ECMO: a lifesaving modality in ARDS during puerperium

Acute respiratory distress syndrome (ARDS) is an uncommon condition encountered in pregnancy. The incidence of ARDS in pregnancy has been reported to be 1 in 6229 deliveries with mortality rates to range from 24% to 39% in pregnant patients. An essential component in management of ARDS involves good communication between the obstetrics team and critical care specialist and a fundamental understanding of mechanical ventilatory support. In critically ill patients where both cardiorespiratory support is required, Extracorporeal Membrane Oxygenation (ECMO) can be used to help maintain the vital functions. ECMO is a temporary cardio respiratory or respiratory support in critically ill patients who are unresponsive to conventional management.  In present case a young female with post-partum ARDS was successfully managed with extra corporeal membrane oxygenation (ECMO)

Patient-Reported Status and Heart Failure Outcomes in Asia by Sex, Ethnicity, and Socioeconomic Status

Background: In heart failure (HF), symptoms and health-related quality of life (HRQoL) are known to vary among different HF subgroups, but evidence on the association between changing HRQoL and outcomes has not been evaluated. Objectives: The authors sought to investigate the relationship between changing symptoms, signs, and HRQoL and outcomes by sex, ethnicity, and socioeconomic status (SES). Methods: Using the ASIAN-HF (Asian Sudden Cardiac Death in Heart Failure) Registry, we investigated associations between the 6-month change in a “global” symptoms and signs score (GSSS), Kansas City Cardiomyopathy Questionnaire overall score (KCCQ-OS), and visual analogue scale (VAS) and 1-year mortality or HF hospitalization. Results: In 6,549 patients (mean age: 62 ± 13 years], 29% female, 27% HF with preserved ejection fraction), women and those in low SES groups had higher symptom burden but lower signs and similar KCCQ-OS to their respective counterparts. Malay patients had the highest GSSS (3.9) and lowest KCCQ-OS (58.5), and Thai/Filipino/others (2.6) and Chinese patients (2.7) had the lowest GSSS scores and the highest KCCQ-OS (73.1 and 74.6, respectively). Compared to no change, worsening of GSSS (&gt;1-point increase), KCCQ-OS (≥10-point decrease) and VAS (&gt;1-point decrease) were associated with higher risk of HF admission/death (adjusted HR: 2.95 [95% CI: 2.14-4.06], 1.93 [95% CI: 1.26-2.94], and 2.30 [95% CI: 1.51-3.52], respectively). Conversely, the same degrees of improvement in GSSS, KCCQ-OS, and VAS were associated with reduced rates (HR: 0.35 [95% CI: 0.25-0.49], 0.25 [95% CI: 0.16-0.40], and 0.64 [95% CI: 0.40-1.00], respectively). Results were consistent across all sex, ethnicity, and SES groups (interaction P &gt; 0.05). Conclusions: Serial measures of patient-reported symptoms and HRQoL are significant and consistent predictors of outcomes among different groups with HF and provide the potential for a patient-centered and pragmatic approach to risk stratification.</p

Effects of combined renin-angiotensin-aldosterone system inhibitor and beta-blocker treatment on outcomes in heart failure with reduced ejection fraction:insights from BIOSTAT-CHF and ASIAN-HF registries

Background: Angiotensin‐converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB) and β‐blockers are guideline‐recommended first‐line therapies in heart failure (HF) with reduced ejection fraction (HFrEF). Previous studies showed that individual drug classes were under‐dosed in many parts of Europe and Asia. In this study, we investigated the association of combined up‐titration of ACEi/ARBs and β‐blockers with all‐cause mortality and its combination with hospitalization for HF. Methods and results: A total of 6787 HFrEF patients (mean age 62.6 ± 13.2 years, 77.7% men, mean left ventricular ejection fraction 27.7 ± 7.2%) were enrolled in the prospective multinational European (BIOSTAT‐CHF; n = 2100) and Asian (ASIAN‐HF; n = 4687) studies. Outcomes were analysed according to achieved percentage of guideline‐recommended target doses (GRTD) of combination ACEi/ARB and β‐blocker therapy, adjusted for indication bias. Only 14% (n = 981) patients achieved ≥50% GRTD for both ACEi/ARB and β‐blocker. The best outcomes were observed in patients who achieved 100% GRTD of both ACEi/ARB and β‐blocker [hazard ratio (HR) 0.32, 95% confidence interval (CI) 0.26–0.39 vs. none]. Lower dose of combined therapy was associated with better outcomes than 100% GRTD of either monotherapy. Up‐titrating β‐blockers was associated with a consistent and greater reduction in hazards of all‐cause mortality (HR for 100% GRTD: 0.40, 95% CI 0.25–0.63) than corresponding ACEi/ARB up‐titration (HR 0.75, 95% CI 0.53–1.07). Conclusion: This study shows that best outcomes were observed in patients attaining GRTD for both ACEi/ARB and β‐blockers, unfortunately this was rarely achieved. Achieving &gt;50% GRTD of both drug classes was associated with better outcome than target dose of monotherapy. Up‐titrating β‐blockers to target dose was associated with greater mortality reduction than up‐titrating ACEi/ARB

Variants in KCNQ1 increase type II diabetes susceptibility in South Asians: A study of 3,310 subjects from India and the US

<p>Abstract</p> <p>Background</p> <p>Polymorphisms in intron 15 of potassium voltage-gated channel, KQT-like subfamily member 1 (<it>KCNQ1</it>) gene have been associated with type II diabetes (T2D) in Japanese genome-wide association studies (GWAS). More recently a meta-analysis of European GWAS has detected a new independent signal associated with T2D in intron 11 of the <it>KCNQ1 </it>gene. The purpose of this investigation is to examine the role of these variants with T2D in populations of Asian Indian descent from India and the US.</p> <p>Methods</p> <p>We examined the association between four variants in the <it>KCNQ1 </it>gene with T2D and related quantitative traits in a total of 3,310 Asian Indian participants from two different cohorts comprising 2,431 individuals of the Punjabi case-control cohort from the Sikh Diabetes Study and 879 migrant Asian Indians living in the US.</p> <p>Results</p> <p>Our data confirmed the association of a new signal at the <it>KCNQ1 </it>locus (rs231362) with T2D showing an allelic odds ratio (OR) of 1.24 95%CI [1.08-1.43], p = 0.002 in the Punjabi cohort. A moderate association with T2D was also seen for rs2237895 in the Punjabi (OR 1.14; p = 0.036) and combined cohorts (meta-analysis OR 1.14; p = 0.018). Three-site haplotype analysis of rs231362, rs2237892, rs2237895 exhibited considerably stronger evidence of association of the GCC haplotype with T2D showing OR of 1.24 95%CI [1.00-1.53], p = 0.001, permutation p = 8 × 10^-4in combined cohorts. The 'C' risk allele carriers of rs2237895 had significantly reduced measures of HOMA-B in the US cohort (p = 0.008) as well as in combined cohort in meta-analysis (p = 0.009).</p> <p>Conclusions</p> <p>Our investigation has confirmed that the variation within the <it>KCNQ1 </it>locus confers a significant risk to T2D among Asian Indians. Haplotype analysis further suggested that the T2D risk associated with <it>KCNQ1 </it>SNPs may be derived from 'G' allele of rs231362 and 'C' allele of rs2237895 and this appears to be mediated through β cell function.</p

Prescribing patterns of evidence-based heart failure pharmacotherapy and outcomes in the ASIAN-HF registry:a cohort study

Background Angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs), beta blockers, and mineralocorticoid receptor antagonists (MRAs) are of proven benefit and are recommended by guidelines for management of patients with heart failure and reduced ejection fraction (HFrEF). We aimed to examine the first prospective multinational data from Asia on prescribing patterns of guideline-directed medical therapies and analyse its effect on outcomes. Methods In the prospective multinational ASIAN-HF registry (with enrolment from 46 centres in 11 countries in Asia), we enrolled patients aged 18 years or older, with symptomatic heart failure (stage C, with at least one episode of decompensated heart failure in the past 6 months that resulted in admission to hospital or was treated in an outpatient clinic) and left ventricular systolic dysfunction (ejection fraction Findings Between Oct 1, 2012, and Dec 31, 2015, we enrolled 5276 patients with HFrEF (mean age 59.6 years [SD 13.2], 77% men, body-mass index 24.9 kg/m(2) [5.1], 33% New York Heart Association class III or IV). Followup data were available for 4544 (90%) of 5061 eligible patients taking medication for heart failure, with median follow-up of 417 days (IQR 214-735). ACE inhibitors or ARBs were prescribed to 3868 (77%) of 5005 patients, beta blockers to 3975 (79%) of 5061, and MRAs to 2998 (58%) of 5205, with substantial regional variation. Guideline-recommended dose was achieved in only 17% of cases for ACE inhibitors or ARB, 13% for beta blockers, and 29% for MRAs. Country (all three drug classes), increasing body-mass index (ACE inhibitors or ARBs and MRAs), and in-patient recruitment (ACE inhibitors or ARBs and beta blockers) were associated with attainment of guideline-recommended dose (all p= 100%]). Interpretation Guideline-directed medical therapies at recommended doses are underutilised in patients with HFrEF. Improved uptake and uptitration of guideline-directed medical therapies are needed for better patient outcomes. Copyright (C) 2018 The Author(s). Published by Elsevier Ltd

A Replication Study of GWAS-Derived Lipid Genes in Asian Indians: The Chromosomal Region 11q23.3 Harbors Loci Contributing to Triglycerides

Recent genome-wide association scans (GWAS) and meta-analysis studies on European populations have identified many genes previously implicated in lipid regulation. Validation of these loci on different global populations is important in determining their clinical relevance, particularly for development of novel drug targets for treating and preventing diabetic dyslipidemia and coronary artery disease (CAD). In an attempt to replicate GWAS findings on a non-European sample, we examined the role of six of these loci (CELSR2-PSRC1-SORT1 rs599839; CDKN2A-2B rs1333049; BUD13-ZNF259 rs964184; ZNF259 rs12286037; CETP rs3764261; APOE-C1-C4-C2 rs4420638) in our Asian Indian cohort from the Sikh Diabetes Study (SDS) comprising 3,781 individuals (2,902 from Punjab and 879 from the US). Two of the six SNPs examined showed convincing replication in these populations of Asian Indian origin. Our study confirmed a strong association of CETP rs3764261 with high-density lipoprotein cholesterol (HDL-C) (p = 2.03×10−26). Our results also showed significant associations of two GWAS SNPs (rs964184 and rs12286037) from BUD13-ZNF259 near the APOA5-A4-C3-A1 genes with triglyceride (TG) levels in this Asian Indian cohort (rs964184: p = 1.74×10−17; rs12286037: p = 1.58×10−2). We further explored 45 SNPs in a ∼195 kb region within the chromosomal region 11q23.3 (encompassing the BUD13-ZNF259, APOA5-A4-C3-A1, and SIK3 genes) in 8,530 Asian Indians from the London Life Sciences Population (LOLIPOP) (UK) and SDS cohorts. Five more SNPs revealed significant associations with TG in both cohorts individually as well as in a joint meta-analysis. However, the strongest signal for TG remained with BUD13-ZNF259 (rs964184: p = 1.06×10−39). Future targeted deep sequencing and functional studies should enhance our understanding of the clinical relevance of these genes in dyslipidemia and hypertriglyceridemia (HTG) and, consequently, diabetes and CAD

Genome-Wide Linkage Scan to Identify Loci Associated with Type 2 Diabetes and Blood Lipid Phenotypes in the Sikh Diabetes Study

In this investigation, we have carried out an autosomal genome-wide linkage analysis to map genes associated with type 2 diabetes (T2D) and five quantitative traits of blood lipids including total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, very low-density lipoprotein (VLDL) cholesterol, and triglycerides in a unique family-based cohort from the Sikh Diabetes Study (SDS). A total of 870 individuals (526 male/344 female) from 321 families were successfully genotyped using 398 polymorphic microsatellite markers with an average spacing of 9.26 cM on the autosomes. Results of non-parametric multipoint linkage analysis using Sall statistics (implemented in Merlin) did not reveal any chromosomal region to be significantly associated with T2D in this Sikh cohort. However, linkage analysis for lipid traits using QTL-ALL analysis revealed promising linkage signals with p≤0.005 for total cholesterol, LDL cholesterol, and HDL cholesterol at chromosomes 5p15, 9q21, 10p11, 10q21, and 22q13. The most significant signal (p = 0.0011) occurred at 10q21.2 for HDL cholesterol. We also observed linkage signals for total cholesterol at 22q13.32 (p = 0.0016) and 5p15.33 (p = 0.0031) and for LDL cholesterol at 10p11.23 (p = 0.0045). Interestingly, some of linkage regions identified in this Sikh population coincide with plausible candidate genes reported in recent genome-wide association and meta-analysis studies for lipid traits. Our study provides the first evidence of linkage for loci associated with quantitative lipid traits at four chromosomal regions in this Asian Indian population from Punjab. More detailed examination of these regions with more informative genotyping, sequencing, and functional studies should lead to rapid detection of novel targets of therapeutic importance