Disseminated Histoplasmosis in an Immunocompetent Host presenting as Pyrexia of unknown origin (PUO)

Histoplasmosis is a progressive granulomatous disease caused by intracellular dimorphic  fungus Histoplasma capsulatum. The fungus present in the soil infects through inhalational route and can manifest as any of the three main types – Acute primary pulmonary type, chronic cavitatory or progressive  disseminated. In Disseminated histopasmosis (DH) the fungus is detected from more than one location in the body. This is the rarest form of all three types and is usually present in immunocompromised individuals. We report the case of a 27-year-old immunocompetent patient who presented with prolonged fever, weight loss, pain abdomen and skin lesions. She was found to have hepatosplenomegaly and pancytopenia. Biopsy from skin lesions and bone marrow stained positive for Histoplasma capsulatum sp. She was treated with amphotericin B for 28 days, followed by oral itraconazole for 6 months, leading to complete resolution of the disease. This case is interesting due to the presence of disseminated histoplasmosis in an immunocompetent host with prominent skin lesions

Can neck irradiation be an alternative to neck dissection in early stage carcinoma oral tongue operated for primary alone? Experience from a single institute

Purpose: To study pattern of failure, locoregional control rates (LCR) and disease free survival (DFS) in post-operative patients of carcinoma oral tongue, and to study the impact of nodal dissection on DFS in stage I and II patients.Methods: 102 patients of carcinoma oral tongue treated between January 2009 and December 2013 were analyzed. All patients were operated for primary disease, but neck dissection was done in 78 (76.5%) patients only. However, radiation to primary site along with neck region was received by all patients. Pattern of failure, LCR and DFS were estimated.Results: At median follow up of 12 months, 10.8% patients failed locally, 10.8% in nodal region, 2.9% both at local and nodal site, and 5.9% patients failed distally. 2 year LCR and DFS was 71.2%, 90.9%, 79.5%, 0% and 55.2%, 64.4%, 57.8%, 0% in stage I, II, III, IV respectively. 2 year DFS in stage I patients, who underwent nodal dissection and post-operative radiation (14 patients) was 64.3% and in whom only neck irradiation was done (15 patients), it was 45.8%, however difference was not significant (p = 0.5). But in stage II patients, 33 patients who underwent nodal dissection and post-operative radiation, 2 year DFS was 85.4% and it was 21.4% in 7 patients who underwent neck radiation only, and difference showed trend towards significance (p = 0.05). 2 or more positive lymph nodes post dissection was the only poor prognostic factor that correlated with DFS (p = 0.02)Conclusion: While in stage I, neck irradiation alone can be a possible alternative to neck dissection and post-operative radiation; for stage II, neck dissection is mandatory

ESSENS dyslipidemia: A placebo-controlled, randomized study of a nutritional supplement containing red yeast rice in subjects with newly diagnosed dyslipidemia

AbstractObjectiveEvidence suggests prolonged exposure to lower levels of low-density lipoprotein cholesterol (LDL-C), starting at a younger age, substantially lowers cardiovascular (CV) risk. Accordingly, the CV pandemic affecting younger population in low- to low-middle-income countries, where statin usage is poor even in secondary prevention, may benefit from lipid-lowering nutritional products, as nutritional intervention is generally preferred in these cultures. However, the safety and efficacy of such preparations have not been systematically tested.MethodsIn this multicenter, double-blind study, 191 statin-free subjects with newly-diagnosed hyperlipidemia (LDL-C >120 mg/dL, 3.11 mmol/L) and no evidence of CV disease were randomized to one capsule of a proprietary bioactive phytonutrient formulation containing red yeast rice, grape-seed, niacinamide, and folic acid (RYR-NS) or matched placebo twice daily, along with lifestyle modification, for 12 wk.ResultsMean baseline LDL-C levels were 148.5 ± 24.0 mg/dL (3.85 ± 0.62 mmol/L) and 148.6 ± 21.9 mg/dL (3.85 ± 0.57 mmol/L) in the RYR-NS and placebo groups respectively. Compared with placebo, RYR-NS resulted in a significant reduction in LDL-C (−29.4% versus −3.5%, P < 0.0001) and non–high-density lipoprotein cholesterol (non-HDL-C; −29.8% versus −10.3%, P < 0.0001) at 12 wk. With RYR-NS, 43.4% individuals attained desirable LDL-C levels and 55.4% desirable non-HDL-C levels by week 12, compared to only 0% and 1.1%, respectively, at baseline. No safety issues were observed.ConclusionThis study demonstrates the efficacy and safety of RYR-NS in lowering LDL-C and non-HDL-C after 12 wk, with magnitude of LDL-C reduction being comparable to that seen with moderate-intensity statin therapy. Further long-term studies are required to determine the impact of RYR-NS on treatment adherence and clinical outcomes

Optimization methods for electric power systems: An overview

Power systems optimization problems are very difficult to solve because power systems are very large, complex, geographically widely distributed and are influenced by many unexpected events. It is therefore necessary to employ most efficient optimization methods to take full advantages in simplifying the formulation and implementation of the problem. This article presents an overview of important mathematical optimization and artificial intelligence (AI) techniques used in power optimization problems. Applications of hybrid AI techniques have also been discussed in this article

Exploring the potential of metallic nanoparticles within synthetic biology

The fields of metallic nanoparticle study and synthetic biology have a great deal to offer one another. Metallic nanoparticles as a class of material have many useful properties. Their small size allows for more points of contact than would be the case with a similar bulk compound, making nanoparticles excellent candidates for catalysts or for when increased levels of binding are required. Some nanoparticles have unique optical qualities, making them well suited as sensors, while others display para-magnetism, useful in medical imaging, especially by magnetic resonance imaging (MRI). Many of these metallic nanoparticles could be used in creating tools for synthetic biology, and conversely the use of synthetic biology could itself be utilised to create nanoparticle tools. Examples given here include the potential use of quantum dots (QDs) and gold nanoparticles as sensing mechanisms in synthetic biology, and the use of synthetic biology to create nanoparticle-sensing devices based on current methods of detecting metals and metalloids such as arsenate. There are a number of organisms which are able to produce a range of metallic nanoparticles naturally, such as species of the fungus Phoma which produces anti-microbial silver nanoparticles. The biological synthesis of nanoparticles may have many advantages over their more traditional industrial synthesis. If the proteins involved in biological nanoparticle synthesis can be put into a suitable bacterial chassis then they might be manipulated and the pathways engineered in order to produce more valuable nanoparticles

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

Background Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH,non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2–F3, or F1 with at least oneaccompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpointsfor the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2–F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1–F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2–F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1–F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Disseminated histoplasmosis in India presenting as addisonian crisis with epiglottis involvement

Histoplasmosis is caused by Histoplasma capsulatum. Like most fungal infections, histoplasmosis is common in immunocompromised patients. In immunocompetent patient, infection is generally asymptomatic and rarely turns into a disseminated form. Addisonian crisis as presentation of disseminated form has been reported in present. Here, we report a case of disseminated histoplasmosis leading to life threatening adrenal crisis and hypercalcemia in an elderly immunocompetent Indian patient. Appropriate diagnosis and anti fungal and steroid treatment lead to dramatic improvement in patient. Histoplasmosis should be considered in a immunocompetent hosts with adrenal involvement

Relationship between different cardiovascular risk scores and measures of subclinical atherosclerosis in an Indian population

Background: Relative accuracy of the various currently available cardiovascular (CV) risk assessment algorithms in Indian patients is not known. Methods: This study included 194 consecutive patients (mean age 49.6 ± 10.3 years, 84.5% males) attending a CV disease prevention clinic at a tertiary center in north India. Four risk assessment models [Framingham Risk score (RiskFRS), American College of Cardiology/American Heart Association pooled cohort equations (RiskACC/AHA), the 3rd iteration of Joint British Societies' risk calculator (RiskJBS) and the World Health Organization/International Society of Hypertension risk prediction charts (RiskWHO)] were applied. The estimated risk scores were correlated with carotid intima-media thickness (CIMT) and coronary calcium score (CCS) using nonparametric statistics (Chi-square test, Kruskal–Wallis test and Spearman rank correlation). Results: Overall, RiskACC/AHA and RiskWHO significantly underestimated CV risk as compared to RiskJBS and RiskFRS, with RiskJBS being the least likely to underestimate the risk (patients with coronary artery disease who were found to have ≥20% CV risk- 21.4% with RiskACC/AHA, 17.9% with RiskWHO, 41.4% with RiskFRS, and 58.6% with RiskJBS). Further, only RiskJBS and RiskFRS, but not RiskACC/AHA and RiskWHO, demonstrated consistent relationship with CIMT and CCS (Spearman rho 0.45 and 0.46 for RiskJBS and 0.39 and 0.36 for RiskFRS for CIMT and CCS respectively, all p values < 0.001). Conclusions: The present study shows that in Indian subjects RiskJBS appears to provide the most accurate estimation of CV risk. It least underestimates the risk and has the best correlation with CIMT and CCS. However, large-scale prospective studies are needed to confirm these findings

Comparative accuracy of different risk scores in assessing cardiovascular risk in Indians: A study in patients with first myocardial infarction

Background: Although a number of risk assessment models are available for estimating 10-year risk of cardiovascular (CV) events in patients requiring primary prevention of CV disease, the predictive accuracy of the contemporary risk models has not been adequately evaluated in Indians. Methods: 149 patients [mean age 59.4 ± 10.6 years; 123 (82.6%) males] without prior CV disease and presenting with acute myocardial infarction (MI) were included. The four clinically most relevant risk assessment models [Framingham Risk score (RiskFRS), World Health Organization risk prediction charts (RiskWHO), American College of Cardiology/American Heart Association pooled cohort equations (RiskACC/AHA) and the 3rd Joint British Societies' risk calculator (RiskJBS)] were applied to estimate what would have been their predicted 10-year risk of CV events if they had presented just prior to suffering the acute MI. Results: RiskWHO provided the lowest risk estimates with 86.6% patients estimated to be having <20% 10-year risk. In comparison, RiskFRS and RiskACC/AHA returned higher risk estimates (61.7% and 69.8% with risk <20%, respectively; p values <0.001 for comparison with RiskWHO). However, the RiskJBS identified the highest proportion of the patients as being at high-risk (only 44.1% at <20% risk, p values 0 < 0.01 for comparison with all the other 3 risk scores). Conclusions: This is the first study to show that in Indian patients presenting with acute MI, RiskJBS is likely to identify the largest proportion of the patients as at ‘high-risk’ as compared to RiskWHO, RiskFRS and RiskACC/AHA. However, large-scale prospective studies are needed to confirm these findings