Medical Bulletin 30/ September/ 2024

Scientists at the National Institutes of Health (NIH) and their colleagues have identified a gene responsible for some inherited retinal diseases (IRDs), which are a group of disorders that damage the eye’s light-sensing retina and threatens vision. The study’s findings were published in. JAMA Ophthalmology

In a small study of six unrelated participants, researchers linked the gene UBAP1L to different forms of retinal dystrophies. The patients had symptoms of retinal dystrophy starting in early adulthood, progressing to severe vision loss by late adulthood.

“The patients in this study showed symptoms and features similar to other inherited retinal diseases, but the cause of their condition was uncertain,” said Bin Guan, Ph.D., chief of the Ophthalmic Genomics Laboratory at NIH’s National Eye Institute (NEI) and a senior author of the report. “Now that we’ve identified the causative gene, we can study how the gene defect causes disease and, hopefully, develop treatment.”

Identifying the UBAP1L gene’s involvement adds to the list of more than 280 genes responsible for this heterogeneous disease.

“These findings highlight the importance of providing genetic testing to our patients with retinal dystrophy, and the value of the clinic and lab working together to better understand retinal diseases,” said co-senior author on the paper, Laryssa A. Huryn, M.D., an ophthalmologist at the NEI, part of the National Institutes of Health.

Genetic evaluation of the six patients revealed four variants in the UBAP1L gene, which encodes for a protein that is abundantly expressed in retina cells, including retinal pigment epithelium cells and photoreceptors. More research is needed to understand the UBAP1L gene’s exact function, but scientists were able to determine that the identified variants likely cause the gene to produce protein that lacks function.

Reference: Ullah E, Lin S, Lu J, Bender C, Webster AR, Malka S, Madusudhan S, Rees E, Williams D, Agather AR, Cukras CA, Hufnagel RB, Chen R, Huryn LA, Arno G, Guan B. “Biallelic loss-of-function variants in UBAP1L and nonsyndromic retinal dystrophies,” sssssSeptember 26, 2024, JAMA Ophthalmology. https://doi.org/10.1001/jamaophthalmol.2024.3836

Rising Concern: The Growing Epidemic of Childhood Overweight and Obesity

Overweight, Obesity, type 2 diabetes, diabetes, lipid disorders

Since 1990, the rise in childhood overweight and obesity has surged across every continent, almost doubling in prevalence. Globally, Asia has nearly half of all overweight children under the age of 5. The deleterious consequences of this epidemic are already evident: childhood hypertension, type 2 diabetes, among others. Researchers from Florida Atlantic University’s Schmidt College of Medicine and colleagues sound the alarm and discuss both challenges and potential solutions in a commentary published in The Maternal and Child Health Journal.

“Pediatric overweight and obesity have reached epidemic levels in the U.S. and are becoming a pandemic globally. These conditions lead to high blood pressure, type 2 diabetes and lipid disorders, which contribute to metabolic syndrome. In adults, these issues significantly increase the risks of heart attacks, stroke, liver disease, obstructive sleep apnea, arthritis and certain cancers – many of which are now occurring at younger ages,” said Charles H. Hennekens, M.D., first author and the first Sir Richard Doll Professor of Medicine and Preventive Medicine, FAU Schmidt College of Medicine. “Through coordinated clinical and public health efforts, we can address these troubling trends and work toward a healthier future for children and families globally.”

The authors report on the leading causes of this epidemic including high body mass index (BMI), which increases the risks of many serious health issues. In the U.S., a preschooler is considered overweight if their BMI exceeds the 85th percentile. Research shows that these children are at a significantly higher risk of being overweight during adolescence compared to those with a BMI at the 50th percentile. This underscores the misconception that children simply “outgrow” overweight issues.

In addition, the authors note that health care providers and public health practitioners face major challenges in boosting daily physical activity among children, which is crucial for increasing metabolic rates, lowering BMI, and reducing future risks of coronary heart disease.

“With declining physical education in schools and excessive time spent on electronic devices, many children fail to meet recommended activity guidelines. This sedentary behavior contributes to overweight and obesity through poor diet, reduced sleep, and decreased physical activity,” said Panagiota “Yiota” Kitsantas, Ph.D., co-author and professor and chair, FAU Department of Population Health and Social Medicine, Schmidt College of Medicine. The authors also caution that while increasing levels of daily physical activity is necessary, it isn’t sufficient to make a major impact on the rates of childhood overweight and obesity. The rise of high sugar containing foods, along with consumption of ultra-processed foods also are major contributors.

Authors say that while there are approved drug therapies available, before prescribing pharmacologic options, maternal and child health care providers should employ therapeutic lifestyle changes.

In conclusion, the authors urge leveraging all available resources to at least stabilize the rising rates of childhood obesity and its associated health issues.

Reference: Hennekens, C.H., Sherling, D.H., Caceres, A. et al. Navigating the Global Pandemic in Pediatric Overweight and Obesity: Emerging Challenges and Proposed Solutions. Matern Child Health J (2024). https://doi.org/10.1007/s10995-024-04001-6

Endovascular Management May Improve Patient Outcomes in Cases of Acute Stroke

Endovascular, Acute Stroke, Stroke, disability, death, large vessel occlusion, LVO

Stroke related to large vessel occlusion (LVO) is a leading cause of disability and death worldwide. Endovascular therapy (minimally invasive procedures like catheterization done inside the blood vessels) has transformed the management of these patients. Evidence for the treatment benefit has also been extended to patients presenting within 24 hours of symptom onset, along with patients with large ischemic core infarct, and patients with basilar artery occlusion.

However, ongoing knowledge gaps remain including: an understanding of which patients with large ischemic infarct are more likely to benefit from endovascular therapy; the role of endovascular therapy in patients who present with low stroke severity scores on the National Institutes of Health Stroke Scale (NIHSS) or have medium or distal vessel occlusion (blood blockage); and optimal management of patients with underlying intracranial atherosclerotic disease.

In a review article in the journal Lancet, researchers from Boston University Chobanian & Avedisian School of Medicine and international collaborators examined the rationale of recent randomized trial designs and results that have proven the benefit of endovascular therapy, including reviewing current devices and addressing ongoing areas under study.

“Our paper is a contemporary update of the role of endovascular therapy (clot retrieval, rescue stenting) in the treatment of patients with acute ischemic stroke as well as patient selection criteria,” says corresponding author Thanh Nguyen, MD, professor of neurology, neurosurgery and radiology at the school.

Using a Medline database search, the researchers reviewed randomized clinical trials from 2015-24 that compared endovascular therapy to medical management for large vessel occlusion stroke. Medical management included thrombolytic drugs, blood pressure medicine, and vascular risk factor management. They found randomized trials using a new generation of devices unequivocally confirmed the benefit of endovascular therapy over best medical treatment in selected patients.

They also found patient selection for endovascular therapy could be summarized by clinical and imaging criteria with a minimalist approach based on the evolving randomized evidence. “Most patients who present with a NIHSS score of higher than five and anterior circulation occlusion along with patients with an NIHSS of 10 or higher and basilar occlusions without extensive infarction on imaging, are good candidates for endovascular therapy up to the 24-hour window,” explains Nguyen, who also is a neurologist and Director of Interventional Neurology/ Neuroradiology at Boston Medical Center.

Reference: Nguyen, T. N., Abdalkader, M., Fischer, U., Qiu, Z., Nagel, S., Chen, H.-S., Miao, Z., & Khatri, P. (2024). Endovascular management of acute stroke. The Lancet, 404(10459), 1265-1278. https://doi.org/10.1016/S0140-6736(24)01410-7