Predictors of spontaneous pregnancy loss in single ventricle physiology.

BACKGROUND: Pregnant patients with single ventricle (SV) physiology carry a high risk of spontaneous pregnancy loss (SPL), yet the clinical factors contributing to this risk are not well defined. METHODS: Single-centre retrospective study of pregnant patients with SV physiology seen in cardio-obstetrics clinic over the past 20 years with chart review of their obstetric history. Patients without a known pregnancy outcome were excluded. Univariable Bayesian panel-data random effects logit was used to model the risk of SPL. RESULTS: The study included 20 patients with 44 pregnancies, 20 live births, 21 SPL and 3 elective abortions. All had Fontan palliation except for two with Waterston and Glenn shunts. 10 (50%) had a single right ventricle (RV). 14 (70%) had moderate or severe atrioventricular valve regurgitation (AVVR). Atrial arrhythmias were present in 16 (80%), Fontan-associated liver disease (FALD) in 15 (75%) and FALD stage 4 in 9 (45%). 12 (60%) were on anticoagulation. Average first-trimester oxygen saturation was 93.8% for live births and 90.8% for SPL. The following factors were associated with higher odds of SPL: RV morphology (OR 1.72 (95% credible interval (CrI) 1.0008-2.70)), moderate or severe AVVR (OR 1.64 (95% CrI 1.003-2.71)) and reduced first-trimester oxygen saturation (OR 1.83 (95% CrI 1.03-2.71) for each per cent decrease in O2 saturation. CONCLUSION: Pregnant patients with SV physiology, particularly those with RV morphology, moderate or severe AVVR, and lower first-trimester oxygen saturations, have a higher risk of SPL. Identifying these clinical risk factors can guide preconception counselling by the cardio-obstetrics team.

Coronary Artery Surgery: Past, Present, and Future.

Coronary artery bypass grafting (CABG) is the most commonly performed and studied major cardiac operation worldwide. An understanding of the evolution of CABG, including the early days of cardiac surgery, the first bypass operation, continuous improvements in techniques, and streamlining of the operation, is important to inform current trends and future innovations. This article will examine how CABG evolved (from techniques to conduits), describe current trends in the field, and explore what lies on the horizon for the future of CABG.

Pathophysiology and management of saphenous vein graft disease.

INTRODUCTION: The saphenous vein graft (SVG) is the most used conduit in CABG. With standardization of its use as a conduit came an understanding of its accelerated atherosclerosis, known as saphenous vein graft disease (SVGD). Given its extensive use, a review of the pathophysiology and management of SVGD is important as we optimize its use. AREAS COVERED: For this review, an extensive literature search was completed to identify and examine the evolution of SVG in CABG, mechanisms driving SVGD, and methods developed to prevent and manage it. This includes a review of relevant major papers and trials in this space. EXPERT OPINION: Eras of evolution in SVG usage in CABG include an experimental era, era of SVG dominance in CABG, and the current era of mixed venous and arterial grafting. As SVGD was studied, the mechanisms behind it became more understood, and prevention and management methods were developed. As advances in surgical techniques and pharmacotherapy continue to reduce occurrence and severity of SVGD, long-term patency of SV grafts continues to improve and remain excellent in optimized settings. With continued innovation and improvement in operative techniques, the SVG conduit is and will remain an important player in the field of coronary bypass.

Predictors of Major Adverse Cardiovascular Events in Patients With Moderate Aortic Stenosis: Implications for Aortic Valve Replacement.

BACKGROUND: Although the prognosis and management of severe aortic stenosis has been extensively studied, the risk stratification and outcomes of patients with moderate aortic stenosis remain elusive. METHODS: This study included 674 patients from the Cleveland Clinic Health System with moderate aortic stenosis (aortic valve area, 1-1.5 cm2; mean gradient, 20-40 mm Hg; and peak velocity <4 m/s) and an NT-proBNP (N-terminal pro-B-type natriuretic peptide) level within 3 months of index diagnosis. The primary outcome of major adverse cardiovascular events (defined as the composite outcome of progression to severe aortic stenosis requiring aortic valve replacement, heart failure hospitalization, or death) was extracted from the electronic medical record. RESULTS: The mean age was 75.3±12 years, and 57% were men. During a median follow-up of 316 days, the composite end point occurred in 305 patients. There were 132 (19.6%) deaths, 144 (21.4%) heart failure hospitalizations, and 114 (16.9%) patients underwent aortic valve replacement. Elevated NT-proBNP (1.41 [95% CI, 1.01-1.95]; P=0.048), diabetes (1.46 [95% CI, 1.08-1.96]; P=0.01), elevated averaged mitral valve E/e' ratio (hazard ratio, 1.57 [95% CI, 1.18-2.10]; P<0.01), and presence atrial fibrillation at the time of index echocardiogram (hazard ratio, 1.83 [95% CI, 1.15-2.91]; P=0.01) were each independently associated with an increased hazard for the composite outcome and when taken collectively, each of these factors incrementally increased risk. CONCLUSIONS: These results further elucidate the relatively poor short-medium term outcomes and risk stratification of patients with moderate aortic stenosis, supporting randomized trials assessing the efficacy of transcatheter aortic valve replacement in this population.

Kinase signaling as a drug target modality for regulation of vascular hyperpermeability: A case for ARDS therapy development.

The endothelial vascular permeability barrier has an important role throughout the body's extensive vasculature, and its disruption leads to vascular hyperpermeability (leakage), which is associated with numerous medical conditions. In the lung, vascular hyperpermeability can lead to pulmonary edema and acute respiratory distress syndrome (ARDS), the most severe and deadly complication of viral and bacterial infections, trauma and radiation exposure. There is currently no pharmacological treatment for ARDS with the only approved options being focused on supportive care. The development of effective treatments for ARDS has a potential to turn infectious diseases such as bacterial and viral pneumonia (including COVID-19) into manageable conditions, saving lives and providing a new tool to combat future epidemics. Strategies that aim to protect and augment the vascular endothelial barrier are important avenues to consider as potential treatments for ARDS and other conditions underlined by vascular hyperpermeability. We propose the activation of the MAPKAPK2 (MK2) kinase pathway as a new approach to augment the endothelial barrier and prevent or reverse ARDS and other conditions characterized by vascular barrier dysfunction.

A Systematic Review to Compare Chemical Hazard Predictions of the Zebrafish Embryotoxicity Test With Mammalian Prenatal Developmental Toxicity.

Originally developed to inform the acute toxicity of chemicals on fish, the zebrafish embryotoxicity test (ZET) has also been proposed for assessing the prenatal developmental toxicity of chemicals, potentially replacing mammalian studies. Although extensively evaluated in primary studies, a comprehensive review summarizing the available evidence for the ZET's capacity is lacking. Therefore, we conducted a systematic review of how well the presence or absence of exposure-related findings in the ZET predicts prenatal development toxicity in studies with rats and rabbits. A two-tiered systematic review of the developmental toxicity literature was performed, a review of the ZET literature was followed by one of the mammalian literature. Data were extracted using DistillerSR, and study validity was assessed with an amended SYRCLE's risk-of-bias tool. Extracted data were analyzed for each species and substance, which provided the basis for comparing the 2 test methods. Although limited by the number of 24 included chemicals, our results suggest that the ZET has potential to identify chemicals that are mammalian prenatal developmental toxicants, with a tendency for overprediction. Furthermore, our analysis confirmed the need for further standardization of the ZET. In addition, we identified contextual and methodological challenges in the application of systematic review approaches to toxicological questions. One key to overcoming these challenges is a transition to more comprehensive and transparent planning, conduct and reporting of toxicological studies. The first step toward bringing about this change is to create broad awareness in the toxicological community of the need for and benefits of more evidence-based approaches.

The global role, impact, and limitations of Community Health Workers (CHWs) in breast cancer screening: a scoping review and recommendations to promote health equity for all.

Introduction: Innovative interventions are needed to address the growing burden of breast cancer globally, especially among vulnerable patient populations. Given the success of Community Health Workers (CHWs) in addressing communicable diseases and non-communicable diseases, this scoping review will investigate the roles and impacts of CHWs in breast cancer screening programs. This paper also seeks to determine the effectiveness and feasibility of these programs, with particular attention paid to differences between CHW-led interventions in low- and middle-income countries (LMICs) and high-income countries (HICs).Methods: A scoping review was performed using six databases with dates ranging from 1978 to 2019. Comprehensive definitions and search terms were established for 'Community Health Workers' and 'breast cancer screening', and studies were extracted using the World Bank definition of LMIC. Screening and data extraction were protocolized using multiple independent reviewers. Chi-square test of independence was used for statistical analysis of the incidence of themes in HICs and LMICs.Results: Of the 1,551 papers screened, 33 were included based on inclusion and exclusion criteria. Study locations included the United States (n=27), Bangladesh (n=1), Peru (n=1), Malawi (n=2), Rwanda (n=1), and South Africa (n=1). Three primary roles for CHWs in breast cancer screening were identified: education (n=30), direct assistance or performance of breast cancer screening (n=7), and navigational services (n=6). In these roles, CHWs improved rates of breast cancer screening (n=23) and overall community member knowledge (n=21). Two studies performed cost-analyses of CHW-led interventions.Conclusion: This review extends our understanding of CHW effectiveness to breast cancer screening. It illustrates how CHW involvement in screening programs can have a significant impact in LMICs and HICs, and highlights the three CHW roles of education, direct performance of screening, and navigational services that emerge as useful pillars around which governments and NGOs can design effective programs in this area.