Effects of Tirzepatide on the Clinical Trajectory of Patients with Heart Failure, a Preserved Ejection Fraction, and Obesity.

Background: Patients with heart failure, a preserved ejection fraction (HFpEF), and obesity have significant disability and suffer frequent exacerbations of heart failure. We hypothesized that tirzepatide, a long-acting agonist of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors, would improve a comprehensive suite of clinical endpoints, including measures of health status, functional capacity, quality of life, exercise tolerance, patient well-being, and medication burden in these patients.

Methods: 731 patients in class II-IV heart failure, ejection fraction ≥50%, and body mass index ≥30 kg/m were randomized(double-blind) to tirzepatide(titrated up to 15mg subcutaneously weekly)(n=364) or placebo(n=367), added to background therapy for a median of 104 weeks (Q1=66, Q3=126 weeks).

Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity.

Background: Obesity increases the risk of heart failure with preserved ejection fraction. Tirzepatide, a long-acting agonist of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors, causes considerable weight loss, but data are lacking with respect to its effects on cardiovascular outcomes.

Methods: In this international, double-blind, randomized, placebo-controlled trial, we randomly assigned, in a 1:1 ratio, 731 patients with heart failure, an ejection fraction of at least 50%, and a body-mass index (the weight in kilograms divided by the square of the height in meters) of at least 30 to receive tirzepatide (up to 15 mg subcutaneously once per week) or placebo for at least 52 weeks.

Effects of tirzepatide on circulatory overload and end-organ damage in heart failure with preserved ejection fraction and obesity: a secondary analysis of the SUMMIT trial.

Patients with obesity-related heart failure with preserved ejection fraction (HFpEF) display circulatory volume expansion and pressure overload contributing to cardiovascular-kidney end-organ damage. In the SUMMIT trial, patients with HFpEF and obesity were randomized to the long-acting glucose-dependent insulinotropic polypeptide receptor and glucagon-like peptide-1 receptor agonist tirzepatide (n = 364, 200 women) or placebo (n = 367, 193 women). As reported separately, tirzepatide decreased cardiovascular death or worsening heart failure.

Prospective evaluation of thin-layer agar colour test in routine diagnosis of multidrug-resistant TB.

This study evaluated the diagnostic performance of the thin-layer agar MDR/XDR-TB Colour Test (CT), a complex (MTBC) detection and direct drug susceptibility testing (DST) method with routine sputum, bronchoalveolar lavage and pleural fluid specimen.In a prospective study, the time and rate of MTBC detection were compared between CT, Löwenstein-Jensen, and MGIT media. Times until DST result, sensitivities, and specificities were evaluated between CT and MGIT 960 indirect DST.

Adiponectin and Glucocorticoids Modulate Risk for Preterm Birth: The Healthy Start Study.

Purpose: Adiponectin is a potent uterine tocolytic that decreases with gestational age, suggesting it could be a maternal metabolic quiescence factor. Maternal stress can influence preterm birth risk, and adiponectin levels may be stress-responsive. We characterized associations between adiponectin and glucocorticoids with preterm birth and modeled their predictive utility.

Correlation of toxoplasmosis with small‑for‑gestational‑age newborns.

Background: Toxoplasma gondii infection in pregnant women could lead to significant changes during the pregnancy, affect the outcomes of pregnancy and the timing of labour. Small‑for‑gestational‑age (SGA) newborns are defined by birthweight below the 10th percentile for gestational age. We tested an association between latent toxoplasmosis in pregnant women and deliveries of SGA babies.

Family medicine physician identification of obstetric lacerations: a US national survey.

Introduction And Hypothesis: We evaluated family medicine obstetric providers' identification and categorization of vaginal delivery lacerations in the USA. We hypothesized that there would be inaccuracy in family medicine physicians' identification of vaginal delivery injuries, similar to our previous studies of midwives and obstetricians (OBs).

Methods: We included clinically active physicians who attended deliveries within 2 years and evaluated their identification and categorization of delivery lacerations using descriptive text and visual images.

Diagnosis, management and training in perineal trauma: a UK national survey of obstetricians.

Introduction And Hypothesis: Perineal trauma during vaginal delivery is very common. Training in diagnosis and repair of trauma, including obstetric anal sphincter injuries, varies in the UK. We aimed to investigate the current knowledge and training received by obstetric physicians.

Hypoxia as a potential cause of dyspareunia.

Unlabelled: Dyspareunia is genital pain before, during or after penile-vaginal sexual intercourse. The prevalence of dyspareunia ranges from 8 to 22%. Sexual intercourse concomitant with a pelvic organic lesion is likely to cause pain in most cases.

A Nested Case-Control Study of Allopregnanolone and Preterm Birth in the Healthy Start Cohort.

Context: Chronic stress is a risk factor for preterm birth; however, objective measures of stress in pregnancy are limited. Maternal stress biomarkers may fill this gap. Steroid hormones and neurosteroids such as allopregnanolone (ALLO) play important roles in stress physiology and pregnancy maintenance and therefore may be promising for preterm birth prediction.

Obstetric anal sphincter injuries and other delivery trauma: a US national survey of obstetrician-gynecologists.

Introduction And Hypothesis: Obstetric lacerations complicate the majority of deliveries. The application of standardized guidelines for assessing delivery trauma has not been assessed thoroughly in the United States. We recently identified gaps in US midwives' clinical assessment of delivery trauma.

Project COALESCE-An Example of Academic Institutions as Conveners of Community-Clinic Partnerships to Improve Cancer Screening Access.

In Virginia, 56% of colorectal cancers (CRC) are diagnosed late, making it one of three enduring CRC mortality hotspots in the US. Cervical cancer (CCa) exhibits a similar pattern, with 48% late-stage diagnosis. Mortality for these cancers is worse for non-Latinx/e(nL)-Black people relative to nL-White people in Virginia, but preventable with equitable screening access and timely diagnostic follow-up.

Toxoplasmosis impact on prematurity and low birth weight.

Background: Toxoplasma gondii, one of the most common parasites, causes toxoplasmosis, one of the most frequent zoonotic diseases worldwide. T. gondii infects about one-third of the world's population.

Abemaciclib plus fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in premenopausal women: subgroup analysis from the MONARCH 2 trial.

Background: In MONARCH 2, abemaciclib plus fulvestrant significantly improved median progression-free survival (PFS, 16.4 vs 9.3 months, hazard ratio [HR] 0.

MONARCH 2: Subgroup Analysis of Patients Receiving Abemaciclib Plus Fulvestrant as First-Line and Second-Line Therapy for HR, HER2-Advanced Breast Cancer.

Purpose: In MONARCH 2, abemaciclib plus fulvestrant significantly prolonged progression-free survival (PFS) and overall survival (OS) versus placebo plus fulvestrant in patients with hormone receptor positive (HR), HER2 advanced breast cancer. This exploratory analysis assessed the efficacy of abemaciclib plus fulvestrant across subgroups of patients receiving study therapy as first- or second-line treatment for metastatic disease.

Patients And Methods: Improvements were estimated using Cox models, and a test of interactions of subgroups with treatment was performed.

Metabolomics in Prenatal Medicine: A Review.

Pregnancy is a complicated and insidious state with various aspects to consider, including the well-being of the mother and child. Developing better non-invasive tests that cover a broader range of disorders with lower false-positive rates is a fundamental necessity in the prenatal medicine field, and, in this sense, the application of metabolomics could be extremely useful. Metabolomics measures and analyses the products of cellular biochemistry.

Extracorporeal shock wave therapy for treating dyspareunia: A prospective, randomized, double-blind, placebo-controlled study.

Background: Dyspareunia is a genital pain during or after penile-vaginal sexual intercourse. It is a painful spasm of the pelvic muscles that partly or entirely disables vaginal penetration.

Objectives: We examined the effect of extracorporeal shock wave therapy (ESWT) on idiopathic non-organic dyspareunia in women.

Cystathionine γ-lyase promotes estrogen-stimulated uterine artery blood flow via glutathione homeostasis.

During pregnancy, estrogen (E) stimulates uterine artery blood flow (UBF) by enhancing nitric oxide (NO)-dependent vasodilation. Cystathionine γ-lyase (CSE) promotes vascular NO signaling by producing hydrogen sulfide (HS) and by maintaining the ratio of reduced-to-oxidized intracellular glutathione (GSH/GSSG) through l-cysteine production. Because redox homeostasis can influence NO signaling, we hypothesized that CSE mediates E stimulation of UBF by modulating local intracellular cysteine metabolism and GSH/GSSG levels to promote redox homeostasis.

A Randomized Phase III Study of Abemaciclib Versus Erlotinib in Patients with Stage IV Non-small Cell Lung Cancer With a Detectable Mutation Who Failed Prior Platinum-Based Therapy: JUNIPER.

Introduction: JUNIPER compared the efficacy and safety of abemaciclib, a selective cyclin-dependent kinase 4 and 6 inhibitor, with erlotinib in patients with non-small cell lung cancer (NSCLC) harboring a Kirsten rat sarcoma () mutation.

Methods: JUNIPER was a Phase III, multicenter, randomized, open-label trial of abemaciclib versus erlotinib in patients with stage IV NSCLC and a detectable mutation in codons 12 or 13 of the oncogene, who progressed after platinum-based chemotherapy and 1 additional therapy (could include immune checkpoint inhibitor therapy). Randomized patients (3:2) received either 200 mg abemaciclib twice daily or 150 mg erlotinib once daily with best supportive care until disease progression or unacceptable toxicity.