Ischemic Stroke and Impact of Thyroid Profile at Presentation: A Systematic Review and Meta-analysis of Observational Studies.

BACKGROUND: Stroke is the fifth leading cause of mortality in the United States and a leading cause of disability. A complex relationship between thyroid hormone levels and severity of, and outcome after, stroke has been described. AIM: Our objective is to identify the association between baseline thyroid function profile and outcome after acute ischemic stroke. METHODS: Studies looking at the association between thyroid function and functional stroke outcomes were identified from available electronic databases from inception to December 16, 2016. Study-specific risk ratios were extracted and combined with a random effects model meta-analysis. RESULTS: In the analysis of 12 studies with 5218 patients, we found that subclinical hypothyroidism was associated with better modified Rankin scale scores at 1 and 3 months (odds ratio [OR] 2.58, 95% confidence interval [CI] 1.13-5.91, P = .03 and OR 2.28, 95% CI 1.13-3.91, P = .003, respectively) compared with the euthyroid cases. Likewise, patients with higher initial thyrotropin-releasing hormone (TSH) and fT3 or T3 levels had favorable outcomes at discharge (mean differences of TSH .12 [95% CI .03-.22, P = .009] and of fT3 .36 (CI .20-.53, P < .0001]) and at 3 months (mean differences of TSH .25 [95% CI .03-.47, P = .03] and of T3 8.60 [CI 4.58-12.61, P < .0001]). CONCLUSIONS: Elevated initial TSH (clinical or subclinical hypothyroidism) may correspond to better functional outcomes, whereas low initial T3/fT3 might correlate with worse outcomes in acute ischemic stroke among clinically euthyroid patients. This complex relation merits further well-designed investigations. Whether correcting thyroid profile with hormone supplementation or antagonism may lead to improved outcomes will require large, prospective, interventional studies.

Statin-Associated Autoimmune Myopathy: A Systematic Review of 100 Cases.

BACKGROUND: Statins are a group of drugs that reduce the levels of triglycerides and cholesterol in blood by inhibiting HMG-CoA reductase, an enzyme involved in rate limiting step in cholesterol synthesis. About 2-20% patients on statins develop toxic myopathies, which usually resolve on discontinuation of statin. More recently, an immune-mediated necrotizing myopathy has been found to be associated with statin use which in most cases requires treatment with immunosuppressants. OBJECTIVE: To perform a systematic review on published case reports and case series of statin-associated autoimmune myopathy. METHODS: A comprehensive search of PUBMED, EMBASE, Cochrane library and ClinicalTrials.gov databases was performed for relevant articles from inception until March 19, 2016 to identify cases of statin-associated necrotizing myopathy and characterize their symptoms, evaluation and response to treatment. RESULTS: A total of 16 articles describing 100 patients with statin-associated autoimmune myopathy were identified. The mean age of presentation was 64.72 years, and 54.44% were males. The main presenting clinical feature was proximal muscle weakness, which was symmetric in 83.33% of patients. The mean creatine kinase (CK) was 6853 IU/l. Anti-HMG-CoA reductase antibody was positive in all cases tested (n = 57/57, 100%). In patients with no anti-HMG-CoA antibody results, diagnosis was established by findings of necrotizing myopathy on biopsy. Among the 83 cases where muscle biopsy information was available, 81.48% had necrosis, while 18.51% had combination of necrosis and inflammation. Most (83.82%) patients received two or more immunosuppressants to induce remission. Ninety-one percent had resolution of symptoms after treatment. CONCLUSION: Statin-associated necrotizing myopathy is a symmetric proximal muscle weakness associated with extreme elevations of CK. It is common in males and can occur after months of statin use. It is associated with necrosis on muscle biopsy and the presence of anti-HMG-CoA reductase antibodies. It usually requires discontinuation and immune suppression for resolution. Rechallenge with statin is unsuccessful in most cases.

Sweet's syndrome in a granulocytopenic patient with acute myeloid leukemia on FLT3 inhibitor.

INTRODUCTION: Gilteritinib is a FLT3 kinase inhibitor approved for FLT3-mutated acute myeloid leukemia (AML). We present a case of febrile neutropenia and neutrophilic dermatosis consistent with Sweet's syndrome (SS). CASE HISTORY: A 55-year-old woman presented with fever and skin lesions after 4 weeks of initiation of Gilteritinib for AML. She was febrile, pancytopenic and neutropenic with absolute neutrophil count (ANC) of 0.1x10E3/UI. Examination revealed reddish and violaceous rashes on her extremities. Pathology showed superficial dermal edema, widespread epidermal spongiosis and multiple neutrophils in the dermal infiltrate. Rash improved with prednisone 60 mg daily and started to flare with taper. She was still on Gilteritinib all this time. Gilteritinib was finally stopped due to non-response and possible contribution in flaring her SS. Shortly after, the patient succumbed to progressive disease and complications of sepsis. DISCUSSION: There have been reports of SS in neutropenic patients although SS is typically a neutrophilic dermatosis. The pathogenesis of SS in neutropenia remains uncertain. Our study represents an additional medication-associated cutaneous complication of AML therapy. Clinicians need to be aware of potential neutrophilic dermatoses with FLT-3 inhibition, even with peripheral neutropenia.

The trend of osteoporosis and osteoporotic fragility fractures in inpatients: results from a national database.

Osteoporosis is associated with an increased risk of pathologic fractures; however, most patients do not receive diagnosis and adequate treatment. The aim of our study was to compare the yearly trends of osteoporosis and osteoporotic fragility fractures in the USA (US) inpatients. We used National (Nationwide) Inpatient Sample database to identify adults ≥18 years with diagnoses of osteoporosis and pathologic fractures and excluded pathologic fractures due to other etiologies. We then studied the annual trends, in terms of annual percentage change (APC), of osteoporosis and osteoporotic fractures. Among overall hospitalizations, osteoporosis was noted to have an increasing trend from 2000 to 2009 (APC = 5.81, p < 0.05) with a decline thereafter (APC = - 3.88, p < 0.05). In contrast, osteoporotic fracture showed an initial downward trend from 2000 to 2010 (APC = -7.31, p < 0.05), followed by a slowly rising trend (APC = 2.0, p = NS). The initially increasing trend of osteoporosis was followed by a decreasing trend thereafter. In contrast, there was a halt in a previously declining trend of osteoporotic fracture. Potential explanations include inadequate screening and treatment per guidelines along with decreasing patient compliance. In conclusion, primary and secondary prevention measures for osteoporosis have been underutilized by both physicians and patients alike.

Atraumatic splenic rupture associated with apixaban.

Apixaban is a direct oral anticoagulant that works by inhibiting factor Xa. It has been associated with adverse bleeding outcomes including atraumatic splenic rupture. We present the case of an 86-year-old man who presented with features of left upper abdominal pain and hemorrhagic shock found to have atraumatic splenic rupture and hemoperitoneum on imaging.

Severe anion gap metabolic acidosis associated with initiation of a very low-carbohydrate diet.

Low carbohydrate diets have been popularized as an effective solution for weight loss. Although rare, life-threatening anion gap metabolic acidosis has been reported in patients on these diets. We present a case of a 31-year-old man with atypical symptoms of chest pain and shortness of breath found to have severe metabolic acidosis after starting low carbohydrate diet for a week.

Statin-induced necrotizing autoimmune myopathy: an extremely rare adverse effect from statin use.

Statins are widely prescribed medications to prevent cardiovascular events. While self-limited statin myopathy is relatively common, statin-induced necrotizing autoimmune myopathy (SINAM) is extremely uncommon, with incidence of two cases per million per year. We present a case of SINAM after a decade of atorvastatin use, leading to debilitating weakness. A 71-year-old male presented with recurrent falls due to extreme bilateral lower-extremity weakness without pain or sensory changes. No fever, chills, rash, joint pain, recent infection or medication changes were reported. Reported taking atorvastatin 80 mg daily for 10 years. Physical examination revealed significant muscle wasting on right deltoid and proximal muscle weakness in all extremities. Lab tests included elevated creatinine kinase, aldolase, ESR, CRP and transaminases. Anti-HMGCR antibody was significantly elevated. TSH, serum protein electrophoresis and RPR were unremarkable. ANA, Anti-Jo-1, anti-Mi2, anti-SRP, anti-ds-DNA, anti-SSA and anti-SSB antibodies were negative. MRI of thigh revealed diffuse myositis. Electromyogram revealed an acute myopathic process. Muscle biopsy showed muscle necrosis and C5b-9 sarcolemmal deposits on non-necrotic fibers without rimmed vacuoles. He was diagnosed with SINAM. Statin was discontinued, and steroid, immunoglobulins and azathioprine were started with gradual improvement. Unlike the self-limiting statin myopathy, SINAM is more severe and is associated with significant proximal muscle weakness, markedly elevated CK and persistent symptoms despite statin discontinuation. Anti-HMGCR antibodies are present in 100% of cases. Immunosuppressants are the mainstay of treatment, and statin rechallenge should never be done in these cases. Although relatively rare, physicians should be cognizant of SINAM.

Acute milk-alkali syndrome

Summary: A 74-year-old woman presented with progressive lethargy, confusion, poor appetite and abdominal pain. She was found to have non-PTH-mediated severe hypercalcemia with renal failure and metabolic alkalosis. Extensive workup for hypercalcemia to rule out alternate etiology was unrevealing. Upon further questioning, she was taking excess calcium carbonate (Tums) for her worsening heartburn. She was diagnosed with milk-alkali syndrome (MAS). Her hypercalcemia and alkalosis recovered completely with aggressive hydration along with improvement in her renal function. High index of suspicion should be maintained and history of drug and supplements, especially calcium ingestion, should be routinely asked in patients presenting with hypercalcemia to timely diagnose MAS and prevent unnecessary tests and treatments. Learning Points: Suspect milk-alkali syndrome in patients with hypercalcemia, metabolic alkalosis and renal failure, especially in context of ingestion of excess calcium-containing supplements. Careful history of over-the-counter medications, supplements and diet is crucial to diagnose milk-alkali syndrome. Milk-alkali syndrome may cause severe hypercalcemia in up to 25­30% of cases.

Agranulocytosis Associated with Topiramate: A Case Report and Review of Published Cases.

A 41-year-old female presented to the hospital with sore throat and shortness of breath. She was hypoxic with an oxygen saturation of 87% in room air. Physical examination revealed swollen uvula with exudates. She had been started on topiramate for treatment of migraine few months ago. The dose of topiramate was increased to 100 mg twice daily 2 weeks ago. Complete blood count revealed an absolute neutrophil count (ANC) of 8 c/mm3. She was intubated and started on broad-spectrum antibiotics. She was transferred to our hospital on the fifth day of hospitalization. On arrival, her absolute neutrophil count was 10 c/mm3. Her agranulocytosis was attributed to topiramate after ruling out other possible causes. ANC improved after topiramate was stopped. ANC increased to 1000 after 5 days of stopping topiramate. We also reviewed published cases of topiramate-associated agranulocytosis. Agranulocytosis is a rare side effect of topiramate, and only 3 case reports have been published so far. In all cases, agranulocytosis developed after months of topiramate therapy and when dose was increased to 200 mg daily suggesting a dose-dependent effect. Next steps would be further research on the pathogenesis of agranulocytosis associated with topiramate and creation of registry for data synthesis.

Daptomycin associated eosinophilic pneumonia: case report and differential diagnoses.

Daptomycin is a bactericidal antibiotic approved for treatment of gram-positive skin and soft tissue infections. We present a case of an 89-year-old man who presented with fever, shortness of breath and nonproductive cough on week 4 of starting daptomycin for infective endocarditis. Computerized tomography scan showed bilateral interstitial infiltrates predominantly affecting the lower lobes. He also had peripheral eosinophilia of 6%. He was diagnosed with eosinophilic pneumonia secondary to daptomycin use. His symptoms improved with discontinuation of daptomycin and initiation of corticosteroids. Clinical correlation of pneumonia-like presentation with recent use of daptomycin should make physicians rule out this rare adverse effect for early institution of correct treatment.

Multifactorial aetiology for non-uremic calciphylaxis: a case report.

Calciphylaxis is commonly associated with end-stage renal disease patients on haemodialysis. We present a rare case of calciphylaxis in a non-uremic patient. The diagnosis was made clinically and confirmed with skin biopsy showing calcification of the dermal and subcutaneous tissues in the von Kossa stain. We believe that the combination of uncontrolled diabetes mellitus, a non-functioning paraganglioma and vitamin D deficiency in a susceptible female patient was responsible for causing calciphylaxis in our patient. An index of suspicion should be maintained by clinicians for calciphylaxis even in patients without uremia.

Primary Hyperparathyroidism in Pregnancy: Successful Parathyroidectomy during First Trimester.

Primary hyperparathyroidism in pregnancy can result in significant maternal and fetal complications. When indicated, prompt parathyroidectomy in the early second trimester is considered the treatment of choice. Pregnant patients with primary hyperparathyroidism who have an indication for parathyroidectomy during the first trimester represent a therapeutic challenge. We present the case of a 32-year-old primigravida who presented with symptomatic hypercalcemia from her primary hyperparathyroidism. She remained symptomatic despite aggressive conservative management and underwent parathyroidectomy in her first trimester with excellent outcomes.

Hypercalcemia associated with cosmetic injections: a systematic review.

INTRODUCTION: Cosmetic injections with silicone and polymethylmethacrylate are not FDA approved for augmentation of body parts such as breast, buttock or legs, but they have been widely used for decades. Cosmetic injections can cause foreign body granulomas and occasionally severe and life-threatening hypercalcemia. We aimed to systematically analyze the published literature on cosmetic injection-associated hypercalcemia. METHODS: We searched relevant articles on hypercalcemia associated with various cosmetic injections and extracted relevant data on demographics, cosmetic injections used, severity of hypercalcemia, management and outcomes. RESULTS: We identified 23 eligible patients from 20 articles. Mean age was 49.83 ± 14.70 years with a female preponderance (78.26% including transgender females). Silicone was most commonly used, followed by polymethylmethacrylate and paraffin oil (43.48, 30.43, and 8.70% respectively). The buttock was the most common site followed by the breast (69.57% and 39.13% respectively). Hypercalcemia developed at mean duration of 7.96 ± 7.19 years from the initial procedure. Mean ionized calcium at presentation was 2.19 ± 0.61 mmol/L and mean corrected calcium at presentation was 3.43 ± 0.31 mmol/L. 1,25-Dihydroxyvitamin D (1,25(OH)2D or calcitriol) was elevated while 25-hydroxyvitamin D (25(OH)D) and PTH were low in majority of cases. Hypercalcemia was managed conservatively with hydration, corticosteroids and bisphosphonates in majority of cases. Surgery was attempted in 2 cases but was unsuccessful. Renal failure was the most common complication (82.35% cases) and 2 patients died. CONCLUSION: Hypercalcemia from cosmetic injections can be severe and life threatening and can present years after the initial procedure. Cosmetic injection-associated granuloma should be considered a cause of hypercalcemia, especially in middle-aged females presenting with non-PTH-mediated, non-malignant hypercalcemia, which is often associated with elevated calcitriol; however, it should be noted that calcitriol level may be normal as well.

Outcomes following transcatheter transseptal versus transapical mitral valve-in-valve and valve-in-ring procedures.

Introduction: Transcatheter mitral valve-in-valve (ViV) & valve-in-ring (ViR) are relatively novel therapeutic alternatives for patients with degenerated bioprostheses or failed annuloplasty rings whose reoperative risk is too high. The predominant procedural access for both procedures is transapical or transseptal. However, whether there are differences in outcomes of this procedure using transseptal versus transapical access has not yet been defined. Methods: We conducted a systematic review of all published articles from MEDLINE and EMBASE to explore the outcomes of these two procedural approaches. Results:total of 55 studies including 183 patients (154 ViV and 29 ViR) were included. Patients that underwent ViV (101 transapical and 53 transseptal) using the transseptal approach required more iatrogenic atrial septal defect (ASD) closure (19% versus 0.0 %; P < 0.001) and hence had a lower device success rate (68% versus 89%; P = 0.001). However, there was no significant difference between the two groups in procedural success and all-cause mortality at 30 days. Overall severe bleeding complications (major or life threatening) were not different the two groups (3.7% versus 7.9%; P = 0.321). In the ViR group (19 transapical and 10 transseptal), no difference in procedural success, device success or 30-day outcomes were identified between transseptal and transapical groups, although sample size was small. Conclusion: In conclusion, mitral ViV and ViR using the two different procedural approaches appear to confer equal and reasonable 30-day outcomes.

Locally Advanced Thyroglossal Duct Cyst Carcinoma Presenting as a Neck Mass.

Thyroglossal duct cyst carcinoma is rare and occurs in just 1% of cases with thyroglossal duct cysts. It is not always possible to distinguish a thyroglossal cyst harboring malignancy from its benign counterparts unless biopsied, thus posing the dilemma. Currently there is no clear consensus on the optimal management of thyroglossal duct cyst carcinoma. Here we present the case of a 69-year-old female who presented with a midline neck mass and dysphagia and was found to have papillary thyroid cancer in the biopsy specimen of the neck mass. She underwent excision of the mass and the thyroglossal duct cyst along with total thyroidectomy; however, the thyroidectomy specimen showed no malignancy. Her lymph node mapping was negative and she is awaiting radioactive iodine treatment.

Autoimmune hepatitis and eosinophilic granulomatosis with polyangiitis: a rare association.

We describe a case of 40-year-old woman who presented to our hospital with symptoms of non-radiating epigastric pain for 4-5 days associated with nausea and vomiting. Her history was significant for asthma with recurrent exacerbations, polyneuropathy and recurrent sinus infections. Liver function tests revealed cholestasis. Antinuclear antibody and antismooth muscle cell antibody were positive. Liver biopsy revealed active chronic hepatitis with cholestasis. A diagnosis of autoimmune hepatitis was made. All other causes of cholestatic jaundice were ruled out. Her history of recurrent asthma exacerbations, eosinophilia, recurrent sinus infections and positive myeloperoxidase antibodies was suggestive of eosinophilic granulomatosis with polyangiitis. She was found to have combination of autoimmune hepatitis and eosinophilic granulomatosis with polyangiitis, a rarely reported association in the medical literature. She was started on prednisone for her autoimmune hepatitis. On follow-up with her gastroenterologist, her transaminases were trending down and she was symptomatically better.

Paralysis that easily reverses: a case of thyrotoxic periodic paralysis.

Thyrotoxic periodic paralysis is a potentially life-threatening condition associated with recurrent episodes of muscle weakness and hypokalaemia due to hyperthyroidism. Diagnosis is often delayed or misdiagnosed due to its rarity in the western world and subtle features of hyperthyroidism on initial presentation. Here we present the case of a 25-year-old man who presented to the emergency department (ED) with sudden onset weakness of bilateral upper and lower extremities. His labs revealed hypokalaemia with elevated T4 and suppressed thyroid-stimulating hormone and he was diagnosed with thyrotoxic periodic paralysis. He was treated with potassium repletion, atenolol and methimazole with complete reversal of his paralysis within the next day. Unfortunately, he failed to keep the follow-up appointment after discharge, ran out of his methimazole and landed up in the ED again.

A rare case of pylephlebitis after colonic polypectomy.

Pylephlebitis or infective suppurative thrombosis of the portal mesenteric venous system is an uncommon condition that can potentially be deadly if not recognized and treated early. Although most commonly associated with pancreatitis and diverticulitis, any intra-abdominal or pelvic infection occurring in the region drained by the portal venous system can cause this rare entity. We report a case of a 75-year-old woman who developed post polypectomy pylephlebitis following colonoscopy, a condition rarely reported in the literature.

Acute myocardial infarction and antiphospholipid antibody syndrome: a systematic review.

BACKGROUND: Antiphospholipid antibody syndrome (APS) is a disorder associated with both arterial and venous thromboembolic disease, including acute myocardial infarction (AMI). Given that management with anticoagulants is critical and differs from usual AMI care, identification of key discriminators of patients with AMI with APS is important. METHODS: We performed an English-language systematic review of the literature of cases and case series of patients with AMI and APS from inception until 20 March 2016, collecting demographics, investigations, and outcomes. RESULTS: Forty cases of AMI because of APS were identified from 27 articles. Patients were younger than typical AMI patients (41.10±13.61 years) and 45% were women. STelevation myocardial infarction was the presentation in 45% (18/40) of cases. The average platelet count was 130 000±138 912 c/mm in the 10 cases reporting it and partial thromboplastin time was elevated in all four reporting it. Coronary arteries were described as normal or with acute thrombosis in 75%. Three died during hospitalization and six had recurrence of myocardial infarction within 3 months after admission. CONCLUSION: APS should be considered in young patients with AMI, especially if previous unprovoked thromboses, lower platelet counts, high partial thromboplastin times, and normal coronary arteries or coronary thromboses are identified.