Cardiac adiposity as a modulator of cardiovascular disease in HIV.

Background: With the number of people living with human immunodeficiency virus (HIV) steadily increasing, cardiovascular disease has emerged as a leading cause of non-HIV related mortality. People living with HIV (PLWH) appear to be at increased risk of coronary artery disease and heart failure (HF), while the underlying mechanism appears to be multifactorial. In the general population, ectopic cardiac adiposity has been highlighted as an important modulator of accelerated coronary artery atherosclerosis, arrhythmogenesis and HF with preserved ejection fraction (HFpEF).

Cardiac Adiposity and Arrhythmias: The Role of Imaging.

Increased cardiac fat depots are metabolically active tissues that have a pronounced pro-inflammatory nature. Increasing evidence supports a potential role of cardiac adiposity as a determinant of the substrate of atrial fibrillation and ventricular arrhythmias. The underlying mechanism appears to be multifactorial with local inflammation, fibrosis, adipocyte infiltration, electrical remodeling, autonomic nervous system modulation, oxidative stress and gene expression playing interrelating roles.

Efficacy and safety of carfilzomib-based regimens in frail patients with relapsed and/or refractory multiple myeloma.

Frailty is most prevalent among elderly multiple myeloma (MM) patients, and frail patients have a higher risk of poor outcomes due to reduced performance status or comorbidities. This post hoc analysis assessed efficacy and safety of carfilzomib combinations in frail patients with relapsed and/or refractory MM from the phase 3 ASPIRE (carfilzomib [27 mg/m2]-lenalidomide-dexamethasone [KRd27] vs lenalidomide-dexamethasone [Rd]), ENDEAVOR (carfilzomib [56 mg/m2]-dexamethasone [Kd56] vs bortezomib-dexamethasone [Vd]), and ARROW (once-weekly carfilzomib [70 mg/m2]-dexamethasone [Kd70] vs carfilzomib [27 mg/m2]-dexamethasone [Kd27]) studies. A frailty algorithm incorporating age, Charlson comorbidity index, and performance status classified patients as fit, intermediate, or frail.

Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): results from a randomised, multicentre, open-label, phase 3 study.

Background: Lenalidomide and bortezomib frontline exposure has raised a growing need for novel treatments for patients with relapsed or refractory multiple myeloma. Carfilzomib in combination with daratumumab has shown substantial efficacy with tolerable safety in relapsed or refractory multiple myeloma in a phase 1 study. In this study, we aimed to compare the efficacy and safety of carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma.

Progression of Subclinical Vascular Damage in People Living With HIV Is Not Predicted by Current Cardiovascular Risk Scores: A Prospective 3-Year Study.

Background: People living with HIV (PLWH) are at high cardiovascular disease (CVD) risk. Traditional CVD risk scores do not accurately reflect their CVD risk. Noninvasive subclinical vascular damage (SVD) biomarkers are valid surrogates of CVD and able to stratify CVD risk.

On the importance of the nonuniform aortic stiffening in the hemodynamics of physiological aging.

Mathematical models of the arterial tree constitute a valuable tool to investigate the hemodynamics of aging and pathology. Rendering such models as patient specific could allow for the assessment of central hemodynamic variables of clinical interest. However, this task is challenging, particularly with respect to the tuning of the local area compliance that varies significantly along the arterial tree.

Chimeric antigen receptor T-cell therapy for multiple myeloma: a consensus statement from The European Myeloma Network.

Adoptive cellular therapy using chimeric antigen receptor T-cell (CART) therapy is currently being evaluated in patients with relapsed / refractory multiple myeloma (MM). The majority of CAR-T cell programs now being tested in clinical trials are targeting B-cell maturation antigen. Several recent phase I / II trials show promising preliminary results in patients with MM progressing on proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies targeting CD38.

Efficacy and Safety of Rivaroxaban Versus Aspirin in Embolic Stroke of Undetermined Source and Carotid Atherosclerosis.

Background and Purpose- The sources of emboli in patients with embolic stroke of undetermined source (ESUS) are multiple and may not respond uniformly to anticoagulation. In this exploratory subgroup analysis of patients with carotid atherosclerosis in the NAVIGATE (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism)-ESUS trial, we assessed whether the treatment effect in this subgroup is consistent with the overall trial population and investigated the association of carotid atherosclerosis with recurrent ischemic stroke. Methods- Carotid atherosclerosis was analyzed either as the presence of mild (ie, 20%-49%) atherosclerotic stenosis or, separately, as the presence of carotid plaque.

Carfilzomib-Dexamethasone Versus Bortezomib-Dexamethasone in Relapsed or Refractory Multiple Myeloma: Updated Overall Survival, Safety, and Subgroups.

Introduction: The phase III RandomizEd, OpeN Label, Phase 3 Study of Carfilzomib Plus DExamethAsone Vs Bortezomib Plus DexamethasOne in Patients With Relapsed Multiple Myeloma (ENDEAVOR) trial showed significantly improved progression-free survival and overall survival (OS) with carfilzomib (56 mg/m) and dexamethasone (Kd56) versus bortezomib and Kd56 (Vd) in patients with relapsed or refractory multiple myeloma (RRMM). We report updated OS and safety data after 6 months of additional follow-up.

Patients And Methods: Patients with RRMM (1-3 previous lines of therapy) were randomized 1:1 to Kd56 or Vd.

Prevalence, Incidence, and Contributors of Subclinical Atheromatosis, Arteriosclerosis, and Arterial Hypertrophy in HIV-Infected Individuals: A Single-Center, 3-Year Prospective Study.

Cardiovascular disease (CVD) is an important comorbidity for people living with HIV infection (PLWH) in the combined antiretroviral therapy era. We prospectively examined the presence of subclinical arterial disease in 138 consecutive CVD-free, HIV-infected individuals compared to 664 HIV-negative individuals. We studied 10 arterial sites in 4 beds using 5 distinct biomarkers of subclinical atheromatosis, arteriosclerosis, and hypertrophy and evaluated the association of subclinical arterial damage with CVD-related and HIV-related factors at baseline and at 3-year follow-up.

Practical Considerations for the Use of Daratumumab, a Novel CD38 Monoclonal Antibody, in Myeloma.

Monoclonal antibodies (mAbs) are a recent addition to multiple myeloma (MM) therapies and a number of mAbs directed at myeloma cell surface molecules are in development. Daratumumab is a CD38 mAb that has demonstrated substantial activity and good tolerability in four phase I, phase I/II and phase II studies as monotherapy, as well as in combination with current standard treatments in MM. The positive results obtained in the relapsed/refractory setting in patients with advanced-stage disease and in a small number of patients with newly diagnosed disease provide the rationale for the investigation of the agent in a number of ongoing phase III trials.