Biomarker Testing Disparities in Metastatic Colorectal Cancer.

Importance: Among patients with metastatic colorectal cancer (mCRC), data are limited on disparate biomarker testing and its association with clinical outcomes on a national scale. Objective: To evaluate the socioeconomic and demographic inequities in microsatellite instability (MSI) and KRAS biomarker testing among patients with mCRC and to explore the association of testing with overall survival (OS). Design, Setting, and Participants: This cohort study, conducted between November 2022 and March 2024, included patients who were diagnosed with mCRC between January 1, 2010, and December 31, 2017. The study obtained data from the National Cancer Database, a hospital-based cancer registry in the US. Patients with mCRC and available information on biomarker testing were included. Patients were classified based on whether they completed or did not complete MSI or KRAS tests. Exposure: Demographic and socioeconomic factors, such as age, race, ethnicity, educational level in area of residence, median household income, insurance type, area of residence, facility type, and facility location were evaluated. Main Outcomes and Measures: The main outcomes were MSI and KRAS testing between the date of diagnosis and the date of first-course therapy. Univariable and multivariable logistic regressions were used to identify the relevant factors in MSI and KRAS testing. The OS outcomes were also evaluated. Results: Among the 41 061 patients included (22 362 males [54.5%]; mean [SD] age, 62.3 [10.1] years; 17.3% identified as Black individuals, 78.0% as White individuals, 4.7% as individuals of other race, with 6.5% Hispanic or 93.5% non-Hispanic ethnicity), 28.8% underwent KRAS testing and 43.7% received MSI testing. A significant proportion of patients had Medicare insurance (43.6%), received treatment at a comprehensive community cancer program (40.5%), and lived in an area with lower educational level (51.3%). Factors associated with a lower likelihood of MSI testing included age of 70 to 79 years (relative risk [RR], 0.70; 95% CI, 0.66-0.74; P < .001), treatment at a community cancer program (RR, 0.74; 95% CI, 0.70-0.79; P < .001), rural residency (RR, 0.80; 95% CI, 0.69-0.92; P < .001), lower educational level in area of residence (RR, 0.84; 95% CI, 0.79-0.89; P < .001), and treatment at East South Central facilities (RR, 0.67; 95% CI, 0.61-0.73; P < .001). Similar patterns were observed for KRAS testing. Survival analysis showed modest OS improvement in patients with MSI testing (hazard ratio, 0.93; 95% CI, 0.91-0.96; P < .001). The median (IQR) follow-up time for the survival analysis was 13.96 (3.71-29.34) months. Conclusions and Relevance: This cohort study of patients with mCRC found that older age, community-setting treatment, lower educational level in area of residence, and treatment at East South Central facilities were associated with a reduced likelihood of MSI and KRAS testing. Highlighting the sociodemographic-based disparities in biomarker testing can inform the development of strategies that promote equity in cancer care and improve outcomes for underserved populations.

Clinico-pathologic factors and survival of patients with breast cancer diagnosed with de novo brain metastasis: a national cancer database analysis.

PURPOSE: Patients with Breast Cancer (BC) with Brain Metastasis (BCBM) have poor survival outcomes. We aimed to explore the clinico-pathologic and therapeutic factors predicting the survival in patients with de novo BCBM using the National Cancer Database (NCDB). PATIENTS AND METHODS: The NCDB was queried for patients with BC between 2010 and 2020. Survival analysis with Kaplan-Meier curves and log rank tests were used to find median overall survival (OS) in months (95% CI) across the different variables. A multivariate cox regression model was computed to identify significant predictors of survival. RESULTS: Out of n = 2,610,598 patients, n = 9005 (0.34%) had de novo BCBM. A trend of decreasing OS was observed with increasing age, Charlson-Deyo score (CDS), and number of extracranial metastatic sites. The highest median OS was observed in the Triple Positive and the lowest OS in the Triple Negative subgroup. Based on treatment regimen, combination of systemic therapy and local therapy achieved the highest OS. A positive trend in OS was observed in the BC subgroup analysis with targeted therapy demonstrating a survival benefit when added to systemic therapy. The multivariate cox regression model showed that age, race, ethnicity, insurance, median income, facility type, CDS, BC subtype, metastatic location sites, and treatment combinations received were significantly associated with risk of death. Receiving only local treatment for BM without systemic therapy more than doubled the risk of death compared to combining it with systemic therapy. CONCLUSIONS: This analysis suggests that treatment of systemic disease is the major factor influencing survival in patients with BCBM. Moreover, targeted therapy with anti-HER2 increased survival when added to systemic therapy explaining the highest median OS noted in the Triple Positive subgroup.

The Gut Microbiome and Alzheimer's Disease: A Growing Relationship.

Evidence that the gut microbiota plays a key role in the pathogenesis of Alzheimer's disease is already un-ravelling. The microbiota-gut-brain axis is a bidirectional communication system that is not fully understood but includes neural, immune, endocrine, and metabolic pathways. The progression of Alzheimer's disease is supported by mechanisms related to the imbalance in the gut microbiota and the development of amyloid plaques in the brain, which are at the origin of Alzheimer's disease. Alterations in the composition of the gut microbiome led to dysregulation in the pathways governing this system. This leads to neurodegeneration through neuroinflammation and neurotransmitter dysregulation. Neurodegeneration and disruption of the blood-brain barrier are frontiers at the origin of Alzheimer's disease. Furthermore, bacteria populating the gut microbiota can secrete large amounts of amyloid proteins and lipopolysaccharides, which modulate signaling pathways and alter the production of proinflammatory cytokines associated with the pathogenesis of Alz-heimer's disease. Importantly, through molecular mimicry, bacterial amyloids may elicit cross-seeding of misfolding and induce microglial priming at different levels of the brain-gut-microbiota axis. The potential mechanisms of amyloid spreading include neuron-to-neuron or distal neuron spreading, direct blood-brain barrier crossing, or via other cells such as astrocytes, fibroblasts, microglia, and immune system cells. Gut microbiota metabolites, including short-chain fatty acids, pro-inflammatory factors, and neurotransmitters may also affect AD pathogenesis and associated cognitive decline. The purpose of this review is to summarize and discuss the current findings that may elucidate the role of gut microbiota in the development of Alzheimer's disease. Understanding the underlying mechanisms may provide new insights into novel therapeutic strategies for Alzheimer's disease, such as probiotics and targeted oligosaccharides.

Latest updates on cellular and molecular biomarkers of gliomas.

Gliomas are the most common central nervous system malignancies, compromising almost 80% of all brain tumors and is associated with significant mortality. The classification of gliomas has shifted from basic histological perspective to one that is based on molecular biomarkers. Treatment of this type of tumors consists currently of surgery, chemotherapy and radiation therapy. During the past years, there was a limited development of effective glioma diagnostics and therapeutics due to multiple factors including the presence of blood-brain barrier and the heterogeneity of this type of tumors. Currently, it is necessary to highlight the advantage of molecular diagnosis of gliomas to develop patient targeted therapies based on multiple oncogenic pathway. In this review, we will evaluate the development of cellular and molecular biomarkers for the diagnosis of gliomas and the impact of these diagnostic tools for better tailored and targeted therapies.

The Use of Hydroxyurea in the Treatment of COVID-19.

INTRODUCTION: The rapid worldwide spread of COVID-19 motivated medical professionals to pursue and authenticate appropriate remedies and treatment protocols. This article aims to analyze the potential benefits of one treatment protocol developed by a group of care providers caring for severe COVID-19 patients. METHODS: The clinical findings of COVID-19 patients who were transferred to a specialized care hospital after unsuccessful treatment in previous institutions, were analyzed. The specialized care hospital used a treatment protocol including hydroxyurea, a medication commonly used for sickle cell treatment, to improve respiratory distress in the COVID-19 patients. None of the COVID-19 patients included in the analyzed data were diagnosed with sickle cell, and none had previously taken hydroxyurea for any other conditions. RESULTS: In all presented cases, patients reverted to their baseline respiratory health after treatment with the hydroxyurea protocol. There was no significant difference in the correlation between COVID-19 and hydroxyurea. However, deaths were extremely low for those taking hydroxyurea. CONCLUSIONS: Fatality numbers were extremely low for those taking hydroxyurea; death could be attributed to other underlying issues.