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Gastrointestinal (GI) cancers, including colorectal, gastric, esophageal, pancreatic, and liver cancers, represent a significant global health burden, with high prevalence and mortality rates driven by aging, lifestyle factors, and infections. Emerging research highlights the role of vitamin D in cancer biology, particularly its potential in the prevention and management of GI cancers. Through its active form, calcitriol, vitamin D regulates cell proliferation, apoptosis, angiogenesis, and immune responses via the vitamin D receptor (VDR). Epidemiological studies suggest an inverse association between vitamin D deficiency and cancer risk, while experimental models demonstrate its anti-tumor effects. Additionally, vitamin D influences gut microbiota composition and immune regulation, potentially enhancing cancer immunity and response to immunotherapy. Despite promising evidence, clinical trials have yielded mixed results, underscoring the need for further research to determine optimal supplementation strategies, individual responses, and genetic influences. This review explores vitamin D’s mechanisms, epidemiological evidence, and therapeutic potential in GI cancers, advocating for personalized approaches in cancer prevention and treatment.

ABSTRACT Background Atrial fibrillation (AF) is a prevalent arrhythmia that frequently coexists with cardiomyopathy, leading to deteriorated cardiovascular outcomes. Analyzing the trends associated with these conditions is essential for improving prevention strategies and management practices. Methods CDC WONDER (1999–2023) data were analyzed to assess AF with cardiomyopathy‐related mortality in patients aged ≥ 25. Using Joinpoint regression analysis, we calculated age‐adjusted mortality rates (AAMRs) per 100,000 patients and average annual percentage changes (AAPCs) to analyze mortality trends. Results AF with cardiomyopathy is responsible for 126,377 deaths among adults aged 25 and older. Alarmingly, AAMRs have surged from 1.8 per 100,000 in 1999 to 3.0 in 2023 (AAPC: 2.11, p < 0.001). The upward trend remains pronounced, particularly between 2016 and 2021, with an annual percentage change of 6.17 ( p = 0.02). Disparities in mortality rates are striking. Men face a higher AAMR than women (3.1 vs. 1.5), and Black individuals bear the heaviest burden at 2.4, closely followed by Whites at 2.3. Regionally, Vermont stands out with the highest AAMR at 3.6, while New York reports the lowest at 1.3. Both rural and urban areas maintain equal AAMRs of 2.1, yet the increase in rural regions is particularly concerning, reflecting an AAPC of 2.44 compared to 1.78 in urban settings. Conclusion The rising mortality rates from AF with cardiomyopathy in patients, particularly among men, Black individuals, and rural residents, demand urgent action. These concerning trends underscore a public health crisis that must be addressed.

Abstract Women make up 51% of the world's population, and the global population of postmenopausal women is growing. About 25% of these women experience debilitating menopausal symptoms. Since it is important that all health care professionals have a fundamental knowledge of managing women presenting with symptoms related to the menopause, this European Society of Endocrinology Clinical Practice Guideline was developed. It provides guidance on evaluation and optimal clinical management of women who go through the menopause in middle age, those with Premature Ovarian Insufficiency (POI), Early Menopause and those for whom hormones are not appropriate, including women with, or at high risk of, breast cancer. This guideline discusses the benefits and risks of hormone therapy administration as well as summarizing other treatments for menopausal symptoms. Further, the contentious issue of the impact of menopausal hormone therapy in the prevention of chronic disease is considered.

Background and Objectives Epinephrine-containing test doses for detection of intravascular injection during epidural anesthesia may be unreliable or hazardous in beta-blocked, elderly, or pregnant patients. Subtoxic injections of lidocaine have been used as an alternative marker of intravascular injection in unpremedicated patients. We studied two groups of premedicated patients and unpremedicated subjects to evaluate the reliability of the local anesthetics bupivacaine (B) and 2-chloroprocaine (2-CP) as test dose injections. Methods Thirty ASA I and II subjects received blinded randomized injections of 2-CP, B, or normal saline via a peripheral vein. Results In group I, 10 healthy unpremedicated volunteers universally recognized injection of 90 mg 2-CP or 25 mg B, but did not reliably detect the injection of 60 mg 2-CP. In group II, 20 patients premedicated with 1 μg/kg fentanyl and 30 μg/kg midazolam could not reliably detect similar injections. Sixteen responded to the injection of 90 mg 2-CP, while 13 detected the 25 mg B test dose. A blinded observer rated only 12 of the subjective reports as conclusive of detection of intravascular injection after each drug. There were no false-positive reports in any group. Conclusions While 90 mg 2-CP or 25 mg B may be reliable alternatives to epinephrine test doses in unpremedicated subjects, they are unreliable indicators of intravascular injection in the premedicated patient.

IDH1/2 mutations (IDH mut ) increase methylation of DNA and histones in gliomas. IDH mut inhibitors are effective against low-grade IDH mut gliomas, but new strategies against high-grade IDH mut gliomas are needed. Although histone deacetylase inhibitors (HDACi) are ineffective against IDH wt glioblastoma (GBM), their potential in IDH mut gliomas has not been extensively studied. We previously established that IDH mut gliomas are more sensitive to HDACi than IDH wt GBM. Here we show that IDH mut is associated with greater sensitivity to HDACi only in glioma, not in IDH mut chondrosarcoma or cholangiocarcinoma. While HDACi induced more histone acetylation and gene regulation in IDH mut glioma than in IDH wt GBM, such acetylation was mostly within gene deserts, whereas IDH mut glioma promoters paradoxically lost histone acetylation. Two mediators of HDACi resistance, YAP and TAZ, were methylated and suppressed in IDH mut gliomas but not in other IDH mut cancers. Inducing YAP or TAZ expression in IDH mut gliomas conferred resistance to HDACi. Finally, belinostat extended in vivo survival only in IDH mut glioma models, not in IDH mut GBM models. Our findings provide a mechanistic rationale for further studies of HDACi in patients with IDH mut glioma, as well as the potential use of YAP/TAZ as a biomarker of HDACi sensitivity in cancers.

Bridging locoregional therapy (LRT) is widely used in liver transplant (LT) candidates with hepatocellular carcinoma (HCC) to minimize waitlist dropout and evaluate tumor biology. While transarterial chemoembolization (TACE) has historically been the predominant approach, the role of transarterial radioembolization (TARE) is expanding. Comparative effectiveness data for these 2 modalities as bridging strategies remain limited. This study assessed the trends, factors influencing therapy selection, and outcomes of transarterial bridging LRT. We conducted a retrospective cohort study of adult LT candidates with HCC listed in the Organ Procurement and Transplantation Network (OPTN) between 2016 and 2024 who received TACE or TARE as their sole bridging LRT. Inverse probability weighting (IPW) was applied to balance baseline covariates. Multivariable Fine–Gray competing risk regression and stratified Cox proportional hazards and logistic regression models were used to assess waitlist dropout, complete pathological necrosis (CPN), recurrence, and overall survival. Among 8367 patients, 5472 (65%) received TACE, and 2895 (35%) received TARE. TARE use increased significantly from 22.5% to 51.7% over the study period. TARE was more likely to be used among patients with MASLD, older age, and high tumor burden, and less likely in those with lower socioeconomic status. TARE recipients had a significantly lower risk of waitlist dropout (sHR 0.83, p <0.001) and a higher likelihood of achieving CPN (aOR 2.24, p <0.001). The overall survival did not differ significantly between groups (aHR 0.94, p =0.19). The use of TARE as bridging therapy in HCC LT candidates has surged and is influenced by socioeconomic factors, comorbidities, and tumor burden. TARE effectiveness has been demonstrated by its advantages in waitlist retention and tumor necrosis. Further studies are warranted to evaluate its impact on post-LT recurrence and to validate the cost-effectiveness among transarterial therapies.

Abstract Chimeric antigen receptor (CAR) T-cell (CAR-T) treatment for B-cell acute lymphoblastic leukemia (ALL) induces high initial response rates, but most patients relapse. Low disease burden (often defined as &lt;5% blasts in the bone marrow) is associated with better outcomes. CAR HEMATOTOX (HT) is a score using prelymphodepletion hematologic and inflammatory parameters to predict outcomes in lymphoma. Here, we assess its prognostic utility in a large multicenter adult B-cell ALL cohort. Patients who received brexucabtagene autoleucel across 33 centers in North America were included as part of the Real-World Outcomes Collaborative of CAR-T in Adult ALL (ROCCA) consortium. An independent cohort of 61 patients with ALL treated with an investigational CD19 CAR-T therapy at 1 center was also described. Among 199 ROCCA consortium patients, 43 (22%) patients with HTlow scores had lower rates of delayed neutrophil recovery than those with HThigh scores (26% vs 52%, P = .002) and fewer severe infections (2.5% vs 18.8%, P = .011). They also had higher response rates, overall survival (OS), and event-free survival (EFS), as well as lower nonrelapse mortality and cumulative incidence of relapse. The survival differences remained significant after multivariable adjustment for disease burden and other covariates. In the investigational cohort of 61 patients, patients with HTlow scores had improved OS and EFS, as well as higher peak CAR-T expansion. In summary, CAR HT score is a prognostic factor independent of disease burden in adult ALL. HTlow score is associated with superior outcomes after CD19 CAR-Ts and higher CAR-T expansion in a single-center cohort. These trials were registered at www.clinicaltrials.gov as #NCT01044069 and #NCT01860937.