Search

There is no cure for HIV infection, and lifelong antiretroviral therapy (ART) is required. N-803 is an IL-15 superagonist comprised of an N72D mutant IL-15 molecule attached to its alpha receptor and a human IgG1 fragment designed to increase IL-15 activity. Preclinical studies with both HIV and SIV suggest that the drug has potential to reduce virus reservoirs by activating virus from latency and enhancing effector function. We conducted a phase 1 study of N-803 ( NCT02191098 ) in people living with HIV, the primary objective of which was to assess the safety and tolerability of the drug, with an exploratory objective of assessing the impact on peripheral virus reservoirs. ART-suppressed individuals were enrolled into a dose-escalation study of N-803 in four different cohorts (0.3, 1.0, 3.0 and 6.0 mcg kg

In the USA, maternal mortality has been rising since the 1980s. Cardiovascular disease is recognized as the leading cause of this worrisome trend, and a multidisciplinary approach to the care of patients with cardiovascular conditions during pregnancy is becoming increasingly important. We outline the literature supporting this multidisciplinary approach, highlight our center’s experience in building and expanding an integrated cardio-obstetrics practice, and provide guidance regarding patient selection and management within a combined practice. Antenatal management patterns and delivery planning for patients with cardiovascular disease during pregnancy vary substantially among cardiovascular and obstetric and maternal fetal medicine practices in the USA. The need for multidisciplinary care between cardiologists and obstetricians is evident and has been supported by best practice statements from the American Heart Association, the American College of Obstetrics and Gynecology, and the Cardiac Disease in Pregnancy Study (CARPREG) investigators, whose CARPREG II risk score included “late first antenatal visit” as a predictor of adverse outcomes of pregnancy. We have solid evidence supporting a multidisciplinary approach to the care of patients with cardiac conditions in pregnancy. This approach is optimal because it facilitates a consistent and clear message to the patient (and those caring for each patient) regarding management and risks associated with pregnancy, as well as subsequent risk and postpartum follow-up. We support the extension of clinical collaboration between obstetricians and cardiologists to the research realm and know that working together to investigate the outcomes of moms with heart conditions and their babies will provide clinically meaningful information to support the care of these unique patients.

Human papillomaviruses (HPVs) are the causative factor for greater than 90% of cervical cancers and 25% of head and neck cancers. The incidence of HPV positive (+) head and neck squamous cell carcinomas (HNSCCs) has greatly increased in the last 30 years. E6 and E7 are the two key viral oncoproteins that induce and propagate cellular transformation. An immune response generated during cisplatin/radiation therapy improves tumor clearance of HPV(+) cancers. Augmenting this induced response during therapy with an adenoviral HPV16 E6/E7 vaccine improves long term survival in preclinical models. Here we describe the generation of an HPV16 E6/E7 construct, which contains mutations that render E6/E7 non-oncogenic, while preserving antigenicity. These mutations do not allow E6/E7 to degrade p53, pRb, PTPN13, or activate telomerase. Non-oncogenic E6/E7 (E6Δ/E7Δ) expressed as a stable integrant, or in the [E1-, E2b-] adenovirus, lacks the ability to transform human cells while retaining the ability to induce an HPV specific immune response. Moreover, E6Δ/E7Δ plus chemotherapy/radiation statistically enhances clearance of established HPV(+) cancer in vivo.

Chronic heart failure (HF) represents a significant health care burden. Over the past few decades, there have been considerable data supporting the benefits of omega-3 polyunsaturated fatty acids (PUFAs) on overall cardiovascular health. Reasons for the potential benefits of omega-3 PUFAs are multifactorial and not completely understood. It is likely that the culmination of multiple effects collectively help to prevent the development and slow the progression of chronic HF. A number of key epidemiologic and randomized trials have provided the basis of evidence in support of omega-3 PUFA supplementation in HF. This article reviews the benefits of omega-3 PUFAs and discusses the implications of recent trials. While the benefits seen in patients with chronic HF are modest at best, we believe the balance of evidence still favors the continuation of omega-3 PUFA supplementation in patients with chronic HF.

Background. The conditions that predispose patients to erectile dysfunction are substantially similar to the coronary artery disease risk factors, including diabetes mellitus, hypertension, hyperlipidemia, obesity, sedentary lifestyle, depression, age, and smoking. Because of these shared risks and overlapping pathophysiologic mechanisms, we designed this pilot study to address the hypothesis that the presence of coronary artery calcium, a known indicator of increased cardiac risk, is associated with erectile dysfunction. Methods and Results. A prospective registry enrolled 9150 men who underwent multidetector computed tomography. Subjects supplied baseline data regarding demographic variables, coronary risk factors, and erectile dysfunction symptoms or lack thereof. The 2 groups then underwent computed tomography to screen for the presence or absence of coronary artery calcium. Subjects with erectile dysfunction were older, had higher triglyceride levels, had higher blood pressures, and were more likely to have measurable coronary artery calcification than men without erectile dysfunction (79% vs 58%,P

Chest pain occurs frequently during dobutamine stress testing and is commonly attributed to ischemia. However, the pathophysiologic significance of dobutamine-induced chest pain is uncertain. The purpose of this study is to explore the correlation between dobutamine-induced chest pain and evidence of ischemia on myocardial perfusion imaging (MPI).This study included 1608 patients who underwent dobutamine stress MPI at the Mid America Heart Institute (Kansas City, Mo) and were analyzed retrospectively. Patients were divided into those with chest pain during dobutamine infusion versus those without it. Multivariate and chi(2) analyses were conducted to explore the relationship between chest pain and ischemic changes on MPI. Of 1608 patients, 208 (13%) had chest pain with dobutamine whereas 1400 (87%) did not. MPI ischemia was seen in 47% of patients with chest pain and 43% without chest pain (P = .28). Chest pain was not any more predictive of ischemia when analyzed separately by gender (P = .31). Multivariate analysis did not identify chest pain as a predictor of ischemia (P = .19). Significant predictors of scintigraphic ischemic changes were age (P = .001), gender (P.0001), smoking (P = .0149), and known coronary artery disease (P.0001).This large retrospective study suggests that chest pain during dobutamine stress testing is not a predictor of ischemia when analyzed against reversible perfusion defects on SPECT MPI.