From the journals

A GENETIC CLUE ABOUT MULTIPLE SCLEROSIS

A genome-wide association study has identified a genetic variant that is linked to faster progression of multiple sclerosis (MS). In the study, published in Nature, David Hafler, MD, William S. and Lois Stiles Edgerly Professor of Neurology and Professor of Immunobiology, worked with international collaborators to look for associations between particular inherited genetic variants and more severe disease in more than 22,000 people with MS. This is the first known genetic variant that’s associated with MS severity and the first that seems to be related to the neurological side of the disease, the researchers say. Hafler and colleagues hope that the variant could lead to the discovery of new drugs that could slow disease progression.

DISPARITIES IN DEATH

Black Americans consistently died at higher rates than white Americans from 1999 through 2020, according to a study published in JAMA. The researchers, led by Harlan Krumholz, MD, SM, Harold H. Hines, Jr. Professor of Medicine (Cardiology) and director of the Center for Outcomes Research and Evaluation (CORE), also calculated how many deaths would have occurred in the Black population and how many more years Black Americans would have lived if the Black population had the lower mortality rates of the white population. According to this analysis, 1.63 million excess age-adjusted deaths occurred, and more than 80 million years of potential life were lost among Black Americans during the study period due to their higher mortality rates. The study should be a call to action for policy makers, the researchers say.

ROUTINE MAMMOGRAM RISKS FOR OLDER WOMEN

Women age 70 and older who receive regular mammograms are more likely to be diagnosed with breast cancers that would not have caused symptoms if they had gone undetected. This phenomenon, known as overdiagnosis, can lead patients to undergo cancer treatments that do not extend or improve their lives, says study author Ilana Richman, MD, MHS, assistant professor of medicine (general medicine). After analyzing data from 54,635 older women who chose either to continue or discontinue their mammography screenings, the rates of overdiagnosis among those who continued screenings and were diagnosed with breast cancer ranged from 31% for those aged 70 to 74 to 54% for those aged 85 and older. The study was published in Annals of Internal Medicine.

TARGETED TREATMENT IMPROVES LUNG CANCER SURVIVAL

Post-surgical (adjuvant) treatment with the targeted therapy osimertinib improved survival in people with early-stage non-small cell lung cancer (NSCLC), according to a clinical trial led by Roy Herbst, MD, PhD, Ensign Professor of Medicine (Medical Oncology), deputy director of Yale Cancer Center, and assistant dean for translational research at Yale School of Medicine. Study participants, whose cancer had epidermal growth factor receptor (EGFR) mutations, were assigned at random to take either oral osimertinib or a placebo pill daily for up to three years following surgery to remove their lung cancers. Five years later, the overall survival of those in the osimertinib group was 88%, compared to 78% in the placebo group. Based on results from this trial, published in The New England Journal of Medicine, the Food and Drug Administration approved adjuvant osimertinib for NSCLC patients with EGFR-mutated tumors—a group representing 10% to 15% of NSCLC patients in the United States.

A PEEK AT EARLY DEVELOPMENT

Thanks to human embryonic stem cells, researchers can model the earliest stages of human development in the lab. But most systems for cultivating stem cells do not allow researchers to study gastrulation, the process in which the embryo begins to differentiate into multiple cell types. Berna Sozen, PhD, assistant professor of genetics and of reproductive sciences, and colleagues have developed a novel way to grow stem cells so that they develop not just the embryonic tissues that give rise to our bodies, but also the extra embryonic tissues, such as the yolk sac and the placenta, that help the embryo on its way and play roles in gastrulation. This model of the human embryo will allow researchers to study gastrulation in the lab, according to the study, which was published in Nature.

BACTERIUM ON THE BRAIN

Hydrocephalus, nicknamed “water on the brain,” is an accumulation of cerebrospinal fluid (CSF) and pressure in the brain. It’s the leading reason for pediatric neurosurgeries worldwide. In Uganda, an unusually high number of babies develop hydrocephalus and die following infections and sepsis. In a study to determine the cause of this hydrocephalus, published in The Lancet Microbe and in Clinical Infectious Diseases, Steven Schiff, MD, PhD, professor of neurosurgery and vice chair for global health, and colleagues found that the bacterium Paenibacillus thiaminolyticus was present in the CSF of 44% of babies with post-infectious hydrocephalus. Among infants with sepsis, 6% had P. thiaminolyticus infections, and of those, 14% developed hydrocephalus. The researchers found no evidence that the infections pass from mothers to babies; instead, the bacteria may come from the environment. Preventing those infections is the next step, Schiff says.