Prospective, randomized, double-blind, placebo-controlled evaluation of the Pharmacokinetics, Safety and Efficacy of Recombinant Antithrombin Versus Placebo in Preterm Preeclampsia.

Background: Despite expectant management, preeclampsia remote from term usually results in preterm delivery. Antithrombin, which displays antiinflammatory and anticoagulant properties, may have a therapeutic role in treating preterm preeclampsia, a disorder characterized by endothelial dysfunction, inflammation, and activation of the coagulation system.

Objective: This randomized, placebo-controlled clinical trial aimed to evaluate whether intravenous recombinant human antithrombin could prolong gestation and therefore improve maternal and fetal outcomes.

Big data in epilepsy: Clinical and research considerations. Report from the Epilepsy Big Data Task Force of the International League Against Epilepsy.

Epilepsy is a heterogeneous condition with disparate etiologies and phenotypic and genotypic characteristics. Clinical and research aspects are accordingly varied, ranging from epidemiological to molecular, spanning clinical trials and outcomes, gene and drug discovery, imaging, electroencephalography, pathology, epilepsy surgery, digital technologies, and numerous others. Epilepsy data are collected in the terabytes and petabytes, pushing the limits of current capabilities.

Racial disparities in post-stroke functional outcomes in young patients with ischemic stroke.

Background And Purpose: Recent studies show rising incidence of stroke in the young, for which risk factors are not well characterized. There is evidence of increased risk in certain racial and ethnic groups. We assessed racial differences in risk factors, stroke etiology, and outcomes among young stroke patients.

Peri-ictal hypoxia is related to extent of regional brain volume loss accompanying generalized tonic-clonic seizures.

Objectives: Hypoxia, or abnormally low blood-oxygen levels, often accompanies seizures and may elicit brain structural changes in people with epilepsy which contribute to central processes underlying sudden unexpected death in epilepsy (SUDEP). The extent to which hypoxia may be related to brain structural alterations in this patient group remains unexplored.

Methods: We analyzed high-resolution T1-weighted magnetic resonance imaging (MRI) to determine brain morphometric and volumetric alterations in people with generalized tonic-clonic seizures (GTCS) recorded during long-term video-electroencephalography (VEEG), recruited from two sites (n = 22), together with data from age- and sex-matched healthy controls (n = 43).

The Management of Women's Health Care by Internists With a Focus on the Utility of Ultrasound.

Adult women require routine care for the acute and chronic health problems found in both sexes, and they require specialized care for women's health problems, including disease prevention, disease screening, and disease management. Internists should direct primary care and participate in specialized care and to the extent possible follow guidelines published by various professional organizations. They should understand the use of ultrasound in breast cancer screening, the management of pregnancy, and other gynecologic problems, including vaginal bleeding, pelvic pain, and investigation for pelvic malignancy.

BET bromodomain inhibition attenuates cardiac phenotype in myocyte-specific lamin A/C-deficient mice.

Mutation in the LMNA gene, encoding lamin A/C, causes a diverse group of diseases called laminopathies. Cardiac involvement is the major cause of death and manifests as dilated cardiomyopathy, heart failure, arrhythmias, and sudden death. There is no specific therapy for LMNA-associated cardiomyopathy.

The Influence of Obesity on Outcomes After Pediatric Reduction Mammaplasty: A Retrospective Analysis of the Pediatric National Surgical Quality Improvement Program-Pediatric Database.

Background: Symptomatic macromastia causes negative physical and psychosocial effects, which support the need for early intervention, even in the adolescent population (Plast Reconstr Surg 2012;130:785-789). Reduction mammaplasty is a proven treatment that reliably addresses symptoms from macromastia. The National Surgical Quality Improvement Program-Pediatric is the leading nationally validated, risk-adjusted, outcomes-based program to measure and improve the quality of surgical care (Pediatrics 2012;130:e339-e346).

Evaluation of Mavacamten in Symptomatic Patients With Nonobstructive Hypertrophic Cardiomyopathy.

Background: Patients with nonobstructive hypertrophic cardiomyopathy (nHCM) often experience a high burden of symptoms; however, there are no proven pharmacological therapies. By altering the contractile mechanics of the cardiomyocyte, myosin inhibitors have the potential to modify pathophysiology and improve symptoms associated with HCM.

Objectives: MAVERICK-HCM (Mavacamten in Adults With Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy) explored the safety and efficacy of mavacamten, a first-in-class reversible inhibitor of cardiac-specific myosin, in nHCM.

Patient and Surrogate Postenrollment Perspectives on Research Using the Exception From Informed Consent: An Integrated Survey.

Study Objective: It is important for researchers interested in trials using the exception from informed consent to understand the views and experiences of enrolled individuals. Previous studies have shown that patient and surrogate attitudes are generally positive. These studies were small and did not include pediatric patients, and interviews were often conducted long after trial enrollment.

Group A Streptococcus Transcriptome Analysis.

Global gene expression analyses in bacteria have undergone a dramatic transformation. Prior to the development of high-throughput sequencing technologies, real-time PCR or microarray studies were the mainstay of assessing differences in gene expression in bacteria. Real-time PCR remains a critical tool for targeted gene expression analyses.

Regional variations in medical trainee diet and nutrition counseling competencies: Machine learning-augmented propensity score analysis of a prospective multi-site cohort study.

Background: Medical professionals and students are inadequately trained to respond to rising global obesity and nutrition-related chronic disease epidemics, primarily focusing on cardiovascular disease. Yet, there are no multi-site studies testing evidence-based nutrition education for medical students in preventive cardiology, let alone establishing student dietary and competency patterns.

Methods: Cooking for Health Optimization with Patients (CHOP; NIH NCT03443635) was the first multi-national cohort study using hands-on cooking and nutrition education as preventive cardiology, monitoring and improving student diets and competencies in patient nutrition education.

Ictal quantitative surface electromyography correlates with postictal EEG suppression.

Objective: To test the hypothesis that neurophysiologic biomarkers of muscle activation during convulsive seizures reveal seizure severity and to determine whether automatically computed surface EMG parameters during seizures can predict postictal generalized EEG suppression (PGES), indicating increased risk for sudden unexpected death in epilepsy. Wearable EMG devices have been clinically validated for automated detection of generalized tonic-clonic seizures. Our goal was to use quantitative EMG measurements for seizure characterization and risk assessment.

An analysis of key indicators of reproducibility in radiology.

Background: Given the central role of radiology in patient care, it is important that radiological research is grounded in reproducible science. It is unclear whether there is a lack of reproducibility or transparency in radiologic research.

Purpose: To analyze published radiology literature for the presence or lack of key indicators of reproducibility.

A Pilot and Feasibility Mobile Health Intervention to Support Healthy Behaviors in African American Breast Cancer Survivors.

African American breast cancer (AA BC) survivors are more likely to have cancer-related comorbidities compared with other women, ultimately putting them at higher risk for overall mortality and breast cancer-specific mortality. Survivorship care guidelines emphasize the importance of attention to obesity, weight management, and physical activity. Mobile technologies have been effective for improving health behaviors among cancer survivors, though few studies have focused on AA BC survivors.

Plasmablastic Lymphomas: Characterization of Tumor Microenvironment Using CD163 and PD-1 Immunohistochemistry.

This study aims to characterize the tumor microenvironment of plasmablastic lymphoma (PBL) in regard to the quantities of CD163(+) tumor associated macrophages (TAM) and PD1(+) tumor infiltrating lymphocytes (TIL). This article also reviews the existing knowledge of the role of PD-1/PD-L1 pathway in the tumor microenvironment of hematopoietic neoplasms, discusses potential mechanisms to explain our findings, and outlines areas for future studies. We performed CD163 and PD1 immunohistochemical studies in 11 cases classified as plasmablastic lymphoma, and recorded the percentages of positive TAMs and TILs.

COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options.

The novel coronavirus disease (COVID-19) outbreak, caused by SARS-CoV-2, represents the greatest medical challenge in decades. We provide a comprehensive review of the clinical course of COVID-19, its comorbidities, and mechanistic considerations for future therapies. While COVID-19 primarily affects the lungs, causing interstitial pneumonitis and severe acute respiratory distress syndrome (ARDS), it also affects multiple organs, particularly the cardiovascular system.

Genetic basis and molecular biology of cardiac arrhythmias in cardiomyopathies.

Cardiac arrhythmias are common, often the first, and sometimes the life-threatening manifestations of hereditary cardiomyopathies. Pathogenic variants in several genes known to cause hereditary cardiac arrhythmias have also been identified in the sporadic cases and small families with cardiomyopathies. These findings suggest a shared genetic aetiology of a subset of hereditary cardiomyopathies and cardiac arrhythmias.

Successful Mastectomy and Chemotherapy in a Patient with Breast Cancer and Active Generalized Pyoderma Gangrenosum.

Introduction: Pyoderma gangrenosum (PG) is a rare, ulcerating neutrophilic dermatosis often associated with inflammatory bowel disease, rheumatoid arthritis, and myeloproliferative disorders. The classic description of PG includes irregularly shaped ulcers with undermined edges with a gun-metal gray or violaceous hue. The etiology remains unclear but appears to be related to genetically predisposed dysregulation of the innate immune system.

Ulnar Artery Aneurysm as a Late Sequela of Marfan Syndrome.

Marfan syndrome (MFS) is a connective tissue disorder caused by mutations of the FBN1 gene encoding fibrillin-1, which leads to overexpression of transforming growth factor-β, increased hyaluronan deposition, and matrix metalloproteinase activity in the media of the aorta and other muscular arteries. Marfan syndrome patients present with connective tissue laxity and aneurysmal changes to muscular arteries. Successful medical and surgical intervention has prolonged the life expectancy of MFS patients, which can allow atypical presentations of the syndrome to manifest.

De novo EIF2AK1 and EIF2AK2 Variants Are Associated with Developmental Delay, Leukoencephalopathy, and Neurologic Decompensation.

EIF2AK1 and EIF2AK2 encode members of the eukaryotic translation initiation factor 2 alpha kinase (EIF2AK) family that inhibits protein synthesis in response to physiologic stress conditions. EIF2AK2 is also involved in innate immune response and the regulation of signal transduction, apoptosis, cell proliferation, and differentiation. Despite these findings, human disorders associated with deleterious variants in EIF2AK1 and EIF2AK2 have not been reported.

An Anti-Wrinkle Diet: Nutritional Strategies to Combat Oxidation, Inflammation and Glycation.

There is growing awareness of the complex link between nutrition and skin. In the last few decades, our understanding of this link has grown significantly with research findings from multiple laboratory, animal, and human studies. From the impact of diet on clinical features of aging skin, to documentation of the biochemical and histologic changes that occur, our understanding of this link continues to expand and evolve.

Digital Receptor Occupancy Assay in Quantifying On- and Off-Target Binding Affinities of Therapeutic Antibodies.

While monoclonal antibodies are the fastest-growing class of therapeutic agents, we lack a method that can directly quantify the on- and off-target binding affinities of newly developed therapeutic antibodies in crude cell lysates. As a result, some therapeutic antibody candidates could have a moderate on-target binding affinity but a high off-target binding affinity, which not only gives a reduced efficacy but triggers unwanted side effects. Here, we report a single-molecule counting method that precisely quantifies antibody-bound receptors, free receptors, and unbound antibodies in crude cell lysates, termed digital receptor occupancy assay (DRO).