures via 5/0 polypropylene. Following the mobilization of the gland, a soft tissue tunnel was prepared between the submandibular space and the defect area and the submandibular gland was rotated by passing the gland through the soft tissue tunnel by preserving the pedicle (). The rotated gland was sutured to the recipient site with 3/0 reabsorbable polyglaction sutures for the stabilization. At the cutaneous site, the flap was closed layer by layer by using 3/0 resorbable polyglaction for the facia and the subcutaneous layers and 3/0 polypropylene sutures for the skin. After the surgery, pressure bandage was applied for the edema control externally and the patient was ordered soft diet for a week. The postoperative healing was uneventful, and at the sixth month follow-up visit, ideal closure of the fistula was observed (Figures and ). |
pmc-6415288-1 | The patient is a 69-year-old gentleman, who is HIV positive. His viral load is undetectable and his CD4 count is 417 cells/mm3. For six years he has been on first line antiretroviral therapy in compliance with the South African Department of Health guidelines i.e. a fixed-dose combination pill taken daily, containing tenofovir, emtricitabine, and efavirenz []. He has no history of seizures or other comorbidities. He is an independent and active member of the community. He does not smoke or abuse alcohol.
He first presented to his local clinic with a history of seizure-like activity beginning approximately one week prior. Subsequent to the onset of seizures, the patient had been unable to walk and was experiencing pain in both his hips. There was no history of trauma otherwise. At his clinic, he had a witnessed generalised tonic-clonic seizure which was aborted with a benzodiazepine. He was then referred to Madadeni Provincial Hospital.
On presentation, the patient was noted to be drowsy but rousable, and cooperative. His vitals were normal. Orthopaedic examination showed bilaterally externally rotated lower limbs, with tenderness in the groin and pain on movement of his hips. He had no neurological deficit with a normal vascular exam. There were no signs of trauma or open wounds. Pelvic radiographs showed bilateral Garden 4 subcapital neck of femur fractures ().
He was admitted for comanagement by internal medicine and orthopaedics. His medical workup revealed an electrolyte abnormality of severe hyponatraemia (115 mmol/L), and, as his other blood tests were normal and CT brain showing only age-related atrophy, the hyponatremia was attributed as the cause of the seizures. The hyponatremia was corrected and he had no further seizures in the ward.
He was kept in bilateral skin traction during his medical optimisation. Staged, bilateral total hip arthroplasties was ultimately performed. Due to lack of theatre time and a high patient load at Madadeni Hospital, the patient waited almost two weeks for his first surgery () and another month before his second surgery (). The patient was assessed as a Dorr B, had good intraoperative bone quality and both arthroplasties were thus uncemented. During the first (left) arthroplasty, there were concerns of fracture extension into the intertrochanteric region, and a cabling system was used to reinforce the stem insertion. For both surgeries, a Mathys RM Pressfit cup, with symarec head and a Zimmer Avenir stem, was used. Several bone biopsies were also taken during the first surgery to exclude a pathological fracture. All biopsies were normal.
Postoperatively, the patient was kept on DVT prophylaxis and began in-bed hip and knee range of motion exercises on day two after surgery. The patient was mobilising with the assistance of a physiotherapist and a walking frame within a week of his second surgery and was discharged home with no postoperative complications. |
pmc-6415289-1 | A 57-year-old male presented to the oral and maxillofacial surgery clinic at our institution with more than a 20-year history of a painless mass in the hard palate region. He elected to have the lesion evaluated due to its increase in size, although indolent. He reported no other symptoms.
His past medical history was significant for hypertension and hyperlipidemia. He denies any past surgical history, he was not taking any medications, and he has no known drug allergies. He presently denies any social history but admits to tobacco use for 15 years and stopped almost 20 years ago.
On examination, it was noted that the patient had a firm, erythematous, raised lesion with a central area of ulceration located at the junction of the hard and soft palate on the right side. The lesion was roughly 2.0 cm × 1.0 cm in size (). There was no palpable lymphadenopathy on head and neck examination.
Computed tomography (CT) and magnetic resonance imaging (MRI) showed a mass involving the right palate measuring 39 mm in the greatest dimension. The CT showed a focal area of bone thinning and focal dehiscence at the floor of the right maxillary sinus without evidence for frank tumor extension into the sinus (Figures and ).
An incisional biopsy was performed and sent for pathology. On hematoxylin and eosin stain, the tumor comprised of cells forming microcystic and glandular spaces containing eosinophilic homogenous material. The secretory material from the glandular spaces was noted to be periodic acid Schiff- (PAS-) positive and diastase-resistant (). The tumor cells had eosinophilic granular cytoplasm with low-grade vesicular nuclei and visible nucleoli (Figures and ). There were rare mitotic figures, and scattered inflammatory cells were present. A broad front pattern of invasion was noted. Immunohistochemical stains showed positivity for cytokeratin 7, SMA, p53, and CK5/6. The tumor was also diffusely positive for both mammaglobin and S100, supportive for the diagnosis of MASC [] (Figures and ). DOG-1 staining was negative. Cytogenic testing was not performed in this case.
Treatment consisted of wide local excision of the lesion with 1 cm margins and a right selective neck dissection levels 1-3. Hemostasis of the greater palatine neurovascular bundle was achieved with bipolar electrocautery and bone wax. The surgical site was allowed to heal by secondary intention with granulation tissue ().
A total of 42 lymph nodes were harvested and all lymph nodes were negative. No lymphovascular and no perineural invasion was noted. All margins were negative with the closest margins at 0.5 mm. The final pathologic diagnosis was MASC with the tumor size measuring 1 × 0.7 × 0.6 cm. Given the negative margins and the lack of consensus regarding the utility of adjuvant therapy in this disease entity, no further treatment was administered.
Patient's postoperative course was uneventful, although a biopsy was done 6 months later which showed no evidence of disease. At his most recent follow-up, 36 months after surgery, the patient was free of tumor (). The patient had no neurologic deficit. He had no range of motion issues with his shoulder, however complained of slight numbness over his right shoulder. He denied any change in speech or swallowing issues. The nasal mucosa was preserved; levator muscles and palatal muscles were preserved. The hard palate site healed well by secondary intention. |
pmc-6415290-1 | A 67-year-old man presented to our hospital with a primary complaint of subcutaneous bleeding in his left thigh and development of purpura, over the last 3 months. It had been pointed out to him that there was a mild anaemia with haemoglobin level of 10.4 g/dL. He had been diagnosed two years previously with myelodysplastic syndromes with multilineage dysplasia (MDS-MLD) considered in the context of the 2016 World Health Organization (WHO) classification criteria. The 46, XY, i(14) (q10) abnormality was detected in 100% of marrow metaphases (). The bone marrow blast was 3.3%. He was categorized as low risk in Revised International Prognostic Scoring System (IPSS-R), and he had not received cytokine therapy or blood transfusion. He had a medical history of hypertension, type 2 diabetes mellitus, spinal canal stenosis, and idiopathic osteonecrosis of the femoral head and underwent right total hip arthroplasty (r-THA).
Physical examination showed conjunctival pallor and a swelling on the left thigh with overlying bruising (). Computed tomography revealed a large bleed in the left quadriceps femoris muscle (). Laboratory data showed the following: white blood cell count, 13.6 × 109/L (normal range 3.5–9.7 × 109/L); monocyte count, 4.6 × 109/L (monocyte percentage, 33.6%); haemoglobin level, 8.8 g/dL (13.2–17.2 g/dL); haematocrit, 28.1% (40–52%); and platelet count, 258 × 109/L (140–370 × 109/L) (). On review, the monocyte count on three months previously too had been elevated (3.0 × 109/L). Activated partial thromboplastin time (APTT) was significantly prolonged (85.8 s, normal range 24–39 s). Prothrombin time was within the normal range (10.5–14 s). Mixing studies demonstrated that the prolongation of APTT was not corrected by the addition of an equal volume of pooled normal plasma either instantaneously or over two hours of incubation, indicating the presence of an inhibitor. When coagulation factors of the intrinsic pathway were measured, FVIII activity was less than 1% (normal range 60–150%), and coagulation factors IX, XI, and XII were also found to be reduced. Further tests did not detect lupus anticoagulant antibody. The inhibitor for FVIII was quantified using the Bethesda method and showed a high level of 166 BU/mL, but there was no inhibitory activity against factor IX inhibitor (). Since the patient's coagulation profile had previously been normal, the current results indicated that he had developed acquired haemophilia A (AHA). |
pmc-6415291-1 | A 41-year-old Caucasian woman noticed left cheek swelling and pain in corresponding upper premolars and molars and attended to a consultation in the Oral and Maxillofacial service at Hospital Municipal do Campo Limpo (São Paulo, Brazil). Her medical history revealed a previously ischemic cerebrovascular accident and continuous use of anticoagulants but no other past disease.
Extraoral examination showed no lymphadenopathy or paresthesia but an evident swelling in the left cheek () with a hardened consistency. The patient mentioned she noticed the symptoms for a period of time higher than a week. Intraorally, she showed severe periodontal disease and pain during vertical/horizontal percussion tests. Pulp vitality could not be determined at this point, due to the severity of pain presented during teeth percussion tests. Buccoalveolar sulcus bulging and a floating tumefaction in the left upper molar root region were observed. Although the first diagnostic hypothesis was dental abscess, due to the unusual duration of the tumefaction, the patient was then referred to imaging examinations (multislice computed tomography—MCT). However, due to the presence of an intraoral floating tumefaction and dental origin symptomatology, drainage was performed, and antibiotic treatment was prescribed.
Despite of accomplishing imaging examinations as requested in the first consultation, the patient only came back to the Oral and Maxillofacial service after three weeks, when she felt paresthesia and severe pain in her left face. exhibits the patient left face swelling aspect at this moment. Due to the increase in painful symptomatology and evident speedy lesion development, the patient was immediately hospitalized, and a new CT examination was performed, as well as routine and biochemical blood test examinations. Intraoral floating was now absented.
No alterations were verified in the patient hemogram, coagulation tests, and immune phenotype (CD3+/CD4+) examinations, as well as blood tests for hormones, especially the parathyroid hormone.
Noncontrast-enhanced, high resolution MCT with 16 slices (Toshiba Activion, Medical Systems Corporation, Japan) was used for MCT imaging. Acquisition imaging parameters were 0.5 mm slice thickness, 1.0 mm Spacing Between Slices, 250 mm field of view, 120 kV peak, and 250 mA. The first consultation MCT axial slices revealed a soft tissue hypodense area in the left side, comprising the maxillary sinus area and bone discontinuity in the anterior and lateral maxillary sinus wall () orbital cavity floor. Frontal slices showed discrete nasal cavity involvement ().
The second consultation MCT axial slices revealed that the soft tissue hypodense area in the left side increased in size, with greater nasal cavity involvement and bone destruction than .
At this point, the main diagnostic hypothesis was osteosarcoma, sinonasal diffuse large B-cell lymphoma, parathyroid brown tumor, and extranodal malignant lymphoma, particularly maxillary ENKL. The hypothesis of dentoalveolar abscess was disregarded: floating tumefaction might be coincidentally previously present due to the periodontal disease severe status.
A biopsy was taken from the lesion (oral cavity) and sent to the hospital's pathology department. The histopathological examination with hematoxylin and eosin (H&E) showed a diffuse proliferation of small to medium-sized atypical lymphocytes with areas showing an angiocentric pattern effacing the normal architecture of the oral mucosa. Mild epithelium tropism and espongiosis were observed (Figures and ). Focal areas of ulceration and necrosis were also seen. Trial immunohistochemical and in situ hybridization reactions were made (Figures –). The findings were consistent with ENKL. As part of staging, a bone marrow biopsy was done, and no abnormalities were found.
Before the diagnostic definition, the patient was treated with one cycle of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone). Once the diagnosis was established, the AspaMetDex (L-asparaginase, methotrexate, and dexamethasone) regimen was started, but no response was observed after two cycles of chemotherapy; on the contrary, the lesion became larger, and the acute inflammatory signs turned more evident. Facing this, the DICE (dexamethasone, isofosfamide, cisplatin, and etoposide) regimen and local radiotherapy (30 Gy) were started. After two cycles, the lesion presented a significant reduction, but her general condition deteriorated and was associated with mucositis and persistent neutropenia. Before even starting another cycle, five months after the diagnosis, the patient passed away. |
pmc-6415304-1 | A 40-year-old man of West African origin was diagnosed with IgG lambda multiple myeloma with urinary free lambda light chains of 0.34 mg/L (normal range: 0.24-6.66 mg/L)) and plasmacytomas involving the pleura and bone marrow. He was treated with bortezomib-based chemotherapy with no response. Salvage chemotherapy resulted in tumor lysis syndrome (K 7.4 mmol/L; uric acid 12.9 mg/dL, serum creatinine 2.0 mg/dL) that resolved with chemotherapy de-escalation, rasburicase, and a single hemodialysis session. His renal function then returned to normal and the patient continued salvage chemotherapy as an outpatient. Eight months later, he presented to the Emergency Department (ED) with abdominal discomfort and AKI (serum creatinine 18.2 mg/dL) and was found to have bilateral severe hydronephrosis, due to upper ureteral obstruction caused by retroperitoneal adenopathy. Upon relief with percutaneous nephrostomy, his renal function normalized (serum creatinine 1.1 mg/dL), with suppression of monoclonal protein (M-spike 1.4 g/dL). Two months later, the patient was admitted to hospital for another episode of AKI that progressed despite supportive care. His M-spike was 5.3 g/dL and urinary free lambda light chain was 5080 mg/dL, consistent with myeloma kidney. He ultimately required hemodialysis support. The patient succumbed to complications of multiple myeloma and sepsis soon after, 14 months after diagnosis. |
pmc-6415304-2 | A 66-year-old man presented to the ED for a 3-week history of bilateral leg edema, distended abdomen, dysuria, and anorexia. He was recently treated for a urinary tract infection. Physical examination disclosed a distended bladder. Initial laboratory data revealed AKI with hyperkalemia (K 7.9 mEq/L, blood urea nitrogen (BUN) was 148 mg/dL and serum creatinine of 35.92 mg/dL); an urgent nephrology consultation was requested for emergency hemodialysis. In the meantime, a bladder catheter was placed with approximately 9 liters of urine output. Over the next 30 hours the patient's laboratory data improved dramatically (). His BUN dropped to 36 mg/dL within one day. The cause of AKI was later found to be UTO secondary to prostatic adenocarcinoma. His renal function improved spontaneously without the need for hemodialysis. |
pmc-6415304-3 | A 58-year-old man with mild mental retardation and diabetes mellitus was brought to the ED for vomiting, diarrhea, and progressive weakness for several days. He had significant azotemia with serum creatinine of 31 mg/dL and BUN of 187 mg/dL with hyperkalemia and high anion gap metabolic acidosis (). Computed tomography (CT) of the abdomen showed moderate to severe bilateral hydronephrosis and a very large prostate gland protruding into the bladder, which is significantly distended. Renal ultrasonography showed mild bilateral hydronephrosis. The patient was treated medically for hyperkalemia, and a Foley catheter was placed with resultant good urinary flow, followed by rapid resolution of his azotemia and electrolyte derangements. His BUN decreased to 41 mg/dL in 2 days. A prostate biopsy performed later revealed benign prostatic hyperplasia. |
pmc-6415304-4 | A 40-year-old woman with a past medical history of hypertension and severe endometriosis presented to the ED with a serum creatinine of 17 mg/dL and BUN of 86 mg/dL. Renal sonogram disclosed moderate hydronephrosis with hydroureter compressed by a large myomatous uterus. A hysterectomy was performed which resulted in renal function improvement but did not normalize. However, the patient continued to develop multiple bouts of AKI and progressive chronic kidney disease (CKD) for the next several years. An episode of lower gastrointestinal bleeding prompted a colonoscopy that revealed a mass at the rectosigmoid junction which was resected and confirmed to be colonic endometriosis and leuprolide was started. By this time, the patient's CKD had progressed to end-stage renal disease and she was placed on maintenance hemodialysis. |
pmc-6415311-1 | A 17-year-old woman was referred to our Oral Pathology Unit by her family dentist to evaluate a solitary asymptomatic, mobile, and well-circumscribed mass in her left cheek.
The patient reported a swelling in the left cheek in the last two months. Her family and medical histories were irrelevant; she was not following any drug therapy; she did not smoke or usually consume alcohol.
Clinically, we observed a palpable hard-elastic mass, measuring 1.5 × 1.0 cm approximately, in the submucosal layer of the left cheek. The patient did not report pain; the skin and the covering mucosa were normal. An ultrasound scan (US) was prescribed and showed a hypoechoic homogenous mass with well-defined margins.
The patient underwent an excisional biopsy under local anesthesia () after received an antibiotic prophylaxis therapy with 2 grams of amoxicillin 60 minutes before the surgery. She continued antibiotic therapy with 1 gram of amoxicillin every 12 hours until the 4th postoperative day. As analgesic therapy, the patient received paracetamol 500 mg immediately after the surgery.
The specimen was stored in a tube containing formalin 10% and sent to a laboratory for histopathological analysis.
The tumor was well circumscribed with a thin fibrous capsule, and a sample obtained was firm, sharply circumscribed, yellow-white round to ovoidal nodule (1 × 0.6 cm in dimension). It was composed of uniform spindle smooth muscle cells with pale eosinophilic cytoplasm and blunt-ended or cigar-shaped nuclei, with slightly wavy contour, vesicular chromatin, and occasionally small nucleolus; in cross-sections, nuclei appeared surrounded by a clear halo as contained in boxes. Mitotic figures were very rarely seen (1/20 hpf). The cells were arranged in uniform interlacing bundles, with interposition of the low amount of fibrous connective tissue, and distributed around numerous small tortuous “slit-like” vessels, with virtual lumen and lined by normal-appearing endothelium but with no elastic lamina present, resembling a solid or capillary subtype appearance (closely compacted smooth muscle bundles), in contrast to venous (vessels have thick muscular walls that merge with smooth muscle bundles) and cavernous (dilated vascular channels with minimal smooth muscle that merges with smooth muscle bundles) subtypes; they have no clinical significance [].
Necrosis, atypical mitoses, and pleomorphism were not observed in the histological examinations ().
In addition to the histopathological analysis, immunohistochemical staining of the sample with α-smooth muscle actin (SMA), CD34, desmin, and vimentin was performed: the proliferating spindle cells were diffusely and strongly immunoreactive for SMA, desmin, and vimentin; the vascular spaces were consistently CD34-positive staining ().
The histopathological and immunohistochemical analysis suggested the diagnosis of AL.
Follow-up examinations at 1 week, 4 weeks, and 6 months showed mucosal integrity and no sign of recurrence. |
pmc-6415314-1 | A 39-year-old male, with no significant medical history, presented to our Otolaryngology Department. He reported several months of worsening nasal congestion, intermittent otalgia, and a progressive change in voice.
Clinical examination confirmed bilateral obstruction of the nasal airway and showed the patient was a habitual mouth breather. Diagnostic flexible nasendoscopy demonstrated significant hypertrophy of the turbinates and the presence of a large homogeneous non-indurated soft tissue mass occupying the nasopharynx.
Computed tomography (CT) showed a well-defined 28 × 31 × 22 mm tumour in the nasopharynx obstructing both Eustachian tube orifices, but with no signs of local or regional lymphadenopathy. Contrast magnetic resonance (MR) imaging () demonstrated a uniformly enhancing pedunculated polypoid mass that displaced the soft palate inferiorly, but without evidence of skull base involvement.
Following an incisional biopsy that showed histological features of pleomorphic adenoma, the multidisciplinary team consensus was to offer surgery to resect the entire tumour for definitive histology. The patient was consented and operated using an endoscopic transnasal approach under general anaesthesia. Standard functional endoscopic surgery instrumentation was used, in a procedure assisted by a radiofrequency coblator device (Smith & Nephew Inc., London, United Kingdom). The tumour's pedicle was identified endoscopically as originating from the left lateral nasopharynx and, using coblation, was carefully dissected en bloc from its mucosal attachment () leaving the wound bed to heal by secondary intention. Finally, the specimen () was delivered transorally with forceps. The procedure was completed uneventfully as a day case without complication.
Definitive histology confirmed the complete excision of a myoepithelial-rich pleomorphic adenoma with negative resection margins. Microscopic sections () showed a circumscribed non-encapsulated tumour with no evidence of perineural or lymphovascular invasion. Immunohistochemical stains were strongly positive for cytokeratin AE1/3, CK5/6, and p63 (with a small portion reverse staining with CK7) and positive for vimentin; however, stains were negative for smooth muscle actin, S100 protein, SOX-10, and CD10. The Ki-67 proliferative index was low at <2%.
The patient was symptom-free postoperatively, and follow-up flexible nasendoscopy at one year demonstrated no signs of local recurrence. |
pmc-6415337-1 | Our patient is a 69-year-old African American woman who presented with gradually decreased and blurred vision of approximately 1 year’s duration without other ocular symptoms. Her past medical history was significant for hypertension, schizophrenia, and depression with no history of diabetes. Her past ocular history was significant for: uncomplicated cataract extraction of both eyes 2 years prior; primary open-angle glaucoma treated with latanoprost, brimonidine, and timolol in both eyes; and dry eye syndrome with past punctal plug placement. Medications included citalopram, risperidone, amlodipine, enalapril, and metoprolol. She reported no difficulty with medication compliance. Of note, an eye examination approximately 1 year prior to presentation showed 20/20 visual acuity bilaterally. A chart review revealed that she had been taking risperidone 2 mg/day for at least 3 years prior to presentation. Her dosage was increased by her psychiatrist 2 years prior to presentation to 3 mg/day, with ocular symptoms developing approximately 1 year after the dosage increase (or 1 year prior to presentation).
Visual acuity on presentation was 20/150 in her right eye and 20/200 in her left eye and intraocular pressures were within normal limits. An anterior segment examination showed decreased tear film, but was otherwise unremarkable. A posterior segment examination showed bilateral CME with no vitreous cells. FA demonstrated bilateral petaloid leakage (Fig. ) and CME was confirmed by OCT (Fig. ). The CME was suspected to be secondary to risperidone and a recommendation about the possible association between the risperidone and macular edema was made to our patient’s psychiatrist, who decreased risperidone dosage from 3 to 2 mg/day when she followed up with them 2 months later. Her psychiatry team expressed concern with fully eliminating her risperidone or switching to another agent and risking a breakthrough psychotic episode. Thus, the psychiatrist recommended to first attempt dose reduction. At 4-months follow-up, her CME resolved bilaterally (Fig. ) and vision improved to 20/40 in both eyes. OCT imaging 6 and 12 months after this visit showed no recurrence of CME. She has had no new ocular complaints since dosage adjustments as per record review, and no edema was noted on funduscopic examination at the last follow-up 18 months after presentation. |
pmc-6415340-1 | A 48-year-old-Asian woman visited the neurosurgical department of another hospital because of chronic mild headache. Head magnetic resonance (MR) imaging incidentally detected a small mass lesion inside the sella turcica. Endocrinological examination showed high concentrations of serum GH (6.83 ng/ml; normal range, 0–2.47 ng/ml) and insulin-like growth factor 1 (IGF-1) (517 ng/ml; normal range, 82–219 ng/ml). Because she had no neurological deficit or medical history of hypertension and diabetes mellitus, surgery was not proposed at the former hospital, and simple observation was continued. She had no family history of cancer or endocrinological diseases. She occasionally drinks alcohol and has no smoking habit. She worked as a school janitor, and a routine medical checkup showed that her systolic and diastolic blood pressure were around 110 and 70 mmHg, respectively. During the follow-up period, head MR imaging showed no significant change in tumor size, and concentrations of serum GH and IGF-1 were not further increased (6.99 ng/ml and 476 ng/ml, respectively). Five years after the initial diagnosis, baseline blood pressure was elevated to 140/80 mmHg. She had an 8-kg weight gain, and her shoe size was enlarged by 1.5 cm during this period. Finally, she was referred to our department for surgical intervention. Head MR imaging showed that the tumor was slightly enlarged (11 × 16 × 16 mm) and sparsely enhanced with gadolinium (Fig. a). On admission, prominent forehead, prominent lower jaw, and bite abnormalities were not observed. A roentgenogram showed cauliflower-like enlargement of the distal phalanx of the fingers (Fig. c). The expansion of maxillary or frontal sinus was not particular, but enlargement of the nose and lips was evident (Fig. d). Serum concentrations of GH (7.33 ng/ml) and IGF-1 (606 ng/ml) had further increased. A preoperative 75-g oral glucose tolerance test (OGTT) showed no suppression of serum GH concentration. To control excess GH secretion, surgery was proposed. Transsphenoidal surgery achieved gross total removal of the tumor (Fig. b). Serum concentrations of GH (1.89 ng/ml) and IGF-1 (422 ng/ml) had rapidly decreased by 1 week after surgery and remained at low levels at 4 months after surgery (GH, 2.91 ng/ml; IGF-1, 339 ng/ml). Postoperative 75-g OGTT showed sufficient suppression of serum GH concentration. She was discharged without neurological deficit. After surgery, the heel pad thickness was decreased by 1 mm, and body weight was decreased by 2.9 kg. The head MR imaging, serum concentration of GH, IGF-1, and 75-g OGTT were followed up for 21 months after surgery, which revealed no evidence of recurrence. Postoperative histological examination of formalin-fixed, paraffin-embedded tumor specimens demonstrated sheet-like proliferation of monomorphic round cells with H&E staining (Fig. e), and tumor cells showed diffuse immunoreactivity for GH (Fig. f). The histological diagnosis was densely granulated somatotroph adenoma. |
pmc-6415340-2 | A 40-year-old-Asian woman visited another general neurosurgeon’s clinic because of chronic mild headache. Head MR imaging incidentally detected a small mass lesion inside the sella turcica. She had no family history of cancer or endocrinological diseases. She has no smoking or drinking habit. She worked as an administrative staff member of an office and had no irregular educational and environmental histories. She had no neurological deficit or medical history of hypertension and diabetes mellitus. Endocrinological examination showed high concentrations of serum GH (11.90 ng/ml; normal range, 0.28–1.64 ng/ml). Because she presented no clinical features of acromegaly, the initial diagnostician did not propose surgery, and simple observation was continued. During the follow-up period, head MR imaging showed no significant change in tumor size, and concentration of serum GH was not further increased (10.10 ng/ml). Three years after the initial diagnosis, radiography showed that the tumor had enlarged, and the patient had weight gain and foot size increase. She accepted surgical treatment and was referred to our department. Preoperative MR imaging showed the tumor with suprasellar extension (14 × 19 × 12 mm), and the optic chiasm was slightly compressed upward (Fig. a). On admission, prominent forehead, prominent lower jaw, and bite abnormalities were not observed. Roentgenogram showed cauliflower-like enlargement of the distal phalanx of the fingers (Fig. c). The expansion of maxillary or frontal sinus was not particular, but enlargement of the nose and lips was evident (Fig. d). Serum concentrations of GH (31.14 ng/ml) and IGF-1 (709.6 ng/ml) were further increased. Preoperative 75-g OGTT showed no suppression of serum GH concentration. To control excess GH secretion, surgery was proposed. Transsphenoidal surgery achieved gross total removal of the tumor (Fig. b). Serum concentration of GH (0.98 ng/ml) and IGF-1 (407.8 ng/ml) had rapidly decreased by 1 week after surgery and remained at low levels at 4 months after surgery (GH, 0.62 ng/ml; IGF-1, 207.9 ng/ml). Postoperative 75-g OGTT showed sufficient suppression of serum GH concentration. The patient was discharged without neurological deficit. After surgery, the heel pad thickness was decreased by 2 mm, and body weight was decreased by 4.0 kg. The head MR imaging and serum concentration of GH and IGF-1 were followed up for 66 months after surgery, which revealed no evidence of recurrence. Postoperative histological examination of formalin-fixed, paraffin-embedded tumor specimens demonstrated sheet-like proliferation of monomorphic round cells with H&E staining (Fig. e), and tumor cells showed patchy immunoreactivity for GH (Fig. f). The histological diagnosis was sparsely granulated somatotroph adenoma. |
pmc-6415340-3 | A 64-year-old-Asian woman visited the neurology department of another hospital because of chronic mild headache. Head MR imaging incidentally detected a small mass lesion inside the sella turcica (Fig. a), and she was referred to our department. Serum concentrations of GH (6.00 ng/ml) and IGF-1 (341 ng/ml) exceeded the normal ranges, but she had no neurological deficit or medical history of hypertension and diabetes mellitus, and no physical characteristics of acromegaly. She had no family history of cancer or endocrinological diseases. She has no smoking or drinking habit. First, she refused surgery, but 8 months after the initial diagnosis, she accepted intervention. She was a homemaker and had no regular work. She requested the shortest hospital stay and did not agree to the preoperative 75-g OGTT. Preoperative MR imaging showed a slightly enhanced tumor without particular enlargement (11 × 17 × 17 mm). Acromegalic hand enlargement was discovered at the time of surgery. To control excess GH secretion, surgery was proposed. Transsphenoidal surgery achieved gross total removal of the tumor (Fig. b). Serum concentrations of GH (0.85 ng/ml) and IGF-1 (104 ng/ml) had rapidly decreased by 1 week after surgery and remained at low levels at 4 months after surgery (GH, 1.76 ng/ml; IGF-1, 174 ng/ml). Postoperative 75-g OGTT showed sufficient suppression of serum GH concentration. She was discharged without neurological deficit. After surgery, her body weight was decreased by 0.5 kg. The head MR imaging, serum concentration of GH, IGF-1, and 75-g OGTT were followed up for 23 months after surgery, which revealed no evidence of recurrence. Postoperative histological examination of formalin-fixed, paraffin-embedded tumor specimens demonstrated sheet-like proliferation of monomorphic round cells with H&E staining (Fig. c), and the tumor cells showed diffuse immunoreactivity for GH (Fig. d). The histological diagnosis was densely granulated somatotroph adenoma. |
pmc-6415464-1 | A 71-year-old female with comorbidities such as hypertension and end-stage renal disease (on hemodialysis) presented to our emergency department with complain of back pain of 1 day duration. Only significant finding noted on physical examination was decreased range of motion in lumbar spine associated with moderate to severe pain. Review of systems was otherwise reported negative. The patient had low-grade fever 100.4°F, tachycardia 115 beats per minute, respiratory rate 22 breaths per minute, and blood pressure 160/78 mm Hg on admission. Complete blood count on admission was significant for macrocytic anemia with hemoglobin 10.1 mg/dL and mean corpuscular volume 101.3. Significant left shift was noted on differential white blood cell (WBC) count with 96.2% neutrophils (total WBC count on admission was 9500/dL). Comprehensive metabolic panel showed deranged renal function blood urea nitrogen 40 mg/dL (8-20 mg/dL) and creatinine 9.79 mg/dL (0.4-1.3 mg/dL). The patient met systemic inflammatory response syndrome criteria; therefore, 2 sets of blood cultures were sent for further sepsis workup and patient was started on broad-spectrum antibiotics (vancomycin and meropenem) empirically. Computed tomography chest/abdomen/pelvis was done, which was negative for any pulmonary or intra-abdominal focus of infection. However, computed tomography abdomen/pelvis showed presence of spinal canal stenosis in the lumbar area. Blood cultures sent on day 1 and day 3 (total 3 sets) grew C septicum. Repeat blood culture sent on day 5 was reported negative. Based on sensitivity report, antibiotics were switched to piperacillin/tazobactam.
Due to patient’s new-onset symptoms of worsening back pain, magnetic resonance imaging lumbar spine was done, which ruled out acute process/any mass lesion in the lumbar spine. Presence of multilevel degenerative disease and spinal canal stenosis was confirmed and any other pathology was ruled out.
The patient improved symptomatically and WBC count also improved over the next few days. However, due to known but rare association of C septicum with GI malignancy, upper GI endoscopy and colonoscopy () was performed on day 6, which showed nonobstructive mass in ascending colon suspicious for malignancy. Biopsy was taken and sent for histopathology examination, which was reported positive for well-differentiated adenocarcinoma ().
As there was no metastasis, the patient underwent hemicolectomy for the aforementioned lesion in the ascending colon. She was followed-up in 3 months and underwent surveillance colonoscopy, which showed no local recurrence of the malignancy. |
pmc-6415696-1 | A 46-year-old woman with sarcoidosis was followed up at Juntendo Urayasu Hospital from May 1993 onward. Her chief complaint was visual disturbance due to uveitis, and steroid-containing eye drops were administered. On 14 March 1994, she visited the hospital complaining of sudden right visual disturbance along with a severe headache and was diagnosed with vitreous haemorrhage. She was admitted to our hospital for surgery on 9 May and started on oral steroid therapy with methylprednisolone (20 mg). On 12 May, she underwent vitrectomy combined with endoscopic photocoagulation surgery for her right eye, and the corticosteroid dose was gradually tapered off before being discontinued.
After the surgery, she was followed up without the oral steroid therapy. In early 1998, she developed some skin eruptions (resembling raised erythematous smooth plaques) on her back that continued to gradually progress (Fig. B). Skin biopsy performed on 14 April 1999 revealed multiple granulomatous lesions, confirming a diagnosis of sarcoidosis (Fig. D). At that time, a chest computed tomography (CT) revealed diffused small nodules and consolidations in her lung field, indicating a pulmonary involvement of sarcoidosis. However, even after sarcoidosis was diagnosed, she refused oral corticosteroid therapy and was followed up without treatment. Her chest X-ray and CT findings were unremarkable, and the serum angiotensin-converting enzyme (ACE) level fluctuated between 25 and 32 U/mL (Fig. A). In early 2014, her skin eruptions became worse, and we decided to treat her skin sarcoidosis with minocycline monotherapy.
Notably, after the initiation of minocycline (11 April 2014), her skin eruptions, which had never improved in >15 years, started resolving gradually. The plaque redness decreased, the bulging started to heal (Fig. B), and her serum ACE level also decreased (Fig. A). After almost one year of the monotherapy, her skin sarcoid plaques almost disappeared with only slight scarring. Moreover, there was a marked decrease in her serum ACE level (from 24.7 to 13.6 U/L). Despite these significant improvements, the amelioration of pulmonary sarcoidosis was minimal. Over the last two years, the patient has continued to receive the minocycline monotherapy without any significant adverse events.
We retrospectively performed immunohistochemical staining on a skin biopsy (paraffin block specimen obtained on 14 April 1999) using a P. acnes-specific monoclonal antibody (PAB antibody) that reacts with cell-membrane-bound lipoteichoic acid . Notably, despite the absence of staining with anti-mycobacterium tuberculosis antibody, the PAB antibody stain was positive (Fig. D), revealing the presence of P. acnes in the skin sarcoid granulomatous lesion. |
pmc-6415980-1 | A 66-year-old male with a past medical history significant for hypertension, hyperlipidemia, ischemic stroke, coronary artery disease, and asthma was admitted for cardiac catheterization for worsening angina. He had symptoms of crescendo angina with New York Heart Association (NYHA) class IV symptoms and was referred by his primary cardiologist for coronary angiography with the intent to pursue revascularization as warranted. He had established coronary artery disease in 2012, with pharmacological myocardial perfusion imaging demonstrating inferior infarct and peri-infarct ischemia with an overall preserved systolic function for which medical treatment was pursued. In 2014, he reportedly underwent coronary angiography, which demonstrated a chronic total occlusion of the right coronary artery with grade III collaterals to the right coronary system and moderate non-obstructive disease of the left circumflex artery. In the interim, he ceased tobacco smoking and received guideline-directed medical therapy. He was doing well with optimal medical therapy, which included aspirin and clopidogrel, until three weeks prior to this presentation when he noted the onset of recurrent angina. Angina initially occurred with mild exertion, subsequently progressed to angina at rest, and he was admitted to hospital with unstable crescendo angina.
On admission, his vital signs were stable. His physical exam was unremarkable. A 12-lead electrocardiogram (EKG) demonstrated inferior Q waves and left ventricular hypertrophy without acute ST-T abnormalities (Figure ). Cardiac biomarkers were normal (peak creatinine phosphokinase-MB (CK MB) fraction and troponin T were 9.9 ng/mL (normal range 0.0-10.4) and less than 0.03 ng/mL (<0.03 negative), respectively. Coronary angiography revealed multi-vessel coronary artery disease with a likely culprit lesion involving the proximal left circumflex artery (Videos -). He underwent successful drug-eluting stent (DES) deployment to the proximal left circumflex artery (Video ). PCI was uneventful and guideline-directed medical therapy was continued. Despite long-term adherence to clopidogrel, platelet reaction unit (PRU) was 235. Due to a high on treatment PRU, with levels greater than 208 associated with an increased risk of stent thrombosis [-], a decision was made to transition to ticagrelor. He received a single 180 mg loading dose of ticagrelor. Four hours after receiving ticagrelor, he complained of shortness of breath, throat pain, neck discomfort, and swelling of the tongue. His vital signs remained stable, and he did not exhibit any skin eruption. He demonstrated mild swelling of the tongue and significant swelling of his throat and uvula. No wheezing was noted on exam. He received supplemental oxygen and otolaryngology (ENT) consultation was sought. He was treated with dexamethasone, as well as H1 and H2 histamine blockers. After the first dose of treatment, his symptoms improved. He was closely monitored. The following morning, ENT performed flexible fiberoptic laryngoscopy, which revealed a mild edematous pharyngeal area. Based on the clinical scenario, a provisional diagnosis of ticagrelor-induced angioedema was entertained. He did not have any history of allergy to any medications, contrast medium, or heparin. The decision was made to discontinue ticagrelor. His symptoms improved over the next few days with a tapering dose of steroids and antihistamines. The final decision was made to double the dose of clopidogrel and the patient was discharged with 150 mg of clopidogrel and 81 mg of aspirin daily. He has not had any ischemic symptoms or coronary events over a six-month period of follow-up. |
pmc-6416107-1 | A 23-year-old man presented to us with a 5 × 1.2 cm full-thickness defect of the nose after falling from a bicycle. The patient wanted to go back to his work as a salesperson as soon as possible, and was prone to hypertrophic scar formation. Thus, 1-stage reconstruction using a free flap was planned. The angular artery with a diameter of 0.8 mm was found through an incision made on the side of the nose (Fig. ). A subcutaneous vein with a diameter of 1.0 mm was located in a deeper layer, and the direction of the venous flow was confirmed using ICG angiography (see Video, Supplemental Digital Content 1, which displays an intraoperative video demonstrating direction of the venous flow using ICG angiography. The vein, the vessel with a background sheet, flowed from the top to the bottom of the screen. ). A 5 × 1.2 cm flap was elevated from the posterior region of the left ear, and the artery and the vein of the pedicle were anastomosed to the angular artery and the subcutaneous vein, respectively, both in an end-to-end fashion (Fig. ). The flap became congested 24 hours after the transfer, but it improved after a venous drainage was added to another subcutaneous recipient vein using a vein graft harvested from the dorsum of the foot. The flap showed excellent color match and satisfying contour 8 months after the reconstruction (Fig. ). |
pmc-6416119-1 | Sixty-three-year-old woman presented with multicentric left breast cancer requiring mastectomy. She is 69 inches tall with a weight of 215 pounds and a corresponding BMI of 31.8 kg/m2. She has a history of inferior pedicle breast reduction surgery performed 20 years ago (Fig. 1). Despite her previous reduction, she has a very large breast volume and footprint that will be difficult to replicate on the reconstructed left side. She desires nipple preservation and wants to keep her native right breast. We proceed with a left nipple-sparing mastectomy through her previous vertical limb and immediate prepectoral reconstruction using a full-height variable-projection tissue expander (width = 16 cm, height = 16.5 cm, projection = 6.8 cm, and volume = 850 ml) with anterior coverage using an acellular dermal matrix. Twelve weeks later, we exchange her tissue expander for the largest anatomical implant available, a full-height extra-projection 775 ml implant (width = 15.5 cm, height = 16 cm, and projection = 7.1 cm). She also undergoes a contralateral reduction of 300 g to achieve better symmetry. The final result is shown in Figure . Despite using the largest and tallest implant available and reducing the right breast by an additional 300 g, the entire upper pole of the left breast was depleted with significant size asymmetry between the breasts. We discussed multiple sessions of lipofilling to fill this defect but felt that an autologous flap would be more definitive. The LICAP flap was chosen to reconstruct the upper pole of the left breast. An intraoperative photograph is shown in Figure , where an extended flap is dissected based off the known perforators that arise anterior to the latissimus muscle at the level of the inframammary fold as previously described. This flap is rotated on its pivot point and used to reconstruct the upper pole of the breast by suturing it to the underlying pectoralis muscle. The final result 6 months after surgery is shown in Figure , where we have reconstructed the upper pole of her breast with the LICAP flap and have acceptable symmetry between the 2 sides. The patient is discharged the same day, and drains are removed on postoperative day 4. |
pmc-6416125-1 | A 53-year-old woman noticed a skin retraction in her right breast and went for a mammogram. The mammogram was suspicious: an ultrasound and magnetic resonance imaging were followed by a core biopsy. The core biopsy rendered a diagnosis of multiple foci of invasive moderately differentiated ductal carcinoma, 1.4 cm in greatest dimension. The patient tested negative for BRCA (breast cancer) gene mutations. She received herceptin and 6 cycles of chemotherapy followed by bilateral skin and nipple-sparing mastectomies with immediate reconstruction with tissue expanders. Pathology of the breast showed residual invasive ductal carcinoma, 2 foci, 0.9 cm in greatest dimension, with probable/definite response to presurgical neoadjuvant therapy in the invasive component. Intramammary LVI was reported as positive and multifocal on routine hematoxylin and eosin stained histologic sections (Fig. ). Three sentinel lymph nodes were removed from the axilla, one was positive for isolated tumor cells only by pancytokeratins immunohistochemistry. All margins, including subareolar margin, were widely negative for tumor. The pathologic stage was reported as ypT1b N0(i+) (sn). The case was reviewed at the Breast Multi-Disciplinary Tumor Conference. Based on the finding of multifocal intramammary LVI, PMRT was considered given the increased risk of local recurrence associated with such finding. Pathology rereviewed the histologic slides to determine the extent of LVI. However, the presence of LVI became questionable upon pathology intrainstitutional peer review. Ancillary studies including ERG and D2-40 (endothelial immunohistochemical markers) were performed on areas with questionable LVI to further verify this finding. The cells lining questionable lymphovascular spaces containing tumor were negative (Fig. ); meaning that these spaces were not lined by endothelial cells, and therefore may represent stromal retraction artifact lined by fibroblasts around tumor cells rather than true LVI (Fig. ). The histologic and immunohistochemical slides were sent out to other prominent pathology departments nationwide for additional consultation. The first outside institution agreed with the initial report of positive LVI based on the presence of the tumor-containing spaces in the right anatomic location (accompanying other big vessels and nerve bundles), whereas the second institution reported absence of LVI based on the endothelial markers that failed to highlight endothelial cells lining the tumor-containing spaces, favoring retraction artifact. The case was presented again at the Breast Multi-Disciplinary Conference, and the decision was made to not advise PMRT. The patient has subsequently completed her implant-based breast reconstruction and is followed without evidence of recurrent breast cancer or capsular contracture of the implant. |
pmc-6416218-1 | A 39-year-old male with a past medical history significant for hypogammaglobulinemia, and asthma, and colectomy status-post bowel perforation, presented with several days of increasing watery ostomy output, non-bloody vomiting, and subjective fevers. The cause of spontaneous bowel perforation is unclear. The diagnosis of hypogammaglobulinemia had been made 1 year prior to presentation when patient had no prior history of any gastrointestinal symptoms. Therefore, excluding any possibility of hypogammaglobulinemia secondary to protein-losing enteropathy. He had been doing well on intravenous immunoglobulin (IVIG) up until this point. A computed tomography scan of the abdomen and pelvis with contrast revealed diffuse small bowel mucosal hyperenhancement consistent with enteritis, with no evidence of free air or recurrent bowel perforation. He underwent EGD and colonoscopy with no complications. Both procedures revealed grossly normal mucosa with the exception of two diminutive sessile polyps at the cecum, which were biopsied. Immunohistochemistry revealed cells positive for cytomegalovirus and evidence of chronic active crypt-destructive colitis related to cytomegalovirus infection. Serum CMV was quantitated by PCR and found to be 9561 IU/ml. He was subsequently started on valgancyclovir with marked improvement in his clinical condition. Results of routine immunological analysis prior to starting immunoglobuline therapy revealed IgG (498 mg/dl; control range 694–1,618 mg/dl), IgA (118 mg/dl; control range 68–378 mg/dl), IgM (92 mg/dl; control range 65–263 mg/dl). At the time of diagnosis of CMV colitis, his lymphocyte subsets were as follow: CD3+ T cells 1,828/μl (control range 502–1,902/μl), CD4+ T-cells 949/μl (control range 338–1,194/μl), CD8+ T-cells 970/μl, (control range 85–729/μl), CD19+ B-cells 86/μl (control range 51–473/μl), and NK cells 86/μl (range 12–349/μl). Proliferative responses to recall antigens (Candida albicans and tetanus toxoid) and mitogens (phytohemagglutinin, concanavalin A, and pokeweed) were also normal. HIV was negative. |
pmc-6416479-1 | A 44-year-old woman with Behçet’s disease presented to the Uvea and Behçet’s Department of our center complaining of reduced vision in her left eye. Ophthalmologic examination showed her visual acuity was decreased from 1.0 in both eyes to 0.9/0.7 (decimal). Optical coherence tomography (OCT) revealed typical lesions consistent with CSCR in both eyes (). Fundus fluorescein angiography (FFA) showed focal areas of leakage from the RPE into the subretinal space in both eyes (). The patient was taking 40 mg/day methylprednisolone, 100 mg/day azathioprine, and 40 mg/day pantoprazole as treatment for Behçet’s disease. She also described panic attack-like symptoms and was referred to the psychiatry department to begin antidepressant therapy. During this time a gradual reduction of her oral steroid dose was planned and antidepressant therapy was initiated. On day 20 of the tapering schedule, her dose of oral methylprednisolone was 32 mg/day and her visual acuity had returned to 1.0 despite persistent bilateral CSCR findings in OCT. On day 90 of the tapering schedule, oral methylprednisolone dose was 16 mg/day, visual acuity remained 1.0 bilaterally, and OCT showed the subfoveal fluid had complete resolved in the right eye but improved only partially in the left eye. Treatment with nepafenac drops 4 times daily was started in the left eye. At 6 months, oral steroid was maintained at 8 mg/day; there were no remaining signs of bilateral serous detachment () and the patient had full vision in both eyes. No recurrence has been observed during 14 months of follow-up. |
pmc-6416479-2 | A 37-year-old man with Behçet’s disease presented to our clinic with complaints of decreased vision in his left eye. Visual acuity was 1.0/0.6 and anterior segment examination was normal. No pathology was detected on fundus examination in the right eye, while macular OCT showed a typical lesion consistent with CSCR in the left eye (). Increasing hyperfluorescence with smoke-stack pattern was observed in the left macula on FFA (). While taking a detailed history, the patient stated he had been prescribed oral methylprednisolone 40 mg/day in the rheumatology department due to arthritis of the left ankle secondary to Behçet’s disease. The patient was referred to the rheumatology department for steroid dose reduction and the psychiatry department due to a stressed psychological state. He was started on oral diazomide 500 mg twice daily and nepafenac drops 4 times daily in the left eye. On day 40 of the steroid tapering schedule, oral methylprednisolone dose was 12 mg/day, visual acuity was improved to 0.7, and OCT showed a significant reduction in subfoveal fluid in the left eye. At 4 months, the methylprednisolone dose was 6 mg/day, his vision was 0.8, and the subfoveal fluid was completely resorbed (). The patient was followed for 16 months. In his final examination, ocular findings were normal with no signs of recurrence. |
pmc-6416481-1 | A 65-year-old man was referred by the otolaryngology department to our outpatient clinic due to sudden swelling and mild pain around the right eye. On examination, the patient exhibited what appeared to be severe edema encompassing the upper and lower lids of the right eye (). Crepitus was clearly audible on palpation of the eyelids. An attempt to open the lids was unsuccessful. Visual acuity and intraocular pressure could not be measured due to extreme lid swelling. The patient reported that he had undergone transnasal endoscopic nasal polypectomy through the right nostril 2 days earlier. He said he had been instructed not to cough or strain after the endoscopic nasal surgery and the sudden swelling occurred immediately after severe coughing and straining. We suspected that the sinus wall was weakened due to his endoscopic surgery and the increased pressure caused by straining had forced air in the nose into the periorbital area. B-mode ultrasonography showed trapped air in the periorbital area ().
Considering the patient’s anxiety, the severity of periorbital emphysema, inability to conduct a full ophthalmologic examination, and the risk of complications such as compressive optic neuropathy, the patient was re-evaluated for a surgical intervention. After consultation, it was decided to evacuate the air using a 21 gauge needle inserted in the subcutaneous tissue of the upper and lower lids. In sterile conditions, the eye area was cleaned with 10% povidone-iodine. A 21-gauge needle was passed through the skin and subcutaneous tissue of the upper and lower lids parallel to the tarsus about 1.5 cm from the lid margin. Evacuation of subcutaneous air was evident from a significant reduction in lid swelling during the procedure (). The patient’s vital signs were stable and the procedure was concluded. He was discharged with systemic antibiotics (cefuroxime axetil 500 mg twice daily) and moxifloxacin drops four times daily.
On follow-up examination the next day, the periorbital emphysema was substantially reduced and the globe could be examined (, ). He had full visual acuity in both eyes; intraocular pressure was 17 mmHg in the right eye and 16 mmHg in the left eye. Dilated fundus examination was normal. No restriction in eye movements was observed. Follow-up examinations at 1 week and 1 month revealed no pathological findings. |
pmc-6416482-1 | A healthy 21-year-old man was admitted to our hospital after being referred from another medical institution because of worsening left eye (LE) uveitis. He was treated 3 weeks earlier with oral acyclovir and topical steroids because of suspected LE herpetic anterior uveitis as serological tests revealed positive immunoglobulin M to herpes simplex virus-1. Initially he responded to treatment but 2 weeks later, his vision declined from 6/9 to counting fingers (CF), resulting in his referral to our center.
The patient denied any relevant past medical history. However, he mentioned that a month earlier he was examined for LE discomfort and diagnosed with allergic conjunctivitis following minor blunt trauma from a tree branch.
On examination, visual acuity (VA) was 6/6 in the right eye (RE) and CF at 1 meter in the LE. Intraocular pressure was 14 mmHg in both eyes. RE anterior and posterior segments were normal. There was a remarkable LE anterior chamber reaction with dust-like keratic precipitates, cells (4+), flare (2+), and some iris nodules. Fundus assessment was not possible because of dense vitritis. B-scan and high-frequency ultrasound did not reveal any intraocular foreign body. Aqueous tap was performed and the sample was sent for culture and polymerase chain reaction analysis. It was negative for all herpes viruses and for 16S rDNA. Meanwhile, with oral steroids and valacyclovir, the patient showed signs of improvement and LE VA improved to 6/15. Despite the remarkable improvement, it was insufficient as the patient continued to have marked anterior uveitis and vitritis. A white shadow was noted in the peripheral temporal retina of the LE which again could not be assessed properly due to vitreous opacities (). The patient eventually underwent pars plana vitrectomy and laser retinopexy was performed around the white peripheral temporal lesion, which was later believed to be the site of penetrating injury by a thorn on the tree branch from the previous trauma described by the patient. Gram staining of the undiluted vitreous samples showed gram-positive cocci. 16S rDNA was positive for S. epidermidis, and blood agar and chocolate agar cultures confirmed the result with moderate growth.
The patient was treated with intravitreal antibiotics (vancomycin 1 mg/0.1 mL and ceftazidime 2.25 mg/0.1 mL) and intravitreal dexamethasone 400 mcg/0.1 mL as well as intravenous (IV) vancomycin (1 g twice/day), and oral prednisone was continued.
After 48 hours of treatment, the patient showed remarkable clinical improvement. LE VA was 6/12. There was no need to administer more intravitreal antibiotics.
After 5 days of IV antibiotic treatment, the patient was discharged on topical and a tapering regimen of oral steroids.
After a follow-up period of 3 months, LE VA was 6/6 with complete resolution of the infectious process (). |
pmc-6416483-1 | A 24-year-old male active military personnel presented with complaints of profound diminution of vision in his right (dominant) eye of 5 days duration. He had been diagnosed with dengue hemorrhagic fever about 20 days earlier, treated with supportive therapy only without any blood/blood component infusion, and discharged from hospital 10 days earlier. During hospitalization, his lowest platelet count was 40,000 per microliter of blood without any ocular symptoms. On initial examination, his best corrected visual acuity Best-corrected distance visual acuity was 20/400 in right eye and 20/20 in left eye. Anterior segment examination in both eyes was normal. Fundus examination in the right eye revealed premacular hemorrhage about 2 disc diameters (DD) in size occupying the central macula and obscuring underlying details due to a splinter hemorrhage at the superonasal aspect of the disc (). There was no evidence of any vasculitis or venous occlusion. Optical coherence tomography (SD-OCT) revealed hemorrhage to be occupying the sub-ILM space, obscuring deeper foveal details (). Fundus fluorescein angiography showed blocked fluorescence due to blood in the sub-ILM space, with no evidence of vasculitis or foveolitis. His present systemic work-up was normal and platelet counts revealed mild thrombocytopenia (120,000 per microliter of blood).
The patient was informed and counseled about different treatment approaches including “wait-and-watch” for spontaneous recovery, pars plana vitrectomy, and a novel technique of pneumatic displacement with intraocular gas tamponade. The patient did not consent to active surgical management by pars plana vitrectomy. Being in active military service with dominant eye involvement, rapid recovery was warranted, so he was treated with 0.3 ml of C3F8 (100%) injected intravitreally in aseptic conditions followed by paracentesis in the operating theatre with prone positioning (). He responded well to treatment with partial displacement and absorption of sub-ILM blood by day 3 post-C3F8 injection () and complete clearing of sub-ILM blood by the end of the first week (). OCT showed normal foveal contour with remnants of ILM () seen over the macula with recovery of vision to 20/20 without any metamorphopsia or scotoma. |
pmc-6416668-1 | A 44-year-old male patient was admitted to our institution with a past medical history remarkable for CKD as a result of congenital left renal hypoplasia and adaptive focal segmental glomerulosclerosis due to long-term obesity. The patient started peritoneal dialysis at the age of 26. After 3 years, he underwent a cadaveric kidney transplant. During the postoperatory period, slow graft function was seen, which recovered satisfactorily over time. Immunosuppressive therapy was initiated with cyclosporine, mycophenolate mophetil and prednisolone. Nevertheless, multiple celular rejection episodes lead to chronic graft glomerulopathy and hemodialysis requirement after 8 years. At the time, the patient’s BMI was 30 kg/m2. Progressively, weight gain increased BMI to 42 kg/m2 with difficult-to-control hypertension and severe sleep apnea. At that point, the patient’s waist circumference was 120 cm and fasting glucose was 100 mg/dL. As for the lipid panel, total cholesterol was 145.8 mg/dL, high-density cholesterol was 33 mg/dL and triglycerides were 117.1 mg/dL. Uric acid was 7.9 mg/dL and albumin was 3.9 g/L. Regarding dialysis adequacy parameters: single-pool Kt/V was 1.47, body fat measured through bioelectrical impedance (BIA) was 45%, phosphorus was difficult to control, and oscillated between 5 and 8 mg/dL.
Behavioral, nutritional and pharmacologic measures were not sufficient for an adequate weight control, thus in order to allow access to a second kidney transplant, the patient’s case was brought to consideration by a multidisciplinary board where a surgical approach was decided. A gastric sleeve was performed. There were no early or late post-operatory complications after a 12-month follow-up period.
On the initial dialysis sessions after surgery, due to rapid weight loss, the patient displayed cramps, dehydration and hypotension, which required several adjustments of dry weight (DW) by BIA, almost daily at first and weekly thereafter in order to better define the optimal ultrafiltration rate and symptom resolution.
The patient achieved a BMI of 28.6 kg/m2, adequate blood pressure control and reduced severity of sleep apnea. He then met all required criteria, and was registered in the kidney transplant waitlist. |
pmc-6416763-1 | A 62-year-old man was diagnosed with lung adenocarcinoma and had right lower lobectomy (pT2bN2M0 stage III A, PD-L1 tumor proportion score <1%; Figure A). Thereafter he received postoperative adjuvant therapy of cisplatin and vinorelbine. After 5 months, he was diagnosed with postoperative recurrence of lung adenocarcinoma with multiple metastasis in both lungs. He received platinum-based chemotherapy as the first-line chemotherapy regimen and nivolumab was selected as the third-line regimen. The patient had no history of asthma, atopy, and drug allergy. The patient had not begun taking any new medications and had no history of cigarette smoking.
After three cycles of nivolumab treatment (3 mg/kg every 2 weeks), he presented with cough and chest computed tomography revealed pulmonary infiltrates in both lungs (Figure B–D). Levofloxacin was administered for 12 days; however, antibiotics did not improve his symptom or radiological findings. Thus, bronchoalveolar lavage was performed from the right upper lobe. Bronchoalveolar lavage cellular analysis showed a significant increase of total cell count of 12.1 × 105 mL, of which 27.1% were eosinophils (normal upper limit, 1.3%), 8.3% were lymphocytes (normal upper limit, 11%). No pathogenic bacterial organism was cultured. The patient was diagnosed with AEP based on the diagnostic criteria for AEP. Nivolumab was suspended and the patient was started on oral prednisolone (0.5 mg/kg/day, 30 mg/day), which is tapered 5 mg weekly. His symptoms and radiological findings had rapidly improved (Figure B–D), which is consistent with AEP., , No sign of lung cancer worsening has been observed since the initiation of treatment with nivolumab or prednisolone. |
pmc-6416866-1 | A 24 years old female delivered a female baby at 38 weeks through cesarean. The baby’s appearance, pulse, grimace, activity, and respiration (APGAR) score at delivery, and at 5 min was normal. Postpartum, a pulmonary systolic murmur was detected during a routine clinical exam. An echocardiogram was performed and showed the presence of a tumor in the right ventricle. The baby was kept under supervision. Her hemodynamic parameters remained stable and presented no symptoms, hence, she was discharged. Nine days later, while the baby was being breastfed, she had a presyncopal episode, shortness of breath and grunting. All of which suddenly resolved after a few minutes. She was brought to the emergency room where she had a second episode.
During examination, her oxygen saturation was 24% in room air. She was resuscitated with mask and balloon until she stabilized and was subsequently hospitalized. The intensivist decided to do a cardiac and cerebral magnetic resonance imaging (MRI) when a third presyncopal episode occurred on the table. She was resuscitated for a second time with success. An echocardiogram was performed and for the first time, it showed cyclic complete obstruction of the right ventricular outflow tract. The recorded echocardiogram is shown in Additional file : Video S1.
Furthermore, the MRI showed a mobile and large mass in the right ventricle which measured 13 mm × 9 mm. The mass was attached to the baso septum of the right ventricle and moved completely to the pulmonary trunk during systole. Pulmonary artery flow measurements showed the presence of pulmonary insufficiency. We observed a patent foramen oval (PFO) and a patent ductus arteriosus (PDA), both of which had right to left shunts. In terms of the global kinetics of the left ventricle, it was homogeneous compared to a slight dilation in the right ventricle. Because of the previous clinical description, and more predominantly the repeated syncopal episodes that only appeared after 9 days postpartum, urgent surgery was indicated.
The surgical procedure was performed under standard cardiopulmonary bypass at systemic hypothermia. A right atriotomy was performed parallel to the atrioventricular groove which exposed the tricuspid valve. Through the valve, we exposed a right ventricular large mass attached to the septum. The mass was removed by excision of the foot like structure in the right ventricular outflow tract septum. The PFO and the PDA were surgically closed.
The macroscopic exam revealed that the tumor resected was a nodular mass of white discoloration which measured 1.5 cm of larger diameter for a total height of 1.7 cm. The body showed two small protuberances measuring 0 .1cm larger diameter (Fig. ). Histopathology revealed fragments of a pseudo nodular structure composed of fibrous stroma axis which contained numerous glandular structures. An epithelial coating of variable histology was observed. Some mucosecretant glands suggested a digestive epithelium. Others had a cylindrical epithelium mucocilia, others a transitional or even squamous epithelium. There were no immature structures. The findings were consistent with a mature teratoma. (Fig. ). |
pmc-6416932-1 | In 2007, an otherwise healthy 75-year-old woman was admitted with progressive dysexecutive and behavioral syndrome, drowsiness, dysarthria and cerebellar signs, starting eight months earlier after severe bronchitis (Additional file ). Neurologic examination revealed a pseudobulbar syndrome resulting in dysarthria and mild dysphagia, gait instability, bradydiadochokinesia, dysmetric finger-to-nose-test and saccadic eye movements. No fasciculations or tongue fibrillations occurred, eutrophic muscles had normal tone, pyramidal signs were negative, masseter reflex and motor-evoked potentials (MEPs) normal, EEG without epileptiform discharges, the patient had no fever or epileptic seizures. Electromyography showed generalized acute denervation and chronic neurogenic changes, nerve conduction studies showed motor-dominant neuropathy. MRI showed global atrophy and multiple white matter lesions (Fig. ). Body CT with contrast and immunofixation was unremarkable. Cerebrospinal fluid (CSF) had elevated protein (90.1 mg/dl), normal cell count (3/μl) and no antibodies against CV2, Hu, Yo, Ri, Amphiphysin or acetylcholine receptors.
Five months later, pseudobulbar symptoms and cerebellar ataxia worsened. Fasciculations appeared at the trunk and all extremities showing an asymmetric but generalized spreading pattern. Bulbar symptoms, paresis and atrophy of limbs, shoulder girdle and hand muscles evolved. There was an increased muscle tone without hyperreflexia. MEPs remained physiological. The diagnosis of ALS was made (probable ALS according to revised El Escorial criteria) [] and treatment with riluzole started. The patient had no family history of ALS. After three months, the patient received percutaneous endoscopic gastrostomy and non-invasive ventilatory support. She died 18 months after symptom onset.
Given some early symptoms not characteristic for ALS such as cerebellar signs, archived CSF and serum were tested for neuronal surface autoantibodies and revealed high titers (1:3200 in serum, 1:320 in CSF; cell-based assay, Euroimmun, Lübeck, Germany) of GABABR IgG antibodies, while approximately 30 further antibodies (including LGI1, Caspr2, GABAA and AMPA receptor) were negative. |
pmc-6416959-1 | A 72 year old female was seen for a regularly scheduled appointment at the renal transplant clinic of our hospital. Ten months previously she had received a cadaveric renal transplant (right lower flank) for chronic renal failure due to focal segmental glomerulosclerosis. Her immunosuppressive medications were prednisone, mycophenolate and tacrolimus. Six weeks prior to this visit she had been treated with valganciclovir for cytomegalovirus viremia. Now, she stated that she had recently begun to experience mild left lower quadrant abdominal pain and that vaginal bleeding had occurred the previous week. Fever was absent. Her bowel movements were unchanged and she did not report blood in her stool.
Her past medical history included iron deficiency anemia, arterial hypertension, diabetes type II, and hysterectomy with right ovariectomy for benign disease.
At physical examination the patient was afebrile with a mildly distended abdomen that was supple without tenderness or guarding. There was no palpable mass. The white blood cell count was 5.6 × 109/L (reference: 4.5–10.8 × 109/L). The hemoglobin was 94 g/L (reference: 123–157 g/L). Renal function was normal. She was admitted to hospital for further investigations.
Abdomino-pelvic computerized tomography (CT) scanning without intravenous iodine contrast was performed (Fig. ). Rectal contrast was used to distend the colon. Two non-stenotic ill-defined moderately dense masses were found in the mesocolon: the first was adjacent to the descending colon, and the second involved the sigmoid colon As the second mass was in a diverticular bowel segment and contained few extraluminal air bubbles, a diagnosis of sub-acute perforated diverticulitis with two phlegmons was proposed. However, the findings were acknowledged as being somewhat atypical for this diagnosis because the proximal mass was completely separate from the distal one and contained no air. The differential diagnosis included a perforated sigmoid neoplasm with a metastatic implant next to the descending mesocolon and post-transplant lymphoproliferative disease. In light of these findings, a planned colonoscopy was canceled.
Given the presumptive diagnosis of perforated diverticular disease, empirical antibiotic therapy was begun and three days later laparotomy was performed. At surgery, two masses involving the descending colon and the sigmoid were found, the latter with perforation. The sigmoid lesion was resected and a terminal colostomy performed. The descending colon lesion was treated by creation of a cutaneous fistula and placement of a Jackson-Pratt drain.
Macroscopic examination (Fig. ) of the 26 cm long sigmoid specimen demonstrated a brownish serosa and a firm mesentery containing a friable, ill-defined mass 4,5 cm in diameter Multiple diverticula were also seen, without accompanying acute diverticulitis or abscess. There was no evidence of neoplasia.
Microscopic examination (Fig. ) showed a massive infiltrate of large non-atypical macrophages with abundant granular cytoplasm. The infiltrate involved the entire thickness of the bowel, causing mucosal ulceration and bowel wall perforation. Calculospherules (MG bodies) were readily identified in the cytoplasm. The cells were positive with the immunohistochemical markers leukocyte common antigen and CD68, confirming their histiocytic nature. The findings were diagnostic of malakoplakia.
The immediate postoperative course was uneventful. She was discharged home in good condition on sulfamethoxazole-trimethoprim 800/160 mg for twelve weeks.
Nine months later, no longer receiving antibiotic therapy, the patient reported lower left quadrant discomfort and episodes of nausea. She had also noted a vulvar nodule which subsequent biopsy, as well as that of a vaginal mass discovered by pelvic examination, showed to be malakoplakia.
The following month she was admitted to hospital because of steadily worsening anal and pelvic pain, anorexia, weight loss, malnutrition, and an inability to walk unaided. She was afebrile. The colostomy site was unremarkable; the cutaneous fistula had a malodorous greenish discharge. There was no evidence of peritonitis. Renal function was normal. A CT scan showed para-rectal and pelvic abdominal masses with cutaneous and intestinal fistulas. Treatment with tazobactam-piperacillin was begun and sulfamethoxazole-trimethoprim 800/160 mg was reinstated, with subsequent slow clinical improvement. The patient was discharged home after several weeks.
Subsequent abdominal CT scans have shown persistence of the lesions. She is currently being closely followed without current antibiotic treatment. |
pmc-6416971-1 | A 35-year-old Indian female, para 1 + 0 gravida 2, was admitted with severe preeclampsia at 31 weeks of gestation after complaints of anasarca for 1 week. She reported normal fetal movements with no epigastric discomfort, headaches or visual blurring. She had a blood pressure of 190/110 mmHg with a regular pulse rate at 70 beats/minute palpable on all extremities. She was afebrile at 36.7°C, had a respiratory rate of 18 breaths per minute and peripheral oxygen saturation of 99% on room air.
Six years prior, she had had severe preeclampsia and a preterm delivery by caesarean section at 29 weeks of gestation. The baby died of infant respiratory distress syndrome shortly after birth causing the patient significant psychological distress requiring counselling. This made her defer the possibility of a pregnancy for years sighting psychological trauma.
This pregnancy, she presented in the first trimester for antenatal care. Her blood pressure was 110/70 mmHg and antenatal profile was unremarkable: Hemoglobin 13.0 g/dl; Hepatitis-B surface Antigen, H.I.V. and Venereal Disease Research Laboratory (VDRL) were negative. Her blood group was O with positive Rhesus factor. The dating scan confirmed a 12-week-old gestation and she was placed on aspirin 75 mg throughout her pregnancy. Subsequent antenatal visits at 16, 20, 24, 28 and 30 weeks were uneventful with normal blood pressures. An anomaly obstetric scan at 20 weeks gestation showed no fetal anomalies with subsequent growth scans at 24 and 28 weeks showing normal growth with normal umbilical and middle cerebral artery doppler flows.
On admission, she had macro albuminuria with elevated urine albumin creatinine ratio of 422 mg/mmol. Her hemoglobin was 12.1 g/dl and the platelet count was 194,000/ml. The renal and liver functions were normal.
She was started on intravenous (IV) magnesium sulphate infusion as per the Zuspan regime [] (4 g slow IV bolus followed by 1 g/hour for 24 h) for maternal seizure prophylaxis and fetal neuro-protection []. She received multiple push doses of IV hydralazine for blood pressure control and was eventually placed on hydralazine infusion at 1 mg/hour. In addition, she received oral nifedipine and oral alpha methyldopa. Two doses of betamethasone 12 mg were administered intramuscularly 24 h apart for fetal lung maturation. She also received low molecular weight heparin (LMWH) for thromboprophylaxis and the total fluid intake was maintained at 80 ml/hr. to minimize the risk of pulmonary oedema.
Thirty hours post-admission, she developed worsening orthopnea with severe sub sternal left sided chest pain radiating to the left axilla without symptoms of diaphoresis, nausea or vomiting. Her blood pressure was 138/82 mmHg, pulse rate of 64 beats per minute, and peripheral oxygen saturation via pulse oximetry was 99% on room air. A chest x-ray revealed no features of pulmonary edema while an electrocardiogram (ECG) revealed a sinus rhythm with ST elevation in the anteroseptal leads (V1–4), Q waves in the septal leads (V1–2) and peaked T waves in V2–4 indicating an acute anteroseptal ST-Elevation Myocardial Infarction (STEMI) (Fig. ). A transthoracic echocardiogram showed wall motion abnormalities with interventricular septum and anterior wall hypokinesia. The left ventricle (LV) was dilated with an ejection fraction of 48% (Fig. ). The right ventricular size was normal whereas the peak pulmonary arterial pressure was elevated at 50 mm/Hg. Lower extremity dopplers revealed no venous thrombus while an assay of cardiac enzymes revealed elevated Troponin I levels of 0.51 ng/ml (normal ≤0.04 ng/ml) and Creatinine Kinase -MB (CK-MB) levels of 54 IU/l (reference range 5–25 IU/l).
Fetal assessment ultrasound done on day 2 of admission revealed an abnormal cerebroplacental ratio (CPR) of 0.57 necessitating delivery by caesarean section. The infant weighed 1 .5kg with Apgar score of 9 at 1 min and 10 at 5 min. Left cardiac catheterization was subsequently done on day 3, approximately 18 h after the last dose of LMWH and showed left ventricular apical ballooning with no evidence of atherosclerosis in the coronaries.
The LMWH thromboprophylaxis (0 .5mg/kg once daily) was restarted 12 h post-delivery for one week. The blood pressure was controlled with amlodipine (10 mg once daily). Postpartum, she remained normotensive and anti-hypertensive medication was stopped after 6 weeks. Cardiac injury biomarkers normalized by the 10th postpartum day. The ECG done at 6 weeks postpartum showed frontal QRS complex of + 100 degrees with QS complexes from V1 to V3 consistent with recent antero-septal myocardial infarction (Fig. ) while that done 6 weeks later showed no significant abnormalities (Fig. ). The echocardiogram at 3 months post-delivery revealed normal cardiac chambers with no regional wall motion abnormalities with a left ventricle ejection fraction of 65%. |
pmc-6417025-1 | A previously healthy 36 year old female of Thai descent presented to the emergency department with a 4 day history of worsening dyspnea and a nonproductive cough. She also reported fevers, chills, and myalgias, for which she had taken both acetaminophen and ibuprofen without relief. The patient had moved to Hawaii in 2013, but had lived until then in her native Thailand. She had not traveled since then, had no sick contacts, no history of tuberculosis or hematologic disease, no unusual occupational exposures, and was not immunocompromised. She was in a monogamous sexual relationship.
Upon initial presentation, the patient maintained oxygen saturation over 90% on room air but was tachypneic to > 50 breaths per minute and tachycardic, with signs of accessory muscle use and increased work of breathing. Chest radiograph performed in the emergency department revealed increased interstitial markings and alveolar airspace disease. Non-contrast computed tomography (CT) of the chest demonstrated diffuse smooth interlobular septal thickening, with superimposed areas of ground glass attenuation and peribronchial airspace consolidation (Fig. ). These nonspecific but significant findings were concerning for acute respiratory distress syndrome (ARDS) and other noncardiogenic causes of pulmonary edema, PAP, atypical infectious processes such as Pneumocystis jirovecii pneumonia, alveolar hemorrhage, or drug-induced lung disease.
Lab abnormalities included microcytic anemia, elevated lactate (2.9 mmol/L, with subsequent 5 h trend to 3.9 mmol/L), mildly elevated procalcitonin (1.91 ng/mL), and lactate dehydrogenase (LDH) of 286 u/L. HIV – 1 + 2 antigen + antibody assay was negative. After volume administration and initial doses of azithromycin and ceftriaxone, the patient was admitted to the intensive care unit. An arterial blood gas drawn shortly after her arrival showed a pH of 7.41, pCO2 24, and pO2 63 on FiO2 0.40. Oxygenation worsened despite empiric antimicrobial therapy, requiring intubation and mechanical ventilation for progressive hypoxic respiratory failure on the first hospital day. Diagnostic bronchoscopy with bronchoalveolar lavage (BAL) was performed; cell count and differential of lavage fluid showed granular amorphous debris with few macrophages and neutrophils. Wright-Giemsa and acid-fast stains of the lavage material were not consistent with Pneumocystis or tuberculous pneumonia, respectively; subsequent Periodic Acid-Schiff staining of the amorphous granular material was positive, consistent with PAP (Fig. ). No findings concerning for hematologic malignancy were seen on peripheral blood smear, lowering suspicion for underlying malignancy. Anti-GM-CSF autoantibody assay was sent and eventually returned positive with a concentration of 7.9mcg/mL, consistent with autoimmune PAP; however, this result was not available for 21 days and thus not useful for clinical decision-making.
WLL was considered, as this is the treatment of choice in symptomatic PAP [, , ]. However, oxygenation transiently worsens during WLL; when this occurs, salvage methods such as ECMO are typically employed []. This patient’s oxygenation was tenuous and ECMO is unavailable in this geographically remote location, so an alternative treatment regimen was devised. The patient was initially treated empirically with aerosolized GM-CSF (dose 250mcg), administered in-line with the endotracheal tube circuit, for two days while awaiting BAL results, but experienced no clinical improvement. Following confirmation of the PAP diagnosis but before anti-GM-CSF antibody results were available, subcutaneous (SQ) GM-CSF (also at 250mcg) was initiated []. This yielded a decrease in LDH measurements and improvement in oxygenation such that the patient was successfully extubated on the fourth day of SQ GM-CSF therapy [–]. However, she continued to require supplemental oxygen at 4 l per minute at rest and remained profoundly dyspneic. In the days following extubation, her LDH also began to rise, from 381 u/L on her first day of SQ GM-CSF to 536 u/L five days later.
Following discussions with colleagues in a large academic center, the patient was offered and elected to undergo sequential lobar lavage of the anatomic lobes most severely affected on CT in order to expedite clearance of the alveolar space. During each treatment session, the patient was intubated under general (total intravenous) anesthesia without neuromuscular blockade. An Olympus P-180 videobronchoscope was introduced through the endotracheal tube and wedged into each compatible segmental or subsegmental airway of the lobe being treated. Each anatomic region was lavaged with warmed normal saline solution in increments of 50-60 mL until the return was clear (Fig. ). The right upper lobe (most radiographically abnormal) was lavaged first and required 1500 mL to return partially-cleared. One week later, the left upper lobe and lingula were lavaged with 4000 mL; an additional week later, segments of the right middle and lower lobes were lavaged with 3500 mL of saline solution. Over the course of three sessions, lavage return was consistently > 85% of instilled fluid.
After each lobar lavage, the patient experienced stepwise improvement in her symptoms, oxygen requirement, and tachypnea. LDH also decreased immediately following her right upper lobe lavage, from 536 u/L to 404 u/L. Repeat imaging showed improvement not only in the areas lavaged, but also in the contralateral lung. The day after her second lobar lavage, she had no oxygen requirement at rest, and denied any shortness of breath even with moderate exertion, although she required 3 l by nasal cannula to maintain saturation > 90% when walking. LDH continued to decrease, to 253 u/L. The patient was discharged shortly thereafter with home oxygen for exertion, and completed a total four week course of SQ GM-CSF. The third lavage was performed on an outpatient basis.
One month after discharge, the patient no longer required supplemental oxygen. Nine months after discharge, surveillance imaging of the lungs showed great improvement in previously visualized ground-glass opacities, with only small areas of residual disease. The patient has not required repeat therapy with either GM-CSF or lavage, and at the time of writing is asymptomatic, with preserved FEV1, FVC, and DLCO. |
pmc-6417066-1 | An 82-year-old Caucasian woman presented to a headache specialty clinic with a 2.5 year history of daily persistent left-sided headaches. The age of headache onset was 79 years. She had a previous history of migraine without aura, also left sided, which would occur approximately once per month. Her headache may have started as a daily persistent headache from onset or become daily over a short period of time. She could not exactly define the temporal profile of onset. The pain location was entire left hemicranium from periorbit/retro-orbit to occipitonuchal region with the forehead and temple being the most significant area for pain. Her average daily pain intensity was 8/10 on a visual analog scale (VAS) and she would also experience exacerbations to 10/10 several times per week and these peak pain periods would last from hours to 1 full day. During the peaks she would develop migrainous (nausea, vomiting, photophobia, and phonophobia) and cranial autonomic symptoms (eyelid ptosis, lacrimation) as well as agitation. Her prior migraines never included any cranial autonomic issues. Very early on in the course of the headaches she developed a left-sided ptosis during a period of pain exacerbation that never resolved. The ptosis was present for at least 2 years at the time of her consultation.
Her past medical history was marked by several concussions during her teens and several whiplash injuries as an adult with resultant neck pain. She had atrial fibrillation and was on chronic anticoagulation therapy. She had hyperlipidemia and ulcerative colitis. Her past surgical history was marked by a cervical spine fusion from C3–7. She was a chronic tobacco smoker × 50 years. Her family history was negative including no headache disorders.
Prior to coming for consultation she had tried and failed various preventive medications including gabapentin (200 mg), valproic acid (1250 mg), amitriptyline (50 mg), nortriptyline (50 mg), propranolol (80 mg), daily oxycodone (10–15 mg per day), and onabotulinum toxin A injections. At the time of presentation she was on no headache preventive medication. She was using daily acetaminophen/aspirin/caffeine tablets up to eight per day as well as injectable sumatriptan up to 4 days per week. Her other daily non-headache-related medications included: apixaban (5 mg twice a day) and darifenacin hydrobromide (15 mg/day).
On examination she was afebrile, normotensive (118/69 mmHg), with a pulse rate of 60 beats per minute (bpm). A general examination was non-focal. Her neurologic/headache examination was abnormal with a positive left eyelid ptosis without a miotic pupil. There was no evidence of blepharospasm or facial spasm noted on examination to mimic the ptosis. She had tenderness to palpation over the left greater occipital nerve, left atlantoaxial joint, and the left C2–3 facet. No tenderness was noted over the left supraorbital or trochlear regions. No temporal allodynia was identified and she had positive temporal artery pulses.
Her history was very suggestive of hemicrania continua (HC) but she could not be prescribed orally administered indomethacin as she was on chronic anticoagulation therapy. HC is a primary headache syndrome marked by persistent one-sided head pain, usually of mild intensity, with pain exacerbation periods consisting of severe headache that lasts from hours to days with associated migrainous and cranial autonomic symptoms. It is one of the indomethacin-sensitive headache disorders. An injectable indomethacin (indo-test) could have been utilized to verify the diagnosis but it is not available in the USA. A presumed diagnosis of probable HC was made as she met all International Classification of Headache Disorders (ICHD-3) criteria except for indomethacin responsiveness []. Based on her cervical examination and past neck traumas with cervical fusion, a secondary form of HC from a cervicogenic generator (head pain originating in the upper cervical spine, most likely from activation of the trigeminocervical complex) was also suggested.
Laboratory testing included a normal erythrocyte sedimentation rate and C-reactive protein (CRP). Neuroimaging including a brain magnetic resonance imaging (MRI) and magnetic resonance (MR) angiography of the intracranial vessels identified a 3 mm left ophthalmic artery aneurysm, but even with surgical repair (coiling) the headaches did not improve. No other secondary issues were noted on imaging including ruling out a carotid dissection with conventional angiography. Pituitary hormones were also tested (prolactin, growth hormone, insulin-like growth factor 1) and were within normal range.
At her headache consultation she was given a high volume suboccipital nerve block (9 cc of 1% lidocaine and 1 cc of triamcinolone 40 mg/ml) leading to complete pain freedom, but only for 2 days. During this time her ptosis did improve or resolve transiently until her pain returned. As the authors previously reported on alleviation of HC with specific nerve injection procedures, our patient underwent a sphenopalatine block with moderate success []. She had no improvement with supraorbital/supratrochlear blocks. An atlantoaxial injection also showed a negative response. She had a positive response to a left C2 dorsal root ganglia (DRG) injection, but a confirmatory procedure did not help. After a C2–3 diagnostic facet injection, not only did she become pain free but her ptosis completely resolved. A confirmatory injection at the same location alleviated her head pain again, thus she underwent a radiofrequency facet neurotomy (a procedure that supplies heat to spinal-based nerves to suppress pain transmission) with complete alleviation of head pain and complete resolution of her ptosis (Fig. a, b). After 3.5 months her headache and ptosis returned so a repeat radiofrequency procedure was completed with subsequent resolution of head pain and ptosis through an additional 3-month follow-up. |
pmc-6417066-2 | A 21-year-old Caucasian woman presented for consultation with a 1-year history of headaches. She had no prior history of head pain when she began to develop right-sided only headaches which would last from 2 to 3 days in duration. The headaches were located in a retro-orbital, periorbital, and temporal distribution. The pain was moderate to severe in intensity and would escalate to maximum intensity over approximately 1 hour. Initially the headaches occurred once per week but escalated to two to three times per week. Associated symptoms included migrainous (nausea and rare vomiting, photophobia, phonophobia, and osmophobia) and cranial autonomic features (right eyelid ptosis and miosis, conjunctival injection, lacrimation, nasal congestion, and orbital edema). Her cranial autonomic symptoms would start several hours before headache onset, last the entire duration of the headache and would then outlast the headache for several hours. Six months into her headache history she developed a right-sided full Horner’s syndrome with a fixed ptosis and miosis during a severe headache that never ceased, even between headache attacks.
Her past medical history was marked by a diagnosis of Turner’s syndrome and she also had major depression controlled on medication. She did not smoke tobacco. She was currently a student. Her family history was only significant for migraine in her sister whose headaches lacked any cranial autonomic symptoms. In regard to medications she was taking acetaminophen abortively but had tried no headache preventive medications prior to consultation. She was on sertraline 75 mg for major depression but that was prescribed long before she developed her headaches.
On examination she was normotensive (100/60 mmHg) with normal pulse (72 bpm) and temperature. A general physical examination was normal except for short stature. A neurologic/headache examination (during a headache) demonstrated right-sided head allodynia with right temple, supraorbital, and trochlear nerve tenderness. She had a right-sided miotic pupil with a ptosis. Her neurovascular examination was normal with no supraclavicular, carotid, cranial, or orbital bruits. She also had no greater occipital nerve or upper cervical facet tenderness to palpation.
A diagnosis of long-lasting autonomic symptoms with hemicrania (LASH) was made based on the one-sided nature of the headaches, their episodic presentation, and, most importantly, the temporal profile of onset and offset of her cranial autonomic symptoms []. At present there are no ICHD-3 criteria for LASH syndrome although more patients with the disorder are being reported and the present case patient’s headache is consistent with prior documented cases [, ]. LASH is considered one of the indomethacin-responsive headaches. The lack of interictal pain in between headache attacks ruled out HC.
Neuroimaging including a brain MRI with pituitary cuts and MR angiography of head and neck vessels with dissection protocol were completed and were normal. Pituitary hormones were also tested (prolactin, growth hormone, insulin-like growth factor 1) and were within normal range.
Short-acting indomethacin was prescribed for LASH syndrome and at a dose of 150 mg per day she was basically pain free with one breakthrough headache per month. At a dose of 200 mg per day she became completely headache free. After achieving 2 months of pain freedom on indomethacin her Horner’s syndrome completely resolved. She was followed-up for another 1 year without headache or miosis/ptosis recurrence, but she was unable to come off indomethacin without her headaches returning. |
pmc-6417121-1 | We here report the case of a 21-year-old Somali woman, who was delivered by emergency caesarean section at 35 weeks of gestational age with acute dyspnea, placental abruption and gross edema due to severe PE/HELLP syndrome. This was her first pregnancy, which had been uneventful up to the 34th gestational week. Her soluble fms-like tyrosine kinase-1/placental growth factor ratio 2 days prior was 211.4 []. After surgery, the patient was immediately transferred to Intensive Care Unit because of lung edema. The laboratory analysis revealed anemia of 7.4 g/dL, thrombocytopenia of 50 G/L, a negative coombs test, increased serum lactate dehydrogenase of 690 U/L, increased bilirubin of 2.2 mg/dL, elevated aspartate transaminase of 150 U/L, elevated alanine transaminase of 140, creatinine of 1.19 mg/dL, and no detectable haptoglobin levels (< 0.09 g/L). The peripheral blood smear showed manifold schistocytes (2.8%) and the activated prothrombin time was 38.2 s (Additional file : Table S1). The PLASMIC score was high indicating a high pretest probability for TTP (> 90%) []. The patient displayed elevated systolic blood pressure between 160 and 200 mmHg despite of intensive blood pressure lowering medication including urapidil, nifedipin, furosemide, and dihydralazine. As concern for the diagnosis TTP was strong, we immediately initiated plasma exchange therapy (PEX) and glucocorticoid medication, and proceeded with further diagnostic evaluation over the next days (Fig. ). While undergoing PEX, the renal retention parameters slowly increased over the next 4 days, reaching a serum creatinine level of 2.09 mg/dL and an estimated glomerular filtration rate of 33 mL/min/1. 73m2. In parallel, fibrinogen levels decreased to a nadir of 103 mg/dL, and the thrombocyte count was still as low as 35 G/L on the 4th postoperative day. This decrease was associated with a peak of D-dimer level (26.27 mg/L) on the 6th postoperative day. The lack of early response to PEX prompted us to discuss the need for anti-complement therapy with eculizumab and to seek for other causes of the patient’s symptoms. There was no retained placental rest after delivery. In the meantime, ADAMTS13 activity had been measured and was found to be only slightly decreased to 39–63%, thus excluding the diagnosis of TTP []. Shiga-toxin, malaria parasites, and HIV antigen/antibodies were not detectable, and the hepatitis B and C serology tests were negative. The screening test for antibodies to extractable nuclear antigens (ENA), antinuclear, antiphospholipid and anticardiolipin antibodies, as well as serum C3c (0.917 g/L) and serum C4 levels (0.113 g/L) were within normal ranges. Urinary analyses revealed an albuminuria of 4.2 g/g and 40% acanthocytes, respectively. Since the patient presented with anasarca, somnolence, partial respiratory insufficiency due to lung edema and pleural effusions as well as still poorly controlled hypertension, we initiated a continuous renal replacement therapy with ultrafiltration on the 4th postoperative day, reducing the body weight of the patient from 70 kg to 49.5 kg in four days. Furthermore, PEX was daily continued. Along with the negative fluid balance of 20.5 L, the patient drastically improved both clinically and with the laboratory parameters. In parallel, kidney biopsy was performed on the 6th postoperative day, which revealed a residual thrombotic microangiopathy and signs of malignant hypertension such as doubling of the basal membrane as well as mild tubular necrosis. Immune complex nephritis, e.g. lupus nephritis, was excluded (Fig. ). Therefore, we stopped PEX on the 6th day postpartum, after having reached a thrombocyte threshold of >100G/L. Dose and number of antihypertensive medication were drastically decreased. In a serum sample drawn prior to PEX, we found no evidence of complement activation using an in-vitro assay for complement deposition on non-activated endothelial cells (Fig. ). C3c and C5b-9 complement deposition assays were performed as described previously by Noris et al. [] Moreover, there were neither anti-complement factor H antibodies as determined by ELISA, nor mutations of atypical hemolytic uremic syndrome-related genes ADAMTS13, C3, CFB, CFB, CFH, CFHR1, CFHR2, CFHR3, CFHR4, CFHR5, CFI, DGKE, MCP/CD46, MMACHC, and THBD as detected by next-generation sequencing []. The patient completely recovered without further need for renal replacement therapy and/or PEX. Thrombocyte count increased to 240 G/L, and creatinine serum levels decreased to 0.99 mg/dL on the 12th day after delivery. The patient was discharged from Intensive Care Unit after 10 days, and dismissed from Hospital on the 16th day postpartum without any chronic impairment of glomerular filtration rate. Twenty-eight days after delivery, the glomerular filtration rate was 127.7 mL/min/1. 73m2, and serum creatinine was 0.64 mg/dL. Moreover, urinary albumin/creatinine ratio recovered from 4.2 g/g to 0.55 g/g within 4 weeks.
The patient had given birth to a daughter who had an Apgar score of 8/9/10, a body weight of 2260 g (26th percentile), and a length of 46 cm. The daughter did not have increased perinatal morbidity. |
pmc-6417165-1 | A 30-year-old woman was presented to a glaucoma clinic due to uncontrolled IOP. She had undergone bilateral LASIK 10 years previously, and had been treated with oral and topical steroids as well as albendazole for 10 months for uveitis associated with ocular toxocariasis in the left eye. Sub-Tenon injection of triamcinolone acetonide (40 mg) had also been performed 5 months previously.
At the first visit, her visual acuity was 20/200 and the IOP was 30 mmHg in the left eye measured by Goldmann applanation tonometry (GAT). Slit-lamp examination revealed Grade 1 posterior subcapsular opacity, and fundus examination showed glaucomatous change in the optic nerve head. Inflammatory cells were not detected in either the anterior or posterior chamber. Despite maximally tolerable medical treatment, the IOP subsequently increased up to 32 mmHg, and her visual acuity worsened to 20/500 with ongoing glaucomatous optic nerve damage and progression of posterior subcapsular opacity. Phacotrabeculectomy with topically applied mitomycin-C (0.04%) was then performed.
The IOP was 3 mmHg by GAT on the first postoperative day but increased up to 21 mmHg on the following day. Her visual acuity was hand movement and could not be corrected. A diffuse corneal edema with a cloudy flap interface was noted in a slit-lamp examination. At 1 week postoperatively, the IOP had decreased to 14 mmHg after the application of brimonidine (0.2%)/timolol (0.5%) twice daily, but the corneal edema did not resolve. Spectral-domain optical coherence tomography (SD-OCT) scanning revealed a diffuse and thin fluid pocket in the corneal interface region (Fig. A). After using an argon laser to perform suture-lysis of the scleral flap on the following day, the IOP decreased to 9 mmHg and the visual acuity improved to 20/150. Resolution of the interface fluid was noted by SD-OCT (Fig. B). Central corneal thicknesses were 553.5μm preoperatively and 576.6μm at 14 days postoperatively. Eight months postoperatively, the IOP was maintained at 8 mmHg without using topical IOP-lowering agents, the cornea was clear without any interface haze by detailed slit-lamp examination, and the corrected visual acuity was 20/100. |
pmc-6417181-1 | A 41-year-old Cameroonian woman was seen in a hospital for progressively worsening occipital headaches of 4 weeks’ duration, associated with phonophobia, photophobia, blurred vision, projectile vomiting, and tonic seizures. In her past history, there was an HIV infection known for 12 years and for which she had been taking (with good compliance) tenofovir-lamivudine-efavirenz-based antiretroviral therapy for the same period. No opportunistic diseases had been noted in the last 11 years. One month prior to the consultation, an upper endoscopy (Fig. ) performed to investigate persistent gastric pain led to the diagnosis of gastric Kaposi’s sarcoma. She had already received a systemic chemotherapy cycle with doxorubicin. Upon admission, her clinical status revealed an ill-looking and alert (Glasgow Scale E4V5M6) patient. Her parameters were: temperature 37.8 °C, blood pressure 176/120 mmHg, pulse rate 153 pulsations/minute, respiratory rate 25 cycles/minute, and weight 59 kg. A computed tomography (CT) scan of her brain with injection of contrast products was normal. Cerebrospinal fluid (CSF) analysis revealed: protein 1.2 g/l, glucose 0.54 g/l (concomitant glycemia 1.25 g/l), leukocyte 1/mm3, positive Indian ink stain and culture for Cryptococcus neoformans, and negative GeneXpert for acid-fast bacilli. Analysis of blood tests revealed: hemoglobin 9.6 g/dl, white blood cell count 2120/mm3, lymphocytes 848/mm3, platelets 604,000/mm3, CD4 count 353/mm3 (350–1600), C-reactive protein 48 mg/l, blood urea nitrogen 0.15 g/l, and creatinine 7 mg/l. Considering the diagnosis of neuromeningeal cryptococcosis, orally administered antifungal treatment with fluconazole (1200 mg/day) and flucytosine (1500 mg × 4/day) was started immediately. During hospitalization, her blood pressure normalized without treatment, but she died on the sixth day of antifungal therapy after a rapid deterioration of the state of conciousness. |
pmc-6417363-1 | A 56-year-old male, without previous systemic disease, presented with body weight loss about 10 kg and dry cough for about two months. He was a heavy smoker with a 40 pack-year history of smoking. Physical examination findings were unremarkable. The chest X-ray showed increased interstitial marking on the right side, and patchy consolidations of the right lung (Fig. A). A chest computed tomography (CT) revealed multiple enlarged mediastinal lymph nodes, unilateral small centrilobular nodules, and smooth peribronchovascular interstitial thickening without traction bronchiectasis particularity in the right lung (Fig. B,C). The differential diagnosis included lung cancer with nodal metastasis and sarcoidosis. The tumour markers were within normal range, and the bronchoscopy showed no endobronchial lesion. In autoimmune biomarkers survey, the only abnormality was the elevation of rheumatoid factor immunoglobulin M (14.5 IU/mL). However, due to the clinical suspicion of malignancy and interstitial lung disease, adequate tissue for diagnosis was crucial. We suggested a parasternotomy approach (Chamberlain procedure) with mediastinal lymph node excision. The pathology of the mediastinal lymph node showed lymphoid follicle proliferation characterized by concentric rings of small lymphocytes and sclerotic blood vessels radially penetrating the germinal centers (Fig. ). Immunohistochemical staining for human herpes virus-8 (HHV-8) was negative. The picture was compatible with hyaline vascular type CD. Screen of blood HHV-8 and human immunodeficiency virus (HIV) test were negative. Then corticosteroid and tocilizumab were prescribed, and the following chest CT showed completely regressive change with significant clinical improvement (Fig. ). |
pmc-6417398-1 | The patient was a 3 day old girl with left sided Bochdalek diaphragmatic hernia diagnosed prenatally. She was born at full term through vaginal delivery. Chest X-ray showed intestinal herniation into the thoracic cavity (A). After intubation and ventilation, we planned to perform elective MIS repair of the hernia. The patient was placed in a right lateral position, and three trocars were inserted (3 mm, middle axillary fourth intercostal space (ICS) for the endoscope; 3 mm, anterior axillary fifth ICS for the operator’s right hand; 3 mm, posterior axillary fifth ICS for the operator’s left hand). Artificial capnothorax by CO2 inflation (5 mm Hg, 1 L/min) was established. Under inspection using a 3-mm 30 degrees endoscope, a hernia sac was found. Instead of initially resecting the hernia sac, we decided to use it to reduce the herniated organs. This was accomplished by grasping the fundus of the hernia sac and twisting it around the instrument. Once maximal reduction with one hand was achieved, the twisted tissue was grasped with the contralateral instrument and the maneuver repeated until the entire hernia content was completely reduced. () Subsequently, the sac was removed circumferentially using the monopolar electrocautery hook. The diaphragm was then closed with interrupted figure-eight sutures of 2-0 silk. The operative time was 65 min, and there were no intraoperative complications (Video, B). She was discharged home on postoperative day 5. Half a year later, she was asymptomatic without any signs of recurrence. |
pmc-6417465-1 | A 38-year-old German man presented with darkly pigmented skin lesions on the back and chest. His past medical history was significant for right-sided cleft lip and cleft palate (which were repaired in early childhood), juvenile nasopharyngeal angiofibroma, and vestibular schwannoma. His family history was remarkable for melanoma in a paternal uncle.
He was diagnosed with a right-sided juvenile nasopharyngeal angiofibroma 25 years ago; the tumor had multiple recurrences and required several surgeries. His most recent recurrence, 18 years ago, involved a large infratemporal fossa approach to the right middle ear that resulted in obliteration of the external acoustic canal and right nasal septum deviation. He has since been without recurrence. However, there is stable decreased sensation in the region innervated by the second and third divisions of the right fifth cranial nerve.
A right-sided vestibular schwannoma was incidentally diagnosed six years ago during routine magnetic resonance imaging (MRI) scan monitoring for recurrent juvenile nasopharyngeal angiofibroma. Subsequently, the schwannoma has grown to 0.9 cm; it has remained stable for the last six years. Therefore, management of the vestibular schwannoma has only consisted of close observation.
Cutaneous examination showed atrophy of the right temporal area secondary to surgical interventions for juvenile nasopharyngeal angiofibroma; in addition, the repair site of the cleft lip and cleft palate is noted on the right side of his upper lip (Figure ).
An 8 x 3 mm oval dark brown patch is present on the right mid-back and a 2 x 2 mm black macule is noted on the right mid-chest (Figures , ). Biopsy of both skin lesions was performed.
Microscopic examination of the back lesion showed a compound dysplastic nevus with mild atypia. The chest lesion showed a combined (blue and intradermal) nevus. Both pigmented lesions had been completely removed at the time of biopsy. |
pmc-6417492-1 | A 34-year-old male labor worker presented with pain and paeresthesias on his right index, middle fingers and palm that had slowly increased in size over 5 years. The patient reported no preceding history of significant trauma or inflammation of the right hand. He complained of paeresthesias and pain in the area of the mass in the index, middle fingers and palm. These symptoms began approximately 2 years earlier. The pain got increased when pressure was applied on the nodules and with finger movements. The patient had no loss of sensation and he had the normal function of grip initially. And through rest and Non-Steroidal Anti-inflammatory Drugs medication (NSAIDs, 200 milligrams of Celebrex, twice a day), the patient's symptoms had been eased. On clinical examination, there were palpable, tender swellings in the middle phalanx of the index, middle fingers and the volar of third metacarpal respectively (Fig. ). There was no discoloration of skin and the nodules had no discharge or bleeding since presentation. Local pain was triggered by applying pressure on the nodules. Movement at distal interphalangeal of the second and third finger were slightly limited because of pain. Tinel-Hoffman sign was positive on percussion of the nodules, accompanied by paraesthesias in the fingerpad of the fingers. Comparing to the opposite side, superficial sensation, as well as, static and dynamic sensory discrimination, was unaltered in the palm and fingerpad of the second and third fingers. Neither muscle atrophy nor impaired digital blood flow in the patient's hand was observed. Tumor biological markers and laboratory analyses including complete blood count, C-reactive protein, and electrolytes were normal. Radiographs of hand were normal. MRI (Fig. ) examination (Siemes Essenza 1.5T) showed a mass in the middle of the second and third metacarpal, and masses in the radial side of index, middle fingers’ middle phalanx and the volar of third metacarpal. The mass showed low signal intensity on T1-weighted images and high signal intensity on T2-weighted images. The tumors showed significant enhancement after administration of contrast agent. The biopsy procedure was not to be performed in order to avoid wound contamination. The tentative diagnosis of neurinoma was made with a differential diagnosis of angioma.
The surgical procedure was performed under brachial plexus block. A brachial tourniquet was used and the procedure was carried out with surgical loupes. With volar approach, a longitudinal incision was made on the middle of the second and third metacarpal. A 12 mm × 7 mm × 4 mm yellowish tan, firm mass was separated from common palmar digital nerves of median nerve (Fig. ). The nerve fascicles were splayed by the tumors and were preserved during the operation. In addition, a nodule located in the index digital nerve on the radical side at the level of the middle phalanx in index finger and another 2 nodules located on the radial side at the level of the distal interphalangeal joint in middle finger were removed. The nodules were 5, 6, and 4 mm in diameter respectively (Fig. ). Surgical treatment was performed using a surgical loupe in order to avoid damaging the fascicular structure of nerves. All nodules were excised carefully without vast dissection of tissues of the fingers.
Grossly the tumor tissue appeared as soft, solitary, encapsulated with well-defined surface and had a yellowish color. Microscopically-well circumscribed tumor composed of spindle shaped cells arranged in a palisading fashion. There was no mitotic activity or malignancy features were seen. Immunostaining demonstrated strong extensive S-100 immunoreactivity of the nodules with CD34, Desmin, SMA, and EMA negativity (Fig. ). These findings confirmed the diagnosis of Schwannomas.
Postoperatively, there were no motor or sensory deficits. No infection was found after surgery. One week after the surgery, the patient was able to perform full motion of his operated hand. Symptoms of pain and paraesthesias resolved, and his finger range of motion recovered to the normal level. Tinel-Hoffman sign was negative. The patient was followed up by clinic every 3 months. Two years after the surgery, the patient had not experienced tumor recurrence. |
pmc-6417543-1 | A 9-month-old infant was diagnosed as developmental delay (DD). She was born after 41 weeks of pregnancy as the first child of healthy and nonconsanguineous parents. One week before birth, the fetus was diagnosed as “hydrocephalus” by ultra-sound. Her bodyweight was 3400 g at birth. She began to hold her head up at 7 months old in prone position, but not stable. At the age of 8 months, she was unable to turn over and to sit. At 9 months old, her head circumference was 41 cm (average size in 9-month normal females: 44.5 cm, ranging 42.1∼46.9 cm). Her knees were hyperreflexia and asymmetric tonic neck reflex was positive. Cranial MRI inspection showed cerebella atrophy and enlargement of bilateral ventricles. The anterior part of the brain was deficient in sickle, septum and corpus callosum. Also, bilateral frontal lobes were fused together, and bilateral ventricles were interlinked to form a single ventricle in the shape of riding boots (Fig. A and B). Notably, an abnormal cystic signal shadow (52 × 36 mm in size) was observed in the occipital region (Fig. C and D), showing clear boundary and even internal signal near the cerebella curtain. According to the MRI analysis, the affected infant was diagnosed having semilobar HPE and arachnoid cysts. The parents were phenotypically normal.
Trio-WES analysis of the family, including the patient and her parents, identified a previously unpublished de novo heterozygous variant (c.1069C >G, p.H357D) in the first exon of the ZIC2 gene (GenBank, NM_007129.4). This rare variant was confirmed by Sanger sequencing in the proband but not present in the parents (Fig. A and B). This substitution of Histidine with Aspartic acid at residue 357 is within the 3rd zinc finger domain (ZFD3) of the ZIC2- encoded protein. Multiple-sequence alignment showed that the ZFD3 is evolutionarily conserved in all vertebrates we examined (Fig. C and D), suggesting its functional importance.
Furthermore, this variant (c.1069C >G, p.H357D) was predicted to be pathogenic by several bioinformatic tools, including SIFT, polyphen-2, and Mutation Taster. According to SWISS-MODEL prediction, substitution of the Histidine by Aspartic acid could disrupt the interactions involving the amino acid residual C335, C340, H353, and H357, which may affect the structural confirmation and charge of the protein (Fig. E).
Current HGMD curated 113 previously published genomic alterations of ZIC2-containing region, including 24 missense mutations (21.2% of total variants, Table ), 14 nonsense mutations, 4 splicing mutations, 7 mutations in regulatory region, 33 small deletions, 13 small insertions, 5 small indels mutations, and 7 gross deletions mutations. Interestingly, most of reported missense mutations (19/24) are located within zinc-finger domain (ZFD) 1, 2, and 5. Only 2 missense mutationsare found in the ZFD3, including the present novel allele and apreviously reported (c.1004G >T; p.C335F, Table ). Genotype–phenotype correlation analysis on all 25 cases with missense mutations, 17 of them was categorized into 3 different subtypes of brain images: 6 in the alobar form, 7 in the semilobar form and 4 in the lobar form. We noticed that most of the alobar forms result from mutations within the N-terminal region of ZIC2, while a majority of the semilobar form is associated with the C-terminal counterpart. |
pmc-6418023-1 | A 45-year-old female presented to our hospital with a 5-month history of an epigastric mass. She had no history of carcinoma. A physical examination revealed a 20 × 18 cm palpable mass in the left-middle-upper abdomen. The laboratory findings, including tumor markers, were all within the normal ranges. Abdominal computed tomography (CT) showed a large 22 × 18 × 9 cm regular hypodense mass in the left lateral lobe of the liver that was progressively enhanced after infusion of contrast material, with blood vessels observed in the tumor (). Magnetic resonance imaging (MRI) revealed a regular heterogeneous mass of 22 × 18 × 9 cm in the left lateral lobe of the liver. The lesion showed a slightly decreased signal intensity on T1-weighted images and a slightly increased signal intensity on T2-weighted images. Progressive, uneven enhancement was observed (). Preoperatively, we regarded the lesion as either an angiosarcoma or hemangioma. Subsequently, a left lateral lobe hepatectomy was performed with no complications. The postoperative recovery was uneventful, and the patient was discharged 7 days after surgery. A macroscopic examination showed a 22 × 18 × 9 cm tumor that was oval, well circumscribed, and soft. The cut surface was whitish, grayish red, with some areas of the tumor being cystic and containing myxoid components. A microscopic examination revealed that the tumor consisted of spindle cells, with vascular proliferation in the myxoid stroma. Immunohistochemistry showed strong and diffuse staining for CD34, smooth muscle actin (SMA) and Ki67 (2%) and negative staining for Estrogen receptor (ER), C-keratin (CK), and Desmin (). The patient was diagnosed with a hepatic AAM instead of a sarcoma or a cavernous hemangioma. The patient was postoperatively monitored for 18 months, and there were no signs of recurrence or metastasis. |
pmc-6418315-1 | KA is a right-handed man who was 36 years-old at the time of assessment. This patient was first seen in the memory clinic of Rennes University Hospital in 2009, when he complained of memory deficits since he was a child which was corroborated by his family. His only and notable antecedent was severe neonatal hypoxia, and his neurological examination proved unremarkable. However, clinical observation revealed obvious limitations in moment-to-moment memory: KA often repeats himself without any awareness and cannot orient himself in an unfamiliar environment. Initial neuropsychological assessment confirmed very severe and selective memory impairment, without any other cognitive deficit (see , and see for details). A 44 points discrepancy was found between Intelligence and Memory Quotients (IQ & MQ), KA scoring 97 and 53, respectively. Patient KA received different neuropsychological assessments between March 2009 and July 2015 without any notable change. A psychometric confirmation of his severe amnesia finally came from his performance on the Rivermead Behavioural Memory Test, patient KA scoring 5 (profile score), which is twice lower from previously well-known cases of early-onset amnesia (e.g., ).
Visual examination of MRI scan (see ) revealed bilateral atrophy of the hippocampal formation, together with severe atrophy of the fornix and bilateral anterior thalamic nuclei. The mammillary bodies as well as the mammillo-thalamic tract remained unidentifiable, an extremely rare condition across the literature.
To further examine patient KA's hippocampus, a dedicated high-resolution (.375*0.375*2 mm) proton-density-weighted MRI sequence was acquired on a 3T-scanner perpendicular to the long axis of the hippocampus. That sequence allowed to segment hippocampal subfields (CA1, Subiculum, and “other subfields”, i.e., CA2-3-dentate gyrus) according to a published protocol () that was developed based on anatomical atlases (, ) and successfully applied to neurodegenerative disorders (). Patient KA's volumes were compared to a group of 20 healthy males who were matched for age (mean: 28.4, SD: 3.4), but more educated than KA (years of education, mean: 14.5, SD: 3.0), after normalizing for total intracranial volume. This confirmed a severe bilateral hippocampal volume loss (volume loss exceeding 55%, z-score = –5.6), which was marked in every segmented subfield in both hemispheres, in particular in the CA1 and subiculum regions (see ).
Altogether, clinical and neuroimaging data suggested that patient KA presented with a developmental amnesia syndrome (DA) as described in and . With patient HC (, ), KA's level of memory impairment is amongst the most severe ever reported across prior cases with DA. Moreover, and as recently reported (), brain abnormalities in KA extended beyond the hippocampal formation, with the involvement of diencephalic structures and thalamus nuclei, suggesting that the whole hippocampal system has been compromised (for further details and a cortical thickness analysis, see Jonin et al., submitted). |
pmc-6418319-1 | P.F., a 75-year-old man presented with a left side submandibular mass, 4 cm in diameter. He had noticed the painless mass 6 months earlier, which had started to grow. The patient did not have any swallowing or breathing problems. Micolaryngoscopy revealed no malignant tumor in the head-neck region. Removal was performed and under the platysma muscle, a solid, encapsulated mass was found. After surgery, the patient lived without any recurrence for 8 years.
Histology described that coagulative necrosis replaced the original histologic structures, and it was surrounded by a thick, artificially damaged fibrotic capsule. Residual lymphoid cell clusters could be seen only within the capsule, referring to the previous lymphoid tissue. Signs of previous bleeding could be detected with intra- and subcapsular accumulation of decompensated red blood cells and haemosiderin-laden macrophages. The capsule showed reactive, reparative changes with macrophages, plasma cells surrounded by fibroblast accumulation and newly formed capillaries. Perinodal connective tissue contained some small vessels showing signs of productive vasculitis with endothelial proliferation, and occasionally lumen obstruction. The wall of obstructed vessels was infiltrated by mononuclear cells. Cross sections of four further reactive lymph nodes could be detected within the surrounded fat tissue with reactive follicular hyperplasia and sinus histiocytosis. The diagnosis was lymph node infarction with negative surrounding lymph nodes and obliterative vasculitis nearby the infarction. No signs of malignancy could be detected. |
pmc-6418319-2 | V.A., a 62-year-old female, presented with a 4 cm in diameter, mobile submandibular mass on the right side in June 2012. Physical examination revealed no further abnormality. Neck CT showed a submandibular mass located just near the submandibular gland (), and the suggested diagnosis was enlarged lymph node or connective tissue tumor. Following the diagnosis, the patient became unreachable and was only encountered again one year later (in May 2013) with similar symptoms, albeit with complaints of a lump enlargement. Her general condition was appropriate; she did not exhibit any weight loss, pain, swallowing or breathing disorders. Blood tests’ values were normal, chest X-ray, abdominal ultrasound did not display any concerning images. Fine needle aspiration cytology suggested the diagnosis of a metastasis of a high-grade malignant tumor or less likely a neuroendocrine tumor (). Repeated neck CT found a right submandibular mass with surrounding lymph nodes, supposedly an inflammatory cyst (). Panendoscopy revealed no head-neck primary tumor. Finally, in November 2013 the lump along with lymph nodes was removed.
Histology showed a cyst-like lesion which contained necrotic tissue mass with peripheral infiltration of histiocytes and macrophages (). Immunohistochemistry of the necrotic area showed pan-CK negativity. Diffused LCA, focal CD-3 and CD-20 positivity could be detected (). The necrotic tissue was surrounded by a thick fibrous capsule (). Additionally, some reactive lymph nodes without any signs of malignancy were found. The histologic diagnosis was enlarged necrotic lymph node (lymph node infarction). Due to extensive necrosis, lymphoproliferative disease or any other malignancy including metastatic tumors could not be definitely excluded.
During the 3-year follow up period, the patient was tumor free, and no lymph node enlargement occurred again. Routine neck CT showed no abnormality in January 2016 (). |
pmc-6418319-3 | SZ.F., a 70 years old male presented with a 4 cm lump in the neck (Level II). There was no significant abnormality in blood tests. Fine needle aspiration cytology showed it was a lymphoproliferative disorder, and hematological examination was suggested. In the neck CT scans a 33x25 mm hypodense, homogenous mass was found, which could be a lymph node (). In the surrounding area, there were other smaller lymph nodes as well. No primary tumor or hematological disorder could be explored. The lump started to grow and became painful and an open surgical biopsy was conducted.
Histology found necrotic tissue with a fibrotic capsule. The capsule contained Vimentin-positive connective tissue components and vessels. Some fragments of skeletal muscle embedded in the capsule could also be detected and the necrotic area seemed to be necrotic lymphoid tissue. Silver impregnation showed a residual reticular sinusoidal structure. CD-20, CD-68 immunohistochemistry in the necrotic area indicated some histiocytes and residual lymphoid cells and the Ki-67 reaction shows a 10% proliferation index of CD-20 positive lymphocytes (Figure 2C, 2D). The diagnosis was subtotal lymph node infarction without any sign of malignancy.
After a few months, the lump decreased in size, but a fistula occurred in the incision area. Routine CT scan only showed a 17 mm in diameter cystic mass (), which was finally removed in toto. The final histologic diagnosis was the same, a lymph node infarction without any sign of malignancy. |
pmc-6418348-1 | The 8-month-old boy was born at term without any unusual birth history (38 weeks, 3,150 g, by Cesarean delivery) to a 45-year-old father and 36-year-old mother. He had one brother (12-year-old) and sister (8-year-old). None of the family members had any medical history during the growth period.
He was admitted to the pediatric department due to an initial seizure event following aspiration pneumonia and was referred to our clinic for the evaluation of unexplained neuroregression. Although he was hypotonic from birth, he achieved a social smile at 3 months and started head control during the first 4 months. He rolled over, and nearly grasped his toys with prone position at 6 months. Generalized tonic–clonic type seizures at 6 months were his first clinical symptom, a detailed history revealed delays in developmental milestones after that. Electroencephalogram (EEG) findings showed abnormal awake and sleep recordings due to slow background activity, suggestive of diffuse cerebral dysfunction with symptomatic or cryptogenic seizures. Magnetic resonance imaging showed cerebral hypoplasia especially in the frontal and temporal lobes at approximately 4 years of age. He was observed at the outpatient clinic for developmental delays associated with encephalopathy and seizure events, which occurred hundreds of times for 2 years and were fairly well-controlled with valproic acid, phenobarbital, and clonazepam.
At 26 months after surgery for bilateral cryptorchidism, progressive respiratory difficulty persisted and weaning from the ventilator was not possible; repetitive aspiration pneumonia occurred as he was unable to proceed with sputum expectoration. Therefore, tracheostomy was performed and night-time breathing using a ventilator was maintained subsequently. At the time of admission, repetitive hand flipping without purpose and lip smacking was observed during examination, although epileptiform discharges were not observed during EEG, we decided to proceed with additional evaluation other than that previously considered at this point. The various clinical features of the patient are described in Table .
There were no abnormal findings based on laboratory investigation, and genetic analysis of mutations including Prader-Willi gene, spinal muscular atrophy gene, and other chromosomal aberrations. Chromosome analysis revealed a 46, XY karyotype. A muscle biopsy also demonstrated no abnormal findings. |
pmc-6418362-1 | The patient is a 9-year-old male child born at full term following an uncomplicated pregnancy and planned caesarian section. The patient was the second child born of a second pregnancy to a 31-year-old mother. Birthweight was 6lbs 12oz and both physical examination and Minnesota newborn screening () were normal. The patient followed the tenth percentile for weight and height for the first two months of life, before dropping off the curve below the third percentile while remaining normocephalic. At 6 months, the patient was diagnosed with failure to thrive. Failure to roll over or sit unaided led to a diagnosis of developmental delay. Recurrent acute otitis media led to the placement of myringotomy tubes at 10 months. Laryngoscopy, GI endoscopy, and swallow study were performed at the same age due to continued poor growth and all were normal. Extensive metabolic evaluations were also negative. A gastrostomy was performed at the age of 13 months and the patient made slow gains while remaining close to the third percentile of the growth chart.
The patient was unable to roll over until 7 months of age and did not sit or raise to his knees independently until 15 months. By 2 years, he could transfer objects between hands but retained difficulty in reaching for smaller objects. He could crawl and cruise unassisted by 18 months but did not walk independently until he was 3 years of age. Gait was noted to be wide and slightly unsteady with some toe-walking and a tendency for tripping. Hyperreflexia of the patella was noted, as well as presence of some beats of clonus. At the age of 5 years, significant delays in receptive and expressive language were present, with an equivalency of 16 months.
The patient was evaluated by a medical geneticist and several dysmorphic features were noted including prominent forehead with slight frontal bossing, mild hypertelorism, prominent eyes, grayish sclera, short, low-positioned nose with prominent columella and hypoplastic alae nasi (Figure b,c). There was mild shortening of the distal phalanges as well as mild overlap of second over third and fifth over fourth digits of the left hand (Figure d). The thumbs were slightly widened. Feet were normal except for slight upward displacement of the third toe of the left foot (Figure e). A skeletal survey was ordered and revealed a benign lucency in the proximal right fibular diaphysis with a pedunculated osteochondroma extending medially. A probable second osteochondroma was observed in the distal aspect of the left small finger proximal phalanx (Figure ). Several wormian bones were noted along the right lambdoid suture.
At the age of 19 months, the patient suffered two febrile seizures. Four months later he had a series of non-febrile seizures and was diagnosed with symptomatic localization-related epilepsy by electroencephalogram (EEG) following status epilepticus. Magnetic resonance imaging (MRI) of the brain revealed diffuse bilateral frontotemporal pachygyria and dilation of the lateral ventricles (Figure f–h). The seizures were completely controlled by levetiracetam treatment.
Further skeletal evaluation at 5 years of age revealed the appearance of new osteochondromas including small sessile protrusions on the proximal left humerus and the proximal and distal femurs as well as left tibia and fibula and ulna. Multiple bilateral metatarsal, metacarpal, and phalangeal osteochondromas were also noted (Figure ). |
pmc-6418371-1 | Family 1406 is a consanguineous family from Colombia in which the proband, now a 21-year-old young man, was diagnosed clinically with paramyotonia congenita. The proband's mother first sought medical attention for him when he was about a year old as she was concerned about his unusual stiff-legged gait. His pediatrician did not find any concerning features on his developmental history or examination at that time. As he continued to develop, his parents noticed he would not bend his knees when jumping, and that his gait would sporadically become “stiff legged.” A neurologist found good reflexes and no weakness. His symptoms worsened over time. He tried to be active in soccer and other sports, but he was slower than his peers. He reports no difficulty initiating movements; however, after running for several yards, he experiences a sudden onset of muscle stiffness in his legs that forces him to stop to take a break. After a brief rest, he can then resume running without difficulty. The stiffness is not accompanied by any pain or weakness, but worsens with exposure to cold temperatures. He also has noticed that after gripping a lacrosse or hockey stick for a length of time, he has difficulty releasing the stick. He also reports jaw stiffness with prolonged chewing but has not experienced choking or dysphagia. Neither parent had any muscle symptoms. Physical examination at 16 years showed eyelid, hand, and foot myotonia with mild percussion myotonia at the thenar eminences and the extensor digitorum communis. Physical examination at 20 years showed eyelid myotonia and mild grip myotonia, with no signs of percussion myotonia. Strength was normal in all extremities, with no muscle hypertrophy or atrophy and no heel cord contractures. Electrocardiogram and echocardiogram were both normal. Nerve conduction studies and electromyography (EMG) performed at 12 years was normal. An EMG at 16 years showed normal sensory and motor nerve conduction studies, while on needle examination, fibrillation potentials were noted, without frank myotonic discharges, in the left extensor digitorum communis. Muscle biopsy showed excess in fiber size variability, increased centralized nuclei, mild fiber type grouping, and focal myofibrillar disarray (Figure ). Clinical genetic testing showed no pathogenic mutations in CLCN1 and SCN4A. Mexiletine did not relieve his symptoms. The clinical impression was that he had an atypical form of paramyotonia congenita. |
pmc-6419343-1 | A 6-month-old boy was referred for a right lower cheek mass and a left thoracic subcutaneous mass both present for 3 months. He was asymptomatic and healthy with no significant medical, surgical or familial history. The thoracic lesion was small (1,0 × 1,6 cm) and mobile. The cheek lesion presented as a deep and firm soft tissue submucosal mass adherent to the mandible (Fig. ).
Ultrasound (US) examination of both masses showed hypoechoic lesions with small calcifications and scant vascularization. Magnetic resonance imaging (MRI) of the neck showed a soft tissue mass of 3.4 (AP) × 2.2 (T) × 3.8 cm (CC), with lobulated contours and a cystic center (Fig. ). The lesion was located within the right buccinator and masseter muscles and showed bony invasion of the right mandible and peripheral enhancement with injection of gadolinium. To rule out other synchronous lesions, cardiac and abdominal US and brain MRI were performed and were negative.
The thoracic lesion was excised and the oral lesion biopsied. The histopathology was similar and showed spindle cell tumors with a storiform pattern (Fig. ) compatible with infantile myofibroma.
Throughout the treatment, the conduct was coordinated by an adult head and neck oncology – reconstructive otolaryngologist and a pediatric oncologist. On multiple occasions, the patient was presented at a multidisciplinary pediatric oncology clinic for medical aspects and at a multidisciplinary head and neck oncology clinic for surgical aspects. The first surgery (debulking) was done jointly by an adult head and neck oncology - reconstructive otolaryngologist and a pediatric otolaryngologist. All other ablative and reconstructive surgeries were performed jointly by two adult head and neck oncology - reconstructive otolaryngologists. Surgical treatment of the mandibular tumor was initially judged too morbid and chemotherapy was started with Methotrexate and Vinblastine. After six cycles, the patient presented feeding difficulties. A computerized tomography (CT) Scan was performed at this time and showed a progression of the lesion with extension to the retromolar trigone and deep mandibular erosion (Fig. ).
Chemotherapy was suspended, and a conservative trans-oral resection of the tumor was done. Only the intraoral exophytic portion of the tumor was excised to allow jaw closure and occlusion on the contralateral side. No other structures were resected, and the main specimen size was 3.5 X 2.8 X 2.5 cm. The surgery was well tolerated with no complications. One month later, an MRI showed progression of the tumor reaching 4.0 (AP) × 3.2 (T) × 4.1 (CC) cm with extension to the medial pterygoid muscle and infiltration of the alveolar nerve. Chemotherapy with Methotrexate and Vinblastine was pursued. Four months later, despite the chemotherapy, the patient had weight loss because of recurrence and progression of the intraoral mass affecting the oral phase of swallowing as well as preventing contralateral occlusion contact. The control MRI demonstrated progression of the tumor now reaching 5.3 (AP) × 3.9 (T) × 4.9 (CC) cm with new tumor extension along the right maxilla and an increased recruitment of peripheral vasculature (Fig. ).
Faced with tumor progression refractory to chemotherapy and conservative surgery, radical excision with segmental mandibulectomy was planned. We decided to stage the reconstruction because of the patient’s age (18 months) and the local aggressiveness of the disease. It was resected with conservative margins and we planned the final reconstruction later when local control was achieved. Also, there are very few precedents of mandibular free flap before 2 years, and the impact on mandibular development at this early age is not well documented. The risk of valgus ankle deformity is significant before 8 years and decreases with age. It can be prevented or corrected by a synostosis. This was considered optional by pediatric orthopedics, only if late deformity would occur. Delaying the free flap to 42 months was therefore judged a good compromise, minimizing the risk of weight-baring plate complications on a solid diet. A combined trans-oral trans-cervical segmental mandibulectomy was done with preservation of the condyle (Fig. ). A temporary mandibular reconstruction was achieved with a bridging titanium plate for the bony defect and intraoral reconstruction with a submental island flap. The plate was adapted to the outer mandibular cortex before osteotomies without preoperative 3D planning. There were no complications and the evolution and function were excellent until definitive bony reconstruction.
Pathology confirmed a 5.6 (CC) × 4.8 (AP) × 3.6 (T) cm myofibroma with gross mandibular invasion. Margins were close but negative. Despite the invasive nature of the tumor, there was no evidence of cancer. The immunostaining was positive for smooth muscle actin (strong and diffuse) and Hhf35 (moderate to strong and local). Rare cells were positive for desmin while the markers caldesmon, MYOD-1, myogenin, CD34 and AE1-AE3 were negative. Subsequently, a control MRI showed no recurrence of the lesion. Because the mandibulectomy spared the condylar growth center, vertical and horizontal remodeling occurred within this region and no drift occurred between 18 and 42 months. The patient retained a functional occlusion on the left side (Fig. ).
At 42-month-old, a delayed microvascular bony reconstruction with a fibula free flap was completed, surgical exploration confirming remission of the tumor (Fig. ). At the time of the reconstruction with the fibula free flap, the exploration revealed a well-tolerated and stable titanium plate with new bone formation around it at both osteotomy sites. To facilitate the procedure and protect the occlusion, it was left in place and used to fix the fibula to the defect. Later removal was planned. The patient had a favorable postoperative evolution. He resumed oral diet three days post op and was discharged from the hospital eight days postop. The only complication was a minor skin dehiscence from the fibula donor site, which completely healed treated with water gel and wound care. He later had 2 revision surgeries without complications, one for titanium plate removal and one for skin paddle thinning. At the time of plate removal, a complete and solid bony union was found at both osteotomy sites well as new bone formation along the reconstruction plate (Fig. ). At the last follow-up at 53/12 years-old and 4 years after the resection, he was doing well and free of disease with an excellent function. Figure is a timeline that summarizes the patient’s evolution and treatments. |
pmc-6419359-1 | A 47-year-old female farmer residing in a semi-rural area of Yaounde was brought to the emergency department of the Yaounde Central hospital of Cameroon with complaint of a bite on the pulp of her right thumb 20 h prior to presentation, while working in her farm by an Echis occellatus viper. She killed and beheaded the snake (Fig. ), then immediately tied a tourniquet round her right wrist, sought a traditional healer who removed the tourniquet and administered her some unknown complementary and alternative medicine both topically and orally. Due to no amelioration of her symptoms within 20 h following the bite incident, she was rushed the aforementioned emergency department and vomited twice during transportation. She complained of severe thirst, fatigue, dizziness, numbness of the entire right upper limb, anuria since the bite incident, but no complaint of haematuria, myalgia, difficult breathing or swallowing.
On examination, she was conscious, oriented, sweating profusely with moderate pallor and cold clammy extremities. Her blood pressure (BP) was undetectable, respiratory rate 28 breaths/minutes, temperature 36.4°C, and a thready pulse of 138 beats/minute. Two unclean puncture wounds were identified on the pulp of the right thumb. The right upper arm was reddish dark in colour with several ruptured blisters and covered by a white traditional balm (Fig. ). This limb was oedematous, indurated, and painless, with loss of all pulsations and all range of active movements. She had no clinical sign of urinary retention. The rest of her physical examination was normal. A provisional diagnosis of severe envenomation complicated by anaphylactic shock, acute pre-renal kidney injury, and gangrene of the upper limb in an ASA IVU patient was made.
She had a difficult peripheral venous access due to circulatory collapse. On admission, an urgent femoral venous access was achieved with the aid of a G 16 cannula, while waiting for central venous catheter. She received normal saline at 20 ml/kg, anti-tetanus serum 1500 IU subcutaneously, ceftriaxone 2 g/24 h intravenously (IV), metronidazole 500 mg/8 h IV, adrenaline 1:1000 dilution at 0.2 mg every 5 min IV, promethazine 25 mg/8 h IV, paracetamol 1 g/06 h IV, tramadol 100 mg/8 h IV, methylprednisolone 80 mg/kg IV, and two vials of polyvalent anti-venom sera IV. Shoulder disarticulation was envisaged after resuscitation.
Laboratory investigations on admission revealed; leucocytosis 18,800/mm3 (neutrophils 66% lymphocytes 24.6%), anaemia 9,9 g/dl, thrombocytopenia 109,000/mm3, altered renal function (serum urea 0. 55 g/l and serum creatinine 32.23mg/l), normal clotting profile and serum electrolytes.
At 4 h of hospitalisation she had received 3 l of normal saline, but was still haemodynamically unstable with persistence of anuria. Her temperature rosed to 38.9°C. Several echymoses and petechiae appeared on her limbs. A second laboratory panel showed increased leucocytosis at 26,800/mm3 (neutrophils 76% lymphocytes 20.6%), severe thrombocytopaenia of 3500/mm3, haemoglobin of 9.6/dl. Here the diagnosis of an anaphylatic shock coupled with a septic shock was made. Noradrenaline was administered at 0.3/kg/min using an electric pump syringe with (objectives to have a mean arterial pressure ≥ 65 mmHg). The management which pursued was administration of a third vial of polyvalent anti-venom serum and transfusion of three units of fresh frozen plasma and continuation of the aforementioned antibiotics, analgesics and promethazine. All attempts of internal jugular and subclavian catheterisations failed due to severe circulatory collapse and marked oedema. After repeated attempts, a left femoral catheter was successfully placed. Blood obtained from the femoral catheterisation was non-coagulable.
At 7 h of hospitalisation her blood pressure was 102/68 mmHg, pulse 108 beats/minutes and of good volume, respiratory rate netly improved. She was fully conscious, less diaphoretic and had a diuresis of 0,35 ml/kg/h. The patient and her family refused shoulder disarticulation.
At 10 h of hospitalisation her level of consciousness dropped to a Glascow Coma score scale of 13/15, with undetectable pulses, BP 88/42 mmHg. Resuscitation was continued. She deceased at 18 h of hospitalisation in a state of shock, sepsis, coagulopathy, renal failure and gangrene of the right forearm. |
pmc-6419360-1 | A 67-year-old man presented with complains of constipation for 6 years. He had undergone LAR for stage II rectal cancer 7 years ago. Postoperatively, he had developed an anastomotic stricture consequent to postoperative leakage and underwent endoscopic balloon dilatation. The symptoms relapsed and after 2 years of first balloon dilatation, it was repeated again. The patient needed the treatment with laxatives for stool softening. Nonetheless, symptoms did not resolve completely and balloon dilatation had to be repeated again with minimal success. Eventually, the patient was referred to our department for surgical management. Then, RIC using TAMIS approach considered the procedure of choice.
The patient had an unremarkable physical and systemic examination. His BMI was 24.07 kg/m2. Medical history revealed hypertension, dyslipidemia, osteoarthritis of the knee, and a past history of pulmonary tuberculosis. The family history was irrelevant. Colonoscopy showed a 1-cm diameter stricture in the lower rectum (Fig. a) through which an endoscope with an external diameter of 9.9 mm could be passed with resistance. Preoperative computed tomography–colonography showed narrowing in the lower rectum (Fig. b), as did magnetic resonance imaging of the pelvis, which showed rectal narrowing accompanied by muscular thickening (Fig. c, d).
The patient was placed in a modified lithotomy position and the anus dilated with a self-retaining anal retractor (Lone Star Retractor; Cooper Surgical, Trumbull, CT, USA). A transanal access device (GelPOINT Path; Applied Medical, Rancho Santa Margarita, CA, USA) was introduced (Fig. ). A pneumorectum was maintained at 12 mmHg with carbon dioxide using an AirSeal platform (AirSeal System; Conmed, Utica, NY, USA), and conventional laparoscopic instruments were used []. A 1-cm stricture was located in the lower rectum (Fig. a) and full-thickness incisions made parallel to the axis of the rectum at the 9 o’clock (Fig. b) and 3 o’clock positions of the stricture (Fig. c). The stricture wall was then cut from 9 o’clock to 7 o’clock and 3 o’clock to 6 o’clock (Fig. d). After intraluminal lavage with saline, hemostasis was secured. The defect was then closed with 3-0 V-Loc suture (Medtronic, Minneapolis, MN, USA), as shown in Fig. a. On the 13th post-operative day, rectal perforation was detected in colonoscopy that resolved with conservative treatment (Fig. b). The perforation had sealed off when inspected on 26th post-operative day (Fig. c). The patient was discharged on the 33rd post-operative day, 36 days after the admission and attended for regular follow-up without experiencing additional complications. One year after surgery, the patient no longer required medication for constipation, and endoscopic examination showed no stricture (Fig. d). |
pmc-6419387-1 | An 82-year-old female with secondary post-herpetic uveitic glaucoma of the right eye presented at the Department of Ophthalmology for an elective trans-scleral laser cyclophotocoagulation. She had a history of chronic heart failure, arterial hypertension, hyperlipidemia, depression and Hodgkin’s lymphoma in remission. Her regular medications included acetylsalicylic acid, bisoprolol, isosorbide mononitrate, telmisartan, atorvastatin and escitaloprame. The patient denied having any allergies. On preoperative assessment she weighed 62 kg, her height was 162 cm and her blood pressure (BP) was 166/83 mmHg with 70/min heart rate (HR). Physical examination was unremarkable.
The patient’s orbit was anatomically normal. She was given a retrobulbar block to the right eye with 2 mL of 0.5% levobupivacaine and 2 mL of 2% lidocaine. No mydriatic agent was used. She did not move her eye during the procedure. Aspiration for blood was negative. Upon injection, no resistance was felt. 2-3 minutes after the injection, she started yawning and feeling progressively drowsy; anaesthesiology team was immediately called. 5-8 minutes after the injection she became unresponsive to verbal and tactile stimuli; her Glasgow Coma Scale (GCS) score was 3. On arrival of the team she had developed bradycardia with hypotension, her HR was 40/min, BP 50/30 mmHg and blood oxygen saturation (SpO2) 85%. 10 mg of ephedrine was promptly administered intravenously (i.v.) with no significant effect, continued by 3 i.v. doses of 0.1 mg adrenaline 2 minutes later. Concurrently the patient developed respiratory arrest, her SpO2 had fallen to 54%, BP was 163/100 mmHg with HR 93/min. A bolus of 200 mL intravenous lipid emulsion (ILE) was given. Anaesthesia was induced with 50 mg of propofol, the patient was intubated and mechanically ventilated, and her vitals had stabilized (SpO2 98%, BP 113/60 mmHg, HR 92/min). She was additionally sedated with 5 mg of midazolam. Because of persistent hypotension (RR 92/58), 500 mL of hydroxyethyl starch (HES 130/0.4) in isotonic sodium chloride solution was also administered.
Surgery was cancelled and the patient was relocated to the ICU. She was additionally sedated with midazolam and propofol, then gradually shifted through supportive ventilation techniques to spontaneous ventilation and extubated 6 hours after admission. There was no need for vasoactive support, oxygen or fluid replacement therapy. Blood test results were within normal range. Her BP was 140/60 mmHg, HR 71/min, SpO2 95%, without additional oxygen. Her GCS score was 15. The next day she was discharged to the Department of Ophthalmology, where the intended procedure was performed under general anaesthesia. The patient was discharged home 6 days later, she was stable and had not suffered any consequences from the adverse reaction.
Informed consent has been obtained from the patient to use the data presented in this case report.
The research has been complied with all the relevant national regulations, institutional policies and in accordance the tenets of the Helsinki Declaration. |
pmc-6419399-1 | A 6-year old boy with a history of 3-week fever (unknown origin) accompanied by weight lost (− 2.5 Kg) was admitted to pediatric department of Guangdong Women and Children Hospital. The boy experienced a 3-week of fever and sweating, which mainly happened at night and peaked at 40.3 C degree. A pain at right patella was also reported. What’s more, the boy had a history of thalassemia with hemoglobin fluctuating between 95 and 100 g/L. Blood transfusion and antibiotic treatment (Cefperazone-Sulbactam, Azithromycin and piperacillin-sulbactam) were conducted at a local hospital before admitting to our hospital, but intermittent fever continued. On admission, physical examination and laboratory detection were conducted. All the physical examinations were normal, except for diffuse enlargement of mesenteric lymph nodes. Laboratory test indicated a drop of white blood cell (3.33*10^9/L, N,26.7% L,64.65) and hemoglobin (71 g/L), and increase of erythrocyte sedimentation rate (ESR,25 mm/h) and ferroprotein (FER, 1669 ng/ml). Slight increase of ALT (105 U/L) and AST (145 U/L) and significant increase of LDH (2082 U/L) were also observed. The serum level of high sensitive c-response protein (hsCRP) was normal (6.81 mg/L), and the level of procalcitonin (PCT) was slight increase (0.16 ng/ml). At the time of admission, two sets of blood culture and two sets of bone marrow culture were obtained. Two marrow culture presented positive 2.6 days post obtained, and one set of blood culture present positive 3.6 days post obtained, while the other set of blood culture remained negative (5 days). |
pmc-6419421-1 | A 59-year-old Japanese man presented to our hospital with the chief complaint of hematochezia and malaise. On the day of admission and 10 days earlier, he had produced a fresh bloody stool. He had undergone open surgery with a bifurcated graft for an AAA 20 months earlier. The course was uneventful, with no remarkable findings on computed tomography (CT) at 6 and 18 months postoperatively. An abdominal examination at our hospital revealed nothing remarkable and no tenderness. His blood pressure was 122/75 mmHg; heart rate, 86/minute; body temperature, 36.6 °C; breathing, 16 per minute; and hemoglobin level, 9.0 g/dL.
Esophagogastroduodenoscopy and total colonoscopy revealed only colon diverticula and no bleeding. Contrast-enhanced CT revealed gas within the aneurysm sac (Fig. a, b, yellow arrowhead) and adhesion between the graft and intestinal tract in three areas: the ileum had attached to the anastomosis between the left branch of the graft and left common iliac artery (Fig. a, yellow circle); the jejunum to the middle of the graft body; and the duodenum to the anastomosis between the aorta and the proximal graft. Enterococcus faecium was isolated from blood culture, suggesting communication between the intestinal tract and aorta at the attached sites, possibly due to infection of the graft. His vital signs were stable, so surgery was scheduled to take place after antibiotic treatment. After admission, he produced another fresh bloody stool, but bleeding ceased immediately. At 18 days after the second fresh bloody stool, however, he suddenly went into a state of shock, with massive fresh bloody stool and hematemesis, followed by cardiac arrest. Despite intensive cardiopulmonary resuscitation, he died from hemorrhagic shock.
An autopsy performed with written consent from the family revealed an ulcerative fistula in the distal ileum that adhered to the anastomosis between the left branch of the graft and the left common iliac artery (Fig. a), with a small hole at the aortic anastomosis (Fig. b). Arterial structure was destroyed at the anastomotic site. There was fibrous thickening of the arterial wall (Fig. a, b) and the external elastic lamina had disappeared. The serosa of the small intestine and adventitia of the artery were firmly adhered (Fig. c, d). There was no marked sign of infection, such as inflammatory cells or phagocytosis, even around the fistula. |
pmc-6419468-1 | A 33-year-old woman without a significant past medical history, was diagnosed with stage IV subcutaneous panniculitis like T-cell lymphoma in 2011, complicated by hemophagocytic lymphohistiocytosis. She completed 6 cycles of CHOEP regimen (cyclophosphamide, doxorubicin, etoposide, vincristine and prednisone) in December 2011. Shortly after completion of the therapy, she relapsed and received multiple salvage regimens including gemcitabine/oxaliplatin, bexarotene/dexamethasone and pralatrexate. She was then initiated on ESHAP regimen; a combination of the chemotherapeutic drugs etoposide, methylprednisolone, a high-dose cytarabine and cisplatin in April 2012, achieving complete response; followed by an allogenic stem cell transplant on June 28, 2012. Since that time, she has been on observation with no evidence of disease recurrence. Subsequent to the treatment, she was found to have high triglycerides (230 mg/dL [2.60 mmol/L] (normal range < 150 mg/dL [1.69 mmol/L]) in 2011, and 613 mg/dL [6.93 mmol/L] in 2013) and loss of fat tissue from her entire body with accompanying muscular prominence. She was also diagnosed with diabetes in 12/2013. Constellation of these findings led to the diagnosis of AGL in 2013.
At her visit in our clinic, her BMI was 24.4 kg/m2. Her leptin level was low at 3.4 ng/mL (182 pmol/mL) (a level of < 4 ng/mL [215 pmol/mL] is accepted as low for women with BMI < 25 kg/m2 despite a wider range provided by some reference labs). Upon obtaining a detailed history, and reviewing her old pictures, it was confirmed that the onset of body fat loss occurred prior to her T-cell lymphoma diagnosis. She also endorsed complaints of hyperphagia and a marked increase in her appetite. Current clinical endocrine problems outside of diabetes and dyslipidemia include increased appetite and hyperphagia, lack of menses and a generalized pain syndrome likely attributable to small fiber neuropathy due to hypertriglyceridemia []. Table summarizes her laboratory findings since the diagnosis until her last visit in our clinic. Figure panels a-d show her pictures; before diagnosis (a), at diagnosis of T-cell lymphoma(b), during chemotherapy (c) and after chemotherapy (d).
At her most recent visit, she was doing well and is in remission for T cell Lymphoma. A “fat shadow” [] representation from her DXA scan (panel a) and her new clinical pictures (panels b-e) are presented in Fig. . For her metabolic complications of her AGL, she is currently not being treated with Metreleptin and this possibility is still under discussion. She is on multiple medications to treat her diabetes, high triglycerides and has been trying to limit her food intake. |
pmc-6419487-1 | A 21-year-old male, who previously suffered only from intermittent asthma, was admitted to the emergency room in March 2018 with a one-day history of headache, nausea, sore throat, and generalised muscle ache. An initial consultation with the family physician had diagnosed influenza but shivers, photophobia, and testicular pain appeared 24 h later. Subsequent physical examination found new purpuric lesions on the trunk and upper limbs (Fig. ) leading to admission to hospital.
At admission, the patient’s blood pressure was 121/47 mmHg, heart rate was 116 bpm, oxygen saturation was 94% in room air, and his temperature was 38.4°C. He was slightly drowsy with a Coma Glasgow Scale score of 13, with left parietal headache, nausea and neck stiffness. Cardiovascular, pulmonary and abdominal examination was normal. Laboratory analysis of blood samples revealed high levels of C-reactive protein (106 mg/L), hyperleukocytosis (24 × 109 white blood cells/L, of which 94% were neutrophils), and acute non-obstructive renal failure (3.46 mg/dL serum creatinine, corresponding to creatinine clearance of 24 mL/min).
Blood cultures were taken and a lumbar puncture was performed, followed immediately by intravenous (IV) administration of 2 g cefotaxime. The CSF was crystal clear and no hyper-pressure was observed upon puncture of the dura mater. Biochemical analysis of the CSF revealed normal glycorrachia (3.0 mmol/L, with 4.8 mmol/L glycaemia), normal protein content (0.22 g/L) and elevated levels of lactate (5.8 mmol/L). Cyto-microbiological analysis found no CSF pleiocytosis (6 leukocytes/mm3) and the absence of bacteria as determined by Gram staining.
The patient was admitted to the intensive care unit (ICU) with a diagnosis of purpura fulminans with uncertain meningitis. During the following 12 h, multiple organ dysfunction syndrome progressively appeared with the following features: disseminated intravascular coagulation (DIC) [elevated prothrombin time (PT) (26%), elevated activated partial thromboplastin time (aPTT) (2.54), low fibrinogen (1 .4g/L), thrombopenia (62 × 109 platelets/L), elevated D-dimers (> 10.000 ng/mL) and low factor V (21%)]; severe hypotension resistant to 20 mL/kg fluid resuscitation and requiring treatment with 0.4 μg/kg/min norepinephrine; non-obstructive acute renal failure; acute lung injury with mild pulmonary oedema upon chest X-ray and no cardiac failure upon the first echocardiographic examination (left-ventricular ejection fraction (LVEF) 70%), requiring oxygen delivery through a mask up to 9 L/min flow, and metabolic acidosis (pH 7.28, lactate 6.4 mmol/L). In addition, plasma procalcitonin (PCT) levels were very high (521 μg/L). Encephalic computerised tomography (CT) scan and magnetic resonance imaging (MRI) ruled out the presence of a pharyngeal or cerebral abscess, cerebral thrombophlebitis, sinusitis, mastoiditis, and ethmoiditis. The patient was treated IV with 250 mg/kg/day cefotaxime.
Neisseria meningitidis was first identified in the blood cultures after 15 h, confirming the diagnosis of meningococcemia with purpura fulminans and shock. Numerous N. meningitidis colony-forming units were then identified in the CSF cultures 24 h after sampling. Furthermore, pathological examination of skin biopsies taken from purpuric areas revealed thrombosis of all the dermal capillaries associated with the presence of cocci in several vessels (Fig. ). The N. meningitidis strain isolated belonged to serogroup C and was fully susceptible to penicillin (minimum inhibitory concentrations for penicillin, amoxicillin and ceftriaxone of 0.047, 0.125, and < 0.016 mg/L, respectively). The patient had never been vaccinated against meningococcus. Human immunodeficiency virus serology was negative.
Organ failure improved by the second day after admission. Oxygen delivery was decreased to 4 L/min and the norepinephrine infusion rate reduced to 0.2 μg/kg/min. Creatinine serum levels decreased to 2.1 mg/dL (estimated clearance of 40 mL/min), haemostasis parameters improved (PT 42%, aPTT 1.85, fibrinogen 4.5 g/L), and the blood lactate concentration decreased to 5.7 mmol/L (Fig. ). A recurrence of hypotension, however, led to the diagnosis of acute myocarditis upon echocardiography, with decreased LVEF (40%), diffuse left-ventricular hypokinesia, and low left-ventricular output (2.4 L/min/m2 with aortic velocity–time integral of 13.5 cm). An electrocardiogram revealed an elevation of the ST segment in the infero-lateral area (Fig. ). Blood levels of hypersensitive troponin Ic increased rapidly to reach a peak of > 13,000 ng/L 44 h after admission, and then decreased and normalized within 14 days. Hypotension was corrected by IV infusion of 10 μg/kg/min dobutamine for 36 h until left-ventricular function was completely restored. A myocardial MRI scan performed at day 8 showed no residual segmental or global left-ventricular dysfunction, no perfusion defect, and no abnormal contrast enhancement after injection of gadolinium.
All organ dysfunctions resolved during further treatment in the ICU. Nevertheless, distal hypoperfusion remained, in particular, in the distal phalanges of both hands. To avoid necrosis of the fingers, the patient was treated for 9 days with systemic (Iloprost 2 ng/kg/min by continuous IV) and local (Trinitrine patches 10 mg/day applied to all distal phalanges) vasodilators. Dermal necrosis occurred only on the pulp of the left index finger, bilaterally on the pulp of the big toes, the left ear lobe and the foreskin. Cefotaxime was discontinued after 7 days. The patient was transferred to the infectious disease ward 7 days after admission into the ICU. He was circumcised at day 12 to treat the foreskin necrosis and was finally discharged from the hospital at day 22 after favourable evolution of all necrotic lesions. |
pmc-6419662-1 | A 73-year-old man underwent PG for gastric cancer. Wall thickening of the common bile duct was detected on a follow-up computed tomography (CT) 2 years after the surgery. Serum biochemistry was as follows: aspartate aminotransferase (AST), 18 U/L; alanine aminotransferase (ALT), 15 U/L; total bilirubin (T-bil), 0.9 mg/dL; carcinoembryonic antigen (CEA), 1.0 ng/mL; and cancer antigen 19-9 (CA 19-9), 12.3 U/mL. A CT scan showed enhanced wall thickening of the common bile duct. Lymph node swelling and vascular invasion were not detected. The right gastric artery (RGA) and right gastroepiploic artery (RGEA) were preserved in the prior operation. Endoscopic retrograde cholangiography (ERC) showed stenosis of the common bile duct with a diameter of 15 mm (Fig. a). Positron emission tomography (PET)-CT revealed abnormal fludeoxyglucose uptake at the common bile duct. We diagnosed the patient with common bile duct cancer, and PPPD with preserving the right gastroepiploic vessels was planned with reference to CT reconstructing blood vessels (Fig. b). During the PPPD procedure, we preserved the RGEA via the gastroduodenal artery (GDA) and right gastroepiploic vein (RGEV) via the gastrocolic trunk (Fig. ). We needed to determine whether the remnant stomach could be safely preserved; therefore, an indocyanine green (ICG) fluorescence test was performed (Fig. ). The results from this test confirmed a good blood supply for the remnant stomach. Pathological examination showed bile duct cancer and pathological stage T2N1M0 stage IIb (TNM classification). The postoperative course was uneventful, and the patient was discharged on postoperative day 29. |
pmc-6419662-2 | A 58-year-old man was initially admitted to a nearby hospital due to jaundice and detected stenosis of the common bile duct. He was referred to our hospital for further examination. He had histories of PG for gastric cancer 20 years ago and laparoscopic cholecystectomy for cholecystolithiasis 2 years ago. Serum biochemistry was as follows: AST, 27 U/L; ALT, 24 U/L; T-bil, 0.4 mg/dL; CEA, 3.5 ng/mL; and CA 19-9, 80.3 U/mL. A CT scan showed wall thickening of the common bile duct, but lymph node swelling and vascular invasion were not detected. We diagnosed the patient with common bile duct cancer, and PPPD with preserving the right gastroepiploic vessels was planned. During the PPPD procedure, we preserved the RGEA via the GDA and the RGEV via the gastrocolic trunk (Fig. ) and confirmed a good blood supply for the remnant stomach. Pathological examination showed bile duct cancer and pathological stage T2N1M0 stage IIb (TNM classification). The postoperative course was uneventful, and the patient was discharged on postoperative day 18. |
pmc-6419825-1 | A 54-year-old man was admitted to Shanghai Chest Hospital due to pulmonary shadow incidentally detected on routine chest roentgenograms. Computed tomography (CT) scan showed a large mass with partial pleural adhesion which seemed to originate from the mediastinal pleura rather than the right middle lobe (Fig. a-b). The tumor was well-circumscribed measuring about 4 cm and displayed heterogeneous enhancement (parenchyma of the tumor showed moderate contrast enhancement; 21 HU (Hounsfield Unit) on pre-contrast image and 63 HU on post-contrast image) (Fig. c). On the lung window image, one discrete 11 mm nodule was also noted in the left lower lobe, raising the possibility of lung-to-lung metastases (Fig. d). Right pleural localized enclosing effusion and mild enlargement of mediastinal lymph nodes were additional radiological findings.
Surgical procedures were tentatively scheduled for tumor dissection of the middle lobe and wedge-resection of the left lower lobe. Intraoperative frozen section of the larger mass was interpreted as indeterminate for malignancy in view of the atypical tumor cells growing in the interstitial surrounding blood vessels while the small solid nodule was diagnosed as a poorly differentiated adenocarcinoma (Fig. ). Based on the above analysis and the patient approval, supplementary lobectomy of the right middle lobe and lymph node dissection were performed subsequently.
Gross specimen of the larger tumor showed a well-demarcated and non-encapsulated mass, with a grayish brown cut-surface and significant cystic lacunar structure (Fig. a). Microscopically, the tumor parenchyma was composed of epithelioid cells ranged in perivascular haemangiopericytoma-like patterns with clear or eosinophilic cytoplasm, with rich sinusoidal blood vessels (Fig. b). Trabecular-like and pellet-like growth pattern can be seen in some areas. Abundant clear intracellular glycogen displays positive Periodic Acid-Schiff staining with and without diastase digestion (Fig. c). Mass emergence of intra-nuclear pseudo-inclusions is an important morphological feature of this case. Neoplastic cells with obvious enlarged nucleoli and pathological mitosis were found. In addition, some dispersed bizarre hyperchromatic tumor giant cell (5/50 high-power fields) throughout the tumor is highly distinctive. The small solid nodular of the left lower lobe was confirmed as classic primary lung adenocarcinoma (Fig. d).
Immunohistochemistry showed strong positivity within tumor cells for Vimentin and Melan-A (Fig. a), weak but diffusely positive for TFE3 protein (Fig. b), while HMB45 was negative. The Ki-67 score was about 10%. The neoplastic cells failed to stain with epithelial marker pan-cytokeratin and epithelial membrane antigen (EMA), myogenic marker caldesmon, myogenin and α-smooth muscle actin (α-SMA), and additional antibodies including neuroendocrine markers.
TFE3 gene rearrangement was not identified by fluorescence in-situ hybridization and reverse transcription polymerase chain reaction (RT-PCR). The results of targeted molecular gene alteration including epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), ROS proto-oncogene 1(ROS1), kirsten rat sarcoma viral oncogene (K-ras) of these two tumors were all negative.
The patient underwent three courses of chemotherapy of combined paclitaxel (300 mg) and carboplatin (600 mg) after surgery. A follow up fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) obtained 12 months after chemotherapy showed no metastatic lesions elsewhere. At present, the disease is stable and the patient is followed-up regularly. |
pmc-6419856-1 | A 79-year-old woman was transferred to a nearby hospital because of presyncope and back pain. She had no history of Kawasaki disease or prior thoracic trauma history. On arrival in the nearby hospital, her heart rate was 90 beats/min, and systolic blood pressure was 60 mmHg. Laboratory analyses showed elevated liver enzymes (glutamic oxaloacetic transaminase, 815 IU/L; glutamic pyruvic transaminase, 240 IU/L; lactate dehydrogenase, 924 IU/L), likely induced in response to shock. Transthoracic echocardiography revealed a 37 × 54-mm spherical mass adjacent to the right lateral atrioventricular groove and decompression of the right ventricle resulting from pericardial effusion. Systolic blood pressure improved to 100 mmHg after pericardial drainage (100 mL of blood) and infusion of a vasopressor. Computed tomography (CT) showed multiple aneurysmal masses in front of the heart communicating proximally with the right coronary artery (RCA) (Fig. ). Coronary angiography was therefore performed, revealing three CAA with CAVF. Two of the aneurysms drained into the pulmonary artery and originated from a branch of the RCA, and another arose from the origin of the left anterior descending artery (LAD) and drained into the pulmonary artery. One of the aneurysms from the RCA was a giant CAA, with a diameter of 55 mm (Fig. ).
The patient was transferred to our hospital for surgical treatment. Cardiac tamponade due to either rupture of CAA or CAVF was diagnosed, and emergency surgery was performed through a median sternotomy. The pericardial sac contained blood and clots. On completion of the pericardiotomy, blood oozing was evident and a rupture site was located on the wall of the giant CAA, originating from the ostium of RCA (Figs. and ). Cardiopulmonary bypass was established via an ascending aortic cannula and bicaval cannula. The patient was cooled to moderate hypothermia, the aorta was cross-clamped, and cold blood cardioplegic solution was delivered. The giant CAA was opened and the contents were evacuated. Suture closure of the inflow and outflow of the aneurysm was carried out, and the aneurysmal cavity was obliterated by multiple sutures. After surgery for the giant CAA, the second biggest CAA was found next to the giant CAA and measured 20 mm in diameter. This CAA was treated using a similar maneuver. No further giant aneurysms were subsequently recognized. Coronary artery bypass grafting was not performed, because the aneurysms were located in a small branch of the coronary artery. The smaller aneurysm of the LAD was not operated on, because this aneurysm was < 10 mm in diameter and this was not thought to represent a site of rupture. Furthermore, the fistula was not ligated because of the predicted difficulty of reconstruction.
The patient made an uneventful recovery and was discharged from hospital on postoperative day 13. A histopathological assessment of the excised CAA revealed coronary artery dissection (Fig. ). Follow-up CT was performed every 1 year after surgery. The patient remained well as of the 4-year follow-up, showing no expansion of the small coronary aneurysm. |
pmc-6419880-1 | A 55-year-old female patient presented to our intensive care unit (ICU) after laparoscopic gastric bypass surgery. She had underlying morbid obesity, with a body mass index of 53.6 kg/m2, hypertension and clinically probable obstructive sleep apnoea. Intra-operatively, the surgery was protracted to about eight hours due to technical difficulties. Due to her underlying comorbidities and prolonged surgery, she was admitted to the ICU for post-operative observation and remained intubated. Following extubation on post-operative day 2, she developed persistent tachycardia and hypoxemic respiratory failure and was commenced on noninvasive ventilation (NIV). A few hours later, she developed epigastric pain. An anastomotic leak was suspected, which was confirmed by endoscopic findings. Subsequently, urgent surgical repair of the leak was carried out. She recovered over a course of 5 days after the re-surgery and was discharged to the ward. |
pmc-6419985-1 | A 55-year old Italian woman with a history of cutaneous melanoma was admitted to the Thoracic Surgery Unit of Policlinico Umberto I due to the appearance of pulmonary nodules on a positron emission tomography/computed tomography follow-up exam (, ).
Physical examination and serum chemistry were normal. She was afebrile and in good condition. Due to the high suspicion of lung metastasis from the previously diagnosed melanoma, she underwent wedge resection in the right lower lobe. Gross examination of the surgical specimen revealed a nodular lesion of soft consistency with areas of necrosis, and histology confirmed extensive necrosis surrounded by chronic inflammatory reaction. The main finding consisted of the presence of worms embedded in the necrotic material, showing a thick cuticle and internal organs and exhibiting morphological features of a filarioid parasite (, ). For identification to the species level, polymerase chain reaction–DNA was performed. DNA was extracted from the paraffin block, and the mtDNA cox1 gene fragment (about 650 bp) was amplified using filarioid-generic primers []. Sequence analysis showed a 100% match with a sequence of the same gene of the species Dirofilaria repens, deposited in GenBank (Accession Number ).
The patient had been born and was living in an urban area of Central Italy (Civitavecchia). Questioned on her habits, she reported recent travels to Northeast Italy and every year, in August, to a rural area in Bosnia Herzegovina. During these periodic trips, she recalled being frequently bitten by mosquitoes. Furthermore, the patient’s dog was analyzed by a veterinarian, and neither Dirofilaria nor any other parasite was found in the blood.
The patient was not given anti-infective therapy. At 3-month follow-up, physical examination and blood analyses were normal. |
pmc-6420025-1 | A 36-year-old man presented with a history of acute anterior wall myocardial infarction (MI) with post-infarct angina. He was stabilised with medical therapy. There was no history of hypertension, diabetes mellitus or hyperlipidaemia. The patient was a non-smoker. He was unable to recall any definite symptoms of acute KD in childhood. The physical examination and laboratory data disclosed no abnormalities. The lipid profile, homocysteine and lipoprotein (a) [Lp(a)] levels were within normal limits.
An ECG showed features of recent extensive anterior wall MI. A two-dimensional Doppler echocardiogram showed a left ventricular ejection fraction of 46% with anterolateral wall hypokinesis. Coronary arteriography (, ) demonstrated severe disease involving the left anterior descending, the circumflex and the right coronary arteries. The proximal segments of the arteries were very ectatic. Multiple aneurysms alternating with severe stenoses were seen along the entire length of the vessels, an appearance typically seen in KD. He was stabilised with medical therapy and referred for coronary artery bypass grafting. |
pmc-6420322-1 | Here, we present a 61-year-old woman who presented to a community hospital with two weeks of progressive confusion and generalized weakness. She had been diagnosed four years earlier with stage IIIA, estrogen receptor-positive, progesterone receptor-positive, human epidermal growth factor receptor 2/neu non-amplified infiltrating lobular carcinoma of the breast. She underwent mastectomy and adjuvant therapy with adriamycin and cyclophosphamide, followed by paclitaxel, radiation, and anastrozole. Three years after her diagnosis, she developed an isolated bone metastasis for which she received local radiation, exemestane, and everolimus. The patient was unable to tolerate everolimus and her therapy was changed to palbociclib and fulvestrant. She was maintained on this regimen for more than one year, with no evidence of disease recurrence. However, in the months leading up to her hospitalization, her serum levels of cancer antigen (27.29 U/mL) and carcinoembryonic antigen began to rise. Despite an increase in these tumor markers, there was no evidence of disease recurrence on physical exam or imaging, including bone scan, computed tomography, and positron emission tomography. The lab results at that time showed hypercalcemia (corrected calcium 11.9 mg/dL), transaminitis (aspartate aminotransferase (AST) 88 U/L, alanine aminotransferase (ALT) 45 U/L), and hyperbilirubinemia (total bilirubin 1.8 mg/dL). Magnetic resonance imaging (MRI) of the brain revealed no abnormalities. Additional workup revealed parathyroid hormone-independent hypercalcemia and an elevated ammonia level (95 µmol/L). The patient's hypercalcemia was attributed to a paraneoplastic syndrome and she was started on gemcitabine. An abdominal MRI revealed a normal appearing liver with a moderate volume of ascites (Figure ). Cytology of the ascites fluid confirmed a metastatic adenocarcinoma consistent with her known history of breast cancer.
The patient continued gemcitabine and her mental status, hypercalcemia, and ammonia level improved. However, she returned to the hospital two months later with jaundice, abdominal distention, and worsening encephalopathy. The lab reports were notable for recurrent hypercalcemia (corrected calcium 12.4 mg/dL), transaminitis (AST 86 U/L, ALT 54 U/L), coagulopathy (international normalized ratio 2.3), and hyperbilirubinemia (16.7 mg/dL). A transjugular liver biopsy revealed an elevated hepatic-portal venous pressure gradient, and histologic analysis confirmed metastatic breast carcinoma infiltrating the portal tracts and associated pericellular bridging fibrosis (Figures -), a finding consistent with metastatic carcinomatosis cirrhosis. The patient enrolled in hospice and died shortly after. |
pmc-6420323-1 | An eight-year-old female presented with a three-day history of epistaxis and fever. On examination, there was no hepatosplenomegaly or lymphadenopathy. She underwent a bone marrow biopsy at an outside institution, where she was diagnosed as acute promyelocytic leukemia (APML) on morphology. Subsequently, she received three doses of all-trans-retinoic acid (ATRA). Her bone marrow aspiration slides and trephine block was referred to our institution for a second opinion. On presentation to our institution, laboratory investigations, including a complete blood count and coagulation studies, were ordered. Her complete blood count showed leukocytosis, with the differential leukocytic count revealing 89% blasts. This was compounded with moderate anemia according to the World Health Organization (WHO) guidelines for her age [] and thrombocytopenia. Her laboratory investigations on presentation are shown in Table .
On review, her bone marrow aspirate revealed a hypercellular specimen with 76% blasts. These blasts were medium to large in size, with immature chromatin and abundant, hypergranular cytoplasm. They also showed cytoplasmic vacuolations, prominent nucleoli, and Auer rods. However, abnormal promyelocytes and Faggot cells (Figure ) diagnostic of APML were not seen. The trephine biopsy showed hypercellular marrow with blasts comprising more than 90% marrow cellularity.
A flow cytometric analysis was done on peripheral blood, which showed these blasts to be positive for CD13, CD33, and CD117, strongly positive for myeloperoxidase (MPO), had low expression of CD34, and were negative for HLA-DR. Chromosomal analysis was performed on unstimulated short-term peripheral blood cultures (24 hours), followed by Giemsa trypsin banding. Cytogenetic findings were described according to the International System for Human Cytogenetic Nomenclature (ISCN 2013). An analysis was performed on 16 metaphases, which showed 46,XX,t(8;21)(q22;q22)/47,idem,+4/46,XX. Figure demonstrates the karyotype analysis of the patient.
Peripheral blood was used for RNA extraction using reverse transcription polymerase chain reaction (RT-PCR) protocols for PML-RARα and RUNX1/RUNX1T1 amplification. Polymerase chain reaction (PCR) for RUNX1/RUNX1T1 was positive and PML-RARα and core-binding factor subunit beta (CBFB) were negative. Deoxyribonucleic acid (DNA) analysis for c-KIT mutation was not performed due to the non-availability of the test.
Consequently, the patient was labeled as WHO category acute myeloid leukemia with t(8;21)(q22;q22);RUNX1/RUNX1T1 and was admitted to the oncology ward. She received conventional chemotherapy through the standard protocol. A repeat bone marrow biopsy was performed on day 29 post-chemo-induction, which revealed bone marrow in morphological and cytogenetic remission.
Following this, the patient was put on maintenance therapy. However, she presented 10 months later to our emergency department with disease relapse. Cytogenetics showed the persistence of the t(8;21) clone with no trisomy 4 seen. The patient was advised regular follow-up at the hematology clinic where workup for hematopoietic stem cell transplant was started. |
Subsets and Splits
Exclude ER emergencies
Retrieves 100 descriptions that do not contain the terms 'ER' or 'emergency', providing a basic filter of the dataset.