EClinicalMedicine最新文献

Background: Individuals with type 2 diabetes mellitus are treated with a growing variety of medications targeting multiple metabolic pathways. In recent years, incretins such as the GLP-1 receptor agonists have proven effective in the control of hyperglycemia but also in weight loss, where they are now separately approved as a treatment for obesity. Given the importance of obesity and metabolic syndrome as risk factors for malignancy, the impact of GLP-1 receptor agonists on cancer risk is of increasing interest. Here, we performed an analysis of the impact of GLP-1 receptor agonists and SGLT2 inhibitors on cancer risk and mortality.

Methods: We performed a multicenter retrospective cohort study using the TriNetX database of electronic health records between 2019 and 2024, including patients with a diagnosis of type 2 diabetes mellitus. Individuals prescribed GLP-1 receptor agonists, SGLT2 inhibitors, or neither were compared for the incidence of four obesity-related hematologic malignancies using a Cox proportional hazards model. Similar analysis was applied to mortality associated with these medication classes in individuals with type 2 diabetes mellitus and the hematologic malignancies under study.

Findings: GLP-1 receptor agonist use is associated with a significantly decreased risk of multiple myeloma (HR 0.64, p = 0.01), but not chronic myeloid leukemia (HR 1.06, p = 0.857), acute myeloid leukemia (HR 0.81, p = 0.354), or myelodysplastic syndrome (HR 0.98, p = 0.996). This effect was preserved in subgroups with BMI >30 and HbA1c >8%. Further, we find that in patients with multiple myeloma and acute myeloid leukemia, SGLT2 inhibitor use is associated with a significantly increased risk of mortality, independent of heart or kidney failure (MM HR 2.27, p < 0.001, AML HR 2.00, p = 0.006).

Interpretation: Our results strengthen the association between metabolic disease and multiple myeloma yet call for prospective investigation into the use of SGTL2 inhibitors in patients with specific hematologic neoplasms.

Funding: National Institutes of Health.

Background: Sleep, physical activity, and nutrition (SPAN) are key determinants of both life expectancy (lifespan) and disease-free life expectancy (healthspan), yet are often studied in isolation. This study aimed to determine the minimum combined SPAN improvements needed for a longer lifespan and healthspan.

Methods: This prospective cohort comprised 59,078 participants from the UK Biobank, recruited between 2006 and 2010 (median age: 64.0 years; 45.4% male). Between 2013 and 2015, a subsample of participants was invited to wear a wrist worn accelerometer for 7 days. Moderate to vigorous physical activity (MVPA; mins/day) and sleep (hours/day) were calculated using a validated wearables-based algorithm. Diet was assessed using a 10-item diet quality score (DQS), including intake of vegetables, fruits, grains, meats, fish, dairy, oils, and sugar-sweetened beverages (ranging 0-100; higher indicates better quality). Lifespan and healthspan (free of cardiovascular disease (CVD), cancer, type II diabetes, chronic obstructive pulmonary disease (COPD), and dementia) were estimated across 27 joint tertile SPAN combinations and a composite SPAN score using life tables.

Findings: Over an 8.1-year median follow-up, 2458 deaths, 9996 CVD, 7681 cancers, 2971 type II diabetes, 1540 COPD, and 508 dementia events occurred. Compared to the least favourable tertiles, the optimal tertiles (7.2-8.0 h/day of sleep; >42 min/day of MVPA; DQS of 57.5-72.5) had 9.35 additional years of lifespan (95% CI: 6.67, 11.63) and 9.45 years of healthspan (95% CI: 5.45, 13.61). Compared to the 5th percentile, a minimum combined improvement of 5 min/day of sleep, 1.9 min/day MVPA, and a 5-point increase in DQS (e.g., additional ½ serving of vegetables/day or additional 1.5 servings of whole grains per day) was associated with 1 additional year of lifespan (95% CI: 0.69, 1.15). For healthspan, a combined improvement of 24 min/day of sleep, 3.7 min/day of MVPA, and a 23-point DQS increase was associated with 4.0 additional years (95% CI: 0.50, 8.61).

Interpretation: Modest concurrent improvements in sleep, physical activity, and diet were associated with meaningful gains in lifespan and healthspan.

Funding: Australian National Health and Medical Research Council.

Background: Post-COVID-19 condition (PCC) affects millions globally, with cognitive dysfunction ("brain fog") impairing daily functioning in up to 88% of patients. No effective treatments exist for PCC-related cognitive impairment. Photobiomodulation (PBM), a non-invasive therapy delivering near-infrared light, enhances mitochondrial function and reduces neuroinflammation, showing promise in neurological disorders. This study aimed to evaluate the efficacy and safety of home-based intranasal and transcranial PBM (itPBM) for PCC cognitive dysfunction.

Methods: This randomized, double-blind, sham-controlled pilot trial in the USA (ClinicalTrials.govNCT05857124) enrolled 43 adults (18-65 years) with PCC cognitive symptoms ≥12 weeks post-infection. Participants were randomized 1:1, stratified by age (<45 vs ≥ 45 years), using computer-generated assignment to 8 weeks of daily 20-min itPBM, 6 days per week, with the Vielight Neuro RX Gamma device or sham, targeting the brain's default mode network, followed by 4 weeks of observation. Participants, investigators, and assessors were masked to group assignment. The primary outcome was mean change in Creyos cognitive battery composite score at Day 56. Secondary outcomes included fatigue, quality of life, and safety. Analyses used mixed-model repeated measures in the per-protocol population.

Findings: The trial was completed, with 43 participants randomized (23 active, 20 sham) and 41 analyzed (21 active, 20 sham). They were recruited between July 5, 2023, and September 1, 2024. Active itPBM improved composite cognitive scores more than sham (mean difference 0.043, 95% CI -0.007 to 0.092, p = 0.088), with significant gains in participants <45 years (prespecified but exploratory, p = 0.028). Attention tasks improved consistently (p < 0.050 at multiple timepoints). Secondary outcomes mobility favored sham (p = 0.007), and fatigue also favored sham. No serious adverse events occurred; compliance was high (median 55 days, interquartile range 2 days).

Interpretation: Home-based itPBM is safe and feasible, showing potential cognitive benefits for PCC brain fog, particularly in younger adults. Larger trials are needed to confirm efficacy and optimize parameters.

Funding: Vielight Inc.

Background: Individuals with Lynch syndrome (LS) are advised to undergo pancreatic ductal adenocarcinoma (PDAC) surveillance if their lifetime risk is ≥5%, however, evidence is limited. This study quantifies lifetime risk and survival of three cancers relevant to PDAC surveillance, including PDAC, ampullary carcinoma (AC) and distal cholangiocarcinoma (dCC), to evaluate whether surveillance is justified.

Methods: This retrospective nationwide Dutch cohort study included individuals with LS pathogenic variants (PVs) in MLH1, MSH2, MSH6, PMS2 or EpCAM (identified between 1985 and 2024) and compared them to sporadic cases from the general population (diagnosed between 2000 and 2022). Cumulative incidence (CI) of PDAC, AC and dCC was estimated using Fine-and-Gray models for LS and a CI formula for sporadic cases. Relative risks (RRs) were calculated by comparing CIs. Survival of the cancers was compared between both cohorts using 1:10 matched analyses by age at diagnosis, sex, stage, and year of diagnosis.

Findings: In total, 2605 individuals with LS were included (median age 63.9 years; IQR 53.7-74.0), of whom 1515 (58.2%) were female. PVs were identified in MLH1 (723, 27.8%), MSH2 (895, 34.4%), MSH6 (731, 28.1%), PMS2 (233, 8.9%) and EpCAM (23, 0.9%). By age 75, the combined CI of PDAC, AC and dCC was 3.0% (95% CIs, 1.5-5.8) in MLH1, 3.4% (95% CIs, 2.0-5.8) in MSH2/EpCAM, 1.0% (95% CIs, 0.3-2.7) in MSH6 and 0% in PMS2. No familial-clustering of cancers was observed. Matched survival did not differ between PDACs in LS and sporadic cases. In contrast, survival was better for AC in LS (34.3 months; 95% CIs, 3.2-Inf) compared to sporadic cases (15.5 months; 95% CIs, 9.9-19.3).

Interpretation: In LS, the combined lifetime risk of PDAC, AC and dCC ranged from 0 to 3.4% across different genes, remaining below the 5% risk threshold for PDAC surveillance. Additionally, having an affected relative did not appear to increase risk. These findings suggest that current surveillance recommendations for individuals with LS should be re-evaluated.

Funding: Lynch-Polyposis.

Background: Data on cancer incidence and associated risk factors among women with HIV are limited. We investigated cancer burden among women with HIV.

Methods: We included all women ≥18 years from the two large multicentre observational cohort collaborations (D:A:D and RESPOND). The primary outcomes were incidence of all cancers, HPV-related and common individual cancers including breast cancer, lung cancer, and non-Hodgkin lymphoma (NHL) from 2006 to 2021. Baseline was defined as the latest date of entry into local cohort enrolment and 1st January 2006 for D:A:D and 1st January 2012 for RESPOND. Participants were followed from baseline until the date of first cancer, final follow-up or administrative censoring-whichever occurred first. We assessed risk factors using multivariable Poisson regression by applying robust standard errors and determined a population attributable fraction (PAF) for key risk factors for cancers.

Findings: Among 17,512 women included, median age at baseline was 39.5 years (interquartile range, IQR 32.5-46.0). Over 141,404 person-years (PYS) and a median 9.2 (5.5-10.1) years of follow-up, 832 women were diagnosed with any cancer; incidence rate 5.9 (95% CI 5.5-6.4)/1000 PYS, 163 HPV-related cancers (1.1 [1.0-1.3]/1000 PYS), 150 breast cancers (1.1 [0.9-1.2]/1000 PYS), 94 lung cancers (0.7 [0.5-0.8]/1000 PYS) and 72 NHL (0.5 [0.4-0.6]/1000 PYS). Older age (≥45 vs. <45 years), Southern Europe (vs. Western Europe) and smoking were associated with an increased risk of overall cancers. Lower pre-ART nadir CD4, time-updated CD4, and a prior AIDS diagnosis were associated with lung- and HPV-related cancer. In PAF analysis, smoking and HIV-related factors such as lower current CD4, nadir CD4 and HIV viremia significantly contributed to cancer risk.

Interpretation: Our findings suggest that women with HIV older than 45 years, past or current immunosuppressed or current smokers could be candidates for intensified cancer screening and prevention.

Funding: The Highly Active Antiretroviral Therapy Oversight Committee, The CHU St Pierre Brussels HIV Cohort, The Austrian HIV Cohort Study, The Australian HIV Observational Database, The AIDS Therapy Evaluation in the Netherlands national observational HIV cohort, The Brighton HIV Cohort, The National Croatian HIV Cohort, The EuroSIDA cohort, The Frankfurt HIV Cohort Study, The Georgian National AIDS Health Information System, The Nice HIV Cohort, The Isabel Foundation, The Modena HIV Cohort, The PISCIS Cohort Study, The Swiss HIV Cohort Study, The Swedish InfCare HIV Cohort, The Royal Free HIV Cohort Study, The San Raffaele Scientific Institute, The University Hospital Bonn HIV Cohort, The University of Cologne HIV Cohort, Merck Life Sciences, ViiV Healthcare, and Gilead Sciences.

Background: Machine Learning (ML) can contribute to reducing child mortality and morbidity in low- and middle-income countries (LMICs), yet its development and clinical adoption remain unclear. This systematic review provides an overview of ML for hospitalised children in LMICs.

Methods: In June 2025, searches in five scientific databases and one scholarly search engine identified 26 eligible peer-reviewed studies using ML on hospitalised children under 18. Studies using only conventional statistics and perinatal data were excluded. Study quality and bias were assessed using PROBAST + AI. Descriptive statistics were used for data analysis. PRISMA reporting guideline was followed.

Findings: These studies were conducted in Asia (58%) and Sub-Saharan Africa (38%), mostly retrospective (62%), and predominantly used patient files (62%). The median sample size was 1291. Prognostic models dominated (69%), primarily targeting mortality (50%). Ensemble methods were most common (50%). The median AUROC was 0.81 (IQR 0.78-0.83). Most models were at a clinical Readiness Level 3-4 (81%). Barriers and facilitators related to data (65%, 34% respectively), implementation (50%, 77%), technology (31%, 42%), and human (19%, 35%) were reported.

Interpretation: We provided evidence of ML's promising performance for LMICs. Mortality prediction was the main focus. Arriving at clinical applications that benefit LMICs, requires investment in high-quality data and alignment to local (clinical) needs.

Funding: This project is part of the EDCTP2 programme (grant number RIA2020I-3294 IMPALA) supported by the European Union.