Dhrubajyoti Bandyopadhyay

Zika and pregnancy: A comprehensive review.

Zika virus (ZIKV) infection is a well‐nurtured topic for healthcare personnel nowadays. Central nervous system involvement including microcephaly and ocular involvements has already been reported in neonates of affected pregnant ladies. In this article, we have discussed these effects on the newborns of ZIKV‐infected mothers. The proposed pathogenesis, modes of transmission of this infection from mothers to the fetuses, diagnosis of the cases and precaution for the pregnant ladies have also been discussed. We have gathered the recently available data on the risk of ZIKV for expectant mothers from PubMed, https://www.gov.uk/guidance/zika-virus as well as from centers for disease control and prevention websites.

Two Uncommon Causes of Guillain-Barré Syndrome: Hepatitis E and Japanese Encephalitis.

We are presenting two cases of Guillain-Barré syndrome where it is preceded by hepatitis E virus (HEV) and Japanese encephalitis virus (JEV) infection, respectively. Our first case is a forty-three-year-old nondiabetic, nonhypertensive female who was initially diagnosed with acute HEV induced viral hepatitis and subsequently developed acute onset ascending quadriparesis with lower motor neuron type of bilateral facial nerve palsies and respiratory failure. Second patient was a 14-year-old young male who presented with meningoencephalitis with acute onset symmetric flaccid paraparesis. After thorough investigations it was revealed as a case of Japanese encephalitis. Our idea of reporting these two cases is to make ourselves aware about this potential complication of these two common infections.

Selexipag in Pulmonary Arterial Hypertension: Most Updated Evidence From Recent Preclinical and Clinical Studies

Pulmonary arterial hypertension (PAH) is a relatively rare disease that, due to its chronic nature, has always been difficult to treat effectively. Selexipag is an oral prostacyclin (PGI2) agonist that was approved by US Food and Drug Administration (US FDA) in December 2015 for the treatment of PAH. After its success in phase 1 and phase 2 clinical trials regarding the convenient oral twice‐daily dosing and low side‐effect profile, selexipag raised the hope of controlling the disease progression in PAH patients. In the recently completed multicentered phase 3 study (GRIPHON), selexipag has been shown to reduce death and hospitalization due to PAH significantly, an effect that was consistent across different ranges of maintenance dose. In the same study selexipag use was also associated with an increase in 6‐minute walk distance (a measure of symptom severity) from baseline, but no significant improvement in all‐cause mortality could be observed. The results of the ongoing phase 3 studies (TRITON and TRANSIT‐1) are expected to throw some more light on the safety and efficacy of this novel molecule across various treatment scenarios. Hence, our article aims to summarize all the available information from preclinical and clinical studies published to date on the pharmacodynamics, pharmacokinetics, efficacy, safety (in general and in scenarios such as hepatic and renal function impairment), significant drug interactions (with warfarin and antiretroviral drugs), and clinical significance of oral selexipag in patients with PAH.

Cardiovascular Outcomes of PCSK9 Inhibitors: With Special Emphasis on Its Effect beyond LDL-Cholesterol Lowering

PCSK9 inhibitors, monoclonal antibodies, are novel antihypercholesterolemic drugs. FDA first approved them in July 2015. PCSK9 protein (692-amino acids) was discovered in 2003. It plays a major role in LDL receptor degradation and is a prominent modulator in low-density lipoprotein cholesterol (LDL-C) metabolism. PCSK9 inhibitors are monoclonal antibodies that target PCSK9 protein in liver and inhibiting this protein leads to drastically lowering harmful LDL-C level in the bloodstream. Despite widespread use of the statin, not all the high-risk patients were able to achieve targeted level of LDL-C. Using PCSK9 inhibitors could lead to a substantial decrement in LDL-C plasma level ranging from 50% to 70%, either as a monotherapy or on top of statins. A large number of trials have shown robust reduction of LDL-C plasma level with the use of PCSK9 inhibitors as a monotherapy or in combination with statins in familial and nonfamilial forms of hypercholesterolemia. Moreover, PCSK9 inhibitors do not appear to increase the risk of hepatic and muscle-related side effects. PCSK9 inhibitors proved to be a highly potent and promising antihypercholesterolemic drug by decreasing LDL-R lysosomal degradation by PCSK9 protein. Statin drugs are known to have some pleiotropic effects. In this article, we are also focusing on the effects of PCSK9 inhibitor beyond LDL-C reduction like endothelial inflammation, atherosclerosis, its safety in patients with diabetes, obesity, and chronic kidney disease, and its influence on neurocognition and stroke.

Cronkhite-Canada Syndrome: A Rare Cause of Chronic Diarrhoea in a Young Man

A young Indian man presented with nine-month history of chronic diarrhea, occasionally mixed with blood and intermittent colicky abdominal pain. He also complained of generalized body swelling for the last three months. On examination, he had diffuse hyperpigmentation of the skin and dystrophic nail changes. Upper and lower gastrointestinal endoscopy revealed multiple sessile polyps in the stomach, small bowel, and colon and rectum. Biopsy of polyps showed adenomatous changes with stromal edema and dilated glands. Cronkhite-Canada syndrome (CCS) was diagnosed and treated with glucocorticoids and enteral nutritional supplementation. There was an associated small intestinal bacterial overgrowth (SIBO) and stool was positive for clostridium difficile toxin. After 12 weeks of treatment, the patient achieved remission. Close correlation with clinical findings, including pertinent ectodermal abnormalities, endoscopic studies, and careful examination of biopsies will ensure a timely and correct diagnosis of CCS.

Comparison of treatment options for depression in heart failure: A network meta-analysis

BACKGROUND Depression independently predicts poor outcomes in heart failure (HF) patients, including increased mortality, morbidity and 30-day re-hospitalization. In this network meta-analysis, we compared different interventions designed to treat depression in HF. MATERIALS AND METHODS Electronic searches were conducted using Ovid MEDLINE, EMBASE, CINAHL, Web of Science, and PsycINFO up to November 2016. Included randomized clinical trials (RCTs) compared interventions (Exercise therapy (ET), cognitive behavioral therapy (CBT) or antidepressant (AD) medications) for depression in heart failure patients. The primary outcome was change in depressive symptoms based on validated measures of depression. Network meta-analysis based on random effects model estimating standardized mean difference (SMD) with 95% confidence interval (CI), compared the effects of the 3 classes of interventions with respect to usual care or placebo control conditions. RESULTS A total of 21 RCTs (including 4563 HF patients) reporting the effects of treating depression in HF patients were included in the analysis. In comparison to placebo or usual standard of care, ET (SMD -0.38; 95% CI -0.54 to -0.22) and CBT (SMD -0.29; 95% CI -0.58 to -0.01) were associated with reduction in depressive symptoms whereas AD (SMD -0.16; 95% CI -0.44 to 0.11) was less effective. CONCLUSIONS This meta-analysis is suggestive of therapeutic benefit of ET and CBT in comparison to usual standard of care in treating depression in HF patients. However, comparison among the three interventions was not conclusive. Future randomized clinical trials are warranted to compare the therapeutic effects of ET, CBT and AD in such patients.

Safety and Efficacy of Extremely Low LDL-Cholesterol Levels and Its Prospects in Hyperlipidemia Management

The risk of cardiovascular disease has been reported to have a linear relationship with LDL levels. Additionally, the currently recommended LDL target goal of 70 mg/dl does not diminish the CV risk entirely leaving behind some residual risk. Previous attempts to maximally lower the LDL levels with statin monotherapy have met dejection due to the increased side effects associated with the treatment. Nevertheless, with the new advancements in clinical medicine, it has now become possible to bring down the LDL levels to as low as 15 mg/dl using PCSK9 monoclonal antibodies alone or in combination with statins. The development of inclisiran, siRNA silencer targeting PCSK9 gene, is a one step forward in these endeavors. Moreover, various studies aiming to lower the CV risk and mortality by lowering LDL levels have demonstrated encouraging results. The current challenge is to explore this arena to redefine the target LDL levels, if required, to avoid any suboptimal treatment. After thorough literature search in the PubMed, Embase, Scopus, and Google Scholar, we present this article to provide a brief overview of the safety and efficacy of lowering LDL below the current goal.

Role of quantitative myocardial-iron in hemodialysis-dependent end-stage renal disease subjects

Article history: Received 20 November 2017 Accepted 21 November 2017 function in hemodialysis-dependent ESRD patients. Their study also demonstrated that regardless of clinical rectification of SF and liver iron level, hemodialysis-dependent ESRDpatients havemyocardial iron inadequacy. Myocardial-iron was found to be an independent and critical indicator of LV dysfunction, as iron deficiency is associated with myocyte

SGLT-2 Inhibitors and Peripheral Artery Disease: A Statistical Hoax or Reality?

Inhibitors of sodium-glucose cotransporters type-2 are the most recent addition to the armamentarium of oral antidiabetic agents. This class of drugs has shown promising results in glycemic control and most importantly to reduce cardiovascular disease (CVD) mortality risk. Despite the encouraging data, there is concern regarding their potential for causing or worsening peripheral artery disease (PAD), which may increase the risk of lower extremity amputations. Following the publication of results of CANVAS and CANVAS-R trials, which revealed that leg and mid-foot amputations occurred about twice as often in patients treated with canagliflozin compared to placebo, the Food and Drug Administration (FDA) in the United States issued a black box warning of leg and foot amputations associated with canagliflozin use. In this article, our main aim is to review the available evidence in preclinical and clinical studies regarding SGLT-2 inhibitors and PAD events, the possible mechanisms related to increased risk of amputation, to evaluate whether it is a class effect or individual drug effect, and most importantly, implications for their continued use as antidiabetic agents. It also raises the issue of including PAD events among the end-points when assessing future antihyperglycemic agents. Thus, we also tried to analyze whether outcomes of SGLT2 inhibitors trials mostly focused on stroke, myocardial infarction, heart failure, and peripheral vascular disease-related outcomes remained underrated.

Significance of pulmonary hypertension in hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is the most prevalent hereditary cardiac disease characterized by the presence of left ventricular and/or septal hypertrophy in the absence of other underlying cardiac disorders. Patients of HCM have a broad range of clinical presentation from being asymptomatic to severely ill condition requires hospitalization and urgent management. Broadly, HCM is classified in two variants: obstructive and nonobstructive. The mainstay of diagnosis is through echocardiography. As HCM chiefly affect the left heart, pulmonary hypertension (PH) is an expected complication of this disease. Though the existence of PH in HCM is known for a long time, its clinical significance, underlying mechanism, and prognostic impact in HCM have been revealed by few recent studies. Specifically, studies have shown increased events of thromboembolism, atrial fibrillation, and heart failure in patients with HCM and PH. These studies elucidated the underlying mechanism of PH in HCM--a rise of pressure in the precapillary and postcapillary pulmonary vasculature. In addition to left ventricular involvement, studies have shown right ventricular involvement and the association of left and right ventricular dysfunction in these patients. Further, it has been shown that surgical intervention to reduce septal thickness improves survival in pharmacotherapy nonresponders and the presence of PH does not increase mortality in these patients. We present a comprehensive review exploring the prevalence, underlying mechanisms, and impact of PH on HCM.