Niranjan Tachamo

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.

Takotsubo cardiomyopathy associated with epinephrine use: A systematic review and meta-analysis

BACKGROUND Takotsubo cardiomyopathy is a syndrome of transient cardiac dysfunction that is frequently associated with sudden emotional or physical stress. Epinephrine use has been implicated in precipitating Takotsubo cardiomyopathy in multiple case reports and case series. We sought to systematically review the current English literature on this association. METHODS We searched relevant articles on Takotsubo cardiomyopathy associated with epinephrine administration and extracted data on demographic characteristics, clinical features, investigations and clinical outcomes. RESULTS We identified total of 41 cases from 36 articles. The mean age of presentation was (47.07±15.73years) with strong female preponderance (83%, P=0.0001). The most common symptom at presentation was chest pain (82%). Mean peak troponin I level was (7.12±11.22ng/ml). The most common EKG abnormality was ST elevation, seen in 40% of patients. The most common finding on echocardiography was apical hypokinesis, seen in 48.78% cases. Patients younger than 45 were less likely to have apical cardiomyopathy (n=5/20, 25%) compared to patients with age >45 (n=14/21, 66%, p value 0.001, OR 0.17). The most common route of administration of epinephrine was intravenous (65.85%). All patients except one survived with complete recovery of systolic function reported in most cases within an average of 14.7days. CONCLUSION Exposure to epinephrine in clinical practice can trigger Takotsubo cardiomyopathy, which is rapidly reversible with good prognosis in most cases. This review further supports the notion that both exogenous and endogenous catecholamines are associated with the pathogenesis of Takotsubo cardiomyopathy.

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/mm3 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.

Omalizumab-associated eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)

Omalizumab is a humanized anti-IgE antibody that has been recommended for the management of persistent asthma associated with high serum IgE levels.1 Several cases have been reported in the literature that suggest its association with eosinophilic granulomatosis with polyangiitis (EGPA), which was previously called Churg-Strauss syndrome (CSS). EGPA is a rare necrotizing systemic vasculitis of medium and small blood vessels characterized by asthma, eosinophilia, and eosinophilic or granulomatous tissue inflammation.2 The pathogenesis of this association is poorly understood. Two mechanisms have been hypothesized. First is that omalizumab plays a direct casual effect in the development of EGPA. Second, reduction of steroid use, achieved by omalizumab treatment, could reveal EGPA that beforehand manifested itself only as asthma (forme fruste of CSS).3 The aim of the present study was to expand the understanding of this association by systematic review of all the published cases in the current literature. A systematic electronic search of MEDLINE (via PubMed), EMBASE, SCOPUS, and the Cochrane Library was performed for case reports, case series, and systematic reviews on EGPA associated with omalizumab use from inception till September 28, 2016. Inclusion criteria were age older than 18 years, use of omalizumab before the diagnosis of CSS, and diagnosis of EGPA based on the American College of Rheumatology diagnostic criteria.2 We identified 8 patients with EGPA associated with omalizumab use from 8 articles (Fig 1). The demographic variables, investigations, treatment, and outcomes were abstracted (eTable 1). The mean (SD) age at presentation was 53.5 (17.5) years with a strong male preponderance (6 men [75%]). The mean (SD) number of doses of omalizumab used before diagnosis of CSS was 21.5 (28) (range, 3e81). The mean (SD) time from omalizumab initiation to disease diagnosis was 73 (125) weeks (range, 4e352 weeks). Steroids were tapered in 3 (43%) of 7 patients before disease diagnosis (regarding denominator variability, see eTable 1). Antineutrophilic cytoplasmic antibody (ANCA) status was mentioned in only 5 patients, and all had a negative ANCA status. Omalizumab treatment was continued in of 1 (16.5%) of 6 patients after diagnosis, discontinued in 3 (50%) of 6 patients, and discontinued but restarted later in 2 (33%) of 6 patients because of worsening asthma symptoms. CSS was treated with systemic steroids in in 8 (100%) of 8 patients, cyclophosphamide plus steroids in 3 (37.5%) of 8 patients, and azathioprine plus steroids in 1 (12.5%) of 8 patients. All 8 patients achieved remission with treatment. All patients survived except one, who died because of advanced brain tumor.

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.

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.

Popliteal arterial thrombosis in nephrotic syndrome: a case report

ABSTRACT Thrombosis is a frequent cause of morbidity and mortality in patients with nephrotic syndrome (NS). Though venous thromboses are common in NS, arterial thromboses are relatively rare. Commonly involved arteries include coronary, iliac, femoral, renal, cerebral, pulmonary, mesenteric, and axillary arteries, and the aorta. Arterial thromboses are associated with poor prognosis; treatment options are limited and patients may not always be amenable to treatment. We present the case of a 39-year-old female with NS who presented with thigh pain and was found to have sub-acute popliteal artery thrombosis.

Strongyloidiasis in the immunocompetent: an overlooked infection

Strongyloidiasis is a parasitic infestation caused by Strongyloides stercoralis. Most cases are asymptomatic; however, symptomatic patients may present with a wide range of non-specific cutaneous, pulmonary, or gastrointestinal symptoms posing a diagnostic dilemma and delay in diagnosis. We report a case of a 58-year-old female who presented with months of generalized pruritus and abdominal discomfort along with persistent eosinophilia due to strongyloidiasis, which completely resolved with treatment.

Low back pain after a dental procedure: a case of Streptococcus viridans vertebral osteomyelitis

Vertebral osteomyelitis due to Streptococcus viridans following a dental procedure is a rarely reported phenomenon. We discuss the case of a 67-year-old immunocompetent woman who presented with low back pain of 3 weeks duration associated with subjective fever and chills. On admission, the MRI of the lumbar spine showed L5-S1 vertebral osteomyelitis with associated paravertebral and epidural abscesses. Subsequently, detailed history was retaken and the patient reported having had a maxillary tooth extraction followed by a dental implant 2 months prior to the onset of her symptoms. Blood and abscess fluid cultures grew S. viridans. Transthoracic echocardiogram showed no evidence of endocarditis. The patient was started on intravenous ceftriaxone but her treatment course was complicated by agranulocytosis requiring a switch to vancomycin. She required a total of 9 weeks of intravenous antibiotics for complete clinical cure.

OUTCOMES FOLLOWING TRANSCATHETER TRANSSEPTAL VERSUS TRANSAPICAL MITRAL VALVE-IN-VALVE AND VALVE-IN-RING PROCEDURES

Introduction Transcatheter mitral valve-in-valve (ViV) and valve-inring (ViR) procedures are relatively novel therapeutic alternatives for patients with degenerated bioprostheses or failed annuloplasty rings whose risk of surgical reoperation is deemed to be too high.1,2 While transapical access was the first described approach,3 this procedure requires a thoracotomy with its attendant risks. As implantable valve technology has evolved, so has the interest in implantation through venous access, performed by accessing the mitral orifice through a puncture in the atrial septum (transseptal) approach. Data from the United States Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy (TVT) registry showed that transseptal placement increased from 14.6 % to 28.2 % in 2015.1 This trend bears some resemblance to procedural trends in transcatheter aortic valve replacement, in which initial experience was with transthoracic deployment approaches, however was soon supplanted by transfemoral placement as reduction in sheath size allowed for placement via peripheral arterial access.1,4 Benefits of transapical placement include better control over the implant position and possibly less device-related complications, while transseptal placement avoids a thoracotomy but involves puncture of the atrial septum and hence possibility of the need to later repair an iatrogenic atrial septal defect (ASD).5 Furthermore, registry data from the VIVID (Valve-in-Valve-International-Data) showed that patients having transseptal procedures had