Proton pump inhibitor: a risk factor for spontaneous bacterial peritonitis in Indian cirrhotics decompensated with ascites

Background: Spontaneous bacterial peritonitis (SBP) is common complication of cirrhosis caused by bacterial translocation. Bacterial colonization and overgrowth may occur in GI tract on suppression of gastric acid secretion. Beta-blockers have been postulated to reduce intestinal permeability. There is no significant Indian study to evaluate association of PPI with SBP in cirrhotic ascites. We aimed to assess the effect of PPI in cirrhotic patients decompensated with ascites.Methods: A retrospective case control study (January 2016 to April 2018), evaluated subjects with cirrhosis and ascites. Two study groups of cirrhotic subjects with and without SBP were formed. In each of the two study groups, 143 subjects, were enrolled by matching for age, year of admission, Child-Pugh-Turcotte (CTP) class after considering the inclusion and exclusion criteria. PPI use and various other correlates were compared in both study groups. SPSS ver 24.0 was used for statistical analysis.Results: About 69.23% subjects were using PPI prior to admission in SBP group, which was significant compared to only 31.47% in cirrhotics without SBP (p 0.003). On multivariate analysis PPI use was an independent risk factor for SBP (OR 2.24, 95% CI: 1.01-4.24; p value 0.033) and beta blocker use was protective (OR 0.58; 95% CI: 0.4-0.8; p 0.001).Conclusions: PPI use doubles the risk of development of SBP in cirrhotics decompensated with ascites. In contrast, Beta blockers use significantly lowers the risk of SBP

Association of non-alcoholic fatty liver disease with chronic kidney disease in type 2 diabetes mellitus

Background: Non-alcoholic fatty liver disease (NAFLD) is closely associated with metabolic syndrome. NAFLD is considered a disease of no consequence. Data on the effect of NAFLD on renal dysfunction in T2DM is sparse. Author aimed to study the association of NAFLD with CKD in Indian T2DM subjects.Methods: In an observational cross-sectional study at Mahatma Gandhi Medical College and Hospital, Jaipur, Rajasthan, India from February 2017 to March 2018. 197 out of 268 randomly selected type 2 diabetes mellitus (T2DM) subjects were selected for the study after considering the inclusion and exclusion criteria. CKD was defined as estimated GFR <60 ml/min per 1.73 m2 and/or albumin to creatinine ratio ≥30 mg/g. NAFLD was diagnosed using ultrasonography. The association between NAFLD and CKD was analyzed using SPSS (version 24.0).Results: On ultrasonography 133 (67.5%) T2DM subjects had NAFLD. Diabetic with NAFLD (133, 67.51%) had significantly more history of hypertension (p 0.006), higher systolic (p 0.03) and diastolic BP (p 0.009), higher BMI (p <0.001), waist circumference (p <0.001), fasting glucose (p 0.03), triglyceride (p<0.001) and higher urinary albumin-to-creatinine ratio (p <0.001). Diabetics with CKD (61, 30.96%), were older (p 0.03), hypertensive (p <0.001) and had higher fasting glucose (p 0.003). Subjects with CKD had a higher prevalence of underlying NAFLD (78.69% vs 62.5%, p 0.03) as compared with diabetics with no CKD. T2DM subjects with NAFLD had more than two times (OR 2.88 (1.1-6.78), p 0.03) the risk of developing CKD after multivariate analysis as compared to subjects without NAFLD.Conclusions: NAFLD is a risk factor for development of CKD in patients of type 2 diabetes mellitus. Screening and early preventive measures may go long way in reducing morbidity

Carotid Intima Media Thickness as a Marker of Atherosclerosis in Ankylosing Spondylitis

Aim. Increased cardiovascular morbidity and mortality have been observed in ankylosing spondylitis because of accelerated atherosclerosis. We measured carotid intima media thickness (CIMT) as a surrogate marker of atherosclerosis in this study. Methods. In this study 37 cases of AS and the same number of matched individuals were recruited. CIMT measurements were done using B-mode ultrasound. Disease activity was assessed using Bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis functional index (BASFI), and Bath ankylosing spondylitis metrological index (BASMI) scores and C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels. Results. Mean age of the study groups was 29.43 ± 9.00 years. Average disease duration was 65.62 ± 54.92 months. Twenty-eight (75.68%) of cases were HLA B-27 positive. A significantly increased CIMT was observed in cases as compared to control group (0.62 ± 0.12 versus 0.54 ± 0.04; P<0.001). CIMT in the cases group positively correlated with age (r=0.357; P<0.05), duration of disease (r=0.549; P<0.01), and BASMI (r=0.337; P<0.05) and negatively correlated with ESR (r=−0.295; P<0.05). Conclusions. Patients of AS had a higher CIMT than those of the control group. CIMT correlated with disease chronicity

Quantum Dot Based Nano-Biosensors for Detection of Circulating Cell Free miRNAs in Lung Carcinogenesis: From Biology to Clinical Translation

Lung cancer is the most frequently occurring malignancy and the leading cause of cancer-related death for men in our country. The only recommended screening method is clinic based low-dose computed tomography (also called a low-dose CT scan, or LDCT). However, the effect of LDCT on overall mortality observed in lung cancer patients is not statistically significant. Over-diagnosis, excessive cost, risks associated with radiation exposure, false positive results and delay in the commencement of the treatment procedure questions the use of LDCT as a reliable technique for population-based screening. Therefore, identification of minimal-invasive biomarkers able to detect malignancies at an early stage might be useful to reduce the disease burden. Circulating nucleic acids are emerging as important source of information for several chronic pathologies including lung cancer. Of these, circulating cell free miRNAs are reported to be closely associated with the clinical outcome of lung cancer patients. Smaller size, sequence homology between species, low concentration and stability are some of the major challenges involved in characterization and specific detection of miRNAs. To circumvent these problems, synthesis of a quantum dot based nano-biosensor might assist in sensitive, specific and cost-effective detection of differentially regulated miRNAs. The wide excitation and narrow emission spectra of these nanoparticles result in excellent fluorescent quantum yields with a broader color spectrum which make them ideal bio-entities for fluorescence resonance energy transfer (FRET) based detection for sequential or simultaneous study of multiple targets. In addition, photo-resistance and higher stability of these nanoparticles allows extensive exposure and offer state-of-the art sensitivity for miRNA targeting. A major obstacle for integrating QDs into clinical application is the QD-associated toxicity. However, the use of non-toxic shells along with surface modification not only overcomes the toxicity issues, but also increases the ability of QDs to quickly detect circulating cell free miRNAs in a non-invasive mode. The present review illustrates the importance of circulating miRNAs in lung cancer diagnosis and highlights the translational prospects of developing QD-based nano-biosensor for rapid early disease detection

Splenectomy and proximal lieno-renal shunt in a factor five deficient patient with extra-hepatic portal vein obstruction

BACKGROUND: The clinico-surgical implication and successful management of a rare case of factor five (V) deficiency with portal hypertension and hypersplenism due to idiopathic extra-hepatic portal venous obstruction is presented. CASE PRESENTATION: A 16-year old boy had gastro-esophageal variceal bleeding, splenomegaly and hypersplenism. During preoperative workup prolonged prothrombin time and activated partial thromboplastin time were detected, which on further evaluation turned out to be due to factor V deficiency. Proximal lieno-renal shunt and splenectomy were successfully performed with transfusion of fresh frozen plasma during and after the surgical procedure. At surgery there was no excessive bleeding. The perioperative course was uneventful and the patient is doing well on follow up. CONCLUSION: Surgical portal decompressive procedures can be safely undertaken in clotting factor deficient patients with portal hypertension if meticulous surgical hemostasis is achieved at operation and the deficient factor is adequately replaced in the perioperative period

Scalable noninvasive amplicon-based precision sequencing (SNAPseq) for genetic diagnosis and screening of β-thalassemia and sickle cell disease using a next-generation sequencing platform

β-hemoglobinopathies such as β-thalassemia (BT) and Sickle cell disease (SCD) are inherited monogenic blood disorders with significant global burden. Hence, early and affordable diagnosis can alleviate morbidity and reduce mortality given the lack of effective cure. Currently, Sanger sequencing is considered to be the gold standard genetic test for BT and SCD, but it has a very low throughput requiring multiple amplicons and more sequencing reactions to cover the entire HBB gene. To address this, we have demonstrated an extraction-free single amplicon-based approach for screening the entire β-globin gene with clinical samples using Scalable noninvasive amplicon-based precision sequencing (SNAPseq) assay catalyzing with next-generation sequencing (NGS). We optimized the assay using noninvasive buccal swab samples and simple finger prick blood for direct amplification with crude lysates. SNAPseq demonstrates high sensitivity and specificity, having a 100% agreement with Sanger sequencing. Furthermore, to facilitate seamless reporting, we have created a much simpler automated pipeline with comprehensive resources for pathogenic mutations in BT and SCD through data integration after systematic classification of variants according to ACMG and AMP guidelines. To the best of our knowledge, this is the first report of the NGS-based high throughput SNAPseq approach for the detection of both BT and SCD in a single assay with high sensitivity in an automated pipeline

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Notes on green munia

Volume: 93Start Page: 588End Page: 58