From the Journals

DIAGNOSING NEONATAL SEPSIS

Infants in a neonatal intensive care unit (NICU) are vulnerable to infection and sepsis. For late-onset neonatal sepsis, which begins three days after birth, it’s well established that babies should be diagnosed by culturing blood samples drawn from two different sites. To diagnose early-onset sepsis, which occurs within 72 hours of birth, however, there’s less evidence for taking two blood samples from babies who may have the condition. After analyzing data about neonatal early-onset sepsis, Noa Fleiss, MD, MPH, assistant professor of pediatrics, and colleagues reported in the Journal of Perinatology (February 2024) that performing two blood cultures rather than one can cause unnecessary pain for these infants and does not improve diagnostic accuracy. “It’s not about how many blood cultures you take, but more about how you obtain the blood and the volume you obtain in a single culture,” Fleiss said.

VASCULAR MIMICRY IN METASTATIC MELANOMA

Melanoma spreads to the brain more often than other solid tumors. According to research led by Lucia Jilaveanu, MD, PhD, associate professor of medicine (medical oncology), the reason may be related to the way in which brain metastases emerge. While cancers sometimes spread to distant organs and stimulate the body to produce more blood vessels (angiogenesis) to support their growth, malignancies may also metastasize by making their own blood vessels (vascular mimicry). In a study published in Cellular and Molecular Life Sciences (April 2024), Jilaveanu reported that melanoma brain metastases used vascular mimicry more often than melanoma metastases outside the brain. Jilaveanu hopes that this research demonstrates the potential therapeutic value of inhibiting both angiogenesis and vascular mimicry when treating melanoma.

INTERLEUKIN-10 AND IBD

Inflammatory bowel disease (IBD) is caused by the absence of the molecule interleukin-10 (IL-10), which prevents inflammation in the gut. A study published in Nature (February 2024) and led by Richard Flavell, PhD, Sterling Professor of Immunobiology, found that production of fatty acids called ceramides increases in mice without IL-10. When ceramide production was prevented, it alleviated IBD in these mice. Additionally, feeding the mice unsaturated fats, such as those found in olive oil, had the same positive effect. The researchers hypothesize that diets high in unsaturated fats could potentially help treat IBD in humans.

A NEWLY IDENTIFIED GENETIC SYNDROME

A new neurodevelopmental syndrome was recently defined after researchers had identified 18 patients with symptoms that included low muscle tone, seizures, and heart problems, among other challenges. In the absence of established genetic diagnoses with clinical testing for these patients, an international research team analyzed the patients’ data alongside Yale’s Saquib Lakhani, MD, clinical director of the Pediatric Genomics Discovery Program, and Lauren Jeffries, DO, associate research scientist in pediatrics. Using next-generation DNA sequencing, the scientists found that the patients shared rare changes in the CRELD1 gene. The variants were confirmed at Yale to be pathogenic by using in vivo modeling in Xenopus tropicalis, the western clawed frog. In a paper published in Genetics in Medicine (February 2024), the researchers posit that certain variants in CRELD1 cause what is now known as Jeffries-Lakhani neurodevelopmental syndrome (JELANS).

A NEW TARGET FOR PKD THERAPY?

The gene mutations that lead to polycystic kidney disease (PKD) have long been identified, but researchers don’t know much about other genetic factors that affect the disease’s severity. Stefan Somlo, MD, C.N.H. Long Professor of Medicine (Nephrology) and professor of genetics, and colleagues reported in Nature Communications (May 2024) that inactivating the transcription factor Glis2 in the kidneys prevented cysts from developing in a mouse model of PKD. According to the study authors, the finding suggests that Glis2 may be a potential therapeutic target.