Findings

Bypass, Not Stents, for Women?

Women with severe coronary heart disease causing narrowing or blockages in the arteries may derive greater long-term benefits from coronary artery bypass grafting compared with percutaneous coronary intervention, also known as stenting, according to a large study by Weill Cornell Medicine investigators.

Bypass surgery uses a blood vessel from another part of the body to reroute blood flow around a narrowed or blocked artery. Stenting is a minimally invasive procedure that uses a catheter to thread a tubelike stent through a blood vessel in the wrist or groin to the heart to open a fully or partially blocked artery.

The study, published Nov. 25 in the European Heart Journal, adds much-needed evidence to guide decisions for women with heart disease — the leading cause of death among women. Historically, women have made up just 20% to 25% of large, prospective clinical trials comparing bypass surgery and stenting, making it hard to draw conclusions about their outcomes.

“For now, treatment decisions should remain individualized,” says lead author Dr. Kevin An, a clinical fellow at NewYork-Presbyterian/Columbia University Irving Medical Center who conducted the study while a research fellow in cardiothoracic surgery at Weill Cornell Medicine. “Although our study suggests that bypass surgery may offer more long-term protection compared to stents, anatomical considerations, individual surgical risk and patient preferences remain critical.”

No Longer a Safe Harbor?

A new study has overcome a long-standing challenge — how to isolate and study elusive HIV-infected cells called authentic reservoir clones (ARCs) that evade the immune system, making the disease difficult to cure. Researchers from Weill Cornell Medicine, The Rockefeller University and collaborating institutions have offered an unprecedented look into these hidden HIV-harboring cells and shown that some may be more vulnerable to immune destruction than previously believed.

The findings, published Feb. 24 in Nature, detail how the researchers collected these rare cells from study participants with HIV and successfully grew them in the laboratory to gain insights that may ultimately lead to a cure.

“For decades, we have known that HIV hides in long-lived immune cells called T cells. But, we have not been able to study those extremely rare — one in a million — [ARCs] cells,” says senior author Dr. Brad Jones, associate professor of immunology in medicine at Weill Cornell. “By isolating ARCs, we can now directly interrogate how they survive and how to eliminate them.”

Early Clues to Cognitive Decline

Two recent preclinical studies led by Weill Cornell Medicine researchers — both focused on brain cells — could hold promise for improved prevention and treatment of neurodegenerative disorders.

In the first study, researchers discovered that free radicals generated at a specific site in non-neuronal brain cells called astrocytes may promote dementia. Their findings, published Nov. 4 in Nature Metabolism, demonstrated that blocking this site lowered brain inflammation and protected neurons, suggesting a novel therapeutic approach for neurodegenerative disorders, including frontotemporal dementia and Alzheimer’s disease.

The second study, published Nov. 14 in Neuron, found that hypertension impairs blood vessels, neurons and white matter in the brain well before the condition causes a measurable rise in blood pressure. The changes help explain why hypertension is a major risk factor for developing cognitive disorders, such as vascular cognitive impairment and Alzheimer’s disease.

The new work reveals that hypertension may induce early gene expression changes in individual brain cells that could interfere with thinking and memory. Investigators say the findings may lead to medications that both reduce blood pressure and prevent cognitive decline.

Dr. Michelle Bradbury, the Endowed Professor of Imaging Research in Radiology and a professor of radiology at Weill Cornell Medicine, describing a class of ultrasmall fluorescent core-shell silica nanoparticles developed at Cornell University that showed an unexpected ability to rally the immune system against melanoma and dramatically improve the effectiveness of cancer immunotherapy.

The particles, known as Cornell prime dots, or C’dots, have already been tested in human clinical trials as a cancer diagnostic and a drug delivery system. The new study she led in collaboration with researchers at Weill Cornell Medicine and Cornell Engineering reports that the nanoparticles themselves can reprogram the tumor microenvironment, transforming immune-resistant tumors into ones that respond far better to treatment. The study was published Dec. 29 in Nature Nanotechnology.

Lasting Imprints from Prenatal Adversity

Increased risk for anxiety may begin before birth, shaped by infection or stressful events during pregnancy, according to a new preclinical study from researchers at Weill Cornell Medicine. While scientists have long known that maternal difficulty during pregnancy may raise a child’s risk for psychiatric illness, the biological pathways between these prenatal experiences and later mental health have been unclear.

The study, published Sept. 10 in Cell Reports, focuses on a region of the brain called the ventral dentate gyrus (vDG), part of the hippocampus that helps a person assess threats in the environment. The researchers discovered that adversity in the womb configured a small percentage of these brain cells to be overly active when faced with a threatening situation, creating a vulnerability to anxiety.

“Our data reveal prenatal adversity left lasting imprints on the neurons of the vDG linking gestational environment to anxiety-like behavior,” says Dr. Miklos Toth, the Arleen B. Rifkind, M.D. Professor who co-led the research. “This mechanism may help explain the persistent stress sensitivity and avoidance seen in some individuals with innate anxiety.”

A New COVID-19 Vaccination Strategy

Prior exposure to coronaviruses that cause ordinary colds can boost the immune system’s ability to attack a vulnerable site on the COVID-19-causing coronavirus SARS-CoV-2, according to a study led by investigators at Weill Cornell Medicine. The finding suggests a new vaccination strategy that might provide broader and more durable protection against SARS-CoV-2 strains compared with existing vaccines — and might also protect against other emergent coronaviral threats.

In the study, published Oct. 9 in the Journal of Experimental Medicine, researchers analyzed human antibody responses to the base of SARS-CoV-2’s outer spike protein. This segment, known as the S2 subunit, mediates the coronavirus’s entry into a host cell, and, because of this critical function, does not vary much between different coronavirus subfamilies. Thus, targeting it successfully could help provide broad protection against existing and future coronavirus threats.

Although exposure to SARS-CoV-2 alone elicits a weak antibody response against S2, the researchers found evidence that prior exposure to common cold coronaviruses, especially one called OC43, can prime the immune system for a much more effective anti-S2 response — one that may be able to neutralize a wide range of coronaviruses.

“This is a proof of principle that targeting S2 can be protective, and that priming the immune system with exposure to a common cold coronavirus can be the key to that protection,” says senior author Dr. Patrick Wilson, the Anne E. Dyson Professor of Pediatric Research, professor of microbiology and immunology in pediatrics and a member of the Gale and Ira Drukier Institute for Children’s Health at Weill Cornell Medicine.

Illustrations: Miriam Martincic