Ontosight^® Newsletter Issue 2

Ontosight^® – Newsletter
June 3^rd – June 16^th, 2024 – Issue 2

Welcome to the 2^nd edition of Ontosight^® – Newsletter! This issue, we spotlight significant advancements across various fields of medical research and treatments. From innovative approaches in infectious diseases and mental health to groundbreaking cancer research and novel strategies in cardiovascular and metabolic diseases, we cover the latest studies shaping the future of healthcare. 

Featured Articles

1. Infectious Diseases and Antibiotic Treatments

• Prolonged vs Intermittent Infusions of β-Lactam Antibiotics in Adults With Sepsis or Septic Shock: A Systematic Review and Meta-Analysis

This study examines whether prolonged β-lactam antibiotic infusions improve outcomes in critically ill adults with sepsis or septic shock compared to intermittent infusions. Through a systematic review of 18 randomized clinical trials involving 9108 patients, it found that prolonged infusions significantly reduced the 90-day mortality rate (risk ratio, 0.86) and intensive care unit mortality (risk ratio, 0.84), while also increasing clinical cure rates (risk ratio, 1.16). The evidence, evaluated with high certainty, supports prolonged infusions as a more effective treatment approach in these patients. [Article]

• Host stress drives tolerance and persistence: The bane of anti-microbial therapeutics

Antibiotic recalcitrance, encompassing persistence and tolerance, involves transient phenotypic changes that enable bacterial survival despite lethal antibiotic concentrations. This phenomenon complicates treatment, especially during infections. Recent research on pathogens like Mycobacterium tuberculosis and Staphylococcus aureus has identified common signals and vulnerabilities in recalcitrant bacteria. These insights are aiding the development of new therapies to better combat these hard-to-treat infections. [Article]

2. Mental Health and Neurological Disorders

• Changes in the prevalence of mental health problems during the first year of the pandemic: a systematic review and dose-response meta-analysis

The study analyzed 41 studies on mental health during the first year of COVID-19, finding increased odds of distress, depression, and anxiety (mean OR 1.23 to 2.08), especially in the first two months with stringent measures and rising cases. Significant heterogeneity indicated varied responses across populations, with low confidence in the findings. [Article]

• Advances in the Understanding of the Correlation Between Neuroinflammation and Microglia in Alzheimer’s Disease

Alzheimer’s disease (AD) is a fatal neurodegenerative disorder with β-amyloid plaques, tau tangles, neuroinflammation, and neuronal loss. Current treatments targeting amyloid and tau proteins are largely ineffective. Neuroinflammation, driven by glial cells and microglia, is crucial in AD progression. Recent studies, aided by genome-wide association studies (GWAS), emphasize the role of microglia-mediated neuroinflammation. This review explores recent advances in understanding neuroinflammation’s role in AD, seeking new therapeutic targets. [Article]

3. Cancer Research and Treatments

• Defining clinically useful biomarkers of immune checkpoint inhibitors in solid tumours

Despite over a decade of using immune checkpoint inhibitors (ICIs) for cancer, many patients show limited responses. FDA-approved biomarkers like PDL1, MSI-H, and TMB have limited utility. Tissue-based analytes are also limited by their static nature and variability in tumors. Dynamic biomarkers such as longitudinal biopsies, blood-based markers, radiomics, and the gut microbiome show promise. Personalized predictors from neoadjuvant trials or ex vivo models can improve treatment. This review assesses new biomarkers and provides recommendations for future clinical trials to advance the field. [Article]

• Cell death shapes cancer immunity: spotlighting PANoptosis

PANoptosis is a novel form of programmed cell death combining elements of pyroptosis, apoptosis, and necroptosis, governed by the PANoptosome complex. Still in early research, its regulatory mechanisms and targets require further exploration. This review outlines PANoptosis’s framework, molecular components, recent advancements, and potential applications in cancer therapy, focusing on its interactions in the tumor immune microenvironment. [Article]

4. Cardiovascular and Metabolic Diseases

• Regulated vascular smooth muscle cell death in vascular diseases

Regulated cell death (RCD) plays a critical role in vascular diseases through various pathways in vascular smooth muscle cells (VSMCs). These include apoptosis, necroptosis, pyroptosis, ferroptosis, parthanatos, and autophagy-dependent cell death (ADCD). These pathways are interconnected and contribute to conditions such as atherosclerosis, vascular calcification, aortic aneurysm, hypertension, and others. Targeting these pathways pharmacologically holds potential for slowing disease progression and addressing cardiovascular risks, though challenges remain in clinical application. [Article]

• Bone health in patients with inflammatory bowel disease

Patients with inflammatory bowel disease (IBD) often face reduced bone density and higher fracture risk, affecting up to 40%. Factors include disease activity, medications, and associated conditions. Screening via DXA is recommended for prolonged disease, repeated steroid use, or specific risk factors. Treatment includes vitamin D, managing steroids, and options like bisphosphonates and RANKL inhibitors. This review outlines IBD-related bone loss: pathophysiology, diagnosis, prevention, and treatment. [Article]

5. Environmental Health and Public Health

• Ambient air pollution and urological cancer risk: A systematic review and meta-analysis of epidemiological evidence

Exposure to ambient air pollution, particularly PM2.5 and NO2, is associated with increased risks of overall urological cancer, bladder cancer, and kidney cancer. A 5 μg/m3 increase in PM2.5 correlates with a 6%, 7%, and 9% higher risk, respectively, while a 10 μg/m3 increase in NO2 is linked to a 3%, 4%, and 4% higher risk. Lowering PM2.5 levels could potentially reduce the global burden of urological cancer. Implementing effective air quality policies globally may mitigate these risks and improve public health outcomes related to urologic cancers. [Article]

• Long term impact on offspring (5-11 years of age) of metformin use in pregnancy in mothers with diabetes: A systematic review and meta-analysis

This review compared the long-term effects of metformin versus insulin for managing gestational diabetes. It found that children born to mothers treated with metformin had similar BMI and metabolic outcomes compared to those treated with insulin. There were no significant differences in obesity rates, diabetes risk, or developmental challenges in children up to 11 years old. Long-term outcomes such as BMI and diabetes risk were also comparable between mothers treated with metformin or insulin. Overall, metformin use during pregnancy did not show adverse effects on long-term health outcomes for children or mothers. [Article]

Additional Highlights

Explore more groundbreaking research and news in our newsletter:

• CircR-loop: a novel RNA:DNA interaction on genome instability [Article]
• Utilizing extracellular vesicles as a drug delivery system in glaucoma and RGC degeneration [Article]
• Remedy hope for polycystic ovary syndrome [Article]
• New Alzheimer’s drug clears FDA advisory vote despite unknowns [News]
• FDA Approves Durvalumab Combo for dMMR Endometrial Cancer [News]

Stay informed about the latest in medical research and innovation. Join us in two weeks for more insights into the dynamic world of healthcare and life sciences advancements.

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