Background Continuous-flow left ventricular assist devices (LVAD) are increasingly used for patients with end-stage heart failure (HF). We analyzed the effects of ventricular decompression by continuous- versus pulsatile-flow LVADs on myocardial structure and function in this population. Methods and Results Sixty-one patients who underwent LVAD implantation as bridge-to-transplant were analyzed (pulsatile-flow LVAD: Group P, n=31; continuous-flow LVAD: Group C, n=30). Serial echocardiograms, serum levels of brain natriuretic peptide (BNP) and extracellular matrix biomarkers (ECM) were compared between the groups. Myocardial BNP and ECM gene expression were evaluated in a subset of 18 patients. Postoperative left ventricular (LV) ejection fraction was greater (33.2±12.6 vs. 17.6±8.8%, p<0.0001) and the mitral E/E′ was lower (9.9±2.6 vs. 13.2±3.8, p=0.0002) in Group P versus Group C. Postoperative serum levels of BNP, metalloproteinases (MMP)-9 and tissue inhibitor of MMP (TIMP)-4 were significantly lower in Group P compared to Group C (BNP: 552.6±340.6 vs. 965.4±805.7 pg/mL, p<0.01; MMP9: 309.0±220.2 vs. 475.2±336.9 ng/dL, p<0.05; TIMP4: 1490.9±622.4 vs. 2014.3±452.4 ng/dL, p<0.001). Myocardial gene expression of ECM markers and BNP decreased in both groups; however, expression of TIMP-4 decreased only in Group P (p=0.024). Conclusions Mechanical unloading of the failing myocardium using pulsatile devices is more effective as indicated by echocardiographic parameters of systolic and diastolic LV function as well as dynamics of BNP and ECM markers. Therefore, specific effects of pulsatile mechanical unloading on the failing myocardium may have important implications for device selection especially for the purpose of bridge-to-recovery in patients with advanced HF.

Background Heart failure (HF) is characterized by inflammation, insulin resistance and progressive catabolism. We hypothesized that patients with advanced HF also develop adipose tissue inflammation associated with impaired adipokine signaling and that hemodynamic correction through implantation of ventricular assist devices (VADs) would reverse adipocyte activation and correct adipokine signaling in advanced HF. Methods and Results Circulating insulin, adiponectin, leptin and resistin levels were measured in 36 patients with advanced HF before and after VAD implantation and 10 healthy controls. Serum adiponectin was higher in HF patients pre-VAD compared to controls (13.3±4.9 vs. 6.4±2.1 μg/ml, p=0.02). VAD implantation (mean 129±99 days) reduced serum adiponectin (7.4±3.4 μg/ml, p<0.05) and improved insulin resistance (Homeostasis Assessment Model of insulin resistance: 6.3±5.8 to 3.6±2.9; p<0.05). Adiponectin expression in adipose tissue decreased after VAD implantation (−65%; p<0.03). Adiponectin receptor expression was suppressed in the failing myocardium compared to controls and increased after mechanical unloading. Histomorphometric analysis of adipose tissue specimens revealed reduced adipocyte size in patients with advanced HF compared to controls (1999±24 μm2 vs. 5583±142 μm2 in controls; p<0.05), which increased after VAD placement. Of note, macrophage infiltration in adipose tissue was higher in advanced HF patients compared to controls (+25%; p<0.01), which normalized after VAD implantation. Conclusions Adipose tissue inflammation and adiponectin resistance develop in advanced HF. Mechanical unloading of the failing myocardium reverses adipose tissue macrophage infiltration, inflammation and adiponectin resistance in patients with advanced HF.

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IMPORTANCE Much research on sanitation and linear growth in low-and middle-income countries focuses on children younger than 5 years. However, poor sanitation may be associated with growth faltering during middle and late childhood to a greater extent than previously recognized. OBJECTIVETo characterize the association of poor sanitation with height-for-age z (HAZ) scores in children and adolescents in India aged 0 to 18 years. DESIGN, SETTING, AND PARTICIPANTSThis cross-sectional study examined 134 882 children and adolescents aged 0 to 18 years who were surveyed in the fourth round of India's District Level

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Background Evidence from past pandemics suggests that fear, uncertainty, and loss of control during large-scale public health crises may lead to increased pandemic-related information seeking, particularly among persons predisposed to high anxiety. In such groups, a greater consumption of information pertaining to the COVID-19 pandemic may increase anxiety. Objective In this study, we examine the association between online activity and Generalized Anxiety Disorder 7 (GAD-7) scores in the United States. Methods We recruited participants for an online survey through advertisements on various platforms such as Google, Facebook, and Reddit. A total of 406 adult US participants with moderate to severe (≥10) GAD-7 scores met the inclusion criteria and completed the survey. Anxiety levels measured using the GAD-7 scale formed our primary outcome. Our key independent variables were average daily time spent online and average daily time spent online searching about COVID-19 within the past 14 days. We used as controls potential confounders of the relation between our key independent variables and GAD-7 scores, namely, sleep quality, the COVID-19 Fear Inventory scale, binge drinking, substance use, prescription drug abuse, and sociodemographic attributes. Results Linear multivariate regression analyses showed that GAD-7 scores were higher among those who spent >4 hours online (per day) searching for information about COVID-19 (coefficient 1.29, P=.002), controlling for all other covariates. The total time spent online was not statistically associated with GAD-7 scores. Conclusions Results from this study indicate that limiting pandemic-related online information seeking may aid anxiety management in our study population.

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