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PubMed2026

Uric Acid-to-HDL Cholesterol Ratio is Associated with Hepatic Steatosis but Not Fibrosis in Nonobese Adults: A NHANES 2017-2020 Study.

BACKGROUND: Although metabolic dysfunction-associated steatotic liver disease (MASLD) has traditionally been regarded as a disease closely related to obesity, its prevalence is gradually rising in nonobese populations. The uric acid-to-high-density lipoprotein cholesterol ratio (UHR) is a novel metabolic biomarker that has been shown to be associated with MASLD. However, its role in nonobese individuals remains unclear. This study aimed to investigate the association between UHR and nonobese MASLD. METHODS: Data from the 2017 to 2020 National Health and Nutrition Examination Survey (NHANES) were analyzed. UHR was calculated as the serum uric acid (UA) divided by the high-density lipoprotein cholesterol (HDL). Liver steatosis (using controlled attenuation parameters, CAP) and fibrosis (using liver stiffness measurement, LSM) were evaluated through vibration-controlled transient elastography (VCTE). Multivariate linear regression was employed to evaluate associations. Nonlinear relationships were examined using smoothed curve fitting. RESULTS: This analysis included 3573 participants (47.41% male; aged 20-80 years). Log2-UHR was positively associated with CAP (β = 9.96, 95% CI: 6.93-12.98, P < 0.001) and MASLD prevalence (OR = 1.64, 95% CI: 1.38-1.95, P < 0.001). Subgroup analyses revealed significant interactions by sex, age, ethnicity, and smoking status (all P for interaction < 0.05), with stronger associations in females, adults aged 40-59 years, individuals of other Hispanic ethnicity, and never-smokers. Moreover, the association between log2-UHR and CAP was linear and positive (P < 0.01). No significant association was found between log2-UHR and LSM (P > 0.05). CONCLUSIONS: UHR is independently associated with hepatic steatosis but not fibrosis in nonobese US adults, suggesting its potential utility as an early risk assessment to tool. Large scale prospective studies are needed in the future to further validate the conclusions of this study.

Humans↗

PubMed2026

Protein persulfidation emerges as a conserved component of the redox response to DNA damage.

Genotoxic stress is frequently accompanied by alterations in cellular redox homeostasis; however, the mechanisms linking redox regulation to the DNA damage response (DDR) remain incompletely understood. Here, we investigated the early redox response to DNA damage induced by methyl methanesulfonate (MMS) in Saccharomyces cerevisiae, focusing on cysteine oxidative post-translational modifications (PTM). We show that activation of the DNA damage response is accompanied by rapid redox changes that occur in the absence of a generalized oxidative stress response. MMS exposure promotes selective remodeling of cysteine oxidative modifications, characterized by decreased free thiols, robust induction of protein persulfidation, and comparatively modest changes in sulfenylation. These alterations are accompanied by increased intracellular hydrogen sulfide levels, supporting the involvement of reactive sulfur species in the cellular response to DNA damage. Proteome-wide analyses revealed that cysteine oxidative modifications preferentially target proteins involved in central metabolism, nucleotide biosynthesis, and genome maintenance. Consistent with these observations, MMS-induced genotoxic stress promotes metabolic adaptation characterized by increased mitochondrial respiration, elevated ATP production, and mitochondrial morphological remodeling, linking bioenergetic adaptation to redox regulation. Importantly, perturbation of intracellular redox balance using N-acetylcysteine compromises survival under DNA-damaging conditions, supporting a functional role for redox signaling during the DDR. Finally, MMS treatment also induces protein persulfidation in mammalian cells. Moreover, exposure to etoposide, a mechanistically distinct genotoxic agent that induces DNA double-strand breaks through topoisomerase II inhibition, showed a similar trend, suggesting that protein persulfidation may not be restricted to alkylation-induced DNA damage. Together our findings identify protein persulfidation as a prominent component of the redox response to DNA damage and provide new insight into the functional interplay between mitochondrial metabolism, cysteine-based redox regulation, and genome maintenance.

Oxidation-Reduction↗

PubMed2026

Therapeutic Exercise Protocol During Hospitalization in Pediatric Oncohematological Patients: Randomized Clinical Trial.

BACKGROUND: Leukemias, lymphomas, and central nervous system tumors are among the most common pediatric cancers and may lead to motor deficits, impaired balance, reduced muscle strength, fatigue, and decreased functional capacity. Early physiotherapy during hospitalization may help prevent inactivity and support functional preservation in this population. OBJECTIVE: To evaluate the effects of a therapeutic exercise program on quality of life, muscle strength, fatigue, and functional capacity in hospitalized pediatric oncohematological patients. METHODS: Thirty participants aged 8-17 years with oncohematological diseases were randomized to an intervention group (IG) or a minimal active physiotherapy comparator group (CG). Assessments included the 6-min walk test, handgrip dynamometry, the PedsQL Multidimensional Fatigue Scale, and the PedsQL Cancer Module at admission and discharge. The IG performed daily 25-min supervised sessions including aerobic, resistance, and breathing exercises with ambulation guidance, whereas the CG received breathing exercises and ambulation guidance. RESULTS: No significant group × time interactions were observed for total fatigue or its domains, overall quality of life or its assessed domains, handgrip strength, or six-minute walk test distance. Time-related changes were observed for some outcomes, but these occurred without evidence of differential change between groups and were not interpreted as effects of the structured exercise protocol. No intervention-related adverse events requiring permanent protocol discontinuation were recorded. CONCLUSION: The structured in-hospital therapeutic exercise protocol could be delivered under close clinical supervision without recorded intervention-related adverse events requiring permanent discontinuation. However, the structured protocol did not demonstrate superiority over the minimal active physiotherapy comparator for fatigue, quality of life, muscle strength, or functional capacity. These findings should be interpreted cautiously because of the small sample size, clinical heterogeneity, variable intervention exposure, and limited intervention-fidelity data. TRIAL REGISTRATION: Brazilian Registry of Clinical Trials (ReBEC), RBR-8sxnfyd.

Humans↗

PubMed2025

Impact of subthreshold troponin levels and temporal trends on short term adverse cardiovascular outcomes in patients discharged from the emergency department: a RACE-IT trial substudy.

BACKGROUND: High-sensitivity cardiac troponin I assays enable early exclusion of myocardial infarction in the emergency department. However, the clinical implications of detectable troponin values below the 99th percentile upper reference limit (4-18 ng/L) remain unclear. OBJECTIVE: To assess the association between subthreshold troponin levels and 30-day outcomes in patients from the RACE-IT trial, using exact troponin values when available. METHODS: This post-hoc analysis of the RACE-IT stepped-wedge randomized controlled trial included patients with troponin ≤ 18 ng/L across nine EDs. Patients were stratified by initial troponin, peak value, absolute change, and percent change. The primary outcome was a 30-day composite of all-cause death, acute MI, percutaneous coronary intervention, and coronary artery bypass grafting. Logistic regression analysis after adjusting for age, sex, race, and coronary artery disease was performed. RESULTS: Among 19,194 patients with troponin ≤ 18 ng/L, 117 (0.6%) experienced the composite outcome. Higher troponin levels were associated with increased event rates in unadjusted analyses. Adjusted analyses showed no independent associations overall, though patients whose highest troponin values fell within the ≥ 11- ≤ 18 ng/L range continued to demonstrate significantly worse outcomes than those with lower peak levels. Elevated troponin values correlated with older age, male sex, and greater comorbidity burden. CONCLUSION: In this post-hoc analysis of patients with troponin values below the 99th percentile URL, absolute levels and temporal changes were not independently associated with 30-day adverse outcomes. These findings support the use of subthreshold troponin values in rapid rule-out protocols, emphasizing the need to consider clinical context and comorbidities in risk assessment.

Humans↗

PubMed2026

Factors associated with successful integration of pharmacists into residential aged care teams: A qualitative study.

BACKGROUND: Australia's Aged Care Onsite Pharmacist program aims to support quality use of medicines in residential aged care homes. This is a novel role introduced into existing teams in a complex environment. Factors associated with successful integration since implementation are currently unknown. AIM: This study aims to explore the perspectives of pharmacists and other stakeholders within aged care homes regarding successful integration of the novel aged care pharmacist service into healthcare teams. METHODS: A qualitative approach, using interpretive descriptive methodology, was used to explore perspectives. Semi-structured focus groups and interviews with pharmacists, nursing and care staff, allied health professionals, general practitioners, residents, and family members were undertaken. Data were collected via Zoom™, audio- and video-recorded, and transcribed verbatim. Two researchers undertook inductive thematic analysis to identify key themes. RESULTS: 30 participants across focus groups, focus-group interviews, interviews, and member-checking processes contributed. An overarching theme of proactivity and showing a genuine interest in others underpinned three key themes. Theme 1: Pharmacists needed to be seen, through physical presence and availability, as well as developing a distinct identity. Theme 2: Pharmacists needed to build trust, through collaboration in real time and demonstrating value. Theme 3: Pharmacists needed to develop an understanding of the aged care home environment, including social and contextual norms, as well as procedures, routines and roles. DISCUSSION: This research complements existing understandings of interprofessional collaboration and teamwork amongst healthcare professionals. Themes were interlinked; we used a sensitising framework, social cognitive theory, to present and explain the findings and interactions that can support pharmacist integration into existing teams. Aged care services should structure onboarding to prioritise early visibility, clarify roles and organisational needs, and foster in-person collaboration. Pharmacists should demonstrate proactivity and an authentic interest in all staff, residents and families.

Humans↗

PubMed2026

Comparing Clinical and Cytokine Profiling of Genital Inflammation as Predictors of HIV Acquisition in Women.

BACKGROUND: Inflammation in the female genital tract is a key risk factor for HIV acquisition, but it remains unclear whether clinical or immunological measures best predict risk. We aimed to compare HIV acquisition among women with clinically and/or immunologically defined inflammation. SETTING: HIV-uninfected women enrolled in the CAPRISA 004 tenofovir gel randomized controlled trial in South Africa were followed for up to 34 months. METHODS: We analyzed data from 889 women, with cytokine measurements available for 774 participants. Clinical genital abnormalities were assessed at scheduled visits, and 9 cytokines were measured in cervicovaginal lavage samples. HIV incidence was compared across categories of clinical and immunological inflammation using time varying Cox proportional hazards models, adjusting for relevant covariates. RESULTS: Immunological inflammation, defined as ≥9 elevated cytokines, was present in 18% (140/774) of women. Among specific clinical signs, abnormal genital discharge (adjusted hazard ratio: 2.67, 95% confidence interval [CI]: 1.14 to 6.23, P = 0.024) and cervicitis (adjusted hazard ratio: 10.34, 95% CI: 2.46 to 43.65, P = 0.001) were significantly associated with increased HIV acquisition. Women with both clinical and immunological inflammation had the highest risk of HIV acquisition, with adjusted hazard ratios of 2.08 (95% CI: 1.10 to 3.91, P = 0.022) and 2.46 (95% CI: 1.21 to 5.03, P = 0.013), respectively. CONCLUSIONS: Clinical and immunological definitions of inflammation were each independently associated with increased HIV acquisition risk and combined, they reflected greater susceptibility. These findings highlight the important role of genital inflammation in women's HIV susceptibility, suggesting that clinical signs may provide practical early indicators of risk even as cytokine profiles provide more sensitive measures of underlying inflammation.

Humans↗

PubMed2026

Molecular evaluation of residual disease following neoadjuvant chemotherapy in triple-negative breast cancer CALGB 40603 (Alliance).

BACKGROUNDDespite therapeutic advances in early-stage triple-negative breast cancer (TNBC), residual disease (RD) following neoadjuvant therapy remains a key predictor of a worse prognosis and obstacle to improving patient outcomes.METHODSTo better characterize RD and identify survival-associated features, we performed comprehensive transcriptomic profiling of 340 pretreatment stage II/III TNBCs and 70 matched posttreatment RD samples from the randomized CALGB 40603 (Alliance) phase II clinical trial. To explore preclinical treatment strategies for RD, patient-derived xenograft (PDX) mouse models mimicking RD were treated with antibody-drug conjugates (ADCs).RESULTSOur study shows prognostic genomic features measured pretreatment may differ from prognostic features measured posttreatment from RD specimens. Patients with a genomic PAM50 subtype of basal-like in RD specimens had a poor survival outcome, and their matching pretreatment tumors were characterized by elevated chromosomal amplifications of oncogenic drivers and significantly reduced B and T cell expression features. Paired analyses of basal-like RD and matched pretreatment tumors revealed further lymphocyte depletion in RD, along with lower expression of MHC class I and interferon signaling, indicating an immune-cold RD microenvironment. Treatment of a basal-like and conventional chemotherapy-resistant PDX model, resembling basal-like RD, with sacituzumab govitecan or trastuzumab deruxtecan produced a marked antitumor response.CONCLUSIONRD biology differs from pretreatment tumors, with basal-like subtype RD following neoadjuvant chemotherapy being immune cold and associated with poor survival. Preclinical modeling suggests this high-risk group may benefit from adjuvant ADC therapy.TRIAL REGISTRATIONClinicalTrials.gov NCT00861705.FUNDINGNIH NCI U10CA180821 (Alliance for Clinical Trials in Oncology), NCI U24CA176171 (Alliance for Clinical Trials in Oncology), NCI UG1CA233373 (Alliance for Clinical Trials in Oncology), NCI Breast SPORE program P50-CA058223; Susan G. Komen SAC-160074; Breast Cancer Research Foundation BCRF-23-127; NIH NCI R01-CA229409; UNC LCCC Triple Negative Breast Cancer Center.

Humans↗

PubMed2026

Exercise prehabilitation in head and neck cancer patients proposed for definitive chemoradiotherapy: The FIT4TREAT randomized controlled trial.

BACKGROUND: Patients with head and neck cancer (HNC) initially scheduled for definitive chemoradiotherapy (CRT) often experience early functional decline and deterioration in health-related quality of life (HRQoL) even before treatment initiation. Evidence for prehabilitation in this non-surgical setting remains limited. This study evaluated whether exercise prehabilitation (EP) initiated before CRT improves functional capacity compared with usual care (UC). METHODS: FIT4TREAT (ClinicalTrials.gov: NCT05418842) was a prospective, single-center, randomized clinical trial. Adults with HNC proposed for definitive CRT were randomly assigned (1:1) to EP or UC. EP consisted of supervised combined aerobic and resistance exercise performed three times per week from baseline until radiotherapy initiation. The primary outcome was the six-minute walk distance (6MWD) at the end of the pre-treatment period. Secondary outcomes included muscle strength, lower-limb functionality, body composition, and HRQoL assessed using the EORTC QLQ-C30 and QLQ-HN43. RESULTS: Between May 2021 and February 2025, 47 patients were enrolled; 40 were included in the primary analysis. After adjustment for baseline 6MWD and the randomization stratification variables, EP resulted in a significantly greater pre-treatment 6MWD than UC (adjusted between-group difference, 28.6 m; 95 % CI, 4.1-53.1; P = 0.023). EP also improved lower-limb functionality (P < 0.001) and was associated with better preservation in the QLQ-C30 summary score (P = 0.008), social functioning (P = 0.038) and body image (P = 0.011). CONCLUSION: EP before definitive CRT improves functional capacity and may help preserve HRQoL in patients with HNC, supporting its potential integration into routine oncology care.

Humans↗

PubMed2028

Parental son preference in childhood and sex differences in the risk of cardiovascular disease in middle-aged and older adults.

INTRODUCTION: Sex differences in cardiovascular disease (CVD) risk are examined through biological and clinical factors, with less attention to early-life social exposures. This study examined associations of childhood parental son preference with CVD risk, sex differences, and mediation by modifiable risk factors. METHODS: This cohort analysis included China Health and Retirement Longitudinal Study participants aged ≥45 years without baseline CVD. Parental son preference was assessed retrospectively in 2014; incident CVD was self-reported physician-diagnosed heart disease or stroke through 2020. Sampling-weighted, community-clustered Cox models estimated adjusted hazard ratios (aHRs) and 95% CIs. Sex was prespecified as an effect modifier; mediation by 13 risk factors used inverse-odds-ratio weighting. Data were collected from 2011 to 2020 and analyzed from 2025 to 2026. RESULTS: Among 8,079 participants (mean age, 57.5 years; 4,216 women [52.2%]), 1,820 (22.5%) reported parental son preference. Son preference was associated with higher CVD risk overall (aHR 1.23 [95% CI 1.04, 1.46]) and among women (aHR 1.25 [95% CI 1.03, 1.53]); among men, the estimate was 1.16 (95% CI 0.87, 1.56), with limited heterogeneity by sex (ratio of aHRs 1.06 [95% CI 0.72, 1.58]). Among women, risk was concentrated in the highest paternal (aHR 1.47 [95% CI 1.14, 1.90]) and maternal (aHR 1.50 [95% CI 1.12, 1.99]) preference categories. Modifiable risk factors mediated 5.8% (95% CI 1.9%, 9.7%) of the association among women, mainly through socioeconomic and psychosocial factors. CVD risk was highest with both son preference and high risk-factor burden overall (aHR 1.97 [95% CI 1.43, 2.73]) and among women (aHR 2.23 [95% CI 1.61, 3.10]). CONCLUSIONS: Parental son preference was associated with higher incident CVD risk, with the largest estimates in the highest paternal or maternal categories among women. Modifiable risk factors explained a modest proportion, supporting life-course cardiovascular prevention that considers sex-differentiated childhood environments alongside risk-factor modification.

cardiovascular disease↗

PubMed2025

Worldwide prevalence of haemorrhoids: a systematic review and meta-analysis.

BACKGROUND: Haemorrhoidal disease (HD) is one of the most common anorectal disorders globally, significantly impacting individuals' quality of life and productivity. Despite its importance, global prevalence remains unclear due to limited population-specific studies. This study aimed to systematically assess the global prevalence of HD through a systematic review and meta-analysis. METHODS: We conducted a systematic review and meta-analysis by searching PubMed, Scopus, Embase, Web of Science, and Google Scholar up to March 31, 2025, without language restrictions. Studies reporting prevalence of haemorrhoids in general, clinical, or high-risk populations were included. Exclusion criteria comprised studies lacking total sample size, focusing on other anorectal conditions, or using duplicate or insufficient data. Four independent reviewers extracted and appraised study quality using the Joanna Briggs Institute tool. The primary outcome was pooled point prevalence of HD, analyzed using a random-effects model with 95% confidence intervals (CIs). The study was registered in PROSPERO (CRD420251045600). RESULTS: From 6,312 records, 150 studies (210 datasets) comprising 8,960,338 individuals were included. The global pooled point prevalence was 25.92% (95% CI: 22.62-29.22). Lifetime prevalence was 27.19% (95% CI: 14.77-39.60), and one-year prevalence was 21.65% (95% CI: 14.33-28.97). Prevalence was higher in women (27.33%, 95% CI: 21.84-32.82) than in men, and highest in the African region 28.07% (95% CI: 15.34-40.79). Invasive diagnostic methods (28.05%, 95% CI: 23.86-32.26) yielded higher prevalence estimates than non-invasive methods. Also, factors showing associations with HD in unadjusted analyses include older age, obesity, pregnancy, diabetes, family history, constipation, and hypertension. CONCLUSION: HD remains a prevalent condition globally, with minor variation across regions. The burden is consistent regardless of socioeconomic context. Diagnostic method and population characteristics influence prevalence estimates. These findings underscore the importance of targeted prevention and early intervention strategies, especially for at-risk groups.

Humans↗

PubMed2026

Mitochondrial dysfunction in muscle cells induced by snoring vibrations.

Snoring-related vibrations have been proposed as a pathogenic factor contributing to upper airway muscle dysfunction in patients with obstructive sleep apnea (OSA). To investigate whether exposure to snoring vibration is linked to muscle weakness, we used an in vitro vibration model to examine its effects on mitochondrial homeostasis in L6 muscle cells at 8, 12, 24, and 48 h. The findings were then compared with mitochondrial alterations in the upper airway muscles from snorers and patients with OSA. Proteomic analysis of L6 myoblasts revealed extensive remodeling of the mitochondrial proteome at 8 h, affecting pathways involved in oxidative phosphorylation, protein import, ribosome biogenesis, and RNA processing. Respiratory chain remodeling was subunit-specific, with increased abundance of selected components of Complexes I, IV, and V, including NDUFS4, COX5A, and ATP5PD. However, reductions in spliceosome-associated factors, such as SRSF2 and DDX46, along with alterations in mitochondrial ribosomal proteins, indicated impaired RNA processing and protein synthesis. Furthermore, both proteomic and transcriptomic analyses revealed activation of a mechanosensing-mechanotransduction axis, with early upregulation of integrin subunits and mechanosensitive ion channels, followed by transient activation of focal adhesion signaling. Despite transcriptional upregulation of selected Complex IV subunits Cox5a and Cox6a2, this response was accompanied by accumulation of unspliced pre-mRNA, indicating impaired RNA processing efficiency and a decoupling between transcript and protein levels. Real-time Seahorse assay revealed a collapse of mitochondrial respiration and glycolytic reserve at 8 h. Although mitochondrial oxygen consumption recovered after 48 h, the ability to dynamically upregulate glycolysis remained impaired. In patients, muscle capillarization was impaired, COX activity was reduced, and mitochondrial organization was disrupted. Moreover, transcription of Complex IV subunits COX5A and COX6A2 was, as in vibrated L6 cells, upregulated, suggesting a mismatch between transcript levels and protein expression. We conclude that snoring-induced vibrations are an unrecognized stressor that disrupts mitochondrial homeostasis in muscle by impairing RNA processing, protein synthesis, and mechanotransduction-driven mitochondrial remodeling, leading to transcript-protein uncoupling and likely muscle dysfunction.

Humans↗

PubMed2026

Pembrolizumab-Chemotherapy Versus Pembrolizumab in Head and Neck Squamous Cell Carcinoma: A PD-L1 CPS-Stratified Analysis of Updated KEYNOTE-048 Data.

Based on KEYNOTE-048, pembrolizumab monotherapy and pembrolizumab-chemotherapy are established category 1 first-line treatments for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) with programmed death ligand-1 (PD-L1) combined positive score (CPS) ≥ 1. We compared their efficacy using updated trial data. We analyzed 4-year progression-free survival on next-line therapy (PFS2) and 5-year overall survival (OS) data from KEYNOTE-048 by reconstructing time-to-event data using KMSubtraction. Efficacy was compared in CPS 1-19 and CPS ≥ 20 subgroups using Kaplan-Meier estimates, Cox models, restricted mean survival time (RMST), and landmark analyses. Among 499 patients with CPS ≥ 1, 240 (48.1%) had CPS 1-19 and 259 (51.9%) had CPS ≥ 20. In the CPS 1-19 subgroup, pembrolizumab-chemotherapy showed numerically longer median PFS2 (10.1 vs. 8.0 months; hazard ratio [HR]: 0.81; 95% confidence interval [CI]: 0.62-1.06) and OS (12.8 vs. 10.8 months; HR: 0.87; 95% CI: 0.67-1.15) versus monotherapy, without statistical significance. For CPS ≥ 20 patients, efficacy was comparable between regimens, with similar median PFS2 (11.3 vs. 11.7 months; HR: 0.95) and OS (14.7 vs. 14.9 months; HR: 0.96). RMST and landmark analyses showed an early PFS2 benefit and a trend toward OS benefit with pembrolizumab-chemotherapy in CPS 1-19, with comparable outcomes in CPS ≥ 20. Pembrolizumab-chemotherapy showed a trend toward improved outcomes in the CPS 1-19 subgroup, with comparable efficacy in the CPS ≥ 20 subgroup, supporting a refined first-line strategy: monotherapy for CPS ≥ 20 to minimize toxicity, and combination therapy for CPS 1-19 to potentially enhance disease control.

Humans↗

PubMed2026

Multimodal Therapy With Metformin, Inositol and Dietary Restriction Improves Insulin Resistance and Endocrine Outcomes in Women With Polyendocrine Metabolic Ovarian Syndrome: A Randomized Controlled Trial.

INTRODUCTION: Polyendocrine metabolic ovarian syndrome (PMOS), formerly known as polycystic ovary syndrome (PCOS), is a common endocrine-metabolic disorder characterized by insulin resistance, hyperandrogenism and ovulatory dysfunction. Metformin, inositol supplementation and lifestyle modification are widely used treatments, but direct comparative evidence remains limited. Multimodal therapy combining metformin, inositol and dietary restriction produces greater metabolic and reproductive improvement than single-modality interventions. METHODS: We conducted a 12-week randomized controlled trial in 192 women aged 18-35 years diagnosed with PMOS according to Rotterdam criteria. Participants were allocated to metformin (1500-2000 mg/day), inositol (myo-inositol 2 g plus d-chiro-inositol 50 mg twice daily), calorie-restricted diet (1200-1500 kcal/day), or combination therapy. Primary outcomes included changes in body mass index (BMI) and insulin resistance assessed by HOMA-IR. Secondary outcomes included testosterone, LH/FSH ratio and menstrual regularity. Analysis was performed using analysis of covariance (ANCOVA), with post-intervention values as dependent variables and corresponding baseline values as covariates. Categorical outcomes were compared using the Chi-square test. RESULTS: All interventions improved metabolic and endocrine parameters. Combination therapy resulted in the greatest reduction in HOMA-IR (- 2.64, 95% CI - 2.82 to -2.46, p < 0.001) and BMI (- 2.8 kg/m2, 95% CI - 3.05 to -2.55, p < 0.001). Menstrual cyclicity improved across all groups, with the highest proportion of participants reporting cycle regularisation in the combination therapy group (85.4%), compared with dietary restriction (72.9%), inositol (64.6%), and metformin (39.6%) (p < 0.001). Given the short follow-up duration, these findings reflect early improvements rather than sustained normalisation. CONCLUSION: Multimodal therapy was associated with superior metabolic and reproductive outcomes compared with single-modality interventions in women with PMOS. CLINICAL TRIAL REGISTRATION: ClinicalTrials. gov (NCT07380841).

Humans↗

PubMed2026

Oliceridine used for patient-controlled analgesia on postoperative quality of recovery in patients undergoing laparoscopic gynecological tumour resection: a randomized clinical trial.

BACKGROUND: Oliceridine, a novel biased μ-opioid receptor agonist, is widely used perioperatively, yet limited data exists regarding its impact on postoperative quality of recovery. This study investigated the effect of oliceridine-based patient-controlled intravenous analgesia (PCIA) on postoperative quality of recovery among patients undergoing laparoscopic gynecological tumour resection. METHODS: Ninety‑four female patients scheduled for elective laparoscopic gynecological tumour resection were included. Patients were randomized to two groups: oliceridine group (loading dose 1.5 mg, PCIA 0.55 mg/kg) or sufentanil group (loading dose 10 μg, PCIA 3 μg/kg). The primary outcome was the Quality of Recovery-40 (QoR-40) score on postoperative day 1. The secondary outcomes included the QoR-40 score, the numeric rating scale (NRS) pain score, the Hospital Anxiety and Depression Scale-Anxiety (HADS-A) score, the Fatigue, Resistance, Ambulation, Illness and Loss of weight (FRAIL) index and adverse events within 3 postoperative days. RESULTS: Higher QoR-40 scores were found in the oliceridine group on postoperative day 1 (182.9 ± 3.1 versus 177.5 ± 3.9, p < 0.001). Compared with the sufentanil group, the oliceridine group showed better QoR-40 scores within 3 days after operation. No significant differences were observed in NRS pain scores or HADS-A scores between the two groups (all p > 0.05). However, the median FRAIL score in the oliceridine group was lower on postoperative day 2 (p = 0.018). CONCLUSION: Oliceridine used in PCIA improves early postoperative recovery quality of patients undergoing laparoscopic gynecological tumour resection. It provides analgesic effect comparable to sufentanil and lowers incidences of postoperative frailty, nausea and vomiting. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR.org.cn, identifier: ChiCTR2400094271.

Humans↗

PubMed2026

Pilot randomized trial of intermittent theta-burst stimulation versus H-Coil transcranial magnetic stimulation for treatment-resistant depression.

BACKGROUND: Intermittent theta burst stimulation (figure-8-coil iTBS) and H7-coil repetitive transcranial magnetic stimulation (rTMS) are FDA-cleared treatments for major depression; yet their comparative effectiveness in treatment-resistant depression (TRD) has not been evaluated in randomized trials. This pilot randomized trial was designed to obtain preliminary comparative estimates and to explore whether baseline cognitive functioning relates to early remission. METHODS: Twenty-eight adults with TRD were randomized to six weeks of figure-8-coil iTBS delivered to the dorsolateral prefrontal cortex (DLPFC) (n = 15) or H7-coil rTMS delivered to the dorsomedial prefrontal cortex (DMPFC) (n = 13). The primary outcome was change in 17-item Hamilton Depression Rating Scale (HRSD-17) score from baseline to week 6, analyzed with ANCOVA. Additional outcomes included response, remission, and symptom trajectories through week 18. Exploratory analyses examined the association between baseline cognitive functioning, such as executive functions and memory, and remission. RESULTS: Twenty-five participants completed all 30 sessions. Adjusted week-6 HRSD-17 scores did not differ between groups (mean difference -0.40, 95% CI -5.23 to 4.43; p=.865). Response rates were 40.0% for figure-8-coil iTBS and 50.0% for H7-coil rTMS (p>.60), and remission rates were identical across groups (20.0%). Remitters showed higher baseline executive functioning than non-remitters in exploratory analyses, although these associations were not confirmed in adjusted models. CONCLUSION: In this pilot trial, figure-8-coil iTBS and H7-coil rTMS showed symptom improvement, with no clear between-group differences. Exploratory findings suggest a potential signal involving executive functioning that warrants further investigation. These results inform the feasibility and design of larger comparative trials. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05902312).

Adult↗

PubMed2026

Externally validated risk prediction models for gestational diabetes mellitus: A systematic review and meta-analysis.

INTRODUCTION: Risk prediction models for gestational diabetes mellitus (GDM) offer potential for early identification and targeted prevention. External validation is crucial to assess model performance across diverse populations. Despite the availability of numerous GDM prediction models, limited evidence exists on their external validation frequency, methodological quality, and clinical applicability. This systematic review evaluated externally validated GDM prediction models, focusing on methodological rigor, reporting standards, and clinical relevance to inform future research and implementation. MATERIAL AND METHODS: Databases including Ovid MEDLINE, Embase, Scopus, Emcare, and CINAHL were searched up to May 1, 2025. Studies reporting external validation of GDM risk prediction models were included. Two reviewers independently screened studies. Data were extracted using the CHARMS framework, and risk of bias and applicability were assessed using PROBAST+AI. The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD420251125758). RESULTS: Twenty-six studies validated 33 models, with validation sample sizes ranging from 50 to 75 161. Over half used the IADPSG criteria to define GDM. Discrimination metrics were commonly reported, but calibration, overall performance, and clinical utility were often lacking. Meta-analysis was feasible for only four models: Teede et al., Nanda et al., Naylor et al., and Van Leeuwen et al., each showing fair discrimination. The Teede et al. model was the most widely validated, with 11 external validations across six continents and a pooled AUC of 0.72 (95% CI: 0.67-0.76). Despite fewer validations, the Nanda et al. model achieved the highest pooled discrimination (5 validations; pooled AUC 0.77, 95% CI: 0.74-0.80). The Naylor et al. and van Leeuwen et al. models also underwent meta-analysis, as sufficient external validation studies were available to support comparative performance assessment. Notably, 69.23% of studies had a high risk of bias. CONCLUSIONS: While many models showed acceptable predictive performance, most validations were methodologically weak. Future studies should follow best-practice guidelines and promote scalable validation strategies, such as algorithm sharing, to enhance clinical utility.

Humans↗

PubMed2026

Paediatric penile length: a systematic review and meta-analysis.

OBJECTIVE: To assess geographical variation in stretched penile length among prepubertal boys and evaluate temporal trends over the past two decades, as defining reference values for genital organ size remains crucial for early identification of development disorders. METHODS: The PubMed, Cochrane and Scopus databases (no deadlines for publishing were imposed) were searched according to the Preferred Reporting Items for Systematic Review and Meta-analyses statement. Five authors independently extracted individual participant data and assessed the risk of bias. Studies with quantitative penile lengths were included; those involving congenital malformations were excluded. The review protocol was prospectively registered in the International Prospective Register of Systematic Reviews (registration number CRD42022335643). RESULTS: A total of 55 studies from 2000 to 2024 were evaluated, including data from 31 915 boys. Pooled mean stretched penile length estimates were 3.07 cm (95% confidence interval [CI] 2.88-3.26 cm) for the 1-week-old boys, 3.73 cm (95% CI 3.53-3.93 cm) for the 1-year-old boys, 4.69 cm (95% CI 4.49-4.88 cm) for the 2-5 year-old boys, and 5.43 cm (95% CI 5.20-5.66 cm) for the 5-10 year- old boys. When comparing data from the 2000s to the 2020s, stretched penile length decreased by 16.2% (from 3.46 to 2.90 cm), 16.3% (from 4.17 to 3.49 cm), 21.5% (from 5.31 to 4.17) and 26.2% (from 6.46 to 4.77 cm) in the 1-week-old, 1-year-old, 2-5-year-old and 5-10-year-old boys, respectively. Subgroup analysis for those aged >2 years showed significant variations by geographical region (P < 0.001). CONCLUSIONS: The present study observed large variations in penile length across geographical regions and among prepubescent boys of different ages, while also suggesting a possible decline over the past two decades.

Humans↗

PubMed2026

Beyond survival: Testicular tissue cryopreservation for fertility preservation during childhood cancer, experiences from a single center.

INTRODUCTION: Approximately 30% of all male childhood cancer survivors receive gonadotoxic therapy increasing their risk for infertility. The only current option for potential fertility preservation in prepubertal males is through testicular tissue cryopreservation (TTC), available through clinical trials. Our aim was to evaluate our experience and identify barriers to enrollment in the TTC study. METHODS: A retrospective review was conducted to describe a single center experience with TTC, including an assessment of factors impacting the decision to enroll or not enroll in the TTC trial. RESULTS: A total of 61 patients were found to be eligible for enrollment in the TTC trial, with 23 patients (34%) choosing to enroll and undergo testicular tissue cryopreservation including 19 (83%) oncology patients. In patients who underwent TTC there were no unexpected delays in starting disease directed therapy. For families that declined enrollment, many did not see fertility preservation as a priority at the time of counseling. (n = 17, 44%). Other barriers included concerns about post-operative complications and a feeling of being overwhelmed at the time of counseling. DISCUSSION: Despite being the only preservation option for pre-pubertal boys facing risk of infertility, TTC enrollment was not pursued by a majority of eligible patients and families. Identifying potential barriers or misconceptions, particularly in regard to post operative complication risks, offer opportunities for improved counseling and education. Early introduction of the Fertility Navigation team allows for procedural coordination success and access for patients that are interested. Success is not measured in how many patients proceed with TTC, rather that all patients have the opportunity for counseling and discussion. CONCLUSION: TTC can be offered and completed safely without delays in disease-directed treatment timelines. A Fertility Navigation Program allows for equal opportunity for education and enrollment on TTC protocol which should be the goal for pediatric institutions, though is not pursued by many patients. A majority of those who declined the study did not see fertility as a priority at the time of treatment while others were concerned regarding peri-operative risks.

Humans↗