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With increasing numbers of patients undergoing transcatheter aortic valve replacement (TAVR), data on management of failed TAVR, including repeat TAVR procedure, are needed. The aim of this study was to assess the safety and efficacy of redo-TAVR in a national registry.

Objective: The prevalence of anemia has remained high among Indian adolescent girls over the past decade, despite the ongoing iron and folic acid (IFA) supplementation program. This study was conducted to assess the impact of daily supplementation of a package of IFA with vitamin B12on hemoglobin levels among adolescent girls. Methods: A community-based cluster-randomized trial was conducted in the rural block of Faridabad District, Haryana, India in the year 2017. A total of 760 adolescent girls in the age group of 12–19 years with mild and moderate anemia were selected from government schools. Daily-supervised administration of iron and folic acid was conducted for 90 days: experimental group—IFA (iron (60 mg), folic acid (500) mcg), and cyanocobalamin (1000 mcg), control group—IFA and placebo. Hemoglobin, serum ferritin, and vitamin B12levels were assessed at baseline and endline. Results: Two-hundred adolescent girls completed 90 doses of daily supplementation. The mean hemoglobin (experimental group: 1.3 ± 1.0 g/dL, control group: 1.6 ± 1.2 g/dL, P= 0.004) and ferritin levels (experimental group: 18.6 ± 31.5 ng/mL, control group: 18.8 ± 35.0 ng/mL, P= 0.188) increased in both the control and experiment groups. Serum vitamin B12deficiency significantly reduced to 2.5% in the experimental group and ferritin deficiency alleviated in more than 96% of the girls post intervention. Conclusions: Daily supplementation of IFA with/without vitamin B12for 90 days eliminated iron, vitamin B12deficiency and reduced the overall proportion of anemia by 53.5%. However, addition of vitamin B12to IFA supplementation had no impact on improving the hemoglobin levels among adolescent girls. The present study does not recommend provision of vitamin B12for prevention and treatment of anemia in this population group.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) pandemic, which has resulted in global healthcare crises and strained health resources. As the population of patients recovering from COVID-19 grows, it is paramount to establish an understanding of the healthcare issues surrounding them. COVID-19 is now recognized as a multi-organ disease with a broad spectrum of manifestations. Similarly to post-acute viral syndromes described in survivors of other virulent coronavirus epidemics, there are increasing reports of persistent and prolonged effects after acute COVID-19. Patient advocacy groups, many members of which identify themselves as long haulers, have helped contribute to the recognition of post-acute COVID-19, a syndrome characterized by persistent symptoms and/or delayed or long-term complications beyond 4 weeks from the onset of symptoms. Here, we provide a comprehensive review of the current literature on post-acute COVID-19, its pathophysiology and its organ-specific sequelae. Finally, we discuss relevant considerations for the multidisciplinary care of COVID-19 survivors and propose a framework for the identification of those at high risk for post-acute COVID-19 and their coordinated management through dedicated COVID-19 clinics.

To study whether combining vital signs and electrocardiogram (ECG) analysis can improve early prognostication.

Although COVID-19 is most well known for causing substantial respiratory pathology, it can also result in several extrapulmonary manifestations. These conditions include thrombotic complications, myocardial dysfunction and arrhythmia, acute coronary syndromes, acute kidney injury, gastrointestinal symptoms, hepatocellular injury, hyperglycemia and ketosis, neurologic illnesses, ocular symptoms, and dermatologic complications. Given that ACE2, the entry receptor for the causative coronavirus SARS-CoV-2, is expressed in multiple extrapulmonary tissues, direct viral tissue damage is a plausible mechanism of injury. In addition, endothelial damage and thromboinflammation, dysregulation of immune responses, and maladaptation of ACE2-related pathways might all contribute to these extrapulmonary manifestations of COVID-19. Here we review the extrapulmonary organ-specific pathophysiology, presentations and management considerations for patients with COVID-19 to aid clinicians and scientists in recognizing and monitoring the spectrum of manifestations, and in developing research priorities and therapeutic strategies for all organ systems involved.

This study sought to develop models for predicting mortality and heart failure (HF) hospitalization for outpatients with HF with preserved ejection fraction (HFpEF) in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial.

Background:There are concerns that transcatheter or surgical aortic valve replacement (TAVR/SAVR) procedures are preferentially available to White patients.Methods:We stratified Medicare beneficiaries hospitalized with principal diagnosis of AS between 2012 and 2019 (n=299,976) by self-reported race/ethnicity (Black, Hispanic, Asian, Native American, and White). We evaluated AVR rates within 6 months of index hospitalization and associated procedural outcomes, including 30-day and 1-year mortality, and discharge disposition. We fitted Cox-proportional hazard models for outcomes, adjusting for demographics and comorbidities using race/ethnicity subgroup-specific-stabilized inverse probability weights.Results:Within 6 months of an index admission for AS, 86.8% (122,457 SAVR; 138,026 TAVR) patients underwent AVR. Overall, compared with White people, Black [HR 0.87 (0.85-0.89)], Hispanic [0.92 (0.88 - 0.96)], and Asian [0.95 (0.91 - 0.99)] people were less likely to receive AVR (Figure). Among patients who were admitted emergently/urgently, White patients (41.1%, 95% CI 40.7-41.4) had a significantly higher AVR rate within 6 months compared with Black (29.6%, 95% CI 28.3-30.9), Hispanic (36.6%, 95% CI 34.0-39.3), and Asian patients (35.4%, 95% CI 32.3-38.9). AVR rates increased annually for all race/ethnicities. There were no significant differences in 30-day or 1-year mortality by race. Black people were significantly more likely to be discharged to a facility compared with others.Conclusion:Within 6 months of AS admission, AVR rates are lower for Black, Hispanic, and Asian people compared with White people. These race-based differences in ultimate treatment of AS likely represent complex issues across the diagnosis and management of AS, warranting a comprehensive reassessment of the entire care spectrum for disadvantaged populations.

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Tumor suppressing transcription factor p53 regulates multiple pathways including DNA repair, cell survival, apoptosis and autophagy. Here, we studied the stress-induced activation of p53 in anoxic crayfish (Faxonius virilis). Relative levels of target proteins and mRNAs involved in the DNA damage response were measured in normoxic control and anoxic hepatopancreas and tail muscle. Phosphorylation levels of p53 were assessed using immunoblotting at sites known to be phosphorylated (serine 15 and 37) in response to DNA damage or reduced oxygen signaling. The capacity for DNA binding by phosphorylated p53 (p-p53) was also measured, followed by transcript analysis of a potentially pro-apoptotic downstream target, the etoposide induced (ei24) gene. Following this, both inhibitor (MDM2) and activator (p19-ARF) protein levels in response to low-oxygen stress were studied. The results showed an increase in p-p53 levels during anoxia in both hepatopancreas and tail muscle. Increased transcript levels of ei24 support the activation of p53 under anoxic stress. Cytoplasmic accumulation of Ser15 phosphorylated p53 was observed during anoxia when proteins from cytoplasmic and nuclear fractions were measured. Increased cytoplasmic concentration is known to initiate an apoptotic response, which can be assumed as a preparatory step to prevent autophagy. The results suggest that p53 might play a protective role in crayfish defense against low-oxygen stress. Understanding how anoxia-tolerant organisms are able to protect themselves against DNA damage could provide important clues towards survival under metabolic rate depression and preparation for recovery to minimize damage.

Atrial fibrillation ablation is an established therapy; however, limited data are available on associated complications. This systematic review determines the incidence and potential predictors of acute complications.

Calcium and its signaling have a role in adipogenesis. Transient Receptor Potential (TRP) channels are non-selective cation channels with a high permeability to calcium.

The following are highlights from the new series, Circulation: Cardiovascular Quality and OutcomesTopic Review. This series will summarize the most important manuscripts, as selected by the Editor, that have been published in the Circulation portfolio. The objective of this series is to provide our readership with a timely, comprehensive selection of important papers that are relevant to the quality and outcomes, and general cardiology audience. The studies included in this article represent the most significant research related to treatment of stable coronary artery disease (CAD).

Background: Calcium and its signaling have a role in adipogenesis. Transient Receptor Potential (TRP) channels are non-selective cation channels with a high permeability to calcium. Methods: In the present study the expression of multiple TRP channels on mouse 3T3-L1 preadipocyte and adipocyte cells, white (WAT) and brown (BAT) adipose tissues was investigated using real time PCR (RT-PCR). Results: TRPV1, TRPV3, TRPM8, TRPC4, TRPC6 were differentially expressed in preadipocytes and adipocytes suggesting their significance in adipogenesis. Genes for multiple TRP channels were also expressed in murine WAT and BAT, out of which TRPV4, TRPV6 and TRPC6 showed differential expression. Conclusion: Present study demonstrates the expression of TRP channels in mouse cell lines and adipose tissues.

The following are highlights from the new series, Circulation: Cardiovascular Quality and Outcomes Topic Review.This series will summarize the most important manuscripts, as selected by the Editor, that have been published in the Circulation portfolio. The objective of this new series is to provide our readership with a timely, comprehensive selection of important papers that are relevant to the quality and outcomes, and general cardiology audience. The studies included in this article represent the most significant research in the area of anticoagulation for cardiovascular disease.

The following are highlights from the new series, Circulation: Cardiovascular Quality and Outcomes Topic Review. This series will summarize the most important manuscripts, as selected by the Editor, that have published in the Circulationportfolio. The objective of this new series is to provide our readership with a timely, comprehensive selection of important papers that are relevant to the quality and outcomes, and general cardiology audience. The studies included in this article represent the most significant research in the area of cardiovascular disease among racial and ethnic minorities.

The following are highlights from the new series, Circulation: Cardiovascular Quality and OutcomesTopic Review. This series will summarize the most important manuscripts, as selected by the Editor, that have published in the Circulationportfolio. The objective of this new series is to provide our readership with a timely, comprehensive selection of important papers that are relevant to the quality and outcomes and general cardiology audience. The studies included in this article represent the most significant research in the area of cardiovascular disease in the elderly.

The following are highlights from the new series, Circulation: Cardiovascular Quality and Outcomes Topic Review. This series will summarize the most important manuscripts (as selected by the Editor) that have published in the Circulationportfolio. The objective of this new series is to provide our readership with a timely, comprehensive selection of important papers that are relevant to the quality and outcomes, and general cardiology audience. The studies included in this article represent the most significant research in the area of health costs, cost-effectiveness, and resource utilization.

Both clinical and experimental reports indicate that aldosterone contributes to the progression of renal failure independent of its hemodynamic effects. In the present study, we evaluated effect of aldosterone on human mesangial cell (MC) growth. Aldosterone induced apoptotic and mitogenic effects on MCs. Aldosterone promoted MC apoptosis in a dose- and time-dependent manner. Spironolactone, a mineralocorticoid receptor antagonist, inhibited aldosterone-induced MC apoptosis. Similarly, antioxidants and free radical scavengers partially attenuated proapoaptotic effects of aldosterone. Aldosterone also enhanced dephosphorylation of phospho-Bad and accumulation of cytosolic cytochrome cin MCs. In in vivo studies, rats were randomly assigned to receive normal saline, aldosterone, or eplerenone + aldosterone for 28 days. Systolic blood pressure, urinary albumin excretion rate, serum creatinine, and aldosterone were measured. Aldosterone-infused rats developed elevated systolic blood pressure and albuminuria when compared with control rats. Aldosterone-treated rats also showed greater numbers of apoptosed MCs. This proapoptotic effect of aldosterone was inhibited by eplerenone, a selective aldosterone antagonist. These findings suggest that aldosterone, besides its hemodynamic effects, may also directly contribute to the occurrence of MC apoptosis.

Catatonic patients may develop deep vein thrombosis (DVT) and pulmonary embolism (PE) due to prolonged periods of immobility. These life-threatening conditions demand prompt recognition and management. We describe the case of a patient with catatonia who presented to anesthesia for electroconvulsive therapy (ECT) at the outset of the current coronavirus disease 2019 pandemic. She complained of breathing difficulty and was suspected to have COVID-19 infection. On further evaluation, she was found to have DVT and PE and required oxygen therapy and intensive care management. The diagnostic delay in our patient would have probably not occurred, had it not been for the existing pandemic situation.

Dexamethasone as adjunct to local anesthetic solution improves the quality of brachial plexus block (BPB). However, evidence for its efficacy at low doses (< 4 mg) is lacking. This study was designed to evaluate the duration of analgesia attained with low dose dexamethasone as adjuvant to local anesthetic for creation of arteriovenous fistula (AVF) under BPB.

IMPORTANCE: Isolated systolic hypertension (ISH) is increasing in prevalence among young and middle-aged adults. However, most studies of ISH are limited to older individuals, and a substantial knowledge gap exists regarding younger adults with ISH. OBJECTIVE: To assess the prevalence, awareness, and characteristics of ISH among younger and middle-aged adults in China. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study was performed as part of the China Patient-Centered Evaluative Assessment of Cardiac Events Million Persons Project, which enrolled 3.1 million community residents aged 35 to 75 years from all of the 31 provinces in China between December 15, 2014, and May 15, 2019. The present analysis included only participants younger than 50 years. Data were analyzed from May to November 2019. MAIN OUTCOMES AND MEASURES: Prevalence and awareness of ISH (defined as systolic blood pressure of 140 mm Hg or higher and diastolic blood pressure of less than 90 mm Hg) and individual characteristics of participants with ISH. RESULTS: Among 898 929 participants aged 35 to 49 years, the mean (SD) age was 43.8 (3.9) years; 548 657 participants (61.0%) were women, and 235 138 participants (26.2%) had hypertension. Of those with hypertension, 62 819 participants (26.7%; 95% CI, 26.5%-26.9%) had ISH (mean [SD] age, 45.0 [3.5] years; 41 417 women [65.9%]), and 54 463 of those with ISH (86.7%; 95% CI, 86.4%-87.0%) had not received treatment. The prevalence of ISH was higher among individuals who were older, were female, were farmers, resided in the eastern region of China, and had an educational level of primary school or lower. Women and older individuals were more likely to have ISH than to be normotensive or to have other hypertension subtypes. Participants who were obese, currently used alcohol, had diabetes, and experienced previous cardiovascular events were more likely to have other types of hypertension and less likely to have normotension than to have ISH. Among the 54 463 participants with ISH who had not received treatment, only 3682 individuals (6.8%; 95% CI, 6.6%-7.0%) were aware of having hypertension, and awareness rates remained low even among those with systolic blood pressure of 160 mm Hg or higher (7135 individuals [13.1%; 95% CI, 12.4%-13.9%]). CONCLUSIONS AND RELEVANCE: In this study, ISH was identified in 1 of 4 young and middle-aged adults with hypertension in China, most of whom remained unaware of having hypertension. These results highlight the increasing need for better guidance regarding the management of ISH in this population.

Introduction:Severe symptomatic aortic stenosis (ssAS) is associated with high mortality without intervention. It is not known how time-to-treatment after symptom onset varies at the national level in the United States, and whether delay in treatment is associated with worse outcomes.Methods:Natural language processing of electronic health records in the claims-linked Optum?database (2011-2018) from over 200 hospitals and 7000 clinics identified date of symptom onset in 23162 patients with severe AS who received treatment with SAVR (11312) and TAVR (8072). We calculated ?time-to-treatment? from symptom onset to procedure (TAVR/SAVR) and defined ?treatment delay? as time-to-treatment > 90 days. We performed logistic regression to examine predictors of treatment delay and Cox proportional hazards modeling to examine the association of treatment delay with 1-year mortality. We estimated cumulative mortality with the Kaplan-Meier method.Results:Median time-to treatment was 43 days (IQR 15-112 days) for SAVR and 78 days (IQR 35-188 days) for TAVR (Figure). Treatment delay was observed in 38% of patients receiving TAVR and 24% of patients receiving SAVR. In multivariable analyses, women were more likely to experience treatment delay for SAVR (HR: 1.14; 95% CI: 1.04 - 1.2) and African-Americans for both TAVR (HR: 1.7; 95%CI: 1.3-2.1) and SAVR (HR 1.5; 95% CI: 1.2-1.9). Treatment delay was significantly associated with lower survival probability at 1 year for both TAVR and SAVR (Figure). This association, however, did not remain significant for TAVR after adjustment.Conclusions:Patients with ssAS wait about twice longer to receive TAVR than SAVR. Women and African-American patients are more susceptible to delay in treatment. Treatment delay is associated with higher 1-year mortality, suggesting need for improved awareness and access to both TAVR and SAVR nationwide.

Introduction:Optimal antithrombotic management of patients with pre-existing atrial fibrillation (AF) undergoing transcatheter aortic valve replacement (TAVR) is challenging given the need to balance the risk of bleeding and thromboembolism. We examined treatment patterns for antithrombotic therapies and associated outcomes in patients undergoing TAVR with concomitant AF in the US.Methods:Patients who underwent TAVR with pre-existing AF from November, 2011 through September, 2015 in the STS/ACC TVT?registry linked to the Medicare database were examined according to receipt of oral anticoagulants (OAC) or antiplatelet therapies (APT) or a combination of these (OAC+APT) at discharge. To assess the associations of antithrombotic therapies with 1-year outcomes of stroke, bleeding and mortality, we utilized inverse probability weighting and multivariable regression modeling adjusting for patient- and hospital-level variables.Results:In the 11382 patients included in our study, 5833 (51.2%) were discharged on OAC+APT, 4786 (42.0%) on APT alone and 763 (6.7%) on OAC alone with significant variability across hospital sites (Figure). In adjusted analyses, the risk for all-cause mortality and stroke was similar when comparing the three different antithrombotic strategies (Figure). Risk of bleeding was similar when comparing APT alone with OAC alone or OAC+APT with OAC alone, and less when comparing APT alone with OAC+APT.Conclusions:There is significant variability in the prescription of antithrombotic therapies in patients with AF who undergo TAVR in the US. The use of OAC+APT (vs. OAC alone or APT alone) was not associated with a reduced risk of stroke or mortality, but was associated with increased risk of bleeding complications at 1-year compared to APT alone. Further research is necessary to determine the optimal antithrombotic therapy for AF patients undergoing TAVR.