BMC Medicine最新文献

Background: Incidence of stroke and certain cancers is increasing at younger ages in many high-income countries, prompting healthcare systems to consider how best to improve prevention, such as earlier primary care health checks. We assessed potential barriers to the success of the current proposal in England to reduce the starting age of the 5-yearly NHS health check from 40 to 30 years.

Methods: In a prospective population-based study (Oxford Vascular Study; 1/4/2002-31/3/23) of 94 567 people in a subpopulation of Oxfordshire, UK, we assessed all participants with incident acute vascular events occurring at age 30-44 years and determined the proportion of those who would have qualified for active risk management were they to have had the proposed new health check prior to their event (i.e. premorbid QRISK3-10-year absolute CV-risk ≥ 10%). We also assessed CV-risk relative to age-specific 'ideal' risk (QRISK3-Relative Risk (RR) score, predicted "healthy-heart-age") and number of risk factors above recommended target.

Results: During 433,797 person-years of ascertainment, 217 individuals aged 30-44 years had an incident vascular event (crude incidence rate 50/100 000 person years). Of these, 155 would have been eligible for an earlier health check. The median 10-year predicted CV risk in this group was only 2.5% (IQR = 1.1-4.8%), with 148 (95%) falling below the 10% threshold for active risk management. The median 10-year risk among the 49 women was 1.1% (IQR 0.5-2.2%), with none having a predicted risk above the 10% threshold. Yet, the mean predicted "healthy heart age" gap was 9 years(SD = 7), and 137(88%) had at least one treatable risk factor above target level.

Conclusions: The majority of vascular events at age 30-44 years occur in individuals with treatable risk factors above target level, yet the vast majority had falsely reassuring premorbid 10-year CV risks that were well below the 10% threshold for treatment, potentially undermining the effectiveness of earlier primary care health checks.

Background: This study aims to assess the efficacy and safety of a triplet adjuvant regimen consisting of tislelizumab, lenvatinib, and capecitabine following radical resection in patients with biliary tract cancer (BTC).

Methods: In this open-label, single-arm trial, patients with histologically confirmed BTC who had undergone curative resection were enrolled to receive adjuvant therapy within 4-16 weeks postoperatively. The treatment regimen consisted of tislelizumab (200 mg), lenvatinib (8 mg), and capecitabine (1250 mg/m²). The primary endpoint was the 1-year disease-free survival (DFS) rate. Secondary endpoints included median DFS, 2-year DFS rate, and 1- and 3-year overall survival (OS) rates, as well as safety profiles. Exploratory analyses were conducted to evaluate genomic alterations and prognostic biomarkers associated with clinical outcomes.

Results: Between February 24 and December 31, 2022, a total of 50 patients underwent treatment. As of the data cutoff (April 30, 2025), the median follow-up duration was 29.3 months (95% CI: 27.2-30.4). Intrahepatic cholangiocarcinoma constituted 78% of cases, with TNM stage III or IV observed in 40% of patients and poorly differentiated tumors identified in another 40%. The median DFS was calculated at 12.7 months (95% CI: 6.4-19.0), with DFS rates being reported as 55.5% (95% CI: 51.4%-57.6%) at 1 year and 30.8% (95% CI: 28.6%-32.9%) at 2 years, respectively. Median OS was not reached; however, the 1-year OS rate stood at an impressive figure of 93.8% (95% CI: 91.7%-95.9%) while the 3-year OS rate declined to 54.4% (95% CI: 50.0%-58.4%). By the exploratory analyses, FSIP2 mutation was associated shorter DFS (P < 0.001). Treatment-related grade 3 adverse events occurred in 20% of patients, with no treatment-related deaths or grade ≥ 4 toxicities reported.

Conclusions: Adjuvant tislelizumab, lenvatinib, and capecitabine demonstrated clinical activity and tolerable safety in patients with resected BTC. Despite not meeting the primary endpoint, continued follow-up and further evaluation are warranted to better define the potential role of this combination regimen.

Trial registration: ClinicalTrials.gov Identifier: NCT05254847; registered prospectively on February 15, 2022.

Background: Hypertension is a major risk factor for cardiovascular disease. Salt substitutes may reduce sodium intake while maintaining palatability, but comparative effects across formulations remain uncertain.

Methods: We conducted a systematic review and frequentist random-effects network meta-analysis of randomised controlled trials in adults comparing salt substitutes with regular salt, other substitutes or no intervention. Databases (PubMed, Embase, CENTRAL, CNKI, Wanfang), WHO-ICTRP and ClinicalTrials.gov were searched from inception to Oct 3, 2025 (PROSPERO CRD42023451859). We assessed the risk of bias using a modified Cochrane tool and conducted a random-effects network meta-analysis, with evidence certainty evaluated through the GRADE approach.

Results: We included 34 randomised controlled trials involving 37,063 participants across 15 countries (17 from China, 17 from other countries; mean age 62.3 years). Our results indicate that moderate-potassium and low-sodium salt substitutes (25-40% KCl, 60-79% NaCl) probably reduce all-cause mortality, cardiovascular mortality, non-fatal cardiovascular events and systolic blood pressure (SBP) compared to regular salt, with reductions of 7-17 deaths per 1000 individuals and 4.39-4.64 mmHg for SBP, based on moderate to high certainty evidence. Mortality and cardiovascular benefits are predominantly driven by one large Chinese trial (SSaSS, n = 20,995); excluding this trial eliminated statistical significance for all-cause mortality. Among non-Chinese studies, none contributed mortality data. Substitutes with higher potassium or very low sodium showed similar blood pressure reductions but provided less certain evidence regarding mortality and events. No substitute increased adverse events or withdrawals, and acceptability was comparable to regular salt.

Conclusions: Salt substitutes, particularly moderate-potassium and low-sodium formulations, represent a promising sodium reduction strategy. However, current evidence for mortality and cardiovascular event benefits is dominated by one large Chinese trial and has very limited generalisability beyond Chinese populations with high discretionary salt use. These products appear acceptable and safe in people without renal impairment, but clinicians should rule out kidney disease and hyperkalaemia risk before recommending them, and large trials in non-Chinese populations are needed.

Background: Air pollution and the rising prevalence of liver diseases have become public health concerns. Nevertheless, the relationship and underlying mechanisms between ambient air pollution and liver function remain inadequately investigated.

Methods: A total of 4096 rural residents living in the suburb of Xinxiang city, China, were recruited from the Henan Rural Cohort. The participants underwent two physical examinations conducted in 2017 and 2021, respectively. A linear mixed-effects model was utilized to evaluate the associations between individual ambient air pollutants and liver function biomarkers. To determine the main air pollutants that impact liver function biomarkers, weighted quantile sum (WQS) regression models were applied. Additionally, the mediating role of fasting insulin (FINS) in these associations was investigated using mediation analysis.

Results: For each increase in the interquartile range (IQR) of fine particulate matter (PM_2.5) (lag03, representing the average exposure over the current and previous 3 days) concentration (IQR 17.73 μg/m³), aspartate aminotransferase levels increased by 2.30% (95% confidence interval [CI]: 1.34%, 3.28%). Similar relationships were also detected between other air pollutants and biomarkers of liver function. WQS regression analysis confirmed that sulfur dioxide (weight: 0.64), nitrogen dioxide (NO₂) (0.13), and ozone (0.18) were the main contributing pollutants associated with total bilirubin (TBIL). FINS was significantly associated with NO₂ exposure and increases in indirect bilirubin (IBIL) (11.41%, 95% CI 9.78%, 16.58%), direct bilirubin (DBIL) (5.32%, 95% CI 5.02%, 8.47%), and TBIL (11.56%, 95% CI 9.97%, 16.58%). The mediating effect of FINS in the relationship between PM_2.5 and alanine aminotransferase levels was significant. It accounted for - 49.92% (95% CI - 96.56%, - 29.99%) of the total effect.

Conclusions: There is a positive association between short-term exposure to ambient air pollutants and biomarkers of liver function. Moreover, FINS may play mediating roles in these associations.

Background: Stillbirth is a profound and devastating outcome of pregnancy that has a long-lasting emotional and physiological impact on parents and families. Current risk assessment approaches largely rely on maternal characteristics and clinical history, yet their predictive accuracy remains poor, particularly among nulliparous women (women with no previous birth beyond 24 weeks of gestation). We evaluated the extent to which routinely collected pregnancy risk factors can predict stillbirth and assessed their contribution among singleton births in nulliparous women.

Methods: We conducted a population-based retrospective cohort study of 876,279 nulliparous women receiving maternity care across 130 National Health Service (NHS) Trusts in England between 2015 and 2019. Thirty-one maternal and pregnancy factors routinely collected during antenatal care were analysed. We used modified Poisson regressions with generalised estimating equations to account for clustering of women within Trusts to compute risk ratios (RR) and 95% confidence intervals (CI). We calculated adjusted population attributable risks (PARs) for significant factors.

Results: Among 876,279 nulliparous women receiving maternity care, 2568 stillbirths occurred. Modifiable maternal characteristics associated with increased risk included elevated body mass index (BMI) (RR 1.22, 95% CI 1.03-1.45 for BMI 35- < 40 kg/m²; RR 1.70, 95% CI 1.39-2.07 for BMI ≥ 40 kg/m², both compared to BMI 18.5- < 25 kg/m²), smoking at booking (RR 1.34, 95% CI 1.19-1.51), current substance misuse (RR 1.52, 95% CI 1.16-1.98), lack of folic acid consumption before conception (RR 1.28, 95% CI 1.16-1.40) or during pregnancy (RR 1.38, 95% CI 1.18-1.61), and late antenatal booking after 12 weeks of gestation (RR 1.18, 95% CI 1.07-1.30). Fetal growth restriction accounted for the largest population attributable risk for stillbirth (RR 2.96, 95% CI 2.73-3.21).

Conclusions: Maternal and clinical risk factors explain only a fraction of stillbirths in nulliparous women and cannot underpin a clinically useful prediction model. These findings demonstrate the limitations of risk-based screening strategies and highlight the need for integrated approaches that combine maternal characteristics with biochemical, biophysical, and system-level factors to achieve meaningful advances in stillbirth prevention.

Background: The anatomical and pathophysiological characteristics of coronary artery disease vary between the sexes. This study investigated the impact of sex on outcomes in patients with de novo coronary artery lesions treated with drug-coated balloons (DCB) or drug-eluting stents (DES).

Methods: REC-CAGEFREE I was an investigator-initiated, non-inferiority trial conducted at 43 sites in China from Feb 5, 2021, to May 1, 2022, which randomized 2,272 patients for treating de novo coronary lesions, regardless of vessel diameter. After successful lesion pre-dilatation, eligible patients were randomized (1:1) to either DCB angioplasty with the option of rescue stenting or intended DES deployment. In this prespecified subgroup analysis, patients were analyzed by sex based on their medical records. The primary endpoint was device-oriented composite endpoint (DoCE), including cardiovascular death, target-vessel myocardial infarction, and clinically and physiologically indicated target lesion revascularization at 2 years. Between-group differences were compared by Cox proportional-hazards models, and imbalances in baseline characteristics were adjusted with inverse probability of treatment weighting (IPTW). The analyses were conducted in the intention-to-treat population.

Results: A total of 2,272 participants underwent randomization, of which 698 (30.7%) were female and 1,574 (69.3%) were male. At 2 years, no statistically significant differences in the incidence of DoCE were observed between sexes (36 [5.2%] for females and 74 [4.7%] for males, HR_IPTW:1.04, 95%CI:0.67 to 1.61, P = 0.877). Compared with DES, DCB was associated with a numerically higher risk of DoCE in females (6.3% versus 3.9%, HR_IPTW:1.55, 95%CI:0.78 to 3.11, P = 0.210) and a statistically significant higher risk in males (6.4% versus 3.1%, HR_IPTW:2.28, 95%CI:1.40 to 3.70, P = 0.001), respectively, with no significant sex-by-treatment (DCB/DES) interaction observed (P_interaction = 0.575). The prognosis of DCB and DES differed significantly between small vessel disease (SVD) and non-SVD among females (P_interaction = 0.007), but not among males (P_interaction = 0.408).

Conclusions: For patients with de novo, non-complex coronary artery disease, DCB was associated with a significantly higher risk of 2-year DoCE compared with DES in males, whereas a consistent but non-significant trend was observed in females.

Trial registration: ClinicalTrials.gov identifier: NCT04561739.

Background: Bariatric surgery and pharmacotherapy represent two major strategies for the treatment of obesity. Sleeve gastrectomy (SG) is the most widely performed surgical procedure and is supported by long-term evidence, while semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), has recently emerged as an effective medical therapy. However, prospective real-world studies directly comparing these interventions are limited.

Methods: We conducted a prospective, non-randomized trial at a single tertiary center (ChiCTR2300070632). Adults with obesity were allocated to SG (n = 36) or once-weekly semaglutide (n = 35) based on shared decision-making. Semaglutide was administered for a planned duration of 24 weeks, after which continuation or discontinuation was determined by patient preference. Primary outcomes were percentage total weight loss (%TWL) and changes in body mass index (BMI) at 1, 3, 6, and 12 months. Secondary outcomes included changes in metabolic parameters.

Results: SG achieved significantly greater weight loss at all time points. At 12 months, mean %TWL was 28.6% for SG versus 11.3% for semaglutide (p < 0.001). Mean BMI decreased from 32.7 ± 2.8 to 23.8 ± 2.6 kg/m² in the SG group and from 32.0 ± 2.6 to 28.4 ± 4.0 kg/m² in the semaglutide group (p < 0.001). Both groups demonstrated metabolic improvements, but SG was associated with greater reductions in triglycerides and greater increases in high-density lipoprotein cholesterol (HDL-C). Among patients who discontinued semaglutide after 6 months (n = 25), mean weight increased from 74.6 ± 11.3 to 83.2 ± 12.3 kg by 12 months, with 32% regaining to baseline weight or higher.

Conclusions: SG achieved greater weight loss and improvements in triglycerides and HDL-C compared with semaglutide. Semaglutide was effective during treatment, but many patients experienced weight regain after discontinuation.

Trial registration: Trial Registry No. ChiCTR2300070632 (2023 April 19).

Background: Patients with asthma have an increased risk of developing depression, affecting their quality of life. To date, the processes contributing to this comorbidity remain unclear.

Methods: We integrated two large genome-wide association studies (88,486 patients with asthma and 447,859 controls; 412,024 patients with depression and 1,587,577 controls) with cross-sectional and longitudinal information available from the All of Us Research Program (N = 87,167) through polygenic risk scoring (PRS), Cox proportional-hazards models, one-sample Mendelian randomization (MR), and gene-set and drug-repurposing analyses.

Results: We observed that depression PRS was associated with increased asthma risk (hazard ratio, HR = 1.13, 95% CI = 1.09-1.17), also when accounting for comorbidity status (HR = 1.08, 95% CI = 1.04-1.12). Conversely, the effect of asthma PRS was null after accounting for comorbidity status. One-sample MR analysis showed an effect of depression genetic liability on asthma, ranging from beta = 0.36 ± 0.03 when considering a linear relationship to beta = 3.21 ± 0.31 when considering possible nonlinear relationships. Conversely, the effect of asthma genetic risk on depression was null after accounting for potential confounders. The gene-set analyses showed that asthma and depression polygenic risks share biological processes, molecular functions, and cellular components related to the immune system and the lung-brain axis.

Conclusions: Genetic predisposition contributes to asthma-depression comorbidity through direct effects and shared pathogenic processes. These findings highlight the potential to develop targeted interventions to prevent and treat the co-occurrence of respiratory and neuropsychiatric disorders.

Background: Children with complicated severe malnutrition (CSM) face high mortality after hospital discharge, yet the underlying mechanisms remain poorly understood. While early post-discharge mortality (< 2 months) has been linked to a sepsis-like inflammatory profile measured at discharge, it is unclear whether this relationship persists (later mortality; 2-6 months post-discharge). This study investigated whether immune, inflammatory, and endothelial dysfunction at 2 months post-discharge are associated with later mortality in children recovering from CSM.

Methods: We conducted a case-control study nested within a randomised placebo-controlled trial of daily co-trimoxazole in HIV-negative children aged 2-59 months with CSM in four Kenyan hospitals. Cases were children who died between 2 and 6 months post-discharge; controls were survivors frequency-matched by sex, site, and trial arm. Plasma cytokines, chemokines, endothelial markers, and untargeted proteomics were measured at discharge and 2 months post-discharge. Conditional Cox regression, adjusted for age, sex, site, mid-upper arm circumference (MUAC), and randomisation arm, was used to identify biomarkers associated with later mortality.

Results: Cases were younger (had a median of 7 vs. 11 months), had longer hospital stays (14 vs. 10 days), and showed lower anthropometry (MUAC = 10.7 vs. 12.0 cm) and lower haemoglobin (9.7 vs. 10.6 g/dL) at 2 months post-discharge (all p < 0.05). Mortality 2-6 months post-discharge was associated with elevated inflammatory mediators (e.g. IL-10 [hazard ratio, HR: 1.47, 95% confidence interval, CI: 1.00-2.14], IL-15 [1.65, 95% CI: 1.08-2.51], IFN-α2 [1.51, 95% CI: 1.02-2.23]), acute phase proteins, apolipoproteins and coagulation markers, including fibrinogen, histidine-rich glycoprotein (1.40, 95% CI: 1.01-1.94), protein C inhibitor (SERPINA5, 1.50, 95% CI: 1.07-2.08), SERPINA10 (1.42, 95% CI: 1.02-1.99), and ADAMTS13 (0.41, 95% CI: 0.24-0.70). Additionally, cardiovascular and muscle-related proteins such as angiotensinogen (1.46, 95% CI: 1.03-2.08), α- and β-tropomyosin (0.68, 95% CI: 0.48-0.98), PI16 (0.72, 95% CI:0.54-0.97), and zyxin (0.61, 95% CI: 0.40-0.92) were elevated in cases.

Conclusions: Later mortality in children recovering from CSM is associated with persistent immune activation, a sepsis-like phenotype involving multiple systems. These findings suggest that children at risk of later mortality may benefit from biomarker-guided interventions initiated at discharge.

Background: Chronic pain is common and debilitating and significantly impacts quality of life (QoL). However, large-scale population-based evidence on general bodily pain, pain sufficient to impact daily life (high-impact pain), and their relation to sociodemographic and health-related outcomes is limited.

Methods: Self-administered questionnaire data from the 45 and Up Study (Wave-2, 2012-2015), an Australian population-based cohort study, were used to estimate the prevalence of general and high-impact pain. Modified Poisson regression estimated age- and sex-adjusted prevalence ratios (PRs) quantified their relation to sociodemographic, behavioural, and health characteristics, as well as physical functioning, psychological distress, QoL, and self-rated health.

Results: Overall, the study included n = 142,313 participants. Among them, 31% reported moderate-to-severe bodily pain, and 13% reported high-impact pain. High-impact pain was more common among females (14.3% versus 12.0% in males; PR = 1.24 [1.21-1.28]), older adults (18.8%, PR = 1.73 [1.66-1.79] for age ≥ 80 years; 14.2%, PR = 1.29 [1.26-1.33] for 65-79 years; versus 11.2% for 45-64 years), those least physically active (versus most active), currently smoking (versus never-smoking), obese, or had chronic health conditions. The prevalence of high-impact pain was markedly higher among those with lower education levels, lower household income, physical disability, psychological distress, or low QoL. Similar patterns were observed for bodily pain, although associations were weaker. Consistently, people reporting greater high-impact pain and bodily pain were substantially more likely to experience severe physical functioning limitations, moderate-to-high psychological distress, and poor/fair self-rated health and QoL compared to people without such pain. For example, 47.2% of the 16,825 people with high-impact pain had severe physical limitations versus 4.0% of 30,748 people without impactful pain (PR = 10.35 [9.78-10.95]); among those with high-impact pain, 40.5%, 36.5%, and 26.7%, respectively, had moderate-to-high psychological distress (PR = 4.61 [4.43-4.80]), poor/fair self-rated health (PR = 8.64 [8.16-9.14]), and poor/fair QoL (PR = 8.73 [8.16-9.34]).

Conclusions: Bodily pain sufficient to interfere with daily life affects around one-in-eight older community-dwelling participants. People of lower socioeconomic position and those with health problems, particularly physical disability, are more likely to experience high-impact pain. Among those experiencing high-impact pain, around half have severely reduced physical functioning or high psychological distress, and a quarter report poor/fair QoL.