BMC Medicine最新文献

Background: Potentially modifiable cardiovascular risk factors, including hypertension, diabetes, obesity, alcohol consumption, and smoking initiation, are associated with hypertrophic (HCM) and dilated (DCM) cardiomyopathies, representing promising targets for interventions. However, the causality and cross-ancestry generalizability of these associations remain uncertain.

Methods: Collecting summary-level data from genome-wide association studies for systolic (SBP) and diastolic (DBP) blood pressure, hypertension, type 2 diabetes, fasting glucose, glycated hemoglobin, body mass index (BMI), waist circumference (WC), alcohol consumption, smoking initiation, HCM, and DCM (sample size ranging from 38,288 to 1,812,017), we performed comprehensive two-sample univariable Mendelian randomization (MR) to evaluate the causal effect of each trait on HCM and DCM in both European and East Asian populations. We performed multivariable MR to investigate the independent effects of interrelated traits (SBP vs. DBP; BMI vs. WC).

Results: MR analyses identified reliable evidence of a causal effect of SBP on HCM (Europeans: odds ratio (OR) = 1.03, 95% confidence interval (CI) = 1.02-1.04; East Asians: OR = 1.06, 95% CI = 1.03-1.08). For DCM, reliable evidence of causal effects was identified for DBP (Europeans: OR = 1.04, 95% CI = 1.03-1.04; East Asians: OR = 1.07, 95% CI = 1.04-1.11), WC (Europeans: OR = 1.73, 95% CI = 1.58-1.89; East Asians: OR = 3.32, 95% CI = 1.22-9.03), and alcohol consumption (Europeans: OR = 1.50, 95% CI = 1.20-1.86; East Asians: OR = 1.32, 95% CI = 1.11-1.56). In Europeans, genetically predicted higher WC (OR = 1.75, 95% CI = 1.53-2.01) and smoking initiation (OR = 1.34, 95% CI = 1.16-1.56) specifically increased the risk of HCM and DCM, respectively, while genetically predicted higher alcohol consumption (OR = 1.68, 95% CI = 1.36-2.07) specifically increased the risk of HCM in East Asians.

Conclusions: This study provided reliable cross-ancestry genetic evidence supporting higher SBP as a causal risk factor for HCM and higher DBP, WC, and alcohol consumption as causal risk factors for DCM. These findings underscore the potential of precision prevention strategies targeting modifiable cardiovascular risk factors to reduce cardiomyopathy burden across populations.

Background: Wastewater and environmental surveillance (WES) has demonstrated the potential to detect signal for the mpox virus (MPXV), thereby supporting public health efforts to mitigate outbreaks. The aim of this scoping review was to document the use of WES as an early warning system and public health tool for mpox outbreak management.

Methods: A systematic search was conducted in PubMed, Web of Science and Scopus in August 2024, and updated in April 2025, to identify eligible studies using the PCC framework.

Results: The search yielded 256 records. Title and abstracts were screened for 140 records. Full text screening was done on the remaining 43 records, of which 10 further records were excluded. A total of 33 studies, published between 2022 and 2024, were included for synthesis in this review. Twenty-two studies reported a positive correlation/association between trends of MPXV in wastewater data and the reported cases on mpox. Four studies included in this scoping review reported the detection of MPXV in wastewater before clinical cases. Other studies reported negative associations, as well as false positive and false negative results from WES for mpox. Surveillance was predominantly conducted at wastewater treatment plants (91%), leaving a gap in surveillance of non-sewered settings. The qPCR method was reported by 61% of studies for molecular analysis. However, assessments of the qPCR method are needed to improve sensitivity and accuracy in the quantification of MPXV in wastewater.

Conclusions: Further research is needed to improve the capability of WES to provide early indication of mpox outbreaks and inform the accurate quantification of MPXV in wastewater to serve as an early warning system.

Background: Climate change is increasing the frequency of hot nights, which may contribute to cardiovascular morbidity and mortality by impairing sleep and autonomic recovery. Despite World Health Organization guidelines for maximum daytime indoor temperatures (26 °C, 79 °F), there are no equivalent recommendations for nighttime conditions. We investigated the impact of nocturnal bedroom temperature on heart rate and heart rate variability (HRV) in free-living older adults.

Methods: In this observational study, 47 community-dwelling adults aged ≥ 65 years in southeast Queensland, Australia, were monitored across one summer (December 2024-March 2025). Wearable devices recorded heart rate and HRV during nighttime periods of sleep between the hours of 9 PM-7 AM, while in-home sensors continuously measured bedroom temperature. The primary outcome was the natural logarithm of the root mean square of successive differences (lnRMSSD). Secondary outcomes were log-transformed frequency-domain HRV indices (high frequency: lnHF, low frequency: lnLF, low to high frequency ratio: lnLF:HF) and heart rate. Generalised mixed effects models analysed associations between wearable derived outcomes and temperature categories (< 24 °C [79 °F], 24-26 °C [75-79 °F], 26-28 °C [79-82 °F], 28-32 °C [82-90 °F]). Clinically relevant thresholds were defined as ≥ 1.5 standard deviation change in HRV or ≥ 5 beats·min⁻¹ change in heart rate.

Results: Across 14,179 valid nighttime hours, median bedroom temperature was 25.9 °C (Q1, Q3; 24.6, 26.9). Compared with < 24 °C (79 °F), nighttime bedroom temperatures of 24-26 °C (75-79 °F; odds ratio: 1.4; 95% confidence interval [1.2, 1.6], P < 0.001), 26-28 °C (79-82 °F; 2.0 [1.8-2.3]) and 28-32 °C (82-90 °F; 2.9 [2.5-3.4]) were associated with greater odds of clinically relevant reductions in lnRMSSD (P < 0.001). Higher temperatures were also linked to reduced lnHF and lnLF, increased ln(LF:HF), and elevated heart rate (all P < 0.001).

Conclusions: Nocturnal bedroom temperatures above 24 °C (79 °F) were associated with greater likelihood of autonomic disruption and increased heart rate in older adults, consistent with a shift toward sympathetic dominance and heightened physiological stress, with greater effects observed as temperature increased. These findings provide real-world physiological evidence supporting the development of nighttime indoor temperature guidelines to protect vulnerable populations in a warming climate.

Background: Immune-mediated inflammatory diseases (IMIDs) are a wide group of autoimmune conditions that share common inflammatory pathways, meaning that people with one IMID are at elevated risk of developing another. People living with IMIDs are at increased risk of co-morbidities and quality of life (QOL) is negatively impacted. The economic cost of IMIDs is high both in terms of healthcare resource and lost productivity. In particular, there is significant unmet need in terms of clinical outcomes and patient satisfaction for people living with complex IMID (multiple IMIDs, co-morbidities and people for whom IMID(s) have a significant impact on QOL).

Main body: Existing clinical service models focused on single specialty management provide fragmented care caught between individual specialities with delays to decisions and treatment plans, with individual IMID specialities competing for the same scarce National Health Service (NHS) resources. This siloed approach often focuses on suppressing inflammatory activity which may not adequately address the range of impacts on the person living with IMID. These issues have prompted a movement towards collaborative cross-specialty care. A collaborative cross-specialty approach has the potential for sharing knowledge and resources, to ensure timely referral and diagnosis, more effective use of available time for clinical consultation and early recognition and treatment of concomitant IMIDs. Compared with a traditional siloed model, a cross-specialty approach was associated with QOL theme benefits including positive patient experience and perceived disease control. Involvement of a cross-specialty team and well-defined referral criteria are key to optimal collaborative cross-specialty working. Existing initiatives have shown that relatively small changes to existing practice and cross-speciality collaborative working can result in bespoke solutions, such as parallel clinics, combined clinics and multidisciplinary team (MDT) sessions, face-to-face or virtually depending on the individual needs. A patient-centric framework, with individualised care, helps to address multimorbidity whilst improving physical and mental well-being.

Conclusions: The development of a cross-specialty service for complex IMID cases has the potential to reduce the number and length of consultations, and available data indicate that such innovations may improve clinical outcomes, patient experience and quality of care in a cost-effective manner and suggest wider societal benefits.

Background: Women who have undergone cervical conization may still experience subsequent pregnancies and delivery. However, it remains unknown whether pregnancy, associated with immune tolerance, might increase the risk of subsequent cervical lesions. This study aims to address this knowledge gap by utilizing the nationwide Swedish registers.

Methods: A total of 60,895 women diagnosed with cervical intraepithelial neoplasia in Sweden between January 1997 and December 2017 and treated with conization were identified through the Swedish National Patient Register and followed for subsequent cervical lesions. Time-dependent Cox regression was used to examine the association of post-conization pregnancies with subsequent cervical lesions.

Results: Among the 60,895 women who underwent conization in Sweden, 15,200 (25%) had post-conization pregnancies and showed a higher incidence of subsequent cervical lesions (hazard ratio = 1.32, 95% confidence interval = 1.13-1.53) compared to women without pregnancies. The increased risk of subsequent cervical lesions was observed only in women who had a pregnancy within 3 years after conization (adjusted hazard ratio = 1.39, 95% confidence interval = 1.19-1.63).

Conclusions: Our study demonstrates that post-conization pregnancies are associated with a higher risk of subsequent cervical lesions compared to women without pregnancies. The risk was particularly significant in women who had a pregnancy within 3 years after conization, suggesting that those who become pregnant within 3 years after conization will need close clinical monitoring.

Background: Physician assistants/associates (PAs) were introduced into NHS secondary care facilities to help address workforce shortages in the UK. However, recent controversy and the government-commissioned Leng Review in England highlighted concerns around role clarity, supervision, and professional boundaries relating to PAs, largely due to inconsistent implementation and local variations. We examined how PA roles are developed and integrated in hospital teams across high-income countries, generating insights relevant to ongoing workforce reforms in the UK, including those recently recommended in England by the Leng Review.

Methods: We conducted a realist review to explain how, why, and under what contexts PA roles are developed and integrated in secondary care. We systematically searched peer-reviewed studies from high-income settings and UK-specific grey literature (Jan 2000-March 2025). We extracted and synthesised data to develop context-mechanism-outcome configurations (CMOCs). We mapped history, regulation, and scope of practice in included countries to support contextual interpretation. We iteratively refined CMOCs to produce a final programme theory.

Results: We developed 56 CMOCs from 122 sources across nine high-income settings, which were synthesised into five inter-related themes: (1) organisational drivers, such as service design, workforce shortages, and policy reforms, created opportunities for new workforce models like introducing PA roles; (2) PAs' role and identity formation were shaped through time, supervision, and opportunities for meaningful, appropriately challenging work; (3) negotiation of professional boundaries revealed unclear or overlapping roles creating tensions, whereas well-defined, complementary roles reducing resistance; (4) role perceptions and acceptance from team members and patients depended on perceived value and relative advantages, also shaped by psychologically safe team cultures; and (5) evidence and impact were difficult to measure using standard metrics, which often overlooked PAs' contributions to teamwork and continuity, and role variations and methodological limitations constrained generalisability.

Conclusions: Our findings offer a transferrable framework for understanding workforce innovations and new roles in complex health systems. We provide practical insights for hospital managers and clinical leaders in the NHS, including those in England who are implementing the reforms recommended by the Leng Review. Realist evaluations are needed to refine our programme theory and inform effective workforce changes.

Background: Infants exposed to hyperglycemia in pregnancy (HIP) in utero are known to have higher risks of macrosomia at birth and obesity in adulthood, but longitudinal growth patterns in early childhood remain poorly characterized. This study aimed to examine HIP-associated differences in early childhood growth trajectories.

Methods: In the population-based prospective Jiangsu Birth Cohort (JBC) study, 8780 children (23.3% HIP exposed) were included. Linear mixed models were used to assess the associations of maternal HIP with repeated growth measures in children. Latent class mixed models (LCMM) were used to identify trajectories for weight-for-age (WAZ), length/height-for-age (LAZ) and weight-for-length z-scores (WFL). Models were fitted to the full 0-36-month age range, with measurements at ages 0, 3, 6, 8, 12, 18, 24, 30, and 36 months, respectively. Adjusted associations between maternal HIP and child trajectory classes were evaluated with modified Poisson regression.

Results: A higher proportion of LGA in the HIP-exposed group was observed. During the follow-up period from birth to 36 months, maternal HIP was associated with lower WAZ (aβ = - 0.075, 95% CI: - 0.117, - 0.034), LAZ (aβ = - 0.054, 95% CI: - 0.099, - 0.009), and WFL (aβ = - 0.061, 95% CI: - 0.100, - 0.022) in children. HIP was also correlated with reduced weight and body mass index (BMI) growth velocity at 0-3 and 6-8 months. Three distinct trajectory groups were identified, namely, moderate-stable, high-decreasing and low-increasing group. HIP exposed children were more likely to follow the high-decreasing WFL trajectory (aRR = 1.14, 95% CI: 1.01, 1.29).

Conclusions: Maternal HIP was associated with slower growth in early childhood and an increased likelihood of following a high-decreasing growth trajectory, suggesting its potential long-term implications for child growth regulation.

Background: Although dendritic cell (DC)- and CD8⁺ T cell-mediated autoimmunity is critical for destroying melanocytes in vitiligo, treatment options remain limited by the absence of therapies that cotarget both cell types.

Methods: We first evaluated the association between the immunoregulatory metabolite itaconate and disease development, by determining human vitiligo serum itaconate levels and monitoring depigmentation progression in Acod1 knockout (KO) mice with endogenous itaconate deficiency. We further evaluated the therapeutic efficacy of the itaconate derivative, dimethyl itaconate (DI) in mice and assessed its effects on cutaneous infiltration and the functional properties of DCs and CD8⁺ T cells in vivo and ex vivo. The gene signatures and signaling pathways involved in DI-treated CD8⁺ T cells were also assessed.

Results: We observed an elevation of circulating itaconate in vitiligo patients, whereas itaconate deficiency accelerated depigmentation in Acod1 KO mice after vitiligo induction. The administration of DI halted vitiligo development and promoted repigmentation, with elevated circulating itaconate levels, increased melanocyte counts, and decreased cutaneous CD8⁺ T cell densities. Mechanistically, DI dampened CD8⁺ T cell activation (CD69), effector function (Interferon-γ, IFN-γ), cytotoxicity (Gzmb), proliferation, and proinflammatory gene expression (Csf1, Ifitm1, CD49a, NKG2D, and NKG2A), partly by suppressing the Janus kinase (JAK)‒STAT pathway. Moreover, DI-treated mice exhibited reduced cutaneous DC infiltration, as well as fewer DCs with mature and migratory phenotypes.

Conclusions: Our findings identify DI as a metabolite-derived small molecule that protects against autoimmune injury by cotargeting DC and CD8⁺ T cell responses, thereby demonstrating a promising therapeutic strategy and providing a foundation for treating vitiligo and other cell-specific autoimmune diseases.

Background: Dyslipidemia is a major cardiovascular risk factor; however, disease patterns-particularly lipid profiles-remain understudied in high-altitude populations. On the Pamirs Plateau (> 4000 m), no relevant epidemiological studies have been conducted to date. This study investigates the disease patterns in this region, with an emphasis on dyslipidemia epidemiology.

Methods: We conducted a serial cross-sectional study (2021-2024) using annual health examination data from Tashkurgan County, Pamirs Plateau. Adults aged ≥ 18 years residing ≥ 1 year were included. We first examined the overall disease patterns, with a focus on dyslipidemia. Age-standardized prevalence was calculated and stratified by sex and ethnicity. Subsequently, lipid profile distributions and temporal trends were analyzed. To place these findings in a global context, LDL-C levels were compared with populations from plains and other high-altitude regions. Finally, potential risk factors were identified using multivariate logistic regression and machine learning models.

Results: Among a representative subset (24.37%) of the Pamirs Plateau population, dyslipidemia was the most prevalent condition, followed by hypertension, sinus bradycardia, and fatty liver. The prevalence of dyslipidemia ranged from 25.24% to 37.64%. LDL-C levels were lower than those in plains and other high-altitude regions. Ethnic disparities were evident: the minority population (predominantly Tajik) maintained stable, favorable lipid profiles across ages, while non-minorities exhibited pronounced age-related fluctuations. Age 70 emerged as a potential inflection point at which sex-related differences in LDL-C levels reversed. Male, non-minority, older age, diabetes, frequent alcohol consumption, and higher education were significantly associated with dyslipidemia. Unexpectedly, improved living conditions (range hood use [OR: 1.839, 95% CI: 1.673-2.021], natural gas use [OR: 1.273, 95% CI: 1.152-1.406], tap water access [OR: 1.315, 95% CI: 1.204-1.436]) were linked to a higher risk, a "modernization paradox". Additionally, distinct temporal fluctuations were observed: LDL-C levels sharply declined in 2022 before rebounding, coinciding with the COVID-19 lockdown period.

Conclusions: This first comprehensive analysis from "the roof of the world" reveals unique lipid patterns, including low LDL-C levels, pandemic-era fluctuations, ethnic disparities, unique age-sex patterns, and a paradoxical association between improved living conditions and increased dyslipidemia risk. These insights should inform context-specific lipid management strategies for this and similar vulnerable high-altitude populations globally.

Background: Defining acute illness decompensation as a single entity limits individualisation of treatments for older patients. Multi-modal and high-dimensional data offer opportunities to derive quantified clusters with clinically meaningful outcomes. We tested the hypothesis that cluster-driven and high-dimensional predictors can be constructed with sufficient fidelity for clinical deployment, concurrently highlighting mechanistic insights into pathophysiological substrates of acute illness decompensation, including where this affected the brain.

Methods: Two independent prospective cohort studies, DELPHIC and DECIDE, were harmonised and utilised as train and test partitions, contributing 209 and 205 unique first-participant acute admission episodes respectively. Baseline and acute illness variables were projected using T-stochastic neighbour embedding onto a two-dimensional manifold and agglomerative hierarchical clustering designated distance-defined subtypes. Predictive performances of clusters and full models were compared for brain decompensation within admission and 2-year mortality. SHapley Additive exPlanations (SHAPs) quantified directional contributions of inputs towards high-dimensional model performances.

Results: Three broad clinical subtypes were identified in older people during decompensation, with similar contributions from baseline and acute illness variables. From baseline to cluster-driven, and then high-dimensional prediction models for brain decompensation in admission, the test area under receiver operating characteristic curve (AUROC) improved from 0.563 to 0.641 and 0.797 respectively. Sleep-wake cycle disturbance was the most important predictor of delirium in admission, while physiological fluctuations within an admission episode, in particular from cognitive domains, were significant predictors of long-term mortality after acute admission.

Conclusions: Robust, generalisable clusters with clinical utility are discernable for older patients during acute illness. Our results demonstrate proof of concept for a longitudinal approach towards defining and modelling acute illness. We illustrate the potential to maximally predict adverse outcomes with high-dimensionality and multi-modality, and highlight the importance of sleep-wake cycle disturbances as a future target in studies of delirium neuropathophysiology.