Medical Bulletin 15/ November/ 2024 - Video

A small clinical trial shows promising results for patients with triple-negative breast cancer who received an investigational vaccine designed to prevent recurrence of tumors. Conducted at Washington University School of Medicine with a therapy designed by WashU Medicine researchers, the trial is the first to report results for this type of vaccine known as a neoantigen DNA vaccine for breast cancer patients. The study, which found the vaccine to be well-tolerated and to stimulate the immune system, is published in the journal Genome Medicine.

The phase I clinical trial — conducted at Siteman Cancer Center, involved 18 patients diagnosed with triple-negative breast cancer that was not metastatic. Each patient received the standard of care and three doses of a personalized vaccine tailored to home in on key mutations in their specific tumor and train immune cells to recognize and attack any cells bearing these mutations.

Following treatment, 14 of 18 patients showed immune responses to the vaccine and, after three years, 16 patients remained cancer-free. On an average, about half of patients remained cancer-free at three years post-treatment.

Triple-negative breast cancer is an aggressive tumor and to date, triple-negative breast cancer has no targeted therapies and is usually treated with traditional methods. For this trial, patients with triple-negative breast cancer who still had evidence of a tumor remaining after a first round of chemotherapy were eligible to participate. Such patients are at high risk of cancer recurrence even after the remaining tumor is surgically removed. After surgical removal, the research team analyzed and compared the tumor tissue with the same patient’s healthy tissue to find unique genetic mutations in the cancer cells. Such mutations in a patient’s cancer cells alter the proteins only in the tumor, making it possible to train the immune system to go after the altered proteins and leave healthy tissues alone.

Using a software they designed, the researchers selected altered proteins — called neoantigens — that were made by the patients’ tumors and that were identified as most likely to trigger a strong immune response. On average, each patient’s vaccine contained 11 neoantigens, ranging from a minimum of four to a maximum of 20 specific to their tumor.

Reference: Zhang X, Goedegebuure P, Chen MY, Mishra R, Zhang F, Yu YY, Singhal K, Li L, Gao F, Myers NB, Vickery T, Hundal J, McLellan MD, Sturmoski MA, Kim SW, Chen I, Davidson JT, Sankpal NV, Myles S, Suresh R, Ma CX, Foluso A, Wang-Gillam A, Davies S, Hagemann IS, Mardis ER, Griffith O, Griffith M, Miller CA, Hansen TH, Fleming TP, Schreiber RD, Gillanders WE. Neoantigen DNA vaccines are safe, feasible, and induce neoantigen-specific immune responses in triple-negative breast cancer patients. Genome Medicine. Nov. 14, 2024.

Over 800 million adults living with diabetes, more than half not receiving treatment, global study published in the lancet suggests.

Key highlights of the study are:

The global rate of diabetes (type 1 and 2 combined) in adults doubled from approximately 7% to about 14% between 1990 to 2022, with the largest increase in low- and middle-income countries (LMICs).

Over the same period, rates of treatment for diabetes stagnated at low levels in many of the same low- and middle-income countries where rates of the disease have drastically increased, resulting in almost 450 million adults aged 30 and over with diabetes globally (59%) who did not receive treatment in 2022.

Meanwhile, people living in North America, Australasia, central and western Europe, and parts of Latin America and East Asia and the Pacific saw a significant improvement in treatment rates for diabetes from 1990 to 2022, contributing to widening global inequities in diabetes treatment.

Authors say the study highlights the urgent need for financing of medicines and comprehensive diabetes programmes that enable early detection and effective treatment of diabetes in low- and middle-income countries.

The study, conducted by the NCD Risk Factor Collaboration (NCD-RisC), in collaboration with the World Health Organization (WHO), is the first global analysis of trends in both diabetes rates and treatment which includes all countries. Researchers used data from over 140 million people aged 18 years or older from more than 1,000 studies in populations of different countries.

The authors used statistical tools to bring all the data across different years, ages and countries together, and estimate diabetes rates and treatment in a way that enables comparisons across countries.

Reference: Worldwide trends in diabetes prevalence and treatment from 1990 to 2022: a pooled analysis of 1108 population-representative studies with 141 million participants, Zhou, Bin et al., The Lancet, Volume 0, Issue 0, http://dx.doi.org/10.1016/S0140-6736(24)02317-1

Adverse events affect more than a third (38%) of adults undergoing surgery, finds a study of admissions to 11 hospitals in the US state of Massachusetts, published by The BMJ. Of the 1009 admissions analysed, nearly half were classified as major resulting in serious, life threatening or fatal harm and the majority were considered as potentially preventable.

Researchers set out to estimate the frequency, severity and preventability of adverse events associated with perioperative care, and to describe the setting and professions concerned.

Their findings are based on a randomly selected sample of 1009 patients aged 18 years and older admitted to 11 hospitals for surgery during 2018. The hospitals were chosen to represent a mix of both large and small facilities across three different healthcare systems and estimates were weighted to take account of differences in the sample population.

Trained nurses reviewed all records and flagged admissions with possible adverse events, which were then adjudicated by physicians. Adverse events were classified as major if they resulted in serious harm requiring significant intervention or prolonged recovery, involved a life threatening event, or led to a fatal outcome. The severity and preventability of adverse events were also assessed according to the type of event, setting, and profession involved. Of the 1009 reviewed admissions, adverse events were identified in 383, with major adverse events occurring in 160.

Of 593 identified adverse events, 60% were potentially preventable and 21% were definitely or probably preventable. The most common adverse events were related to surgical procedures (49%), followed by adverse drug events (27%), healthcare associated infections (12%), patient care events, such as a fall or pressure ulcer (11%), and blood transfusion reactions (0.5%). Half of these events took place in general care units, followed by operating rooms (26%), intensive care units (13%), and other in-hospital locations (7%). Professions most often involved were attending physicians (90%), followed by nurses (59%), residents (50%), and advanced level practitioners (29%).

People living in areas with higher levels of air pollution are more likely to have eczema, according to a new study published in the open-access journal PLOS ONE.

The prevalence of eczema has increased globally with industrialization, suggesting a possible contribution from environmental factors. In the new study, researchers used data from the U.S. National Institutes of Health All of Us Research Program, covering hundreds of thousands of U.S. adults. The current study included 286,862 people for whom there was available demographic, zip code and electronic health record data.

Overall, 12,695 participants (4.4%) were diagnosed with eczema. After controlling for demographics and smoking status, people with eczema were more likely to live in zip codes with high levels of fine particulate matter, or PM2.5, in the air. For every increase of 10 µm/m3 in average PM2.5 air pollution in their zip code, people were more than twice as likely to have eczema.

The authors conclude that increased air pollution, as measured by PM2.5, may influence the risk of developing eczema, likely through its effects on the immune system.

The authors add: “Showing that individuals in the United States who are exposed to particulate matter are more likely to have eczema deepens our understanding of the important health implications of ambient air pollution.”

Reference: Chen, G. (2024). Association Between Fine Particulate Matter And Eczema: A Cross-Sectional Study Of The All Of Us Research Program And The Center For Air, Climate, And Energy Solutions.