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Purpose: Mutations in human telomerase reverse transcriptase (TERT) are associated with increased telomerase activity in cutaneous melanomas. Conjunctival squamous cell carcinoma, also referred to as ocular surface squamous cell carcinoma, is cancer on the surface of the eye. Recent studies have identified UV signature mutations in TERT promoters in ocular melanoma and ocular surface squamous neoplasia. However, its immunohistochemical status has not been reported in ocular surface squamous cell carcinoma. This study aimed to explore the immunohistochemical and mutational status of TERT in ocular surface SCC. Methods: The immunohistochemical expression of TERT and mutational status of TERT promoter was evaluated in 19 ocular surface squamous cell carcinoma cases. Conjunctival melanoma tissue was used as a positive control. Results: The cytoplasmic overexpression of TERT was detected in 11/19 (57%), and TERT promoter mutations were identified in 6/19 (31%) of ocular surface squamous cell carcinoma. Out of these, 66% had a C228T mutation, and 33% had a C250T mutation. The TERT expression was found to be associated with a high (?T3) AJCC category (P = 0.023), and TERT immunoexpression was significantly correlated with reduced disease?free survival (P = 0.024, log?rank analysis) in ocular surface squamous cell carcinoma patients. Conclusion: The present study demonstrates that TERT promoter mutations with UV signatures are frequent in ocular surface squamous cell carcinoma. The increased expression of TERT could be of biological significance in aggressive ocular surface squamous cell carcinoma.
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Angiotensin II receptor blockers (ARBs) are the antihypertensive drugs associated with side effects, majorly such ascough and electrolyte disturbance. Azilsartan is a newly marketed ARB in India, not even having a well-establishedadverse effect profile. Here, we present a 58-year-old female who was admitted to the emergency department showingsigns and symptoms of delirium, disorientation, and vomiting for 4 days. The patient is known to have coronaryartery disease so that she underwent coronary artery bypass grafting. She was recently started on azilsartan for herchronic hypertension, along with other drugs. The presence of electrolyte imbalance in laboratory reports and currentsymptoms suggested azilsartan-induced encephalopathy. The patient was recovered after discontinuation of azilsartan.This case enlightens the clinical characteristics, possible mechanism, and treatment strategy opted to correct thecondition.
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Heart failure (HF) is responsible for 1.8 million admissions annually in India with an additional burden of mortalityand re-hospitalizations. Positive inotropes with multiple mechanisms, such as dopamine and levosimendan, are beingused for more than three decades to treat the patients of acute HF with reduced ejection fraction (HFrEF). This studycompared the outcomes of the dopamine and the levosimendan up to 180 days. We have selected the patients fromManipal Heart Failure Registry who were diagnosed to have HFrEF (left ventricular EF less than 50%) and wereinitiated on either dopamine or levosimendan in first 6 hours of hospitalization. The study included a total of 187patients; among them, 120 patients were analyzed in the dopamine group, and 67 patients in the levosimendan group.Dopamine was initiated as intravenous infusion with the dose of 2.5 microgram/kilogram/minute (mcg/kg/minute)and up-titrated up to 10 mcg/kg/minute. Levosimendan was also administered intravenously with a dose of 0.1 mcg/kg/minute and up-titrated up to 0.4 mcg/kg/minute. The primary outcomes include a composite of all-cause mortalityand re-hospitalization at 30-days and 180-days follow-ups. The in-hospital mortality, 30-days mortality and 180-daysmortality, and composite outcomes were noted higher in levosimendan treated patients even after matched demographicparameters (age and gender) and comparable comorbidities and risk factors, i.e., smoking, alcohol consumption,hypertension, diabetes mellitus, and atrial fibrillation. However, reduced EF, raised serum creatinine, procalcitonin,and N-terminal pro b-type natriuretic peptide levels and high use of digoxin were noticed in levosimendan groupduring the initial period of index-hospitalization and these can be considered as confounding factors for future studies.
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The evaluation of coronary artery disease (CAD) concerning the metabolic status and body mass index (BMI) is poorlystudied. This study was designed to observe the relationship between insulin resistance (IR) and the severity of CADon the basis of the metabolic and phenotypic status in stable-angina patients. A cross-sectional study was conductedon 532 patients with stable angina and coronary angiogram was done to diagnose the CAD for all. Determination ofmetabolic obesity was done using the National Cholesterol Education Program-Adult Treatment Panel III criteria.Phenotypic obesity was defined as BMI ≥ 25 kg/m2. Homeostasis model assessment IR in correlation with the severityof CAD was measured using SYNTAX (TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for theTreatment of Narrowed Arteries) Score. The average age of the patients was 57.58 ± 10.40 years, and 69.4% weremales. Out of 532 subjects, 51.3% were hypertensive, 14.5% were smokers, 29.1% consumed alcohol, 49.3% weremetabolically obese, and 50% were phenotypically obese. Increase in IR increased the risk of severity of CAD inmetabolically obese subjects (OR = 2.51, p = 0.048). In the phenotypically obese group, the relationship between IRand the severity of CAD was not statistically significant (OR = −2.19, p = 0.08). The study concludes that the increasedIR increases the risk of severity of CAD in metabolically obese subjects.