PLoS Medicine最新文献

Background: Excess body adiposity is an established cause of renal cancer, but underlying molecular pathways mediating this relationship remain unclear. This study aimed to systematically evaluate a panel of obesity-related risk factors as potential mediators in renal cancer etiology.

Methods and findings: We used two complementary approaches to evaluate obesity-related risk factors in renal cancer etiology: (i) direct risk factor assessment in longitudinal cohorts and (ii) genetically proxied risk factors through two-sample mendelian randomization (MR). Direct risk-factor association-analyses (i.e., cohort analyses) were based on the UK Biobank cohort study (472,337 cohort participants, including 1,382 incident renal cancer cases diagnosed during 5,586,414 person years of follow-up) and the Northern Sweden Health and Disease Study (NSHDS) for fasting insulin (204 pairs of cases and controls, ongoing recruitment and follow-up since 1985). We used Cox proportional hazards regression models to evaluate the association between risk factors and renal cancer risk with adjustment for age, sex, center of recruitment, education, smoking and alcohol drinking status. Two-sample MR analyses were based on a genome-wide association study (GWAS) of renal cancer (27,213 cases, 486,846 controls). We used the inverse-variance weighted (IVW) approach to estimate the association between risk factors and renal cancer risk. Mediation analyses were performed for traits displaying directionally consistent associations with renal cancer risk in both the cohort and MR analyses using the product method. We found consistent positive associations with renal cancer risk for fasting insulin (odds ratio per standard deviation increment [ORMR]: 2.24, 95% confidence interval [95% CI]: 1.19, 4.22; p = 0.01; hazard ratio per standard deviation increment [HRcohort]: 1.43, 95% CI: 1.02, 2.00; p = 0.04), triglycerides (ORMR: 1.11, 95% CI: 1.05, 1.17; p < 0.001, HRcohort: 1.23, 95% CI: 1.11, 1.38; p < 0.001), diastolic blood pressure (DBP) (ORMR: 1.14, 95% CI: 1.04, 1.26; p < 0.001, HRcohort: 1.11, 95% CI: 1.05, 1.17; p < 0.001) and consistent inverse associations with renal cancer risk for sex-hormone binding globulin (SHBG) (ORMR: 0.80, 95% CI: 0.70, 0.90; p < 0.001, HRcohort: 0.67, 95% CI: 0.58, 0.76; p < 0.001) and high-density lipoprotein (HDL) cholesterol (ORMR: 0.93, 95% CI: 0.88, 0.98; p < 0.001, HRcohort: 0.72, 95% CI: 0.66, 0.77; p < 0.001). The main limitation of this study was that we had limited statistical power to evaluate some risk factors.

Conclusions: Our study highlights roles for fasting insulin, HDL cholesterol, DBP, triglycerides and SHBG in mediating the relationship between body adiposity and renal cancer risk.

Despite many antihypertensive options, uncontrolled hypertension remains pervasive. Aldosterone synthase inhibitors show robust blood pressure reductions and have the potential to reshape hypertension treatment, though cost and access may impact broad adoption.

Background: The Lancet Commission proposed an update in January 2025 on the definition of obesity which requires at least one anthropometric measurement in addition to body mass index (BMI) to confirm excess adiposity. Also, the presence of obesity-related organ dysfunction is used to differentiate between clinical and pre-clinical obesity. We evaluated how applying the Lancet Commission proposed definition of obesity, which required an additional anthropometric measurement to verify excess adiposity, would affect its prevalence, and its implications on the cardiovascular-kidney-metabolic health.

Methods and findings: We used two representative Chinese community-based cohorts and compared five categories of participants with (i) clinical obesity, (ii) preclinical obesity, (iii) BMI ≥25 kg/m2 without confirmed excess adiposity, (iv) overweight and (v) normal/underweight in the cross-sectional cohort for cardiometabolic risk profiles and in the longitudinal cohort for long-term cardiovascular-kidney-metabolic outcomes. In the cross-sectional cohort, the prevalence of obesity was 44.5% in men and 26.7% in women defined by the Asian BMI cutoff of ≥25.0 kg/m2, and decreased to 33.8% and 24.1%, respectively, using the Lancet Commission definition (BMI ≥ 25.0 kg/m2 and elevated waist circumference). Applying the Lancet Commission definition would reclassify a portion of individuals who are initially classified as having obesity based on BMI criteria alone (BMI ≥ 25.0 kg/m2) but with normal waist circumference to be non-obese (category iii). The individuals falling into category iii had an adverse cardiometabolic health profile which was intermediate among the five categories regarding insulin resistance and visceral adiposity (falling in between categories ii and iv). In the longitudinal cohort with a median follow-up of over 20 years, people with clinical obesity had the poorest cardiovascular-kidney-metabolic outcomes including all-cause mortality, whereas those reclassified as non-obese had an intermediate risk of adverse cardiovascular-kidney-metabolic outcomes among the five categories. The main limitation of the study was that all participants were Chinese and findings might not apply to other ethnic groups.

Conclusion: Adoption of the Lancet Commission definition would classify a small proportion of individuals with BMI of ≥25.0 kg/m2 as non-obese. People with clinical obesity identified by the revised criteria had the highest risks of cardiovascular-kidney-metabolic outcomes including all-cause mortality, whereas individuals reclassified as non-obese had intermediate risks of cardiovascular-kidney-metabolic outcomes between those in pre-clinical obesity and overweight categories.

Background: Estimating the proportion of individuals currently infected with Mycobacterium tuberculosis (Mtb) is key for informing global health policies. Although a substantial portion of the global population exhibit tuberculous immunoreactivity, not all have a viable Mtb infection. Moreover, individuals with recent infections are at a higher risk of developing tuberculosis (TB). Here, we present estimates of the global burden of viable Mtb infection, using new insights into the natural history of TB.

Methods and findings: We constructed country-specific trends in annual risk of infection considering estimates of TB burden, immunoreactivity reversion, and age-specific mixing. We applied these trends to a deterministic mathematical model incorporating reinfection and self-clearance to estimate recent (within 2 years) and total viable Mtb infections. Empirical data on self-clearance are limited, so rates were informed by modelling estimates. In 2022, we estimated that 133.7 million people (95% uncertainty interval [UI]: 104.0, 171.1) had a recent Mtb infection, representing 1.7% (95% UI: 1.3, 2.2) of the global population. In total, 288.9 million people (95% UI: 242.2, 342.7)-or 3.7% (95% UI: 3.1, 4.3) globally-were estimated to harbour a viable Mtb infection. Among those recently infected, 12.0% (95% UI: 11.4, 12.7) were children under 15 years of age. Most recent infections were found in the World Health Organization regions of South-East Asia (49.0%; 95% UI: 37.2, 62.4), the Western Pacific (19.7%; 95% UI: 12.6, 30.5), and Africa (17.9%; 95% UI: 12.9, 24.1). India, Indonesia, and China had the highest burden, with 39.1 million (95% UI: 18.0, 73.6), 12.0 million (95% UI: 5.8, 22.9), and 11.2 million (95% UI: 5.0, 25.5) people, respectively, recently infected with Mtb. Sensitivity analyses of varying self-clearance scenarios showed significant changes in global estimates of viable Mtb infection, particularly in total burden, with lower self-clearance rates. Overall uncertainty in the estimates was considerable, reflecting limitations in the underlying data informing key model parameters.

Conclusions: Our findings offer global burden estimates of viable Mtb infection and reveal a sizable population recently infected with Mtb and at high risk of progression to disease. New diagnostic tools that can detect individuals with viable Mtb-particularly those who would benefit from TB preventive therapy-are urgently needed.

While global interest in mpox may be waning, outbreaks, illness, and death continue across Africa and the world. Ending transmission requires a sustained global response that moves beyond reactive measures.

Background: Reducing health inequalities is of national importance. Total hip replacement (THR) is a commonly used elective surgical procedure. Few studies have examined area-level inequalities for a wide range of outcomes following THR. The aim of this study is to compare area-level socioeconomic differences in outcomes following primary THR surgery for osteoarthritis in England.

Methods and findings: This is a population-based prospective cohort study of the National Joint Registry (NJR). Data from the NJR were linked to national mortality, Hospital Episode Statistics and Patient Reported Outcome Measures (PROMs) databases for England from 2007 to 2017 with follow-up to 2023 for outcomes, for patients aged 50 years and over with osteoarthritis. Outcomes of 90-day mortality; 5-year revision rate; 6-month health complications; 1-year rehospitalisation and reoperation for orthopaedic indications; and patient-reported Oxford Hip Score (OHS), post-THR surgery were examined by area-level Index of Multiple Deprivation quintiles. Modified Poisson regression was adjusted for patient age, sex, body mass index, pre-operative physical state and comorbidity. Among 448,184 patients with primary THR, mean age was 70 years (standard deviation: 9 years) and 61% were women. Patients from the most deprived group were more likely to die within 90 days of the operation compared to the least deprived group (adjusted rate ratio, RR: 1.25 (95% confidence interval (CI) [1.07, 1.46]); adjusted risk difference, RD: 9 (95% CI [2, 16]) per 10,000. Similarly, those from the most deprived group were more likely to experience complications (RR: 1.26 (95% CI [1.21, 1.32]); RD: 1.14% (95% CI [0.92, 1.36])); be rehospitalised (RR: 1.16 (95% CI [1.14, 1.19]; RD: 2.78% (95% CI [2.39, 3.17])) or reoperated (RR: 1.23 (95% CI [1.13, 1.33]); RD: 0.31% (95% CI [0.19, 0.44])) and report poorer OHS (adjusted score: -2.97 (95% CI [-3.10, -2.84]) N = 200,522). There was no variation by deprivation level for THR revision rates at 5 years (RR: 1.02 (95% CI [0.94, 1.10]); RD: 0.02% (95% CI [-0.10, 0.15])). The main study limitations are the lack of complete PROMs data, and the exclusion of self-funded patients or those with private insurance for THR procedures in independent hospitals.

Conclusions: Inequalities in several outcomes after THR are present in England by area-level deprivation. These findings are useful to inform shared decision-making for patients deciding whether to undergo hip replacement and to benchmark the effectiveness of policies which aim to reduce health inequalities following THR.