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Associations of Creatinine Muscle Index with markers of sarcopenia and mortality in chronic kidney disease: A prospective cohort study.
McDonnell T, Phillips T, Kalra PA … +5 more , Fraser SDS, Banks RE, Vuilleumier N, Taal MW, NURTuRE-CKD academic steering group
PLoS Med · 2026 Feb · PMID 41678444 · Full text
BACKGROUND: Sarcopenia is common in chronic kidney disease (CKD) and linked to higher mortality, but identifying those at risk remains challenging. Indices combining serum creatinine and cystatin C (eGFRratio and eGFRdif...
BACKGROUND: Sarcopenia is common in chronic kidney disease (CKD) and linked to higher mortality, but identifying those at risk remains challenging. Indices combining serum creatinine and cystatin C (eGFRratio and eGFRdifference) have been studied, but have tended to perform worse in those with CKD. This study aimed to examine the relationship of Creatinine Muscle Index (CMI), an estimate of glomerular filtration of creatinine, with sarcopenia and mortality in a non-dialysis CKD population. METHODS AND FINDINGS: NURTuRE-CKD is a prospective, multicentre cohort study of people with non-dialysis CKD in the UK. Two thousand nine hundred ninety-six individuals were enrolled between July 2017 and September 2019. Cystatin C measurements were available in 2,930 adults. CMI (mg/day) was calculated as eGFR cystatin C × serum creatinine concentration. The relationships between CMI and: (1) probable sarcopenia (defined as the best hand grip strength of <27 kg for males and <16 kg for females); (2) individual muscle function measures including hand grip strength (kg) and timed get-up-and-go (TUG) (seconds); (3) all-cause mortality were assessed using Spearman's correlation, logistic regression, and Cox proportional hazards models, stratified by sex and adjusted for age, ethnicity, body mass index, smoking status, Charlson Comorbidity Index, urine albumin-to-creatinine ratio, and C-reactive protein. TUG test is the time taken to stand from a chair, walk 3 m, turn, return, and sit down. Among 1,723 males and 1,207 females, the median (IQR) age was 66 (53-74) years, and the median eGFRcreatinine was 34 (24-47) ml/min/1.73m2. A total of 806 participants (27.5%) had probable sarcopenia, and over a median follow-up period of 50 (41 to 56) months, 527 (18%) died. The adjusted OR for probable sarcopenia per 100 mg/day increase in CMI was OR 0.72 (95% CI 0.67, 0.78 p value <0.001) in males and OR 0.81 (95% CI 0.73, 0.89 p value < 0.001) in females. CMI correlated positively with grip strength (ρ = 0.47 [0.43, 0.50] and 0.45 [0.40, 0.49]) and negatively with TUG (ρ = -0.37 [-0.41, -0.32] and -0.44 [-0.49, -0.40]) in males and females, respectively. In adjusted models, the HR for mortality per 100 mg/day increase in CMI was HR 0.85 (95% CI 0.78, 0.90 p value < 0.001) in males and HR 0.77 (95% CI 0.67, 0.87 p value < 0.001) in females. In males and females, respectively, the C-index of CMI for probable sarcopenia (0.73 and 0.71) and mortality (0.70 and 0.76) was higher than that of the eGFR ratio (probable sarcopenia: 0.64 and 0.61; mortality: 0.60 and 0.65; all p < 0.001) and the eGFR difference (probable sarcopenia: 0.59 and 0.57; mortality: 0.56 and 0.59; all p < 0.001) Limitations include the observational design, the assessment of muscle function without direct measurement of muscle mass, and limited generalisability to CKD populations not followed in secondary care. CONCLUSIONS: In persons with CKD, CMI-a biomarker reflecting creatinine generation-was independently associated with muscle function and mortality, supporting its utility in populations with reduced kidney function.
Systematic assessment of obesity-related risk factors in renal cancer etiology: A longitudinal risk and Mendelian randomization analysis.
Alcala K, Mariosa D, Jacobson S … +10 more , Coscia-Requena C, Dimou N, Franklin O, Martin RM, Smith GD, Gunter MJ, Brennan P, Pollak M, Langdon R, Johansson M
PLoS Med · 2026 Feb · PMID 41666231 · Full text
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-rela...
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.
Let her shine: Empowering women and closing India's gender gap in STEM.
Chattopadhyay A
PLoS Med · 2026 Feb · PMID 41666218 · Full text
Despite globally increasing numbers of women in the STEM workforce, levels still remain suboptimal. Closing the gender gap in an emerging economic power such as India, requires a cultural shift, active support of girls'...
Despite globally increasing numbers of women in the STEM workforce, levels still remain suboptimal. Closing the gender gap in an emerging economic power such as India, requires a cultural shift, active support of girls' education, and more secure job opportunities for graduates.
Acceptability and safety of one versus three months of rifapentine and isoniazid to prevent tuberculosis in people exposed in the household or workplace in Brazil: The Ultra-Curto randomized controlled trial.
Durovni B, Cordeiro-Santos M, Cavalcante SC … +11 more , Spener-Gomes R, Garcia J, Cohn S, Saraceni V, Kohler B, Moulton LH, Brito da Souza A, Berihun A, Marzinke M, Chaisson RE, Ultra Curto Study Team
PLoS Med · 2026 Feb · PMID 41666121 · Full text
BACKGROUND: Short-course tuberculosis preventive therapy with isoniazid and rifapentine (HP) is widely recommended, but the acceptability and safety of one month of daily HP (1HP) compared to three months of weekly HP (3...
BACKGROUND: Short-course tuberculosis preventive therapy with isoniazid and rifapentine (HP) is widely recommended, but the acceptability and safety of one month of daily HP (1HP) compared to three months of weekly HP (3HP) is uncertain. We compared treatment with these two regimens in people with a positive latent tuberculosis infection test and without HIV infection. We hypothesized that 1HP would have greater treatment completion and fewer targeted safety events than 3HP. METHODS AND FINDINGS: We conducted a Phase 4 randomized trial of 1HP versus 3HP in adolescents and adults without HIV infection with recent tuberculosis exposure and a positive latent tuberculosis infection test in two sites in Brazil. The primary outcomes were successful completion of >90% of medication as ascertained by self-report, pill counts, and pharmacologic monitoring, and safety. Treatment safety was defined as occurrence of Grade >2 targeted events or discontinuation of treatment for side effects. We randomized 500 individuals to 1HP (249) and 3HP (251); 193 males and 307 females, with a median age of 39 years. Treatment completion was 89.6% for 1HP recipients versus 84.1% for 3HP recipients (site-adjusted risk difference 5.2%, [95% CI: [-0.1%, 11.2%], p = 0.10). Targeted >Grade 2 adverse safety events or treatment discontinuation occurred in 16.1% of 1HP recipients and 10.4% of 3HP recipients (site-adjusted risk difference 6.1%, [95%CI: [-0.04%, 12.3%], p = 0.05). The proportions who discontinued treatment for any side effect were 7.2% for 1HP and 4.4% for 3HP. The risk difference for the primary safety outcome adjusted for site and baseline demographic and clinical covariates was 3.4% (95% CI [-2.3,9.1%], p = 0.24). The trial was not designed to ascertain efficacy. CONCLUSION: Both 1HP and 3HP had high rates of treatment success. Participants assigned to 1HP had more targeted safety events, mostly low-grade. Neither regimen was superior to the other. These results will inform global guidelines for tuberculosis preventive therapy. NCT04703075 (clinicaltrials.gov).
The impact of the Lancet Commission definition of obesity on its prevalence and implications on long-term cardiovascular-kidney-metabolic outcomes in East Asians: Observational study of two community-based cohorts.
Lui DTW, Fong CHY, Zou X … +10 more , Xu A, Tse HF, Woo J, Lam TH, Woo YC, Cheung BMY, Janus E, Lam KSL, Tan KCB, Lee CH
PLoS Med · 2026 Feb · PMID 41662368 · Full text
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. A...
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.
Aldosterone synthase inhibitors for hypertension: A breakthrough facing barriers to adoption.
Laffin LJ, Nissen SE
PLoS Med · 2026 Feb · PMID 41662225 · Full text
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 c...
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.
Teleultrasound in obstetrics: A systematic review and meta-analysis.
Le Vance J, Vaughan M, Bhatia T … +3 more , Gurney L, Hodgetts Morton V, Morris RK
PLoS Med · 2026 Feb · PMID 41650130 · Full text
BACKGROUND: Ultrasound is a common diagnostic modality in obstetrics to evaluate the fetal condition, frequently used in pregnant women classifying as high-risk. Modifications to guidelines, implementation of national in...
BACKGROUND: Ultrasound is a common diagnostic modality in obstetrics to evaluate the fetal condition, frequently used in pregnant women classifying as high-risk. Modifications to guidelines, implementation of national initiatives, combined with an aging obstetric population has led to an increased number of high-risk patients. This places a substantial strain on outpatient obstetric services to accommodate the increased demand for serial antenatal ultrasound scans. Recent advancements in digital technology have enabled the swift innovation of teleultrasound development. The recent pandemic has also substantially influenced technological development, as obstetric services considered alternative solutions to healthcare provision standards. This review aims to assess whether teleultrasound is feasible, acceptable, diagnostically accurate, and cost-effective for antenatal care. METHODS AND FINDINGS: We searched MEDLINE, Embase, Cochrane Database of Clinical Trials (CENTRAL), Web of Science, and PubMed databases from inception to December 2025. Primary research studies evaluating the feasibility, diagnostic accuracy, clinical utility, educational utility, acceptability, and economic viability of antenatal teleultrasound usage were included. Random effects meta-analysis was used, and results were reported as pooled proportions or risk ratio (RR) with 95% confidence interval (CI). Diagnostic accuracy was further assessed using a hierarchical summary receiver operating characteristic model. Of the 6,561 papers screened, 71 studies (60 clinical observational studies, five qualitative studies, four economic evaluation studies, and two randomized controlled trials) were included. Image transfer was feasible for both synchronous and asynchronous teleultrasound transmission, in a wide range of settings. Adequate technological infrastructure, including appropriate bandwidth and framerate requirements were vital factors for sufficient image quality and minimizing transmission delays. Visualizing gross fetal and placental structures using teleultrasound was frequently high; however, more specialized anatomy such as cardiac and neurological demonstrated lower visualization rates. Overall meta-analysis of 20 anatomical structures demonstrated teleultrasound is non-inferior at identification versus the reference standard RR 1.02 (95% CI [1.00,1.03]; n = 4 studies). Pooled diagnostic accuracy demonstrated excellent performance, with an AUC of 0.93 (n = 8 studies). The overall sensitivity was moderate at 0.70 (95% CI [0.44,0.84]), with a low false positive rate of 0.03 (95% CI [0.01,0.12]). There was evidence of educational and clinical utility for obstetric teleultrasound, particularly with novice users, demonstrating improved access to care in rural areas and low- and middle-income countries. Patient-operated telesonography demonstrated feasibility and high acceptability for performing basic fetal assessments. Three-dimensional, four-dimensional, and robotic teleultrasound did not highlight superiority to two-dimensional scanning. Patients and provider acceptability was high, citing benefits in relation to satisfaction, confidence, economic savings, and balancing healthcare equity. Teleultrasound implementation costs can be high, but were frequently accrued due to monthly savings. High-quality studies were underrepresented, suggesting a need for further research. The reporting of clear methodological and technological capabilities of the teleultrasound systems represent the main limitations, proving difficulty to replicate studies adequately. CONCLUSION: This review demonstrated the potential applicability and value of obstetric teleultrasound. This novel care model is everchanging and new devices/systems capable of telesonography are of clinical and scientific relevance. Presently, additional high-quality evidence is required, particularly using teleultrasound in a clinical context, whilst ensuring sufficient methodological detail and consistent outcome reporting.
Estimating the global burden of viable Mycobacterium tuberculosis infection: A mathematical modelling study.
Schwalb A, Dodd PJ, Rickman HM … +3 more , Ugarte-Gil CA, Horton KC, Houben RMGJ
PLoS Med · 2026 Feb · PMID 41642936 · Full text
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 t...
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.
Targeting spinal cord perfusion pressure in acute spinal cord injury through cerebrospinal fluid drainage: A prospective multi-center clinical trial.
Gee CM, Tsang A, McKenzie M … +17 more , Belanger L, Ritchie L, Ailon T, Dandurand C, Paquette S, Charest-Morin R, Dea N, Street J, Fisher CG, Wilson J, DiGiorgio A, Mac-Thiong JM, Christie S, Wilson J, Ricks C, Okonkwo D, Kwon BK
PLoS Med · 2026 Feb · PMID 41642932 · Full text
BACKGROUND: The hemodynamic management of acute spinal cord injury (SCI) aims to improve perfusion and mitigate ischemic secondary injury to the injured spinal cord, traditionally through the augmentation of mean arteria...
BACKGROUND: The hemodynamic management of acute spinal cord injury (SCI) aims to improve perfusion and mitigate ischemic secondary injury to the injured spinal cord, traditionally through the augmentation of mean arterial pressure (MAP). Recently, there has been interest in managing spinal cord perfusion pressure (SCPP)-the difference between MAP and intrathecal pressure (ITP) -after acute SCI. SCPP may be more physiologically relevant than MAP for neurologic recovery after traumatic SCI. Drainage of cerebrospinal fluid (CSF) through a lumbar intrathecal catheter to reduce ITP and increase SCPP is commonly performed to reduce the risk of ischemic paralysis in thoracoabdominal aortic aneurysm (TAAA) surgery. We investigated a protocol for CSF drainage through intrathecal catheters to maintain SCPP ≥65 mmHg in participants with acute traumatic SCI. We sought to determine if managing SCPP was associated with better neurologic recovery compared to traditional MAP targets. METHODS AND FINDINGS: Fifty-eight participants with acute SCI (51 ± 19 years, 46M/12F) were enrolled across eight North American sites between August 2019 and May 2024 into this prospective single-arm multi-center clinical trial of CSF drainage for SCPP management (NCT03911492). Data were compared to data from a historical cohort of 86 participants (44 ± 19 years, 72M/14F) who had intrathecal catheters inserted for SCPP measurement only; these participants were managed according to conventional MAP guidelines with a target MAP of 85-90 mmHg (NCT01279811). MAP, ITP, SCPP, intrathecal waveform morphology, vasopressor use, and CSF drainage volume were reported for up to 7 days following SCI. Fifteen participants in the intervention group were lost to follow-up. Neurological assessments at enrollment and 6-months post-SCI were compared. The investigator team ended the trial when it was clear that adherence to the protocol was inconsistent across study sites. Participants managed according to the SCPP management protocol had an intrathecal catheter in place 138 hours (95% CI [129,147]) and 495cc (95% CI [350,641]) of CSF drained. No CSF was drained from seven participants. There were no significant differences in hemodynamic measures such as ITP and SCPP between groups, indicating that the SCPP management protocol did not alter the hemodynamic management. Subsequently, there were no differences in measures of neurological recovery between participants managed according to SCPP management protocol and conventional MAP guidelines (p = 0.897). Participants managed according to an SCPP target had more ITP waveform recordings noted as dampened or fully pulsatile suggesting a patent subarachnoid space (p = 0.006) and were administered vasopressors on fewer hourly observations (p = 0.004). Six reported adverse events were probably related to the intervention. Adherence to a protocol for managing SCPP through CSF drainage across multiple sites was challenging. CONCLUSIONS: Ultimately, our protocol resulted in little CSF being drained, limited modification of ITP and SCPP, and no effect on neurological recovery. The relationship between CSF drainage volume and change in ITP was surprisingly unclear. This study revealed that draining CSF is more complex in traumatic SCI than in TAAA surgery patients. Future efforts to reduce ITP through CSF drainage likely need to address the occlusion of the subarachnoid space at the injury site through aggressive surgical decompression techniques.
Mother and child health 4.5 years after gestational diabetes mellitus managed using tight or less tight targets for glycaemic control: Post-hoc follow-up study of the TARGET trial.
Douglas LJ, Gamble GD, Harding JE … +7 more , Samuel D, Eagleton CL, Alsweiler JM, Wouldes TA, Thompson B, McKinlay CJD, Crowther CA
PLoS Med · 2026 Feb · PMID 41632754 · Full text
BACKGROUND: Optimal glycaemic targets for women with gestational diabetes mellitus (GDM) are unclear. The aim of this study was to compare maternal and child health 4.5 years after women with GDM had been randomised to u...
BACKGROUND: Optimal glycaemic targets for women with gestational diabetes mellitus (GDM) are unclear. The aim of this study was to compare maternal and child health 4.5 years after women with GDM had been randomised to use tight or less tight targets for glycaemic control during their pregnancy. METHODS AND FINDINGS: The TARGET trial was a stepped-wedge, cluster-randomised trial conducted between May 29, 2015 and November 7, 2017 at 10 hospitals in New Zealand. All hospitals were initially allocated to use less tight glycaemic treatment targets (fasting plasma glucose (FPG) <5.5 mmol/L (<99 mg/dL), 1-hour <8.0 mmol/L (<144 mg/dL), 2 hour postprandial <7.0 mmol/L (<126 mg/dL)) for women with GDM and every 4 months two hospitals were randomised to use tighter targets (FPG ≤ 5.0 mmol/L (≤90 mg/dL), 1-hour ≤7.4 mmol/L (≤133 mg/dL), 2 hour postprandial ≤6.7 mmol/L) (≤121 mg/dL). Women with GDM, blinded to the targets in use, were eligible. The primary outcome was large for gestational age. This is a post-hoc follow-up study of the TARGET randomised trial, conducted from October 2020 to June 2022. We assessed 315/427 (74%) eligible mothers and 313/427 (73%) of their children. Primary outcomes were maternal glycated haemoglobin (HbA1c) and child body mass index (BMI) z-score. Secondary outcomes included maternal cardiometabolic risk, body size, and healthcare utilisation, and for the child, body size, vision, hearing, motor function, and behavioural outcomes. Data were collected from maternal and child health questionnaires, and their health records. Maternal HbA1c results were similar between tight and less tight glycaemic groups (40 mmol/mol standard deviation (SD) 12.6 versus 38 mmol/mol SD 8.8; adjusted mean difference (adjMD) 2.17 (95% confidence interval (CI) [-0.26, 4.60]; P = 0.080)). Child BMI z-scores were similar between groups (mean z-score 0.83 SD 1.72 versus 0.75 SD 1.48; adjMD 0.12 (95% CI [-0.24, 0.48]; P = 0.498)), although children in the tight glycaemic group were taller (107.8 cm SD 5.5 versus 106.0 cm SD 5.5; adjMD 1.83 (95% CI [0.58, 3.08]; P = 0.004)). Worse child outcomes were seen in the tight glycaemic group for coordination difficulties (31/109, 28.4% versus 21/118, 17.8%; adjusted relative risk (adjRR) 1.66 (95% CI [1.01, 2.73]; P = 0.044)), behaviour (likely on the autism spectrum 10/108, 9.3% versus 3/117, 2.6%; adjRR 3.67 (95% CI [1.02, 13.23]; P = 0.047)) and total difficulties scores from the strengths and difficulties questionnaire (mean score 8.4 SD 5.1 versus 6.8 SD 4.5; adjMD 1.75 (95% CI [0.51, 3.00]; P = 0.006)). The main limitation was the use of questionnaires rather than health professional assessments for some of the outcomes. CONCLUSIONS: Tight compared to less tight glycaemic targets in women with GDM during pregnancy did not result in lower maternal HbA1c or lower child BMI z-scores 4.5 years later, and may be associated with adverse child motor and behavioural outcomes.
The mpox epidemic is not over: Reducing disproportionate burden in Africa and persistent global risk require a sustained response.
Kazadi DM, Lewis RF, Akilimali P … +3 more , Kalala D, Van Kerkhove M, Ihekweazu C
PLoS Med · 2026 Feb · PMID 41632719 · Full text
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.
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.
Social inequalities in patient outcomes after total hip replacement surgery for osteoarthritis in England: A population-based cohort study of the National Joint Registry.
Patel R, Lenguerrand E, Ben-Shlomo Y … +8 more , French J, Rangan A, Brittain R, Deere K, Sayers A, Blom AW, Whitehouse MR, Judge A
PLoS Med · 2026 Feb · PMID 41628226 · Full text
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 outcom...
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.
Metabolomic insights into associations between adiposity markers and liver cancer risk: Results from a prospective cohort study and Mendelian randomization analysis.
Li ZY, Li HL, Wang J … +5 more , Shen QM, Zou YX, Yang DN, Tan YT, Xiang YB
PLoS Med · 2026 Feb · PMID 41628182 · Full text
BACKGROUND: The association between adiposity and increased liver cancer risk is well-recognized, yet underlying metabolic mechanisms require elucidation. This study aimed to identify metabolic mediators linking adiposit...
BACKGROUND: The association between adiposity and increased liver cancer risk is well-recognized, yet underlying metabolic mechanisms require elucidation. This study aimed to identify metabolic mediators linking adiposity markers to liver cancer and assess their potential causality using two-sample Mendelian randomization (MR) analysis. METHODS AND FINDINGS: We conducted a 1:1 matched nested case-control study within a population-based and prospective cohort study-the Shanghai Men's Health Study (SMHS). The SMHS was initiated in 2002-2006, including 61,469 Chinese men aged 40-74 years, and has been followed up for over 20 years. Targeted metabolomic profiling was performed on baseline plasma samples. Associations between seven anthropometric measurements (body mass index [BMI], waist circumference, waist-to-hip ratio, waist-to-height ratio, a body shape index, hip circumference, and adult weight gain), 186 circulating metabolites, and liver cancer risk were assessed. Linear and conditional logistic regression model adjusted for multiple confounders (including smoking, alcohol drinking, physical activity, chronic hepatitis and cirrhosis, diabetes, etc.) were used. Pathway analysis and network analysis were conducted to explore the biological functions of these metabolites. Parallel mediation analysis was employed to quantify the mediating effects through metabolites. Subsequently, MR analysis was performed to investigate potential causal relationships. This study incorporated 322 incident liver cancer cases and 322 cancer-free controls. Participants diagnosed with liver cancer had higher proportions of seropositive hepatitis B surface antigen (63.7%) compared to their matched controls (6.2%). We identified 27 intermediate metabolites associated with both adiposity markers and liver cancer risk, which formed an interconnected functional network. Pyroglutamic acid demonstrated the most robust consistency, being significantly associated with seven anthropometric measurements (β per doubling with BMI = 0.17; 95% confidence interval [CI]: [0.09, 0.24]) and liver cancer (odds ratio per doubling = 1.56; 95% CI: [1.13, 2.15]). Pathway analysis highlighted significant alterations in energy, lipid, and amino acid metabolism. Specifically, Phenylalanine, tyrosine, and tryptophan biosynthesis showed the highest impact, suggesting a key role for aromatic amino acid metabolism. Parallel mediation analysis demonstrated significant indirect effects via intermediate metabolites for six of the seven anthropometric measurements, with the proportion mediated by the identified metabolite clusters reaching 0.16 (95% CI: [0.05, 0.29]) for BMI. MR analysis provided evidence supporting potential causality for 23 of 108 initially observed associations. The strongest association was observed between WC and oxoglutaric acid (βIVW per standard deviation = 0.31; 95% CI: [0.17, 0.43]). Notably, while the observational analysis suggested a broad metabolic mediation of the adiposity marker-liver cancer association, the MR findings pinpointed a more specific and limited set of causal metabolic mediators. The main limitation of this study was the population mismatch between the observational (Chinese men) and the MR (European ancestry) analyses, which may limit the generalizability of the findings to other populations. CONCLUSIONS: Integrating prospective observational and genetic evidence, we identified specific metabolic mediators linking adiposity to liver cancer, particularly involving amino acid, lipid and energy metabolism. These findings enhanced molecular understanding of adiposity-driven hepatocarcinogenesis and provided potential metabolic targets for future primary prevention strategies.
Leukemia in users of contemporary hormonal contraception: A nationwide registry-based cohort study among premenopausal women in Denmark.
Hemmingsen CH, Kjaer SK, Arvedsen J … +4 more , Dahl EO, Meaidi A, Hargreave M, Mørch LS
PLoS Med · 2026 Jan · PMID 41616041 · Full text
BACKGROUND: Sex hormones have been implicated in leukemogenesis, but evidence regarding hormonal contraceptive use and leukemia risk remains limited and primarily based on older formulations. Given the widespread use of...
BACKGROUND: Sex hormones have been implicated in leukemogenesis, but evidence regarding hormonal contraceptive use and leukemia risk remains limited and primarily based on older formulations. Given the widespread use of contemporary hormonal contraceptives, clarification of this potential association is needed. This study examines the association between contemporary hormonal contraceptives and leukemia risk. METHODS AND FINDINGS: In a nationwide cohort design, we assessed associations between the use of contemporary hormonal contraceptives and the risk of leukemia based on a cohort of all women aged 15-49 years residing in Denmark from 1995 to 2021 with no previous cancer, hysterectomy, oophorectomy, or sterilization. Information on hormonal contraception use, leukemia diagnoses, and potential confounders (age, calendar year, education) was obtained from nationwide registries. Adjusted incidence rate ratios (IRRs) and 95% confidence intervals [CIs] were estimated for any leukemia, and specific types of leukemia, associated with any hormonal contraceptive use, current and recent use, and previous use, type of product used, duration, and time since last use. Among 1,957,490 pre-menopausal women followed for 24.5 million person-years (median 12.5 years, interquartile range: 5.9,20.5), 671 were diagnosed with leukemia. The incidence rate for leukemia among current and recent users was similar to that among women who had never used hormonal contraception: IRR 0.95 (95% CI [0.78,1.16]; p = 0.62). No association with different durations of use was found: 0-5 years; IRR 0.93 (95% CI [0.75,1.14]; p = 0.48), >5-10 years; IRR 1.16 (95% CI [0.84,1.61]; p = 0.37), >10 years; IRR 0.67 (95% CI [0.33,1.37]; p = 0.27); nor for time since last use: 0-5 years; IRR 1.01 (95% CI [0.78,1.29]; p = 0.96), >5-10 years; IRR 1.05 (95% CI [0.76,1.45]; p = 0.75), >10 years; IRR 0.88 (95% CI [0.60,1.29]; p = 0.52). Also, the IRRs for leukemia with use of different hormonal contraceptive types (e.g., combined products; IRR 0.91 (95% CI [0.73,1.14]; p = 0.42) and progestin-only products; IRR 1.05 (95% CI [0.78,1.40]; p = 0.75)), as well as for product-specific durations of use, were for the majority close to 1. The IRRs were similar for different types of leukemia. Main study limitations include small case numbers in some analyses; therefore, additional large-scale studies are warranted to reliably exclude weak associations. CONCLUSIONS: Contemporary hormonal contraceptives were not associated with leukemia, independent of product used, duration of use, time since last use, and type of leukemia. While estimates were imprecise for some subgroups, the overall findings do not support an association.
Beyond the hype: Antibody-Drug Conjugates are advancing faster than our clinical strategy.
Notini G, Bianchini G, Pérez-García JM … +1 more , Cortés J
PLoS Med · 2026 Jan · PMID 41616036 · Full text
Antibody-drug conjugates are redefining treatment options in advanced breast cancer, demonstrating efficacy across all breast cancer subtypes. However, their rapid clinical expansion has resulted in several unresolved ch...
Antibody-drug conjugates are redefining treatment options in advanced breast cancer, demonstrating efficacy across all breast cancer subtypes. However, their rapid clinical expansion has resulted in several unresolved challenges, including the need for rational sequencing strategies, appropriate and ethical trial design, drug tolerability, and the limitation of mono-national development programs.
Intervention research to protect human health in the era of climate extremes.
Bärnighausen T, Lumbard H
PLoS Med · 2026 Jan · PMID 41610164 · Full text
Climate change is accelerating the frequency and severity of extreme weather events and increasingly threatening human health and life, particularly in low- and middle-income countries. Research on the effectiveness of c...
Climate change is accelerating the frequency and severity of extreme weather events and increasingly threatening human health and life, particularly in low- and middle-income countries. Research on the effectiveness of climate adaptation interventions for human health, as well as their desirability, implementation, and financial viability, are urgently required.
Pregnancy outcomes in women at high risk of preterm birth receiving a vaginal cervical cerclage with, or without, progesterone: A retrospective, secondary analysis of the C-STICH randomised controlled trial data.
Hodgetts Morton V, Morris K, Toozs-Hobson P … +10 more , Middleton L, Pilarski N, Bell L, Hogg M, Man R, Israfil-Bayli F, Shennan A, Simpson N, Lees C, Moakes C
PLoS Med · 2026 Jan · PMID 41576138 · Full text
BACKGROUND: Vaginal cervical cerclage and progesterone are established treatments for prevention of pregnancy loss and prematurity. There is limited data to assess the effect of these treatments in combination. The objec...
BACKGROUND: Vaginal cervical cerclage and progesterone are established treatments for prevention of pregnancy loss and prematurity. There is limited data to assess the effect of these treatments in combination. The objective of this study was to investigate the association between progesterone and no progesterone treatment on pregnancy outcomes in women at high risk of preterm birth who had received a vaginal cervical cerclage. METHODS AND FINDINGS: This is a secondary post-hoc analysis of women recruited to the C-STICH randomised controlled trial, which recruited in 75 obstetric units in the UK between 2015 and 2021. In the C-STICH trial, women with a singleton pregnancy, receiving a vaginal cervical cerclage due to a history of pregnancy loss or premature birth, or if indicated by ultrasound, were randomised to cerclage with braided or monofilament suture, with a primary outcome of pregnancy loss, defined as miscarriage, stillbirth, or neonatal death in the first week of life. In this secondary analysis, the primary outcome was pregnancy loss, defined as miscarriage and perinatal mortality, including any stillbirth or neonatal death in the first week of life. Secondary maternal outcomes included miscarriage and previable neonatal death; stillbirth; gestational age at delivery; preterm pre labour rupture of membranes, and sepsis. Secondary neonatal outcomes included early/late neonatal death and sepsis. For each outcome, regression models were fitted adjusting for prespecified prognostic variables. From the 2,048 women recruited to C-STICH, 1943 (95%) women had a vaginal cerclage placed and available progesterone data. Of these, 834 (43%) women received progesterone and 1,109 (57%) did not receive progesterone. In women with primary outcome data available, in our predefined analysis pregnancy loss occurred in 49 (5.9%) of 832 women who received progesterone and 91 (8.3%) of 1,103 women who did not receive progesterone (adjusted* risk ratio 0.70 (95% confidence interval (CI) [0.50, 0.99]); adjusted risk difference -0.02 (95% CI [-0.04, -0.001], *adjusted for indication, obstetric history, surgical technique, and maternal age). Further exploratory analysis excluding women who had termination of pregnancy for foetal anomaly demonstrated a nonsignificant reduction in the risk of pregnancy loss. Key limitations of this study include a nonrandomised trial design and unknown confounding relating to variation in progesterone use. CONCLUSION: In women with a vaginal cervical cerclage and concomitant progesterone there appears to be an association with a reduced risk of pregnancy loss. This combination therapy may be an important opportunity to further reduce the risk of pregnancy loss in this high-risk cohort.
Correction: Sex-specific associations of adiposity with cardiometabolic traits in the UK: A multi-life stage cohort study with repeat metabolomics.
O'Keeffe LM, Bell JA, O'Neill KN … +5 more , Lee MA, Woodward M, Peters SAE, Smith GD, Kearney PM
PLoS Med · 2026 Jan · PMID 41575927 · Full text
[This corrects the article DOI: 10.1371/journal.pmed.1003636.].
[This corrects the article DOI: 10.1371/journal.pmed.1003636.].
Psychological distress among Japanese high school students during the COVID-19 pandemic: An energy landscape analysis.
Tatematsu D, Nakamura N, Abe MS … +11 more , Ishikawa T, Ezaki T, Cai L, Kawakami E, Aihara K, Nishida A, Okada N, Masuda N, Kasai K, Koike S, Iwami S
PLoS Med · 2026 Jan · PMID 41569975 · Full text
BACKGROUND: The stay-at-home orders, lockdowns, and states of emergency of the Coronavirus Infectious Disease emerged in 2019 (COVID-19) pandemic have affected the mental health of school-aged children. Previous reports...
BACKGROUND: The stay-at-home orders, lockdowns, and states of emergency of the Coronavirus Infectious Disease emerged in 2019 (COVID-19) pandemic have affected the mental health of school-aged children. Previous reports of psychological distress in adolescents during the pandemic have been mixed, however, with some reports showing increases in psychological distress and others suggesting decreases. To accurately assess the impact of the pandemic, we need to be able to compare psychological assessments longitudinally, both before and during the pandemic. However, current statistical methods have limitations for reconstructing the complex trajectory of psychological states as captured by short-item questionnaires. METHODS AND FINDINGS: In this study, we analyzed monthly Kessler 6-item Psychological Distress Scale (K6) questionnaire responses collected from 16- to 18-year-old high school students participating in the population-neuroscience Tokyo TEEN Cohort (pn-TTC) in Japan (1,278 responses from 84 participants). Participants included 42 males and 42 females. The pn-TTC is a population-based longitudinal study conducted in Tokyo, Japan that follows children to investigate their developmental and mental health trajectories. In addition to conventional statistical approaches that summarize multiple questionnaire items into a composite score, we applied "energy landscape analysis," a method derived from statistical physics that models multivariate psychological states as a dynamic system of interactions among K6 questionnaire items, to visualize longitudinal changes in psychological distress before and during the COVID-19 pandemic (July 2019 to September 2021). Here, we define the depressive and healthy states as configurations in which all six K6 items are above or below each participant's individual mean, respectively. Before the pandemic, the healthy state occurred 11.0 times as frequently as the depressive state. In contrast, during the pandemic, the relative frequency of the healthy state increased to 18.2, 18.5, and 15.0 times that of the depressive state, respectively. The evolving energy landscape revealed an association between the pandemic period and a lower likelihood of being in a depressive state. We also identified two groups of students with different K6 dynamics and energy landscapes. The first group consisted of 61 participants whose total K6 score was relatively low (less than 5) and stable over time, and the second group consisted of 23 participants whose total K6 score was higher (with most being higher than 5) and less stable. The latter group showed a greater change in cortical thickness in the caudal part of the middle frontal gyrus (cMFG) (t-statistic = -2.36, p-value = 0.019, q-value = 0.048) and the temporal pole (TP) (t = 3.08, p = 0.0023, q = 0.012), as measured by magnetic resonance imaging, in the direction of accelerated adolescent brain development. Because all participants lived in Tokyo, generalizability remains limited, and as the association between psychological states and brain development is descriptive, future studies in diverse cohorts are needed to examine causality. CONCLUSIONS: By revealing associations between the COVID-19 pandemic and lower levels of psychological distress and healthier mental health states, our work demonstrates the potential of using dynamical systems theory, such as the energy landscape analysis, to interpret health and disease metrics in psychology and psychiatry. This approach may improve mental health surveillance for the next pandemic.
The benefits and risks of maternal RSV vaccination on mortality in South Africa: A modeling study.
Monoi A, Endo A, Procter SR … +4 more , Leuba SI, Flasche S, Jit M, Maternal RSV Vaccine Benefit-Risk Advisory Group
PLoS Med · 2026 Jan · PMID 41557631 · Full text
BACKGROUND: Maternal respiratory syncytial virus (RSV) vaccine, RSV prefusion F protein vaccine (RSVpreF (Abrysvo)), was found to be safe and efficacious in the MATISSE trial. However, post-hoc stratified analyses identi...
BACKGROUND: Maternal respiratory syncytial virus (RSV) vaccine, RSV prefusion F protein vaccine (RSVpreF (Abrysvo)), was found to be safe and efficacious in the MATISSE trial. However, post-hoc stratified analyses identified an excess of preterm births in the intervention arm in two upper-middle-income countries, most prominently in South Africa. This study weighs the potential benefits and risks in mortality associated with maternal RSV vaccination in South Africa, assuming the increased risk of preterm births observed in the trial was caused by vaccination. METHODS AND FINDINGS: We compared the estimated RSV-associated infant deaths averted by vaccination (benefits) and neonatal mortality potentially associated with vaccine-associated risk in preterm birth (risks) in South Africa. The benefit model estimated the South African RSV disease burden in 2011-2016 and waning vaccine protection during infancy. The risk model estimated excess neonatal mortality using gestational age (GA)-specific mortality data from the Drakenstein Child Health Study and the GA-specific birth distribution in South Africa in the MATISSE trial, but did not incorporate the mortality risk found in the MATISSE vaccine trial in which no excess deaths occurred. The benefit model estimated that vaccination would reduce RSV-associated infant deaths by 31 (95% credible interval (Crl): 27, 35) per 100,000 live births born to vaccinated mothers in South Africa. Using the number of infants born to mothers vaccinated at 24-36 GA weeks in the MATISSE trial, if the association in South Africa between vaccination and preterm birth is actually causal, the risk model suggested that neonatal deaths would increase by 44 (95%CrI: -43, 210), totaling 1.4 (95%CrI: -1.4, 6.9) excess neonatal deaths for every infant RSV death prevented. When this was changed to the number of infants born to mothers vaccinated at 27-36 GA weeks in the MATISSE trial, the predicted risks dropped and in 97% of the simulations the benefits outweighed the risks. The outcome was sensitive to the GA window that we used to determine which infants to include in the analysis. The study was limited by only considering mortality associated with RSV disease and preterm birth. CONCLUSIONS: If RSVpreF increases preterm birth risk, and if this increases neonatal mortality, then the benefit-risk analysis failed to show that the direct benefits of vaccination in reducing RSV-associated infant mortality would substantially outweigh the risks of preterm birth-associated neonatal mortality in South Africa with vaccination from 24 GA to 36 GA weeks. There was large uncertainty in the analyses due to small numbers of preterm births. With vaccination from 27 GA weeks, the benefit-risk analysis favored vaccination. RSVpreF vaccination has the potential to be safe and effective when used from the third trimester.
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