Allogeneic BCMA-targeting CAR T cells in relapsed/refractory multiple myeloma: phase 1 UNIVERSAL trial interim results.

ALLO-715 is a first-in-class, allogeneic, anti-BCMA CAR T cell therapy engineered to abrogate graft-versus-host disease and minimize CAR T rejection. We evaluated escalating doses of ALLO-715 after lymphodepletion with an anti-CD52 antibody (ALLO-647)-containing regimen in 43 patients with relapsed/refractory multiple myeloma as part A of the ongoing first-in-human phase 1 UNIVERSAL trial. Primary objectives included determination of the safety and tolerability of ALLO-715 and the safety profile of the ALLO-647-containing lymphodepletion regimen.

Prevention Starts in the Womb: Opportunities for Addressing Cardiovascular Risk Factors During Pregnancy and Beyond.

Early identification and mitigation of sex-specific cardiovascular disease risk factors is a potential trajectory-changing strategy to improve lifelong cardiovascular health in women. These sex-specific risk factors include adverse pregnancy outcomes, polycystic ovarian syndrome, and premature menopause. We start by discussing the impact and management of risk factors for adverse pregnancy outcomes as an upstream intervention for cardiovascular disease risk reduction and then address the long-term effect and mitigation of sex-specific risk factors for cardiovascular disease.

Associations between menopause, cardiac remodeling, and diastolic function: the CARDIA study.

Objectives: Heart failure with preserved ejection fraction (HFpEF) affects more women than men. Menopause may influence HFpEF development in women. We assessed cross-sectional and longitudinal associations between menopause and echocardiographic measures of left ventricular (LV) function and cardiac remodeling.

Visceral adiposity, muscle composition, and exercise tolerance in heart failure with preserved ejection fraction.

Aims: Visceral adipose tissue (AT) promotes inflammation and may be associated with disease progression in heart failure with preserved ejection fraction (HFpEF). We characterized regional AT distribution in HFpEF patients and controls and analysed associations with co-morbidities and exercise tolerance.

Methods And Results: Magnetic resonance imaging was performed to quantify epicardial, liver, abdominal, and thigh skeletal muscle AT.

Cyclic guanosine monophosphate and 10-year change in left ventricular mass: the Multi-Ethnic Study of Atherosclerosis (MESA).

Cyclic guanosine monophosphate (cGMP) is a second messenger for natriuretic peptide (NP) and nitric oxide pathways; its enhancement a target for heart failure and cardiovascular disease (CVD). We evaluated whether plasma cGMP was associated with change in left ventricular mass (LVM) among individuals free of CVD and if this differed by sex. In 611 men and 612 women aged 45-84 years with plasma cGMP measured at baseline and cardiac MRI performed at baseline and 10 years later, we tested associations of cGMP [log-transformed, per 1 SD increment] with LVM, adjusting for CVD risk factors and N-terminal pro-B-type-NP (NT-proBNP).

The Association of Adverse Pregnancy Outcomes and Cardiovascular Disease: Current Knowledge and Future Directions.

Purpose Of Review: Adverse pregnancy outcomes are associated with increased risk for future cardiovascular disease. The goal of this review is to share what is currently known about the increased risk and to identify areas for future research.

Recent Findings: Severe studies have identified a strong association between adverse pregnancy outcomes and cardiovascular disease such as heart failure, valvular disease, ischemic heart disease, stroke, hypertension, and metabolic syndrome.

The Importance of Cardiovascular Risk Assessment and Pregnancy Heart Team in the Management of Cardiovascular Disease in Pregnancy.

Pregnancy-related maternal morbidity and mortality is increasing because of complications from cardiovascular disease. Pregnancy results in physiologic changes that can adversely impact the cardiovascular system and lead to adverse pregnancy outcomes. A multidisciplinary pregnancy heart team is essential to safely navigate women with heart disease through pregnancy.

Sex Hormones and Incident Heart Failure in Men and Postmenopausal Women: The Atherosclerosis Risk in Communities Study.

Context: Sex differences exist in heart failure (HF) phenotypes, but there is limited research on the role of sex hormones in HF and its subtypes.

Objective: To examine the associations of total testosterone, dehydroepiandrosterone sulfate (DHEA-S), and sex hormone-binding globulin (SHBG) with incident HF, HF with preserved ejection fraction (HFpEF), and HF with reduced ejection fraction (HFrEF).

Design: Atherosclerosis Risk in Communities (ARIC) study (prospective cohort study).

Endomyocardial Biopsy Characterization of Heart Failure With Preserved Ejection Fraction and Prevalence of Cardiac Amyloidosis.

Objectives: This study prospectively evaluated endomyocardial biopsies in patients with heart failure with preserved ejection fraction (HFpEF) to identify histopathologic phenotypes and their association with clinical characteristics.

Background: Myocardial tissue analysis from a prospectively defined HFpEF cohort reflecting contemporary comorbidities is lacking.

Methods: Patients with HFpEF (EF ≥50%) referred to the Johns Hopkins HFpEF Clinic between August 2014 and September 2018 were enrolled for right heart catheterization and endomyocardial biopsy.

Acute myopericarditis as a cause of isolated right ventricular failure.

Myopericarditis is characterized by pericardial and myocardial inflammation and is a known cause of chest pain and heart failure. It is primarily associated with biventricular or left ventricular dysfunction. We describe an unusual case of a 57-year-old woman with myopericarditis causing isolated right ventricular (RV) failure.

Cyclic Guanosine Monophosphate and Risk of Incident Heart Failure and Other Cardiovascular Events: the ARIC Study.

Background Cyclic guanosine monophosphate (cGMP) is a second messenger regulated through natriuretic peptide and nitric oxide pathways. Stimulation of cGMP signaling is a potential therapeutic strategy for heart failure with preserved ejection fraction (HFpEF) and atherosclerotic cardiovascular disease (ASCVD). We hypothesized that plasma cGMP levels would be associated with lower risk for incident HFpEF, any HF, ASCVD, and coronary heart disease (CHD).

Associations Between the Cyclic Guanosine Monophosphate Pathway and Cardiovascular Risk Factors: MESA.

Background cGMP mediates numerous cardioprotective functions and is a potential therapeutic target for cardiovascular disease. Preclinical studies suggest that plasma cGMP is reflective of natriuretic peptide stimulation. Epidemiologic associations between cGMP and natriuretic peptide, as well as cardiovascular disease risk factors, are unknown.

Multiparity is associated with poorer cardiovascular health among women from the Multi-Ethnic Study of Atherosclerosis.

Background: Multiparity is associated with a greater risk of incident cardiovascular disease. However, the relationship of parity with cardiovascular health, as measured by the American Heart Association Life's Simple 7 metrics, is uncertain.

Objective: We aimed to examine the association between parity and ideal cardiovascular health among 3430 women, aged 45-84 years, free of clinical cardiovascular disease enrolled in the Multi-Ethnic Study of Atherosclerosis.

Association of endogenous sex hormone levels with coronary artery calcium progression among post-menopausal women in the Multi-Ethnic Study of Atherosclerosis (MESA).

Background: Sex differences in the incidence and manifestation of cardiovascular disease (CVD) suggest the involvement of sex hormones in disease pathogenesis. Coronary artery calcium (CAC) and its progression, measured by non-contrast cardiac computed tomography, are markers of subclinical atherosclerosis and predict CVD, even among low-risk women. We hypothesized that sex hormone levels were associated with CAC progression among women in the Multi-Ethnic Study of Atherosclerosis.

Sex Hormones and Change in N-Terminal Pro-B-Type Natriuretic Peptide Levels: The Multi-Ethnic Study of Atherosclerosis.

Context: Sex hormones may influence sex differences in cardiovascular disease (CVD). N-terminal pro-B-type natriuretic peptide (NT-proBNP), a predictor of CVD, is higher in women than men, which may relate to sex hormones.

Objective: To evaluate whether total testosterone (T), bioavailable T, free T, estradiol, dehydroepiandrosterone (DHEA), and SHBG are associated with NT-proBNP.

Adverse pregnancy outcomes and future maternal cardiovascular disease.

Cardiovascular disease (CVD) remains the leading cause of death in women. Although traditional risk factors increase later-life CVD, pregnancy-associated complications additionally influence future CVD risk in women. Recent guidelines for the prevention of CVD in women have added adverse pregnancy outcomes as major CVD risk factors.

Bone-related Parameters are the Main Prognostic Factors for Overall Survival in Men with Bone Metastases from Castration-resistant Prostate Cancer.

Background: Previous studies have reported on prognostic factors for castration-resistant prostate cancer (CRPC); however, most of these studies were conducted before docetaxel chemotherapy was approved for CRPC.

Objective: To evaluate the prognostic value of multiple parameters in men with bone metastases due to CRPC using a contemporary dataset.

Design, Setting, And Participants: The analysis included 1901 patients with metastatic CRPC enrolled in an international, multicenter, randomized, double-blind phase 3 trial conducted between May 2006 and October 2009.

Denosumab for treatment of hypercalcemia of malignancy.

Context: Hypercalcemia of malignancy (HCM) in patients with advanced cancer is often caused by excessive osteoclast-mediated bone resorption. Patients may not respond to or may relapse after iv bisphosphonate therapy.

Objective: We investigated whether denosumab, a potent inhibitor of osteoclast-mediated bone resorption, reduces serum calcium in patients with bisphosphonate-refractory HCM.

Denosumab for patients with persistent or relapsed hypercalcemia of malignancy despite recent bisphosphonate treatment.

Hypercalcemia of malignancy (HCM), caused primarily by tumor-induced bone resorption, may lead to renal failure, coma, and death. Although HCM can be treated with intravenous bisphosphonates, patients may not respond or may relapse on therapy. Denosumab binds the bone resorption mediator RANKL.

Characterization and fate of telomerase-expressing epithelia during kidney repair.

After acute kidney injury, mice with short telomeres develop increased damage with reduced proliferative capacity, which suggests an important role for telomere length in kidney repair. The enzyme telomerase reverse transcriptase (mTert) regulates telomere length; embryonic stem cells and certain adult stem cells express mTert, but whether cells in the adult kidney express mTert and whether these cells play a role in renal repair are unknown. Here, we found that telomerase protein and mRNA were highly enriched in renal papilla, a proposed niche of kidney stem cells.