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Importance: National implementation of rapid trio genome sequencing (rtGS) in a clinical acute setting is essential to ensure advanced and equitable care for ill neonates., Objective: To evaluate the feasibility, diagnostic efficacy, and clinical utility of rtGS in neonatal intensive care units (NICUs) throughout Israel., Design, Setting, and Participants: This prospective, public health care-based, multicenter cohort study was conducted from October 2021 to December 2022 with the Community Genetics Department of the Israeli Ministry of Health and all Israeli medical genetics institutes (n = 18) and NICUs (n = 25). Critically ill neonates suspected of having a genetic etiology were offered rtGS. All sequencing, analysis, and interpretation of data were performed in a central genomics center at Tel-Aviv Sourasky Medical Center. Rapid results were expected within 10 days. A secondary analysis report, issued within 60 days, focused mainly on cases with negative rapid results and actionable secondary findings. Pathogenic, likely pathogenic, and highly suspected variants of unknown significance (VUS) were reported., Main Outcomes and Measures: Diagnostic rate, including highly suspected disease-causing VUS, and turnaround time for rapid results. Clinical utility was assessed via questionnaires circulated to treating neonatologists., Results: A total of 130 neonates across Israel (70 [54%] male; 60 [46%] female) met inclusion criteria and were recruited. Mean (SD) age at enrollment was 12 (13) days. Mean (SD) turnaround time for rapid report was 7 (3) days. Diagnostic efficacy was 50% (65 of 130) for disease-causing variants, 11% (14 of 130) for VUS suspected to be causative, and 1 novel gene candidate (1%). Disease-causing variants included 12 chromosomal and 52 monogenic disorders as well as 1 neonate with uniparental disomy. Overall, the response rate for clinical utility questionnaires was 82% (107 of 130). Among respondents, genomic testing led to a change in medical management for 24 neonates (22%). Results led to immediate precision medicine for 6 of 65 diagnosed infants (9%), an additional 2 (3%) received palliative care, and 2 (3%) were transferred to nursing homes., Conclusions and Relevance: In this national cohort study, rtGS in critically ill neonates was feasible and diagnostically beneficial in a public health care setting. This study is a prerequisite for implementation of rtGS for ill neonates into routine care and may aid in design of similar studies in other public health care systems.

Bereavement increases in prevalence as people age and is associated with multiple psychological and health risks, including cardiovascular risk. Religious and existential variables may play an important role in the health impacts of bereavement. Theorized pathways linking religious and existential variables with health have suggested these associations are due to intermediary psychosocial variables, but have not been tested in bereavement. This research empirically tested these pathways in a bereaved population. In N = 73 adults within 1 year of bereavement (mean age = 64.36), this study examined associations between (1) religious and existential characteristics (religious and spiritual struggles, intrinsic religiosity, and existential quest) and intermediary psychosocial variables (depression, loneliness, and difficulties in emotion regulation), and between (2) intermediary psychosocial variables and bereavement-relevant health outcomes (self-reported health, change in health since last year, grief severity, and cardiovascular biomarkers). Cardiovascular biomarkers (heart rate, heart rate variability, and blood pressure) were collected before, during, and after a laboratory grief recall emotion elicitation. Anticipated associations between self-reported religious and existential characteristics and intermediary variables, and between intermediary variables and self-reported bereavement-relevant outcomes, were consistently observed. However, associations between intermediary variables and cardiovascular biomarkers were largely unobserved. This study examined the role of religious and existential variables in whole-person health after bereavement and is among the first to include biomarkers of cardiovascular risk. Results suggest that although religious and existential variables are associated with important bereavement-related outcomes, these associations may be "skin-deep," and extensions to cardiovascular functioning should be re-examined., (© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Introduction: Accurate assessment of right ventricular (RV) systolic function has prognostic and therapeutic implications in many disease states. Echocardiography remains the most frequently deployed imaging modality for this purpose, but estimation of RV systolic function remains challenging. The purpose of this study was to evaluate the diagnostic performance of a novel measurement of RV systolic function called lateral annular systolic excursion ratio (LASER), which is the fractional shortening of the lateral tricuspid annulus to apex distance, compared to right ventricular ejection fraction (RVEF) derived by cardiac magnetic resonance imaging (CMR)., Methods: A retrospective cohort of 78 consecutive patients who underwent clinically indicated CMR and transthoracic echocardiography within 30 days were identified from a database. Parameters of RV function measured included: tricuspid annular plane systolic excursion (TAPSE) by M-mode, tissue Doppler S', fractional area change (FAC) and LASER. These measurements were compared to RVEF derived by CMR using Pearson's correlation coefficients and receiver operating characteristic curves., Results: LASER was measurable in 75 (96%) of patients within the cohort. Right ventricular systolic dysfunction, by CMR measurement, was present in 37% ( n = 29) of the population. LASER has moderate positive correlation with RVEF (r = 0.54) which was similar to FAC (r = 0.56), S' (r = 0.49) and TAPSE (r = 0.37). Receiver operating characteristic curves demonstrated that LASER (AUC = 0.865) outperformed fractional area change (AUC = 0.767), tissue Doppler S' (AUC = 0.744) and TAPSE (AUC = 0.645). A cohort derived dichotomous cutoff of 0.2 for LASER was shown to provide optimal diagnostic characteristics (sensitivity of 75%, specificity of 87% and accuracy of 83%) for identifying abnormal RV function. LASER had the highest sensitivity, accuracy, positive and negative predictive values among the parameters studied in the cohort., Conclusions: Within the study cohort, LASER was shown to have moderate positive correlation with RVEF derived by CMR and more favorable diagnostic performance for detecting RV systolic dysfunction compared to conventional echocardiographic parameters while being simple to obtain and less dependent on image quality than FAC and emerging techniques., Competing Interests: The 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 Stock, Rothstein, Friedman, Gemignani, Costa, Milbridge, Zhang, Taub, O'Rourke and Palac.)

Close monitoring of the QT interval, timely and aggressive management of withdrawal, repletion of electrolytes, and telemetry monitoring may prevent life-threatening arrhythmias for patients being treated for acute alcohol withdrawal., Competing Interests: Author disclosures The authors report no actual or potential conflicts of interest with regard to this article.

Objective: Stripping of the membranes is an established and widely utilized obstetric procedure associated with higher spontaneous vaginal delivery rates, reduced need for formal induction of labor and a lower likelihood of post-term pregnancy. Due to the theoretical concern of bacterial seeding during the procedure many practitioners choose not to sweep the membranes in Group B Streptococcus (GBS) colonized patients. We conducted 'the STRIP-G study' in order to determine whether maternal and neonatal outcomes are affected by GBS carrier status in women undergoing membrane stripping., Study Design: We conducted a prospective study in a tertiary referral center, comparing maternal and neonatal outcomes following membrane stripping among GBS-positive, GBS-negative, and GBS-unknown patients. We compared the incidence of composite adverse neonatal outcomes (primary outcome) among the three study groups, while secondary outcome measure was composite adverse maternal outcomes., Results: A total of 542 women were included in the study, of which 135 were GBS-positive, 361 GBS-negative, and 46 GBS-unknown status. Demographic, obstetric, and intra-partum characteristics were similar for all groups. Adverse neonatal outcomes were observed in 8 (5.9%), 31 (8.6%), and 2 (4.3%) in the GBS-positive, GBS-negative, and unknown groups, respectively (P = 0.530), (Odds Ratio between GBS-Positive vs. GBS-Negative groups 0.67 (95%, CI = 0.30-1.50)); while composite adverse maternal outcomes occurred in 9 (6.66%), 31 (8.59%), and 5 (10.87%) in the GBS-positive, GBS-negative, and unknown groups, respectively (P = 0.617)., Conclusions: Antepartum membrane stripping in GBS carriers appears to be a safe obstetrical procedure that does not adversely affect maternal or neonatal outcomes.

Pulmonary hypertension (PH) is a potentially life-threatening condition arising from a wide variety of pathophysiologic mechanisms. Effective treatment requires a systematic diagnostic approach to identify all reversible mechanisms. Many of these mechanisms are relevant to those afflicted with obesity. The unique mechanisms of PH in the obese include obstructive sleep apnea, obesity hypoventilation syndrome, anorexigen use, cardiomyopathy of obesity, and pulmonary thromboembolic disease. Novel mechanisms of PH in the obese include endothelial dysfunction and hyperuricemia. A wide range of effective therapies exist to mitigate the disability of PH in the obese.

Background and Objectives: Candidates for renal transplantation are at increased risk for complications related to cardiovascular disease; however, the optimal strategy to reduce this risk is not clear. The aim of this study was to evaluate the variability among existing guidelines for preoperative cardiac evaluation of renal transplant candidates., Design, Setting, Participants, & Measurements: A consecutive series of renal transplant candidates (n=204) were identified, and four prominent preoperative cardiac evaluation guidelines, pertaining to this population, were retrospectively applied to determine the rate at which each guideline recommended cardiac stress testing., Results: The rate of pretransplant cardiac stress testing would have ranged from 20 to 100% depending on which guideline was applied. The American Heart Association/American College of Cardiology (ACC/AHA) guideline resulted in the lowest rate of testing (20%). In our population, 178 study subjects underwent stress testing: 17 were found to have ischemia and 10 underwent revascularization. The ACC/AHA approach would have decreased the number of noninvasive tests from 178 to 39; it would have identified only 4 of the 10 patients who underwent revascularization. The three other guidelines (renal transplant-specific guidelines) recommended widespread pretransplant cardiac testing and thus identified nearly all patients who had ischemia on stress testing., Conclusions: The ACC/AHA perioperative guideline may be inadequate for identifying renal transplant candidates with coronary disease; however, renal transplant-specific guidelines may provoke significant overtesting. An intermediate approach based on risk factors specific to the ESRD population may optimize detection of coronary disease and limit testing., (Copyright © 2011 by the American Society of Nephrology)