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Purpose of Review: The purpose of this review is threefold: (i) to give an overview of well-established invasive methods for assessing patients with ischemia with no obstructive coronary arteries (INOCA) in the cardiac catheterization laboratory; (ii) to describe the prognostic and treatment implications based on these findings, and (iii) to discuss current knowledge gaps and future perspectives., Recent Findings: Recent studies have demonstrated that invasive coronary function testing not only allows for risk stratification of patients with INOCA but also guides medical therapy with improvement in symptoms and quality of life. Based on these findings, invasive coronary function assessment is now a class 2a recommendation in the 2021 ACC/AHA chest pain guideline to improve the diagnosis of coronary microvascular dysfunction and to enhance risk stratification. Invasive functional testing for patients with INOCA is well established and easily performed in the catheterization laboratory. Comprehensive invasive assessment is a key to differentiating INOCA endotypes and optimizing both medical therapy and preventive strategies including lifestyle modification., (© 2023. The Author(s).)

Background Though associations between obstructive sleep apnea (OSA) and cardiovascular outcomes are well described, limited data exist regarding the impact of OSA on sex-specific outcomes after acute myocardial infarction (AMI). Methods and Results The VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) study enrolled 3572 adults aged 18 to 55 years with AMI from the United States and Spain during 2008 to 2012. We included patients for whom the Berlin Questionnaire for OSA was scored at the time of AMI admission (3141; 2105 women, 1036 men). We examined the sex-specific association between baseline OSA risk with functional outcomes including health status and depressive symptoms at 1 and 12 months after AMI. Among both groups, 49% of patients were at high risk for OSA (1040 women; 509 men), but only 4.7% (148) of patients had a diagnosed history of OSA. Though patients with a high OSA risk reported worse physical and mental health status and depression than low-risk patients in both sexes, the difference in these functional outcomes was wider in women than men. Moreover, women with a high OSA risk had worse health status, depression, and quality of life than high-risk men, both at baseline and at 1 and 12 months after AMI. Conclusions Young women with a high OSA risk have poorer health status and more depressive symptoms than men at the time of AMI, which may place them at higher risk of poorer health outcomes over the year following the AMI. Further, the majority of patients at high risk of OSA are undiagnosed at the time of presentation of AMI.

Background and Aims: Preoperative anxiety is a common problem among children undergoing surgery. The aim of the study was to assess the incidence and identify various predictors of preoperative anxiety in Indian children., Material and Methods: A prospective, observational study was conducted on 60 children of the American Society of Anesthesiologists Physical status 1/2, aged 2-6 years and scheduled for elective surgery under general anesthesia in a tertiary care teaching hospital. Preoperative parental anxiety was assessed using the State-Trait Anxiety Inventory questionnaire. The children's anxiety was assessed in the preoperative room, at the time of parental separation, and at the induction of anesthesia using modified Yale Preoperative Anxiety Scale (mYPAS) scoring by an anesthesiologist and a psychologist. Sedative premedication was employed prior to parental separation. Logistic regression analysis was carried out to identify the possible predictors of anxiety., Results: The incidence of high preoperative anxiety among the studied children was 76% in the preoperative room, 93% during parental separation, and 96% during anesthetic induction. Among the nine possible predictors identified on univariate regression, the presence of siblings was found to be a significant independent predictor on multivariate regression analysis ( P = 0.04). The inter-rater agreement was excellent for the assessment of preoperative anxiety using mYPAS by the anesthesiologist and psychologist (weighted Kappa, k = 0.79)., Conclusion: The incidence of preoperative anxiety in Indian children in the age group of 2-6 years is very high. The preop anxiety escalates progressively at parental separation and induction of anesthesia despite sedative premedication. The presence of siblings is a significant predictor of preoperative anxiety., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Anaesthesiology Clinical Pharmacology.)

Rana sylvatica (also known as Boreorana sylvatica ) is one of the few vertebrates that spend extreme winters showing no physiological signs of life. Up to 70% of the total body water of the wood frog freezes as extracellular ice. Survival in extreme conditions requires regulation at transcriptional and translational levels to activate prosurvival pathways. N6-methyladenosine (m 6 A) methylation is one of the most common RNA modifications, regulating transcript processing and translation by executing important functions that affect regulatory pathways in stress conditions. In the study, regulation of m 6 A-related proteins in the liver of R. sylvatica was analyzed during 24 h frozen and 8 h thaw conditions. Decreases in the activity of demethylases of 28.44 ± 0.4% and 24.1 ± 0.9% of control values in frozen and thaw tissues, respectively, were observed. Total protein levels of m 6 A methyltransferase complex components methyltransferase-like 14 and Wilm's tumor associated protein were increased by 1.28-fold and 1.42-fold, respectively, during freezing. Demethylase fat mass and obesity, however, showed a decreasing trend, with a significant decrease in abundance during recovery from frozen conditions. Levels of mRNA degraders YTHDF2 and YTHDC2 also decreased under stress. Overall, increased levels of m 6 A methylation complex components, and suppressed levels of readers/erasers, provide evidence for the potential role of RNA methylation in freezing survival and its regulation in a hypometabolic state.

Background: Use of intravascular ultrasound (IVUS) or optical coherence tomography (OCT) during percutaneous coronary intervention (PCI) is endorsed by society guidelines, but US data on real-world outcomes are lacking., Methods: Medicare claims data were identified for inpatient PCIs performed October 2015 to March 2020, with IVUS/OCT captured by ICD-10-PCS codes. Three-way propensity score matching (angio vs IVUS vs OCT) on baseline and procedural characteristics was performed. Major adverse cardiovascular events (MACE), a composite of death, myocardial infarction (MI), or repeat revascularization, was evaluated through 3 years, with a 30-day blanking window after index PCI to exclude staged procedures., Results: Of the 502,821 PCI procedures, 463,201 (92%) were guided by angiography alone, with IVUS or OCT used in 37,908 (7.5%) and 1712 (0.3%), respectively. After propensity matching, compared with angiography, the risk of major adverse cardiovascular event was similar for IVUS (hazard ratio [HR], 0.97; 95% CI, 0.91-1.03; P = .285) but lower for OCT (HR, 0.85; 95% CI, 0.77-0.94; P = .001). A similar trend was observed in clinically relevant subgroups. Compared with angiography alone, the risk of MI or repeat revascularization was lower with OCT (HR, 0.86; 95% CI, 0.76-0.97; P = .015), and the risk of MI alone was lower with IVUS (HR, 0.90; 95% CI, 0.82-0.99; P = .038)., Conclusions: In a real-world US cohort, IVUS and OCT were used infrequently during PCI. Compared with angiography alone, use of intracoronary imaging during index PCI was associated with lower rates of clinical events through 3 years., Competing Interests: Dr Bergmark receives grant support through institution from Pfizer, Ionis, AstraZeneca, Abbott Vascular, Philips; receives consulting/personal fees from Abiomed, SpectraWAVE, Endovascular Engineering, CSI, Philips, Abbott Vascular, Servier, Daiichi-Sankyo, Janssen, and Quark; and is a member of the TIMI Study Group, which has received institutional grant support through the Brigham and Women's Hospital from Abbott, Amgen, Anthos Therapeutics, AstraZeneca, Bayer HealthCare Pharmaceuticals, Daiichi-Sankyo, Eisai, Intarcia, MedImmune, Merck, Novartis, Pfizer, Quark Pharmaceuticals, Regeneron Pharmaceuticals, Roche, Siemens Healthcare Diagnostics, The Medicines Company, and Zora Biosciences. Dr Osborn receives research grant support from NIH/NHLBI (K08 HL130465); sponsored research from Dyad Medical, NuPulseCV, and Opsens; and consulting/personal fees from Abbott Vascular, Canon, Opsens, and Philips; is a scientific advisory board member of Dyad Medical; and holds equity in this company. Dr Ali receives grants from NIH/NHLBI, Abbott, Philips, Boston Scientific, Abiomed, Opsens, Acist Medical, Medtronic, Cardiovascular Systems; personal from Boston Scientific, Abiomed, Amgen, and Astra Zeneca; and equity from Shockwave Medical. Dr Gupta receives payment from the Arnold & Porter Law Firm for work related to the Sanofi clopidogrel litigation and from the Ben C. Martin Law Firm for work related to the Cook Celect IVC filter litigation; receives consulting fees from Edwards LifeSciences; and holds equity in Heartbeat Health, a telecardiology healthcare platform. Drs Koli, Prillinger, West, and Hasegawa are employees of and holds stock in Abbott. Dr Croce receives grant support from Abbott, Takeda, Teleflex, and CSI; receives honoraria from Abbott, Biotronik, Philips, Abiomed, CSI, Takeda, and Cordis; and is a major stock shareholder in Dyad Medical. Dr Secemsky receives research grants to BIDMC: NIH/NHLBI K23HL150290, Food and Drug Administration, Harvard Medical School’s Shore Faculty Development Award, AstraZeneca, BD, Boston Scientific, Cook, CSI, Laminate Medical, Medtronic and Philips and consulting/speaking fees from Abbott, Bayer, BD, Boston Scientific, Cook, CSI, Endovascular Engineering, Inari, Janssen, Medtronic, Philips, and VentureMed., (© 2022 The Authors.)

Data on depression and stress among patients with spontaneous coronary artery dissection (SCAD) are limited. Using data from the VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) study, which prospectively enrolled 3,572 acute myocardial infarction (AMI) patients between 18 and 55 years of age, we identified 67 SCAD cases. We compared Patient Health Questionnaire-9 (PHQ-9) and 14-item Perceived Stress Scale (PSS-14) scores obtained at baseline, 1 month, and 12 months between SCAD and AMI of all other causes. Using longitudinal linear mixed-effects analysis, we compared depression and stress scores between SCAD and other AMI, adjusting for time and selected covariates. Patients with SCAD had lower baseline PHQ-9 scores (6.1 ± 6.0 vs 7.7 ± 6.4 for other patients with AMI, p = 0.03), similar 1-month scores, and lower 12-month scores (3.2 ± 4.3 vs 4.9 ± 5.5, p = 0.004). At baseline and 1 month, patients with SCAD had similar PSS-14 scores to those of other patients with AMI. At 12 months, patients with SCAD had lower scores (18.4 ± 8.8 vs 21.5 ± 9.3 for other patients with AMI, p = 0.009). After adjustment for cardiovascular risk factors, co-morbidities, and clinical acuity, no differences in PHQ-9 or PSS-14 scores remained between SCAD and other AMI. Similar results were obtained in a subgroup analysis of only women with SCAD and other AMI. In conclusion, patients with SCAD had a relatively lower burden of depression and perceived stress than other patients with AMI, potentially because of fewer co-morbidities and favorable socioeconomic factors. However, given high depression and stress burden in both SCAD and other patients with AMI, routine screening can help identify and treat these patients., Competing Interests: Disclosures Dr. Bueno receives research funding from the Instituto de Salud Carlos III, Spain (PIE16/00021 and PI17/01799), Sociedad Española de Cardiología, Astra-Zeneca, Bayer, PhaseBio, and Novartis; has received consulting fees from Astra-Zeneca, Novartis, and Organon; speaking fees from Novartis, and is a scientific advisor for MEDSCAPE-the heart.org. In the past 3 years, Dr. Krumholz received expenses and/or personal fees from UnitedHealth, Element Science, Aetna, Reality Labs, Tesseract/4Catalyst, F-Prime, the Siegfried and Jensen Law Firm, Arnold and Porter Law Firm, and Martin/Baughman Law Firm. He is a co-founder of Refactor Health and HugoHealth, and is associated with contracts, through Yale New Haven Hospital, with the Centers for Medicare & Medicaid Services and through Yale University with Johnson & Johnson. The remaining authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The ability of an animal to survive prolonged periods of oxygen deprivation is a critical area of study, both in terms of its importance to better understanding the physiology of these incredible animals and to its potential applicability to medical fields. The freshwater crayfish, Faxonius virilis, is one such animal capable of resisting anoxia, but it remains understudied and much of the metabolic mechanisms underlying this anoxia tolerance remain largely unprofiled. This study examines the activity and regulation of apoptosis and autophagy in F. virilis in response to 20-h anoxia. Apoptosis signaling was assessed through pro- and anti-apoptosis targets, whereas autophagy was assessed via expression response of multiple autophagy proteins. An anoxia-triggered, tissue-specific result arose, potentially based on the importance of individual organ integrity through hypometabolism. Tail muscle, which showed increased expression profiles of all three target groups, contrasted with hepatopancreas, which appeared to not be susceptible to either apoptotic or autophagic signaling during anoxia. This is likely due to the importance of the hepatopancreas, given that apoptosis or autophagy of this organ at any significant level could be fatal to the organism. The data provides a comprehensive overview of the responses and integration of multiple stress-responsive signaling pathways in F. virilis that provide a novel contribution to our understanding of pro-survival mechanisms supporting invertebrate anoxia resistance., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Studies examining outcomes among individuals with COronaVIrus Disease 2019 (COVID-19) have consistently demonstrated that men have worse outcomes than women, with a higher incidence of myocardial injury, respiratory failure, and death. However, mechanisms of higher morbidity and mortality among men remain poorly understood. We aimed to identify mediators of the relationship between sex and COVID-19-associated mortality., Methods: Patients hospitalized at two quaternary care facilities, New York Presbyterian Hospital (CUIMC/NYPH) and Massachusetts General Hospital (MGH), for SARS-CoV-2 infection between February and May 2020 were included. Five independent biomarkers were identified as mediators of sex effects, including high-sensitivity cardiac troponin T (hs-cTNT), high sensitivity C-reactive protein (hs-CRP), ferritin, D-dimer, and creatinine., Results: In the CUIMC/NYPH cohort ( n = 2,626, 43% female), male sex was associated with significantly greater mortality (26 vs. 21%, p = 0.0146) and higher peak hs-cTNT, hs-CRP, ferritin, D-dimer, and creatinine ( p < 0.001). The effect of male sex on the primary outcome of death was partially mediated by peak values of all five biomarkers, suggesting that each pathophysiological pathway may contribute to increased risk of death in men. Hs-cTnT, creatinine, and hs-CRP were the strongest mediators. Findings were highly consistent in the MGH cohort with the exception of D-dimer., Conclusions: This study suggests that the effect of sex on COVID-19 outcomes is mediated by cardiac and kidney injury, as well as underlying differences in inflammation and iron metabolism. Exploration of these specific pathways may facilitate sex-directed diagnostic and therapeutic strategies for patients with COVID-19 and provides a framework for the study of sex differences in other complex diseases., Competing Interests: AF receives sponsored research support from Bristol Myers Squibb/Pfizer and Fitbit and has received expert witness testimonial fees from Round Table Group. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lumish, Kim, Selvaggi, Cao, Gupta, Foulkes and Reilly.)

Patients with pre-existing cardiovascular disease (CVD) are at high risk for adverse outcomes with coronavirus disease 2019 (COVID-19). Further, COVID-19 infection is associated with numerous cardiovascular (CV) complications including arrhythmia, myocardial injury, cardiomyopathy, and thrombotic events. Increased susceptibility to COVID-19 and CV complications related to COVID-19 may be in part related to immune dysregulation and inflammation associated with CV disease which is exacerbated with viral infection. Vitamin D plays a major role in immune function and exerts anti-inflammatory effects, which may prove important in the context of CVD and COVID-19. To date, studies have shown minimal benefit for vitamin D supplementation in patients with COVID-19, though there are no studies specific to patients with CVD and related complications. Further, given that vitamin D has important protective effects on the CV system, including augmentation of myocardial contractility and anti-thrombotic effects, it is unknown if supplementation with vitamin D can mitigate CVD complications associated with COVID-19., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: High burden of anaemia exists amongst rural adolescent girls in India. The objective of this study was to characterise anaemia in school going adolescent girls in rural Haryana, India., Design: Linear and multiple logistic regression analysis of data collected prior to an intervention trial was conducted. Participants were classified into anaemic (haemoglobin <12 g/dl) and non-anaemic group and were further classified into deficiencies of Fe, folate or vitamin B12, mixed, anaemia of other causes and inflammation., Setting: Three schools in Ballabgarh block of Faridabad District, Haryana, India., Participants: One hundered and ninety-eight non-anaemic and 202 anaemic adolescent girls (12-19 years)., Results: Anaemic girls had 29·6 % Fe deficiency, 28·1 % folate or vitamin B12 deficiency, 15·8 % mixed deficiency and 9·7 % acute inflammation. Anaemia of other causes was found in 16·8 % of the anaemic participants. Girls with Fe and isolated folate deficiency had 2·5 times and four times higher odds of developing anaemia, respectively, as compared with non-anaemic girls. Fe deficiency with no anaemia was found amongst 11 % non-anaemic girls. Non-anaemic girls had a high prevalence of combined deficiency of folate or vitamin B12 (29·5 %) and acute inflammation (14·4 %)., Conclusions: The current strategy of Fe and folic acid supplementation alone will not suffice for achieving the desired reduction in the prevalence of anaemia as unknown causes and anaemia of inflammation contribute to a substantial proportion of anaemia. Integrating other nutrition-specific components like improving water, sanitation and hygiene practices with the ongoing micronutrient supplementation program will comprehensively tackle anaemia. Unknown causes of anaemia warrant further research.

Rationale: Two distinct subphenotypes have been identified in acute respiratory distress syndrome (ARDS), but the presence of subgroups in ARDS associated with coronavirus disease (COVID-19) is unknown. Objectives: To identify clinically relevant, novel subgroups in COVID-19-related ARDS and compare them with previously described ARDS subphenotypes. Methods: Eligible participants were adults with COVID-19 and ARDS at Columbia University Irving Medical Center. Latent class analysis was used to identify subgroups with baseline clinical, respiratory, and laboratory data serving as partitioning variables. A previously developed machine learning model was used to classify patients as the hypoinflammatory and hyperinflammatory subphenotypes. Baseline characteristics and clinical outcomes were compared between subgroups. Heterogeneity of treatment effect for corticosteroid use in subgroups was tested. Measurements and Main Results: From March 2, 2020, to April 30, 2020, 483 patients with COVID-19-related ARDS met study criteria. A two-class latent class analysis model best fit the population ( P  = 0.0075). Class 2 (23%) had higher proinflammatory markers, troponin, creatinine, and lactate, lower bicarbonate, and lower blood pressure than class 1 (77%). Ninety-day mortality was higher in class 2 versus class 1 (75% vs. 48%; P  < 0.0001). Considerable overlap was observed between these subgroups and ARDS subphenotypes. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RT-PCR cycle threshold was associated with mortality in the hypoinflammatory but not the hyperinflammatory phenotype. Heterogeneity of treatment effect to corticosteroids was observed ( P  = 0.0295), with improved mortality in the hyperinflammatory phenotype and worse mortality in the hypoinflammatory phenotype, with the caveat that corticosteroid treatment was not randomized. Conclusions: We identified two COVID-19-related ARDS subgroups with differential outcomes, similar to previously described ARDS subphenotypes. SARS-CoV-2 PCR cycle threshold had differential value for predicting mortality in the subphenotypes. The subphenotypes had differential treatment responses to corticosteroids.

Background: Recent trends, including survival beyond 30 days, in aortic valve replacement (AVR) following the expansion of indications for transcatheter aortic valve replacement (TAVR) are not well-understood., Objectives: The authors sought to characterize the trends in characteristics and outcomes of patients undergoing AVR., Methods: The authors analyzed Medicare beneficiaries who underwent TAVR and SAVR in 2012 to 2019. They evaluated case volume, demographics, comorbidities, 1-year mortality, and discharge disposition. Cox proportional hazard models were used to assess the annual change in outcomes., Results: Per 100,000 beneficiary-years, AVR increased from 107 to 156, TAVR increased from 19 to 101, whereas SAVR declined from 88 to 54. The median [interquartile range] age remained similar from 77 [71-83] years to 78 [72-84] years for overall AVR, decreased from 84 [79-88] years to 81 [75-86] years for TAVR, and decreased from 76 [71-81] years to 72 [68-77] years for SAVR. For all AVR patients, the prevalence of comorbidities remained relatively stable. The 1-year mortality for all AVR decreased from 11.9% to 9.4%. Annual change in the adjusted odds of 1-year mortality was 0.93 (95% CI: 0.92-0.94) for TAVR and 0.98 (95% CI: 0.97-0.99) for SAVR, and 0.94 (95% CI: 0.93-0.95) for all AVR. Patients discharged to home after AVR increased from 24.2% to 54.7%, primarily driven by increasing home discharge after TAVR., Conclusions: The advent of TAVR has led to about a 60% increase in overall AVR in older adults. Improving outcomes in AVR as a whole following the advent of TAVR with increased access is a reassuring trend., Competing Interests: Funding Support and Author Disclosures Dr Mori is a PhD student in the Investigative Medicine Program at Yale, which is supported by CTSA grant number UL1 TR001863 from the National Center for Advancing Translational Science (NCATS), a component of the National Institutes of Health (NIH). Dr Gupta was supported by NIH training grant T32 HL007854. The contents of this paper are solely the responsibility of the authors and do not necessarily represent the official view of NIH. Dr Gupta has received payment from the Arnold & Porter Law Firm for work related to the Sanofi clopidogrel litigation and from the Ben C. Martin Law Firm for work related to an IVC filter litigation; holds equity in Heartbeat Health, Inc; and has received consulting fees from Edwards Lifesciences. Dr Vahl has received institutional funding from Boston Scientific, Edwards Lifesciences, JenaValve, Medtronic, and Siemens Healthineers; and has personally received consulting fees from Abbott Vascular, Boston Scientific, and Siemens Healthineers. Dr Kirtane has received institutional funding from Medtronic, Boston Scientific, Abbott Vascular, Abiomed, CSI, CathWorks, Siemens, Philips, and ReCor Medical; has received fees paid to Columbia University and/or Cardiovascular Research Foundation for speaking engagements and/or consulting; has been a consultant for Neurotronic; and has received travel expenses/meals from Medtronic, Boston Scientific, Abbott Vascular, Abiomed, CSI, CathWorks, Siemens, Philips, ReCor Medical, Chiesi, OpSens, Zoll, and Regeneron. Dr Leon is an early physician founder and has an equity relationship (<1% of the company) with Mitralign. Dr Kodali has received consultant honoraria from Admedus, Dura Biotech, and TriCares; has equity in Dura Biotech, MicroInterventional Devices, Thubrikar Aortic Valve Inc, Supira, Admedus, TriFlo, and Adona; and has received institutional research funding from Edwards Lifesciences, Medtronic, Abbott Vascular, Boston Scientific, and JenaValve. Dr. Krumholz, in the past 3 years, has received expenses and/or personal fees from UnitedHealth, IBM Watson Health, Element Science, Aetna, Facebook, Massachusetts Medical Society, the Siegfried and Jensen Law Firm, Arnold and Porter Law Firm, Martin/Baughman Law Firm, F-Prime, and the National Center for Cardiovascular Diseases in Beijing; is a co-founder of Refactor Health and HugoHealth; and has received grants and/or contracts from the Centers for Medicare & Medicaid Services, Medtronic, U.S. Food and Drug Administration, Johnson & Johnson, Foundation for a Smoke-Free World, State of Connecticut Department of Public Health, Agency for Healthcare Research and Quality, National Institutes of Health, American Heart Association, and the Shenzhen Center for Health Information. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021. Published by Elsevier Inc.)

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 B 12 on 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 B 12 levels 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 B 12 deficiency 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 B 12 for 90 days eliminated iron, vitamin B 12 deficiency and reduced the overall proportion of anemia by 53.5%. However, addition of vitamin B 12 to IFA supplementation had no impact on improving the hemoglobin levels among adolescent girls. The present study does not recommend provision of vitamin B 12 for prevention and treatment of anemia in this population group., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

We aimed to investigate the relationship of modified body mass index (mBMI), the product of BMI and serum albumin, with survival after transcatheter (TAVI) and surgical aortic valve implantation (SAVI). Frailty is associated with poor outcomes after TAVI and SAVI for severe aortic stenosis (AS). However, clinical frailty is not routinely measured in clinical practice due to the cumbersome nature of its assessment. Modified BMI is an easily measurable surrogate for clinical frailty that is associated with survival in elderly cohorts with non-valvular heart disease. We utilized individual patient-level data from a pooled database of the Placement of Aortic Transcatheter Valves (PARTNER) trials from the PARNTER1, PARTNER2 and S3 cohorts. We estimated cumulative mortality at 1 year for quartiles of mBMI with the Kaplan-Meier method and compared them with the log-rank test. We performed Cox proportional hazards modeling to assess the association of mBMI strata with 1-year mortality adjusting for baseline clinical characteristics. A total of 6593 patients who underwent TAVI or SAVI (mean age 83±7.3 years, 57% male) were included. mBMI was independently associated with all-cause one-year mortality with the lowest mBMI quartile as most predictive (HR 2.33, 95% CI 1.80-3.02, p < 0.0001). Notably, mBMI performed as well as clinical frailty index to predict 1-year mortality in this cohort. In conclusion, modified BMI predicts 1-year survival after both TAVI and SAVI. Given that it performed similar to the clinical frailty index, it may be used as a clinical tool for assessment of frailty prior to valve implantation., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: The optimal choice of oral P2Y12 receptor inhibitors has the potential to significantly influence outcomes. We seek to compare the safety and efficacy of the three most commonly used oral P2Y12 receptor inhibitors (clopidogrel, prasugrel, and ticagrelor) in acute coronary syndromes (ACS) via a comprehensive systematic review and network meta-analysis., Evidence Acquisition: In line with the Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines, we performed a comprehensive search for RCTs which compared cardiovascular and hemorrhagic outcomes after use of at least two of the distinct oral P2Y12 receptor inhibitors (i.e. clopidogrel, prasugrel, and ticagrelor). A search strategy has been designed to systematically search multiple databases, including MEDLINE with PubMed interface, The Cochrane Central Register of Controlled Trials, and Embase. In addition, key inclusion criteria will be trial size of at least 100 patients and at least 1 month of follow-up time. Several prespecified subgroups will be explored, including Asian patients, patients presenting with ST-elevation myocardial infarction, patients of advanced age, and others., Evidence Synthesis: Exploratory frequentist pairwise meta-analyses will be based primarily on a random-effects method, relying on relative risks (RR) for short-term outcomes and incidence rate ratios (IRR) for long-term outcomes. Inferential frequentist network meta-analysis will be based primarily on a random-effects method, relying on RR and IRR as specified above. Results will be reported as point summary of effect, 95% CI, and P values for effect, and graphically represented using forest plots., Conclusions: An international collaborative network meta-analysis has begun to comprehensively analyze the safety and efficacy of prasugrel, ticagrelor and clopidogrel, each on a background of aspirin, for management of patients with ACS. It is our hope that the rigor and breadth of the undertaking described herein will provide novel insights that will inform optimal patient care for patients with ACS treated conservatively, or undergoing revascularization.

Anesthetics such as isoflurane are known to cause apoptosis in the developing mammalian brain. However, isoflurane may have protective effects on the heart via relieving ischemia and downregulating genes related to apoptosis. Ischemic preconditioning, e.g. through the use of low levels of carbon monoxide (CO), has promise in preventing ischemia-reperfusion injury and cell death. However, it is still unclear how it either triggers the stress response in neonatal hearts. For this reason, thirty-three microRNAs (miRNAs) known to be differentially expressed following anesthesia and/or ischemic or hypoxic heart damage were investigated in the hearts from neonatal mice exposed to isoflurane or low level of CO, using an air-exposed control group. Only miR-93-5p increased with isoflurane exposure, which may be associated with the suppression of cell death, autophagy, and inflammation. By contrast, twelve miRNAs were differentially expressed in the heart following CO treatment. Many miRNAs previously shown to be responsible for suppressing cell death, autophagy, and myocardial hypertrophy were upregulated (e.g., 125b-3p, 19-3p, and 21a-5p). Finally, some miRNAs (miR-103-3p, miR-1a-3p, miR-199a-1-5p) which have been implicated in regulating energy balance and cardiac contraction were also differentially expressed. Overall, this study demonstrated that CO-mediated miRNA regulation may promote ischemic preconditioning and cardioprotection based on the putative protective roles of the differentially expressed miRNAs explored herein and the consistency of these results with those that have shown positive effects of CO on heart viability following anesthesia and ischemia-reperfusion stress.

Importance: Thrombotic events are commonly reported in critically ill patients with COVID-19. Limited data exist to guide the intensity of antithrombotic prophylaxis., Objective: To evaluate the effects of intermediate-dose vs standard-dose prophylactic anticoagulation among patients with COVID-19 admitted to the intensive care unit (ICU)., Design, Setting, and Participants: Multicenter randomized trial with a 2 × 2 factorial design performed in 10 academic centers in Iran comparing intermediate-dose vs standard-dose prophylactic anticoagulation (first hypothesis) and statin therapy vs matching placebo (second hypothesis; not reported in this article) among adult patients admitted to the ICU with COVID-19. Patients were recruited between July 29, 2020, and November 19, 2020. The final follow-up date for the 30-day primary outcome was December 19, 2020., Interventions: Intermediate-dose (enoxaparin, 1 mg/kg daily) (n = 276) vs standard prophylactic anticoagulation (enoxaparin, 40 mg daily) (n = 286), with modification according to body weight and creatinine clearance. The assigned treatments were planned to be continued until completion of 30-day follow-up., Main Outcomes and Measures: The primary efficacy outcome was a composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days, assessed in randomized patients who met the eligibility criteria and received at least 1 dose of the assigned treatment. Prespecified safety outcomes included major bleeding according to the Bleeding Academic Research Consortium (type 3 or 5 definition), powered for noninferiority (a noninferiority margin of 1.8 based on odds ratio), and severe thrombocytopenia (platelet count <20 ×103/µL). All outcomes were blindly adjudicated., Results: Among 600 randomized patients, 562 (93.7%) were included in the primary analysis (median [interquartile range] age, 62 [50-71] years; 237 [42.2%] women). The primary efficacy outcome occurred in 126 patients (45.7%) in the intermediate-dose group and 126 patients (44.1%) in the standard-dose prophylaxis group (absolute risk difference, 1.5% [95% CI, -6.6% to 9.8%]; odds ratio, 1.06 [95% CI, 0.76-1.48]; P = .70). Major bleeding occurred in 7 patients (2.5%) in the intermediate-dose group and 4 patients (1.4%) in the standard-dose prophylaxis group (risk difference, 1.1% [1-sided 97.5% CI, -∞ to 3.4%]; odds ratio, 1.83 [1-sided 97.5% CI, 0.00-5.93]), not meeting the noninferiority criteria (P for noninferiority >.99). Severe thrombocytopenia occurred only in patients assigned to the intermediate-dose group (6 vs 0 patients; risk difference, 2.2% [95% CI, 0.4%-3.8%]; P = .01)., Conclusions and Relevance: Among patients admitted to the ICU with COVID-19, intermediate-dose prophylactic anticoagulation, compared with standard-dose prophylactic anticoagulation, did not result in a significant difference in the primary outcome of a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days. These results do not support the routine empirical use of intermediate-dose prophylactic anticoagulation in unselected patients admitted to the ICU with COVID-19., Trial Registration: ClinicalTrials.gov Identifier: NCT04486508.

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.

The coronavirus disease 2019 (COVID-19) can result in a hyperinflammatory state, leading to acute respiratory distress syndrome (ARDS), myocardial injury, and thrombotic complications, among other sequelae. Statins, which are known to have anti-inflammatory and antithrombotic properties, have been studied in the setting of other viral infections, but their benefit has not been assessed in COVID-19. This is a retrospective analysis of patients admitted with COVID-19 from February 1 st through May 12 th , 2020 with study period ending on June 11 th , 2020. Antecedent statin use was assessed using medication information available in the electronic medical record. We constructed a multivariable logistic regression model to predict the propensity of receiving statins, adjusting for baseline sociodemographic and clinical characteristics, and outpatient medications. The primary endpoint includes in-hospital mortality within 30 days. A total of 2626 patients were admitted during the study period, of whom 951 (36.2%) were antecedent statin users. Among 1296 patients (648 statin users, 648 non-statin users) identified with 1:1 propensity-score matching, statin use is significantly associated with lower odds of the primary endpoint in the propensity-matched cohort (OR 0.47, 95% CI 0.36-0.62, p < 0.001). We conclude that antecedent statin use in patients hospitalized with COVID-19 is associated with lower inpatient mortality.

Background: Oldest-old patients (≥85 years) constitute half the acute myocardial infarction hospitalizations among older adults and more commonly have atypical presentation, under-treatment, and functional impairments. Yet this group has not been well characterized. We characterized differences in presentation, functional impairments, treatments, health status, and mortality among middle-old (75-84 years) and oldest-old patients with myocardial infarction., Methods: We analyzed data from the ComprehenSIVe Evaluation of Risk Factors in Older Patients with AMI (SILVER-AMI) study that enrolled 3041 patients ≥75 years of age from 94 hospitals across the US between 2013 and 2016. We performed Cox proportional hazards regression to examine the association between the oldest-old (n = 831) and middle-old (n = 2210) age categories with postdischarge 6-month case fatality rate adjusting for sociodemographic and clinical variables, and mobility impairment., Results: The oldest-old were less likely to present with chest pain (52.7% vs 57.7%) as their primary symptom or to receive coronary revascularization (58.1% vs 71.8) (P < .01 for both). The oldest-old were more likely to have functional impairments and had higher 6-month mortality compared with the middle-old patients (hazard ratio 1.78, 95% confidence interval, 1.39-2.28). This association was substantially attenuated after adjusting for mobility impairment (hazard ratio 1.29, confidence interval, 0.99-1.68)., Conclusions: There is considerable heterogeneity in presentation, treatment, and outcomes among older patients with myocardial infarction. Mobility impairment, a marker for frailty, modifies the association between advanced age and treatments as well as outcomes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The SARS-CoV-2 virus responsible for the COVID-19 pandemic has generated an explosion of interest both in the mechanisms of infection leading to dissemination and expression of this disease, and in potential risk factors that may have a mechanistic basis for disease propagation or control. Vitamin D has emerged as a factor that may be involved in these two areas. The focus of this article is to apply our current understanding of vitamin D as a facilitator of immunocompetence both with regard to innate and adaptive immunity and to consider how this may relate to COVID-19 disease. There are also intriguing potential links to vitamin D as a factor in the cytokine storm that portends some of the most serious consequences of SARS-CoV-2 infection, such as the acute respiratory distress syndrome. Moreover, cardiac and coagulopathic features of COVID-19 disease deserve attention as they may also be related to vitamin D. Finally, we review the current clinical data associating vitamin D with SARS-CoV-2 infection, a putative clinical link that at this time must still be considered hypothetical.

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.

Zinc is an essential micronutrient that impacts the cardiovascular system through modulation of oxidative stress. It is unknown whether zinc levels are affected in heart failure (HF), and whether the association, if present, is causal. A systematic search for publications that report coexisting zinc deficiency in patients with HF was performed to provide an overview of the pathophysiological and epidemiological aspects of this association (last search April 2019). Review of the literature suggests multiple potential pathophysiologic causes for zinc deficiency in HF as a result of impaired micronutrient consumption, hyper-inflammatory state, upregulation of the renin-angiotensin-aldosterone axis, diminished absorption, and hyperzincuria from HF medications. In a longitudinal study of patients with HF in the setting of intestinal malabsorption, there was partial cardiomyocyte and left ventricular ejection fraction recovery with intravenous selenium and zinc supplementation. Two randomized double-blind control trials evaluating micronutrient and macronutrient supplementation including zinc in patients with HF found improvement in echocardiographic findings compared with placebo. Two recently completed studies evaluated the role for zinc supplementation in 2 different HF populations: a trial of zinc supplementation in patients with non-ischemic HF, and a trial of micronutrient supplementation (including B vitamins, vitamin D, and zinc) in veterans with systolic dysfunction; the results of which are still pending. Several pathobiological pathways to link zinc deficiency with the development and deterioration of HF are presented. Preliminary clinical data are supportive of such an association and future studies should further investigate the effects of zinc supplementation on outcomes in patients with HF., (Copyright © 2020. Published by Elsevier Inc.)

Objectives: 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: Although risk assessment models are available for patients with HF with reduced ejection fraction, few have assessed the risks of death and hospitalization in patients with HFpEF., Methods: The following 5 methods: logistic regression with a forward selection of variables; logistic regression with a lasso regularization for variable selection; random forest (RF); gradient descent boosting; and support vector machine, were used to train models for assessing risks of mortality and HF hospitalization through 3 years of follow-up and were validated using 5-fold cross-validation. Model discrimination and calibration were estimated using receiver-operating characteristic curves and Brier scores, respectively. The top prediction variables were assessed by using the best performing models, using the incremental improvement of each variable in 5-fold cross-validation., Results: The RF was the best performing model with a mean C-statistic of 0.72 (95% confidence interval [CI]: 0.69 to 0.75) for predicting mortality (Brier score: 0.17), and 0.76 (95% CI: 0.71 to 0.81) for HF hospitalization (Brier score: 0.19). Blood urea nitrogen levels, body mass index, and Kansas City Cardiomyopathy Questionnaire (KCCQ) subscale scores were strongly associated with mortality, whereas hemoglobin level, blood urea nitrogen, time since previous HF hospitalization, and KCCQ scores were the most significant predictors of HF hospitalization., Conclusions: These models predict the risks of mortality and HF hospitalization in patients with HFpEF and emphasize the importance of health status data in determining prognosis. (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist [TOPCAT]; NCT00094302)., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background Heart failure (HF) is an emerging epidemic in China and accounts for significant healthcare resource utilization in the inpatient setting. To create evidence-based, life-saving, and cost-saving hospitalization systems, the first step is to characterize the contemporary national landscape of inpatient HF care. Methods and Results In the China PEACE 5r-HF study (China Patient-centered evaluative Assessment of Cardiac Events Retrospective Study of Heart Failure), we used 2-stage random sampling to create a nationally representative cohort of 10 004 admissions for HF from 189 hospitals in 2015 in China. Data on patient characteristics, management, and outcomes were obtained through centralized medical record abstraction. The median age of the cohort was 73 years (interquartile range, 65-80), and 48.9% were women. More than half (56.2%) of the patients were hospitalized in rural areas. Prevalence of ejection fraction ≥50%, 40% to 50%, and <40% was 60.3%, 17.7%, and 22.0%, respectively. We identified substantial gaps in care, including underutilization of diagnostic tests such as echocardiograms (63.6%), chest imaging (75.2%), and biomarker testing (56.4%), low prescription rates of guideline-recommended medications during hospitalization and at discharge, suboptimal rates of follow-up appointments (24.3%), and widespread utilization of traditional Chinese medicine (74.8%). The combined rate of in-hospital mortality and treatment withdrawal in our study was 3.5%, and median length-of-stay was 9 days (interquartile range, 7-13). Conclusions Patients admitted with acute HF in China have distinctive epidemiology and receive substandard care, but have low inpatient mortality despite long length of stay. These findings provide opportunities for streamlining efficiencies while improving quality of inpatient HF care in China. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT02877914.

Anemia is a major public health problem in India with prevalence of more than 50% amongst children and adolescents. The decline in the burden of anemia has been insignificant over the past 5 decades. The present review assesses the National Guidelines for Prevention and Control of Anemia in India, the current status of the program implementation and possible reasons for the continued high prevalence of anemia in the country.

Young women with acute myocardial infarction (AMI) have a worse prognosis than their male counterparts. We searched for differences in the electrocardiographic presentation of men and women in a large, contemporary registry of young adults with AMI that could help explain gender differences in outcomes. The qualifying electrocardiogram was blindly assessed by a central core lab in 3,354 patients (67% women) aged 18 to 55 years included in the Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients study. Compared with men, women did not have a different frequency of sinus rhythm, and they had shorter PR and QRS intervals and longer QTc intervals. Intraventricular conduction disturbances were not different among genders. Notably, women were more likely than men to have abnormal Q waves in anterior leads and a lower frequency of Q waves in other territories. ST-segment elevation myocardial infarction (STEMI) diagnosis was less frequent in women than in men (44.6% vs 55.1%, p < 0.001). Among patients with STEMI, women had less magnitude and extent of ST-segment elevation than men. In patients with non-STEMI, the frequency, magnitude, and extent of ST-segment depression were not different among genders, but women had anterior ST-segment depression less frequently and anterior negative T waves more frequently compared with men. These differences remained statistically significant after adjusting for baseline characteristics. In conclusion, there are significant gender differences in the electrocardiographic presentation of AMI among young patients. Further studies are warranted to evaluate their impact on gender-related differences in the management and outcomes of AMI., (Copyright © 2017 Elsevier Inc. All rights reserved.)

According to RSOC (2013-2014) data, high prevalence of stunting (26.7%) and wasting (13.0%) exists amongst under-five children belonging to highest wealth index communities. India possibly cannot achieve the 2025 Global nutrition targets for reducing the rate of stunting and wasting amongst Under-five children, unless efforts are also directed towards this group.

Objective: To assess the prevalence of vitamin B 12 and folate deficiencies among children residing at high altitude regions of Himachal Pradesh, India., Methods: A total of 215 school children in the age group of 6-18 y were included. Biochemical estimation of serum vitamin B 12 and folate levels was undertaken using chemiluminescence immunoassay method. The consumption pattern of foods high in dietary vitamin B 12 and folate was recorded using Food Frequency Questionnaire., Results: The median levels (interquartile range) of serum vitamin B 12 and folate were 326 (259-395) pg/ml and 7.7 (6-10) ng/ml respectively. The prevalence of vitamin B 12 and folate deficiency amongst school age children was found as 7.4% and 1.5% respectively., Conclusions: A low prevalence of vitamin B 12 and folate deficiencies was found amongst children aged 6-18 y living at high altitude regions in India. This is possibly due to high frequency of consumption of foods rich in vitamin B 12 and folate.

Background: 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., Methods and Results: Electronic searches were conducted in MEDLINE and EMBASE for English scientific literature up to the 18th June 2012. A total of 2065 references were retrieved and evaluated for relevance. Reference lists of retrieved studies and review articles were examined to ensure all relevant studies were included. Data were extracted from 192 studies, total of 83 236 patients. The incidence of periprocedural complications for catheter ablation of atrial fibrillation was 2.9% (95% confidence interval, 2.6-3.2). There was a significant decrease in the acute complication rate in 2007 to 2012 compared with 2000 to 2006 (2.6% versus 4.0%; P=0.003). The complication rates reported were higher in prospective studies compared with those that retrospectively described complications (3.5% versus 2.7%; P=0.03). There were no significant associations among procedure duration, ablation time or ablation strategy, and acute complication rate., Conclusions: Catheter ablation of atrial fibrillation has a low incidence of periprocedural complications. The acute complication rate has decreased significantly in recent years. This may reflect improved catheter technology and experience. The use of different strategies across centers worldwide seems to be safe with no established relationship between procedural variables and complication rate.

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, which have 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, as well as general cardiology audience. The studies included in this article represent the most significant research related to hypertension.

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 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: It is uncertain how intracranial stenting (ICS) has been adopted nationally during a period characterized by a restrictive payment policy by the Centers for Medicare & Medicaid Services, humanitarian device exemption approval by the Food and Drug Administration, and insufficient evidence of effectiveness. We sought to determine the trends in rates of ICS use and associated outcomes in the United States., Methods and Results: From 65 211 328 Medicare Fee-for-Service beneficiaries hospitalized between 2006 and 2010 in acute care hospitals in the United States, we included patients with ICD-9-CM procedure codes for intracranial angioplasty and stenting, excluding those with a principal discharge diagnosis code of cerebral aneurysm or subarachnoid hemorrhage. We report operative rates per 1 000 000 person-years and outcomes including 30-day and 1-year mortality rates. There were 838 ICS procedures performed among Fee-for-Service beneficiaries. The overall hospitalization rate for ICS increased significantly from ≈1 per 1 000 000 person-years (n=35 procedures) in 2006 to 9 per 1 000 000 person-years (n=258 procedures) in 2010 (P=0.0090 for trend). Procedure rates were higher in men than in women, and were highest among patients aged 75 to 84 years and lowest among those ≥85 years. The 30-day mortality rate increased from 2.9% (95% CI, 0.1 to 15.3) to 12.9% (95% CI, 9.0 to 17.6), P=0.1294 for trend, and the 1-year mortality rate increased from 14.7% (95% CI, 5.0 to 31.1) to 19.5% (95% CI, 14.9 to 24.9), P=0.0101; however, the annual changes were not significant after adjustment., Conclusions: ICS utilization in the United States has modestly increased during a period of inadequate supportive evidence. Humanitarian device exemption and a restrictive payment policy appear to have caused slow adoption of the technology.

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.

Mucormycosis, although said to be less common than candidiasis and aspergillosis is becoming increasingly associated with many co-morbid conditions and immunosuppression. Renal involvement, rarely reported previously, has also been documented with increasing frequency in recent times in both diseased as well as apparently healthy individuals. The kidneys may be involved in disseminated disease or have an isolated involvement for unexplained reasons. The manifestations are very serious particularly in patients with bilateral renal mucormycosis who often develop acute kidney injury and usually have a fatal outcome. The diagnosis of the renal mucormycosis is based on renal histology sections of renal biopsy or nephrectomised kidneys. Imaging with computerised tomography with contrast is of tremendous help in early identification of these cases before histological diagnosis. Once diagnosis is established, prompt treatment with antifungal medication, including Amphotericin-B (and its lipid formulations) and posaconazole, and removal of infected tissue is necessary to save from otherwise fatal infection.

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 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 cardiovascular disease among racial and ethnic minorities.

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 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 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 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 health costs, cost-effectiveness, and resource utilization.

Respiratory syncytial virus (RSV) is commonly known to cause an influenza-like illness. However, it can also cause more severe disease in young children and older adults comprising of organ transplant patients with immunocompromised status. Till date, only four cases of RSV infections have been reported in HIV-positive adults. We describe here a case of HIV-positive female with relatively preserved immune function who presented with RSV infection requiring ventilation and showed improvement after prompt treatment with intravenous immunoglobulin.

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 c in 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.