The association between visceral adiposity and multimorbidity in Chinese middle-aged and older adults remains underexplored. This study used data from the China Health and Retirement Longitudinal Study (CHARLS) to examine the relationship between visceral adiposity, measured by the Chinese visceral adiposity index (CVAI), and multimorbidity. This prospective cohort study analyzed data from 6,410 participants who were multimorbidity-free in the 2015 CHARLS wave, with follow-up assessments in 2018 and 2020. CVAI was calculated using age, body mass index, waist circumference, triglycerides, and high-density lipoprotein cholesterol. Latent class analysis (LCA) identified multimorbidity patterns, defined as the presence of ≥2 chronic conditions based on self-reported physician diagnoses. Cox regression and restricted cubic spline (RCS) analyses assessed the impact of CVAI on multimorbidity risk. Over a median 5.0-year follow-up (interquartile range [IQR], 3.0 to 5.0), 2,809 participants (43.8%) developed multimorbidity. Each IQR increase in CVAI significantly elevated the risk of multimorbidity (hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.16 to 1.24). Higher risks were observed in the second (HR, 1.16; 95% CI, 1.04 to 1.30), third (HR, 1.28; 95% CI, 1.14 to 1.43), and fourth (HR, 1.76; 95% CI, 1.58 to 1.96) quartiles compared with the first. The RCS analysis demonstrated a dose-response relationship (Pnonlinearity=0.109). LCA identified four multimorbidity clusters. CVAI increments were significantly associated with the cardio- metabolic cluster (HR, 1.51; 95% CI, 1.42 to 1.62) and the arthritis-renal cluster (HR, 1.29; 95% CI, 1.21 to 1.39). Elevated CVAI is a strong risk factor for incident multimorbidity among middle-aged and older Chinese adults, emphasizing its importance in the development of distinct disease clusters.

To evaluate the clinical efficacy of the combined technique involving Hem-o-lok clip closure of the uterine artery trunk and uterosacral ligament plication in laparoscopic complex hysterectomy. A prospective study included 100 patients undergoing laparoscopic complex hysterectomy at our hospital from January 2021 to June 2022. Patients were divided into the conventional group (n = 50) and the combined group (n = 50) based on surgical techniques. The conventional group underwent standard electrocoagulation closure of the ascending uterine artery branch at the cervical isthmus level and simple vaginal cuff suture, while the combined group utilized Hem-o-lok vascular clips for early uterine artery trunk closure and additional uterosacral ligament plication fixation to the vaginal cuff. Intraoperative blood loss, operative time, postoperative recovery indicators, and 3-year follow-up outcomes-including pelvic floor function (POP-Q staging, PFDI-20 score) and sexual quality of life (FSFI score)-were compared. Compared with the conventional group, the combined group demonstrated significantly reduced intraoperative blood loss (68.7 ± 15.2 vs.95.2 ± 18.4mL, P < 0.001) higher surgical field visibility scores (4.8 ± 0.3 vs. 3.1 ± 0.7, P < 0.01), faster postoperative recovery, and lower hospitalization costs. At 3-year follow-up, the combined group exhibited lower rates of POP-Q stage ≥Ⅱ (6% vs. 24%, P < 0.01), longer vaginal length (8.1 ± 0.8 vs. 7.0 ± 1.2cm, P < 0.01), lower PFDI-20 scores (18.5 ± 4.5 vs. 35.7 ± 7.8, P < 0.01), and higher FSFI scores (25.2 ± 2.6 vs. 20.3 ± 4.1, P < 0.01). T The combined technique of uterine artery trunk closure with Hem-o-lok clips and uterosacral ligament plication significantly improved surgical efficiency without increasing major complications. Furthermore, in this prospective cohort, it was associated with a shorter operative time, less blood loss, and better pelvic floor and sexual function metrics at the 3-year follow-up compared to the conventional technique.

Severe infections can lead to substantial reductions in T cell counts, yet its prognostic relevance and potential cytokine-mediated mechanisms remain poorly defined in pediatric populations. This study aimed to investigate whether T cell counts are associated with mortality, and to what extent this association is mediated by circulating cytokines. Prospective cohort study. A 55-bed PICU. Children 28 days to 18 years old admitted to the PICU due to infections, excluding those with preexisting conditions known to potentially impact T cell counts. None. A total of 252 patients were enrolled, with a median age of 4.16 years (interquartile range: 1.18-7.73), and 56.35% were male. CD3+ T cell count was nonlinearly associated with mortality (p overall = 0.027; p nonlinear = 0.013), with a risk plateau beyond the inflection point at 705.14 cells/μL in restricted cubic spline models. The lower T cell group had markedly increased 30-, 60-, and 90-day mortality (p < 0.05). Kaplan-Meier analysis showed that patients in the lower T cell group had significantly higher mortality (p = 0.011). Multivariable Cox models confirmed an independent association between low T cell group and increased mortality risk, with a hazard ratio of 2.62 (95% CI, 1.12-6.14) for 90-day mortality. Mediation analysis showed that platelet-derived growth factor (PDGF)-AA mediates a substantial portion of this effect, accounting for 71.19% of the total pathway. Early T cell depletion independently predicts mortality in critically ill children with severe infections. These findings support the prognostic value of early immune profiling and suggest a potential immunoregulatory role for PDGF-AA.

Comparing the predictive accuracy of life's essential 8 and life's crucial 9 scores for all-cause mortality in COPD patients among US adults: a prospective cohort study.

Objectives: Vitamin D levels in neonates at birth are directly dependent on maternal vitamin D levels. This study aims to determine the prevalence of vitamin D deficiency in mothers at the time of delivery and in neonates at birth, explore their correlation and assess the effects of routine vitamin D supplementation on serum vitamin D levels in infants at 6 weeks and 6 months. Material and Methods: This prospective cohort study was conducted in a medical college setting in North India, after obtaining ethical clearance. A total of 83 mother-baby dyads were enrolled. Venous blood samples were collected at predefined times, and vitamin D, serum calcium and phosphorus levels were measured using chemiluminescence microparticle immunoassay, calcium assay and phosphomolybdate methods, respectively. Data were analysed using the Statistical Package for the Social Sciences (SPSS) (SPSS 20). Results: Among the 83 mother-baby dyads, 57.8% of the neonates were male, and the majority were term (78.3%) and appropriate for gestational age (83.1%). Vitamin D deficiency was found in 62.7% of mothers and 86.7% of neonates. Calcium deficiency was observed in 9.6% of neonates and 1.2% of mothers. Maternal serum vitamin D, calcium and phosphorus levels were directly correlated with neonatal levels at birth. Significant improvements in vitamin D and calcium levels were observed with routine supplementation at 6 weeks and 6 months. Conclusion: This study reveals a high prevalence of vitamin D deficiency in both mothers and neonates, with a direct positive correlation between maternal and neonatal levels.

Previous studies specific to breast nodules are relatively scarce and mainly rely on cross-sectional research methods, overlooking the dynamic evolution of breast nodules over time. Thus, the objective is to analyze the impact of lifestyle, mental health, and metabolic characteristics on the occurrence and progression of breast nodules by conducting a longitudinal study. This retrospective, longitudinal cohort study conducted from 2012 to 2021 included 114,774 measurements from the Health Management Center at the Third Xiangya Hospital of Central South University in China. All data were collected from the results of anthropometric measurements, laboratory tests, breast ultrasound and online questionnaire surveys. Generalized estimating equations (GEE) models were developed to examine the relationship. Women who always ate punctual meals or consumed soy products ≥ 5 times per week had lower odds of breast nodule occurrence (adjusted odds ratio [aOR] 0.798, 95% CI 0.761-0.836, p < 0.001; aOR 0.791, 95% CI 0.689-0.908, p = 0.001). In contrast, women who had socializing meals of ≥ 3 times per week had higher odds of breast nodule occurrence (aOR 1.315, 95% CI 1.124-1.538, p = 0.001). Higher serum creatinine and lower serum uric acid were also associated with increased risk of breast nodule occurrence (aOR 1.001, 95% CI 1.000-1.001, p = 0.012; aOR 0.999, 95% CI 0.999-1.000, p < 0.001). Women with fair sleep quality had higher breast nodule occurrence (aOR 1.074, 95% CI 1.027-1.122, p = 0.002) but a lower risk of progression to BI-RADS ≥ 4A (aOR 0.760, 95% CI 0.607-0.952, p = 0.017). Our study revealed significant correlations between breast nodules and various lifestyle factors and metabolic characteristics, but the correlations between breast nodules and mental health were not found. These findings may provide insights into potential factors related to breast nodules and guide future research on their prevention and management.

Traumatic life events are hypothesized to be triggers for the onset of fibromyalgia. Posttraumatic stress disorder (PTSD) is a common comorbidity of fibromyalgia. However, limited prospective data are available on the development of fibromyalgia after exposure to high magnitude stress. This longitudinal cohort study of US military service members (N = 1761) assessed fibromyalgia and PTSD before and upon return from combat deployment. Fibromyalgia was assessed with the 2010 American College of Rheumatology fibromyalgia questionnaire. The PTSD Checklist Stressor-Specific Version (PCL-S) was used to assess symptoms of PTSD. The prevalence rates of fibromyalgia in service members at predeployment (males = 2.2%; females = 2.0%) were similar to rates in civilian populations. Following deployment, the prevalence of fibromyalgia increased significantly to 8.0% in males and 11.1% in females (P < 0.001). The prevalence of PTSD symptoms at predeployment was 20.7% in males and 18.3% in females. The prevalence postdeployment increased slightly to 22.7% in males and 25.5% in females (P > 0.05). By odd ratios, service members with PTSD predeployment were 2.96 times more likely to develop fibromyalgia postdeployment, and those with fibromyalgia predeployment were 3.12 times more likely to develop PTSD postdeployment. This study provides the largest prospective data to date to support exposure to the stress of deployment to a warzone as a significant factor related to the onset of fibromyalgia. The bidirectional comorbidity between fibromyalgia and PTSD suggests a potential link in the central nervous system and has implications for management.

ABSTRACT Objective To assess sex-based differences in the frequency and characteristics of pediatric lateral ankle avulsion fractures. Methods This prospective observational cohort study (Level II) was conducted at a tertiary sports medicine clinic between July 2022 and March 2025. This study included a total of 132 patients with 133 injuries aged 5 to 12 years presenting within 30 days of a first-time lateral ankle injury (67.4% female and 32.6% male). Injuries were categorized as avulsion or non-avulsion using ultrasound as the reference standard. Demographics, injury type and mechanism, sport type, and validated patient-reported measures were analyzed by sex using chi-squared and Mann-Whitney U tests. Results Males were found to be significantly more likely to sustain lateral ankle avulsion fractures than their female counterparts (50.0% vs 24.1%, p < 0.01). There were no statistically significant differences between the avulsion and non-avulsion group for age, race, ethnicity, BMI, or days to presentation. Sport during injury did vary by sex (p = 0.02), but the cause of injury did not. Pain, mobility, anxiety, and Pedi-FABS scores did not vary between sexes at presentation, regardless of their avulsion status. Conclusions Our study demonstrated that males with lateral ankle injuries were more likely to sustain avulsion fractures than females in this pediatric population. Despite these differences in injury type, both sexes reported similar levels of function, anxiety, pain, and activity at initial presentation. Understanding early sex-based differences in lateral ankle fracture patterns may inform diagnostic evaluation and management in pediatric patients.

Norovirus is the leading cause of medically attended acute gastroenteritis in the United States. Efforts to reduce the disease burden are constrained by uncertainty around fundamental aspects of norovirus epidemiology. This study describes characteristics of norovirus infections and explores potential risk factors for symptomatic infections in early life. The Pediatric Respiratory and Enteric Virus Acquisition and Immunogenesis Longitudinal birth cohort study followed 245 children from birth to 2 years of age with weekly stool sample collection and symptom surveys. Stool samples were tested by reverse transcriptase-realtime polymerase chain reaction to detect norovirus genogroup (G)I and GII; positive samples were genotyped. Infections accompanied by diarrhea and/or vomiting were considered symptomatic. Children were categorized as adherent if they participated for ≥18 months and submitted ≥70% of samples. A total of 72 GI and 330 GII norovirus infections (among 156 children) were identified. One-fifth (20.8%) of adherent children experienced ≥1 norovirus infection by 6 months of age, increasing to 84.2% children by 2 years of age. About one-third of infections were symptomatic, including half of infections with cycle threshold values <25. Infection with norovirus genotype GII.4 Sydney was the strongest predictor of symptomatic infection in adjusted analyses, as was older age and higher viral load. Childcare attendance, breastfeeding, mother's secretor status, and prior infections were not predictive of symptom status. This study highlights fundamental characteristics of norovirus epidemiology in early life with implications for understanding the full natural history of the disease, disease transmission and prevention approaches.

Obesity is associated with a high risk of vascular-related dementia with metabolic risk factors as potential mediators, but questions of causality remain unanswered. We aimed to determine whether high body mass index (BMI) is a causal risk factor for vascular-related dementia, and whether any effect is mediated by hypertension, hyperlipidemia, hyperglycemia, and low-grade inflammation. Prospective cohort studies of the general populations from the Copenhagen area and from across the United Kingdom and consortia data were included in the study. Interventions included one-sample mendelian randomization (MR), two-sample MR, and MR in mediation analyses. Both individual-level and summary-level data was used. Main outcome measures included risk of vascular-related dementia, Alzheimer's disease, and ischemic heart disease. In a meta-analysis of 2 one-sample MR studies, the odds ratio (OR) for 1-SD higher BMI in predicting vascular-related dementia was 1.63 (95% CI, 1.13-2.35). In a two-sample MR study, the OR for vascular-related dementia per 1-SD higher BMI was 1.54 (1.10-2.16) using the inverse-variance weighted, 1.87 (1.22-2.85) using the weighted median, and 1.98 (1.21-3.22) using the weighted mode methods. Results from MR analyses including extended numbers of genetic variants were directionally consistent. Finally, systolic blood pressure mediated 18% (95% CI, 10%-61%) and diastolic blood pressure mediated 25% (13%-75%) of the genetic effect of BMI on vascular-related dementia. Observationally (U-shaped) and genetically (linearly), high BMI is associated with a higher risk of vascular-related dementia, an association partly mediated through high blood pressure. This suggests that high BMI and high blood pressure are important modifiable risk factors for dementia prevention.

Gestational diabetes mellitus (GDM) is associated with adverse metabolic and obstetric outcomes, yet its impact on behavioral, psychosocial, and chronobiological factors remains inadequately characterized. This prospective cohort study aimed to evaluate sleep quality, chronotype, daytime sleepiness, fatigue, perceived social support, and depressive symptoms in women with GDM using the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Morningness-Eveningness Questionnaire (MEQ), Multidimensional Scale of Perceived Social Support (MSPSS), and Edinburgh Postpartum Depression Scale (EPDS). A total of 618 pregnant women (273 with GDM and 345 normoglycemic controls) were enrolled. Women with GDM exhibited significantly poorer sleep quality (p < 0.001), heightened fatigue severity (p < 0.001), and excessive daytime sleepiness (p < 0.001), lower perceived social support (p < 0.001) compared to controls. Evening chronotype was higher in the GDM group (p < 0.001), whereas controls were predominantly morning types. Although EPDS scores were elevated in GDM (p < 0.001), rates of clinically significant depression (EPDS ≥ 13) did not differ. Neonates of GDM mothers had higher birth weights (p < 0.001) and greater NICU admission rates (p < 0.001). In conclusion, GDM is associated with poorer sleep quality, greater fatigue, higher daytime sleepiness, evening chronotype, and reduced perceived social support, alongside adverse neonatal outcomes.

Classified as carcinogenic to humans by the International Agency for Research on Cancer, aluminum production has been transitioning towards lower polycyclic aromatic hydrocarbon-emitting prebake smelters. This study explored the risk of cancer and mortality over 20 years follow-up among a cohort of aluminum prebake smelter workers. Time-weighted average estimated exposure to the following airborne contaminants was available: total fluoride, sulfur dioxide, asbestos, oil mist, inhalable dust, benzene (a) pyrene (BaP), and benzene soluble fraction (BSF). Data about diagnosed cancers were accessed from the Australian Cancer Database and deaths and cause of deaths from the National Death Index, updating a previous linkage 9 years earlier. The cohort included 4495 male smelter workers. Mesothelioma was associated with historic asbestos exposure. BaP/BSF exposure were found associated with stomach cancer (10-year lag RR = 2.89 (1.19-6.98) [BaP], 2.88 (1.21-6.87) [BSF]), liver and prostate cancers, and Alzheimer's disease mortality. Oil mist exposure was associated with chronic obstructive pulmonary disease (COPD) mortality. There was no association between any smelter exposure and incidence of either lung or bladder cancer. In this updated linkage of aluminum prebake smelter workers' data, the association between respiratory cancer and fluoride, inhalable dust and BaP exposure (found in the 2002 linkage analysis) was not confirmed. There was also no increased incidence of bladder cancer. However, compared with the earlier linkage, a stronger association was found for stomach cancer and BaP/BSF exposure. The strong association between mesothelioma and asbestos exposure, found in earlier linkages, remains. Other associations identified will require further investigation.

A polygenic risk score approximates an individual's genetic susceptibility to disease, while the Life's Essential 8 (LE8) score captures a healthy lifestyle. This study applied the LE8 score and a polygenic risk score to severe diverticulitis. Multiple variations in lifestyle scores were compared. We hypothesized that genetics would complement lifestyle information in risk stratification. A polygenic risk score for severe diverticulitis (operative intervention or at least two inpatient admissions) was optimized in BioVU, followed by application to an independent prospective cohort from the UK Biobank. The LE8 score uses patterns in diet, exercise, smoking, sleep, weight, cholesterol, blood sugar, and blood pressure. Cox proportional hazards models evaluated relationships between high-risk groups and severe diverticulitis. Interactions were quantified through the relative excess risk due to interaction (RERI). A disease-specific lifestyle score was derived by assigning weights to LE8 components according to their association with the outcome. Among 225,592 eligible UK Biobank participants, 2,584 developed severe diverticulitis over a median 14 years of follow-up. The at-risk group from a lifestyle and genetic perspective had greater hazard of severe diverticulitis (HR [95% CI] 4.71 [4.15 - 5.35], p < 0.01), with a cumulative incidence of 3.50% versus 0.75% in the rest of the cohort. The combined effect of genetic and lifestyle risk was greater than the sum of the individual effects (RERI [95% CI] 0.98 [0.39, 1.57]). A diverticulitis-specific lifestyle score prioritized body mass index, blood glucose, and smoking. Both polygenic risk and lifestyle scores were associated with severe diverticulitis; joint consideration yielded additional information relative to either variable alone. Future personalized profiles may inform shared decision-making discussions about operative intervention.

Abstract Sepsis-induced immunosuppression leads to poor prognosis. Circulating lymphocyte count (LC), as an easily accessible clinical marker, closely reflects the immune status of sepsis. The study aims to perform immune phenotyping of sepsis patients using dynamic LC for early identification of high-risk individuals. A latent class trajectory model (LCTM) was used to analyze the dynamic trajectories of lymphocyte count (LC) based on repeated measurements obtained within at least two measurements of lymphocyte count (LC) within the first 24 h after sepsis diagnosis, followed by two more between day 2 and day 7. Survival differences among subphenotypes were assessed using Kaplan–Meier curves and Cox regression. Feature selection was conducted via the Boruta algorithm, and a high-precision machine learning model was developed to predict the target trajectory. Model interpretability was ensured through SHapley Additive exPlanations (SHAP). The predictive performance of the model for ICU mortality was assessed using the receiver operating characteristic (ROC) curve. The derivation cohort included 2085 sepsis patients from the China Multicenter Sepsis database, and the external validation cohort of 1299 sepsis patients. We identified four trajectory patterns of LC dynamics, among which the persistent lymphopenia (PL) subgroup exhibited the highest disease severity and poorest prognosis. The trajectory model demonstrated consistent patterns in external validation. Six machine learning models were utilized to determine the best model to identify the PL subphenotype, and an online prediction tool was developed for clinical application. Incorporating the PL trajectory subphenotype significantly improved the predictive performance for ICU mortality. Dynamic LC trajectories effectively capture immunological heterogeneity in sepsis, encompassing immunocompromised and immunocompetent hosts. These findings underscore the importance of early identification of patients with persistent lymphopenia to better target populations for future sepsis immunotherapy.

Opportunistic infections (OIs) remain a leading cause of morbidity and mortality among people living with HIV (PLHIV). Early identification of high-risk individuals is vital to guide the preventive measures and the efficient use of healthcare resources. We conducted a prospective longitudinal cohort study involving 223 PLHIV at a tertiary care center in Western India. Baseline demographic, clinical, and laboratory data were collected, including CD4 count, nutritional status, serum albumin, and ART (antiretroviral therapy) history. Patients were followed for the development of OIs. Logistic regression was used to identify independent predictors of OIs. Kaplan-Meier curves were used to assess OI-free survival across different groups. Out of 223 patients, 97 (43.5%) developed at least one OI. The maximum duration of follow-up was 36 months for OI development. Tuberculosis (41.2%), candidiasis (16.5%), and NTM (Non-tuberculous mycobacteria) infections (11.3%) were the most common OIs. On multivariable analysis, low body mass index (BMI < 18.5kg/m2; OR 2.5, 95% CI 1.1-4.2, p = 0.037), hypoalbuminemia (OR 2.3, 95% CI 1.2-3.5, p = 0.011), and CD4 count < 250 cells/µL (OR 2.1, 95% CI 1.3-4.2, p = 0.043) were identified as independent predictors of OIs. Kaplan-Meier analysis showed significantly reduced OI-free survival among patients with albumin < 2.5g/dL (adjusted HR 1.8; 95% CI 1.1-2.9; p = 0.017) and BMI < 18.5kg/m2 (adjusted HR 2.1; 95% CI 1.3-3.2; p = 0.001). Low BMI, hypoalbuminemia, and CD4 count < 250 cells/µL are independent predictors of OIs in PLHIV. Integrating these markers can mitigate the OI-related adverse outcomes, particularly in low-resource healthcare settings.

Prospective cohort study. Determine whether epigenetic age (EA), calculated via DNA methylation analysis, is associated with early postoperative complications in adult spinal deformity (ASD) surgery. ASD is increasingly prevalent in the aging population, with postoperative complication rates ranging from 37% to 71%. While chronological age (CA) and frailty scores are known predictors of poor outcomes, they may not fully capture biological vulnerability. EA, derived from DNA methylation patterns, may better reflect a patient's physiological reserve and stress response capacity. Thirty patients undergoing ASD surgery were prospectively enrolled and provided peripheral blood samples on the day of surgery. DNA methylation of peripheral blood mononuclear cells (PBMCs) was analyzed using the Illumina EPIC v2.0 array. EA was computed using the Horvath DNAmAge algorithm. Associations between EA, CA, and the Edmonton Frailty Index (EFI) with postoperative complications at 30 days were assessed using appropriate parametric and non-parametric statistical tests. Differentially methylated positions (DMPs) were identified between complication and non-complication group. Of the 30 enrolled patients (mean CA: 68.4y, 21 female), 14 (47%) experienced postoperative complications. Sixty-three DMPs were found between the two groups, with 35 hypomethylated and 28 hypermethylated CpG sites in the complication group. Genes affected were linked to immune response, including LRBA and NFACT2. Regulators of EGFR and WNT pathways were also differentially methylated. Patients with EA greater than CA were significantly more likely to experience complications (86% vs. 14%, P=0.038). The difference between EA and CA was greater in the complication group (5.07 vs. 0.87y, P=0.029). No significant differences were found in mean CA, EA, or EFI alone between the groups. Postoperative complications in ASD patients were associated with epigenetic alterations and elevated EA relative to CA. These findings suggest EA may be a novel biomarker for preoperative risk stratification in ASD surgery.

We evaluated the effects of growth hormone (GH) pretreatment on oocyte retrieval and embryo quality in patients undergoing assisted reproductive technology (ART) for diminished ovarian reserve (DOR). In this prospective cohort study, conducted at Shahida Islam Medical Complex from October 2023 to June 2025, 2,000 women aged ≤40 years with DOR were recruited before starting ART. DOR diagnosis was based on the 2017 criteria and the 2011 Bologna criteria. Participants were nonrandomly allocated to four equal groups: G1 (1 month of GH before ovulation induction+standard ART), G2 (2 months of GH pretreatment+ART), G3 (GH supplementation during the ovulation induction phase+ART), and G4 (control; standard ART). Hormonal and metabolic profiling was performed before, during, and after GH treatment. Accordingly, secondary stratification was applied to enable personalized treatment. Based on early response to GH pretreatment, participants underwent dynamic regrouping into good and poor responders. Key outcomes included oocyte retrieval, embryo quality, and maternal-fetal outcomes. GH pretreatment improved ART results, with the G2 group achieving the best estradiol levels, follicular growth, and oocyte retrieval, albeit with increased insulin resistance (homeostatic model assessment of insulin resistance [HOMA-IR]). The G1 and G3 groups also outperformed controls (G4). GH dose and anti-Müllerian hormone (AMH) level strongly predicted successful oocyte retrieval. Testosterone was negatively associated with retrieval; interleukin 6 and dehydroepiandrosterone sulfate (DHEA-S) had weaker effects. G2 embryos exhibited the best development and blastocyst formation outcomes, with the most advanced development by day 5. A nomogram was developed to predict oocyte retrieval outcomes from GH dose, AMH, HOMA-IR, and testosterone. In patients with DOR, GH pretreatment improves treatment outcomes. Over 1 month of pretreatment can increase the oocytes retrieved but confers higher insulin resistance. Thus, when using GH for more than 4 weeks, clinicians should closely monitor HOMA-IR and perform continuous glucose monitoring; otherwise, 1-month GH pretreatment is preferred when initiating ART.

Background: Pseudoxanthoma elasticum (PXE) is a rare disease caused by pathogenic ABCC6 variants, leading to arterial calcifications and increased cardiovascular risk. Validated intermediate endpoints are needed to evaluate cardiovascular risk-reducing therapies in PXE. This prospective cohort study investigates the relationship between arterial stiffness and cardiovascular events in patients with PXE. Methods: This prospective cohort study obtained patients from the Dutch University Medical Center Utrecht Expertise Center for PXE. Arterial stiffness was measured with carotid-femoral pulse wave velocity (cfPWV) and the augmentation index (AIx). Cardiovascular endpoints were cardiovascular death, cerebrovascular and coronary events, and peripheral artery interventions. Cox proportional hazard models analyzed associations between arterial stiffness and cardiovascular events, adjusting for confounders. Results: Among 390 patients (mean age 51 ± 15 years, 60% women), 45 cardiovascular events occurred during a median follow up of 6.1 years (IQR 3.2; 9.2). A 1-m/s higher cfPWV was related to an increased risk of cardiovascular events (hazard ratio [HR]: 1.28; 95% CI 1.06-1.53). The effect of cfPWV depends on age (p-value = 0.03), with a lower cardiovascular risk HR at older age (HR age at 40 years: 1.51; 95% CI 1.11-1.97 to HR age at 60 years: 1.12; 95% CI 1.00-1.26). A 10% higher AIx at baseline was related to future cardiovascular events (HR 1.46; 95% CI 1.10-1.95). No significant interaction between the AIx and age was found. Conclusion: This prospective cohort study shows that arterial stiffness, measured by cfPWV and AIx, is independently associated with increased cardiovascular risk in PXE. Measures of arterial stiffness could be explored as intermediate endpoints in trials evaluating cardiovascular risk-reducing therapies in PXE.

Self-harm represents a significant public health concern and is a common reason for contact with urgent and emergency care (UEC) services among young people. Although young people frequently interact with multiple components of the urgent care system following self-harm, there is limited system-level evidence describing patterns of service use, transitions between services and repeat emergency department (ED) attendance. An improved understanding of how young people use UEC services after self-harm is needed to inform the design of more effective and appropriate care pathways. This protocol describes a prospective cohort study using an extract from the Centre for URgent and Emergency care research database (CUREd+) research database, which comprises routinely collected, linked healthcare data from the National Health Service 111 (NHS 111), ambulance services, urgent care centres, walk-in centres and EDs across Yorkshire and the Humber, England. The study population will include young people aged ≤25 years presenting to UEC services between April 2019 and March 2022 with self-harm coded as the reason for attendance. Analyses will describe the prevalence of self-harm presentations across UEC settings, quantify the proportion of NHS 111 and ambulance contacts resulting in ED attendance within 24 hours and examine factors associated with ED reattendance at 3 and 12 months. Mixed-effects logistic regression models will be used to account for repeated attendances, confounding variables and temporal variation, including changes related to the COVID-19 pandemic. Anticipated analysis period: January 2026-January 2027. Ethical approval has been granted by the University of Leeds (MREC 22-079 Amd1) and the University of Sheffield (Ref 068194). The CUREd+ research database operates under Research Ethics Committee approval (23/YH/0079) and Confidentiality Advisory Group approval (18/CAG/0126). Individual consent is not required as all data are pseudonymised at source. Findings will be disseminated through peer-reviewed publications, conference presentations and public-facing outputs coproduced with patient and public involvement groups.

Background The evidence of relationships between tea and coffee consumption with lung cancer risk remains inconsistent, with few prospective studies exploring dose-response relationships. Results This prospective cohort study included 276,209 participants recruited from the UK Biobank (131,567 male and 144,642 female, mean age of 55.38 ± 8.01 years). Baseline coffee and tea intake was assessed via a touchscreen questionnaire. Hazard ratios (HRs) with 95% confidence intervals (CIs) were derived using Cox proportional hazards regression. Dose-response relationships were assessed via restricted cubic splines. During a median follow-up of 13.26 years, 3,821 participants developed lung cancer. The consumption of coffee and tea demonstrated non-linear associations with lung cancer risk ( P for nonlinear &amp;lt; 0.001). Individuals consuming 0.5–1 cup (adjusted HR: 0.72, 95% CI: 0.64–0.81), or 2–3 cups (adjusted HR: 0.77, 95% CI: 0.69–0.86) of coffee daily had a lower risk of lung cancer relative to non-drinkers. Compared with non-tea drinkers, those who drank 0.5–1 cup (adjusted HR: 0.80, 95% CI: 0.70–0.93), 2–3 cups (adjusted HR: 0.67, 95% CI: 0.60–0.76) or ≥4 cups (adjusted HR: 0.86, 95% CI: 0.77–0.95) per day had a lower risk of lung cancer. Conclusions This study demonstrated that moderate consumption of coffee and tea was associated with a lower risk of lung cancer. Further studies are needed to confirm these findings and elucidate underlying mechanisms.