This is a randomized, open-label study comparing the efficacy and safety of adjuvant sacituzumab tirumotecan (MK-2870) in combination with pembrolizumab compared to treatment of physician's choice (TPC) in participants with triple-negative breast cancer (TNBC) who received neoadjuvant therapy and did not achieve a pathological complete response (pCR) at surgery. The primary objective is to compare sacituzumab tirumotecan plus pembrolizumab to TPC (pembrolizumab or pembrolizumab plus capecitabine) with respect to invasive disease-free survival (iDFS) per investigator assessment. It is hypothesized that sacituzumab tirumotecan plus pembrolizumab is superior to TPC with respect to iDFS per investigator assessment.
This is a phase 2 stratified, randomized, multicenter, study investigating the efficacy of a triplet arm treating with nivolumab 480 mg every 4 weeks (Q4W), relatlimab 160 mg Q4W and ipilimumab 1 mg/kg every 8 weeks (Q8W) intravenous (IV) versus a doublet arm treating with nivolumab 480 mg Q3W and ipilimumab 1mg/kg Q3W IV in first-line advanced RCC.
Excessive consumption of dietary sodium (salt) is a significant, independent risk factor for new-onset heart failure, according to a report from Vanderbilt Health.
In a group of predominantly Black and low-income people from the southeastern United States, consuming a population average of about 4,200 milligrams of dietary sodium a day (the recommended maximum is 2,300 milligrams) was associated with a 15% increase in the risk of incident (new) cases of heart failure.
Deepak Gupta, MD, MSCI
“Even modest reductions in sodium consumption may significantly reduce the burden of heart failure in this high-risk population,” the researchers reported March 17 in the Journal of the American College of Cardiology: Advances.
Reducing dietary salt consumption is not a simple matter, however, cautioned the paper’s corresponding author, Deepak Gupta, MD, MSCI, associate professor of Medicine and director of the Vanderbilt Translational and Clinical Cardiovascular Research Center (VTRACC).
Multilevel, public health strategies may be required to address grocery store availability and limited transportation options that make it difficult for residents of many low-income, high-risk communities to access healthier food options, Gupta said.
Leonie Dupuis, MD
Leonie Dupuis, MD, a third-year resident physician in internal medicine at Vanderbilt Health, is first author of the paper, which analyzed dietary and health records of more than 25,300 participants in the federally funded Southern Community Cohort Study.
The SCCS has tracked the health of predominantly Black and low-income residents of 12 southeastern states since 2001. Most of them were enrolled in this and other studies through community health centers.
Average daily sodium consumption in this group was 4,269 milligrams per day, well above the daily, 2,300-milligram limit recommended by federal dietary guidelines.
The increased risk of heart failure linked to sodium was independent of sociodemographic factors, including diet quality and caloric intake, as well as health conditions such as high blood pressure and high lipid blood levels.
Heart failure contributes to 425,000 deaths in the United States each year. The cost of caring for the estimated 1 million new cases of heart failure diagnosed annually runs into the tens of billions of dollars.
Even a modest reduction in dietary salt, to 4,000 milligrams a day or less, could reduce heart failure cases by 6.6% over 10 years, the researchers predicted. That would translate into fewer deaths from heart failure and a nearly $2-billion-a-year reduction in national health expenditures.
Co-authors of the paper are Meng Xu, MS, Audrey White, MD, Debra Dixon, MD, MS, Jane Ferguson, PhD, Xiao-Ou Shu, PhD, Danxia Yu, PhD, and Loren Lipworth, ScD. The SCCS is supported by National Cancer Institute grants R01CA092447, U01CA202979 and 3R01CA029447, with additional research support from National Institutes of Health grants R01HL133860, R01HL153607, K23HL168331, P30HS029767 and R38HL167237.
The primary purpose of this study is to assess the effectiveness of zanzalintinib compared to everolimus in participants with previously treated, unresectable, locally advanced or metastatic neuroendocrine tumors.
The clonal growth of precancerous blood cells known as CHIP (clonal hematopoiesis of indeterminate potential) occurs in 1 in 10 people over age 70. It is known to increase the risk of blood cancer and death from cardiovascular, lung and liver disease.
Last year, researchers at Harvard’s Massachusetts General Hospital reported that CHIP also dramatically increased the risk of inflammatory heart disease. Their study analyzed genomic and health records data from more than 335,000 participants in the England-based UK Biobank.
To validate these findings, Vanderbilt Health researchers analyzed data from more than 361,000 participants in two large U.S. biobanks — one of them, BioVU, based at Vanderbilt Health, and the other, part of the National Institutes of Health’s All of Us Research Program.
Their report, published March 18 in the journal JAMA Cardiology, identified a specific link between CHIP and pericarditis, a potentially life-threatening inflammation of the thin sac surrounding the heart. It suggests that treating patients for the blood condition could reduce their risk of heart inflammation.
Pershad Yash
“Both CHIP and pericarditis are thought to be a result of the same types of inflammation,” said the paper’s first author, Yash Pershad, an MD/PhD student in the lab of Alexander Bick, MD, PhD. “Targeting CHIP-associated inflammation may represent a therapeutic strategy for preventing or treating pericardial inflammation in some at-risk individuals.”
Each year in the United States, an estimated 160,000 people develop pericarditis, which can cause sharp chest pain and often requires hospitalization. The condition, which also is associated with autoimmune disease, cardiac procedures, and infections, can lead to a dangerous buildup of fluid around the heart that impairs heart function.
CHIP is thought to fuel inflammation through specific molecular pathways — including a cellular alarm system called the NLRP3 inflammasome and a signaling protein called interleukin-1beta — that are also central to pericarditis.
Drugs that block these pathways are already approved to treat recurrent pericarditis and potentially could be used as preventive therapy, Pershad noted.
Bick, the paper’s corresponding author, directs the Division of Genomic Medicine and Clinical Pharmacology at Vanderbilt Health. Other co-authors are Kun Zhao, PhD, a postdoctoral researcher in the Bick lab, and Brett Heimlich, MD, PhD, assistant professor of Medicine. The research was supported by National Institutes of Health grants DP5OD029586, R01AG088657 and K08HL171833, a Burroughs Wellcome Fund Career Award for Medical Scientists, a Pew-Stewart Scholar for Cancer Research award, and a Hevolution/AFAR New Investigator Award in Aging Biology and Geroscience Research.
Lung screenings are an important diagnostic tool for early detection of cancer, but low-dose CT scans cannot determine whether the pulmonary nodules identified in the imaging are cancerous or benign.
Specially trained radiologists, pulmonologists and thoracic surgeons analyze the imaging and then decide whether invasive biopsies are warranted to make that determination — a process called risk stratification of indeterminate pulmonary nodules.
An estimated 10% to 15% of the resections of these nodules turn out to be surgeries for benign tissue. Risk prediction software using artificial intelligence, such as the Lung Cancer Prediction Score, which was developed by Optellum, a lung health technology company, and approved by the Food and Drug Administration in 2021, aids clinicians in determining whether surgical resections are necessary. In a recent study, Vanderbilt Health researchers determined that AI-assisted decision-making with this software is cost-effective compared to clinician assessment alone.
The study, published March 5 in PLOS ONE, showed that AI-assisted decision-making resulted in an incremental cost-effective ratio of $4,485 per life year gained.
Eric Grogan, MD, MPH
“Artificial intelligence-based tools offer promising assistance to busy clinicians who evaluate suspicious lung nodules and seem to be cost-effective,” said the study’s corresponding author, Eric Grogan, MD, MPH, Ingram Professor of Cancer Research and professor of Thoracic Surgery at Vanderbilt Health.
To determine cost-effectiveness, the researchers constructed a decision model assuming guideline-based care from a payer perspective with a lifetime horizon. The base case is a 1.1 centimeter indeterminate pulmonary nodule in a 60-year-old patient who benefits from surgery. This nodule’s risk for lung cancer is about 65%. The model classified patients as low, medium or high risk using either clinician reasoning or clinician-plus-AI reasoning.
Stephen Deppen, PhD
“When we think of these AI clinical decision aids, they may not really help the true clinical expert, the thoracic radiologist or pulmonologist who sees 20 of these a day. Where the larger health care system impact occurs is when generalist physicians can rely on these tools to remove the easy, cancer and not cancer cases, so they can focus or get a consult on the most difficult,” said the study’s senior author, Stephen Deppen, PhD, associate professor of Thoracic Surgery and co-director of the Early Detection Research Network Lung Group’s National Clinical Validation Center.
Other Vanderbilt Health authors are Caroline Godfrey, MD, MPH, Ashley Leech, PhD, MS, Kevin McGann, MD, Jinyi Zhu, PhD, MPH, Hannah Marmor, MD, MPH, Sophia Pena, Fabien Maldonado, MD, MSc, Evan Osmundson, MD, PhD, and Stacie Dusetzina, PhD. The researchers received support from National Institutes of Health grants T32CA106183, K01DA050740, R01CA253923, P30CA068485, U01CA152662, R01CA252964 and U01CA152662.
Open-label Phase 1b/2 study with primary objective of this study is to evaluate the safety, tolerability and efficacy of AZD0120 in participants with light chain (AL) amyloidosis.
The objective of this study is to evaluate the preliminary safety and effectiveness of the Cephea Mitral Valve System for the treatment of symptomatic patients with mitral valve disease (including mitral regurgitation, mitral stenosis and mixed mitral valve disease) in whom transcatheter therapy is deemed more appropriate than open heart surgery.
