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pmc-6545755-1 | An 18-year-old male initially presented at age 9 with symptomatic iron-deficiency anemia (IDA). He was otherwise healthy and had no family history of GI disorders. Serological evaluation including a leukocyte count, comprehensive metabolic panel, and fecal occult blood testing (FOBT) revealed no abnormalities at that time. Nearly a decade later, persistent IDA in the setting of new FOBT and fecal calprotectin positivity prompted endoscopic evaluation. He was found to have small, sessile polyps in the gastric body and antrum as well as the duodenum with underlying patchy erythema. Tissue biopsy of the gastric mucosa showed moderate, chronic inflammation, without true polyp formation. Biopsy specimens were negative for intraepithelial eosinophils, lymphocytosis, parasites, H. Pylori, or intestinal metaplasia. Colonoscopy revealed an ileocecal valve “polyp” that displayed mild, chronic active ileitis not accompanied by villous distortion, intraepithelial lymphocytosis, pyloric metaplasia, or granuloma formation.
A video capsule endoscopy (VCE) was deployed to evaluate for evidence of small bowel pathology. Multiple small sessile polyps were seen in the stomach; however visualization of the small bowel was limited due to obstruction of visualization by fecal material in the proximal small bowel. VCE was spontaneously passed and a subsequent push enteroscopy was performed to complete examination of the small bowel. Enteroscopy confirmed the presence of numerous polyps, ranging from 4 to 15 mm in size, along the greater curvature of the gastric body (), as well as throughout the entire duodenum and in the proximal jejunum (beyond the ligament of Treitz) ().
Biopsies of the polypoid duodenal mucosa and endoscopic mucosal resection (EMR) of the proximal jejunum () revealed focally increased chronic as well as acute inflammation with pseudopolyp formation, evidence of reactive lymphoid hyperplasia in the lamina propria, focal cryptitis, and villous blunting and epithelial regenerative changes (Figures and ). Sampling of the gastric mucosa revealed inflammatory polypoid gastric mucosa, focal crypt abscesses, and increased chronic inflammation in the lamina propria, glandular epithelial reactive changes, and superficial foveolar epithelial regenerative changes (). No increased intraepithelial lymphocytosis, granuloma, or dysplasia was identified. |
pmc-6545763-1 | A 54-year-old male with a history of type 1 diabetes mellitus and biopsy confirmed IgA nephropathy and received a simultaneous pancreas-kidney (SPK) transplant in 1996. He received induction immunosuppression with OKT3, methylprednisolone (MPN), cyclosporine A (CyA), and azathioprine (AZA). The immediate posttransplant period was complicated with acute cellular grade Ia kidney rejection (treated with three bolus of MPN), and a biopsy confirmed Herpes simplex virus (HSV) and cytomegalovirus (CMV) esophagitis (treated with acyclovir and ganciclovir, respectively). At six months, seroconversion of hepatitis C virus (HCV) was diagnosed following transient elevation of transaminases and cholestasis. HCV infection route could not be determined, since donor was HCV negative (ELISA), and HCV detection (ELISA) was standard protocol at hospital blood bank previous to blood transfusions. Azathioprine was withdrawn due to the hepatotoxicity risk. Follow-up from month 6 onwards was uneventful while on maintenance immunosuppression with CSA and prednisone 5mg and with functioning allografts (serum creatinine 0.9mg/dL, HbA1c <6% and normal serum amylase and lipase). Despite positive HCV viremia (latest RNA determination with 1.637.000 copies/mL), a conservative management was decided due to the increased treatment induced rejection risk.
In October 2014, patient was diagnosed with an IgG-kappa monoclonal gammopathy of undetermined significance (serum M protein of 24 g/L, serum κ/λ ratio of 5.2, proteinuria of 249 mg/24h with the presence of monoclonal IgG-kappa by immunofixation in urine, and <10% plasma cells in the bone marrow aspirate), without end-organ damage that could be attributed to the gammopathy. Both grafts presented normal function (HgA1C 5.9%, serum creatinine 1.5mg/dL).
Nine months later (19 years after transplant) patient presents a new-onset hyperglycemia (HgA1C 8.6%, C-peptide 6.15ng/mL, anti-GAD 0.9U/mL). Ultrasound revealed a globular and heterogeneous pancreas allograft, with biopsy evidencing a diffuse monotypic plasma cell infiltrate, with scarce normal parenchyma observed. Plasma cells were CD19, CD79a, CD138, and IgG-κ positive, with a cell proliferation index (Ki-67) under 3% (). In situ hybridization for EBV (EBER) was negative. Serum calcium and hemoglobin remained normal, and kidney function was stable (serum creatinine 1.4mg/dL). Serum M protein had increased up to 34 g/L (), serum κ/λ ratio was 8.2, urinary protein excretion was normal, and 7% plasma cells were with abnormal phenotype identified on a bone marrow aspirate. Solid-phase Luminex® bead array was negative for HLA class I and class II antibodies. Positron emission tomography (PET) scan revealed a fludeoxyglucose (FDG) uptake limited to pancreas allograft (Figures and ). Serum EBV and HHV-6 PCR were negative.
Tumor origin determination was attempted using DNA extracted from a highly infiltrated section of the paraffin block. HLA phenotyping revealed a mixed chimerism (Figures –). Sex mismatching was unsuitable for determination of tumor origin (male donor).
Diagnosis of extramedullary plasmacytoma localized to the pancreas allograft was established and treatment with bortezomib and dexamethasone initiated, following CSA withdrawal. Patient eventually died one month following the beginning of treatment due to spontaneous cerebral hemorrhage, secondary to a hypertensive emergency. |
pmc-6545764-1 | A 25-year-old woman gravida 2 para 1 (G2P1) sent by the Maternity Department for an exaggerated bilateral breast enlargement at 32-week gestation. The first pregnancy went on well. There are no similar cases in the family. She did not show signs suggestive of systemic disease including systemic lupus erythematosus. The examination showed bilateral giant breasts with collateral venous circulation and trophic changes marked by the necrosis of the distal third of the mammary skin involving the nipple-areolar complex (). The histology of the biopsied ulcerative mammary gland was in favour of a subchronic inflammatory tissue without abscess. The biological search for autoantibodies like ANA, anti-ENA, and anti-dsDNA could not be done because it is not available.
Through this consultation between obstetricians and surgeons, a normal delivery was conducted after foetal lung maturation. Twenty-one days postpartum, a reductive mammary surgery was performed with nipple plasty (Figures –).
After a short period of lymphangitis (), postoperative follow-up was normal. Cosmetic and psychological result was satisfactory after 18 months (); the patient does not want to get pregnant again, but we are following her up regularly to appreciate long-term evolution. |
pmc-6545788-1 | A 27-year-old man with history of polysubstance abuse was witnessed to inhale “K2,” a synthetic cannabinoid. Over the next hour, he became unresponsive and was brought to an emergency room where he was found to be hypoxemic. There was no evidence of traumatic injury. He was intubated and admitted to the intensive care unit (ICU).
He had no other significant past medical history. Physical examination revealed an intubated and sedated patient; temperature was 97.1 °F, blood pressure was 144/84 mmHg, pulse was 98 beats/min, and oxygen saturation was 100% on FiO2 0.5; and bilateral coarse crackles were audible on chest auscultation.
Laboratory evaluation revealed WBC 10,900/dL, hemoglobin 12.6 g/dL, hematocrit 39.8 %, platelets 191,000/dL, sodium 140 meq/L, potassium 3.7 meq/L, chloride 102 meq/L, bicarbonate 19 mmol/L, BUN 13 mg/dL, creatinine 1.2 mg/dL, and creatine kinase 1,952 IU/L. Computed tomography (CT) of the brain showed no acute intracranial pathology. His initial arterial blood gas (ABG) values were pH 7.28, pCO2 58 mmHg, and pO2 125 mmHg on 50% oxygen. Chest radiography revealed alveolar opacities in the right upper lobe ().
The patient was started on broad-spectrum antibiotics. A urine and blood toxicology screen was positive for benzodiazepines (which he received after intubation) and negative for amphetamines, barbiturates, cocaine, opiates, phencyclidine, methadone, and cannabinoids. On the second day, frank blood was noted on suction from the endotracheal tube. His gas exchange worsened requiring a FiO2 1.0 to maintain adequate oxygenation. A blood gas showed profound hypoxemia with a pO2 110 mmHg. A chest radiograph revealed worsening bilateral alveolar infiltrates (). A CT of the chest revealed patchy ground glass opacities and diffuse lung consolidation (). Bronchoscopy was performed and showed oozing of blood from all right lung airways and the left lower lobe bronchus. Sequential bronchoalveolar lavage (BAL) confirmed diffuse alveolar hemorrhage by demonstrating increasingly bloody return. Hemosiderin laden macrophages were seen in BAL fluid on microscopy. Measurements of serum anti-nuclear antibody, anti-neutrophil cytoplasmic antibody, and anti-glomerular basement membrane antibody were negative. Urine analysis was negative for hematuria. BAL was negative for an infectious etiology. An echocardiogram was normal. There was no evidence of coagulopathy. UR- 144 N (4/5-hydroxypentyl), a metabolite of UR-144, was identified in the patient's blood by qualitative enzyme-linked immunosorbent assay (ELISA).
The patient was empirically treated with high-dose steroid for 3 days, followed by prednisone 40 mg/day that was tapered to 10 mg/day over 4 days and then discontinued. Over the 48 hours after corticosteroid administration, his oxygenation improved significantly. A chest radiograph performed 96 hours after admission showed complete resolution of the alveolar opacities. The patient was successfully extubated and transferred out of ICU. He was discharged 10 days after admission, neurologically and functionally intact. |
pmc-6545809-1 | A 29-year-old Saudi male presented to our institution (King Khaled Eye Specialist Hospital, KKESH) on 2007 seeking a refractive procedure. The patient had a history of cleft lip repair and had no systemic illness at presentation. The patient denied ocular trauma, ocular surgery or a family history of visual dysfunction. On ocular examination, the visual acuity in the right eye (OD) was 20/50 with a subjective cycloplegic refraction of +15.25 - 0.75 x 140° and 20/30 in the left eye (OS) with a subjective cycloplegic refraction of +15.00 -0.50 x 30°. The interpupillary distance was 63 mm. Intraocular pressure in both eyes (OU) was 19 mmHg. Slit lamp examination was unremarkable OU. White-to-white corneal measurements were 12.2 mm OD and 11.5 mm OS as measured with the slit lamp. The steepest keratometry (K) was 48.3 D at 31° OD and 48.8 D at 116° OS. The corneal thickness measurements were 512 μm OD and 511 μm OS. The biometric measurements as measured by (Orbscan IIz, Bausch and Lomb, Rochester, NY, USA) of the anterior chamber depth revealed 3.32 mm OD and 3.49 mm OS. Iris examination indicated patent peripheral YAG laser iridotomies bilaterally without correctopia OU Piggyback intraocular lenses were present OU.
Indirect ophthalmoscopy was remarkable for crowded optic discs and subretinal drusenoid yellow-white dots symmetrically distributed in the posterior pole OU. Bilaterally, the retinal blood vessels appeared normal, with no clinically obvious papillomacular folds and peripheral pigmentary bone spicule pigmentation.
Macular spectral-domain optical coherence tomography (SD-OCT) revealed inverted U-shaped papillomacular folds OU (). Posterior microphthalmia was then suspected and A–scan axial length measurements were 16.40 mm OD and 16.65 mm OS. Fluorescein angiography showed no optic nerve head staining or leakage. Staining of the yellowish subretinal drusenoids deposits was seen in the later frames OU (). The diagnosis of posterior microphthalmia was confirmed with the given findings and no further intervention was recommended. |
pmc-6545821-1 | A 19-year-old male patient was referred to the Immunology clinic by his General Practitioner (GP). He presented with a two-month history of urticaria with intermittent episodes of angioedema. His initial symptoms included facial pruritis, periorbital erythema and angioedema involving the upper and lower lips. Within 30 minutes of his first episode of angioedema, he developed widespread urticaria which responded to treatment with antihistamines. The following day, he experienced a recurrence of the symptoms and continued to have almost daily symptoms of urticaria with intermittent episodes of angioedema. He was commenced on an alternative anti-histamine by his GP but continued to develop urticaria and experience swellings of the hands and feet. His treatment was escalated at his initial visit to Immunology Clinic to fexofenadine 180mg twice a day with an additional 10–20mg of cetirizine. In addition, montelukast, a leukotriene receptor antagonist, was commenced.
The number of hives and degree of pruritis were graded using an objective scoring system known as the Urticaria Activity Score 7 (UAS7) that provides a weekly average score out of a maximum score of 42. The patient recorded weekly UAS7 scores of 30, despite treatment with maximum doses of antihistamines and montelukast. Therefore, Anti-IgE therapy with the monoclonal antibody ‘Omalizumab’ was offered. In the interim, he presented to his dentist with a broken tooth and was found to have carious molars requiring root canal treatment. One week after this intervention, his UAS7 score fell to 4 and then to 0, and he has remained in remission (UAS 7 score 0) for 9 months. As he was rather needle-phobic, he was delighted that this obviated the need for Omalizumab injections. Initial investigations including full blood count, renal function, liver function and thyroid function tests were all within the normal ranges. |
pmc-6546259-1 | A 23-year-old previously healthy Chinese female who was 4 weeks gravid at admission presented with 2 weeks of nausea, vomiting, abdominal pain and chest pain. Her chest pain was sharp and retrosternal, unrelated to activity, and did not vary with position or respiration.
On admission, she was tachycardic but otherwise haemodynamically stable. Physical exam was notable for decreased heart sounds, abdominal distention and ascites. Electrocardiogram (EKG) findings demonstrated sinus tachycardia and low voltage QRS. Labs were significant for hyponatremia (131 mEq/L), anion gap metabolic acidosis, elevated International Normalized Ratio (INR) (1.8), Aspartate Aminotransferase (AST) (64 U/L) and Alanine Aminotransferase (ALT) (58 U/L). Chest x-ray revealed bilateral pleural effusions, and abdominal ultrasound showed hyperechoic masses on the liver.
Paracentesis of the ascitic fluid suggested a transudative process. Abdominal magnetic resonance imaging (MRI) demonstrated a 3.7 cm mass in the right hepatic lobe with decreased signal intensity on T1 and numerous hyperintense nodules on T2-weighted imaging concerning for metastatic disease. Marked cardiomegaly was incidentally noted. Liver biopsy showed anastomosing hemangiomas without evidence of malignancy. During workup, she developed hypotension, tachycardia and dyspnoea. An emergent transthoracic echocardiography (TTE) showed a large pericardial effusion with early tamponade (). She had an emergent pericardial window with mediastinal drain placement; cytopathologic and microbiologic analysis from pericardial fluid were negative for malignancy and infection. Two subsequent TTEs showed right ventricular systolic dysfunction, right atrial enlargement and an ejection fraction (EF) of 40%–44%. Due to the patient’s tamponade and worsening cardiac function without an identifiable cause, a cardiac MRI (CMRI) was done to better assess the patient’s cardiac structure and function (). Her CMRI demonstrated a large, ill-defined right atrial mass isointense on T1 and hyperintense on T2 ( and ).
The patient had an open biopsy of the cardiac mass via a right anterior thoracotomy approach that indicated a high-grade PCAS (). Staging workup with Positron Emission Tomography (PET)-CT showed increased uptake in the right atrial mass. Despite a non-diagnostic liver biopsy for metastasis, imaging raised concern for metastatic disease and the patient was treated as such. The patient opted for elective termination of pregnancy and was started on combination adriamycin and ifosfamide chemotherapy. Her EF dropped by 10% after completing two cycles of therapy and was subsequently switched to a second-line regimen with gemcitabine and docetaxel chemotherapy. Repeat staging 4 months later showed absent Fluorodeoxyglucose (FDG) uptake in the right atrium and decreased tumour burden (1.3 cm × 1.0 cm) () along with a decreased size of the hepatic lesions. Nine months after initial diagnosis, she continues to receive chemotherapy without disease progression. |
pmc-6546307-1 | We present the case of a 28-year-old male who suffered a high-energy motorcycle accident. At admission, the patient was conscious, Glasgow coma scale (GCS) 15, hemodynamically stable, and presenting superficial excoriations on the trunk and lower limbs. However, there was a wound of approximately 20 cm on the lateral aspect of the right hip at the level of the greater trochanter, exposing the entire proximal end of the femur (Figure ).
After a clinical evaluation and imaging tests that excluded cranial or abdominal disorders, we prioritized the neurovascular examination of the affected limb, which did not present complications, and the protection of the femoral head with the use of moistened gauze and saline solution. Radiographs in the anteroposterior view of the right hip showed a hip dislocation with a greater trochanter fracture (Figure ).
An exhaustive irrigation of the acetabular cavity and the exposed femur was performed, using 10 liters of saline solution at 9% when the patient was in the surgical room. The procedure happened under sedation and spinal anesthesia. A large debridement of muscle, fascia, and bone tissues was required to remove all the devitalized tissue, considered viable only when active bleeding and the clean appearance of the open wound was observed through direct vision by the surgeons.
The fractured fragment of the greater trochanter was fixed with two 6.5 mm cancellous screws and washers at the proximal end of the femur (Figure ). After a revision of the debridement sites and radioscopic control of the hip reduction and fixation, the wound was closed (Figure ).
After the first 48 hours of surgery, the wound was releasing a significant amount of secretion, bloody and serum like, and a strong odor was observed, with no laboratory exams indicating infection. At this time, a new surgical procedure (second look) with greater aggressiveness was obtained, removing all devitalized tissue and bad-in-appearance cutaneous cover, which was not necrotic but had an unhealthy appearance (Figure ). A vacuum-assisted closure was used (Figure ).
The vacuum-assisted closure was changed every week for four weeks until the appearance of granulation tissue at the surface of the surgical wound (Figure ). During this period, the patient's laboratory exams showed a drop in the hemoglobin level, resulting in a 7.1 g/dl result, which was corrected with a transfusion of 600 ml of red blood cell (RBC) concentrate. As a rehabilitation procedure, we started daily physiotherapy with passive limb mobility and activity, within pain limits, with no load on the right hip.
In the fifth week, a new surgical procedure was performed for skin grafting. It was performed with no major occurrences and implantation of the graft was successful. Shortly after the removal of the stitches from the graft surgery, in about eight weeks, partial weight bearing on the affected limb was initiated with the use of two crutches.
After a one-year follow-up, the patient had good mobility of the affected limb (Figure ) without significant pain during mobilization and examination of the joint, with a Harris Hip Score of 93 points. The radiograph showed a decrease of the articular space in the right hip (Figure ) but the magnetic resonance imaging (MRI) showed no necrosis of the femoral head. (Figure ). He was able to ride a bicycle, run, and do squats. |
pmc-6546833-1 | Mrs. G.F., 60 years old, married, oceanographer, civil servant. She exhibited behaviors such as inattentiveness and forgetfulness dating back to childhood, when they were associated with poor performance at school to the point where she had to repeat grade 1. In adulthood, she exhibited significant functional impairment due to the inability to self-organize or prioritize tasks, a tendency to procrastinate, and a need for silence to concentrate and be productive. Eventually, she resigned from a management position at work because she was not able to finish assignments on time and had to take work home, which affected her family life. Psychiatric care was initially sought due to a depressive episode with persistence, even after remission, of the following symptoms: inattentiveness, forgetfulness, difficulty falling asleep, delays meeting her commitments, and lack of planning.
No family history of dementia and no clinical problems were reported at the first assessment. Neuroimaging exams (MRI) revealed normal morphology and size for the patient’s age group. There was no evidence of acute ischemic injury.
Attention-deficit/hyperactivity disorder (inattentive subtype) and depressive disorder (remitted). The proposed medical treatment was venlafaxine 75 mg/day and methylphenidate up to 60 mg/day. |
pmc-6546833-2 | Mrs. T.B, 77 years old, widowed, four completed years of formal schooling, retired. In 2001, she was 67 years old and healthy; however, a friend observed that she was quite absent-minded and advised her to seek help. The patient reported that she was agitated and forgetful during childhood and was the only one of three siblings who failed to complete a higher education. As a child, she was restless, used to escape from school to play, and did not pay attention when she was in the classroom. As a consequence, she often failed school assignments, needed to repeat some school years, and dropped out of school in her early teens. She worked many years for a company where the work was mechanical and repetitive, and she rarely arrived on time at work, missed appointments, and was less efficient than her colleagues. She never read an entire book because of her difficulty concentrating. She always forgot to pay bills, lost or misplaced personal objects, and needed the help of her family to remember commitments. She married at 20, and her husband took care of everything. After he died, her everyday life was seriously affected. Eventually, her children had to assume the task of organizing her life. Some years later, before treatment, she left home forgetting a roast in the oven.
At the first assessment, in 2001, the patient reported no clinical problems, no signs of depression or anxiety, and denied having ever experienced any psychiatry conditions. At that assessment, an electrocardiogram (ECG; results were within the limits of normality) and a computerized tomography scan of the brain (presented as preserved, with normal attenuation values to X-rays) were collected.
Attention-deficit/hyperactivity disorder (inattentive subtype). The proposed medical treatment was methylphenidate up to 10 mg/day. In the period leading up to the last evaluation, she took methylphenidate 20 mg/day. |
pmc-6546850-1 | A 68-year-old male patient was transferred to our neurological department after he had been admitted to another hospital twice before. The first admission had taken place 3 months before in July 2018 due to visual impairments (hemianopsia to the right) and uncommon behavior. The MRI had shown a T2-weighted (T2w)-FLAIR hyperintensity in the left temporooccipital lobe that had been interpreted as an ischemic stroke. The results of cardiovascular investigations had been normal and the patient had been discharged. In August 2018 he had been admitted again with a progression of symptoms consisting of severe sensory aphasia, psychomotoric deficits and progressive visual impairments. The MRI had displayed a massive enlargement of parietooccipital lesions in both hemispheres predominantly affecting the left white matter (). The polymerase chain reaction (PCR) for JCV in the cerebrospinal fluid (CSF) had been positive whereas routine analysis of the CSF had shown normal results (cell count and distribution, lactate, protein). PCR for Varizella zoster virus had been negative. Serologic tests for Borrelia burgdorferi, Treponema pallidum, Herpes simplex virus, measles, Varizella zoster virus, HIV and hepatitis B and C had also been negative.
The patient was then transferred to our department for further diagnostics. His general physician and relatives revealed that the medical history contained no record of frequent or severe infections. He had never received any kind of immunosuppressive treatment. In 1999 the patient had suffered from a myocardial infarction. The medical history was unremarkable apart from arterial hypertension and a helicobacter-positive gastritis. In 2017 he had got a viral infection with mild influenza-like-symptoms. Neither the patient nor his family knew of any recent vaccinations.
Upon admission to our neurologic department he had developed a right sided homonymous hemianopsia, severe sensory aphasia and disorientation. Our CSF analysis showed a pleocytosis (22 cells/μl) and an elevated protein concentration (0.72 g/l). The cell-distribution was mostly lymphocytic, but monocytes and granulocytes were found as well. CSF specific oligoclonal bands (type 2) were present and there was an intrathecal production of IgG and IgM. The JCV-PCR (1E3 c/ml) from CSF and the JCV-antibody-index (24.000 AU/ml serum) were positive. All additional tests were negative (HSV, VZV, and Ebstein-barr-virus (EBV) in the CSF by PCR, as well as tickborn encephalitis (TBE), enterovirus, and cytomegalovirus serologically; CSF-antibody-indices for HSV, EBV, VZV and CMV). All investigated autoimmune encephalitis antibodies (anti-NMDAR, -AMPAR1/2, -CASPR2, -LGI1, -GABAR-b1/b2, -Yu, -Hu, -Ri, -Amphiphysin, -CV2/CRMP-5, -Ma1/2, -GAD, -SOX1, -Tr(DNER), -Zic4) were negative in serum and CSF.
Further investigations concerning an immunodeficiency were inconspicuous. An HIV-test was negative. The blood tests including peripheral blood cell count and inflammatory parameters showed mild eosinophilia (10,3%), elevated rheumatoid factor (60.5 IU/ml), Cardiolipin-IgM-antibodies (14 MPL-U/ml), and antinuclear antibodies (ANA, 1:320) of unspecific speckled pattern in the immunofluorescence and without specificity against ds-DNA or extractable nuclear antigens. An abdominal sonography showed a splenomegaly and prominent lymph nodes but no sign of neoplasia. We performed a whole-body PET/CT (including the brain) with 296 MBq 18F-Fluorodeoxyglucose (18F-FDG) 60 min p.i. to search for a malignancy or an inflammatory disease. The PET scan showed prominent mediastinal lymph nodes with moderately high metabolism, however, it did not reveal any profound hypermetabolic lesions. 18F-FDG uptake in the brain was further evaluated using statistical parametric mapping (SPM) for comparison with a reference group. The cerebral glucose metabolism was lowered bilaterally in parietotemporal and occipital areas with a clear predominance on the left side. The metabolism in the frontal cortex, basal ganglia, and cerebellar regions appeared to be normal ().
A biopsy of the prominent mediastinal lymph nodes identified in the PET investigation showed no signs of malignancy or granuloma. Additionally ACE and the soluble IL-2-receptor in the blood were normal, so sarcoidosis seemed unlikely. The HLA-DR-expression and phenotyping of lymphocytes showed normal results [amount and distribution of CD3+, CD4+, CD8+, B-cells (CD20+), and natural killer cells (CD16+)]. In addition to extensive phenotyping of peripheral blood mononuclear cells (PBMC) even the functional analyses by proliferation assays of PBMC by plant lectins (PHA, Con A, PWM), tuberculin (PPD) and anti-CD3, spontaneous and antibody-dependent NK-cell activity (ADCC) were within normal range.
During inpatient treatment the patient developed a cough and had impaired breathing. The tracheal exudate was positive for HSV using PCR so we started a therapy with intravenous aciclovir which improved the respiratory symptoms markedly. In September 2018 a progression of the patient's symptoms with focal and generalized seizures occurred. We started a medication with levetiracetam and had to add valproate and lacosamide to the antiepileptic treatment due to recurring seizures. The MRI showed a further expansion of the lesions with a new peripheral contrast enhancement () as a sign of a PML-related immune reconstitution inflammatory syndrome (PML-IRIS). We treated the patient with a high dose of corticosteroids (1 g/d methylprednisolone for 5 days intravenously). After this therapy the seizures decreased and the anticonvulsive treatment could be reduced to levetiracetam and valproate. Finally, we applied a treatment with mirtazapine to our patient, which is able to block the specific serotonin-receptors used by JCV, since this was beneficial in a previous report of a PML in an immunocompetent patient (). Mefloquine, another drug with potentially antiviral effects against JCV, was not included to the treatment as seizures are a strict contraindication ().
After nearly 2 months the patient was transferred to a rehabilitation facility. Visual impairments, disorientation and a sensory aphasia were still persistent. During the following weeks the patient developed severe dysphagia until oral intake of food and fluids was no longer possible. The patient died 2 months after the transfer to a nursery home due to a respiratory infection and pulmonary insufficiency. |
pmc-6547021-1 | The patient was a 23-year-old woman (height: 167 cm, weight: 72.3 kg) from a non-consanguineous family, with asymptomatic parents and brothers. From 14 years of age she had 19 episodes of rhabdomyolysis, all of them requiring hospitalization (two of them after the genetic diagnosis), with a median duration of 4 days (range 1–14), and a maximum creatine kinase (CK) concentration of 39,994 ± 66,148 U/L (range 2,121–276,000 U/L). Three episodes of rhabdomyolysis were accompanied by renal failure (). Physical examination and CK levels were normal between the episodes. At 21 years of age, the patient was assessed using a targeted next-generation sequencing-based panel containing 256 neuromuscular disease genes, and found to have a compound heterozygous mutation c.589G > A (p.Val197Met)/c.1742T > C (p.lle581Thr) in the gene (ACADVL, MIM 609565) encoding VLCAD. The patient gave her written consent to participate in the study and for the data to be published, after a thorough explanation about VLCADD and the purpose of the study, which was approved by the local institutional ethics committee.
At the first visit to our laboratory (March 2017), the patient underwent ergospirometry. It was our intention to use a stepped incremental ergospirometry protocol with an initial power of 0 watts and a power increase of 30 watts/3 min, at 60 rpm of pedaling rate (), but the patient developed muscle pain and was unable to complete the 1st step (0 watts). Thus, she was asked to maintain a high pedaling rate (∼100 rpm) with the aim of recruiting type IIA and IIX fibers (not dependent on fatty acids) (). As the patient reported no pain at these pedaling cadences, a test was performed on an electromagnetic cycle ergometer (Ergometrics 900, Ergoline, Barcelona, Spain) using an incremental discontinuous step protocol, with steps of 1 min of exercise interspersed with periods of 1 min of passive recovery, always maintaining a high cadence. The test was started at 10 watts, with a load increase of 10 watts/step. At the end of each step, a rating of perceived effort (RPE) was assessed according to the OMNI scale (), and lower limb pain perception was scored using a numeric rating scale (NRS) (0–10) (). She was also asked at the end of the test whether she had a perception of muscle crises. The test was performed in the exercise physiology laboratory of Pablo de Olavide University under medical supervision, and the intensive care unit of Hospital Virgen del Rocío (Seville, Spain) was advised to be prepared.
Heart rate (HR, in bpm) was continuously monitored during the test from a 12-lead ECG. A breath-by-breath automatic system (CPX ultima, Medical Graphics Corporation, St Paul, MN, United States) was used to measure gas-exchange parameters: oxygen uptake (VO2, in mL⋅min−1 and mL⋅kg−1⋅min−1), carbon dioxide production (VCO2, mL⋅min−1), ventilation (VE, in L⋅min−1), and ventilatory equivalent for O2 (VE⋅VO2−1). Average values of the last 10 s of each step were obtained.
One hour before evaluation the patient ingested 500 mL of an isotonic drink (30 g CHO) Gatorade, PepsiCo, Purchase, NY, United States) with 15 g of MCT (Myprotein, Cheshire, United Kingdom), proportions that have been recommended for intestinal absorption (; ). It is known that MCT can circumvent the block in the β-oxidation of long-chain fatty acids in VLCADD and can provide an alternative energy substrate to long-chain triglycerides (LCT) (), in addition to decreasing the oxidation of CHO, and reducing the risk of lactic acidosis induced by exercise (). Moreover, supplementation with CHO increases blood glucose levels and improves performance (). Accordingly, the role of this supplement was to (i) increase the work capacity during the test, (ii) maintain the glycemia level to reduce fat oxidation during recovery, and (iii) provide MCT for oxidation during the hours after assessment, thereby reducing the risk of post-exercise rhabdomyolysis (). Blood samples were collected 2 days before each evaluation to measure CK concentration. Laboratory evaluations were repeated at the end of the 3rd and 6th month.
The patient followed a 6-month combined (HIIT + strength training) exercise program supervised by a fitness specialist. The first month consisted of only HIIT (2 days⋅week−1), while in the following 5 months combined training was carried out 4 days⋅week−1 (HIIT 2 days⋅week−1 and strength training 2 days⋅week−1). HIIT was done in cycle ergometer and consisted of 6 sets of 70–80 s performed at maximum intensity with a minimum cadence of 100 rpm, with 1 min passive recovery periods between sets. We chose this type of training to maintain a high demand for glycolysis during exercise and, therefore, avoid the dependence of lipolysis on energy production (at the highest possible intensity, well above FATMAX) (). HR and RPE were registered at the end of each set, while pain perception was registered at the end of the training session (). Three hours later, the patient was asked if she had a perception of (i) muscle swelling similar to that experienced before her hospital admissions (in order to anticipate a possible muscle crisis) and (ii) risk of actual muscle “crisis” (i.e., rhabdomyolysis).
The following strength training exercises were performed with dumbbells and elastic bands: bench press, biceps curl, bent-over dumbbell row, lying triceps extension and dumbbell lateral rise, and also ½ squat using body weight. The exercise routine was designed as a circuit, with 2 laps of 4–7 repetitions, with 2 min rest between sets and 4 min rest between laps. The OMNI Resistance Exercise Scale () was used to measure RPE. The initial load was fixed at 5–7 of this 0–10 scale. Three hours after each strength session the patient was asked about muscle swelling. The morning after each session, she was asked if she had delayed-onset muscle soreness (using a scale of 0–10 in case of presentation).
Given the high intensity of HIIT, and the excess post-exercise oxygen consumption (EPOC) elicited by intense exercise bouts (; ; ; ), all training sessions were performed 60 min after ingestion of the pre-exercise supplement (30 g CHO + 15 g MCT). Warm-up sessions were also designed specifically to avoid fat oxidation and comprised 30 s bouts of intense exercise (at 80% of VO2peak achieved in the incremental step test) before HIIT and sets of low repetitions at high speed (without weights) before strength training. With the same objective, we decided not to include a cool-down phase after HIIT sessions. |
pmc-6547174-1 | A 57-year-old previously healthy Caucasian male presented to a community hospital
with a 3-day onset of epigastric abdominal pain, nausea, vomiting, and new-onset
ascites. Initial workup revealed normal liver function studies. His lipase was
elevated. Diagnostic paracentesis was consistent with hemorrhagic fluid with red
blood cell count of 640 504/mm3 and white blood cell count of
1440/mm3. Computed tomography scan of the abdomen was concerning for
a 15 mm lesion in the pancreatic head, peripancreatic stranding, and large-volume
ascites. He was transferred to this tertiary care hospital for further workup of
acute hemorrhagic pancreatitis and possible endoscopic ultrasound/endoscopic
retrograde cholangiopancreatography for further workup of the pancreatic head
lesion.
He had been in good health prior to this presentation. Past medical history was
pertinent for hypertension and chronic obstructive pulmonary disease. He had no
history of pancreatitis, gallstones, or other hepatobiliary disease. Social history
revealed that he was active, independent, and lived by himself. He had 1 rum drink
daily and smoked 2 cigarettes per day. Review of systems was pertinent for
blistering of the hands, with subsequent scabbing and pigmentation changes, with
onset a few days prior to the abdominal pain. He was not sure if there was a
relationship to sun exposure. Associated with the blisters, the patient described
unrelenting pruritis of his hands bilaterally. This was the first time in his life
he was experiencing cutaneous symptoms as he had never had skin problems before.
On admission to our institution, vital signs demonstrated temperature 37.0°C, blood
pressure 146/95 mm Hg, heart rate 112 beats per minute, respiratory rate 20 breaths
per minute, and oxygen saturation 96% on room air. On examination, he was in mild
distress from abdominal pain and nausea. Abdomen was distended and mildly tender in
the epigastric region. A fluid wave was appreciated. There was no
hepatosplenomegaly. Dermatology examination revealed vesicles and bullae with
erythematous bases, in different stages of healing seen over the dorsal aspects of
the both hands with scaling, scarring, and hypopigmentation and hyperpigmentation of
the skin (). They
were pruritic but not painful. There was no hypertrichosis appreciated. There were
no stigmata of chronic liver disease and no scleral icterus.
Complete blood count demonstrated hemoglobin of 8.5 gm/dL (mean corpuscular volume 95
fL), white blood cell count of 10 500/mm3 (76% polymorphonuclear cells),
and platelets 328 000/mm3. Renal function tests were normal. Liver
function tests demonstrated total bilirubin 0.3 mg/dL, aspartate aminotransferase 16
U/L, alanine aminotransferase 7 U/L, alkaline phosphatase 88 U/L, and albumin 1.6
g/dL. The international normalized ratio was 1.35. Lipase was elevated to 352 U/L.
Repeat diagnostic paracentesis again demonstrated grossly bloody fluid with an
amylase of 2866 U/L.
Further workup for acute hemorrhagic pancreatitis included a computed tomography
angiogram, which did not show active bleeding. The nature of the pancreatic head
lesion was still indeterminate so an endoscopic ultrasound was performed, which did
not show any focal lesion concerning for malignancy. Endoscopic retrograde
cholangiopancreatography done showed a large proximal pancreatic duct disruption,
which was treated with a plastic stent. He was managed supportively with intravenous
fluids and pain relief for acute hemorrhagic pancreatitis.
Further workup of his skin lesions was initiated due to the concern for porphyria
cutanea tarda (PCT). Skin biopsy showed blistering dermatosis, subepithelial with
evidence of re-epithelialization. Periodic acid–Schiff stain (PAS) with diastase
highlighted increased PAS+ deposition around vessel walls and focal PAS+ deposits
within the epidermis (). Direct immunofluorescence demonstrated homogenously thickened dermal
blood vessels highlighted by immunoglobulin (Ig)G, IgA, C1q, fibrin, kappa, and
lambda. The specimen was negative for deposition of IgM and C3. Findings were
consistent with PCT. Serum porphyrin levels came back strongly positive with levels
of 8 µg% (upper limit of normal <0.9 µg%). Fractionation revealed high
heptacarboxyl, hexacarboxyl, and pentacarboxyl porphyrins as expected with the
heptacarboxyl highest at 2.6 µg% and the other 2 at 1.4 µg% each. After confirmation
of the diagnosis, hepatitis C, hepatitis B, and HIV were ordered and returned
negative.
Unfortunately, our patient developed secondary bacterial peritonitis and quickly
deteriorated. His repeat ascitic fluid grew Candida and
Enterococcus. His respiratory status declined as he developed
acute respiratory distress syndrome and needed mechanical ventilation. He then
progressed to multiorgan failure a few days later and eventually died. |
pmc-6547447-1 | Patient 1 is a 15-year-old male (lock time September 2017) and the only child of a healthy non-consanguineous Ukrainian family (family 1) (Fig. b). His mother had her first pregnancy without a history of miscarriages. The pregnancy was full term without any health concerns. The patient’s birth weight was 3.5 kg (Z score − 0.06, 48% centile), his birth length was 52 cm (Z score 0.76, 78% centile), and he was in good condition immediately after birth. The patient’s current weight is 45 kg (Z score − 1.32, 9% centile) with a height of 135 cm (Z score − 3.93, 0% centile). The patient has grayish eye sclera, brittleness of teeth, and hearing loss, which started at the age of 14. The patient suffers from headaches, urolithiasis, and pyelonephritis.
The total number of fractures was eight. Patient 1 suffered his first fracture at the age of 1 year and 3 months in the right hip. The next fracture happened in the jaw, at the age of four, due to a fall. At the age of seven, the patient fractured his lower left leg. At the age of eight, the patient re-fractured their lower left leg along with fracturing their left arm. At the age of nine, the patient had received a blow to their hip, and within a month the patient had developed an irregular-shaped crack of the cortex where the blow had been dealt. The patient had equal thickening of the cortex on both side femurs. Within 2-months, a sarcoma-like ossification was discovered, sized 5 × 4 cm, without a clear contour line. After 1.5 months, the ossification enlarged to 7 × 5 cm with some thickening and a clearer contour line. In 2017, hyperplastic callus formation was extreme (Fig. c). The lower limb developed inflammatory symptoms: redness, fever, and enlarged in size (Fig. a). Patient 1 was diagnosed with pseudo osteosarcoma. Patient 1 underwent osteosynthesis. After a few months, the patient suffered a right hip fracture and underwent osteosynthesis of his right femur.
The patient developed deformation of the spine and combined deformities of his lower, upper limbs, and chest. The patient has HPC of the right humerus and both femurs (Fig. c), congenital synostosis of the right forearm (radioulnar interosseous membrane calcification), and contracture of his right elbow joint (radial head dislocation) (Fig. c). The patient suffers from severe HPC formation in the hips (from 2011, age 9). Due to severe callus, the patient is immobile and unable to sit (Fig. c). The bone mineral density (BMD) Z-score of the spine was − 5.9 and the lower arm received a Z-score BMD of − 3.6. The patient underwent bisphosphonate treatment with pamidronate.
Results of histological bone biopsy analysis showed that his callus bone tissue is immature and hypercellular. The patient’s new grown bone trabeculae have a high number of osteoblasts located at the basophil intercellular matter, with the inclusion of cartilage regions. Both the patient’s osteoblasts and osteocytes do not show any abnormalities. On the contour line, there is quite a significant number of osteoclasts. The intertrabecular space is filled with numerous blood vessels and fibroreticular tissue. The blood vessels are sinusoidal with large wide pores. The patient’s bone marrow is hypocellular and hydropic with regions with hemorrhagic infiltration. |
pmc-6547447-2 | Patient 2 is a 4-year-old boy (lock time May 2016) from a Ukrainian family with three generations of OI history from the mother’s line (family 2) (Fig. a). The mother had a healthy full-term pregnancy, without any previous miscarriages. His birthweight was 2.5 kg (Z score − 1.68, 5% centile), and his birth length was 51 cm (Z score 0.38, 65% centile). There were no signs of deformities or fractures after delivery.
The patient’s first fracture appeared at the age of 7 months in the femur during massage. At 8 and 11 months, the patient fractured both their right and left femur. Afterwards, the patient followed treatment with pamidronate. The last fracture happened at the age of 4, in the left forearm. The total number of fractures was 4.
The patient’s current weight is 15 kg (Z score − 0.68, 25% centile) and their height is 105 cm (Z score 0.66, 74% centile). The patient has bluish eye sclera and joint laxity. He is active and able to move independently. Signs of DI and hearing loss are absent.
Patient 2 has mild phenotype, mild deformities of chest, long lower and upper limb bones, with radial head dislocation and radioulnar interosseous membrane calcification (Fig. c). Investigation of X-rays showed the presence of HPC and a metaphyseal radiodense band (Fig. c). |
pmc-6547447-3 | Patient 3 is a 34-year-old female from Ukraine (lock time May 2016) and the mother of patient 2 (family 2) (Fig. a). Her birthweight was 3.3 kg (Z score − 0.2, 42% centile), and her birth length was 52 cm (Z score 1.0, 85% centile). During being born, she had numerous fractures: both elbow, left hip, and both lower legs. The total number of fractures was 26. The majority of the fractures affected the lower limbs, especially the femur. She became immobile between the ages of 9 and 14.
At the age of 9, the lower and upper limbs developed HPC. She also has calcification of the interosseous membrane in the fibula and tibia along with radial head dislocation. An investigation of X-rays revealed the presence of a metaphyseal radiodense band. The patient had chest deformation, scoliosis, and deformities of the long bones in both upper and lower limbs (Fig. a). The patient currently walks independently. The patient has moderate phenotype, mimicking OI type IV, no DI, or hearing loss. Her eye sclera is bluish. The patient has joint laxity. Her current weight is 42 kg and her height is 145 cm (Z score − 2.70, 0% centile). |
pmc-6547447-4 | Patient 4 is a 7-year-old girl from Ukraine (lock time May 2016). The patient has moderate OI phenotype, mimicking OI type IV without any visible features of OI type V. The patient was initially misdiagnosed with OI type IV. Patient 4 has no family history of OI (family 3) (Fig. a). Her birthweight was 2.8 kg (Z score − 1.18, 12% centile), and her birth length was 50 cm (Z score 0.28, 61% centile). There were no deformities or fractures during delivery; however, she had an unmineralized skull. At the age of 3 months, the first fracture appeared in the scapula during massage. The total number of fractures is 16. Most fractures affected the lower limbs. The patient’s left lower leg was fractured ten times. She had osteosynthesis on left lower and upper leg (Fig. b). The patient follows treatment with pamidronate. She has some deformities of lower limbs, spine, and chest (Fig. b). The patient had no hearing loss, DI, or joint laxity. Her eye sclera are gray. Her current weight is 17 kg (Z score − 2.22, 1% centile) and her height is 107 cm (Z score − 2.83, 0% centile). The patient is active and able to walk independently. Typical characteristics of OI type V, like HPC, interosseous membrane calcification, radial head dislocation, and a metaphyseal radiodense band, are absent. |
pmc-6547447-5 | Patient 5 is a 7-year-old girl from Vietnam, with mild OI phenotype (lock time 2015). Her father suffered some fractures in his forearms when he was under 10 years old. We do not have additional evidence of fractures in any of the other family members (family 4). An absence of consanguineous marriage was also confirmed (Fig. a). The mother had full-term pregnancy with 40 weeks of gestation, good health, and no history of miscarriages. Her birthweight was 2.8 kg (Z score − 1.18, 12% centile). Current clinical examination showed a weight 19 kg (Z score − 1.27, 10% centile) and height 115 cm (Z score − 1.22, 11% centile). She has blue sclera.
The patient suffered her first fracture at the age of 2 years old. The patient had five fractures on both side tibias. Mild deformities appeared in the long bones of the forearms and lower legs (Fig. b). She is able to move normally. The patient did not follow bisphosphonate treatment. On the radiological examination, ossifications of the interosseous membrane between the ulna and radius and congenital dislocation of the radial head were present (Fig. b). |
pmc-6547457-1 | A 72-year-old male patient with ALS suffered from moderate dyspnea (DALS-15 sum score: 14 out of 30 points) about 13 months after the diagnosis of ALS (spinal form with upper limb onset, ALSFRS-EX score 40/60, ALSFRS-R score 31/48). However, in tests of pulmonary function he still performed quite well (FVC upright 123%, FVC supine 104%, ΔFVC 15%). Blood gas results showed hypocapnia (pH 7.5, pCO2 25 mmHg, partial pressure of oxygen (pO2) 89 mmHg, standard bicarbonate (sHCO3) 23 mmol/l, base excess (BE) -3.5). With regard to the results of the DALS-15 and after exclusion of other stress factors, the findings of the blood gas analysis were interpreted as hyperventilation (respiratory rate: 18 breaths per minute) due to the distressing sensation of dyspnea. The results of the spirometric tests and blood gas analysis did not point towards NIV. However, the DALS-15 identified dyspnea as an indicator for NIV consideration. As a consequence, the patient was referred to a sleep laboratory and nocturnal NIV was started. Six months later, the patient reported that dyspnea had increased in the preceding weeks, which was reflected by a higher DALS-15 sum score of 19 points. At the same time, we observed a rapid deterioration of the spirometric test results (FVC upright 74%, FVC supine 41%). The percentage of decline in FVC upon changing from the upright to supine position (ΔFVC) reached 45%, now indicating severe diaphragmatic weakness. The spirometric test results thus indicated NIV initiation 6 months later than the assessment of the subjective feeling of dyspnea by the DALS-15 did. Blood gas analysis now showed normocapnia. Due to the increase in the DALS-15 score and the rapid decline in the tests of pulmonary function, a scheduled appointment in the sleep laboratory was brought forward to optimize the ventilator settings. The patient was prescribed lorazepam 0.5 mg sublingually for episodes of paroxysmal breathlessness to reduce the associated anxiety and referral to a home palliative care service was recommended. Another 2 months later the patient was no longer able to visit our outpatient clinic and asked for a telephone consultation. He reported that dyspnea had even worsened and persisted at rest for some days now. He already received additional morphine. Nevertheless, dyspnea became a major burden (DALS-15 sum score: 24 points). He still declined tracheostomy and invasive ventilation. When asked about the current dosage of lorazepam, the patient said, that he had so far hesitated to take it. We addressed his concerns regarding lorazepam and strongly recommended to take this medication every four to 6 hours as needed. For further symptom relief we recommended to extend NIV into daytime hours beginning with about 3 h. Three weeks later the patient died peacefully at home. |
pmc-6547457-2 | Another 51-year-old male patient, who was diagnosed with bulbar ALS 13 months ago, attended the emergency department due to dyspnea and was admitted to the ward (ALSFRS-EX score 38/60, ALSFRS-R score 28/48). He was unable to communicate verbally and used a communication device. The severity and impact of dyspnea were evaluated using the DALS-15. This short bedside test with only ticking the answers did not bother the patient but gave us a good impression into the dyspnea-related distress the patient endured. According to the DALS-15, the patient suffered from severe dyspnea (DALS-15 sum score: 26 out of 30 points). He affirmed items of the DALS-15 representing a high symptom and emotional burden like “I have highly threatening dyspnea” (occasionally), “I am short of breath, while sitting still” (occasionally), “I wake up because of breathlessness at night” (often) and “I have fear of suffocation” (often). Blood gas analysis showed hypercapnia (pH 7.35, pCO2 47 mmHg, pO2 75 mmHg, sHCO3 23 mmol/l, BE 4.6) corresponding to a later stage of respiratory impairment. Due to distinct bulbar impairment the patient could not perform spirometry. NIV was clearly indicated due to the blood gas analysis and the test results of the DALS-15 signaling the presence of severe dyspnea but was refused because of the patient’s claustrophobia. He decided against tracheostomy and invasive ventilation. Treatment of the patient’s respiratory complaints focused on secretion management and symptom-oriented drug administration beginning with morphine 2.5 mg orally three times daily for longer phases of dyspnea which occurred at rest and at night (see items of the DALS-15 above). Additionally, he was treated with lorazepam 0.5 mg two times a day sublingually and up to two rescue medications to reduce the affective distress caused by dyspnea (e.g. “fear of suffocation”). The patient was referred to a specialized palliative care team at his home place and died after 2 months. |
pmc-6547577-1 | A 30-year-old female (gravity 0, parity 0) was referred to our hospital for routine uterine cervical cancer screening, and her Pap smear indicated the possible existence of atypical glandular cells. A colposcopic examination revealed dense white lesions in the 1 and 11 o’clock directions (Fig. a, b). Punch biopsies were performed after the colposcopic examination. Histopathological analysis of punch biopsies showed a SMILE on the cervix (Fig. a) as well as extensive immunopositivity for Ki-67, which is consistent with previous reports that cells undergoing endocervical differentiation are neoplastic and not entrapped benign columnar cells [] (Fig. b). The involvement of HPV in the development of SMILE was also suggested by the positive p16 staining (Fig. c). The lesion was found to be negative for HPV genotypes 16, 18, 45, 31, 33, 35, 39, 45, 51, 56, 58, 59, and 67 but positive for HPV genotypes 52 and 68 by multiplex PCR.
We next examined lesions by single-molecule RNA fluorescent ISH using the RNAscope system (Advanced Cell Diagnostics, Newark, CA, USA) [] and specific RNA probes targeting HPV 52 (catalog no. 311611) and 68 (catalog no. 478631-C2). Frozen cervical tissue sections (10 μm thick) were fixed with 4% paraformaldehyde in phosphate-buffered saline for 15 min at 4 °C, dehydrated by serial immersion in 50, 70, and 100% ethanol for 5 min each at room temperature, and treated with protease for 30 min at room temperature. The probes were then hybridized for 2 h at 40 °C, followed by RNAscope amplification. The sections were labeled with conjugated wheat germ agglutinin (Thermo Fisher Scientific, Waltham, MA, USA) diluted 1:100 to detect cell borders, and were counterstained with 4′,6-diamidino-2-phenylindole, according to the manufacturer’s instructions. Images were acquired on an LSM 510 META confocal microscope (Zeiss, Oberkochen, Germany). HPV 68 RNA was detected in the lower epithelial layers of the SMILE along with cytoplasmic mucin (red: Fig. a). Notably, all basal lesions in the SMILE were positive for HPV type 68 based on ISH analysis using the corresponding probe (Fig. a, upper and lower images). The stratified epithelium had architecture similar to that of a high-grade squamous intraepithelial lesion and was positive for HPV 52 (blue: Fig. b). The patient underwent conization of the uterine cervix, and since the surgery there has been no evidence of abnormal cytology. |
pmc-6547582-1 | This was a 76-year-old man who was admitted to the hospital due to abnormal liver function tests and septic shock associated with systemic bacterial infection. Further workup during hospital stay revealed multifocal lymphadenopathy including cervical and inguinal regions. Ultrasound guided biopsy was performed from an inguinal lymph node. The patient was discharged after treatment of infection, improving cardiovascular symptoms and liver function. The patient electively refused treatment for lymphoma.
The biopsy showed diffuse large lymphoid cell infiltration with necrosis without recognizable follicular architecture. The lymphocytes showed moderate amount of cytoplasm and round nuclei with prominent nucleoli.
Immunohistochemical stains (IHC) with the following antibodies were performed following standard IHC protocol on Leica Bond Max stainer. The following antibodies from DAKO were used for staining: CD20, PAX5, CD3, CD5, CD10, CD23, CCND1, BCl-2, BCL-6, MUM1, SOX11 and Ki67.
IHC stains showed that the tumor cells were positive for CD20, cyclin D1, BCL6 and MUM-1. There was no CD5 or CD10 expression. SOX11 was negative (Fig. ). EBER was negative. Proliferation index by ki67 was 80%.
Interphase fluorescence in situ hybridization (FISH) was performed in the cytogenetic laboratory at Department of Pathology, Duke University Health System. Briefly, 4um sections were cut and de-paraffinized, FISH for CCDN1/IgH was performed using dual color, dual fusion probe from Abbott Molecular. This probe targets the CCND1 locus at 11q13 and the IgH locus at 14q23 for detection of the fusion gen associated with the translocation of 11;14. FISH for BCL-2, BCL-6 and myc were also performed using the probes from Abbott molecular.
Abnormal hybridization patterns with at least 2 fusion signals were overserved in 23/100 (23%) of the nuclei examined. The predominant abnormal signal pattern, presented in 13 cells, was consistent with two CCND1, one IgH and two fusion signals. Additional abnormal signal patterns with a single fusion signal were also observed. Gain and loss of signals, likely related to the truncation of nuclei in paraffin sections, was also observed.
39–52% of interphase nuclei examined showed an atypical pattern for the BCL6 locus consistent with either atypical rearrangement or partial deletion of the locus, and 3 signals for the IGH locus, consistent with CCND1/IGH fusion. No evidence of MYC (8q24.2) rearrangement or IGH/BCL2 fusion was observed. Taken together all the results from histology and molecular studies, this case was diagnosed to be diffuse large cell lymphoma (DLBCL) with BCL-1 expression (Fig. ). |
pmc-6547583-1 | A 48-year-old gravida 5 para 5 Moroccan woman with no significant past medical history, including no personal history of thrombophilia or recent surgery and no family history of thromboembolic events or autoimmune disease, presented to our emergency department with a 10-day history of epigastric pain radiating to the back and vomiting. Clinical examination revealed epigastric tenderness. The patient was apyrexic with no jaundice or clinical features of hepatic failure. She was hemodynamically stable; her visual analogue scale score was between 6 and 8; she was conscious with a Glasgow Coma Scale score of 15; she had no hemorrhagic manifestations; and she denied drug intake or alcohol consumption. The result of a urine dipstick test was negative for blood and protein. Biological investigation revealed an elevated lipase level (600 IU/L). Her C-reactive protein level was 28 mg/L. The rest of the blood test results were within normal range, including renal function, hepatic function tests, and coagulation. Her platelet count was 240,000/mm3.
Contrast-enhanced computed tomography (CECT) of the abdomen was performed, which revealed Balthazar grade C pancreatitis with multiple splanchnic thromboses involving the portal vein, superior mesenteric vein, and left renal vein and enteromesenteric venous infarct with no signs of bowel perforation. No free intraperitoneal fluid was observed (Fig. ). The patient had multiple liver lesions with double components: isodense and hypodense lesions in segments V, VI, and VII and a hypodense lesion in segment VIII of ischemic origin (Fig. ). Lower limb venous Doppler sonography ruled out DVT.
The result of a thrombophilia screen was negative. Anti-DNA, antinuclear, and anticardiolipin antibodies; anti-β2-glycoprotein 1; and anti-factor II were all negative. Functional activity of antithrombin III, protein C, and protein S were 79%, 80%, and 74.5%, respectively. Viral serology results were negative as well.
Therapeutic anticoagulation was started using enoxaparin 1 mg/kg twice daily. The patient had a nasogastric tube inserted for 72 h. She was started on proton pump inhibitors and was kept nil by mouth until the vomiting settled, then oral feeding was gradually introduced. For analgesia, we used regular paracetamol 3 g daily and nefopam 100 mg daily. The evolution was favorable, and the patient was discharged 1 week later to the care of the gastroenterology team.
Two months later, the patient was readmitted to the intensive care unit with a 4-day history of confusion. Physical examination revealed jaundice, mild tachycardia with normal blood pressure, and hypoglycemia 0.4 g/L. The patient’s abdomen was distended, tense, and tender to palpation with ascites. Computed tomography (CT) of the abdomen revealed persistent splanchnic and renal thrombosis and worsening of hepatic lesions with extension of bowel ischemia. The hepatic artery was patent, and there were no signs of necrosis or bowel perforation (Fig. ). Prothrombin time was 25%, aspartate aminotransferase was 10 times normal, alanine aminotransferase was 8 times normal, and total bilirubin was 180 mg/L. Repeat viral serology results were all negative.
Anticoagulation was stopped, and therapeutic measures for hepatic failure were initiated. The patient deteriorated to multiple organ failure with grade 4 hepatic encephalopathy, and she died 48 h later. The patient’s history, symptoms, diagnostic and management are summarized in Additional file . |
pmc-6548783-1 | A 24-year-old woman was examined for the first time 3 months after the onset of symmetrical polyarthritis with major synovitis of 2nd, 3rd, 4th metacarpophalangeal joints of both hands, wrists, elbows, knees, ankles, forefeet, without any spinal signs. The disease activity score of 28 joints (DAS28) and DAS28 using the C-reactive protein (DAS28-CRP) were 8.09 and 7.75, respectively. Increased ferritin and thrombocytosis in the absence of detectable levels of RF, anti-CCP and antinuclear antibody (ANA) were also noticeable. Her liver function tests and lipid panel were normal and no bone erosion was visible by X-rays. She was diagnosed with active early rheumatoid arthritis (RA) (Table ).
Initial treatments with prednisone, methotrexate, hydroxychloroquine and naproxen were without efficacy. The anti-TNF adalimumab was added to the treatment regimen for 2 years. After only mild improvement, she experienced a progressive flare-up of polyarthritis and a loss of treatment efficacy. Two years after the onset of the disease, wrist and tarsal (right and left) demineralization, as well as bone erosions of ulnar styloids (right and left), appeared. Erythrocyte sedimentation rate (ESR), CRP and ferritin were persistently increased while RF and anti-CCP remained undetectable. The diagnosis was revised as possible RA-like psoriatic arthritis (PsoA), especially as her mother has skin psoriasis. Bone lesions were increased rapidly, in particular at both wrists. Adalimumab was replaced by abatacept (IgG1 Fc-CTLA-4) with a mild effect on arthritis. Five years after disease onset, psoriatic skin lesions appeared, and diagnosis of cutaneous psoriasis was confirmed by a dermatologist. The final diagnosis was aggressive RA-like PsoA with bone erosions, without RF and anti-CCP. Abatacept was replaced by the anti-interleukin (IL)-12/IL-23 ustekinumab with an increase of prednisone dosage. A mild relieve of polysynovitis was noted, which was dependent on prednisone. Reduction of prednisone led to a major flare-up of polysynovitis associated with asthenia, and after 3 months of ustekinumab administration, no objective effect on the patient’s symptoms was noted.
The patient was enrolled in a prospective study based on the quantification of cytokines secreted by peripheral blood leukocytes. Blood (50 mL) of the patient as well as of healthy donors was drawn after informed consent was obtained. Plasma was collected following centrifugation (400×g for 10 min) of anti-coagulated blood and stored at − 80 °C for further protein quantification. Peripheral blood mononuclear cells (PBMCs) were obtained following centrifugation (600×g for 20 min) of the cellular fraction of blood over density gradient medium (Lymphocyte separation medium, density 1.077–1.080 g/mL; Wisent Bioproducts Inc., St-Bruno, Québec, Canada). Density gradient-purified PBMCs were stimulated with well-known immune activators of pattern recognition receptors and cytokine signalling for 24 h at 1 × 106/mL in RPMI 1640 (Wisent Bioproducts Inc., St-Bruno, Québec, Canada) supplemented with 10% fetal bovine serum (VWR Life Science Seradigm, Mississauga, Ontario, Canada) and 1% primocin (InvivoGen, San Diego, California, USA) in the absence (control) or presence of plate-bound mouse anti-human CD3 (1 μg/mL, clone OKT3) + anti-human CD28 (10 μg/mL, clone 9.3), lipopolysaccharides (LPS—100 ng/mL; 45 nM, InvivoGen, San Diego, California, USA) + adenosine triphosphate (ATP—1 mM; added for the last 30 min, Sigma-Aldrich Canada Co., Oakville, Ontario, Canada), L18-muramyl dipeptide (L18-MDP—1 μg/mL; 1.32 μM, InvivoGen, San Diego, California, USA), Poly(deoxyadenylate–thymidylate) [Poly(dA:dT)—1 μg/mL; 1.57 μM, InvivoGen, San Diego, California, USA], anisomycin (20 μM, Millipore (Canada) Ltd, Etobicoke, Ontario, Canada) or pro-inflammatory cytokines IL-1β (100 ng/mL; 5.85 nM, PeproTech US, Rocky Hill, New Jersey, USA), TNF (100 ng/mL; 5.85 nM, STEMCELL Technologies Canada Inc., Vancouver, British Columbia, Canada), IL-6 (100 ng/mL; 3.83 nM, PeproTech US, Rocky Hill, New Jersey, USA) and IFN-γ (100 U/mL; 0.30 nM, PeproTech US, Rocky Hill, New Jersey, USA) to respectively activate T cells, the NLRP3, NOD2, AIM2 and pyrin inflammasomes as well as cytokine signalling. Following stimulation, cell supernatants were collected and stored at − 80 °C for further protein quantification. Proteins involved in inflammation (IL-1α, IL-1β, IL-6, IL-9, IL-15, IL-17A, IL-18, IL-21, IL-31, TNF, LT-α, IFN-γ), immunoregulation (IL-1RA, IL-4, IL-7, IL-10, IL-12, IL-13, IL-22, IL-23, IL-27, IFN-α), chemotaxis (CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β, CCL5/RANTES, CCL11/Eotaxin, CXCL1/GROα, CXCL8/IL-8, CXCL10/IP-10, CXCL12/SDF-1α) and cellular growth (IL-2, IL-5, GM-CSF) were quantified by multiplex analyses in plasma and cell supernatants using Luminex technology according to the manufacturers’ instructions (Cytokine & Chemokine 34-Plex Human ProcartaPlex™ Panel 1A, Thermo Fisher Scientific Inc., Burlington, Ontario, Canada).
The results of this study revealed that plasma concentrations of cytokines were similar between the patient and healthy donors (Fig. and data not shown). In comparison to leukocytes from healthy donors, the patient’s secretome showed a unique overproduction of IL-6 in response to multiple stimuli, including the inflammasome activators LPS + ATP, MDP and poly(dA:dT), as well as the pro-inflammatory cytokines IL-1β, TNF and IFN-γ, to levels (up to 133,000 pg/mL) at least twice the ones produced by healthy donors’ cells (Fig. ). This overproduction of IL-6 occurred without substantial increase of pro-inflammatory cytokines such as TNF, IL-12 and IL-23, which correlates with the inefficacy of the anti-TNF adalimumab and the anti-IL-12/IL-23 ustekinumab treatments. No substantial differences were observed for members of the IL-1 cytokine family (IL-1α, IL-1β, IL-18), as well as IFN-γ and IL-17. Increased secretion of the IL-1 receptor antagonist (IL-1RA) was shown upon stimulation with the AIM2 inflammasome activator poly(dA:dT) as well as IFN-γ, suggesting that the patient’s leukocytes can synthesize high amounts of IL-1RA to neutralize the production of IL-1. Of note, the stimulation of the patient’s T cells using a combination of anti-CD3 and anti-CD28 also led to increased production of IL-6, as well as IL-23, IL-1RA and IL-17, but not to the levels observed for IL-6 (Fig. ). Finally, no substantial differences were observed between the patient and the healthy donors regarding the production of IL-2, IL-4, IL-5, IL-7, IL-9, IL-10, IL-13, IL-15, IL-21, IL-22, IL-27, IL-31, LT-α, IFN-α, CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β, CCL5/RANTES, CCL11/Eotaxin, CXCL1/GROα, CXCL8/IL-8, CXCL10/IP-10 and CXCL12/SDF-1α by unstimulated or stimulated PBMCs (data not shown).
Thus, considering the unique major overproduction of IL-6 by the patient’s leukocytes, the anti-IL-6 receptor tocilizumab was administered with a rapid improvement of her active PsoA that remained dependent on low prednisone dosage. DAS28 and DAS28-CRP were greatly improved at 3.76 and 4.34, respectively. ESR, CRP and ferritin were progressively normalized. Her quality of life was greatly improved with, in particular, a progressive reduction of asthenia. Have the patient been enrolled in this prospective study sooner, her refractory PsoA would have probably benefited from the personalized treatment without the current associated irreversible destructive arthritis and partial functional handicap, especially at both wrists. |
pmc-6548797-1 | A 73-year-old male with edentulous maxilla was referred to the University Department of Oral and Maxillofacial Surgery of the “Evaggelismοs” general hospital due to a migrated implant into the right maxillary sinus. The patient suffered from chronic obstructive pulmonary disease and therefore he had quitted smoking. Five years ago he underwent dental rehabilitation with the placement of six implants in the maxilla and four in the mandible. In less than 2 months after initial placement, all implants had failed to osseointegrate. A year and a half later the patient underwent guided bone regeneration with bovine-derived xenograft and 7 months after this point, another 10 implants were inserted into both the maxilla and mandible. Two months later, all implants had once again failed to osseointegrate. During the attempt of removal by the dentist, one of the implants was displaced into the maxillary sinus, without the dentist being able to retrieve it. The patient then visited another dentist, who could not either remove the migrated implant.
Upon arrival to our clinic, a full medical and dental record was retrieved from the patient, and he was scheduled for surgical removal of the implant. Prior to operation, the patient underwent a radiographic examination with water’s X-ray (Fig. ), as well as CBCT examination (Fig. ) which confirmed implant migration and revealed its exact position inside the maxillary sinus.
Surgical procedure initiated with local anesthesia by injecting xylocaine 1% andepinephrine 1:100,000 solution in the soft tissues involving the right half of the maxilla. After a crestal incision, a full-thickness mucoperiosteal flap was raised, exposing the anterior-lateral wall of the maxilla in an area extending from canine to molar region. Using a high-speed rotary instrument under sterile saline solution irrigation, a rectangular window was created in the anterior-lateral maxillary wall. The implant was detected through the bony window and captured by a mosquito forceps (Fig. ). The mucoperiosteal flap was then placed back at its initial position and was anchored with 4.0 resorbable sutures (Fig. ). Amoxicillin (1 g twice daily) was prescribed for 1 week with analgesic treatment. Sutures were removed 2 weeks after surgery. The patient was advised to follow a soft diet plan for 4 weeks and was provided with proper oral hygiene instructions. He underwent scheduled visits on a monthly basis to check the course of healing for the following 6 months. |
pmc-6548797-2 | A 55-year-old female patient underwent a radiographic examination with a panoramic X-ray prior to the exposure of two bone level implants which were placed by a general dentist, when their migration into the right maxillary sinus was revealed (Fig. ). Dental scan confirmed the full migration of both implants into the maxillary sinus around the areas of #15 and #17 (Fig. ). The implants were mobile inside the sinus, and although the patient was asymptomatic, there were signs of mucosal thickening in the CBCT.
After the administration of a local anesthetic solution (2% lidocaine with 1:100,000 epinephrine), a vestibular incision was made, and a mucoperiosteal flap was raised to expose the lateral bony wall of the right maxillary sinus. Osteotomyperpendicularly to this wall was then performed. The bony window was detached carefully and after removal of the sinus membrane, both implants were exposed (Fig. ). The implants were then captured with a mosquito forceps (Figs. and ). Both implants were successfully removed from the right maxillary sinus (Fig. ). The mucoperiosteal flap was anchored to its initial position with 4.0 resorbable sutures to achieve passive primary wound closure. Amoxicillin (1 g twice daily) was prescribed for 1 week with analgesic treatment. Sutures were removed 10 days postoperatively. Visits on a monthly basis were then scheduled to check the course of healing for 6 months. |
pmc-6548841-1 | The 55-year-old Caucasian woman enrolled in the study was diagnosed with CCD (CCD; OMIM# 117000) at the age of 44 (Center for Neuromuscular Diseases; Ospedale Clinicizzato SS. Annunziata, I-66100 Chieti, Italy). CCD was confirmed by histological examination of muscle biopsies at the time of the initial diagnosis (not shown). Presence of areas of internal disarray in skeletal muscle fibers was also confirmed in the present study (please see , for more detail). The patient reported that her disease had been aggravated by orthopedic complications (scoliosis diagnosed at the age of 17 years) that limited her daily activities to a point in which she retired from working activities at the age of 54. At the time of enrolment in the present study a medical check-up was performed (anthropometric data, medical aptitude, and anamnesis): her vital signs were all within normal limits, except for a moderately high body mass index (). The score of muscle strength test by the Medical Research Council scale was 3/5 in both upper and lower limbs (). Patient had a waddling gait and difficulty in climbing stairs. |
pmc-6549265-1 | A 4 years old female alpaca was referred to the clinic for ruminants, University of Veterinary Medicine Vienna, Austria. The alpaca had a 6 month history of neurologic disorder signs. The main clinical signs were head tilt to the right and emaciation (Fig. a). The owner reported that he had treated the alpaca subcutaneously against mites several months before referral and that he had observed a slow deterioration of the clinical signs within the last 3 months. The alpaca separated from the herd but never showed inability to feed or dislike of the feeding. The alpaca was kept with other alpacas on a pasture, and all animals had access to additional feed such as hay and mineral supplements. No other alpacas on the farm were affected. The alpaca had given birth to a healthy cria 1 month before referral to the clinic.
On initial physical examination the female alpaca showed a quiet behavior, the body weight was 46.2 kg. Heart rate and respiratory rate were within reference ranges. The rectal temperature was 37.8 °C. Auscultation of lungs and heart was uneventful. No abnormalities were detected at abdominal palpation and auscultation. On both forelimbs the skin between the toes was hairless, thickened and crusty.
A neurologic examination was performed to determine the region of the nervous system being most likely affected.
Postural assessment of the alpaca revealed a lowered neck with a head tilt to the right and an ipsilateral lip droop with small amounts of cud dropping from the affected side. However, the animal was able to prehend food, chew and swallow. Further, collapse of the right nostril and deviation of the nasal philtrum to the left was observed (Fig. b). Atrophy of the muscles of mastication on the right side was diagnosed by palpation.
Additionally a plum-sized solid swelling at the base of the right ear was palpable. While the left ear was held in vertical position and moved constantly in response to sound, the right ear was held horizontally, never changing its position. No movement of the pinna occurred when testing the sensitivity of the right ear canal. There were no visible signs of trauma, alopecia or inflammation at the external pinna of the right ear.
In addition the alpaca showed loss of the menace reflex on the right side where the corneal as well as palpebral reflexes were impaired in contrast to the left side where immediate closure of the eyelid could be induced. Moreover, the alpaca was able to pass obstacles in a normal manner implying absence of significant visual impairment.
Observational gait analysis showed no ataxia or circling. Postural reaction (limb correction of awkward position) and spinal reflexes (withdrawal reflex, perineal reflex) were unremarkable.
In summary, neurological examination revealed multiple cranial nerve deficits. Dysfunction of the trigeminal nerve was linked to the observed atrophy of the masticatory muscle. Facial nerve defect was mainly responsible for pathological impaired corneal, palpebral and menace reflexes. Additionally, the defect of the facial nerve could have been causative for asymmetry of nose and lips, and even immobility of the right pinna, since no reflex could be induced by sensitivity testing. Dysfunction of the vestibulocochlear nerve resulted in head tilt.
Based on the neurological deficits identified by physical examination of this alpaca (cranial nerve deficits evident, no involvement of spine and limbs) the primary differential diagnosis included otitis media and interna.
For further diagnostic purposes, blood cell count was analyzed and showed a mild regenerative anemia (RBC 9.97 1012/L, Hb 6.5 mmol/L, MCV 31.9 fl, MCH 6.5 fmol/L, MCHC 20.5 mmol/L). Blood gas analysis and biochemistry profile were within reference ranges []. PCR analysis of whole blood was negative for Cand. Mycoplasma haemolamae. Parasitological examination of feces showed mild infection with Coccidia spp. Skin biopsies of the area between the toes of the forelimbs was tested positive for Chorioptes spp.
Otoscopic examination of the right external ear canal was performed, using a flexible endoscope with a diameter of 3.8 mm (Karl Storz Endoskop Austria GmbH). It was noticeable that the endoscope could be inserted into the external vertical ear canal for just about 0.5 cm, further insertion of the endoscope was not possible due to ear canal stenosis. The visible part of the external ear canal showed endoscopically no signs of inflammation and no pathological content (e.g. foreign body or parasites).
Ultrasound examination of the swelling at the base of the right ear was performed using a 7.5 MHz linear transducer and alcohol (ethanol 70%) as contact medium between probe and skin. At the area of interest a spheric inhomogenic hypoechogenic structure with small echoic spots was seen (loss of normal connective tissue and muscle architecture), sonographically resembling an inflamed tissue []. No cranial bone could be visualized in this area.
Analysis of cerebrospinal fluid (CSF) is one of the most commonly performed ancillary diagnostic tests when investigating the cause of a neurologic disease. Changes in protein concentration, cell count, and cell differentiation can help to distinguish between inflammatory/infectious and non inflammatory/non infectious diseases []. Nevertheless, in this case, CSF analysis was not considered, since physical examination implicated pathological changes of the middle and inner ear structures. Although there is limited information on the use of computed tomography (CT) to visualize brain and skull alterations in SACs [, ], the decision was made to perform a CT scan, since this imaging technique has been shown to be very effective in locating space-occupying lesions and pathological changes in brain tissue of other animal species.
CT examination (multi-slice helical CT, Siemens Somatom Emotion using 80 mAs, 130 kV, rotation time 1.5 s, pitch 0.8, and slice thickness 0.75 mm) took place at the Clinical Unit of diagnostic Imaging, University of Veterinary Medicine Vienna. The alpaca was examined under general anesthesia in sternal recumbency, using butorphanol (0.2 mg/kg IM) and xylazine (0.4 mg/kg IM) as premedication, followed by maintenance medication with ketamine (5 mg/kg IM) and isoflurane in oxygen (Fig. ).
At CT examination (Fig. a-c, 4A) the right osseous external ear canal was not apparent. A large space-occupying mass was replacing the right external acoustic meatus, and osseous ear canal, the area of the former tympanic bulla, tympanic cavity and inner ear. Remnants of the bulla wall were thickened and sclerotic. The ventral part of the tympanic bulla showed increased density with loss of all aerated areas of its usually honeycomb-like structure. The temporal bone showed thickening and intracranial irregular periosteal reactions dorsal to the right temporomandibular joint. The visible mass lesion was up to 6x7x4 cm (height x length x width) and was therefore occupying nearly 40% of the cranial cavity. The mass was mildly hyperintense with multiple, somehow onion shell-like calcified areas. No capsule was found. Both lateral cerebral ventricles were moderately enlarged, more on the right than on the left side. Marked midline-shift to the left was seen, causing complete compression of the caudal part of the right cerebral ventricle. The cerebellum was partially displaced into the great foramen of occipital bone resulting in a mild cerebellar herniation. Mild atrophy of the right temporal muscle was visible. The lymph nodes in the upper neck region were unremarkable.
Due to the poor prognosis, the owners decided to have the alpaca euthanized.
A full necropsy was performed at the Institute of Pathology, University of Veterinary Medicine Vienna. The skull was cut into coronary sections by a diamond saw. Samples of brain, skull and organs were fixed in 4% buffered formaldehyde solution. Samples containing bone were decalcified for 12 h in Decal® (quartett GmbH, Berlin, Germany). All samples were then embedded in paraffin wax. Sections of 1.5 μm thickness were cut and stained with hematoxylin and eosin (HE) for histological examination. Masson’s trichrome staining was performed to demonstrate collagenous fibers in the abscess capsule and Brown and Brenn staining was performed to detect gram positive and negative bacteria. A primary antibody against smooth muscle actin (SMA, mouse monoclonal antibody, no: M0815, dilution 1:1500, Agilent Technologies Österreich GmbH, Austria) was used to demonstrate vessels and a primary antibody against glial fibrillary acidic protein (GFAP, rabbit polyclonal antibody, no: Z0334, dilution 1:3000, Agilent Technologies Österreich GmbH, Austria) was used to identify astrocytes in brain sections by immunohistochemistry (IHC).
On gross examination the animal was cachectic. An asymmetry of the skull was evident after the skin was removed. A mild swelling of firm consistency of the right base of the skull and discoloration and atrophy of the lateral portion of the right cerviculoscutular muscle were present. Coronary sections of the skull and brain showed a light brown-whitish gelatinous to firm mass of up to 7 cm in diameter replacing bone and muscle of the right cranium and expanding into the cranial cavity. The mass had a thin capsule of fibrous tissue (Fig. b). It encompassed the right middle and inner ear and occluded the right ear canal. The right tympanic bulla was completely destroyed in contrast to the normal left tympanic bulla (Fig. a, b). The mass caused severe midline shift in the caudal brain and displaced medulla oblongata, cerebellum, mesencephalon, and the caudal part of the right hemisphere to the left (Fig. b). The right hippocampus and thalamus were displaced cranially. A mild hydrocephalus of the lateral ventricles was evident due to obstruction of the mesencephalic duct.
Histologically the mass turned out to be an abscess with a great amount of necrotic debris in the center, followed by a layer of degenerated neutrophils adjacent to a capsule of granulation tissue and mature connective tissue (Fig. c). Mild to moderate infiltration of the outer layers of the capsule with lymphocytes and plasma cells was present and collagenous fibers were detectable by Masson’s trichrome staining (Fig. c). Within the necrotic debris degenerate bone fragments were present, while bone adjacent to the abscess capsule was resorbed by osteoclasts. Focally in the temporal bone, irregularly arranged osteoid was surrounded by osteoblasts and embedded in fibrous tissue adjacent to bone. Areas of bone resorption by osteoclasts were noted. In the neuropil adjacent to the abscess severe astrogliosis was detectable. Acute neuronal degeneration was not detectable, but regions with gliosis showed a marked loss of neurons (Fig. d). The neuropil was edematous and showed small foci of malacia in gray and adjacent white matter. Atrophy of the cerebral cortex by pressure was evident in the right occipital lobe directly adjacent to the abscess. In some regions vascular proliferation and infiltration of vessels from the abscess capsule into the neuropil as well as mild perivascular infiltration with lymphocytes were present (Fig. d, e). By immunohistochemistry severe diffuse astrogliosis was detectable in brain regions adjacent to the abscess (Fig. f). No bacteria were detectable histologically by Brown and Brenn staining in the brain abscess. |
pmc-6549268-1 | A 74-year-old Japanese man with no particular medical history fell down from a ladder and sustained a left abdominal stab wound from an L-shaped metal peg on the ground, which he removed by himself. He was brought to the emergency department in our hospital. He had no relevant family or past medical history and no history of smoking or alcohol consumption. Physical examination showed a 5-cm, jagged linear wound on the left abdomen. Computed tomography (CT) showed the trace of the L-shaped metal peg from the left abdomen to the left rib and left kidney, anterolateral bone avulsion of the left T12 vertebral body, and fracture of the L1 left transverse process and the left 10th–12th ribs (Fig. ). The result of the patient’s neurological examination was normal. Surgical exploration was performed with the patient under local anesthesia in the emergency department, which showed no evidence of peritoneal penetration. The wound was washed with 6 L of physiological saline, and a drain was inserted; the patient was hospitalized for 6 weeks. Ceftriaxone sodium hydrate was administered for 7 days to prevent bacterial infection. One week after the event, the patient started to walk with a rigid corset, and he was discharged in 6 weeks. X-ray images showed narrowing of T11–T12 intervertebral disc space at 6 weeks and 10 weeks. He was readmitted to the hospital with complaints of back pain, numbness of both legs, and inability to walk 13 weeks after the fall. The patient was hospitalized in the orthopedic surgery department. CT showed numerous irregular osteolytic cavities in T11 and T12 vertebral bodies and destruction of the inferior endplate of T11 and the superior endplate of T12 (Fig. ). This appearance was highly suggestive of septic spondylodiscitis. Magnetic resonance imaging (MRI) findings were typical of spondylodiscitis. Gadolinium-enhanced T1-weighted MRI indicated increased signal intensity at T11–T12 vertebral bodies and severe cord compression and epidural abscess at T11–T12 associated with infiltration of soft paravertebral tissues (Fig. ). Laboratory findings showed C-reactive protein of 0.51 mg/dl and a white blood cell count of 6100/ul. The result of the patient’s blood culture was negative. On the seventh day after readmission, he underwent partial laminectomy at T11 and posterior fusion at T9–L2. A. terreus was isolated from the material of T11–T12 intervertebral disc and vertebral bodies. His Aspergillus antigen was positive in the blood examination. The operative specimen from the T12 vertebra revealed inflammatory granulation between trabecular bone and the presence of numerous neutrophils in the granuloma. Histological examination showed chronic suppurative osteomyelitis (Fig. ). On the 35th day after admission, he underwent anterior fusion at T11 and T12 with a rib bone graft (Fig. ). Voriconazole (VRCZ) 600 mg intravenous was administered for 2 months, and VRCZ 600 mg oral was subsequently administered for 3 months. The patient wore a rigid corset for 5 months. Posterior partial laminectomy at T11 and anterior fusion at T11 and T12 resulted in a good clinical course. The patient’s neurological dysfunction was completely recovered, and his back pain had disappeared. Two years after the operation, CT showed bone fusion at T11 and T12 (Fig. ). MRI revealed no evidence of increased signal intensity at T11–T12 vertebral bodies and severe cord compression and epidural abscess at T11–T12 (Fig. ). |
pmc-6549270-1 | The male 18-days-old Caucasian newborn was admitted to our department for ineffective breastfeeding and failure to thrive. He was born at term from spontaneous delivery, small for gestational age to non-consanguineous parents []. Pregnancy was uneventful except for a delayed intrauterine growth restriction detected during the last month of gestation. External genitalia were of normal appearance, prepubertal, with testicular volumes of 1 ml. Blood tests showed a severe hyponatremia (Na + 110 mEq/l; NR 136–146 mEq/l), hyperkalemia (K+ 7.5 mEq/l; NR 3.5–5.30 mEq/l), hypochloremia (Cl- 81 mEq/l; NR 97–110 mEq/l) and metabolic acidosis with increased lactate. Glycemia was within the normal range for age (68 mg/dl); urinary sodium loss was also detected (Natriuria 16 mEq/l).
Endocrinological tests revealed low plasmatic aldosterone levels (38.6 pg/ml; NR 50–300 pg/ml), dramatic increased renin (44,100 μU/ml; NR 4.4–46.1), elevated levels of adrenocorticotropic hormone (ACTH, 91.4 pg/ml NR 4,3–52) and normal plasmatic cortisol (13.7 μg/dl NR 6.7–22.6). Skin pigmentation was normal except for mild pigmentation of the external genitalia. Neonatal screening for 17-OH-progesterone was within the normal range. Electrolytes replacement first intravenous and then oral, and therapy with Fludrocortisone (50 μg/die) and salt integration were started with normalization of clinical and hormonal conditions. Treatment revealed to be effective and the newborn started growing properly, with normal electrolytes. Cerebral ultrasounds and cerebral magnetic resonance (MRI) were normal, as well as the elettrocardiogram (ECG) and chest X-rays. Abdominal MRI showed normal size of the adrenal glands. A diagnosis of Primary Hypoaldosteronism was entertained and genetic analysis of the CYP11B2 gene (encoding aldosynthase) was requested.
During the follow up after the first 5 months of life, ACTH levels started increasing again although there was a good treatment compliance, normal electrolytes, good weight and length gain and slightly low basal cortisol levels, within the normal range for age (Table ).
At 9 months of age the result of the CYP11B2 gene sequencing did not show any mutation. The parents refused to accomplish a short synacthen test (SST), however basal ACTH was 300 pg/ml and 24-h urine collection pointed out low levels of urinary cortisol (20 μg/24 h, NR 58–403 μg/24 h) with normal Na/K urinary ratio. Moreover, normal serum 17-OH-progesterone was found, ruling out the hypothesis of congenital adrenal hyperplasia (CAH).
Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were found, respectively, of 1 IU/l and 2.2 IU/l, and Testosterone of 0.2 ng/ml, being to the highest levels of the normal range for age.
A diagnosis of adrenal insufficiency was made and replacement therapy with Hydrocortisone (10 mg/m2/day), joint to already in use Fludrocortisone therapy (100 μg/day) and salt integration, was started. An abnormal development of adrenal glands rather than an enzymatic defect was hypothesized. Adrenal antibodies and very long chain fatty acids (VLCFA) were negative. DNA analysis performed by Sanger sequencing identified a novel in frame indel mutation in the NROB1 gene (c.848_849delinsCC or p.(Gln283Pro)), confirming the diagnosis of AHC. As expected the same mutation was carried by the mother as hemizygous (see Fig. ). |
pmc-6549271-1 | A 62 year-old man presented with a 3-month history of obscure abdominal discomfort accompanied by sensation of mass in his right loin. He also complained from voiding difficulty and frequency. Physical examination confirmed the presence of a large, mobile and non-tender mass in the right flank. His past medical history was uneventful. Hematological tests showed leukocytosis (12.9 × 103 μL) with thrombocytosis (664 × 103 μL), elevated erythrocyte sedimentation rate (87 mm/hr) along with increased C-reactive protein level (86.2 mg/L). Urine analysis showed a number of RBC (15–16/hpf) in urine, explaining the microscopic hematuria. Tumor markers test revealed a raised prostate specific antigen level (PSA = 4.195 ng/ml). Serum biochemistry and chest X-ray were unremarkable. Ultrasound examination demonstrated a hypervascular encapsulated Solid cystic tumor (114 × 108 × 97 mm) in the lower zone of the right kidney. Mild hydronephrosis was seen as a result of the tumor compression. Computerized tomography (CT) also detected a large heterogeneous solid mass (131 × 129 mm) in the lower-mid portion of the right kidney with the extension to the hilum causing renal parenchymal destruction. The mass adhered to inferior vena cava (IVC) without the invasion of tumor to the IVC or thrombosis. There was no involvement of adjacent structures. In addition, a non-specific calcified nodule (12 mm) was disclosed next to the upper pole of the right kidney. The preoperative metastatic work-up showed no abnormalities. With the great suspicious to RCC, the patient underwent right nephrectomy via thoracoabdominal approach.
During hospitalization, hematological and biochemical tests were evaluated again. The levels of the erythrocyte sedimentation rate, white blood count and platelet count were all normalized. However, the laboratory data showed that creatinine level briskly increased to 4 mg/dl without oliguria. After nephrology consult and appropriate measures, the patient was discharged 7 days postoperatively in a satisfactory condition and with the following laboratory data: urea = 55.4 mg/dl, BUN = 25.9 mg/dl, creatinine = 2.25 mg/dl, glomerular filtration rate = 32 ml/min. To date, 6 months after surgery, the patient is alive with no evidence of disease recurrence.
Considering to pathological study, nephrectomy specimen was grossly 21 × 16.5 × 11 cm in size and consisted of a huge tumor attached to the kidney with the prerenal fat. The cut incision disclosed a relative hypervascular tumor with almost soft consistency arising from medial portion of upper pole to lower lobe with the extra-renal extension. The tumor was mostly separated from renal parenchyma with a definite border except some upper parts of the tumor which were admixed to the renal parenchyma. There was no evidence of adrenal gland or pericolic fat on the surface of tumor and the tumor did not invade into the perinephric tissue.
Microscopic examination showed a mesenchymal tumor with different patterns, including uniformed to sometimes pleomorphic nuclei spindle cells in a storiform arrangement embedded in variant amount of fibrous stroma (Fig. (a)). Most part of the tumor was occupied by pleomorphic and atypical histiocytic cells arranged in a cartwheel or storiform pattern. Mononuclear to multinucleated giant cells were presented with bizarre-shaped hyperchromatic nucleus and frequent mitotic activity (Fig. (a)). Areas of myxoid change and hyalinization along with aggregates of lymphocytes were also seen throughout the lesion. The tumor was not extended to pelvic, renal vessels and ureter segment. Immunohistochemical analysis revealed strong reactivity for CD68 (Fig. (a)), vimentin and CD34 (Fig. (b)), but the tumor was negative for CD10, Pan-cytokeratin (Fig. (d)), S100 protein, desmin and H.coldesmon. Based on histological and immunohistological studies, a diagnosis of pleomorphic malignant fibrous histiocytoma was established. |
pmc-6549281-1 | A 24-year old man with mediastinal seminoma was referred to a local hospital for the management of left pleural effusion. He underwent previous radiotherapy, and was then scheduled for standard BEP (Bleomycin, Etoposide, and Cisplatin) protocol consisted of Cisplatin 20 mg/m2 days 1 through 5; Etoposide 100 mg/m2 days 1 through 5 for four cycles; Bleomycin 30 mg weekly for 12 weeks (total dose of bleomycin, 360 mg). However, the occurrence of left pleural effusion did not allow to complete the first cycle of treatment. A chest drainage was placed in the left pleural cavity. The fluid had a triglyceride level of 450 mg/dL, and resulted to be positive for chylomicrons. Despite Non-oral feeding (NPO) and TPN were provided for 30 days, output chylothorax > 800 ml/24 h persisted. Chest computed tomography scan confirmed the persistence of left pleural effusion with atelectasis of left lower lobe. Thus, he was referred to our attention for surgical treatment.
Under general anaesthesia and selective intubation, the patient was placed in right lateral decubitus. Heavy cream was administered via a nasogastric probe producing a copious white chyle dropping which allowed to identify the leakage. Endoscopic view showed diffuse, tenacious and bleeding pleural adhesions that made difficult the identification of TD at level of Poirier’s triangle and of diaphragm. The uniportal incision was converted to a mini-thoracotomy, and TD was identified near to the esophagus in the anatomical space delimited by descending thoracic aorta, the 4th and the 5th posterior intercostal arteries and the vertebral column (Fig. ). Ability to aspirate chyle using a small needle, confirmed that the isolated structure was the TD rather than retroaortic artery (Fig. /a). Thus, it was clipped at multiple locations along its path (Fig. /b). A mechanical debridement of pleural adhesions were performed and associated to pleural lavage with warm povidone-iodine solution diluted with saline. Two chest tubes were left in the chest. The procedure is summarized in Additional file 1: Video S1.
Complete resolution of chylothorax was obtained the day after. Patient was discharged on post-operative day 5, and no recurrence of chylothorax was observed during the follow-up. One month later, the patient re-started chemotherapy and completed the four cycles of treatment with complete remission of disease. At 15 months from surgery, the disease is stable without sign of progression. |
pmc-6549290-1 | A 65-year-old female complained headache, tinnitus and eye discomfort and even blurred vision consisted for 10 years. Four months ago, she felt a hearing loss in her left ear. Comorbid medical issues included the history of diabetes mellitus, coronary heart disease, sleep apnea syndrome, and lumbar disc herniation and sinusitis surgery. Physical examination showed left ear hearing loss, the pinprick and vibration feelings mildly diminished in bilateral glove-and-stocking territories.
No positive findings identified in the image of brain computed tomography (CT), magnetic resonance imaging (MRI), as well as trans-cranial color Doppler (TCCD). Carotid ultrasound revealed intima-media thickening and plaques in bilateral carotid arteries. Computed tomography angiography (CTA) revealed arteriosclerosis in head and neck without significant stenosis. Contrast-magnetic resonance venography (MRV) identified bilateral IJVS in J3 segment accompanied with distorted and dilated vertebral venous plexus (Fig. a-c). Three-dimensional (3D)-CTV images showed the stenosis at J3 segment of bilateral internal jugular vein (IJV) (Fig. d-f). The axial computed tomography venography (CTV) images (Fig. g-h) and 3D-CTV images with bone remodeling (Fig. i-k) indicated that elongated styloid process compressed bilateral IJV against the transverse process of C1 vertebra. The styloid oppression-induced IJVS in bilateral J3 segment was also identified by Digital subtraction angiography (DSA), and cerebral venous sinuses and IJV thrombi were excluded by Black-blood thrombus image (BBTI).
After she underwent xueshuantong (panax notoginseng saponins) 450 mg (mg)/ intravenous/ daily for 10 days, and aspirin 100 mg/ per oral/ daily and rosuvastatin 10 mg/ per oral/ qn. for 30 days, her symptoms were not improved. |
pmc-6549290-2 | A 58-year-old male complained intermittent dizziness, accompanied with insomnia for 3 years. He developed intermittent headache and numbness of scalp 3 months ago. Comorbid medical issues included the history of hypothyroidism. No positive findings were in his neurological examination.
Brain MRI showed ischemic focus in bilateral subfrontocortical region. Carotid ultrasound and CTA showed mild arteriosclerosis. Contrast-MRV showed focal stenosis at J2-J3 segment of the right IJV and J3 segment of right IJV, accompanied with dilated vertebral venous plexus (Fig. a-b). 3D-CTV showed stenosis at bilateral IJV-J3 segment (Fig. c-d) and dilated vertebral venous plexus. Axial CTV (Fig. e-f) and 3D-CTV with bone remodeling (Fig. g-i) showed J3 segment of bilateral IJV was compressed by styloid process and transverse process of C1 vertebra.
He was treated with xueshuantong (panax notoginseng saponins) 450 mg/ intravenous/ daily and alprostadil 10 μg/ intravenous/ daily for 10 days, combined with betahistine 6 mg/ per oral/ daily and pitavastatin 4 mg/ per oral/ qn. for 3 months. All his symptoms were not attenuated. |
pmc-6549290-3 | A 61-year-old female complained insomnia for 10 years. She had no other past medical history. No positive findings were in her neurological examination.
CTA showed mild arteriosclerosis in the head and neck. Jugular ultrasound revealed malformation of right IJV-J3 segment. Contrast-MRV identified the stenosis at the junction of right transverse sinus and sigmoid sinus, and the superior and inferior segment of the left IJV, dysplasia of the superior segment of the right IJV and dilated right vertebral venous plexuses (Fig. a-b). 3D-CTV indicated the stenosis at the junction of right transverse sinus and sigmoid sinus, and at J3 segment of the bilateral IJV (Fig. c-e). Axial CTV images (Fig. f-g) and 3D-CTV with bone remodeling (Fig. h-j) showed the styloid oppression on bilateral IJV-J3 segments against the transverse process of C1 vertebra.
After underwent xueshuantong (panax notoginseng saponins) 450 mg/ intravenous/ daily for 10 days and aspirin 100 mg/ per oral/ daily for 30 days, all her symptoms were not attenuated. |
pmc-6549290-4 | A 60-year-old male patient is with a stridulous tinnitus existed continuously in both earsand hearing decline in left ear for 2 years. He has no other past medical history. Neurological examination is negative except for hearing decline in both ears.
Brain MRI images revealed no positive finding. Lumbar puncture showed the intracranial pressure (ICP) was 200mmH2O. Jugular vein ultrasound identified the elongated venous valve and focal stenosis in left IJV-J2/ J3 segment and right IJV-J3 segment.
The catheter venography indicated the trans-stenotic pressure gradient was 80mmH2O. Two stents (sinus-SuperFlex 10*60) were placed at the stenotic segment in left IJV-J3. DSA showed the corrected blood reflow after stenting. Jugular vein ultrasound after stenting prior to discharge showed normal blood flow in left IJV and focal stenosis in right IJV-J3 segment. The patient then was treatment with warfarin 3 mg/ per oral/ daily combined with aspirin 100 mg/ per oral/ daily for one year and his symptoms were completely disappeared at 19 days followed-up after stenting.
However, his symptoms reoccurred at the 20th day after stenting. Jugular vein ultrasound showed restenosis in left IJV-J3 segment and focal stenosis in right IJV J3 segment. 3D-CTV revealed the stenosis in bilateral IJV-J3 segment (Fig. a-b). Axial CTV images (Fig. c-d) and 3D-CTV (Fig. e-g) with bone remodeling revealed the bilateral IJV J3 segment was compressed by elongated styloid process and transverse process of C1 vertebra. Although given advices, he refused to receive styloidectomy. |
pmc-6549290-5 | A 49-year-old male complained intermittent dizziness for 3 months. His past medical history included hypertension. No positive findings were in his neurological examination.
Lumbar puncture showed the intracranial pressure (ICP) was 220mmH2O. Jugular vein ultrasound indicated stenosis at bilateral IJV-J3 segment. Contrast-MRV (Fig. a-b) and 3D-CTV (Fig. c-d) revealed the stenosis at bilateral IJV-J3 segment and dilated vertebral venous plexus. DSA identified a severe stenosis at bilateral IJV-J3 segment and occlusion in the superior trunk of middle cerebral artery. Axial CTV (Fig. e-f) and 3D-CTV (Fig. g-i) displayed that the J3 segment of bilateral IJV was compressed by styloid process and transverse process of C1 vertebra.
After underwent styloidectomy in the left side, symptoms of the patient were partially attenuated, the CTV follow-up images at the 5th day post- styloidectomy revealed an absence of left styloid process and left transverse process of C1 vertebra (Fig. k-l), and both the results of Jugular vein ultrasound and CTV images (Fig. k-l) followed-up at the 5th day post-styloidectomy showed that the stenosis at left IJV-J3 segment still existed, whereas, symptoms of the patient were obviously attenuated at the 11st day after styloidectomy and the blood flow in left IJV Jugular vein was partly improved confirmed by ultrasound. At 3 months follow-up after styloidectomy, the jugular vein blood flow in left IJV was turned to normal confirmed by ultrasound follow-up. |
pmc-6549302-1 | An 82-year-old male was diagnosed with bronchial asthma at 10 years of age and treated with inhalants and he did not receive treatment for asthma since the age of 30 because of the resolution of bronchial asthma. He was followed at our hospital for idiopathic interstitial pneumonia by annual regular chest X-ray and computed tomography (CT) scans for 4 years. The patient’s interstitial pneumonia, with minimal change in radiological findings was stable over the years, he complained no symptoms. He did not indicate exposure to fungus. Chest X-ray and CT scan obtained in December 2017 revealed high-attenuation mucus plug in right intermediate bronchial trunk, right pleural effusion (Fig. a), and infiltration in the right lung field (Fig. b).
We also found unilateral bronchiectasis in the right upper lobe.
Additionally, a slight fibrotic change along the pleural line reflecting interstitial pneumonia was observed. CT of paranasal sinuses obtained to investigate nasal congestion for 3 years, revealed high-attenuation mucus plug in the left ethmoid sinuses (Fig. ). Physical examination revealed decreased breath sounds in the right lower lung field. No wheezing and rhonchi were observed on auscultation.
Blood tests showed a total leucocyte count of 9300/mm3 with 8% eosinophils (absolute eosinophil count, 744/mm3) and elevated C-reactive protein. Radioimmunosorbent test revealed elevated IgE levels (1460 IU/ml), and the radioimmunosorbent test for specific IgE antibodies against Aspergillus, Penicillium and Candida were positive. Serum precipitins to Aspergillus were also positive. We confirmed local urticaria and lash 15 min after subcutaneous injection of A. fumigatus antigen and this was positive of immediate cutaneous hypersensitivity reaction. He had a history of right nephrectomy because of renal cancer and did not experience recurrence.
Pulmonary function test showed the following: forced vital capacity (FVC), 1.86 L (55.4% of predicted value); forced expiratory volume in 1 s (FEV1), 1.60 L (64.3% of predicted value); and FEV1/FVC, 86.0%. Bronchoscopy for definite diagnosis confirmed bronze-colored, hard mucus plug in the right intermediate bronchial trunk (Fig. a), and pathological examination of multiple biopsy specimens stained by hematoxylin–eosin revealed allergic mucin with layers of mucus, eosinophils, and eosinophil-predominant mixed inflammatory cell infiltrate and Charcot–Leyden crystals (Fig. a). Grocott’s stain revealed fungal hyphae with a 45° branch angle within the allergic mucin (Fig. b). We performed open biopsy of the ethmoid sinuses and found similar mucus plug there, which revealed similar pathological findings in the right intermediate bronchial trunk (Fig. b), including fungal hyphae with a 45° branch angle within allergic mucin (Fig. c). Mucus plug cultures were positive for A. fumigatus. The patient met of the diagnostic criteria for ABPA by Rosenberg and Patterson [] as well as those for AFRS [], and thus he was diagnosed with SAM syndrome [].
The patient was treated with 0.5 mg/kg prednisolone daily for 1 month, which was reduced to 0.35 mg/kg prednisolone daily. His total IgE levels fell to 206 IU/ml after 3 months. CT of the lung and paranasal sinuses showed apparent amelioration (Fig. a–c), and nasal congestion was resolved after 3 months steroid therapy. Now, there has been about 1 year and 4 months after the diagnosis, the patient is currently receiving oral steroid therapy (0.1 mg/kg) and remains in good condition with no deteriorations. |
pmc-6549332-1 | Case 1 was 5 years-old, female, neutered, 18 kg hunting dog, guested in a public kennel in Sassari (Italy). The dog resulted positive to A. vasorum infection during a parasitological faecal screening examination. Three months before, the dog started a treatment against leishmaniasis infection with oral miltefosine (Milteforan®, Virbac S.r.l.) at 2 mg/kg/day for 28 days and oral allopurinol (Zyloric®, Teofarma S.r.l.) at 10 mg/kg every 12 h for six months. Then, at the time of presentation the dog was still on therapy with allopurinol. At presentation (T0), the dog was bright, alert and responsive. The physical examination evidenced an increase in respiratory rate (40 beats per minute) and the presence of moderate lung inspiratory crackles, localized in the left caudal lung. The dog did not present clinical signs relative to neurological or coagulation disorders. The kennel’s employees did not report symptoms related to respiratory disease (e.g. cough). |
pmc-6549332-2 | Case 2 was a 10 years-old, female, neutered, 19 kg dog, presented because of exercise intolerance, chronic cough, dyspnoea, weight loss and abdominal distension. The dog did not present symptoms related to neurological or coagulation disorders. On physical examination the dog showed tachypnoea, abdominal distension, pale mucous membranes, jugular vein pulse and distension, right systolic heart murmur (grade III/VI) and severe crackle sounds diffused on both lungs.
Each dog underwent parasitological examination, blood analysis, chest radiography, standard echocardiography and a saline contrast echocardiography (SCE) test. |
pmc-6549348-1 | A 69-year-old Chinese woman was admitted to our hospital with fever and myalgia persisting for 2 days on August 12, 2017. The patient was not treated at a local clinic. Except a history of hypertension for 3 years, she had no other specific diseases or familial medical history. She lived in a rural area from her birth and often worked in fields. The vital signs were body temperature 39.0 °C, heart rate 122/min, respiratory rate 23/min and blood pressure 130/80 mmHg. The positive physical examination included a poor general condition, petechiae in the chest, palpable lymph nodes in the neck and axilla, and rough breathing sounds in lungs. Upon admission, hematologic tests revealed that her leukocyte count was 1.1 × 109 /L, erythrocyte count 2.88 × 1012 /L, hemoglobin 102 g/L, platelet count 36.0 × 109 /L, and abnormal lymphocytes 3%. Blood biochemistry showed blood urea nitrogen 14.17 mmol/L, creatinine 135.1 μmol/L, lactic dehydrogenase 989.4 IU/L, ferritin > 2000 μg/L and procalcitonin 66.29 ng/ml. The prothrombin time was 18.7 s, partial thromboplastin time 86.3 s, fibrinogen 1.90 g/L and D-Dimer over 20 μg/ml. Enzyme-linked immunosorbent assays of IgM and IgG antibodies for HFRS were both positive and the serotype of hantaviruses was HTNV. Additional serologic tests showed that antibodies against EBV, cytomegalovirus, herpes, adenovirus, respiratory syncytial virus, influenza virus A and B, human immunodeficiency virus, Hepatitis A, B, and C viruses, Legionella pneumophila, mycoplasma pneumoniae, chlamydia pneumoniae and rickettsia were negative. The scan of chest and abdomen by computed tomography demonstrated that hypostatic pneumonia and hepatosplenomegaly. The ultrasound examination to superficial lymph nodes revealed that multiple lymphadenectasis in the neck, axilla and groin. After 4-day hyperthermia (a peak temperature of up to 42 °C) from admission, the patient’s condition deteriorated gradually. Blood test showed that leukocyte count was 2.6 × 109 /L, erythrocyte count 1.91 × 1012 /L, hemoglobin 70 g/L, platelet count 10.0 × 109 /L, abnormal lymphocytes 18%, blood urea nitrogen 13.64 mmol/L, creatinine 200.6 μmol/L, lactic dehydrogenase 1169.0 IU/L, alanine aminotransferase 63.4 U/L, aspartate aminotransferase 260.7 U/L, albumin 28.3 g/L, creatine kinase 1859.4 U/L, creatine kinase-MB 58.3 IU/L, hydroxybutyrate dehydrogenase 816.0 IU/L, HDL-cholesterol 0.51 mmol/L, LDL-cholesterol 0.38 mmol/L, total cholesterol 1.34 mmol/L, triglyceride 1.04 mmol/L, the prothrombin time 18.5 s, partial thromboplastin time 100.2 s and fibrinogen 1.34 g/L. For clear comparison and understanding, the results of these blood parameters with their normal range on admission day 1 and day 4 were listed in Table . The immature cells and nucleated erythrocytes were found by peripheral blood smears. The concurrently cultures of blood, urine and sputum did not reveal any pathogen. The formation of histiocytes with prominent hemophagocytosis was discovered through bone marrow aspiration (Fig. ).
In the treatment of the patient, we just focused on the original disease HFRS, mainly taking the measurements of antiviral agent ribavirin, diuretic and intermittent hemodialysis in the initial and oliguric stages, antibacterial drug cefoperazone sodium and sulbactam sodium in dealing with pulmonary infection, maintenance of water and electrolyte acid-base balance and other supportive therapies when needed. No corticosteroids and specific therapy were applied. The patient recovered completely after the above comprehensive treatments on day 26. Bone marrow aspiration was performed again on September 7 and the result only showed secondary anemia but no signs of hemophagocytosis. The 3 months follow-up blood tests after her discharge from our hospital demonstrated normal outcomes. |
pmc-6549366-1 | A 73-year-old man with unresectable stage IIIB MCC was referred to the National Institutes of Health for treatment with the monoclonal anti-programmed cell death ligand 1 (PD-L1) antibody avelumab. On physical examination, there were multiple pink to deep red smooth tumors with prominent vasculature on the central scalp (Fig. a) and left cervical lymphadenopathy was palpable. Biopsy of a scalp tumor revealed neuroendocrine carcinoma with positive staining for cytokeratin 20 (CK20) and synaptophysin, confirming the diagnosis of MCC. Positron emission tomography/computerized tomography (PET/CT) scanning showed metabolically active cutaneous and subcutaneous nodules on the vertex of the scalp, and multiple metabolically active enlarged cervical and supraclavicular lymph nodes.
The patient was started on avelumab at a dose of 10 mg/kg infused every two weeks. He was pre-medicated with acetaminophen, diphenhydramine and ranitidine. Two weeks after his first infusion his scalp lesions were inflamed and enlarged, consistent with pseudo-progression (Fig. b). The scalp tumors and lesions on CT scans subsequently regressed (Fig. c).
Between his second and third infusions, the patient developed a pruritic erythematous eruption on the chest, upper back, upper arms and right lower extremity. Examination revealed numerous thin, pink-brown scaly plaques ranging in size from 1.0 cm to 1.5 cm and involving sites of pre-existing seborrheic keratoses (SK) and solar lentigines (Fig. d, f & g). A shave biopsy of an affected lesion on the right posterior shoulder was performed and histology demonstrated papillomatous epidermal hyperplasia with hyperkeratosis and focal parakeratosis. The epidermis contained scattered exocytosed lymphocytes associated with mild spongiosis, intermittent hypergranulosis, and copious dyskeratotic keratinocytes. The dermal-epidermal junction was obscured by a lichenoid infiltrate primarily composed of T-lymphocytes. These clinical and histological finding are consistent with lichen planus-like keratosis (Fig. a-e). Treatment with topical triamcinolone 0.1% ointment twice daily provided symptomatic relief. Inflammation of affected lesions diminished over the following two weeks (Fig. e & h), however, the patient experienced intermittent inflammation in scattered keratoses and lentigines during continued therapy with avelumab. Treatment with cryotherapy was effective at ablating individual symptomatic lesions and resolving the local inflammation. |
pmc-6549368-1 | Patient 1 (III-2 in Fig. a) is a 35-year-old male who is the second child of non-consanguineous Japanese parents. He presented with fever and lymphadenopathy at the age of 6. He was diagnosed with BD at 7 years of age because of recurrent oral and perianal ulcers and was prescribed with oral prednisolone (PSL). He had recurrent episodes of high-grade fever (up to 39 °C) associated with lymphadenopathy, pharyngalgia, and nausea. PSL dosage was adjusted according to the patient’s condition, and the withdrawal of PSL was difficult. He did not show any ophthalmological or neurological symptoms. He is currently treated with PSL (12.5 mg/day) and colchicine (1.0 mg/day). |
pmc-6549368-2 | Patient 3 (III-1 in Fig. b) is a 12-year-old girl who is the first child of non-consanguineous Japanese parents. At 2 months of age, she presented with 38–39 °C fever accompanied by abdominal pain, diarrhea, ankle arthralgia, oral ulcers, pharyngalgia, and an enlarged tonsil. Febrile attacks were recurrent every 1–2 weeks and resolved within 4 days. She presented with perianal ulcers (at 4 years old), bloody stool, and weight loss (at 5 years old), but colonoscopy did not identify any abnormality. At 9 years of age, she was prescribed with naproxen and methotrexate (MTX) because of left ankle arthritis, but MTX was stopped because of abdominal pain. She was treated with colchicine and mesalazine for abdominal pain, but they were not effective. At 10 years of age, she was suspected of having a periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome and was treated with cimetidine, which contributed to a reduction in the number of febrile attacks. Gastrointestinal and capsule endoscopy revealed multiple ulcers throughout the intestinal tract (Fig. ), and mesalazine was re-administered. Histopathology of ulcer biopsies showed infiltration of lymphocytes and plasma cells. There was no evidence of granuloma, cryptitis, or crypt abscess, and the findings were thought to indicate nonspecific chronic inflammation. At 11 years of age, bilateral non-granulomatous acute anterior uveitis was revealed by ophthalmologic examination and diagnosed as BD. She did not show any neurodevelopmental delay. Currently, she experiences genital ulcers and has been treated with colchicine (400 mg/day), cimetidine (1.0 mg/day), and corticosteroid eye drops. The severity of abdominal pain is milder than before and fever is less frequent. |
pmc-6549489-1 | A 33-year-old female developed a disseminated vesicular rash on trunk and extremities with 40–50 non-synchronously evolving lesions, 2 weeks after receiving post-partum attenuated varicella vaccine. All lesions eventually crusted and resolved within 10 days from onset without any other clinical complications. Splenomegaly was noted on physical exam; it was previously documented in her physical exams since age 5 and was considered to be a sequela of infectious mononucleosis. With the exception of recurrent mild upper respiratory infections, she did not have any history of specific health complaints, hospitalizations, infectious complications, or lymphoadenopathy.
The concern for varicella zoster virus (VZV) vaccine strain disseminated infection and the persistent leucopenia led to an initial work-up, which revealed selective IgA deficiency and CD4 lymphopenia (111–118 cells/μL). A presumed diagnosis of Idiopathic CD4 lymphopenia (ICL) was formulated, and she was referred to the NIH Clinical Center for further evaluation. Imaging confirmed splenomegaly (17 cm cranio-caudal length) and revealed modest mesenteric and retroperitoneal adenopathy (). Flow cytometric analysis of T-cell subpopulations confirmed CD4 lymphopenia (CD4 189 cells/μL), normal numbers of CD8 T cells (383 cells/μL), and an increased proportion and absolute number of CD3+TCRαβ+CD4−CD8− double negative T cells (DNT) (4.3%, 33 cells/μL). In addition, high proportion of cycling of CD4 T-cells and DNT (Ki67 12 and 42%, respectively) as well as increased PD-1 expression in CD4 T-cells (42%) were found. The proportion and absolute number of total B cells were within normal range (CD19+: 16.4%, 75 cells/μL). Total IgG levels were moderately elevated (1,716 mg/dL), IgM were within normal range (54 mg/dL), while IgA undetectable. Bone marrow biopsy showed scattered lymphocytic aggregates with prevalence of CD8+ cells, consistent with previously reported findings in bone marrow biopsy of patients with ALPS () (). Targeted NGS with custom target enrichment revealed a novel heterozygous missense variant in the death domain (NM_000043 c.719T>A p.M240K) of the FAS gene and was confirmed by direct Sanger sequencing ().
FAS-induced apoptosis was evaluated in a crosslinking assay to determine the functional effect of such novel genetic variant (). Apoptosis was expressed as normalized fold-change of Annexin-V expression at different concentrations of crosslinking FAS antibody. In effector memory CD4 T-cells (CD3+CD4+CD45RA−CCR7−CD27−) from healthy individuals (n = 8), an average increase of 1.93 ± 0.2-fold increase in Annexin-V expression was found with 1,000 ng/mL of crosslinking FAS antibody. At the same concentration of crosslinking FAS antibody (1,000 ng/mL), the Annexin-V expression remained unchanged in the index patient (1.06 ± 0.1-fold, n = 4, p = 0.01) (). Similarly, while Annexin-V expression increased significantly in DNT TCRαβ+ T-lymphocytes of healthy individuals (1.57 ± 0.07 with 1,000 ng/mL, n = 8), it remained unchanged in the index patient (0.94 ± 0.03-fold, n = 4, p = 0.0002).
Functional characterization of the novel FAS genetic variant also included FAS-induced apoptosis and sensitivity to activation-induced-cell-death (AICD) assays on T cell blasts (, ). A significant reduction of FAS-induced apoptosis was found in T cell blasts from the index patient at all concentration of crosslinking FAS antibody: at the highest concentration (1,000 mg/mL), Annexin-V expression increased in CD4 (3.06 ± 0.2-fold, n = 6) and CD8 (2.8 ± 0.3-fold, n = 6) blasts from healthy individuals but remained substantially unchanged in CD4 (1.2 ± 0.05-fold, n = 3, p = 0.02) and CD8 (1.2 ± 0.1-fold, n = 3, p = 0.02) blasts from the index patient (). Similarly, a significant reduction in AICD was found in T cell blasts of the index patient: the proportion of dead cells after stimulation with the highest concentration of PHA (50 μg/mL) increased in CD4 (6.8 ± 0.3-fold, n = 6) and CD8 (13.7 ± 2-fold, n = 6) blasts from healthy individuals but to a lower extent in CD4 (3.3 ± 0.25-fold, n = 3, p = 0.02) and CD8 (8 ± 1.2-fold, n = 3, p = 0.09) blasts from the index patient ().
Further immunological evaluation of the patient included measurement of plasma cytokines and showed an increased level of soluble FAS ligand (801 pg/mL, normal level < 200 pg/mL) and increased levels of Interleukin-18 (7,248 pg/mL). A definitive diagnosis of ALPS-FAS was formulated based on the 2010 revised diagnostic criteria as both required criteria were satisfied (chronic lymphadenopathy, splenomegaly, and increased TCRαβ+ DNT cells), in addition to one primary criterion (pathogenic germline mutation in FAS death domain). |
pmc-6549525-1 | A 19-year-old male presented with gross total painless hematuria of a 5 days duration. There was no past family history of cancer. General physical examination and systemic examination were normal. Blood workup showed anemia. Renal function and liver functions were within normal limits. An ultrasound showed a polypoidal mass attached to the anterior wall of the bladder of 7 × 5 cm in size, which was further confirmed by a contrast enhanced CT scan (CECT) of abdomen. There was no evidence of lymph node or visceral metastasis. Transurethral resection of the bladder mass was performed. The upper gastrointestinal tract (GI) and lower GI endoscopy was within normal limits. A bone scan did not show any skeletal metastasis. Thereafter, the patient underwent robot assisted partial cystectomy and bilateral lymph node dissection till aortic bifurcation. The histopathology was suggestive of a high-grade urothelial carcinoma with six out of seven nodes showing metastasis. Post operatively, the patient developed fever and intestinal obstruction, initially managed conservatively, however, the patient did not show improvement. A repeat CECT abdomen was done which showed soft tissue lesions in both lungs, with pleural effusion, multiple liver lesions and ascites, suggestive of disseminated metastasis. The patient's general condition deteriorated, and he subsequently succumbed to his disease. An overview of the medical disease history is illustrated in a timeline (). Photomicrographs of the tumor from the urinary bladder showed a high-grade urothelial carcinoma with plenty of large pleomorphic cells and infiltrating the detrusor muscle ().
Whole-exome sequencing (WES) analysis of the paired tumor-normal sample from the patient was performed. A detailed description of the sequencing methods is provided in the . WES data analysis revealed 558 exonic somatic mutations, of which 360 missense, 26 nonsense, 30 frameshift deletions/ insertions and, also 10 splice site mutations were annotated (). Thirty mutations are reported in COSMIC database () including in genes, such as TP53, ABL1, ARID5B, and P2RX7 (). In addition, using Cancer Genome Interpreter (), we predicted eight potential driver mutations among all the somatic mutations detected in this rare tumor. These predicted driver mutations including loss-of-function mutations in TP53, RB1, MED23, CTNND1 and activating mutations in NSD1and MED17 (). The TP53 p.V157L a known oncogenic mutation was identified as a recurrent hotspot in various cancer types (). RB1 is involved in the regulation of the cell cycle checkpoint and DNA damage response. The RB1 c.1498+1G>T alteration is likely oncogenic. Mutations in RB1 is associated with poor overall survival in patients with urothelial carcinoma (). Domain structures of these genes highlighting the predicted deleterious mutations were generated using MutationMapper ().
Given that the above predicted driver mutations are in the genes that are limited to already known/predicted cancer driver genes, we carried out a network analysis of 347 genes that harbor a missense mutation using the STRING database. An analysis of the enriched interaction network was performed against the whole genome genes and the enrichment of ion channel pathways was identified (). Ion channels play a pivotal role in regulating self-sufficiency in growth, insensitivity to anti-growth signals, evasion of apoptosis, limitless replication potential, sustained angiogenesis, tissue invasion and metastasis (, ). We identified somatic alterations in 22 genes involved in the ion channels. shows the list of seventeen missense and one frameshift insertion somatic mutations in genes involved in the ion channels. The human genome encodes approximately 328 ion channel genes (). Mutated genes in this patient belong to 11 groups of ion channels (). We generated the ion channels interaction network of 141 genes () comprising of 11 groups using STRING database. Interaction network shows the highly connected network of voltage-gated calcium, cation channels, voltage-gated potassium and voltage-gated sodium channels (). Domain structures of nine genes highlighting the predicted deleterious somatic mutations are shown in . |
pmc-6549556-1 | A 63-yr-old Caucasian woman of Polish descent presented with a recent onset of visual symptoms. She was initially diagnosed with paramacular drusen associated with age-related macular degeneration (AMD). Best-corrected visual acuity (BCVA) was 20/25 OD and 20/40 OS and remained stable in the following 2 years. A history of smoking was noted, but no history of ocular trauma or inflammation was reported. A positive family history consisted of a brother diagnosed with advanced neovascular AMD. Slit-lamp examination of the anterior segment was within normal limits. Fundus examination revealed healthy optic nerves with no disk pallor and normal retinal vasculature appropriate for age without significant thinning or attenuation; there were diffuse yellow flecks in the peripheral macula extending out into the mid-periphery. Clustered, confluent patterns were observed in the temporal macula and arranged radially in the central macula. Pigment stippling/mottling around the fovea were also observed (A, inset, blue arrowheads).
Flecks were autofluorescent with dark borders. Spectral-domain optical coherence tomography (SD-OCT) revealed a loss of foveal pit contour, inner retinal thickening, and a hyper-reflective inner limiting membrane (ILM) in the left eye consistent with a developing epiretinal membrane. Flecks were visible as hyper-reflective deposits traversing photoreceptor layers emanating from the RPE (B). Ellipsoid zone (EZ) and external limiting membrane (ELM) layers are disrupted at the position of flecks (C, red arrowheads). Flecks of sufficient height impinged on the outer nuclear layer (ONL). Microperimetry (MP-1) testing (10-2 visual field pattern) showed reduced visual sensitivity and function over flecked areas (10–16 dB). Foveal fixation was stable (BCEA = 1.26 deg2) at 95.4% (). Full-field electroretinogram (ffERG) testing was conducted and analyzed in accordance with International Society for Clinical Electrophysiology of Vision (ISCEV) standards (). Results from single flash cone and 30-Hz flicker stimuli showed normal waveform amplitudes and no implicit time delays indicating no generalized dysfunction of the cone system (). See for a summary of the clinical findings. |
pmc-6549557-1 | A 69-year-old man with a past medical history of hypertension and coronary artery disease presented with hematuria and a 2.6-cm mass in the left kidney. He underwent left radical nephroureterectomy and was found to have a high-grade papillary urothelial carcinoma (UC) in the renal pelvis with invasion into renal parenchyma and lymph node metastasis (AJCC 8th edition: pT3N1). One month later, a magnetic resonance imaging (MRI) scan demonstrated metastatic disease in his liver, cervical and lumbar spines, humerus, and retroperitoneal lymph nodes. A liver biopsy confirmed the presence of metastatic UC (A). He received eight cycles of carboplatin and gemcitabine that resulted in disappearance of the liver lesion and decrease in size of the bone lesions and lymphadenopathy. He also received denosumab (Xgeva) during this time. He required several blood transfusions for iron deficiency anemia and experienced mild neuropathy as a side effect of chemotherapy.
Two months after completing chemotherapy, an MRI scan showed disease progression in the liver and retroperitoneum. The patient enrolled in a phase II trial of nivolumab (Opdivo), an anti-PD-1 antibody. He tolerated the therapy well, but 2 months later, restaging imaging showed an increase in the size of the liver, retroperitoneum, pelvic, and inguinal lymph node disease. A second biopsy of the liver lesion was evaluated with the FoundationOne test (Foundation Medicine) and at our institution using next-generation sequencing (NGS)-based panels. An NRF1-BRAF fusion was detected by both laboratories.
Based on the genomic findings, the patient opted to begin a trial of trametinib (Mekinist), a second-generation mitogen-activated protein kinase kinases (MEK) inhibitor. After two and a half months of treatment, a MRI scan demonstrated an overall 48.4% decrease in size of the liver lesions: from 6.3 cm to 2.4 cm in segment 8; from 6.6 cm to 3.6 cm in segment 5; and from 2.8 cm to 1.6 cm in segment 2. However, at 3 months post-initiation of treatment, the patient's chest computed tomography (CT) scan showed ground-glass opacifications concerning for pneumonitis, a known adverse effect of trametinib. The patient was advised to stop taking his medication for 3 weeks. In the interim period, he developed cyclic fevers, fatigue, and confusion with leukocytosis and elevated liver enzymes. An MRI scan demonstrated new liver lesions suspicious for disease progression, and a repeat liver biopsy confirmed new foci of metastatic UC. Given his poor performance status, the patient opted to enter hospice care and died shortly afterward. |
pmc-6550493-1 | A 32-year-old female presented to the emergency department with a four-month history of confusion, psychosis, slurred speech, nausea, vomiting and dizziness. Her symptoms included abdominal pain, headache, and depressed mood, lack of motivation and concentration, anorexia and associated 10 pounds weight loss in the prior three months. She had lost interest in her daily activities, and suffered considerable personality changes. All her symptoms were aggravated during periods of emotional and physical stress at her workplace, to the extent that she experienced episodes of panic attacks and insomnia. She consulted a psychologist for her depression and psychological symptoms, and was advised to engage in breathing exercises and yoga, neither of which improved her symptoms. On clinical examination, her pulse was 110 beats/min and blood pressure (BP) was 90/60 supine, thin brittle nails, scanty body hair, hyperpigmented knuckles, elbows and intraoral pigmentation of buccal mucosa. Laboratory investigations revealed anemia with hemoglobin level of 7.6 mg/dl, normal red blood cell morphology, erythrocyte sedimentation rate (ESR) 60 mm/h, and fasting blood sugar of 80 mg/dl. Her metabolic profile, including serum urea, creatinine, and electrolytes were within normal range. Mantoux tuberculin skin test was negative and her chest radiograph ruled out tuberculosis. Her thyroid and parathyroid hormone profiles were normal. Her morning serum cortisol (4.54 micrograms/dl, N: 4.3-22.4 micrograms/dl) and serum aldosterone levels (27.50 pg/dl, N: 25-315 pg/dl) were also normal. An ACTH stimulation test showed poor response (prestimulation level of 14.64 micrograms/dl, poststimulation level of 13.87 micrograms/dl and normal expected rise of 10 micrograms/dl). Antinuclear antibodies, rheumatoid factor, hepatitis B, hepatitis C and HIV were negative. Based on the patient’s self-reported history, clinical history and laboratory investigations, the diagnosis of Addison’s disease was established. She was managed with IV hydrocortisone, parenteral fluids, and glucose supplements during her Addisonian crisis. She recovered after two days of hospitalization. After a complete evaluation, cortisol replacement in the form of methylprednisolone 10 mg in the morning and 5 mg in evening was started. Her skin pigmentation, appetite, neuropsychiatric symptoms, mood and sleep disturbance have improved with cortisol replacement therapy, and she feels more motivated at her workplace. |
pmc-6550496-1 | A 50-year-old Hispanic male was admitted with a three-day history of progressively worsening headaches. Computed tomography (CT) and magnetic resonance imaging (MRI) identified a pineal region mass measuring 3.5 x 2 x 3 cm (Figure ).
A supracerebellar infratentorial approach in the sitting position was planned for resection of the pineal mass. Preoperatively, the patient was evaluated by transthoracic echocardiography (TTE) with agitated saline and Valsalva maneuver, to attempt to identify intracardiac shunts and none were identified.
In the operating room, invasive arterial blood pressure monitoring, five-channel electrocardiogram (ECG), transesophageal echocardiogram (TEE), and a peripherally inserted central catheter (PICC) with the tip in the right atrium were placed. Following standard anesthetic induction and total intravenous maintenance consisting of propofol, dexmedetomidine, and remifentanil, an extensive TEE was performed in the supine position using contrast-enhanced ultrasound with agitated saline during a simulated Valsalva maneuver to rule out any possible right-to-left intracardiac shunts, including PFO, atrial septal defect (ASD) or ventricular septal defect (VSD) (Figure ).
After confirming that no defect was present, the patient was placed in three-point pin fixation and was placed in the sitting position. Intracardiac shunt testing via TEE was repeated once again after the final position was reached. Again, no evidence of intracardiac shunt was noted.
Upon drilling of our initial burr hole, a small amount of air entrainment was noted on TEE. The operative field was flooded with irrigation which improved this; however, it did not completely resolve. The burr hole was waxed, and the patient remained hemodynamically stable. As further burr holes were drilled, air continued to entrain. We then completed our craniotomy, and elevated the bone flap. At this point, a large VAE was noted on TEE. The bone edges were quickly waxed, and continuous irrigation was performed. The patient was then noted to become acutely hypotensive with a coincident precipitous drop in end-tidal CO2 from 30 mm Hg to 21 mm Hg, despite unchanged pulse oximetry reading 100%. The field was covered with a wet lap pad and the head of the bed was lowered and rotated slightly to the left. Hemodynamics were supported with repeated doses of epinephrine 10-50 mcg. The fractional inspired oxygen (FiO2) was increased to one. Air was also aspirated via the previously placed PICC. Despite elevated right atrial pressures, no intracardiac shunt was noted. After hemodynamic recovery, air was noted on the left side of the heart (Figure ).
This finding led to a presumptive diagnosis of right-to-left transpulmonary arteriovenous shunting allowing transmission of air during the transition to the supine position, solidified by increases in left atrial air during a Valsalva maneuver. The patient remained in the supine position until the left ventricle was free of air. A norepinephrine infusion was initiated to maintain a mean arterial pressure greater than 80 mm Hg. After the patient was stabilized, a discussion was made about continuing with the operation. Electroencephalography (EEG), motor-evoked potentials and somatosensory-evoked potentials remained stable. Considering the patient’s worsening pre-operative condition, the decision was made to proceed with the case. The patient was returned to the sitting position and the planned surgical procedure was completed resulting in gross total resection of the pineal mass (histologic diagnosis of pineal parenchymal tumor of intermediate differentiation).
Postoperatively, the patient remained intubated and underwent a CT scan of the head, which revealed air inside the ventricular system and the superior sagittal sinus. He was admitted to the neurological intensive care unit (ICU). On post-operative exam, upward gaze palsy, right gaze preference, left neglect and left hemiplegia were observed. CT angiography and perfusion showed no perfusion mismatch, but subsequent MRI of the brain showed acute cortical infarcts in the right frontal and parietal lobes involving the pre- and postcentral gyri (Figure ).
There were also small acute infarcts in the left frontal lobe and the vermis. Systolic blood pressure was maintained between 100 and 160 mm Hg. The patient was evaluated for possible seizure activity with continuous EEG which was negative. The patient was successfully extubated and placed on a nonrebreather mask for 24 hours to speed resolution of his pneumocephalus. Over the following days, his left-sided weakness and neglect resolved completely. He was discharged to an inpatient rehabilitation facility with upward gaze palsy, but otherwise intact on POD six. |
pmc-6550516-1 | A 17-year-old male presented with persistent pain of the right shoulder for two months. The pain was exacerbated during abduction and external rotation of the shoulder. The clinical examination was consisted with supraspinatus tendinopathy. The plain radiographs of the right shoulder revealed a solitary lesion of the distal clavicle suggestive for a benign bone lesion (Figure ).
The magnetic resonance imaging (MRI) was consisted with a distal clavicle tumor with benign characteristics arising from the distal posterior-inferior surface of the bone (Figure ).
The mass seemed to limit the available space for the supraspinatus muscle near to the musculotendinous junction. An open resection of the tumor was scheduled. With the patient in beach chair position, a longitudinal incision between the distal clavicle and the coracoid process was performed followed by superficial and deep dissection of the soft tissues. The distal clavicle was palpated and a subperiostical exposure of the anterior surface was performed. Because of the posterior-inferior location of the tumor, a distal clavicle resection about one centimeter (cm) from the acromioclavicular (AC) joint was necessary for better approach. With the use of a saw and a curved osteotome the tumor was completely resected including the adjacent clavicle cortex (Figure ).
The coracoclavicular ligaments were checked intraoperatively and found intact. However, an anterior deltoid reattachment to the distal clavicle, through transosseous nonabsorbable sutures, was performed to secure the stability of the clavicle (Figure ).
The postoperative radiograph showed complete resection of the tumor (Figure ).
The arm was protected in sling immobilization for three weeks. The pathology report confirmed the diagnosis of osteochondroma. Gentle exercises were permitted after three weeks with full range of motion (ROM). In six weeks postoperatively, the patient returned to his normal activities and 10 weeks postoperatively he got back in sport activities. |
pmc-6551195-1 | An 82-year-old woman with known osteoporosis presented with several weeks of unrelenting axial lower back pain. After conservative management with pain medication and rest, she was referred to a pain management clinic for further evaluation. On examination, the patient had tenderness to percussion at the 2nd lumbar vertebral body (L2) without evidence of radiculopathy. T2-weighted magnetic resonance imaging (MRI) revealed an acute compression fracture with inferior endplate involvement at the level of L2 (Figures -). After extensive discussion, the patient elected to proceed with L2 balloon kyphoplasty.
The patient was brought to the operating room, placed in the prone position, and prepped and draped in the standard fashion. Under direct fluoroscopic guidance, the left L2 pedicle was successfully cannulated on the first attempt using a 10-gauge access cannula. The trocar-tip stylet was removed and a curved coaxial needle with a radiopaque introducer was inserted through the access cannula and advanced to the proper midline position within the L2 vertebral body (targeted site location). The curved coaxial needle was then removed, leaving the introducer and access cannula in place. A flexible kyphoplasty balloon was then placed through the introducer and access cannula. Cavity creation was performed with the inflation of the balloon system and completed without complications. The balloon was deflated and removed simultaneously with the introducer, leaving just the access cannula in place. The curved coaxial needle was primed with polymethylmethacrylate (PMMA) and reinserted into the vertebral body through the access cannula. A total of 2.5 cc of PMMA was used and an even fill was seen on fluoroscopic imaging.
Attempts were made to remove the curved coaxial needle from the access cannula, but it was found to be fastened in place. The time elapsed since cement creation was nine minutes. Multiple attempts were made to remove the needle but it remained firmly in place despite the use of a mallet to loosen the instrument. After consultation with the physician representatives of the device company and two independent spine surgeons, the decision was made to dissect down to the level of the pedicle and cut the flexible needle at the level of entry into the bone.
After additional local anesthetic was injected, the subcutaneous layer was dissected and muscle tissue was retracted. The proximal handle of the curved coaxial needle was cut with a bone rongeur (Figure ) and the access cannula was removed from around it. The curved needle was cut to be as flush as possible to the level of the left L2 pedicle (Figure ) and palpated for sharp edges or protrusions from the pedicle border. Profuse irrigation was completed with bacitracin and the pocket and incision were closed in layers and dressed. Final images were then taken (Figures -).
The patient tolerated the procedure well and had no postoperative neurological compromise or injury. Her recovery period was uneventful. At all follow-up appointments through a 12-month period, the patient had sustained relief from her back pain and remained without evidence of neurological complications. |
pmc-6551196-1 | A 74-year-old Hispanic woman presented with an asymptomatic lesion of one-year duration on the nasal tip. Clinical examination showed a nodular tumor; in addition to being black, there was ulceration (Figures -). There was no palpable neck lymphadenopathy. Morphologically, the clinical differential diagnosis included malignant melanoma.
A biopsy was performed. Microscopic examination showed nodular aggregates of basaloid tumor cells extending from the epidermis into the dermis. There was pigment not only in the tumor cells but also within the melanophages in the adjacent dermis. Correlation of the clinical presentation and pathology established the diagnosis of pigmented nodular basal cell carcinoma.
Mohs surgery was performed. The tumor was cleared after three stages. A left paramedian forehead flap was performed to treat the surgical wound. Follow-up three months later showed excellent healing without recurrence of the skin cancer. However, there was significant hypertrichosis involving the tissue flap on the nasal tip (Figures -). This was remedied by using electrolysis to eliminate the hair. |
pmc-6551196-2 | A 63-year-old Hispanic man presented with an asymptomatic lesion on his left nasal bridge of nine months duration. The tumor appeared as an ulcerated plaque with black pigmentation; there were also red and flesh-colored areas (Figure ). There was no palpable neck lymphadenopathy. The clinical differential diagnosis included ulcerated malignant melanoma.
A biopsy was performed. Microscopic examination showed nodular aggregates of basaloid tumor cells extending from the epidermis into the dermis. There was pigment not only in the tumor cells but also within the melanophages in the adjacent dermis. Correlation of the clinical presentation and pathology established the diagnosis of pigmented nodular basal cell carcinoma.
Mohs surgery was performed. The tumor was cleared in two stages. A full thickness graft was used to treat the surgical wound. Follow-up after three months did not reveal any recurrence of the cancer. |
pmc-6551196-3 | A 77-year-old Hispanic woman presented with a lesion of one-year duration that was progressively enlarging on her left breast; the lesion would occasionally bleed. Clinical examination showed a 2 x 1 cm black nodule; in addition, extending from the base of the tumor onto the adjacent skin, was macular brown pigmentation (Figures -). There was no palpable neck, axillary, or inguinal lymphadenopathy. The clinical differential diagnosis included a nodular malignant melanoma.
A biopsy was performed. Microscopic examination showed that the lesion consisted of two concurrent tumors. The first was an ulcerated nodular basal cell carcinoma with aggregates of basaloid tumor cells extending from the epidermis into the dermis; there was pigment in both the tumor cells and within the melanophages in the adjacent dermis. The second was a seborrheic keratosis showing acanthosis and hyperpigmentation. Correlation of the clinical presentation and pathology established the diagnosis of a collision tumor consisting of an ulcerated nodular basal cell carcinoma and a seborrheic keratosis.
Mohs surgery was performed. The tumor was cleared in one stage. A layered closure was used to repair the surgical defect (Figures -). Follow-up after three months did not reveal any recurrence. |
pmc-6551201-1 | A 33-year-old woman reported to the Department of Periodontology, Sri Ramachandra Dental College, Sri Ramachandra Institute of Higher Education & Research (DU), with the chief complaint of a missing tooth and the inability to masticate. She had no relevant medical history and had a history of undergoing orthodontic treatment, extraction of the lower left first molar, and endodontic treatment done three years back in relation to the left lower second molar. The patient had presented with fair oral hygiene.
On clinical examination, a gingival growth was present on the floor of the endodontically treated tooth (#37), as seen in Figure .
The tooth had no pain, probing pocket depth, and mobility associated with it. A provisional diagnosis of a gingival polyp was given. An intraoral periapical radiograph was taken, and it revealed no crestal bone loss or bone loss involving the furcation. However, radiolucency was seen on the distal surface of the tooth near the cementoenamel junction (Figure ).
To substantiate the radiographic and clinical features and to establish the pathway of the polyp, a periodontal probe was inserted horizontally from the lingual aspect of the tooth and a small perforation was noticed on the distolingual aspect of 37. Furthermore, a Gutta Percha Point was inserted from the distolingual aspect and a pathway was established from the lingual marginal gingiva to the floor of the cavity.
A final diagnosis of gingival enlargement - gingival overgrowth due to accidental perforation was established. Treatment options included the extraction of the said tooth or the preservation of the tooth with a combination of periodontal procedures and endodontic materials, though it had a questionable prognosis. Both options were explained to the patient and the patient was willing to save the natural tooth, as she had extracted the tooth mesial to it.
The treatment plan included laser-assisted excision of the polyp followed by the restoration of the perforation with mineral trioxide aggregate (MTA). After obtaining informed consent from the patient, initial cause-related treatment was carried out, following which the patient was taken up for the procedure. After sufficient anesthesia was given, laser-assisted excision was carried out with a diode laser (BioLase ezlaseTM 940; BioLase, CA, US), as shown in Figure .
The excision was carried out in contact mode, with universal protocols from the lingual aspect of the tooth. After excision of the polyp, the perforation was checked for any tissue remnants. As there was no significant postoperative bleeding, the perforation was sealed using MTA. The sealant was mixed and placed in the perforation as per manufacturer’s instructions and restored with Glass Ionomer Cement - Type II (GC Fuji®, Tokyo, Japan) (Figure ) [].
A periapical radiograph was taken to confirm the seal postoperatively (Figure ).
No antibiotics or analgesics were prescribed postoperatively. Oral hygiene instructions were given to the patient.
The patient was reviewed the following day, and one week later, and the patient had no complaints or discomfort associated with the procedure. The patient was reviewed three months postoperatively and was asymptomatic and referred for further prosthodontic rehabilitation. |
pmc-6551479-1 | A 43-year-old previously healthy woman presented for right-sided flank pain, fever, chills with leukocytosis, history of UTI treated by antibiotics 2 weeks ago, with long history of recurrent intermittent right-sided flank pain not investigated. Renal ultrasound showed severe right-sided hydronephrosis () and computed tomography scan suggested the presence of a RCU ().
Serum testing demonstrated preserved renal function, urine culture turned positive for proteus mirabilis. The patient was treated with intravenous antibiotics and drainage of the right kidney by a double J stent () with retrograde ureteropyelography that confirmed the diagnosis of retrocaval ureter (), antibiotic treatment continued for 2 weeks orally, and laparoscopic repair of retrocaval ureter was planned after sterilization of the urine. |
pmc-6551479-2 | A 38-year-old man previously healthy presented for a recurrent intermittent right-sided flank pain exacerbating since about 1 year ago, aggravated by water intake and associated with irritative (urinary frequency) lower urinary tract symptoms (LUTS), history of left renal colic with spontaneous passage of small stone about 3 years ago not investigated. Renal ultrasound demonstrated sever right-sided hydronephrosis () and computed tomography scan suggested the presence of a retrocaval ureter (), Serum testing demonstrated preserved renal function, and a laparoscopic repair of retrocaval ureter was planned, with a right retrograde ureteropyelography (), done just before the surgery for a retrograde double J stent placement (), and confirmed the diagnosis of retrocaval ureter. |
pmc-6551541-1 | A 16-year-old male complained of inability to flex his left elbow since 1 year prior to admission. One and a half year before, he fell down and hit his elbow during football practice. He felt pain and there was swelling on his elbow. However, he didn't seek for medical treatment. He had his elbow massaged every week for 5 months but there was no improvement. His elbow became fixed in extended position. A month later, he went to an orthopaedic surgeon and underwent x-ray examination which revealed a fracture and dislocation on his left elbow. He was then referred to our institution for further treatment.
From clinical examination, range of flexion-extension of the elbow was 300-00 with normal pronation-supination. There was no neurological deficit (). From radiological examination, there was a malunion of medial epicondyle with subluxation of left proximal ulna (). From 3D CT reconstruction, there was a deformity and malunion fracture in humeral capitellum with radial and ulnar postero-superior dislocation (). The patient was diagnosed with extension contracture of the left elbow due to malunion of left capitellum, neglected dislocation of the radiohumeral joint, and neglected dislocation of the ulnohumeral joint. The patient was scheduled to have a contracture release, open reduction and internal fixation, and ulnar interposition.
Intraoperatively, we did a posterior approach to the elbow. The ulnar nerve was identified and preserved. The fibrotic tissues and heterotopic ossification were excised. We did a contracture release and open reduction and internal fixation using K-Wire. The flexion and extension of the elbow were evaluated and we managed to get 300 - 130° of flexion-extension ROM. Afterwards, ulnar interposition was performed to prevent ulnar impingement. The wound was closed and a single drain was placed. The elbow was immobilized with back-slab in 900 flexion position for two weeks.
After 1 week, the patient went back to our hospital for follow-up examination. In the 1st evaluation, we tried to remove the back slab and moved the elbow passively. The movement is restricted due to pain and the patient went back home with the back slab on. In the 2nd week follow-up, we permanently remove the back slab and the stitches. At that time, the pain still persisted and the patient was planned to have physical rehabilitation.
On the 4th week after surgery, the surgical wound was infected. We performed debridement, implant removal, and manipulation under general anesthesia. Two weeks later, patient came back to our hospital. We removed the stitches and started rehabilitation. Later on, he continued his rehabilitation in his previous hospital.
After 6 months, he visited our outpatient clinic for medical checkup. From physical examination, the elbow flexion-extension ROM was 1100 - 300 (). The patient is able to do normal daily activities (). |
pmc-6551867-1 | A 75 years old man, smoker, with a past history of a hepatic transplantation 13 years earlier for a hepatocellular carcinoma, was admitted to hospital with hemoptysis and dyspnea. He performed a chest CT scan, showing a solid lesion in the apical segment of right lower lobe with multiple confluent mediastinal adenopathies and right paratracheal lymphadenopathy (Fig. ).
We practiced a videobronchoscopy that showed two small sessile lesions approximately 4.5 cm far from the carina on the right lateral wall of the trachea, which were removed with biopsy forceps. EBUS-TBNA was performed on the right paratracheal lymph node. The pathological findings were suggestive for hepatocarcinoma metastases and the patient was underwent chemotherapy.
After six months, the patient returned to the emergency room for wheezing and acute respiratory failure. Chest x-ray and CT scan showed deterioration of the radiological picture with stenosis of the tracheal lumen (Fig. ).
The patient made videobronchoscopy that showed a vegetative neoformation which obstructed the tracheal lumen about 6.5 cm far from the true vocal cords (Fig. ). The patient was intubated with a rigid bronchoscope Storz n°14 and we used laser photocoagulation to devascularize the lesion that was subsequently removed with a debulking maneuver, recanalizing the trachea (Fig. ). The anatomopathological findings confirmed the previous diagnosis of hepatocarcinoma metastases (Fig. ). |
pmc-6551893-1 | A 27-year-old man was admitted to the hospital owing to “double vision 6d.” His admission examination results revealed absence of left eye adduction, and he had an outward squint. His auxiliary examination results were as follows: proteinuria: 3+, urinary occult blood: 1+, 24-h proteinuria: 3.44 g/24 h (normal: < 0.20 g/24 h); cerebrospinal fluid pressure: 240 mmHg, glucose: 2.05 mmol/L, white blood cell count: 23 × 106/L, protein: 0.67 g/L, and cerebrospinal fluid immunoglobulin IgG: 68.00 mg/L (normal: 0–34.0 mg/L); activity of α-galactosidase A: 0.9 nmol/(h.mg) (normal: 25.5~64.1 nmol/(h.mg)). MR-fluid attenuated inversion recovery (FLAIR) imaging of the brain showed abnormal signals in the left oculomotor nucleus (Fig. a), and no obvious abnormality was noted on three-dimensional time-of-flight magnetic resonance angiography (3D-TOF-MRA) (Fig. b). The black-blood sequence showed partial thickening and mild enhancement of basilar artery and bilateral posterior cerebral artery (Fig. c). A pathological biopsy of the kidney revealed a large number of myeloid bodies and zebra bodies (Fig. d). Genetic testing revealed a nucleotide mutation in the GLA gene c.426C > A (nucleotide in the coding region 426 from C to A), which caused the Cys 142 amino acid-translating codon to function as a stop codon (p. Cys142Ter); this phenomenon led to the early termination of peptide chain synthesis. The mutation has been reported in the literature to be associated with Fabry disease (reference databases HGMD Pro and PubMed) []. The frequency of this mutation in the population is extremely low (reference databases: 1000 Genomes, dbSNP). According to the abovementioned test results, the diagnosis was Fabry disease. Subsequently, we treated our patient with corticosteroids, and he was discharged after his symptoms ameliorated. The patient was treated with long-term aspirin after discharge from the hospital. The patient returned to our observation after 2 months; MR-FLAIR imaging of the patient’s brain revealed new abnormal signals in the left temporal lobe (Fig. a), but we could not detect any obvious abnormality on the 3D-TOF-MRA (Fig. b). Furthermore, the black-blood sequence revealed an abnormal enhancement of the left middle cerebral artery (Fig. c), and the abnormal enhancement of the basilar artery and bilateral posterior cerebral artery had disappeared (Fig. d). Four months later after initial treatment, the black-blood sequence revealed that the abnormal enhancement of the left middle cerebral artery had disappeared, and no obvious abnormality could be detected in the 3D-TOF-MRA (Fig. e); however, local thickness and abnormal enhancement of the right middle cerebral artery was detected in the black-blood sequence (Fig. f). There were no symptoms during follow-up. |
pmc-6552941-1 | The patient is an 85-year-old Caucasian female (5′1″, 30.2 kg/m2 BMI) who presented with proximal, distal, dorsal, and ventral pain of her left wrist. Her medical history was notable for type 2 diabetes, hypercholesterolemia, and hypertension. The aching, dull and stiff pain in her left wrist gradually started one year prior. Diagnostic X-ray examination showed severe degenerative joint disease of the left wrist with scapholunate dissociation, scapholunate ligament tear, and avascular necrosis of the lunate (Figure ). The patient was subsequently treated with corticosteroid injection of the wrist which only provided relief for less than a week. Other treatments including home care and over-the-counter pain medication did not provide relief. Due to the recalcitrant nature, the attending physician recommended fusion or wrist replacement, which the patient declined and sought for a second opinion.
At presentation, her pain score was an average of 6 out of 10, but periodically reached 10 out of 10 on a numerical rating scale (0 being no pain, 10 being worst possible pain). The pain was reportedly constant but worsened with gripping, twisting, and bending. She also noticed decreased strength in addition to tenderness, swelling, and crepitus during movement. The wrist range of motion (ROM) was 0-20° flexion and extension, and 10° lateral deviation ulnar or radially. An informed consent was obtained after risks, and benefits were reviewed to receive the treatment via intra-articular injection of AMUC particulate (Clarix FLO®; Amniox). In brief, the left wrist was prepped with povidone-iodine (Betadine; Purdue Pharma) and vapocoolant (Pain Ease, Gebauer Company) followed by injection of 2 cc of 1% lidocaine (Hospira) using a 30G needle. The 100 mg of AMUC particulate was reconstituted with 2 cc of preservative-free normal saline and injected in an equal volume into the scapholunate joint and mid-carpal joint using a 25G needle under ultrasound guidance (LOGIQ e, GE Healthcare) using a 12 MHz linear probe. No complications were observed within 30 minutes, and the patient was released home with the instruction to wear a neutral carpal tunnel splint for 6 weeks.
Within 3-5 days after injection, the patient noted similar pain while on acetaminophen (Tylenol). However, at one month post-injection, the patient reported no pain with and without (during showers) the splint aside from “an occasional ache” as described by the patient. Physical examination revealed decreased swelling, crepitus, and tenderness. The ROM had also improved to 30 degrees of flexion and extension without pain. At 3 months post-injection, the patient reported no sharp pains with occasional dull aches that had severity of 2-3 out of 10. Patient also discontinued use of the splint 2 weeks prior to the 3-month visit and subsequently reported weakness in her hand and arm due to deconditioning. Overall, the patient reported her overall patient global impression of change as 70% improved compared to pre-injection (on a scale from 0% to 100%, with 0% the same as before injection and 100% was completely normal). No complications or adverse events were encountered. |
pmc-6552942-1 | The patient is a 61-year-old Korean male with a significant past medical history of rheumatoid arthritis, hypertension, and diabetes mellitus who presented to the hospital with sudden onset of blurry vision in his left eye three days prior. A head CT had been performed at an outside facility, which was negative for acute ischemia, hemorrhage, midline shift, or extra-axial fluid collection. The patient denied visual complaints in his right eye and had no history of similar events.
Ophthalmologic and Neurologic consultations initially revealed visual acuity was 20/40 on right eye; however, on the left eye, there was an apparent left-sided visual loss. Patient's intraocular pressure was normal in both eyes, pupils were equally round and reactive to light, and no afferent pupillary defect was observed. Moreover, the extraocular muscles were intact and with full range of motion. In the right eye, visual fields were full to finger count. In the left eye, the acuity in the nasal visual field was greater than that in the temporal visual field. In the nasal visual field, the patient was able to count fingers; however, in the temporal visual field, the patient could barely detect gross hand movement at one foot out. External examination was within normal limits, and pen light examination was only remarkable for nuclear sclerotic cataracts bilaterally. Dilated fundus examination demonstrated no evidence of pathology to the vitreous, optic nerve, or retina that might explain the vision loss. Four days later, repeat examination by Ophthalmology demonstrated a stable right eye; nonetheless, the left eye temporal visual field was 20/25 and patient was able to count fingers without mistake on left visual field. Pupil and retina examination were unchanged from previous examination. However, visual field mapping could not be done as this patient was seen in the inpatient setting.
Consequently, an initial head MRI with and without contrast was performed, which showed focal areas of restricted diffusion in the right medial temporal lobe, inferior right basal ganglia with possible involvement of the right lateral geniculate nucleus. The head MRI did not show any other pathology such as masses or hemorrhages (Figure ). The subsequent head MR angiogram done demonstrated no focal occlusion or stenosis, and the MRI of the orbits showed no focal defects bilaterally. At this point, it was evident that the patient was suffering from a left temporal monocular hemianopia and that there must be a correlation with the subtle but definitely present right LGN ischemic lesion. An infarct affecting the right lateral geniculate nucleus would most likely cause bilateral left homonymous hemianopia. Nevertheless, a lesion at the vicinity of right LGN that had taken out the inputs going to layers 1, 4, and 6 became generally accepted among all physicians involved at this point in the care of this patient as the only possible explanation. Patient's left visual symptoms slowly started to improve, and after four days of hospitalization and monitoring, patient's left monocular temporal hemianopia had almost resolved and his vision had almost returned to his normal baseline. |
pmc-6552943-1 | The patient was referred to the reproductive endocrine and infertility medicine department as a 31-year-old nulliparous woman, married for five years with primary infertility for in vitro fertilization (IVF). She had a history of irregular periods mainly oligomenorrhea with prolonged irregular menstruation. She had no acne, hirsutism, weight gain, or symptoms of PCOS. She reported no hot flashes or night sweating. She was not having diabetes, thyroid problem, or other immunological problems. As childhood, she did not have the intellectual delay or behavioral problems. She had no family history with a similar condition. Her mother's age at the time of her birth was unknown. Her general examination was normal. Her BMI was 23.7 kg/m2. She was tall, with a height of 170 cm and an arm span of 173 cm. Hands showed nevi on the outer aspect of the left side. Teeth and feet were normal. The thyroid examination was normal. However, there was a loud mid-diastolic murmur upon examination of the cardiovascular system. She had reported easy bruisability and eosinophilia. Her investigations revealed a hemoglobin 12.50 g/dl (11-16g/dL), platelet count 276.0 10 × 9/L (155-435/L), serum prolactin 10.4 ng/mL (5.18-26.53), serum follicular hormone (FSH) 18 IU/L, repeated FSH 26.72 IU/L (3.03-8.08 IU/L), serum luteal hormone (LH) 14.8 IU/L, serum estradiol (E2) 229 pmol/L, serum vitamin D 25-OH (total) 38.7 nmol/L (75 - 350), serum TSH 2.035 mIU/L (0.35-4.94), serum T4 free 12.1 pmol/L (9-19), and serum T3 free 3.8 pmol/L (2.6-5.7). Pelvic ultrasound of the uterus was normal for size, shape, and texture, and endometrium of 3 mm and both ovaries were seen; right ovarian volume was 0.33 mL, and the left ovarian volume was 1.15 mL; and the antral follicle count was zero in both ovaries. (Figure
) The patient underwent diagnostic laparoscopy for tubal patency that showed normal uterus with bilateral streak ovaries and patent tubes.
Karyotype analysis revealed a female karyotype with an additional X chromosome. Cytogenetic test was consistent with triple X syndrome, and FISH analysis revealed a female genotype, an X (FISH) was carried out using the CEPX (DXZ1) and Y(SRY) DNA probe panel (Abbott, USA) to screen for the copy number of chromosomes X and Y and the presence of the SRY gene region. A total of 500 interphase nuclei were scored for each chromosome, and the signal pattern revealed three copies for the X chromosome (DXZ1). FISH signal pattern confirmed the presence of three copies of the X chromosome, which was also consistent with triple X syndrome.
The patient was started on a noncontraceptive HRT regime and calcium supplement. Her echocardiography was done and reviewed by a cardiologist who cleared her from any cardiac anomalies. Genetic counseling and evaluation by a clinical geneticist were done. Consequently, she had ovulation induction with high doses of both recombinant human follicle stimulating hormone 300 IU (rFSH (follitropin alpha, Merck Serono, Gonal-F)) and 150 IU of human menopausal gonadotropin (HMG, Merional, IBSA). Subsequently, there was no response to treatment and eventually no pregnancy. |
pmc-6552944-1 | A 61-year-old Caucasian male patient presented for concerns of sepsis. He had a medical history of diabetes type II, renal transplant on tacrolimus and mycophenolic acid, chronic kidney disease stage III, heart failure due to ischemic cardiomyopathy, hypertension, atrial fibrillation, and chronic obstructive pulmonary disease. The patient was unable to provide an adequate history at the time of admission due to acute metabolic encephalopathy.
According to documentation provided by emergency medical services, the patient had experienced multiple episodes of emesis and diarrhea. His presenting vitals are available in Table . Upon arrival, blood and urine cultures were obtained, a peripheral blood smear ordered and the patient was started on empiric antibiotics with vancomycin and piperacillin/tazobactam. He received 4 L of normal saline. A chest X-ray (CXR) revealed bilateral pleural effusions consistent with volume overload. A computed tomography (CT) scan of the abdomen and pelvis without contrast revealed moderate right and small left pleural effusions, pancreatic atrophy, renal atrophy, and a right iliac transplanted kidney. An electrocardiogram (ECG) revealed junctional tachycardia with questionable atrial fibrillation. Nephrology was consulted secondary to elevated blood urea nitrogen (BUN) and creatinine and recommended continuous renal replacement therapy (CRRT).
The patient was admitted to the Intensive care unit (ICU) where his mentation continued to worsen and he became hypotensive (BP: 91/41). Physical exam revealed bibasilar rhonchi, tachycardia without a murmur, and pitting edema bilaterally. A Foley catheter was placed, and the patient received 40 mg of IV furosemide. He was started on bilevel positive airway pressure (BiPAP) for a deteriorating respiratory status. Overnight, the patient became increasingly bradycardic and developed asystole. ACLS protocols were performed resulting in the return of spontaneous circulation (ROSC). The patient required three additional rounds of ACLS for a total cumulative code time of approximately one hour. Following ROSC, the patient was intubated without sedation. The patient was started on norepinephrine and vasopressin continuous infusions for hemodynamic support. Later that morning, a central venous catheter was placed in the left internal jugular vein and the patient was started on epinephrine and bicarbonate continuous infusions.
Postarrest laboratory results, which can be seen in Table , revealed lactic acidosis with a pH of 7.135 and peak lactic acid of 9.5 mg/dL. A complete metabolic panel revealed elevated transaminases with peak aspartate aminotransferase (AST) >1600 U/L and alanine aminotransferase (ALT) of 3490 U/L consistent with hepatic shock. Sedation weaning trials the following morning revealed that the patient was tolerating mechanical ventilation without sedation. At that time, neurology was consulted secondary to suspicion for anoxic brain injury. Examination of the patient's lower extremities revealed the presence of bullae and erythema. Due to a lack of clinical improvement in empiric antibiotic therapy, the infectious disease service was consulted.
On day three, the findings of the peripheral blood smear were finalized which revealed pancytopenia with macrocytic anemia. It was noted that a rare neutrophil contained a few green crystals as seen in Figure . The pathologist noted that these findings could be seen in patients with critical illnesses in the face of acute hepatic failure. These inclusion bodies are also known as “green crystals of hematology.” The patient's case was discussed with the pathology department and further review of the slide revealed multiple neutrophils with similar findings described above.
On the fourth day, the patient's lactic acidosis and transaminases improved (Lactic acid: 1.7 mg/dL3, AST: 144 U/L, ALT: 1229 U/L); however, the patient showed no clinical change. Blood and urine cultures showed no growth to date. A neurologist evaluated the patient and ordered an electroencephalogram (EEG) revealing findings consistent with anoxic brain injury. Three physicians reviewed and discussed the patient's case and determined that further care was futile. The correctional facility was contacted, and the patient was made comfort care with the agreement of the warden and next of kin. The patient expired later that morning. |
pmc-6552945-1 | Our patient is a 2-year-old male who presented with a 1-day fever (Temperature: 103.6°F), cough, congestion, and inadequate oral intake. The patient's history was obtained from the patient's mother. She denied any signs of vomiting, abdominal pain, diarrhea, respiratory distress, ear pain, or a sore throat. Additionally, the patient showed signs of dehydration. Upon an initial examination, he was agitated but consolable. An examination of his ears revealed no external deformities; his canals were patent and without inflammation, and his tympanic membranes were intact, gray, translucent, and mobile. His nose showed no external deformities, and the nares were patent. His nasal turbinates were erythematous, but no inflammation was exhibited. His oral structures were normal for a child of his age, and the mucous membranes were moist and pink, without any lesions or exudates. His teeth did not have any dental caries. His neck was supple, and no cervical lymphadenopathy was present. The rest of his physical examination also revealed negative findings. The patient's fever and irritability warranted initial laboratory tests, including a rapid influenza test, a complete blood cell count (CBC), a C-reactive protein (CRP) test, and a blood culture. Abnormal values included leukocytosis that exhibited a left shift (26 500 cells/µL) and an elevated CRP (24.7 mg/L).
Due to his elevated CBC and CRP, the patient was called back into the office for a re-evaluation the next day. His physical examination revealed new findings of erythematous tonsils with a midline uvula, as well as left and right posterior cervical nodes. The tenderness of the nodes was difficult to decipher because the patient was irritable throughout the examination. The hydration status of the patient had improved from the previous night. The rest of his physical examination revealed similar findings as the previous day. A urinalysis was obtained via catheterization and revealed negative results. Since his elevated WBC count raised concerns of the possibility of a bacterial infection, an intramuscular ceftriaxone injection was given. The patient was sent home with instructions to the parents to report any changes in his symptoms or any reactions to the antibiotics. Subsequent tests for CBC and CRP, which were obtained on the 4th day of the patient's symptoms, were still elevated, although the levels had improved (20 000 cells/µL and 14.6 mg/L, respectively). The patient initially responded well to the antibiotics; however, his fever returned, with a temperature of 103.8°F. He was seen again in the office on the 6th day of his symptoms. At this point, he presented with a new finding of left neck swelling. He had cervical asymmetry, and his left tonsil was deviated toward the midline, due to soft tissue swelling. |
pmc-6552948-1 | A 21-year-old male patient, of Senegalese origin, with no relevant medical history, was admitted in January 2018 to the Department of Internal Medicine at Rouen University Hospital for deterioration of the general state, asthenia, weight loss of 18 kg in 8 weeks (20% of his usual weight), and neuropathic lower limb pain. Clinically, the general condition was maintained with a performance status (PS) of 1 and vitals were in the normal range. His BMI was 16, 68. The clinical examination revealed severe undernutrition, orthostatic hypotension, and bilateral neuropathic pain predominating in the right lower limb; the rest of the examination was without abnormalities. The baseline and follow-up cell blood count, biochemical data, and other important parameters such as NT-pro-BNP are provided in Table .
Protein electrophoresis found hypogammaglobulinemia at 5.9 g/L. The determination of serum free light chains found a high level of lambda at 918 mg/L, kappa at 7.6 mg/L, ratio at 120, and DFLC = 910.4. The myelogram on a bone marrow aspirate found a reduced cellularity bone marrow (cellularity was estimated at 1.5 on a scale of 0-4) with rare plasma cells representing 1.5% of the global cellularity. Immunophenotyping by flow cytometry found a very low percentage of plasma cells with a lambda type monoclonal appearance, CD56+ in 2% of plasma cells and loss of CD19 in 79% of plasma cells. Whole-body bone scan was normal, as it was spinal magnetic resonance imagery (MRI). cTnT was slightly elevated at 0.042 µg/L and NT-proBNP at 500 ng/L. Holter ECG, diphosphonate cardiac scintigraphy, electromyogram (EMG), and biopsy of the accessory salivary glands revealed no abnormalities. Cardiac MRI revealed diffuse hypertrophy of both ventricles with apex-predominant hypertrophy of the right ventricle, with preserved left ventricular ejection fraction consistent with diffuse fibrosis.
The patient was then transferred to the Hematology Department of the Henri Becquerel Center in February 2018 due to the suspicion of lambda light chain myeloma with concomitant diffuse amyloidosis.
Cardiac MRI acquisition at baseline showed prolonged T1 mapping consistent with the diagnosis of amyloidosis (Figure ).
Two serial transthoracic echocardiographic (TTE) acquisitions (Figure ) demonstrated thickened left ventricle (LV) with concentric hypertrophy. The atria were not dilated. LV hypertrophy was symmetrical with mild medio-ventricular obstruction, max gradient = 15 mm Hg, without segmental contractility disorder with 63% of LV ejection fraction, without valvulopathy or effusion. Full-body positron emission tomography (PET) with 18-F fluorodeoxyglucose was negative. Cerebrospinal fluid (CSF) analysis was normal. The patient temporarily refused myocardial biopsy and then returned to his home at his request.
Due to a worsening of his symptoms (weight loss, severe asthenia, neuropathic lower limb pain), the patient was then readmitted in April 2018 to our Hematology Department. Control of troponin and NT-proBNP levels increased to 0.239 µg/L and 7823 ng/L, respectively. Bone marrow biopsy showed massive medullary invasion (about 80% of medullary cellularity) by well-differentiated plasmacytic proliferation with lambda light chain monoclonality, associated with medullary hypoplasia of the three cell lines (Figure ). The conventional bone marrow karyotype failed twice, but the interphase FISH, on CD138+ sorted cells, found the presence of a double IGH/CCND1 fusion t(11;14) and the loss of an undisturbed IGH copy.
Myocardial biopsy of the right ventricle, performed because of the high suspicion of cardiac involvement, confirmed the diagnosis of lambda light chain AL amyloidosis (Figure ).
We concluded to the diagnosis of lambda light chain myeloma complicated by multi-organ AL amyloidosis with severe heart involvement (Mayo Clinic stage III) and dysautonomic neuropathy with diarrhea and orthostatic hypotension which was extremely incapacitating. The myeloma CRAB features were as follows: a ratio of lambda/kappa free light chains greater than 100% and 80% of plasma cells on the bone marrow biopsy.
The patient received a first course of treatment with bortezomib (V) (1.3 mg/m2 day (D) 1, D4, D8, D11 subcutaneous), lenalidomide (R) (25 mg/d, D1-D14), and dexamethasone (Dex) (20mg D1-2, D4-5, D8-9, D11-12) for two 21-day cycles. The evaluation after C2 showed no therapeutic response (stable disease, IMWG criteria) with lambda light chains at 610 mg/L and kappa light chains at 0 mg/L (DFLC = 610). We proposed a second-line chemotherapy regimen with two 35-day cycles of bortezomib 1.3 mg/m2 (D1, D8, D15, D22), cyclophosphamide (C) (300 mg/m2 D1, D8, D15), dexamethasone (20 mg D1-2, D8-9, D15-16, D22-23), and daratumumab (16 mg/kg IV weekly) (daratumumab + VCDex regimen). An autologous stem cell transplant procedure with melphalan 200 mg/m2 conditioning regimen was considered in case of good therapeutic response and normalization of cardiac markers. The patient presented a biological partial response (PR) with an 80% drop in serum lambda light chain value (lambda light chain 118.9 mg/L, kappa 0.1 mg/L, DFLC = 118.8), and we were able to obtain a collection of peripheral stem cells by two consecutive cytaphereses (under intensive care unit monitoring), which were well tolerated clinically, with a graft of five Million CD34+ cells/kg. Unfortunately, biological PR was not correlated with either clinical response, echocardiographic response (the ventricular hypertrophy was worse, 15-17 mm against 14 mm at diagnosis), or blood cardiac markers with persistent high levels of troponin (0.174 µg/L) and NT-proBNP (20174 ng/L). In addition, the patient displayed repeated hypotensive discomfort in connection with dysautonomia, despite midodrine treatment. Given the significant aggravation of weight loss of nearly 5 kg since the beginning of the treatment, the patient underwent nasogastric tube insertion for enteral nutrition to correct severe undernutrition with hypo-albuminemia at 28 g/L. The patient also presented lower limb edema treated with compression stockings and intravenous 20% albumin supplementation. Finally, the patient was considered not eligible for autologous stem cell transplant because of cTnT >0.06 µg/L and systolic blood pressure <90 mm Hg, leading to the administration of a third cycle of daratumumab-VCDex. The patient refused to stay in hospital despite hypotension and major risk of acute heart failure.
Despite all the treatment received, the patient died suddenly at home of probable heart failure, but no medical autopsy was performed. The patient had given his informed consent for the publication of a case report from his clinical history before he died, and we obtained consent to publish this rare case from the patient's next of kin. |
pmc-6552962-1 | Hairy cell leukemia was diagnosed in a 72-year-old male with no particular antecedent. There was bone marrow infiltration (15%) by lymphoid cells expressing B-cell markers CD19, FMC7, CD20, and CD79b, as well as a monotypic kappa light chain and the CD11c and CD103 without expressing CD25 and CD123 (Figure C). One year after diagnosis, treatment with cladribine for 5 days was started, but the splenomegaly remained bulky. The hemogram showed a moderate anemia (11.7 g/dL), thrombocytopenia (107 × 109/L), and a leukocytosis at 5.6 × 109/L (Figure D), with 46% of lymphocytes suggestive of hairy cells (Figure A). Medullary infiltration persisted with 8% of abnormal cells (Figure B). The peripheral karyotype showed a reversal of chromosome 7 and trisomy 5, which are frequent abnormalities in HCL. A splenectomy was performed: splenic histological examination showed infiltration by small cells of B phenotype CD20 positive, CD5 negative, and CD10 negative. The diagnosis between SDRPL and vHCL persisted. The presence of cells with bulky nucleoli however suggested the diagnosis of vHCL. Splenectomy corrected thrombocytopenia and anemia. Four years later, the patient's condition was stable. High-throughput sequencing analyses show no mutation of the BRAF gene but the presence of a KDM6A gene mutation. Sequencing of the variable part of the immunoglobulin heavy chains showed a non-mutated IGHV profile VH4-34. |
pmc-6553344-1 | A 27-year-old woman in gestational week of 40 + 2 was admitted to the hospital with chest discomfort, orthopnea, and sinus tachycardia 140 beats per minute (bpm) with QRS 96 ms.
She had a history of childhood focal glomerular sclerosis with nephrosis, which became steroid resistant and treated with chlorambucil, but recovered completely. Except for migraine occasionally, she was feeling healthy despite adiposity and body mass index 32 kg/m2 before pregnancy.
A computed tomography (CT) of the chest ruled out pulmonary embolism, but showed signs of edema enlargement of the left cardiac chambers; and echocardiography confirmed severe systolic dysfunction with left ventricular EF of 15%. The biomarker NT-proBNP was elevated (1799 ng/L) but Troponin was normal. A suspicion of life-threatening PPCM resulted in urgent air ambulance transport to the nearest university hospital, where caesarian section was promptly performed and a healthy child was delivered. At the intensive care unit, levosimendan was continued and standard HF initiated including furosemide, ramipril, metoprolol, aldosterone, digoxin, and warfarin. ECG showed premature ventricular complexes (PVCs). After 8 days, NT-proBNP dropped to 881 ng/L.
Repeated echocardiography showed slight improvement; however, due to still deteriorated EF (28%), a wearable cardioverter defibrillator (WCD) or an implantable cardioverter defibrillator (ICD) were deemed unnecessary after extended discussions. In addition to low EF, secondary mitral insufficiency and elevated systolic right ventricular artery pressure (SPAP) developed in the patient.
In the following months, she suffered from HF in scale of New York Heart Association (NYHA) functional class III A-B. The blood pressure (BP) was 90/60 mm Hg, and NT-proBNP was increased to 813-976 ng/L. Echocardiography confirmed an EF <30% and tricuspid annular plane systolic excursion (TAPSE) 1.6 cm.
In the meantime, the patient was repeatedly hospitalized for dizziness, dyspnea, and chest pain. After the sixth hospitalization, 3 months after onset of symptoms, she could not walk 50 m without limiting dyspnea; thus, she was referred to NYHA III or even IV. She was again transferred to the university hospital and, during the transportation, syncope spells occurred due to asystole. Based on the overwhelming risk of circulatory collapse, it was decided to start extracorporeal membrane oxygenation (ECMO). Echocardiography on the operating table showed stagnant left ventricle and the prognosis was considered extremely poor, and this was the reason that a left ventricular assist device (LVAD) HeartMate II™ was inserted. The insertion was complicated by critical ischemia in the right femoral communis artery, which was successfully treated with an embolectomy. Notably, even though the right ventricular function was moderately affected, the hemodynamic situation was stable after LVAD. Following HeartMate II™ initiation, she presented an infection, where an X-ray later revealed tooth abscess but the dental procedure was postponed for 2 months because of instability; finally, eight teeth were extracted. Following HeartMate II™, her physical stamina improved (NYHA II), but syncopal spells occurred without detection of arrhythmia.
After HeartMate II™ insertion, she suffered from recurrent infection of the external driveline, with ultimate suspicion of biofilm around the cable. She was treated with long-term antibiotics and symptoms improved. After 2 years with HeartMate II™, the decision was taken to initiate a transplant evaluation, and after another 6 months, she was placed on the waiting list.
During the period with HeartMate II™, the patient repeatedly experienced paroxysmal palpitations for less than a minute with dizziness, usually in the evenings and nights. Thumb-ECG revealed monomorphic VT, and she was scheduled for a discussion about ICD. But at the following return visit, it appeared that the patient had hit her head and CT showed a small left occipital infarction. The contributing cause of the stroke was attributed to subtherapeutic international normalized ratio (INR). Two days later, a 24-hour ambulatory ECG showed approximately 200 PVCs, 23 runs of nonsustained ventricular tachycardia (VT), at the most 20 beats in a row. Telemetry in the ward a few days later showed multiple broad complex tachycardias, likely of ventricular origin around 140 bpm. The patient received Mg2+, Na+, K+ drip, and amiodarone. Notably, she did not receive an ICD. She was advised to seek medical attention if the tachycardia was sustained for eventual cardioversion.
The patient experienced recurrent arrhythmias during the following years. One time at the emergency department, telemetry showed suspected polymorphic VT (torsade de pointes). It was speculated whether amiodarone caused proarrhythmia and was thus discontinued. A few months later, the patient suffered from repeated VTs followed by bradycardia with presyncope. Again, a discussion concerning ICD was initiated, but due to circulatory support of HeartMate II™, it was not implanted.
There were recurrent arrhythmias including atrial fibrillation, and the dose of beta-blocker was increased. Notably, low levels of thyroid-stimulating hormone with normal levels of thyroid hormones T4 (thyroxine) and T3 (triiodothyronine) and negative thyrotropin receptor antibodies were found. Thyroid scintigraphy revealed thyroiditis, assumed as a complication of amiodarone and was treated with glucocorticosteroids.
Due to adiposity and several treatment attempts by physiotherapists and dieticians, the body mass index ranges from 32 to 39 kg/m2 and the transplant team hesitated to offer her a transplant. However, 45 months after the onset of PPCM she finally received a new heart.
The transplant procedure was complicated due to the explant of HeartMate II™, and there was a weight mismatch between the donor and recipient. The subsequent HF required long-term inotropic support. In the aftermath, she had renal failure with elevated creatinine (270 µmol/L). She also got another stroke in the right occipital lobe and suffered from visual defect. In addition, she had reactivation of cytomegalovirus infection and postoperative left-sided diaphragm’s paralysis. Twelve days after heart transplantation, she had a witnessed cardiac arrest, with alternating QRS-amplitude and axis, interpreted as torsade de pointes/ventricular fibrillation (Figure ). Cardiopulmonary resuscitation (CPR) was performed for a few minutes including one successful defibrillation. Coronary angiography revealed no stenosis, and endomyocardial biopsy did not show any signs of rejection. After CPR, the patient developed an intense pain in the chest cavity resistant to treatment. There was no clear trigger for the cardiac arrest.
In the ward, there were runs of VTs after discontinuation of mexiletine and explant of a temporary pacemaker. Then she received an ICD (Current™ + DR). Echocardiography of the transplanted heart, performed during sinus rhythm of 65 bpm, showed EF 60%-65%, TAPSE 6 mm, and SPAP 35 mm Hg. During the following year, the transplant resulted in rejection problems. At one time, combined cellular and humoral rejection occurred that was treated with high dose steroids and one dose of rituximab. Endomyocardial biopsy during the following years showed signs of mild to moderate rejection. Due to immunosuppression, she had pneumonia—four times during 18 months. After two strokes, the patient had sequelae in terms of some vision loss of the left eye. Unfortunately, she suffered from continued pain of different intensities since the PPCM diagnosis, accentuated by various causes such as the HeartMate II™, heart transplantation, and cardiac arrest with CPR and ICD implantation. During 2017, she experienced a lot of pain around the ICD pocket; therefore, it was decided to extract the ICD system 19 months after it has been implanted due to the severe pain problems and lack of need of pacing or antitachycardia pacing/cardioversion during the period, even though EF was 45%. |
pmc-6553347-1 | We are presenting a 24-year-old male patient who, 1 and 1/2 years prior to presentation at our institution noticed swelling of his feet, had New York Heart Association (NYHA) three symptoms, paroxysmal nocturnal dyspnea, and a 4-pillow orthopnea. The patient had a transthoracic echocardiogram (TTE) done 2 months prior to admission at another institution which showed an ejection fraction of 50% and mitral regurgitation and tricuspid regurgitation and was subsequently commenced on frusemide 80 mg orally once daily, spironolactone 25 mg orally once daily, and captopril 25 mg orally three times daily. When he presented to us, he had been having hemoptysis and episodes of fever. The patient had no history of rheumatic fever as a child or any known congenital cardiac condition. He did have a chronic cough as a child which was not investigated. The patient denied smoking and taking alcohol and was not an intravenous drug user. His last positive TB contact had been 5 years prior to admission. The patient was unemployed presently but had worked as an illegal gold miner for 7 years.
On examination, he was ill-looking, in respiratory distress with a respiratory rate of 40 breaths per minute. He had a temperature of 37.4°C with records of low-grade pyrexia 37.6°C in his outpatient book. He was pale and had grade 1 clubbing, poor dentition, and foul-smelling breath, and there were no other stigmata of infective endocarditis. His pulse rate was 128 beats per minute, and it was regular and full volume. He was normotensive with a BP of 114/71 mm Hg, his jugular venous pressure (JVP) was not elevated, but his precordium was active and the apex was hyperkinetic, thrusting and displaced in the 6th intercostal space anterior axillary line, there was no thrill, 1st and 2nd heart sounds were present and normal, there was a 3rd heart sound, and there was a grade 3 pansystolic murmur in the apical region radiating to the axilla. His chest was clinically clear, and he had a tender hepatomegaly and a mild splenomegaly.
We managed the patient as infective endocarditis with empirical ceftriaxone and gentamicin as well as standard antifailure treatment on the basis of the left-sided heart failure symptoms that the patient presented with. Other differentials included tuberculosis and suppurative lung disease. The patient presented with a chest radiograph which was a week old which showed a cardiomegaly and clear lung fields. A TTE showed a large submitral aneurysm under the posterior leaflet of the mitral valve. The neck was 34 mm in diameter, and the aneurysm area was 22 mm2 which accommodated most of the left ventricle stroke volume (hence probably why the patient appeared to have heart failure). There was moderate mitral regurgitation due to disruption of posterior leaflet by aneurysm (see Figures and ). The left ventricle ejection fraction was 59%. There was a probable abscess in the interventricular septum (IVS) just under the aortic valve (see Figure ). There was marked pulmonary hypertension and cor pulmonale.
He had a normal hemoglobin of 12.8 g/dL and an elevated white cell count of 18 900 mm3 with polymorphonuclear leukocytosis. His abdominal ultrasound scan was normal. A repeat chest radiograph showed bilateral infiltrates in both lung fields with a mottled appearance. Sputum for gene expert was negative for Mycobacterium tuberculosis. The patient was HIV negative. Blood cultures could not be obtained due to financial constraints. A discussion to move the patient to a facility where surgical options were available was made, but the patient and his relatives were unwilling due to the distance and the costs of going to a city where they did not have any relatives who could support them. We therefore continued with our treatment of intravenous antibiotics and antifailure treatment. The patient did initially show a slight improvement of symptoms; however, on day 6 of treatment, the patient developed interstitial nephritis and gentamicin had to be discontinued. He was also commenced on tranexamic acid 1 g orally once daily as he continued to have hemoptysis. The patient's condition steadily deteriorated over the next couple of days, and he subsequently developed gangrene of all his digits and on day 10 of admission succumbed to his illness on day 11. |
pmc-6553348-1 | A 3-year-old girl presented with a painless and progressively increasing lateral neck mass since birth. Examination revealed a nontender, mobile, and multinodular left-sided neck mass measuring 8 cm × 6 cm in dimension and there were no cervical or supraclavicular lymphadenopathies.
Thyroid function test was normal while ultrasound of the neck revealed a solid lesion mainly on the upper pole of the left lobe of the thyroid gland. Fine needle aspiration cytology was suspicious of malignancy. Plain radiograph of the neck showed deviation of the trachea to the right side. At surgery, the left lobe of the gland was involved and a left lobectomy was done with no adjuvant therapy. Gross (macroscopic) examination of the tumor showed a nodular mass measuring 6 cm × 4 cm × 4 cm and weighing 35 g. Cut sections revealed a tan colored lobulated tumor, firm in consistency, and disposed in whorled appearance. Focal areas of cystic spaces were seen. The tumor was highly cellular with proliferating spindle and polygonal (epithelial) cells occurring predominantly in lobulated and fasciculated patterns (Figure ). The spindle cell component had hyperchromatic oval nuclei with scanty to moderate eosinophilic cytoplasm (Figure A-C), whereas the polygonal cells exhibited large vesicular nuclei. (Figure D) Foci of cystic spaces lined by epithelia cells that were disposed in irregular papillary patterns were also seen. (Figure ) There was no area of necrosis. The resection margin was free of tumor but has residual unremarkable thyroid tissue. Based on initial hematoxylin and eosin sections, the differential diagnosis considered were solitary fibrous tumor, a peripheral nerve sheath tumor, and hyalinizing trabecular tumor.
Immunohistochemical study showed that both the spindle and polygonal cells were positive for pan cytokeratin (AE1/AE3), galectin-3, and HBME but were negative for CEA, S-100, CD 31, CD 34, chromogranin, calcitonin, p53, and CD117. Cytoplasmic positivity for smooth muscle actin (SMA) was seen in few of the spindle cells while about 5% of the tumor cells were Ki-67 nuclear positive suggestive of low proliferative index. The final diagnosis of spindle epithelial tumor with thymus-like differentiation (SETTLE) was made based on the histopathologic features and immunohistochemistry. Postoperatively, the recovery was good. She was discharged and followed up for about six years with no recurrence. |
pmc-6553561-1 | A 76-year-old woman was treated with a left TKA for osteoarthritis of the knee. Femoral and tibial cuts were achieved with preoperative planning using IM femur jig and extramedullary tibial jig, respectively. We visually analyzed and evaluated the tracer distribution around the TKA site 2 weeks after implantation. Interestingly, we recognized the “hammer sign,” which is hammer-like increased signal intensity at the distal femur (high bone metabolic activity at the distal half of the right femur in addition to the bone-prosthesis interface; Figure ). We believe that the area with “hammer sign” is correlated with the surgical stress of the IM femoral canal, probably due to the IM drill for insertion of the femoral IM guiding rod for an appropriate femoral component positioning. |
pmc-6553561-2 | An 86-year-old woman was treated with simultaneous bilateral TKA for knee osteoarthritis. For bilateral replacement, femoral and tibial cuts were achieved with IM femur jig and extramedullary tibial jig, respectively. During the surgery, we carefully reamed the entrance point and gently inserted a femoral IM rod, with the central axis of the distal femur as the ideal entry point. Unexpectedly, postoperative NaF PET imaging on POD 14 (Figure ) demonstrated that the intensity of radiotracer uptake of the left femur was dramatically reduced without a typical “hammer” configuration, although a slight bone metabolic activity was detected at the middle third of the left femur. More interestingly, there was no upregulation of the NaF uptake in the right femur (Figure ). |
pmc-6553561-3 | An 81-year-old woman, who suffered from right femoral intertrochanteric fracture and had right hip open reduction and internal fixation (ORIF) with gamma nail 5 months earlier, was treated with simultaneous bilateral TKA for knee osteoarthritis. Simultaneous bilateral TKA was performed with the extramedullary guide for the right femur and the IM alignment system for the left femur. KneeAlign 2, a simple palm-sized navigation device, was used for extramedullary femoral alignment. As shown in Figure , NaF PET image on POD 14 showed no significant difference in signal intensity between the right and left distal femurs, although the high intensity around the right hip may be triggered by a previous trauma and surgery. This indicates that gentle IM rod insertion with scrupulous care could minimize breaching of the femoral canal as well as the extramedullary femoral alignment guide system with KneeAlign 2. |
pmc-6553562-1 | Written informed consent was obtained from the patient. The patient verbally consented to the use of his clinical images for this report.
A 60-year-old man was referred to Imam Reza hospital of Mashhad for loss of consciousness. The patient of the present case had no history of severe cirrhotic change before admission to hospital.
A review of the patient history did not reveal previous or current history of similar illness in his siblings and close contacts. Both his parents were Iranian, of the Fars ethnic group from northeast Iran.
On examination, he was afebrile with a normal blood pressure measuring 125/80 mm Hg and heart rate of 80 beats/min. Physical examination supports the diagnosis of hepatic encephalopathy.
Hepatic presentation
After admission, he developed hepatic encephalopathy and cirrhosis with abnormal liver function.
Neurologic presentation
After admission, patient was conscious and well oriented.
Ophthalmic presentation
The patient had normal ocular results without Kayser-Fleischer rings (KF rings).
Psychiatric presentation
His neurologic status was unremarkable.
Other organs
Kidney function tests were normal. Central nervous system examination showed normal higher mental functions.
Laboratory studies revealed abnormal liver function, including an elevated serum total bilirubin (T-Bil) level of 2.06 mg/dL (upper limit of normal [ULN]: 1.2 mg/dL), direct bilirubin level of 0.55 mg/dL (ULN: 0.25 mg/dL), an elevated liver enzymes SGOT level of 45 IU/L (ULN: 31 IU/L), ALK phosphatase level of 588 (ULN: 306 U/L) with hypoalbuminemia (Serum Albumin-3.3 g/dL; lower limit of normal [LLN]: 3.5 g/dL).
Elevated urinary copper excretion (270 μg/24 h) observed (ULN: 70 μg/24 h) in urine biochemistry.
Ceruloplasmin level in patient was 221.9 mg/L (LLN: 150 mg/L, ULN: 300 mg/L). Serum ceruloplasmin concentration was measured by using a nephelometric method. In the coagulation profile, prothrombin time (PT) level was 15.5 seconds (LLN: 10.5, ULN: 13 seconds) with partial thromboplastin time (PTT) level of 43 seconds (LLN: 28, ULN: 45 seconds), elevated international normalized ratio (INR) level of 1.4 ratio (ULN: 1 ratio) and fibrinogen level of 1941 mg/dL (LLN: 150, ULN: 350 mg/dL).
Also, low level of ammonia (128 µg/dL) was detected (LLN: 130, ULN: 145 µg/dL). The patient tested negative for hepatitis B virus (HBV) by TaqMan real-time PCR. Antinuclear antibody (ANA) was 5 U/mL (LLN: 10 U/mL) when measured with immunochemiluminescenc procedure, and HCV Ab test was negative.
Ultrasonography of the abdomen revealed features suggestive of chronic liver disease and splenomegaly (longitudinal diameter 179 mm). The gallbladder was not visualized due to previous cholecystectomy. Normal size of portal vein diameter and common bile duct (CBD detected, respectively, 11 and 4 mm (Figures and ). The present case had no history of severe cirrhotic change before admission to hospital.
Endoscopic examination showed 2-3 rows varices at the distal esophagus and proximal lesser curvature (Figure ).
Liver biopsy revealed cirrhotic change with moderate to severe steatosis, portal inflammation, liver cell degeneration and necrosis, and glycogenation of periportal hepatocytic nuclei.
Masson's trichrome stain revealed the collagenous fibers surrounding nodules of hepatocytes.
For liver copper concentration detection, liver sample was obtained by needle biopsy. The liver copper concentration in the present case was 1016 mcg/g dry weight liver when measured by neutron activation analysis.
Background patient liver parenchyma showed heterogeneously fibrotic from 19 to 45 kilopascals (kPa). The median fibrosis was 35.5 kPa (equal to F4 based on a Metavir histological index).
The controlled attenuation parameter (CAP) score for liver steatosis was 211 db/m (Figure ).
The liver of the patient showed chronic liver disease symptoms in which another cause has not been established. Therefore, the diagnosis of WD was considered.
After diagnosis of WD, the patient was prescribed Pantazol (40 mg/d), Amilodipin (5 mg/d), and zinc sulfate (150 mg/d) on day 9 of hospitalization. During the treatment, the diet of the patient was restricted to low-copper, high-calorie, and low-protein meals.
After treatment, central nervous system examination showed normal higher mental functions. Other systemic examination was normal. Hepatic copper measurement showed decreased hepatic copper concentration. The use of zinc significantly improved the majority of clinical symptoms of WD. The patients completely responded to the therapy, at the end of the follow-up. |
pmc-6553675-1 | A 28-year-old female with a history of gestational diabetes mellitus diagnosed eight years prior to presentation and subsequent type two diabetes mellitus (T2DM), one prior episode of HTG-induced pancreatitis three years prior to presentation, and obesity with a body mass index (BMI) of 33.5 kg/m2, presented with a one-week history of polyuria, polydipsia, poor appetite, and vomiting. Two weeks prior to presentation, she was treated with a five-day course of amoxicillin for a respiratory tract infection. She was on metformin, glipizide, and dapagliflozin for T2DM and atorvastatin and gemfibrozil for HTG. She had been on dapagliflozin for six months at the time of presentation. Physical examination on presentation was significant for dry oral mucosa; significantly, her abdominal examination was benign with no tenderness, guarding, or rigidity. Pertinent laboratory findings on admission were: serum glucose 111 mg/dl, bicarbonate 18 mmol/l, anion gap 20, creatinine 0.4 mg/dL, triglycerides 508 mg/dL, total cholesterol 122 mg/dL, glycated hemoglobin (HbA1c) 10%, and venous pH 7.27. Serum lipase was normal at 43 U/L. Serum acetone levels could not be assessed as blood samples kept hemolyzing due to significant lipemia. The patient was initially admitted for starvation ketosis, as she reported poor oral intake for three days prior to admission. However, serum chemistry obtained six hours after presentation revealed her glucose was 186 mg/dL, the anion gap was still elevated at 21, serum bicarbonate was 16 mmol/L, triglyceride level peaked at 2050 mg/dL, and lipase was 52 U/L. The β-hydroxybutyrate level was obtained and found to be elevated at 5.29 mmol/L - the original sample was centrifuged and the chylomicron layer removed prior to analysis due to interference from turbidity caused by lipemia again. The patient was treated with an insulin drip for euDKA and HTG with a reduction in the anion gap to 13 and triglycerides to 1400 mg/dL, within 24 hours. Her euDKA was thought to be precipitated by her respiratory tract infection in the setting of SGLT2 inhibitor use.
The patient was seen by the endocrinology service and she was discharged on 40 units of insulin glargine at night, 12 units of insulin lispro with meals, and metformin 1000 mg two times a day. It was determined that all SGLT2 inhibitors should be discontinued indefinitely. She had close follow-up with endocrinology post discharge.
Limitations of this case
Many of the reported cases of euDKA in the literature have developed in patients with type-one diabetes mellitus, due to the off-label use of SGLT2 inhibitors, or in patients previously misdiagnosed as having T2DM, who, in fact, had the latent autoimmune diabetes of adults [-]. The limitations in the workup of our patient are that c-peptide, islet cell antibodies, or glutamic acid decarboxylase antibodies were not checked at any point during her diagnosis of diabetes mellitus. |
pmc-6553676-1 | We present a 35-year-old Hispanic male with no significant medical history and a social history remarkable for occasional cocaine and marihuana use who presented complaining of a right-sided parietal headache and dizziness. A review of his systems was also positive for intermittent nausea and vomiting for four days. Examination revealed an alert and oriented patient, with no focal deficits appreciated, moving all extremities with sensation grossly intact. Lung auscultation and abdominal examination did not disclose any abnormal findings. His laboratory workup was unremarkable, without significant electrolyte imbalances noted. A computed tomography (CT) scan of the brain was done, which revealed intracranial hemorrhages, with a prominent 12 mm hemorrhagic component layering along the right side of the fourth ventricle, trace hemorrhage along the bilateral tentorium and posterior interhemispheric fissure as well as a punctate hemorrhagic focus about the left paracentral frontal lobe, as can be seen in Figure . There was also demonstration of caput medusae appearance of small branching veins draining into a single vein adjacent to the lesion, suggestive of a deep venous anomaly. Brain MRI revealed an isolated rounded lesion in the right cerebellum adjacent to the fourth ventricle measuring up to 10 mm suggestive of a cavernous hemangioma as the primary cause of bleeding, as can be seen in Figure . The patient’s symptoms resolved over a period of two months following onset and he continued without development of neurologic symptoms. The treating physicians elected to continue to monitor the patient clinically and surgical resection was deferred. |
pmc-6553679-1 | A 38-year-old woman with a past medical history of chronic alcohol abuse, seizures, and recurrent hospitalizations for profound lactic acidosis of unknown etiology presented to the Emergency Department (ED) with altered sensorium and shortness of breath. The patient had been discharged from the hospital 12 hours earlier after management of a similar illness. The current presentation was her sixth hospital admission within the previous six months. All prior presentations shared similar symptoms and laboratory findings: acute onset altered mental status, slurred speech, unsteady gait, tachycardia, and tachypnea in the setting of leukocytosis, acute kidney injury, profound lactic acidosis (ranging from 10-30 mmol/L), high anion gap (often greater than 30 mEq/L), normal osmolal gap (5-10 mOsm/kg), and negative toxicology studies. Although EG ingestion had been considered during many of these prior admissions, the patient’s uniformly low osmolal gap, normal urinalysis, marked lactic acidosis, and negative blood volatile studies had prompted broadening of the differential and extensive evaluation for a suspected mitochondrial, infectious, or inherited metabolic disorder. Despite repeated and exhaustive evaluations, no definitive toxic, infectious, or metabolic etiology had been identified.
On arrival to the ED, the patient was afebrile (36.3 °C), tachycardic (114 beats per minute), and tachypneic (22 breaths per minute) with an oxygen saturation of 100% while breathing ambient air. Her initial laboratory studies were remarkable for a white blood cell count of 18.9 K/uL (ref: 4-10.9 K/uL), pH 7.13 (ref: 7.35-7.45), anion gap 35 mEq/L (ref: 3-15 mEq/L), lactic acid 14 mmol/L (ref: 0.5-2.0 mmol/L), osmolal gap 5 mOsm/L (ref: <10 mOsm/L), normal chemical and microscopic urinalysis, negative serum and urine toxicology studies, and undetectable blood volatile organic compounds. Despite the absence of an osmolal gap, her anion gap and lactic acidosis prompted concern for EG ingestion and fomepizole therapy was prophylactically initiated.
Three hours after her arrival to the ED (15 hours after her most recent hospital discharge), the patient declined with a rapid deterioration in mental status accompanied by acute hypoxemic respiratory failure. She was intubated and admitted to the medical intensive care unit. The first 24 hours of her hospital course were complicated by refractory shock, complete heart block, new non-ST elevation myocardial infarction accompanied by severe systolic heart failure with an estimated left ventricular ejection fraction of 15%, and persistence of the severe anion gap metabolic acidosis (30 mEq/L). Hemodialysis was initiated. On hospital day 2, she became febrile to 40.3 °C with worsening hyperkalemia and hyperphosphatemia despite hemodialysis. The neurologic examination declined from Glasgow Coma Scale (GCS) 15 with no focal neurologic deficits on admission to GCS 3 with absent brainstem reflexes. Repeat noncontrast head computed tomography acquired 36 hours after presentation revealed interval development of bilateral basal ganglia and midbrain hypoattenuation, a nonspecific radiographic finding that can arise secondary to infectious etiologies, toxic insults, inflammatory conditions, or metabolic disorders (Figure ) [].
In accordance with the family’s wishes, the supportive care was withdrawn 72 hours after the admission. All the final culture results and toxicology studies returned negative. At the request of the family, an autopsy was performed and the case was referred to the medical examiner.
Autopsy revealed extensive intravascular and perivascular oxalate crystal deposition. Intravascular foreign material, consistent with oxalate crystals, was identified throughout the renal parenchyma and brain. These findings are pathognomonic for EG ingestion (Figure ). |
pmc-6554361-1 | A 65-year-old male presented to the emergency department with a complaint of nausea and vomiting and reported no bowel movement or passing of flatus for 5 days. Upon further questioning, he recalled that he fell from a tractor while working in his farm 2 months earlier and sustained blunt trauma to his abdomen for which his initial evaluation revealed no serious injury except some bruises.
On physical examination, the patient was alert and responsive, his vital signs were stable, and dry mucous membranes were noted. Abdominal examination revealed distended abdomen, increased bowel sounds, and generalized tenderness without rebound tenderness, guarding, or any other significant findings. Fluid resuscitation and nasogastric (NG) tube insertion were initiated for a patient with a suspected diagnosis of intestinal obstruction. His initial lab tests on admission were normal except a mild increase in amylase level (Table ).
The patient underwent an upright abdominal X-ray and chest X-ray. On the abdominal X-ray, multiple air-fluid levels were observed (Fig. ). Both chest and abdominal X-rays revealed the niveau formation of the small intestine on the right side above the liver and right hemidiaphragm (Fig. ). Abdominal sonography reported the presence of dilated intestinal loops. Further evaluation with CT scan confirmed the presence of a few small intestinal loops behind the liver and also in the chest through a rupture in the right hemidiaphragm (Fig. ).
The patient opted for the surgery and exploratory laparotomy was performed. Some small intestine loops had gone behind the liver and through 4 cm rupture in the posterior aspect of the diaphragm into the chest. Displaced intestinal loops were relocated and no sign of ischemia or necrosis was observed. Afterward, the ruptured portion of the diaphragm was closed with Prolene 1 suture by using continuous suturing technique. No other complications were found.
The patient had no postoperative complications and he was symptom-free within 2 days. The patient was discharged after 4 days. |
pmc-6554698-1 | A 39-year-old man attended our clinic in March 2017 with a two-year history of Ph+ precursor B-cell ALL. In June 2015 he had attended an emergency department with a 2-week history of fatigue, lethargy, backache, leg and rib pain refractory to opioids. Blood counts revealed a leukocytosis with white cell count of 67 × 109 cells/l with 34% lymphoblasts measured by flow cytometry. Hemoglobin was 12.3 g/dl and platelet count at 49 × 109/l. Bone marrow aspirate/biopsy showed a precursor B-cell ALL, Ph+ (t 9; 22). The patient was enrolled in the UKALL14, version 6 Protocol (NCT01085617: ClinicalTrials.gov) which included a five-drug induction regimen in adults with de novo ALL between 25 and 65 years. Induction Phase I: PEG-ASP (1000 IU/m2) on days (d) 4 and 18, daunorubicin 30 mg/m2 and vincristine 1.4 mg/m2 on d1,8,15 and 22, dexamethasone 10 mg/m2 d1–4, 8–11,15–18 and intrathecal methotrexate (ITMTX) 12.5 mg on d14. Patient received continuous imatinib 400 mg escalating to 600 mg daily throughout induction treatment. Phase II induction: cyclophosphamide 1000 mg/m2 d1,15, Ara-C 75 mg/m2 d2–5, 9–12, 16–19 + 23–26, mercaptopurine 60 mg/m2 throughout and intrathecal methotrexate d1, 8, 15, 22.
After Phase II induction the patient achieved a complete molecular remission with negative BCR-ABL1 p190 transcripts by reverse transcription polymerase chain reaction (RT-PCR). Complications included constipation, febrile neutropenia and pneumonia. He was consolidated with myeloablative conditioning including cyclophosphamide/total body irradiation (TBI), followed by a matched (brother) allogeneic stem cell transplant. Post-transplant he developed hyponatremia, total body irradiation somnolence and grade IV acute cutaneous GVHD managed with steroids. Post-transplant maintenance included imatinib, infection prophylaxis and GVHD prophylaxis with methotrexate and cyclosporine. Disease relapse occurred at 6 months post-transplant with BCR-ABL1 p190 transcript expression at a level of 18.23%, confirmed on bone marrow biopsy at 9 months post allo-HCT. Imatinib was replaced by the TKI dasatinib 140 mg daily, and followed by DLI (3 × 106 CD3 cells/kg), resulting in second remission with negative minimal residual disease (MRD) by flow cytometry. Three months later, disease progression occurred with expression for BCR-ABL1 p190 in 163275 copies of control gene. He was given an overall life expectancy of less than 1 year.
The patient attended our clinic for evaluation and treatment. Options discussed included responses and side effects of chimeric antigen receptor T cells cell therapy, antibody–drug conjugates, such as InO or blinatumomab, chemotherapy, a second HCT and/or DLI, no therapy and palliative care or experimental personalized low-dose immunotherapy. The patient gave informed consent for the experimental immunotherapy including publication of results.
The treatment consisted of daily low-dose subcutaneous rIL-2 with variation of dosing and frequency of administration based on measurement of an extensive peripheral blood immune panel including NK cells, NK cell cytotoxicity, B cells, T cells and Treg cells to selectively stimulate a graft-versus-leukemia response while minimizing GVHD. Simultaneously, cytokine levels including IFNγ in plasma were measured. The patient received a total of four cycles (4–7 weeks) of rIL-2 injections of 10–20,000 IU/kg, 5 days per week. The daily dose and duration of each cycle was based on the results of the peripheral blood immune panels. Cycles 1 and 2 were 6 weeks, cycle 3 was 7 weeks and cycle 4 was 4 weeks. Dasatinib was continued at 140 mg daily. Expression of BCR-ABL1 p190 transcript was monitored intermittently using RT-PCR throughout his rIL-2 treatment cycles.
Results showed NK cell activity improvement from 0% prior to initiation of cycle 1 of rIL-2 to 5.08% at the end of cycle 3 and to 9.68% by the end of cycle 4 (). The CD56brightCD3-NKcells were high prior to starting rIL-2 and remained in the upper normal range throughout treatment. IFN-γ increased from 0.0 pg/ml prior to cycle 1, peaked at 6.6 pg/ml at the end of cycle 1 and remained elevated through cycles 2, 3 and 4 with a level of 1.9 pg/ml at the end of the cycle 4 (). CD2+CD26+ (T cells + NK cells expressing dipeptidyl peptidase) increased from 7.1% prior to initiation of cycle 1 of rIL-2 to 63.4% at the end of the cycle 4 (). The CD4+CD25+ Tregs which were at the upper end of the normal range showed a progressive decrease to the lower end (). After cycle 2 bone marrow showed no abnormal lymphoid cells by flow cytometry, normal cytogenetics and no detectable levels of BCR-ABL, p190. Following cycle 3 peripheral blood showed no detectable levels of BCR-ABL, p190 or p210 transcripts (), consistent with a complete molecular and cytogenetic remission with recombinant IL2 and a TKI. Immunotherapy with rIL-2 and TKI was well-tolerated; the only side effect was erythema (Grade1) at the injection site, which cleared rapidly after rIL-2 stopped. Dasatinib was continued at 140 mg daily. BCR-ABL1 p190 transcript. Tregs, CD56brightCD3-NK cells and NK cell activity were not repeated since the patient returned to his home country. 21 months after starting rIL-2 the patient is well, asymptomatic and he has a normal quality of life. Notably, he successfully completed a triathlon. |
pmc-6554701-1 | The patient was a 43-year-old woman with invasive ductal carcinoma in the left breast who was treated with skin-sparing mastectomy. She then underwent total breast reconstruction using a deep inferior epigastric artery perforator (DIEP) flap simultaneously with fat grafting with harvesting from zone IV in the DIEP flap. In the procedure, fat tissue was harvested from zone IV in the DIEP flap using the wet technique with a 3-mm cannula and a 20-mL Luer-Lok syringe under manually generated negative pressure (). Fat was centrifuged at 2000 rpm for 2 minutes and then injected with a blunt Coleman cannula and 5-mL syringes. Fat injections were performed along the muscular fascicle of the pectoralis major in the subcutaneous tissue, if possible into the subcutaneous layer (). The volume of the fat graft depends on the size of the harvested DIEP flap, but 20 to 30 mL of fat tissue can usually be injected. In this case, there was no local recurrence or systemic metastasis during a 2-year follow-up period, and no cysts were detected by ultrasonography, indicating that no fat necrosis occurred. The patient was highly satisfied with the cosmetic results (). |
pmc-6554954-1 | A 48-year-old Caucasian woman was referred to the oral medicine department at the University of Liverpool School of Dentistry with new-onset oral pigmentation to the left buccal mucosa. Her past medical history revealed a diagnosis of “oculodermal nevus.” She recalled having pigmentation in her left eye from birth and pigmentation of skin of the left face since the age of 13 years, for which she received laser treatment for cosmetic purposes. The patient also reported annual monitoring of a benign intracranial tumor along with close monitoring by ophthalmology and dermatology divisions. She did not take any regular medications. She did not smoke or consume alcohol. She is single and lives on her own with no dependents. She lives close to her mother, who attended the appointments with her.
On examination, a subtle but diffusely speckled bluish pigmentation was observed to the left midface involving the infraorbital and zygomatic regions. A post–laser therapy yellow hue was noted on the left periorbital skin. Pigmentation of the sclera and conjunctiva was also observed. Intraorally, an inhomogeneous, blue-gray, diffuse hyperpigmentation affecting the entire left buccal mucosa was noted. Mild pigmentation of the left hard palate was also noted (Figs. , , , and ).
An incisional biopsy of the left buccal mucosa was completed. The report stated that histological and immunohistochemical features were in keeping with a blue nevus, but within the context of the preexisting occulodermal pigmentation, a diagnosis of oculodermal melanocytosis, also known as “nevus of Ota,” was made. No other investigations were required. The patient will be kept under 6-monthly review with the oral medicine department because the progression of the lesion on the left buccal mucosa requires active monitoring owing to the potential for malignant change. |
pmc-6554973-1 | A 35-year-old woman, gravida 1, para 0, with end-stage kidney disease caused by IgA nephropathy was referred for kidney transplantation. Hemodialysis was initiated when she was 33 years old. She first became pregnant after starting hemodialysis and experienced spontaneous abortion at 5 months after initiation of hemodialysis. After experiencing spontaneous abortion, she received fertility treatments and tried in timed intercourse with fertility drugs. She decided to receive kidney transplantation in order to restore fertility. Embryo cryopreservation was performed considering her age before her first visit to our hospital, because she and her husband desired childbearing. She underwent an ABO-incompatible living-donor kidney transplant using rituximab from her 66-year-old father at the age of 36. Initial anti-A antibody titers were 1:128 (IgM) and 1:128 (IgG). Because she underwent two doses of rituximab infusion (150 mg/m2 on day 14 before and at transplantation) for B cell depletion and four courses of plasma exchange and double filtration plasmapheresis to remove antibodies, anti-A antibody titers were reduced to 1:8 (IgM) and 1:8 (IgG). She received maintenance immunosuppressive therapy including cyclosporine, mycophenolate mofetil and methylprednisolone after transplantation. The serum creatinine level increased from 1.3 to 1.6 mg/dl on the postoperative day 18. Two years after the transplant, because she had no rejection during the past year and had adequate and stable graft function with no acute infections as well as stable maintenance immunosuppression, she desired pregnancy. Although immunoglobulin levels such as IgG, IgA and IgM had recovered to almost normal range, the peripheral CD19+ cells and CD20+ cells remained depleted (Fig. ). At 6 months after conversion from mycophenolate mofetil to azathioprine, frozen embryo transfer was performed during the hormone replacement cycle.
During pregnancy, the serum creatinine level was 0.8–1.0 mg/dl, and blood pressure was 120–130/70–80 mmHg. Although the cyclosporine trough level decreased to approximately 50 ng/ml after the 10th week of pregnancy, the dose of cyclosporine was not adjusted, because pregnancy seems to be a state of immunological tolerance associated with immunosuppressant activity of lymphocytes which creates tolerance to fetus []. The serum creatinine level elevated to 1.15 mg/dl at 36 weeks and 3 days gestation, and labor was induced at 37 weeks and 1 day gestation. At 37 weeks and 4 days gestation, a baby girl weighing 2220 g was delivered by cesarean section for arrest of labor, with Apgar scores of 8 and 9 at 1 and 5 min, respectively. The baby exhibited no malformation and was healthy. Serum IgG and IgM levels in the maternal cord blood were 912 and 16 mg/dL, respectively. The serum creatinine level improved to approximately 0.8–1.0 mg/dl after childbirth without treatment. Her blood pressure was stable until delivery but elevated to approximately 160/100 mmHg 4 days after childbirth, and she required antihypertensives for two weeks. She did not breastfeed her baby. Depletion of the peripheral blood CD19+ cells and CD20+ B cells due to administration of rituximab continued during pregnancy (Fig. ). After pregnancy, anti-A antibody titers were 1:2 (IgM) and 1:2 (IgG). There were no complications in both the recipient and her baby during the perinatal period. At 5 years after the transplant, the recipient has had no major complications including rejection or infection, while the peripheral blood CD19+ cells and CD20+ B cells remain depleted due to administration of rituximab, and she is in good clinical condition with only mild renal insufficiency (serum creatinine 1.47 mg/dL) (Table ). She said that she was completely happy with childbirth after kidney transplantation and is satisfied with childcare. |
pmc-6555169-1 | A Gleason score of 3 + 3 prostatic adenocarcinoma was detected at 12-quadrant transrectal ultrasound (TRUS)-guided prostate biopsy performed after determination of a serum prostate specific antigen value of 8.1 ng/mL in a 65-year-old man presenting with lower urinary tract symptoms. Prostate volume was calculated at 202 g at TRUS. No lymph node of pathologic size was determined at multiparametric prostate MRI. During RALRP, a 2/0 Vicryl suture was applied on the median lobe for traction to supply a better view for bladder neck and exposure of the large median lobe. We subsequently observed an injury of the left ureter orifice occurred during dissection with monopolar scissors. At inspection, the right ureter orifice was natural in appearance, whereas the left orifice had lost its natural appearance in association with a laceration. However, peristalsis and urinary flow from the area thought to be the left ureter orifice were observed. Online video call was made with experienced colleagues who were in another city (A.F.A. and A.E.C.) and the surgical fields on the screen were presented to them to get advice. Owing to their suggestion, two 4.7F 28 cm Double-J stents were inserted through the assistant port into the abdomen and installed in the both ureteral orifices, and RALRP was completed. The second orifice was also stented to prevent injury (). Postoperative prostate weight was measured as 202 g. Estimated blood loss was 250 mL. During control ultrasonography (USG) performed on postoperative day 1, the bilateral kidneys were normal, and no hydronephrosis was observed. Postoperative follow-up was uneventful and the patient was discharged on day 7. Cystography was performed on day 21 that showed no leakage and urethral catheter was removed. Control USG was performed periodically during hospitalization and no hydronephrosis was observed. The pathology report was pT2a with negative surgical margins. The Double-J stents were removed with the assistance of a flexible endoscope on the second month. The ureter orifices remained behind the neck of the bladder with normal appearance. |
pmc-6555177-1 | A healthy 16-year-old boy was brought to the Level 1 trauma center with a GSW to the right flank. On initial evaluation, he had a heart rate of 115 and blood pressure of 120/80. Glasgow Coma Scale score was 15. Examination of the abdomen revealed a tender right lower quadrant with a bullet entry wound in the right flank and no exit wound. Foley catheter was in place without any macroscopic hematuria.
A CT scan of the abdomen and pelvis with intravenous contrast was performed en route to the operating room that revealed a shattered right kidney with active contrast extravasation and apparent ureteral discontinuity. There appeared to be a laceration of the posterior right hepatic lobe and a fracture of the L1 vertebral body with a paraspinal hematoma with metal fragments. A bullet was lodged in the upper pole of the left kidney (). The left collecting system was intact with opacification of the left ureter. |
pmc-6555179-1 | The patient is a 56-year-old woman who has a history of morbid obesity (body mass index: 49.23 kg/m), decompensated nonalcoholic steatohepatitis with cirrhosis and refractory ascites requiring three prior paracenteses each draining 4.5–8.5 L (Model for End Stage Liver Disease score: 31), hypertension, type 2 diabetes mellitus, and nephrolithiasis treated with five prior ureteroscopic laser lithotripsies.
She presented to the emergency department (ED) at our institution with fever and left flank pain. Before presentation, she had suffered from calcium phosphate kidney stones for several years and was taking daily potassium citrate. Ten months prior, she had been found to have a partial staghorn calculus in the left kidney, measuring 3.8 × 2.2 cm and causing incomplete obstruction. Her right kidney was unremarkable. Extracorporeal shockwave lithotripsy was not recommended. The patient opted against a left percutaneous nephrolithotomy, and instead underwent five ureteroscopic laser lithotripsies at another institution for the next 4 months.
Each of the first three sessions took place roughly 1 week apart, after which she developed Steinstrasse extending from the distal to proximal ureter. As a result, she was taken back for a fourth session within 3 weeks of her previous ureteroscopy, and then a fifth session 2 months later. During these procedures, the patient had vancomycin-resistant enterococcus in her urine by culture for which she received ciprofloxacin continuously. Owing to the size of her stone burden, each procedure was lengthy (>2 hours), and ureteral access sheaths were used to facilitate drainage. A stent was placed at the conclusion of each ureteroscopy.
After her last ureteroscopy, now 5 months before the index presentation to the ED, she developed worsening flank pain, which prompted a CT scan that revealed a 19.4 × 13.4 × 15.8 cm subscapular hematoma and a 10.4 × 3.3 × 13.5 cm perinephric hematoma along the lateral aspect of the left kidney. A ureteral stent was replaced and per report frank pus effluxed from the stent. A nuclear medicine lasix renal imaging study was attempted to assess left kidney blood flow, which showed left renal activity of 3% but was inconclusive secondary to the patient's morbid obesity and the large hematoma. At this point, she was offered a simple nephrectomy owing to a loss in renal parenchyma with residual stones despite her five ureteroscopies. Two weeks before her planned simple nephrectomy, which had been delayed several months because of her comorbidities, her index presentation to our institution with fever and flank pain occurred.
In the ED, the patient had signs consistent with severe pyelonephritis. On arrival, her blood pressure was 105/57 mm Hg, heart rate was 97 beats/min, oxygenation was 100% on room air, and temperature was 100.2°F. Laboratory values included creatinine of 1.7 mg/dL (baseline of 1.0 mg/dL), leukocytosis at white blood cell count of 13.1 × 103/mm3, anemia at hemoglobin of 9.3 g/dL, and hematocrit of 28%. Her urinalysis was significant for leukocyte esterase, large amount of red blood cells, and bacteria. Despite fluid resuscitation, her blood pressure continued to trend down and she was given vasopressors before being admitted to the intensive care unit on intravenous antibiotics. A repeat CT abdomen and pelvis with contrast showed again the left subscapular hematoma measuring 15.6 × 12.2 × 17.5 cm containing locules of gas with surrounding inflammatory perinephric fat stranding (). At this point, she was taken to interventional radiology for drainage of the presumed large hematoma. During initial puncture, there was 300 mL of frank pus that drained. Fluoroscopic imaging during interventional radiology (IR) drainage revealed a fistula from the left subcapsular abscess to the proximal descending colon (). Drain cultures ultimately confirmed a superimposed polymicrobial infection.
The patient was determined to be an extremely poor surgical candidate owing to her comorbidities; she had an 82% perioperative mortality risk from Child–Pugh class C nonalcoholic steatohepatitis complicated by coagulopathy. Extensive counseling on the risks of nephrectomy and colectomy was provided to the patient over the course of a few days, and palliative management was offered as well. The patient elected to optimize her nutritional and functional status before proceeding with surgery in an effort to improve her perioperative morbidities. The patient was then discharged to a skilled nursing facility 1 month after the index admission with continued intravenous antibiotics. She continued to decline over the next month with recurrent sepsis and cirrhosis-related complications and unfortunately passed away. |
pmc-6555203-1 | A 66-year-old man presented to our emergency department (ED) after sliding down a ladder approximately 6-meters after the ladder kicked out from underneath him. When emergency medical services (EMS) arrived on scene they witnessed a man lying in the prone position with his face on a pile of wood and arms raised neck high. The left shoulder had obvious deformity with subjective loss of sensation. The right shoulder appeared normal with intact sensation. In the emergency room, the patient underwent a primary and secondary survey in accordance with the Advanced Trauma Life Support (ATLS) protocol. Physical examination revealed both shoulders to be above his head in a fixed position with extreme pain with any attempted shoulder movement. Radiographs () confirmed the suspected diagnosis of bilateral inferior shoulder dislocations.
Closed reduction under anesthesia (Fetanyl 50mcg, Etomidate 5mg, Midazolam 2mg and Ketamine 40mg administered intravenously) was performed by the emergency room physician with external rotation and axial traction to the left shoulder. The right shoulder was unable to be reduced after multiple attempts. Post reduction radiographs () were obtained which demonstrated interval reduction of the left shoulder and unsuccessful reduction of the right shoulder. Shoulder 3-D CT reconstruction images () were obtained which revealed the right shoulder to be dislocated anterioinferiorly with an acute Hill-Sachs impaction fracture and an acute Bankart fracture measuring 5mm. The left shoulder was dislocated anteriorly with an avulsion fracture of the lateral acromion. The patient reported decreasing pain in the left shoulder and continued pain in the right shoulder. Orthopedic surgery was consulted for further management.
Closed reduction was performed by the orthopedic surgeon with pain medication (Fentanyl 100mcg administered intravenously). The right shoulder was reduced with traction-countertraction and the left shoulder was reduced with traction with anterior and downward pressure. Bilateral reductions were felt to be achieved after a palpable clunk and the ability of a smooth, pain free shoulder range of motion. Post-reduction radiographs () confirmed successful reduction. Bilateral well-padded shoulder slings were placed. The patient was instructed to be non-weight bearing and limit shoulder motion for 2-3 weeks. He was admitted for observation and discharged two days later. Two weeks following discharge, the patient presented to the orthopedic clinic. Radiographs () were obtained which demonstrated bilateral high-riding humeral heads with reduced shoulder joints. On physical exam, the patient was unable to actively flex either shoulder. An MRI was ordered on both shoulders which revealed the left shoulder to have a massive full thickness tear of the supraspinatus and infraspinatus retracted to the level of the glenoid. In addition, the subscapularis was torn, and the long head of the biceps dislocated medially in the intertubercular groove. The right shoulder revealed a full thickness tear of the supraspinatus and infraspinatus with 3-3.5cm of retraction. Two months after his initial injury, the patient underwent a left shoulder arthroscopic extensive glenohumeral joint debridement. Pre-operatively the operating surgeon planned to perform a superior capsular reconstruction but abandoned this as surgery revealed extensive cartilage loss throughout the shoulder joint. Based on the intra-operative findings, arthroplasty was recommended at a later time. |
pmc-6555205-1 | A 55-year-old man presented to the emergency department (ED) with acute onset abdominal pain started insidiously approximately 1-hour prior to presentation. He was discharged only a week before from the same hospital when he was admitted with acute abdominal pain when he underwent a CT-angiogram and a digital subtraction angiography (DSA) of the abdomen, which showed incidental finding of Arc of Buhler (). There was discussion regarding management of this incidental finding and decision was taken not to embolize it by intervention radiology as it was incidental finding and pain was not attributed to that. He was subsequently discharged after observation in the hospital for a couple of days when his labs remained steady. During this admission the patient was alert and oriented in time and place. Abdomen was soft to palpation and tender on deep palpation without peritoneal signs on clinical exam. The abdominal radiography showed partial small bowel obstruction. The CT-scan of the abdomen showed big retroperitoneal hematoma and free fluid around the liver (). Review of systems was grossly nonspecific on arrival to the ED except sharp abdominal pain. His past medical history was essentially negative for any chronic diseases; his surgical history consisted of inguinal hernia repair. After 40-min the patient had sudden cardiac arrest and cardiopulmonary resuscitation as per ACLS protocol was initiated. The patient was emergently intubated. A right subclavian central line was placed. Volume resuscitation was initiated, patient was started on pharmacologic presser agents and massive transfusion protocol was set up. We were working on provisional diagnosis of ruptured Arc of Buhler. Seven units of packed red blood cells (PRBC), 6 units of fresh frozen plasma (FFP) and 2 units of platelets were transfused. His abdomen was massively distended. His vitals were recorded as BP 90/52; HR 120; oxygen saturation at 90%. His labs showed Hb/Hct of 4.8/14.8; and platelet of 90. His serum chemistry was normal at this time with Na 135; K 3.6; Cl 93; CO2 21; BUN 17; Cr 0.1. The patient was taken to the operating room (OR) emergently. A midline trauma incision was made extending from the xiphisternum to the symphysis pubis. Two cell saving suctions were used. About 2L of hemoperitoneum and clotted blood were suctioned out. Massive transfusion was continued intraoperatively. Four quadrant packing was used to temporize the bleeding. A window through the gastrohepatic ligament was used to clamp the supra celiac aorta. There was large bulging retroperitoneal hematoma with gross distortion of anatomy. The spleen was ruptured. There was significant generalized diffuse oozing suggestive of disseminated intravascular coagulation (DIC). We used packs and hemostatic gauze were placed to tamponade the bleeding. The abdomen was left open with an Abthera and Vaccum assisted closure (VAC) with a plan to return to the OR when the acidosis, hypothermia and coagulopathy is corrected. The patient was transferred to the PACU in critical condition. Early next day morning the patient had a sudden cardiorespiratory arrest. ACLS protocol along with CPR was initiated. However, the attempt was futile and the patient was pronounced dead after all resuscitative efforts. |
pmc-6555212-1 | A 18-year-old nulliparous woman gravida 1, para 0 with no remarkable medical history, was referred to Fatemieh Hospital Hamadan-Iran, due to labor pain and premature rupture of membrane (PROM). She had the sign of moderate to severe pre-eclampsia and delivered by normal vaginal delivery at 38 weeks of gestation. Following the delivery, she developed right upper quadrant pain, which was constant. The pain was not positional, and there was no nausea and vomiting. She had tachycardia and significant drop in hemoglobin level. Laboratory testing revealed hepatic dysfunction (AST:535 U/L; ALT:1146 U/L) and thrombocytopenia (platelet count: 77×108 per mL), with moderate to severe hemolysis (LDH:1891 U/L; HB:8/8 g/dL). She was admitted to Intensive care unit (ICU). Ultrasonography revealed intraparenchymal liver hematoma. There wasn't active bleeding and it was confirmed by computed tomography (CT) scan (). She was transferred to surgical department and it was planned to treat conservatively. After four days, the patient improved and the pain was resolved. She was discharged and underwent follow-up monitoring. She is now alive and free from disease after a follow-up of 24 months. |
pmc-6555215-1 | A 17-year-old boy with history of fall from height of approximately 15 meters presented to our institution after receiving primary care at another hospital. At presentation, he was conscious, hemodynamically stable maintaining oxygen saturation at 98% on room air with no visible signs of respiratory distress. His Glasgow coma scale (GCS) was 15, and was able to move all four limbs. The patient had sustained open fracture both bone left leg along with fracture right ankle.
Chest radiograph showed no intrathoracic injury with normal lung parenchyma. Computed Tomography showed burst fracture of fifth lumbar vertebra with canal compromise () and ruled out any injury to head, cervical spine, thorax and abdomen. After primary care, patient was admitted to the orthopedic ward for spine stabilization surgery and surgery for lower limb fracture.
On day four post-admission, an emergency consultation call was sent to our intensive care unit (ICU) in view of patient’s deteriorating status. When seen, he was grossly pale and febrile at 101 F, pulse rate of 140 per minute, systolic blood pressure of 80 mmHg and respiratory rate of 32 per minute maintaining oxygen saturation around 90% on oxygen face-mask. Patient’s GCS was 15. Chest auscultation revealed bilateral diffuse coarse crepitation and he was immediately transferred to the ICU. Initial arterial blood gas (ABG) showed partial pressure oxygen (pO2) of 49mm Hg on oxygen by face mask. Patient was intubated, sedated, paralyzed and put on mechanical ventilation with initial settings of volume assist control and high positive end expiratory pressure (PEEP). Central venous catheter was secured in right internal jugular vein under ultrasound guidance. An arterial line was secured in right radial artery for invasive blood pressure and arterial blood gas analysis. Chest radiograph showed bilateral fluffy opacities (). Preliminary blood investigations were mostly unremarkable except for hemoglobin of 6.8 mg/dl and raised ESR of 44. Fundus exam specific for FES was normal and there was no petechial rash on general examination. Urine for fat globules was positive. Over the next few hours, patient’s hypoxemia worsened requiring higher fraction inhaled oxygen (FiO2) of up to 0.8 and PEEP of 16 cm water. A decision was made to turn the patient into prone position after discussion with the orthopedic surgery team in view of unstable lumbar spine fracture. Patient’s family were informed about the specific risks and benefits of prone positioning, particularly in a patient with pre-existing unstable lumbar spine fracture and a written consent for the same was obtained. Positioning was done with the help of 5 trained ICU staff, using logrolling technique for turning the patient lateral followed by a 6th member placing the spinal board under the patient. After securing the patient on the spinal board, he was then shifted to one edge of the bed while the head gel support, chest and pelvic roll were placed in position. Patient was then shifted to prone position and spinal board was removed. Patient’s hands were abducted and placed next to the head and all the pressure points were padded using pillows and cotton rolls.
Over the next 16 hours, we kept our patient sedated and paralyzed in prone position during which he received targeted fluid therapy and remained hemodynamically stable. Wake up test and pupil examination were done at regular intervals. Serial ABG’s showed dramatic improvement with Fio2 requirement decreasing to 0.4 and PEEP of 8 following which patient was repositioned supine. Two units packed red cells were transfused while the patient was prone. Chest radiograph showed resolving lung infiltrates and we decided to electively mechanically ventilate our patient for next 24 hours in supine position. Weaning was started next day and patient was extubated a day after and transferred back to ward 24 hours later.
The patient later on went on to have multiple surgical procedures for injuries to spine and bilateral lower limbs. He was then followed for 8 weeks in the out-patient department following discharge during which he recovered well without any neurovascular deficit. |
pmc-6555491-1 | A 29-year old male presented to the ED with chief complaint of pain in the right eye, inability to open the eye, and excessive tearing in the right eye. He stated that, one day before arriving at the ED, his 3-year-old child poked him with a wooden skewer in his right eye. There was no active bleeding in the eye. He denied experiencing fever, chills, headache, nausea, or vomiting. Remainder of the review of systems was negative. The patient did not use glasses or contact lenses. His past medical and surgical history were noncontributory.
His vital signs were pulse 72, blood pressure 142/78 mmHg, temperature 37.2° C, respirations 17/min, and pulse oximetry 99%. Visual acuity was 20/50 in his left eye and 20/70 in his right eye. Intraocular pressure (IOP) in the left eye was 18 mmHg and 20 mmHg in the right eye (normal IOP is less than 22 mmHg). Pupillary shape was normal. There was no hyphema, and Seidel’s test was negative. Fluorescein staining revealed an abrasion at the superior aspect of the cornea, as depicted in Figure . The patient was discharged home with pain control and erythromycin antibiotic ointment. He was instructed to follow up with his primary care physician and ophthalmology within 24 hours, and to return to the ED should symptoms worsen. |
pmc-6555492-1 | A 25-year-old male with a remote history of migraine headaches without aura in childhood presented to the emergency department (ED) with a three-day history of bitemporal and occipital throbbing headache. The headache was mild in intensity and it was associated with photophobia. It was non radiating. He did not endorse any other symptoms. He was hemodynamically stable. There were no focal neurological findings on exam. His symptoms were attributed to a migraine headache. His headache improved after administration of non-steroidal anti-inflammatory drugs (NSAIDs). He was subsequently discharged home.
However, he returned to the ED three days later with a persistent headache of similar nature as prior, but this time associated with four hours of intermittent left arm tingling. He did endorse one episode of projectile vomiting a day before this presentation. On further history, he denied dizziness, vertigo, diplopia, visual changes, ear fullness, tinnitus, neck pain, palpitations, weakness or numbness. He had not had a migraine headache since the age of 15 and was not on any medications. Family history was significant for hypertension in his mother and a maternal cousin who passed away at the age of 41 due to a ruptured intracranial aneurysm. There was no family history of hematologic disorders. He was a full-time student and occasionally smoked marijuana.
On examination, the patient’s temperature was 98.4 F, blood pressure was 136/71 mmHg and oxygen saturation at 97% on ambient air. He was a healthy appearing male in no acute distress. Cardiovascular, respiratory, abdominal, and skin examination was unremarkable. Neurological exam did not reveal any cognitive, language, cranial nerve, motor or sensory deficits. Gait was normal. The patient’s complete blood count with differential and basic metabolic panel were unremarkable.
However, the patient kept complaining of severe photophobia, headache, and intermittent left arm tingling. He did not experience relief with intravenous pain medications. Given his second visit to the ED and symptoms of intermittent left arm tingling, it was decided to order a computed tomography (CT) of the head without contrast.
CT head without contrast, as seen in Figures -, unexpectedly revealed a well-circumscribed hyperdensity at the inion corresponding to the torcula as well as a prominent hyperdense right transverse sinus. Therefore, CT angiogram of head and neck vessels was performed which showed extensive CVT of the superior sagittal sinus, right transverse sinus with extension into the sigmoid sinus, and jugular bulb (Figure ).
There was also involvement of the cortical veins with evidence of trace subarachnoid hemorrhage in the left frontal sulcus. Magnetic resonance imaging (MRI) of the brain without intravenous contrast confirmed these findings (Figure ).
Hypercoagulability panel was sent which included partial thromboplastin time, prothrombin time, antithrombin III activity, protein C activity and antigen, protein S activity and antigen, Anti-nuclear antibody screen, serum beta-2 glycoprotein antibodies (IgA, IgM, IgG), serum cardiolipin antibodies (IgA, IgM, IgG), lupus anticoagulant with reflex to dilute Russell’s viper venom time (dRVVT), serum homocysteine level, lipoprotein (a) and sickle cell screen. Genetic analysis for mutations or polymorphisms in methyl tetrahydrofolate reductase (MTHFR) gene, factor II prothrombin gene, and Factor V Leiden gene were also tested.
Subsequently, the patient was started on a full dose of heparin infusion with goal anti-Xa level between 0.3-0.7 IU/mL. The patient had one generalized tonic-clonic seizure the day after admission for which he was started on levetiracetam. His neurological exam and repeat CT head without contrast remained stable.
The hypercoagulable panel was only notable for slightly elevated homocysteine level at 13.8 umol/L (normal <11.4 umol/L) and one copy of the c.665C>T GenBank#NM_005957.4 (previously known as C677T polymorphism in the MTHFR gene). Serum folic acid was normal. Further work up including CT of the chest, abdomen and pelvis, transthoracic echocardiogram, venous duplex ultrasound of the lower extremities were all unremarkable.
The patient was started on long-term anticoagulation with warfarin with goal international normalized ratio (INR) between 2.0 and 3.0 and discharged home with plans for outpatient follow up. |
pmc-6555494-1 | A three-year-old male presented to the emergency room (ER) with persistent thrusting of his pelvis anteriorly and inconsolable crying. The patient has a complex past medical history significant for hypotonia, developmental delays, and poor weight gain due to a UNC80 mutation of 44 Mb homozygosity of 2q33.1-q37.3 and smaller regions of homozygosity on chromosomes two, three, 11, and 16. Due to this mutation, the patient has a past history of reactive airway disease and recurrent pneumonia. He requires BiPap to assist his oxygenation during the night. He uses a cough assist machine four times daily to help clear his secretions. He is unable to clear the secretions due to his hypotonia caused by the chromosomal abnormality. Nutrition is received via his G-tube. He is non-verbal at baseline due to significant developmental delay.
Eighteen days prior to admission, the patient developed a low-grade fever, non-productive cough, and nasal congestion. He was diagnosed with pneumonia, given one dose of intramuscular ceftriaxone, and given a five-day course of oral cefdinir with subsequent improvement of his symptoms. Three days prior to admission, the patient’s fever, rhinorrhea, and cough worsened. On the day prior to admission, the patient developed projectile non-bloody, bilious emesis. In the ER, the patient appeared distressed, had a fever (38.0℃), heart rate of 168 beats per minute, and a respiratory rate of 30 breaths per minute.
On admission, the patient was placed on oxygen via nasal cannula and given acetaminophen, ketamine, and fentanyl for pain control. Following medication, the physical exam yielded a happy child in a non-toxic state. His abdomen was soft, non-tender, with normal bowel sounds. The liver edge was palpable, and his gastrostomy tube (G-tube) feeding site was free of infection. A chest X-ray was consistent with viral pneumonia as mild perihilar bronchial wall thickening and interstitial opacities were visualized (Figure ). An abdominal computerized tomography (CT) scan showed copious amounts of stool in the large intestine without evidence of intussusception, appendicitis, colitis, or a volvulus (Figures -). The patient’s parents stated his last bowel movement was one day prior and was semi-soft and normal. They also stated that he typically stooled a small amount, several times a day. A viral panel from a nasopharyngeal swab was ordered, which was positive for enterovirus. All other labs were within normal limits. The patient was diagnosed with viral gastroenteritis and pneumonia.
Constipation remained an issue despite the diagnosis of viral gastroenteritis. The patient was given polyethylene glycol for treatment of his constipation. After a period of no bowel movements, the dose was increased. Subsequently, the patient had two medium bowel movements and one smaller movement during the night.
The patient received intravenous (IV) normal saline at 30 mL/hr for presumed dehydration along with IV ceftriaxone at admission. The patient pulled out the IV during his hospital stay, and IV antibiotic access was not further pursued or continued due to viral infectious etiology. The patient took polyethylene glycol during his stay for his constipation. The patient was given nutrition via his G-tube.
The patient was discharged after improving on oral polyethylene glycol with instructions on oral rehydration and home-based monitoring. |
pmc-6555496-1 | A 21-year-old male presented to our emergency department (ED) following a high-velocity road traffic accident (RTA), sustaining an injury to his left hip. While riding his motorcycle, he lost control of his bike and fell on his left hip. Immediately, he felt severe pain in the left hip and was unable to bear weight over the left hip. On arrival to the ED, the patient was managed according to the advanced trauma life support (ATLS) protocol. The left lower limb was grossly shortened and externally rotated (Figure ). Swelling was noted in the left hip and thigh region. Tenderness was present near the hip joint and movements were painful. An abrasion of approximately 10 cm x 15 cm was present over the medial aspect of the left thigh. The neurovascular status was normal. Standard radiographs showed an anterior dislocation of the hip with an intra-articular bone fragment (Figure ). After stabilizing the vitals, the patient underwent a computed tomography (CT) scan of the pelvis, with both hips, which showed an anteriorly dislocated femoral head lying externally rotated in relation to the superolateral aspect of the acetabulum. In addition, a displaced posterior wall fracture fragment was found within the acetabulum and a separate anterior wall fracture was noted (Figure ). The patient was immediately rushed to the operation theater after consenting for both closed and open reduction. After general anesthesia, closed reduction was attempted by the Allis method under image guidance. The femoral head could not be displaced from its position despite three attempts and a decision was made to proceed with open reduction using the Smith-Peterson approach. It was found that the head was trapped in the iliopsoas muscle and the detached fragment was found to be the posterior acetabular wall (Figure ). The capsule was found to be torn. Open reduction was performed and the position of the posterior wall was restored (Figure ). The anterior wall, being a very small fragment, did not need reduction. The walls' fragments were not fixed, as they were completely reduced and the hip remained stable after reduction. Rehabilitation consisted of on-traction mobilization exercises of the hip in bed. At six weeks, non-weight bearing mobilization was initiated with the help of crutches. By 12 weeks, the fracture showed signs of union and partial weight-bearing mobilization was started. At the end of one year, the patient was independently mobile and was able to sit cross-legged, squat, and use public transport. The outcome was assessed by using the Modified Harris Hip score at six months and one year, which was 66 points at six months and 87 points at one year. The CT images at the one-year follow-up showed complete union (Figure ). |
pmc-6555497-1 | A 51-year-old man with no history of coronary artery disease presented to the ED after he was awoken by sudden onset of left-sided chest pain. The pain escalated over 15 minutes. He described it as severe, radiating from the left anterior chest to his left scapula as well as down his left arm. The patient reported that he got out of bed and tried to "walk it off." At this time, he developed diaphoresis, nausea, and some light-headedness. He described his pain as 10/10 at its worst. His initial ECG was unremarkable. The patient was treated with aspirin, nitrates, and oxygen. His pain resolved within 15 minutes of arrival, or soon after vasodilators and anti-platelet therapy had been initiated.
Repeat ECG (Figure ) upon resolution of pain revealed biphasic T-waves in leads V2, V3, and V4, consistent with WS. The patient underwent urgent cardiac catheterization which did demonstrate a 90% proximal left anterior descending artery (LAD) lesion (Figure ). The patient was stented and discharged the next day. |
pmc-6555498-1 | A 39-year-old White female presented to the hospital with a three-day history of epigastric pain. She described her pain as a burning pain that started at rest and was radiating to her neck. Her pain was associated with shortness of breath, and she denied any episodes of nausea, vomiting, cough, fevers, chills, or sweating. She recently had a twin pregnancy and gave birth at about 32 weeks of gestation via caesarian section, but lost both her children after birth. This event had been very emotionally taxing on her for the past three months.
Her past medical history was only remarkable for gestational diabetes during her last pregnancy. She typically smoked one pack per day of cigarettes for the last 20 years. Recently, she increased her smoking to two packs per day for the past few months. She denied any use of alcohol or recreational drugs. She also denied any other cardiac risk factors, significant family history of cardiac disease, sudden cardiac death, or connective tissue disease. She had no allergies and was not taking any medications.
On examination, she was afebrile with a temperature of 36.9°C, heart rate of 82 beats/min, a blood pressure of 165/110, respiratory rate of 18 breaths/minute, and oxygen saturation of 99% on room air. Her head and neck examination were unremarkable with no jugular venous distention. On auscultation, there was good air entry bilaterally and normal heart sounds with no murmurs, rubs, or gallops. There was no edema on examination of the lower extremities.
An initial electrocardiogram (EKG) was obtained as can be seen in Figure .
Her EKG showed sinus rhythm with sinus arrhythmia and anterolateral T wave inversions concerning for anterior ischemia. Cardiac biomarkers included a creatine kinase level of 261 U/L (normal range, 33-211 U/L), a creatine kinase-MB fraction of 13 U/L (normal, <10 U/L), and a troponin I level of 5.22 ng/mL (normal, <0.01 ng/mL). She was transferred from an urgent care facility after aspirin and ticagrelor loading for percutaneous coronary intervention. Her peak troponin I was 5.4. Angiography revealed spontaneous coronary artery dissection (SCAD) of the distal left anterior descending (LAD) artery without any other atherosclerotic disease (Figures -). The other coronary arteries were normal. Catheterization also revealed a mildly reduced left ventricular ejection fraction of 45% and akinetic apical segments of the left ventricle.
She was started on medical management for SCAD, which included low dose aspirin, metoprolol, and captopril. Dual antiplatelet therapy and heparin were not given because of the risk for increased bleeding and no clear evidence of benefit. She was admitted to the cardiac critical care unit for observation and remained hemodynamically stable during her stay. Echocardiography done after one day confirmed wall motion abnormalities of the left ventricular apex with an estimated low normal left ventricular ejection fraction of 50%-55% (Figure ). Laboratory workup for possible connective tissue disorders or vasculitis was done as underlying coronary vasculitis may increase the risk for spontaneous dissection and it was negative for rheumatoid factor, anti-CCP and ANA and only positive for atypical perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA). She was discharged two days after the presentation on medical therapy. The patient was doing well on the subsequent follow-up visit. |
pmc-6555499-1 | A 40-year-old male suffering from hallucinations and bizarre behavior was brought by police to our emergency room (ER). His vitals on arrival were: temperature 36.9°C, pulse 124 BPM, respiration 20 per minute, blood pressure 104/57, and pulse oximetry 95% on room air. A urine drug screen was positive for amphetamines and his blood alcohol level was 0.029 mg/dL. His past medical history was significant for alcohol use disorder, end-stage liver disease, portal hypertension, ascites, esophageal varices, and hepatic encephalopathy. On examination, the patient was lethargic and difficult to arouse with an ammonia level of 109.5 umol/L. He was admitted for acute treatment of hepatic encephalopathy but developed hematochezia within 24 h of admission. An esophagogastroduodenoscopy (EGD) demonstrated grade II esophageal varices, which were banded, and portal hypertensive gastropathy. This seemed to resolve the hematochezia; however, two days later he had another episode of bright red blood per rectum. Sigmoidoscopy was performed, which demonstrated nonbleeding internal hemorrhoids. Over the next 36 h the patient complained of increasing lower abdominal pain and had intermittently bloody stools; however, a computed tomography (CT) scan of the abdomen and pelvis was negative for any acute changes. He then had two large, bloody stools and developed hypotension overnight; additionally his creatinine increased from 0.6 to 1.2 within 12 h. Given the intermittent nature of his gastrointestinal bleeding, a Model for End-Stage Liver Disease (MELD) score of 20 and concerns that he may have been developing hepatorenal syndrome, the gastroenterologist determined colonoscopy too risky. Instead, a tagged red blood cell scan was ordered as a less invasive modality to seek out intermittent bleeding. It showed abnormalities in the duodenum and stomach as well as bleeding from the right colon. The patient was taken to interventional radiology for a mesenteric angiogram. No active bleeding was identified; however, the portal venous phase of the superior mesenteric arteriogram did show dilated varices within the mesentery of the right colon.
Given the grave prognosis, the patient decided to transition to palliative care and became no code status for four days. He continued to worsen during this time period, though he later decided he would like to transition off palliative care and after much discussion, he elected to proceed with transjugular intrahepatic portosystemic shunt (TIPS) procedure in an effort to reduce his portal hypertension in hopes of reducing his bleeding risk. Interventional radiology first recommended a triphasic CT scan to better evaluate arterial/venous anatomy relative to cross-sectional anatomy. Triphasic CT scan was performed and demonstrated varicosities throughout the abdomen with a focus of varicosities in the right lower quadrant, likely the right colon (Figure ). TIPS was performed without complications (Figure ). Later that evening, the patient developed significant hemorrhage with rectal bleeding; massive transfusion protocol and disseminated intravascular coagulation panel were ordered. Another triphasic CT was performed which demonstrated brisk cecal hemorrhage (Figure ). The patient was again brought to interventional radiology for an angiogram and embolization of the ileocolic and right colic veins. Mesenteric angiogram demonstrated marked enlargement of the superior mesenteric vein with hepatofugal flow, filling of numerous varicosities in the right lower quadrant, and significant mesocaval shunting (Figure ). The ileocolic and right colic veins were coil embolized and subsequent venography demonstrated return of hepatopedal flow (Figure ). Immediately after embolization, the patient’s hemodynamic status improved with normalization of his blood pressure from 80/45 to 115/60. He was transferred back to the ICU in stable condition. Two days later the patient began to develop right lower quadrant pain and his D-Dimer began trending up, which was concerning for possible ischemic colitis; however, this abated after a few hours. He remained an inpatient for an additional five days and on the day of his discharge he was awake, oriented, polite, and cooperative.
During the first nine months of follow-up, the patient has had a complicated course related primarily to his chronic liver disease. He has suffered from intermittent abdominal pain and has been hospitalized or seen in clinic for lactic acidosis, bouts of abdominal pain, an incarcerated right inguinal hernia, significant scrotal edema, and methicillin-resistant Staphylococcus aureus bacteremia. He has, however, attempted positive lifestyle changes, including abstaining from alcohol and illicit drugs and improving his social support. He has had neither recurrent episodes of hematochezia nor has he suffered additional bouts of hepatic encephalopathy. The patient continues to be followed closely as an outpatient. |
pmc-6555500-1 | A 14-year-old boy with morbid obesity and no known prior psychiatric history underwent sleeve gastrectomy. Prior to the surgery, he weighed 167 kilograms with a body mass index (BMI) of 54.5. Within a few months postoperatively, he weighed 70 kilograms with a BMI of 22.8. The patient’s substance use disorder started at the age of 15, one year after the bariatric surgery. Of note, the patient's parents were separated and he lived with his mother and siblings. None of his family members or relatives had a history of substance use disorder. He initially started using fenethylline (marketed under the brand name Captagon), as it was a common substance used by his peers at school. He started with two tablets daily and increased his use gradually up to 15 tablets daily. He started smoking cannabis a year later, at the age of 16, starting with one cigarette per day and increasing his use gradually until reaching a peak of 20 cigarettes per day. The patient started drinking alcohol occasionally at the age of 16 as well, and it soon became an issue of excessive use on a daily basis. The patient drank different types of alcoholic beverages. He reported incidents of fainting in relation to alcohol use but had never experienced withdrawal. He mentioned that he started using alcohol as a way to reduce his use of other substances. Two years later, at the age of 18, the patient started using methamphetamine, which caused him to develop paranoid ideation, auditory hallucinations, severe insomnia, and aggressive behavior. The patient was admitted to an inpatient psychiatric unit for a few days and was started on haloperidol 3 mg orally twice daily, benztropine 2 mg orally twice daily, and quetiapine 50 mg orally as needed for insomnia. His psychotic disorder improved with the cessation of substance use and the treatments initiated on the inpatient side. After his discharge, he unfortunately relapsed and continued to use the aforementioned substances.
After arranging for close follow-up, the patient voluntarily presented to the rehabilitation center, motivated to stop using all substances, as he was legally and financially burdened by this disorder. He was incarcerated twice for substance use-related criminal charges. He was also motivated to start a new life and to enroll again in higher education, as he dropped out of school previously due to his polysubstance use disorder. The patient has thereafter been involved in a rehabilitation and relapse prevention program, which included inpatient admissions as needed to the rehabilitation center, involvement in individual and group therapy, occupational therapy, and addiction counseling. |
pmc-6555583-1 | A 16 years old inbred girl was referred to the cardiology clinic because of
paroxysmal palpitation. Her parents are consanguineous. The 12-lead
electrocardiogram (ECG) showed short PR interval and Delta waves, and widened QRS
complexes (). The patient was
considered as type-A WPW syndrome. Transthoracic echocardiography was normal.
Patient, her sister and father have molecularly confirmed CFNS and both have
heterozygous missense mutation (c.451G > A; Gly151Ser) in exon 3 of EFNB1 gene.
She has undergone surgery for frontonasal dysplasia. Father was also had WPW
syndrome and he had a successful catheter ablation for left lateral accessory
pathway. The patient was refereed to electrophysiology department for
electrophysiological study and transcatheter ablation of the accessory pathway. |
pmc-6555724-1 | The patient was a 45-year-old male who was admitted to our institution due to uremia. He had no diabetes and biliary tract disease history, and his BMI (body mass index) was 22.99 kg/m2 (183cm, 77 kg). He underwent kidney transplantation in our institution on 9th August, 2017. The donor was from donation after cardiac death (DCD). Before surgery, he received antilymphocyte therapy of basiliximab (20 mg i.v.). The surgery was successful and the initial immunosuppressive regimen consisted of tacrolimus (6 mg/day, 0.078 mg/kg/day), mycophenolate mofetil (1500 mg/day) and corticosteroids (initial dose 35 mg/day). The patient recovered well after surgery and was discharged on day 26+ with blood creatine level 156.6umol/L and trough concentration of tacrolimus 10.6 ng/ml then. After discharged, He reexamined in our institution once a week. From day 26+ to day 60+, the reexamine results showed his blood creatine level continued to decline to 101.7umol/L (day 60+), the dosage of corticosteroids was gradually tapered from 35 mg/day to 5 mg/day, and the dosage of tacrolimus was maintained at 6 mg/d with trough concentration ranged from 9.5–11.2 ng/ml. In addition, the recipient neither had a history of high fat diet nor presented hyperlipidemia from day 1+ to 67+ posttransplant, the laboratory analysis results showed the serum triglyceride (TG) level was in the range of 0.71–1.43 mmol/L while the cholesterol (CHOL) level was 3.3–4.5 mmol/L during the period.
On day 67+, he presented with acute abdominal pain in middle and left area of abdomen accompanied with nausea and vomiting. Physical examination showed diffuse abdominal tenderness with diminish bowel sound. Laboratory analysis showed WBC 9.16 × 109/L, neutrophils 7.98 × 109/L, hemoglobin 73 g/L, platelets 78 × 109/L, blood creatinine 147.4umol/L, blood urea nitrogen (BUN) 17.79 mmol/L, calcium 2.52 mmol/L, potassium 4.72 mmol/L, sodium 138 mmol/L, serum amylase 679.3 IU/L (normal 15–115), lipase 755 U/L (normal 6–51), trough concentration tacrolimus> 30 ng/ml (dosage was 6 mg/day) accompanied with elevated fasting blood glucose (29.49 mmol/L) and diabetic ketoacidosis (DKA) tendercy (blood ketone body test +). Abdominal computed tomography scan showed enlarged pancreatic head with peripancreatic inflammation and inflammatory exudate without dilatation of biliary tract (Fig. ). Pancreatitis diagnosis was made on the basis of the information all above.
Tacrolimus treatment was discontinued, somatostatin (3 mg, q12h, i.v.) was administrated to treat pancreatitis, other treatments included fluid replacement, insulin (i.v.) and imipenem (1 g, q12h, i.v.). Three days after somatostatin using (day 70+), patient’s condition improved significantly, abdomen symptoms relieved, blood amylase level were normalized (72 IU/L) and lipase level deceased to 69 U/L, blood glucose level maintained around 10–15 mmol/L. Cyclosporine (4 mg/kg/day) was administrated as an alternative for tacrolimus on day 75+, and the patient was discharged on day 80 + .
There was no recurrence of pancreatitis in 7 months follow up. |
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.