Age-stratified comorbid and pharmacologic analysis of patients with glioblastoma.

Background: Increased age is a strong and unfavorable prognostic factor for patients with glioblastoma (GBM). However, the relationships between stratified patient age, comorbidities, and medications have yet to be explored in GBM patient survival analyses. Objective: To evaluate co-morbid conditions, tumor-related symptoms, medication prescriptions, and subject age for patients with GBM and to establish potential targets for prospective studies. Methods: Electronic health records for 565 patients with IDHwt GBM were evaluated at a single center between January 1, 2000 and August 9, 2021 were retrospectively assessed. Data were stratified by MGMT promoter methylation status when available and were used to construct multivariable time-dependent cox models and intra-cohort hazards. Results: Younger (<65 years of age) but not older (≥65 years) GBM patients demonstrated a worse prognosis with movement related disabilities (P < 0.0001), gait/balance difficulty (P = 0.04) and weakness (P = 0.007), as well as psychiatric conditions, mental health disorders (P = 0.002) and anxiety (P = 0.001). In contrast, older but not younger GBM patients demonstrated a worse prognosis with epilepsy (P = 0.039). Both groups had worse survival with confusion/altered mental status (P = 0.023 vs < 0.000) and an improved survival with a Temozolomide prescription. Older but not younger GBM patients experienced an improved hazard with a prescription of ace-inhibitor medications (P = 0.048). Conclusion: Age-dependent novel associations between clinical symptoms and medications prescribed for co-morbid conditions were demonstrated in patients with GBM. The results of the current work support future mechanistic studies that investigate the negative relationship(s) between increased age, comorbidities, and drug therapies for differential clinical decision-making across the lifespan of patients with GBM.

On the Operating Table: A Student's Experience in Surgery.

The role of medical students in patient care is complex. Students suggest plans but are not responsible for enacting them. We are anticipated to make mistakes but expected to perform tasks with excellence. Regardless of the field, physicians are tasked with the responsibility and burden of making decisions. Students are at the interface between the patient and the surgical team; their interactions with the patient can be life-changing and potentially lifesaving. Choosing to not operate on patients, deemed inoperable, can be morally challenging. As students, we may not have the power to make decisions but can be present and learn from our patients.

Clinical significance of culture-negative, PCR-positive bronchoalveolar lavage results in severe pneumonia.

Some culture-negative, PCR-positive BAL samples may represent true infection. A subset of patients with a culture-negative, PCR-positive BAL result will have a subsequent BAL culture positive for the organism initially identified by PCR alone. https://bit.ly/3DWoFPo.

Alpha-T-catenin is expressed in peripheral nerves as a constituent of Schwann cell adherens junctions.

The adherens junction component, alpha-T-catenin (αTcat) is an established contributor to cardiomyocyte junction structure and function, but recent genomic studies link CTNNA3 polymorphisms to diseases with no clear cardiac underpinning, including asthma, autism and multiple sclerosis, suggesting causal contributions from a different cell-type. We show Ctnna3 mRNA is highly expressed in peripheral nerves (e.g. vagus and sciatic), where αTcat protein enriches at paranodes and myelin incisure adherens junctions of Schwann cells. We validate αTcat immunodetection specificity using a new Ctnna3-knock-out fluorescence reporter mouse line yet find no obvious Schwann cell loss-of-function morphology at the light microscopic level. CTNNA3/Ctnna3 mRNA is also abundantly detected in oligodendrocytes of the central nervous system via public databases, supporting a general role for αTcat in these unique cell-cell junctions. These data suggest that the wide range of diseases linked to CTNNA3 may be through its role in maintaining neuroglial functions of central and peripheral nervous systems. This article has a corresponding First Person interview with the co-first authors of the paper.

A systematic review of pharmacologic treatment efficacy for depression in older patients with cancer.

Background: Older adults ≥65 years of age represent the majority of new cancer diagnoses and are vulnerable to developing depression-like symptoms. Evaluation and management of depression in older cancer patients is underappreciated despite its high prevalence and impact on health-related quality of life. Although antidepressants are the primary pharmacologics used to treat depressive-like symptoms, the efficacy and overall benefit(s) are not well-characterized in older adult patients with cancer. The objective of this investigation was to review what is known about the efficacy of pharmacologic treatment for older adults with depression and cancer. Methods: PubMed (Medline) and EMBASE (Elsevier) databases were analyzed for relevant literature in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: 1,919 unique studies were identified for title and abstract screening. Forty-eight publications were retrieved for full review. None of the identified studies evaluated the potential for benefit after pharmacological treatment among older adults with cancer and depression. Twenty-seven publications met all study criteria except for an analysis focused on older patients. Conclusion: We discovered a universal absence of literature with a relevance to pharmacologic antidepressant treatment effects in older adult patients with cancer. This included a lack of evaluation in patients with brain tumors who have an unusually high predilection for developing depression. Our findings suggest that new research is critically needed for understanding optimal clinical management strategies in older adults with cancer and depression who are treated with antidepressants.

Outcomes and complications of minimally invasive transforaminal lumbar interbody fusion in the elderly: a systematic review and meta-analysis.

OBJECTIVE: Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) may be used to treat degenerative spinal pathologies while reducing risks associated with open procedures. As an increasing number of lumbar fusions are performed in the aging United States population, MIS-TLIF has been widely adopted into clinical practice in recent years. However, its complication rate and functional outcomes in elderly patients remain poorly characterized. The objective of this study was to assess complication rates and functional outcomes in elderly patients (≥ 65 years old) undergoing MIS-TLIF. METHODS: The PubMed, Embase, and Scopus databases were searched for relevant records in accordance with the PRISMA guidelines. Inclusion criteria were peer-reviewed original research; English language; full text available; use of MIS-TLIF; and an elderly cohort of at least 5 patients. Risk of bias was assessed using the ROBINS-I (Risk of Bias in Nonrandomized Studies-of Interventions) tool. Pooled complication rates were calculated for elderly patients, with subgroup analyses performed for single versus multiple-level fusions. Complication rates in elderly compared to nonelderly patients were also assessed. Postoperative changes in patient-reported outcomes, including Oswestry Disability Index (ODI) and visual analog scale (VAS) back pain (BP) and leg pain (LP) scores, were calculated. RESULTS: Twelve studies were included in the final analysis. Compared to nonelderly patients, MIS-TLIF in elderly patients resulted in significantly higher rates of major (OR 2.15, 95% CI 1.07-4.34) and minor (OR 2.20, 95% CI 1.22-3.95) complications. The pooled major complication rate in elderly patients was 0.05 (95% CI 0.03-0.08) and the pooled minor complication rate was 0.20 (95% CI 0.13-0.30). Single-level MIS-TLIF had lower major and minor complication rates than multilevel MIS-TLIF, although not reaching significance. At a minimum follow-up of 6 months, the postoperative change in ODI (-30.70, 95% CI -41.84 to -19.55), VAS-BP (-3.87, 95% CI -4.97 to -2.77), and VAS-LP (-5.11, 95% CI -6.69 to -3.53) in elderly patients all exceeded the respective minimum clinically important difference. The pooled rate of fusion was 0.86 (95% CI 0.80-0.90). CONCLUSIONS: MIS-TLIF in elderly patients results in a high rate of fusion and significant improvement of patient-reported outcomes, but has significantly higher complication rates than in nonelderly patients. Limitations of this study include heterogeneity in the definition of elderly and limited reporting of risk factors among included studies. Further study of the impact of complications and the factors predisposing elderly patients to poor outcomes is needed.

Glioblastoma as an age-related neurological disorder in adults.

BACKGROUND: Advanced age is a major risk factor for the development of many diseases including those affecting the central nervous system. Wild-type isocitrate dehydrogenase glioblastoma (IDHwt GBM) is the most common primary malignant brain cancer and accounts for ≥90% of all adult GBM diagnoses. Patients with IDHwt GBM have a median age of diagnosis at 68-70 years of age, and increasing age is associated with an increasingly worse prognosis for patients with this type of GBM. METHODS: The Surveillance, Epidemiology, and End Results, The Cancer Genome Atlas, and the Chinese Glioma Genome Atlas databases were analyzed for mortality indices. Meta-analysis of 80 clinical trials was evaluated for log hazard ratio for aging to tumor survivorship. RESULTS: Despite significant advances in the understanding of intratumoral genetic alterations, molecular characteristics of tumor microenvironments, and relationships between tumor molecular characteristics and the use of targeted therapeutics, life expectancy for older adults with GBM has yet to improve. CONCLUSIONS: Based upon the results of our analysis, we propose that age-dependent factors that are yet to be fully elucidated, contribute to IDHwt GBM patient outcomes.

αT-catenin: A developmentally dispensable, disease-linked member of the α-catenin family.

α-Catenins are actin-filament binding proteins and critical subunits of the cadherin-catenin cell-cell adhesive complex. They are found in nominally-defined epithelial (E), neural (N), and testis (T) forms transcribed from three distinct genes. While most of α-catenin research has focused on the developmentally essential founding member, αE-catenin, this review discusses recent studies on αT-catenin (CTNNA3), a developmentally dispensable isoform that is emerging as relevant to cardiac, allergic and neurological diseases.