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PubMed2026

Development and protective efficacy of a live attenuated vaccine candidate against goose astrovirus.

Goose astrovirus (GAstV) is a significant pathogen affecting goslings by inducing visceral gout, yet no commercial vaccine is currently available. This study involved the serial passaging of the GAstV-GXNN strain in LMH cells to investigate alterations in viral replication, genomic stability, and pathogenicity, as well as to assess the potential of a vaccine candidate. The findings indicated that the viral titer increased progressively with each passage, reaching 107.35 TCID50/mL by the 120th passage (GAstV-GXNNP120). Whole-genome sequencing revealed the presence of 6, 19, 26, and 28 nucleotide mutations at the 30th, 60th, 90th, and 120th passages, respectively. Pathogenicity assays demonstrated a reduction in virulence with successive passages, culminating in the complete attenuation of GAstV-GXNNP120, which did not induce clinical signs or lesions in one-day-old goslings. Following five successive passages in goslings, the attenuated strain exhibited stable genetic characteristics without any reversion to virulence. Goslings aged one day, inoculated with GAstV-GXNNP120 at dosages ranging from 102.0 to 105.0 TCID50, developed neutralizing antibodies by the third day post-vaccination. Antibody levels increased in a dose-dependent manner, peaking at day 21 and remaining elevated through day 42. Challenge experiments utilizing the virulent GAstV-GXNN strain revealed that groups vaccinated with doses of 103.0 TCID50 and above achieved complete protection. These groups exhibited no clinical symptoms or pathological damage post-challenge, and both tissue viral loads and virus shedding levels were significantly reduced compared to the control group. Consequently, the minimum effective vaccination dose was established at 103.0 TCID50. These results provide a crucial foundation for the development of a live attenuated GAstV vaccine.

Animals↗

PubMed2026

Efficacy and safety of mitapivat in adults with transfusion-dependent α-thalassaemia or β-thalassaemia (ENERGIZE-T): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial.

BACKGROUND: The absence of disease-modifying therapies for patients with α-thalassaemia and oral disease-modifying therapies for patients with β-thalassaemia has been a substantial unmet need in these patients. We assessed the efficacy and safety of mitapivat, an oral allosteric activator of pyruvate kinase, in adults with transfusion-dependent thalassaemia. METHODS: ENERGIZE-T is a global, double-blind, randomised, placebo-controlled, phase 3 trial, conducted across 19 countries in North America, Europe, Asia-Pacific, South America, and the Middle East. Patients aged 18 years or older with transfusion-dependent α-thalassaemia or β-thalassaemia were randomly allocated (2:1) with a central interactive response technology system, stratified by geographical region and thalassaemia genotype, to receive 100 mg mitapivat or placebo orally twice a day for 48 weeks. The primary endpoint was transfusion reduction response (TRR), defined as a reduction of at least 50% in transfused red blood cell units with a reduction of at least two units in any consecutive 12-week period until week 48 compared with baseline. Efficacy was analysed in the full analysis set, comprising all randomly allocated patients. Type, severity, and relationship of adverse events and serious adverse events were assessed in patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov (NCT04770779) and is active but not recruiting. FINDINGS: Between Nov 30, 2021 and May 2, 2023, 305 patients were screened, of whom 258 were randomly allocated (median age 33·5 years [IQR 27·0-44·0]; 136 [53%] female and 122 [47%] male participants). Of 258 patients allocated, 238 (92%) completed the double-blind treatment period. All patients were required to have a safety follow-up approximately 4 weeks after the final dose of study drug, regardless of completion of the double-blind period or continuation into the open-label extension period. In the full analysis set, TRRs occurred in 52 (30%) of 171 patients in the mitapivat group and 11 (13%) of 87 in the placebo group (adjusted difference 18 percentage points [95% CI 8-27]; two-sided p=0·0003). The safety analysis set comprised 172 patients in the mitapivat group (including one patient allocated to the placebo group who received one dose of mitapivat in error) and 85 in the placebo group. Adverse events were reported in 155 (90%) patients treated with mitapivat and 71 (84%) treated with placebo; the most common events with mitapivat were headache, upper respiratory tract infection, initial insomnia, diarrhoea, and fatigue. Serious adverse events were reported in 19 (11%) patients treated with mitapivat and 13 (15%) treated with placebo. Ten (6%) patients who received mitapivat and one (1%) who received placebo discontinued study treatment due to adverse events. No deaths were reported. INTERPRETATION: Mitapivat significantly reduced the transfusion burden and was generally well tolerated, showing a favourable benefit-risk profile. These findings support mitapivat as the first oral disease-modifying therapy for adults with transfusion-dependent α-thalassaemia or β-thalassaemia, providing a new treatment option to reduce transfusion burden in this patient population. FUNDING: Agios Pharmaceuticals, Inc.

Adult↗

PubMed2026

Comparison of immunogenicity, safety, and efficacy of EVA71 vaccine in children: a systematic review and meta-analysis.

INTRODUCTION: Enterovirus 71 (EV-A71) is a principal cause of hand, foot, and mouth disease (HFMD), potentially leading to severe neurological complications in children. Inactivated EV-A71 vaccines have been introduced. This study compares the immunogenicity, safety, and efficacy of EV-A71 vaccines versus placebo in pediatric populations. RESEARCH DESIGN AND METHODS: Following a PROSPERO-registered protocol, RCTs involving EV-A71 in children were identified via PubMed, Scopus, Cochrane, and ClinicalTrials.gov. Two independent reviewers performed screening, extraction, and RoB assessments (RoB 2.0). RESULTS: Five phase III RCTs involving 36,659 children were included. EV-A71 vaccination significantly increased seropositivity across follow-up periods, including early (RR 5.8), medium-term (RR 3.09), and long-term (RR 2.95) response. Seroconversion was significantly higher in the vaccinated group (pooled RR 13.04, 95% CI 2.80-60.61; p < 0.001). Geometric mean titers, analyzed using the ratio of means approach, were significantly higher in the vaccinated group during early and medium-term follow-up. Vaccine efficacy against EV-A71-associated HFMD exceeded 98% (pooled RR 0.02, 95% CI 0.01-0.09; p = 0.0028; I2 = 50%). Solicited local and systemic adverse events were mild and comparable between groups. CONCLUSION: Inactivated EV-A71 vaccines robust immunogenicity, high clinical efficacy, and an acceptable safety profile in children. Future studies should explore long-term protection, booster schedules, and multivalent formulations against non-EV-A71 serotypes.

Humans↗

PubMed2026

Nociception-guided opioid administration within multimodal analgesia for laparoscopic endometriosis surgery: a randomized controlled trial.

Women with endometriosis are at increased risk of severe postoperative pain due to nociceptive sensitization. While multimodal analgesia reduces opioid use, the added value of objective nociception monitoring remains unclear. This study evaluated whether NOL®-guided opioid titration improves perioperative outcomes within a standardized multimodal regimen. In this prospective, randomized, single-blinded trial, premenopausal women undergoing laparoscopic surgery for suspected endometriosis or adenomyosis were assigned to NOL®-guided analgesia or standard care based on clinical assessment. All patients received a standardized multimodal protocol. The primary outcome was total perioperative opioid consumption. Secondary outcomes included postoperative pain scores (NRS) and PACU length of stay. Exploratory analyses assessed the association between preoperative pain (Mankoski Pain Scale, MPS) and postoperative outcomes. A total of 111 patients were analyzed (NOL®: n = 54; control: n = 57). Total perioperative opioid consumption did not differ significantly between groups (adjusted mean difference = 14 μg for Fentanyl and 52 μg for Remifentanil; p = 0.8). Surgery duration was an independent predictor of opioid use (p < 0.001) and PACU length of stay (p = 0.01), whereas treatment group had no significant effect. Postoperative pain scores were comparable between groups at all time points. NOL®-derived metrics were not associated with opioid consumption or pain. Higher preoperative MPS scores independently predicted higher pain scores in the late PACU phase. NOL®-guided opioid titration did not reduce perioperative opioid consumption or improve early postoperative outcomes compared with standard multimodal analgesia in women undergoing laparoscopic surgery for endometriosis.

Humans↗

PubMed2026

Efficacy and safety of human albumin combined with furosemide in acute decompensated heart failure with hepatic dysfunction.

BACKGROUND: Congestion is the most common clinical presentation on admission of patients with acute decompensated heart failure (ADHF). Finding effective ways to alleviate congestion has become a pivotal management step. This study sought to investigate the efficacy and safety of intravenous (IV) albumin use in conjunction with furosemide in patients hospitalized for ADHF with hepatic dysfunction in terms of subjective regression of congestion symptoms and worsening renal function. METHODS: This prospective, open-label, randomized-pragmatic trial recruited 241 patients with hepatic dysfunction hospitalized for ADHF. Patients (78 years, 54% female) were assigned to receive IV albumin with furosemide or IV furosemide alone. The coprimary study endpoints were patients' global assessment of symptoms score, quantified as the area under the curve (AUC) of the score on a visual analog scale, and the change in creatinine levels over 72 hours from admission. RESULTS: The experimental treatment group demonstrated a greater improvement in patients' global assessment of symptoms scores (AUCbaseline-72 h 3,767 vs 3,457 points; P < .001) and a milder increase in creatinine levels (0.07 vs 0.18 mg/dL; P = .045) than the IV furosemide group. The length of stay was 1 day shorter (4 vs 5 days; P < .001) and the incidence of worsening renal function was lower (25% vs 38%; P = .037) in the experimental treatment group. CONCLUSIONS: In this hypothesis generating study, among patients with ADHF and hepatic dysfunction, concomitant use of IV albumin and furosemide for the first 72 hours resulted in a significant improvement in subjective perception symptoms of decongestion and a milder increase in creatinine levels than IV furosemide alone.

Aged↗

PubMed2026

Integrative genomic and transcriptomic analyses identify key regulators of skin pigmentation in Larimichthys crocea.

The yellow body coloration of large yellow croaker (Larimichthys crocea) constitutes a crucial economic trait, yet its underlying genetic regulatory mechanisms remain poorly understood. This study systematically elucidated the molecular basis of body color variation by integrating genome resequencing and skin transcriptome analyses, combined with the contextual analysis of key pigmentation-related genes and phenotypic histological validation. 200 phenotyped individuals (including yellow-selected lines, F1 progeny, and normal control groups, all derived from a well-characterized aquaculture stock) identified 39 significantly associated SNPs (-log₁₀(P) ≥ 6), mapping to multiple candidate genes. These genes were significantly enriched in pathways related to pigment deposition (GO:0033059), melanosome organization (GO:0032438), melanogenesis, and tyrosine metabolism. Cross-developmental stage transcriptome analysis revealed 2395 differentially expressed genes (DEGs). Multi-omics integration identified eight overlapping candidate genes, including tyrp1, slc45a2, oca2, and dgat2, among which tyrp1 was prioritized for in-depth validation based on its core regulatory role in eumelanin synthesis, significant SNP association signal, and consistent downregulation in transcriptomic data. Experimental validation demonstrated that the g.895C > T mutation in exon 2 of tyrp1b was strongly significantly associated with the yellow phenotype: the frequency of mutant genotypes (TT/CT) reached 92.86%in the yellow-selected group, whereas the control group exclusively exhibited the wild-type genotype (CC). qPCR confirmed significantly downregulated tyrp1b expression in the skin of yellow individuals, consistent with the transcriptome trend. Histological and stereomicroscopic observations of skin tissues further validated the physiological basis of the yellow phenotype, revealing a significant reduction in melanophore number and abnormal melanosome morphology in yellow-phenotype individuals, accompanied by increased xanthophore density. These results suggest that tyrp1b mutation is strongly associated with the yellow phenotype. However, the presence of a wild-type CC individual in the yellow group indicates that this mutation is not strictly required for yellow coloration, suggesting that other genetic or environmental factors may also contribute to the phenotype, Additionally, downregulation of the carotenoid metabolism gene bco2 coupled with upregulation of xdh, together with the functional changes of slc45a2 and oca2, may synergistically promote xanthophore pigment deposition, contributing to the yellow phenotype. As melanin synthesis in large yellow croaker relies on the conserved tyrosinase pathway and transporter proteins, mutations in associated genes (tyrp1b, slc45a2, oca2) represent a primary underlying cause for the loss of melanin-based coloration and transition to a yellow phenotype in L. crocea. These findings provide key molecular targets and a theoretical foundation for molecular breeding of body color in this species, and also enrich the understanding of xanthism regulatory mechanisms in teleosts.

Animals↗

PubMed2026

Evolutionary conservation of heat shock proteins in Blattodea and their roles in wing morphogenesis and ovarian development of Blattella germanica.

Heat shock proteins (Hsps) are essential molecular chaperones for protein homeostasis and stress responses. However, the Hsp repertoires and functions in Blattodea remain underexplored. Our genome-scale survey of nine Blattodea species revealed 37-46 conserved Hsp90, Hsp70, and DNAJ (Hsp40) genes, with DNAJ the most abundant and Hsp90 the least. Phylogenetic analysis confirmed the evolutionary conservation of three Hsp90, seven Hsp70, and 29 DNAJ subclades in Blattodea. Selection pressure analysis revealed predominant purifying selection (dN/dS ≪ 1) across lineages, strongest in DNAJ and highest in Hsp90 conservation. In Blattella germanica, expression of six representative BgHsp genes progressively increased during development, peaking in fifth-instar nymphs. Tissue expression profiling revealed that BgHspA1-2/3/4 were predominantly expressed in legs, BgDNAJB5 and BgHsp90AB1-2 were enriched in the fat body, and BgHsp90AB1 was highly expressed in the head. dsRNA injection targeting conserved Hsp gene regions achieved 61.9-94.1% knockdown of all six target genes. RNAi knockdown of six BgHsp genes disrupted wing morphogenesis, causing distinct phenotypes: wing whitening (56.7%, dsBgHspA1-4), unequal length (66.7%, dsBgHspA1-3; 76.7%, dsBgDNAJB5), and wing wrinkling (70%, dsBgHspA1-2; 63.3%, dsBgHsp90AB1; 76.7%, dsBgHsp90AB1-2). During ovarian formation, the developmental delay was most severe in the dsBgHsp90AB1 group, moderate in the dsBgHsp90AB1-2 and dsBgHspA1-2/3/4 groups, and weakest in the dsBgDNAJB5 group. Besides, knockdown significantly downregulated key developmental genes (apterous-a, nubbin, scalloped, ultrabithorax, wingless, and vitellogenin). These findings provide a reference for understanding the evolutionary patterns of Hsps in Blattodea, and offer mechanistic insights into the developmental regulation mediated by Hsps in this important public-health pest.

Animals↗

PubMed2026

Phase 3 Trial of Oral Infigratinib in Children with Achondroplasia.

BACKGROUND: Achondroplasia is a genetic skeletal condition caused by FGFR3 pathogenic variants. Infigratinib, an oral FGFR1-3 tyrosine kinase inhibitor, down-regulates key pathways in the pathogenesis of achondroplasia. METHODS: In this phase 3, multicenter, double-blind, placebo-controlled trial, we randomly assigned children with achondroplasia (3 to 17 years of age) in a 2:1 ratio to receive infigratinib (at a dose of 0.25 mg per kilogram of body weight) or placebo once daily for 52 weeks. The primary end point was the change from baseline in the annualized height velocity in the infigratinib group as compared with the placebo group at week 52. Key secondary end points were the change from baseline in the height z score and in the upper-to-lower body segment ratio at week 52. The primary analysis evaluated the treatment effect at week 52 in the full analysis population, with missing data handled with a prespecified imputation approach. RESULTS: In all, 114 patients underwent randomization: 75 patients to receive infigratinib (with 1 withdrawal before treatment) and 39 patients to receive placebo. The difference between infigratinib and placebo in the least-squares mean change from baseline to week 52 was 1.74 cm per year (95% confidence interval [CI], 1.31 to 2.17; P<0.001) for the annualized height velocity, 0.32 (96% CI, 0.23 to 0.41; P<0.001) for the height z score, and -0.02 (96% CI, -0.06 to 0.01) for the upper-to-lower body segment ratio. Adverse events occurred in 71 of 74 patients (96%) in the infigratinib group and in 37 of 39 patients (95%) in the placebo group; serious adverse events occurred in 4 of 74 patients (5%) and 1 of 39 patients (3%), respectively. No serious adverse events or adverse events leading to treatment discontinuation were considered by the investigator to be related to infigratinib or placebo. CONCLUSIONS: In children with achondroplasia, treatment with once-daily oral infigratinib for 52 weeks resulted in a significantly greater increase from baseline in the annualized height velocity than placebo. (Funded by BridgeBio Pharma; PROPEL 3 ClinicalTrials.gov number, NCT06164951; EudraCT number, 2023-506130-67.).

Adolescent↗

PubMed2026

Hip Arthroscopy-Assisted Management of Pipkin Types I and II Femoral Head Fracture-Dislocations: Mid-Term Clinical and Radiographic Outcomes.

OBJECTIVES: Hip arthroscopy-assisted surgery has been proposed as a minimally invasive option for femoral head fractures; however, evidence with mid-term follow-up remains limited. This study aimed to evaluate the clinical and radiographic outcomes of arthroscopy-assisted management for Pipkin Types I and II femoral head fracture-dislocations with a minimum follow-up of 5 years. METHODS: This retrospective study included 23 consecutive adults (19 Pipkin I and 4 Pipkin II) treated with hip arthroscopy-assisted fragment excision or internal fixation between March 2013 and January 2020. Preoperative computed tomography was used for surgical planning, and fixation was placed with arthroscopic headless screws. Clinical outcomes were assessed using the Harris Hip Score (HHS) and Thompson-Epstein (T-E) criteria. Radiographic evaluation included avascular necrosis (AVN), heterotopic ossification (HO; Brooker), osteoarthritis (OA; Tönnis), and fracture reduction quality (Matta's criteria). Group comparisons were evaluated using independent samples t-tests, Mann-Whitney U tests, and Fisher's exact test. The mean follow-up was 86.2 ± 21.2 months. RESULTS: The cohort consisted of 19 males and 4 females with a mean age of 28.7 ± 9.9 years. Fifteen patients underwent fixation and eight underwent excision. The final mean HHS was 98.3 ± 1.9, with 21 patients (91%) achieving excellent and 2 (9%) good T-E criteria. There were no significant differences between the fixation and excision groups in demographic characteristics, operative time, or functional outcomes (all p > 0.05); however, hospital stay was significantly shorter in the excision group (2.9 ± 0.6 vs. 5.5 ± 4.6 days, p = 0.028). In the fixation group, mean maximal displacement improved from 7.6 mm preoperatively to 2.6 mm postoperatively, with anatomic reduction achieved in 6 cases (40%), imperfect in 6 (40%), and poor in 3 (20%). Patients with Pipkin Type I fractures had significantly higher HHS than those with Type II fractures (98.7 ± 1.7 vs. 96.0 ± 0.8, p = 0.018). Complications were rare, with one case of Brooker Grade I HO and one case of mild OA. No AVN or total hip arthroplasty occurred during the follow-up. CONCLUSIONS: Hip arthroscopy-assisted management of selected Pipkin Type I and II femoral head fractures yields excellent mid-term clinical outcomes with acceptable radiographic reduction and a low complication rate. This minimally invasive technique represents a viable alternative in appropriately selected patients when fragment characteristics and surgical expertise permit.

Humans↗

PubMed2026

Pharmacological therapies for the prevention of fractures in men.

RATIONALE: Pharmacological therapies for fracture prevention usually target osteoporosis, a skeletal disorder characterised by compromised bone mass or quality (or both). As most participants in osteoporosis trials are women, a review of pharmacological therapies for fracture prevention in men was warranted. OBJECTIVES: To determine the benefits and harms of bisphosphonates, parathyroid (PTH) or parathyroid-related protein (PTHrP) analogues, denosumab, and romosozumab therapy for the prevention of fractures in men. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and two trial registries (ClinicalTrials.gov and WHO ICTRP) until 14 October 2025, with no restrictions on date or language of publication. ELIGIBILITY CRITERIA: We included randomised controlled trials that compared bisphosphonates, PTH or PTHrP analogues, denosumab, or romosozumab (alone or with calcium or vitamin D, or both) with placebo, other drugs, or non-pharmacological therapies in men aged 50 years or older. Our primary comparison was bisphosphonates versus placebo. OUTCOMES: Critical outcomes were incidence of hip fractures, symptomatic vertebral fractures, other (not hip or vertebral) fractures, disability, participants with adverse events, study withdrawals due to adverse events, and participants with serious adverse events. Our primary time point was the final time point reported in the trials. RISK OF BIAS: We used Cochrane's RoB 2 tool to assess risk of bias. SYNTHESIS METHODS: We used a random-effects model for meta-analysis employing the Mantel-Haenszel approach, and the DerSimonian and Laird method to estimate between-trial variance. We assessed the certainty of evidence using GRADE. INCLUDED STUDIES: Seventeen trials (4132 participants) met our inclusion criteria. The average age of participants ranged from 52 to 73 years. Twelve trials used a placebo comparator versus bisphosphonate (7 trials, 2548 participants), PTH or PTHrP analogues (4 trials, 569 participants), denosumab (1 trial, 240 participants), and romosozumab (1 trial, 244 participants). For the other planned comparisons, a bisphosphonate was compared to vitamin D/vitamin D analogues (2 trials, 434 participants), to calcitonin (1 trial, 32 participants), to PTH or PTHrP analogues (1 trial, 19 participants), or to another bisphosphonate (1 trial, 301 participants), and one trial compared a bisphosphonate plus calcium to calcium tablets alone (46 participants). SYNTHESIS OF RESULTS: Placebo-controlled trials were largely susceptible to bias in selection of the reported result (83%), while most trials without a placebo control were also susceptible to bias arising from the randomisation process (100%) and in measurement of the outcome (80%). We are very uncertain about the effect of bisphosphonates on the incidence of hip fractures, symptomatic vertebral fractures, or other (non-hip non-vertebral) fractures compared to placebo at the final follow-up (up to two years). We downgraded the certainty of evidence once for risk of bias, twice for imprecision (very low event rates), and once for suspected publication bias. The certainty of evidence for incidence of other fractures was further downgraded for indirectness, as it was unclear if hip fractures were also included in the outcome. At up to two years, 2/875 participants (2 per 1000) in the bisphosphonate group reported hip fractures compared with 2/760 (3 per 1000) in the placebo group (risk ratio (RR) 0.73, 95% confidence interval (CI) 0.06 to 8.51; I² = 36%; 4 trials, 1635 participants); 5/1021 (4/1000) participants in the bisphosphonate group had a symptomatic vertebral fracture compared to 7/855 (8/1000) participants in the placebo group (RR 0.49, 95% CI 0.14 to 1.74; I² = 0%; 5 trials, 1876 participants); 25/1130 participants (16/1000) in the bisphosphonate group reported other (non-hip non-vertebral) fractures compared to 19/913 participants (21/1000) in the placebo group (RR 0.78, 95% CI 0.42 to 1.45; I² = 0%; 6 trials, 2043 participants). Bisphosphonates probably do not increase the risk of adverse events: 1024/1374 participants (746/1000) receiving bisphosphonates reported adverse events compared to 826/1174 participants (704/1000) receiving placebo (RR 1.06, 95% CI 0.93 to 1.19; I² = 75%; 7 trials, 2548 participants; moderate-certainty evidence) or serious adverse events: 329/1329 participants (272/1000) receiving bisphosphonate reported serious adverse events compared to 323/1128 participants (286/1000) receiving placebo (RR 0.95, 95% CI 0.84 to 1.08; I² = 0%; 6 trials, 2457 participants; moderate-certainty evidence). We downgraded the certainty of evidence once due to potential bias for adverse events and serious adverse events. We are very uncertain if bisphosphonates result in more withdrawals due to adverse events: 41/1374 participants (25/1000) in the bisphosphonate group withdrew due to adverse events compared with 43/1174 participants (37/1000) in the placebo group (RR 0.68, 95% CI 0.39 to 1.18; I² = 37%; 7 trials, 2548 participants; very low-certainty evidence). We downgraded the certainty of evidence once for risk of bias, once for indirectness, and once for imprecision. No trial reported disability. We are very uncertain about the effects of PTH or PTHrP analogues, denosumab, or romosozumab compared to placebo on fracture outcomes. We are very uncertain about the effects of PTH/PTHrP analogues on total adverse events, withdrawals due to adverse events, and serious adverse events. Denosumab may not increase the risk of adverse events or serious adverse events compared to placebo, while the evidence for withdrawals due to adverse events is very uncertain. Romosozumab probably does not increase the risk of adverse events and may not increase the risk of serious adverse events or result in more withdrawals due to adverse events. AUTHORS' CONCLUSIONS: We are very uncertain about the effects of bisphosphonates compared to placebo on the incidence of hip fractures, symptomatic vertebral fractures, or other (non-hip non-vertebral) fractures in men at up to two years of use. Bisphosphonates probably do not increase the risk of adverse events or serious adverse events, and we are very uncertain if they result in more withdrawals due to adverse events. We downgraded the certainty of evidence for indirectness, imprecision (low event rate), and serious risk of bias in selection of the reported result, as it was unclear if all studies fully reported every fracture. We found similar results for PTH or PTHrP analogues, denosumab, or romosozumab versus placebo. Larger, longer placebo-controlled studies are needed to determine whether pharmacological therapies are beneficial for reducing fractures in men. FUNDING: This Cochrane review had no dedicated funding. REGISTRATION: Protocol (2021): https://doi.org/10.1002/14651858.CD014707.

Humans↗

PubMed2026

Extent of resection as an independent predictor of survival for patients with glioblastoma as defined by the new WHO 2021 classification.

OBJECTIVE: Extent of resection (EOR) has previously been demonstrated to have an impact on survival in patients with glioblastoma (GBM). However, with the World Health Organization (WHO) 2021 reclassification of GBMs based on IDH-mutation status, patients with "IDH-mutant GBMs," who typically survive long term, were reclassified as WHO grade 4 IDH-mutant astrocytomas and removed from the GBM taxonomy. Therefore, it is unknown whether the previously reported impact of resection on survival was a false-positive result due to the inclusion of the less aggressive IDH-mutant tumors in previous datasets. This study aimed to determine the extent to which EOR remains an independent predictor of survival in patients with WHO 2021 GBM after the reclassification of IDH-mutant grade 4 astrocytomas. METHODS: All cases of GBM tumors (based on the pre-2021 GBM classification) that were newly diagnosed between 2005 and 2021 were identified in our institutional database and subsequently reclassified based on the updated WHO 2021 criteria using IDH status. Multivariable statistical analyses of demographic information, survival time, and EOR based on volumetric MRI were performed to determine the independent predictors of survival for the whole group of patients and for IDH-wildtype GBM patients exclusively. Additional analyses were performed to identify an EOR threshold for improvement in survival. RESULTS: Of the 523 tumors classified as GBM based on the pre-2021 taxonomy, 52 (9.9%) cases were reclassified as WHO grade 4 IDH-mutant astrocytomas, and the median survival of patients in this group was 7.9 years, whereas median survival of the IDH-wildtype GBM patients was 1.4 years. Multivariate analyses of the whole group demonstrated that IDH-mutant astrocytomas were associated with reduced hazard of death. In both the whole group (n = 523) and in IDH-wildtype GBMs (n = 471), higher EOR of the contrast-enhancing (CE) tumor was associated with reduced hazard of death, whereas older age or male sex was associated with increased hazard of death. Because most patients (90%) had high EOR values (> 81%), a statistically meaningful EOR threshold could not be established. CONCLUSIONS: These analyses demonstrated that EOR of the CE tumor is an independent predictor of survival and that greater EOR is associated with improved survival in WHO 2021 IDH-wildtype GBMs even after excluding grade 4 IDH-mutant astrocytomas. However, an absolute EOR threshold below which resection did not improve survival could not be established, raising concerns about prior cutoff assessments.

Humans↗

PubMed2026

Sustained effects of auricular point acupressure on chemotherapy-induced neuropathy: a randomized controlled trial follow-up study.

PURPOSE: Chemotherapy-induced neuropathy (CIN) is a persistent condition that impairs function and quality of life. Auricular point acupressure (APA) has shown short-term benefit for CIN, but the durability of these effects after treatment completion is unknown. This study evaluated the sustainability of symptom improvements for 3 months following a 4-week APA intervention. METHODS: This prespecified secondary analysis of a randomized wait-list controlled trial compared mobile-supported APA (mAPA) and virtual APA (vAPA) in adults with moderate or greater CIN who received APA during the initial treatment phase (mAPA, n = 80; vAPA, n = 75). Outcomes at 1, 2, and 3 months post-intervention were analyzed using generalized estimating equations with multiple imputation. The primary outcome was CIN severity, measured with an individualized composite outcome (ICO); the secondary outcome was CIN interference. RESULTS: Reductions in CIN severity and interference were maintained throughout follow-up in both groups (all p < .001). ICO scores decreased by 3.10, 3.36, and 3.61 points in mAPA and by 2.88, 2.90, and 3.21 points in vAPA at 1, 2, and 3 months, respectively. Benefits were maintained post-treatment, with higher retention in the mAPA group. CONCLUSIONS: Improvements in CIN severity and interference after APA were sustained for up to 3 months post-treatment, suggesting a durable benefit as a self-management strategy. Larger studies with longer follow-up and untreated comparison groups are needed. IMPLICATIONS FOR CANCER SURVIVORS: APA may offer survivors a durable, self-administered, nonpharmacologic option for managing CIN well beyond active treatment, without requiring ongoing clinical visits. TRIAL REGISTRATION: ClinicalTrials.gov, ID NCT04920097 registered on 3 June 2021.

Acupressure↗

PubMed2026

Comparing the efficacy of chlorhexidine and povidone-iodine for surgical site disinfection: a systematic review and meta-analysis from randomized controlled trials.

BACKGROUND: Randomized controlled trials report conflicting evidence on the efficacy of different skin disinfectants for preventing surgical site infection (SSI). METHODS: We systematically searched PubMed, Web of Science, Cochrane Library, and Embase for RCTs published up to February 2025 comparing preoperative skin disinfection with povidone-iodine (PVI) versus chlorhexidine (CH). Primary outcomes were overall, superficial, deep, and organ/space SSI rates. Secondary outcomes included hospital stay, readmission, and reoperation. RESULTS: CH was superior to PVI in preventing overall SSI (26 studies, n = 29,356; RR: 0.89; 95% confidence interval [CI]: 0.80 to 0.99). The overall SSI incidence rate in the CH group was 7.1% (1,045/14,677), compared with 7.8% (1,152/14,679) in the PVI group, equating to an 11% reduction in relative risk and a 0.7% reduction in absolute risk. The number needed to treat to prevent one SSI was 143. CH demonstrated superiority over PVI in preventing superficial SSI (13 studies, n = 16,867; RR: 0.77; 95% CI: 0.64 to 0.92), but not for deep SSI (11 studies, n = 15,842; RR: 1.00; 95% CI: 0.77 to 1.29) or organ SSI (9 studies, n = 9,471; RR: 1.17; 95% CI: 0.89 to 1.53). No significant differences were found in hospital stay, readmission, or reoperation rates between the two groups. CONCLUSION: CH demonstrates statistical superiority over PVI in preventing overall and superficial SSI, though the absolute clinical benefit is modest. No significant differences were observed for deep or organ/space SSI, nor for secondary outcomes including hospital length of stay, readmission, or reoperation rates.

Humans↗

PubMed2026

Effectiveness of transcranial direct current stimulation with and without positive mood induction on worry and transdiagnostic cognitive-emotional processes: A randomized controlled trial.

The present study investigated the effectiveness of transcranial direct current stimulation (tDCS), with and without positive mood induction, on worry and key transdiagnostic cognitive-emotional processes, including attentional bias, working memory, problem solving, and emotion regulation, in individuals with high levels of worry. This single-blind randomized controlled trial included 45 individuals with high levels of worry. After a structured clinical interview, participants were randomly assigned, with gender balancing, to one of three groups: (1) tDCS alone, (2) tDCS combined with positive mood induction, or (3) a sham control group. Outcome measures were administered at three time points (pretest, posttest, and one-month follow-up) and assessed attentional bias (Dot Probe Task), working memory (1-back task), problem solving (Tower of London task), emotion regulation (Gross's Emotion Regulation Questionnaire), and worry severity (Penn State Worry Questionnaire; PSWQ). Repeated-measures ANOVA showed that both active groups (tDCS alone and tDCS + positive mood induction) significantly improved attentional bias, worry, working memory, problem solving, and emotion regulation compared to controls (p < 0.05). The combined intervention produced significantly greater gains than tDCS alone in working memory, problem solving, emotion regulation (p < 0.05), and reductions in attentional bias and worry (p < 0.001). All effects persisted at one-month follow-up (p < 0.05). tDCS reduces worry and attentional bias and enhances cognition and emotion regulation in individuals with high levels of worry. The combined intervention produced larger and more sustained improvements than tDCS alone across the assessed behavioral outcomes. These findings support further investigation of combining tDCS with structured positive mood induction while the mechanisms underlying the additional benefits remain to be established.

Humans↗

PubMed2026

A Phase I Study Assessing the Safety, Tolerability, and Pharmacokinetics of Yinfenidone: A Novel, Potent Drug for Idiopathic Pulmonary Fibrosis Treatment in Healthy Chinese Subjects.

PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease with a median survival of only 2-3 years after diagnosis. Yinfenidone (HEC585) possesses the potential to inhibit the proliferation of pulmonary fibroblasts, making it a promising candidate for the treatment of IPF. This study assessed the safety, tolerability, pharmacokinetics, and metabolic profile of Yinfenidone hydrochloride capsule in healthy Chinese subjects. METHODS: This single-center, randomized, double-blind, placebo-controlled, single ascending-dose trial included seven dose groups(20, 50, 100, 200, 400, 600, and 800 mg). Each group enrolled8 healthy subjects: 6 received Yinfenidone hydrochloride capsules and 2 received matching placebo under fasting conditions. Serial pharmacokinetic (PK) blood samples were collected pre-dose and post-dose, liquid chromatography-tandem mass spectrometry was used to analyze the plasma concentrations of Yinfenidone. Additionally, metabolic biotransformation of Yinfenidone in plasma were conducted in the 100 mg dose group. Safety and tolerability endpoints were monitored via physical examinations, vital signs measurements, clinical laboratory tests, 12-lead electrocardiography (ECG), and adverse events (AEs) documentation throughout the trial. FINDINGS: Yinfenidone was rapidly absorbed, with a median maximum plasma concentration (Tmax) of 1.8-3.0 hours, and had a mean half-life (t1/2) ranging from 31.9 to 62.0 hours. Within the 20-100 mg dose range, systemic drug exposure generally increased with ascending dose, above 100 mg, exposure increased less than proportionally to dose. Metabolite profiling in the 100 mg group revealed that the parentcompound predominated in plasma, with metabolic pathways including mono-oxygenation and N-dealkylation. All reported AEswere mild, classified as Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 grade 1. No serious AEs observed; no subject discontinued the trial due to AEs. Single oral doses of 20-800 mg Yinfenidone hydrochloride capsules administered under fasting conditions demonstrated favorable safety and tolerability profiles in healthy Chinese subjects. IMPLICATIONS: Yinfenidone exhibited rapid absorption (median Tmax, 1.8-3.0 hours) and a long terminal t1/2 ranging from 31.9 to 62.0 hours in this single ascending-dose study, indicating that Yinfenidone can be taken once a day in subsequent clinical studies. Yinfenidone mainly exists in human plasma as the original drug and is metabolized through a variety of metabolic pathways. The AEs observed with Yinfenidone in this study, such as diarrhea, nausea, and dizziness, were similar to those reported with pirfenidone. Overall, Yinfenidone demonstrated a favorable safety and tolerability profile in this cohort of healthy subjects.

Adult↗

PubMed2026

Excess iodine induces lipid metabolic disorders by the gut microbiota SCFAs/H2S-p-AMPKα/PPARγ/SREBP-1c pathway in female rats.

With the development of living standards, the problem of excess iodine has long been overlooked. This study aimed to investigate the detrimental effects of long-term excess iodine exposure on lipid metabolism in female Sprague-Dawley rats from the gut-liver axis perspective, and to elucidate the underlying molecular mechanisms by which the gut microbiota and its metabolites mediate iodine-induced lipid metabolic disorders. The results indicated that abnormal iodine nutrition has a negative effect on the health of rats. Specifically, excess iodine not only causes thyroid disorders but also leads to liver lipid metabolism disorders, including elevated serum and hepatic total cholesterol/triglyceride levels and lipid accumulation in the liver. Further investigation revealed that excess iodine causes liver lipid metabolism disorders by altering the gut microbiota, which resulted in an increase in the relative abundance of Desulfovibrio and Lachnospiraceae NK4A136_group, and a decrease in the relative abundance of Akkermansia and Blautia in excess iodine groups. A decrease in the relative abundance of Blautia and an increase in Lachnospiraceae NK4A136_group were strongly correlated with reductions in short-chain fatty acids (acetic, propionic, and valeric acids), whereas an increase in Desulfovibrio was strongly correlated with an increase in H2S. Additionally, acetic acid was negatively correlated with H2S in serum and liver. Excess iodine reduced hepatic p-AMPKα expression while upregulating key regulators of lipid metabolism, including SREBP-1c, PPARγ and ACC1. These changes may represent one of the key mechanisms by which excess iodine induces lipid metabolism disorders through the microbiota-metabolite axis. Overall, these findings suggest that excess iodine influences lipid metabolism through the gut-liver axis. The results of this study provide scientific references and guidance for the appropriate intake of iodine and offer novel insights for early nutritional interventions targeting lipid metabolism disorders.

Journal Article↗

PubMed2026

A Qualitative Analysis of Cancer Survivors' Experience in a Time-Restricted Eating vs Control Clinical Trial to Address Cancer-Related Fatigue.

PURPOSE: To describe cancer survivors' lived experiences in a clinical trial that tested an individualized nutrition counseling with or without time-restricted eating to address cancer-related fatigue. METHODS: The Fatigue REDuction After cancer study was a two-arm, randomized controlled trial. Participants were adult cancer survivors who were 2 months to 2 years post-treatment. All participants received individualized nutrition counseling; those in the time-restricted eating group self-selected a consistent 10-hour eating window for 12 weeks. After the study, semi-structured exit interviews were conducted to gauge participants' experiences in the trial. Interviews were transcribed and two independent coders thematically analyzed the interviews using inductive and deductive coding. NVivo software was used for data organization and analysis. RESULTS: Participants (n = 24; TRE = 11; Control = 13) were 55 ± 13 years old, 75% were female, and they had a variety of cancer types. The majority of participants found that being in the study helped them to set and achieve lifestyle goals and would therefore recommend the study to others. Participants in the time-restricted eating group noted that time-restricted eating helped them set a better routine, providing a positive sense of control. However, some noted difficulty switching to a 14-hour fasting schedule, as it can interfere with their regular routine or employment schedules. Many participants noted they were happy that cancer-related fatigue was gaining more attention, hoping to find solutions for persistent cancer-related fatigue. CONCLUSION: The majority of participants found the study useful and, regardless of their group assignment or the intervention's impact on their fatigue, found the study helped them to gain better control of their dietary habits.

Humans↗

PubMed2026

Multiparametric flow cytometry immune profiling of pulmonary and extra-pulmonary tuberculosis reveals distinct blood-based biomarker signatures.

This study investigated immune cell distributions, cell-specific immune markers, and selected biomarker targets in pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) using multiparametric flow cytometry (MFC). Whole blood was collected from 45 individuals, including healthy controls (HC), EPTB, and PTB patients (n = 15/group). Peripheral blood leukocytes were analysed by MFC to characterize CD4+ and CD8+ T cells, natural killer (NK), invariant NKT (iNKT) and NKT cells, classical (CM), intermediate (IM) and non-classical monocytes (NCM), and activated monocytes (AM). Expression of GBP1, CALCOCO2, IFIT3, SNX10, ARG1, PD-1, and PD-L1 was assessed across these immune subsets. Increased frequencies of NK, NKT, and monocytes were observed in PTB and EPTB compared with HC, while CD4+, CD8+, iNKT, and AM were reduced. Monocyte-to-lymphocyte ratios were incrementally elevated in EPTB and PTB compared with HC. Despite variability of expression within groups, median biomarker fold-change expression changes were found between HC, EPTB and PTB groups; (i) (>2.0FC) for ARG1 in CD4, CD8, CM and AM, for CALCOCO2 in AM, GBP1 in CD8 and NCM, PD-1 in CD4, CD8, NK, IM and AM, PD-L1 in CD4, CD8, iNKT and NKT, NK, IM and AM and SNX10 in CD4, CD8, NCM, IM and AM (ii) (<2.0FC) in TB vs HC for CALCOCO2 in iNKT and NKT, IFIT3 in NCM, PD-1 in NK and NCM, PD-L1 in NCM, IM and AM and SNX10 in AM. Statistical significance was achieved for ARG1 (P = 0.017) in CD4 cells. Our findings highlight distinct immune cell and biomarker signatures in PTB and EPTB.

Humans↗