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PubMed2026

Diagnosis, treatment and monitoring of pediatric Behçet's disease: Systematic literature review informing the ISSAID/PRES recommendations.

BACKGROUND: Pediatric-onset Behçet's disease (BD) accounts for up to 20% of cases and represents a distinct clinical entity characterized by evolving phenotypes and age-specific patterns of organ involvement. This systematic literature review synthesizes current evidence on pediatric BD, informing forthcoming recommendations by the International Society of Systemic Auto-Inflammatory Diseases (ISSAID) and the Pediatric Rheumatology European Society (PReS). METHODS: A systematic search was conducted according to PRISMA guidelines. Observational studies reporting clinical features, diagnostic criteria, management strategies, and outcomes in BD patients diagnosed before the age of 16 years were included. Proportional meta-analysis was performed to give pooled estimates for organ system involvement. RESULTS: Fifty-two studies, encompassing 2929 patients, met inclusion criteria. Sex distribution was balanced, with a 1:1 male-to-female ratio. The age of onset differed, with 1 year old being the lowest median age of onset and 2 years the lowest median age of diagnosis. The pooled random-effects estimate demonstrated that 50% of patients were HLA-B51 positive (95% CI, 0.5-0.6). Mucocutaneous manifestations were nearly universal (97.8%) and frequently represented the initial feature (80.9%). Musculoskeletal (36%), ocular (35%), neurological (17.9%), gastrointestinal (20%), vascular (15.4%) manifestations showed substantial variability in prevalence. Therapeutic approaches varied widely and were extrapolated from adult practice, with treatment guided by organ involvement and severity. CONCLUSIONS: Pediatric BD encompasses a heterogeneous spectrum of phenotypes requiring harmonized diagnostic frameworks, structured phenotypic stratification, and standardized monitoring to improve long-term outcomes. The relative burden and combination of organ manifestations varied across cohorts, reflecting both biological heterogeneity and differences in study design.

Humans↗

PubMed2026

Effects of semaglutide and empagliflozin on markers of endothelial function in persons with type 2 diabetes: A post hoc analysis of a randomized clinical trial.

AIMS: The endothelium maintains vascular health by regulating blood flow and protecting against inflammatory damage. In type 2 diabetes (T2DM), however, hyperglycemia, hypertension, and hyperlipidemia place a significant burden on the endothelium, potentially leading to atherosclerosis and cardiovascular disease (CVD). While semaglutide and empagliflozin have been shown to reduce CVD risk in T2DM, it remains unclear whether these benefits are mediated by improved endothelial function. This post-hoc analysis explores the effects of these agents on markers of endothelial function, i.e. the reactive hyperaemic index (RHI) and the endothelial-derived cell adhesion molecules (CAMs) E-Selectin, ICAM-1, P-Selectin, and VCAM-1. METHODS: This was a post-hoc analysis of a 32-week randomized trial evaluating the separate and combined effects of semaglutide and empagliflozin on cardio-renal organ damage. One hundred and twenty participants with type 2 diabetes, age ≥ 50 were randomized to four groups (semaglutide, empagliflozin, the combination or placebo). An increase in RHI and/or a decrease in CAMs were considered beneficial. RESULTS: RHI increased compared to baseline (0.11, 95%CI [0.008;0.21], p = 0.03) but not compared to placebo in the semaglutide group (0.11, 95%CI [-0.04;0.24], p = 0.16). There was no effect on RHI in the empagliflozin group. Compared to placebo, E-Selectin decreased significantly in the semaglutide and combination groups (-9, 95%CI [-14.1;-5.1] p < 0.01 and - 9, 95%CI [-14.3; -5.2] p < 0.01, respectively). VCAM-1 increased in the same groups, compared to placebo (12.3, 95%CI[2.8;20.8] p = 0.01 and 16.2, 95%CI [7.2;24.3], p < 0.01, respectively).P-Selectin and ICAM-1 was not significantly affected in any of the groups, compared to placebo (p ≥ 0.11 and p ≥ 0.09, respectively). CONCLUSION: Semaglutide improved endothelial function compared to baseline, but not significantly versus placebo, which likely is due to limited power. CAM responses were heterogeneous, suggesting distinct roles in endothelial dysfunction and atherosclerosis. ClinicalTrialsRegister.eu: EudraCT 2019-000781-38.

Aged↗

PubMed2026

Structural and tissue-specific organisation of endocrine Fgf19 and Fgf21 signalling in rainbow trout.

Endocrine fibroblast growth factors (FGF19 subfamily) play a key role in regulating metabolic homeostasis in vertebrates. However, their functional diversification in salmonids remains poorly understood. In this study, we conducted an integrative characterisation of Fgf19 and Fgf21 signalling in rainbow trout (Oncorhynchus mykiss) by combining phylogenetic, structural and expression analyses. Phylogenetic analyses revealed the conservation of single fgf19 and fgf21 genes, despite the extensive expansion of receptors post-Ss4R (salmonid-specific fourth-round whole genome duplication). Structural modelling and molecular dynamics simulations demonstrated the stable interactions of both ligands to multiple Fgfr isoforms, with receptor-specific energetic profiles and conserved core interaction residues. Tissue expression profiling revealed clear differences from mammalian models, such as predominant hepatic fgf19 expression and the absence of hepatic fgf21 under basal conditions. In addition, there were complex and tissue-dependent distributions of fgfr and klotho transcripts. These findings support a receptor-driven diversification model of endocrine Fgf signalling in salmonids, suggesting enhanced endocrine plasticity associated with the retention of receptors following post-genomic duplication. Taken together, our findings provide new insights into the structural and regulatory organisation of endocrine Fgf signalling, as well as its potential role in metabolic regulation in rainbow trout.

Animals↗

PubMed2026

Efficacy and Safety of iGlarLixi Versus IDegAsp by Baseline Age, Disease Duration and HbA1c in Chinese People With Type 2 Diabetes: Post Hoc Analyses of the Soli-D Study.

AIMS: To compare the efficacy and safety of insulin glargine 100 U/mL plus lixisenatide (iGlarLixi) with insulin degludec plus insulin aspart (IDegAsp) by baseline age, Type 2 diabetes (T2D) duration and glycated haemoglobin (HbA1c) in the Soli-D study. MATERIALS AND METHODS: In Soli-D, Chinese adults with T2D suboptimally controlled on oral antidiabetic drugs (OADs) were randomized to iGlarLixi or IDegAsp for 24 weeks. These post hoc analyses evaluated glycaemic efficacy, insulin dose, body weight and hypoglycaemia outcomes in subgroups defined by baseline age (< 65, ≥ 65 years), T2D duration (< 10, ≥ 10 years) and HbA1c (≥ 7% to ≤ 8% [≥ 53 to ≤ 64 mmol/mol], > 8% to ≤ 9% [> 64 to ≤ 75 mmol/mol], > 9% [> 75 mmol/mol]). RESULTS: Among 582 participants (iGlarLixi n = 291; IDegAsp n = 291), baseline age was < 65 years in 442 and ≥ 65 years in 140; T2D duration was < 10 years in 366 and ≥ 10 years in 216; and HbA1c was ≥ 7% to ≤ 8% in 205, > 8% to ≤ 9% in 209 and > 9% in 168. At Week 24, HbA1c reductions were greater with iGlarLixi versus IDegAsp, with no treatment-by-subgroup interactions for baseline age, T2D duration or HbA1c. Change in other glycaemic outcomes, insulin dose and body weight generally showed no interaction across subgroups. Total insulin daily doses during treatment and hypoglycaemia event rates were consistently lower with iGlarLixi versus IDegAsp in all subgroups. CONCLUSIONS: iGlarLixi provides improved glycaemic control at lower insulin doses with reduced risk of hypoglycaemia in Chinese adults with suboptimally controlled T2D on OADs, regardless of baseline age, disease duration or HbA1c.

Humans↗

PubMed2026

Efficacy and Hypoglycaemia Outcomes With Once-Weekly IcoSema Versus Comparators in Individuals With Type 2 Diabetes by Kidney and Liver Function: A Post Hoc Analysis of the COMBINE 1-3 Trials.

AIMS: This post hoc analysis of COMBINE 1-3 assessed efficacy and hypoglycaemia outcomes with IcoSema (once-weekly combination therapy of basal insulin icodec and semaglutide [a glucagon-like peptide-1 analogue]) versus comparators in adults with type 2 diabetes (T2D) by kidney and liver function subgroups. MATERIALS AND METHODS: Treatment outcomes were analysed by trial according to kidney (estimated glomerular filtration rate ≥ 90; 60-< 90; 30-< 60; < 30 mL/min/1.73 m2) and liver (total bilirubin ≤ 21 μmol/L or aspartate aminotransferase [AST] ≤ 31/≤ 37 [female/male] U/L; total bilirubin > 21 μmol/L or AST > 31/> 37 [female/male] U/L) function subgroups. RESULTS: In COMBINE 1-3, across kidney and liver function subgroups, there were no statistically significant treatment by subgroup interactions for change in glycated haemoglobin (HbA1c) (baseline to week 52), change in body weight (baseline to week 52) or rates of combined clinically significant or severe hypoglycaemia (not assessed by kidney function for COMBINE 2) (all p > 0.05). There were statistically significant treatment by kidney function subgroup interactions for the achievement of HbA1c < 7.0% without weight gain and without clinically significant or severe hypoglycaemia in COMBINE 3 (p < 0.05) but not COMBINE 1 or 2, and statistically significant treatment by liver function subgroup interactions in COMBINE 1 (p < 0.05) but not COMBINE 2 or 3. For COMBINE 1 and 3, there were statistically significant treatment by kidney function subgroup interactions for mean weekly total insulin dose, but not statistically significant treatment by liver function subgroup interactions. CONCLUSIONS: Efficacy and hypoglycaemia outcomes with IcoSema versus comparators were generally consistent among adults with T2D with mild to moderate kidney impairment or impaired liver function. TRIAL REGISTRATION: The COMBINE 1-3 trials were sponsored by Novo Nordisk and are registered with ClinicalTrials.gov (NCT05352815; NCT05259033; NCT05013229).

Humans↗

PubMed2026

Weight and metabolic changes in patients with schizophrenia treated with paliperidone palmitate 6-month formulation versus paliperidone palmitate 3-month formulation: a post-hoc analysis.

OBJECTIVE: To determine the effect that paliperidone palmitate 6-month long-acting injectable formulation (PP6M) had on metabolic parameters including body weight (BW), and blood lipid profiles, a post-hoc analysis was conducted to assess changes in BW from baseline to the end of study based on age, body mass index (BMI), and changes in blood lipid profiles during a 12-month, phase 3, double-blind (DB) clinical study. Long term effects of PP6M on BW and BMI were further explored during a 24-month extension study in which participants were treated exclusively with PP6M. METHOD: In the 12-month DB phase, participants were randomized to receive PP6M or paliperidone palmitate 3-month long-acting injectable formulation (PP3M). The mean change in BW and abnormal weight percent change from baseline were calculated at endpoint by age, gender, and BMI. Additionally, treatment-emergent shifts from baseline for the four key lipid parameters (fasting low density lipoprotein [LDL], fasting triglycerides [TG], fasting total cholesterol [TC], and fasting high density lipoprotein [HDL]) during DB were assessed. Following this study, participants were given the opportunity to transition to a 24-month extension study and be treated with PP6M. The mean change and percent change in BW, and the mean change in BMI from DB baseline to the end of the extension study (36 months total) were calculated. RESULTS: Participants who were treated with PP6M showed numerically less weight gain, BMI, waist circumference, and more weight decrease compared to PP3M group during 12-month DB phase, though the proportion of participants reporting an abnormal change (≥7% change) in BW did not significantly differ between PP3M and PP6M. The weight differences were more pronounced in the younger age group (18-25 years) and those who were overweight (BMI: 25 to <30 kg/m2. Numerical differences in favor of PP6M were found in fasting blood lipids (HDL, LDL, TG, and TC). The changes in BW and BMI over time remained consistent throughout the 24-month extension, favoring PP6M in each instance. CONCLUSIONS: This post-hoc analysis demonstrated that PP6M was comparable to PP3M in terms of metabolic parameters; however, it may have a beneficial effect on weight gain, especially in young patients. TRIAL REGISTRATION: Post-Hoc Analysis of Studies NCT03345342 and NCT04072575 (ClinicalTrials.gov). Significant outcomes The findings from this study have highlighted that participants who were treated with the 6-month long-acting injectable formulation of paliperidone exhibited less weight gain during treatment overall, and significantly less weight gain in adolescents and young adults. Importantly, this trend continued over the course of long-term treatment, regardless of age. Participants treated with the 6-month formulation also had fewer shifts in blood lipids outside of the normal range and had more favorable changes in body mass index and waist circumference. These results suggest that when considering metabolic dysregulation as a factor in choosing a long-acting injectable antipsychotic, the 6-month formulation is a viable alternative to the 3-month formulation, particularly in younger patients with schizophrenia. Limitations Because this is a post hoc analysis and the study was not powered to test weight and metabolic changes, most endpoints were summarized descriptively and the statistical test was limited to the main endpoint (abnormal percent weight gain and loss).

Adult↗

PubMed2026

King's Mill anterior-posterior and transverse versus paracervical block in operative outpatient hysteroscopy: a randomised trial.

BACKGROUND: Pain control during operative outpatient hysteroscopy remains a clinical challenge, with the paracervical block (PCB) showing inconsistent efficacy. The King's Mill Anterior-Posterior and Transverse (KAPT) block targets the Lee-Frankenhauser plexus within the uterosacral ligament complex, where the highest density of uterine and cervical sensory fibres lies. We compared the KAPT block with the PCB in operative outpatient hysteroscopy. METHODS: Single-centre, participant- and outcome assessor-blinded randomised controlled trial in a UK district general hospital. Forty-eight women undergoing operative outpatient hysteroscopy were randomised 1:1 to the KAPT block or the PCB, each delivered with 10 ml of prilocaine. Pain was measured on a 10-point Visual Analogue Scale (VAS) during the procedure and 10 minutes post-procedure (co-primary endpoints), and during cervical dilatation (exploratory). Analyses used the Mann-Whitney U test on an intention-to-treat basis, with Hodges-Lehmann median differences, percentile bootstrap 95% confidence intervals, and a hierarchical fixed-sequence testing strategy. RESULTS: Median intra-procedural VAS was 1 (IQR 0 to 3) with the KAPT block versus 2 (IQR 1 to 6) with the PCB (Hodges-Lehmann median difference -1.00, 95% CI -3.00 to 0.00; p = 0.040). At 10 minutes post-procedure, median VAS was 0 (IQR 0 to 1.25) versus 2 (IQR 0 to 3.25) (median difference -1.00, 95% CI -2.00 to 0.00; p = 0.011). Both co-primary endpoints reached significance under hierarchical testing. Cervical dilatation pain did not differ significantly (p = 0.146). Satisfaction was 100% in both arms; willingness to recommend was 100% (KAPT) versus 95.8% (PCB). No serious adverse events occurred. CONCLUSIONS: The KAPT block was associated with lower intra-procedural and post-procedural pain than the PCB, with effect sizes consistent with a clinically meaningful difference. These findings support the KAPT block as a superior, anatomically targeted alternative to the PCB and justify evaluation in a larger multicentre trial.Trial registration: ISRCTN15619382.

Humans↗

PubMed2026

Effects of Digital Mental Health Screening Alone and With the Online MINDBODYSTRONG CBT-Based Program on Burnout, Depression, Anxiety, Healthy Behaviors, and Suicidal Ideation in at-Risk Nurses at 3- and 6-Months Post-Intervention: An RCT.

BACKGROUND: Burnout and mental distress among nurses are global public health epidemics that adversely affect nurse well-being and healthcare quality. Evidence-based, scalable mental health interventions are urgently needed. AIMS: To evaluate the 3- and 6-month outcomes of a randomized controlled trial (RCT) comparing a psychologically safe, digital mental health screening and referral program alone versus the same screening and referral program combined with the video-based online MINDBODYSTRONG (MBS) cognitive behavioral therapy (CBT)-based skills-building program among nurses at risk for mental distress. METHODS: 501 nurses were recruited from professional organizations and healthcare systems across the United States by email and randomized to either mental health screening and referral (standard care) or standard care plus the MBS cognitive behavioral skills-building intervention (the intervention). All study activities were conducted remotely. Follow-up surveys administered at 3- and 6-months assessed anxiety, depression, suicidal ideation, burnout, healthy lifestyle beliefs, and healthy lifestyle behaviors using valid and reliable scales. RESULTS: Compared with the screening and referral only group, participants in the intervention group had greater reductions in anxiety and depression and significantly greater increases in healthy lifestyle beliefs and behaviors at 3 and 6 months post-intervention. After controlling baseline risk, the intervention group had a lower risk of suicidal ideation than the screening and referral group at 3 months (relative risk ratio [RRR] = 0.717; 95% CI: 0.320-1.606) and 6 months (RRR = 0.329; 95% CI: 0.101-1.072). The intervention group also had a significantly lower risk of burnout at 6 months (RRR: 0.698, 95% CI: 0.528, 0.929, p = 0.012). Nurses who completed more MBS sessions had less suicidal ideation at 6 months and those who completed more MBS skills-building activities had less burnout at 3 and 6 months. LINKING ACTION TO EVIDENCE: Integrating psychologically safe mental health screening combined with the scalable online CBT-based intervention, MBS, can produce sustained improvements in burnout, mental health symptoms, including suicidality, and healthy lifestyle beliefs and behaviors among nurses experiencing mental distress.

Humans↗

PubMed2026

HSK21542 for Postoperative Analgesia in Gynecological Surgery: A Pooled Post-Hoc Analysis of Two Phase III Randomized Controlled Trials.

BACKGROUND: Effective postoperative pain management in gynecological surgery is challenging because of complex visceral-somatic pain interactions and the adverse effects of conventional analgesics. HSK21542, a novel peripherally restricted kappa-opioid receptor (KOR) agonist that selectively targets visceral pain pathways enriched with KORs, may provide adequate analgesia without systemic adverse events. METHODS: We conducted a pooled post-hoc analysis of data from two phase III, multicenter, triple-blinded, randomized controlled trials (Study 301, HSK21542 vs placebo; Study 303, HSK21542 vs tramadol vs placebo). Eligible patients undergoing elective gynecological surgery were included. The primary outcome was the summed pain-intensity difference over 12 and 24 hours (SPID 12h and SPID 24h ). Secondary outcomes were pain-relief quality (proportion of patients relieved from severe pain with a pain numerical rating score ≤ 3 between 0 and 24 hours) and rescue-analgesic requirements (number of doses and time to first rescue analgesic). Adverse events were also assessed. RESULTS: A total of 370 patients were analyzed: 150 received HSK21542, 139 received a placebo, and 81 received tramadol. After inverse probability of treatment weighting (IPTW) adjustment, baseline characteristics were well-balanced across treatment groups (all standardized mean differences [SMD] <0.1; see Table 1 for 95% CIs). HSK21542 produced greater reductions in pain intensity over 12 and 24 hours than placebo (least-squares mean differences -8.1 and -16.3 for SPID 12h and SPID 24h , respectively. Both P < .001) and no statistically significant difference was observed between HSK21542 and tramadol ( P > .05). Significantly more patients in the HSK21542 group were relieved from severe pain at 0 to 12 hours (92.7% vs 82.7%, P < .001) and required fewer rescue doses at 0 to 12 hours (0.00 [IQR 0.00-1.00] vs 1.00 [IQR 0.00-2.00], P < .001) and 0 to 24 hours (0.00 [IQR 0.00-1.00] vs 1.00 [IQR 0.00-2.00], P < .001) than those in the placebo group, whereas no significant differences with tramadol both in 0 to 12 and 0 to 24 hours. HSK21542 was also associated with significantly lower incidences of nausea (24.7% vs 66.7%) and vomiting (21.3% vs 60.5%) than tramadol. Only one case of dizziness occurred in the tramadol group. CONCLUSIONS: HSK21542 could provide adequate postoperative analgesia with few adverse events in patients undergoing gynecological surgery.

Humans↗

PubMed2026

Effect of adding umbilical cord blood derived stem cells to haploidentical stem cell transplant (haplo-cord) on post-transplant survival and graft-versus-host disease in patients with hematological malignancies: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Haploidentical stem cell transplantation (haplo-SCT) carries a substantial risk of graft-versus-host disease (GvHD), whereas umbilical cord blood (UCB) transplantation offers lower GvHD risk but slower engraftment. The haplo-cord approach combines both graft sources, aiming to mitigate GvHD while ensuring timely engraftment. This meta-analysis compares haplo-cord transplantation with haplo-SCT alone for the treatment of hematological malignancies. METHODS: Four electronic databases and two clinical trial registries were systematically searched. Effect sizes from eligible studies were pooled using odds ratios (ORs) for dichotomous outcomes and hazard ratios (HRs) for time-to-event outcomes. RESULTS: Twelve studies met the inclusion criteria. Haplo-cord was associated with a statistically significant reduction in chronic GvHD (OR = 0.62, 95%-CI: 0.42-0.93), while no significant difference was observed for grade II-IV acute GvHD (OR = 0.75, 95%-CI: 0.52-1.09). Survival outcomes favored haplo-cord, with lower HRs for overall survival (HR = 0.68, 95%-CI: 0.53-0.86) and event-free survival (HR = 0.61, 95%-CI: 0.52-0.72), while non-relapse mortality was not significant. Relapse at 3 years was significantly lower with haplo-cord (OR = 0.54, 95%-CI: 0.35-0.82). Haplo-cord also demonstrated higher day-30 engraftment, along with lower relapse-related and GvHD-related mortality, while CMV and EBV viremia showed no difference between groups. CD34 selection in the haplo graft significantly influenced effect sizes and heterogeneity in both subgroup analyses and meta-regression for acute GvHD. CONCLUSION: Haplo-cord transplantation improves GvHD outcomes, survival, and relapse risk compared with haplo-SCT alone. However, whether protocol optimization, possibly via CD34 selection, confers additional benefit remains uncertain and requires confirmation in future studies.

Humans↗

PubMed2026

Effectiveness of symptom map-based education in the management of premenstrual syndrome: a randomized controlled trial.

PURPOSE: To evaluate the effectiveness of a symptom map-based educational intervention for the non-pharmacological management of premenstrual syndrome (PMS), with a focus on symptom reduction among women with differing baseline symptom severity. METHODS: This randomized controlled study was conducted between May and December 2024. A total of 110 women meeting diagnostic criteria for PMS were randomly assigned to an intervention group (n = 55) or a control group (n = 55) using block randomization, and 101 participants completed follow-up assessments. The intervention comprised structured education based on a PMS symptom map and evidence-based self-care strategies. Outcomes included PMS symptom severity (Premenstrual Syndrome Scale), pain intensity (Visual Analog Scale), psychological symptoms (Depression Anxiety Stress Scale-21), and PMS-specific life satisfaction. CLINICAL TRIAL REGISTRATION: NCT06585475. RESULTS: Compared with the control group, women in the intervention group reported significantly lower pain (adjusted mean 4.21 vs. 6.81, p < .001) and stress levels (8.54 vs. 12.03, p < .001) at follow-up. The intervention was particularly effective in reducing PMS symptom severity and depressive symptoms among participants with higher baseline symptom burden. Improvements in PMS-specific life satisfaction were observed, with reductions in depressive symptoms contributing to this effect. CONCLUSION: A symptom map-based educational intervention is a clinically applicable, non-pharmacological approach for PMS management. This structured education appears especially beneficial for women with more severe baseline symptoms and may be integrated into routine gynecological care to support individualized symptom management.

Humans↗

PubMed2026

Mortality of Individuals With PRNP Variants Associated With Prion Disease in the United States, 1998-2024.

BACKGROUND AND OBJECTIVES: To characterize the survival of individuals with pathogenic PRNP variants-including to estimate annual hazards, to judge the accuracy of previously reported survival data, and to evaluate the utility of public record searches in determining vital status. METHODS: In this single-center cohort study, we gathered data on individuals who received positive antemortem PRNP genetic tests at the US National Prion Disease Pathology Surveillance Center (NPDPSC), including both diagnostic tests in symptomatic individuals, and predictive tests in asymptomatic individuals. Genetic test and autopsy results were queried from the NPDPSC database, and public record searches were conducted using online tools. RESULTS: Four hundred four individuals received positive genetic test results. Of 206 cases symptomatic at the time of genetic testing, 188 are likely now deceased based on typical disease duration for their genetic variants. Combined autopsy and public record searches in combination confirmed 174 of these deaths, for an estimated 92.6% sensitivity. We evaluated the age-dependent penetrance of the reportedly highly penetrance variants D178N and E200K and the reportedly low-penetrance variant V210I. Among 99 initially asymptomatic individuals with the pathogenic E200K variant, more than 936 person-years of follow-up, 18 deaths were observed, significantly fewer than 27.4 expected according to life tables based on retrospective data. The age-dependent penetrance of E200K calculated from these longitudinal data was significantly lower than that from retrospective data, with 69% penetrance by age 80 and a median age at death of 75. For the pathogenic D178N variant, the median age at death was 57, which was numerically later, but not significantly different from, that seen in retrospective data. For V210I, just 2 deaths occurred, both after age 90, consistent with minimal penetrance. DISCUSSION: Our data support high penetrance of PRNP D178N and E200K variants and low penetrance of V210I. For E200K, the age at onset distribution appears to be shifted slightly later, and lifetime risk slightly lower, than previously reported. Autopsy data and public death records in combination were sensitive and concordant for determining long-term outcomes, but additional prospective data should be gathered to support future preventive trials.

Journal Article↗

PubMed2026

Impact of early nurse-led implementation of an intensive care unit diary following major trauma on quality of life: The QUALITRAU randomized controlled trial.

BACKGROUND: Survivors of major trauma often experience long-term impairments in health-related quality of life (HRQoL) and post-traumatic stress disorder (PTSD). Intensive care unit (ICU) diaries have been proposed to reduce psychological sequelae, but evidence remains conflicting and not specific to trauma patients. OBJECTIVE: To assess whether, in patients with major trauma, a nurse-led ICU diary implemented within the first 48 h after trauma improves HRQoL at 1 year vs. usual care. METHODS: The QUALITRAU randomized controlled trial was conducted in three ICUs of a French tertiary hospital. Adult patients with major trauma (Injury Severity Score > 15) were randomized within 48 h of admission to receive either an ICU diary combined with usual care or usual care alone. The primary outcome was HRQoL at 12 months, assessed with the 4 domains of the WHOQOL-BREF questionnaire. Secondary outcomes included PTSD severity measured with the Impact of Event Scale (IES). Analyses were performed on an intention-to-treat basis. RESULTS: Between November 2014 and November 2016, 208 patients were randomized (101 intervention, 107 control), with primary outcome available for 121 (53 intervention, 68 control). Median age was 35 years [IQR 25-51], 81% were men, and 63% had severe traumatic brain injury. At 12 months, there were no differences between intervention and control groups in the WHOQOL-BREF domains (physical: 5.7 [IQR 4.6-11.4] vs 9.1 [IQR 4.6-13.1],P = 0.16; psychological: 8.0 [IQR 6.7-13.3] vs 11.3 [IQR 6.7-13.3],P = 0.08; social: 5.3 [IQR 4.0-14.7] vs 12.0 [IQR 4.0-14.7],P = 0.10; environment: 8.0 [IQR 5.5-14.5] vs 12.0 [IQR 5.5-15.5], P = 0.05). IES scores were also not different. CONCLUSIONS: Early implementation of nurse-led ICU diaries was not associated with improved long-term HRQoL or reduced PTSD symptoms in patients with major trauma. IMPLICATION FOR CLINICAL PRACTICE: These findings suggest that ICU diaries may need to be integrated into broader, multimodal rehabilitation strategies and may depend on factors such as timing, content, or patient characteristics.

Humans↗

PubMed2026

Psychedelic-induced hypomania and mania: a systematic review and meta-analysis.

Serotonergic psychedelics are increasingly investigated as treatments for affective disorders. Concerns persist regarding their potential to induce hypomania or mania, particularly in individuals with bipolar spectrum vulnerability. Whether these substances precipitate transient mood switches or contribute to persistent bipolar illness or diagnostic transition remains unclear. We conducted a systematic review of human studies examining manic or hypomanic symptoms following exposure to serotonergic psychedelics (psilocybin, LSD, mescaline, DMT/ayahuasca) or MDMA (CRD420251160656). Databases and trial registries were searched through January 26, 2026. Eligible designs included randomized and non-randomized clinical studies, registry-based cohorts, cross-sectional surveys, and longitudinal observational studies. Outcomes included dysphoria/euphoria, manic or hypomanic symptoms and transition to bipolar disorder. Risk of bias was assessed using ROBINS-I, ROB2 or NIH tools. Twenty-three studies met inclusion criteria, four contributing to meta-analysis. Rates of psychedelic-associated dysphoria/euphoria, hypomania or mania ranged from 5.8% in controlled trials of psilocybin-assisted psychotherapy for major depressive disorders to 30% in naturalistic studies of individuals with bipolar disorder. When present, manic symptoms were typically acute and self-limited. Observational studies identified higher risks among individuals with bipolar I disorder, familial vulnerability, polysubstance use, and unsupervised or illegal use. Registry-based cohorts examining diagnostic transitions showed a prevalence of subsequent transition to bipolar disorder of 4% (95% CI 2-8%; N = 7478; I² = 32.1%), with little evidence for a hallucinogen-specific signal. Overall, serotonergic psychedelics appear to pose a low but clinically meaningful relative risk of transient mood-related symptoms in susceptible individuals while remaining relatively safe in controlled clinical settings. Long-term outcomes and repeated exposure remain insufficiently studied, underscoring the need for rigorous longitudinal research.

Humans↗

PubMed2026

Silent crises in the COVID-19 pandemic shadow: a six-year medico-legal review of non-lethal intimate partner violence in Morocco.

Intimate partner violence (IPV) is a major global public health concern and one of the most prevalent forms of gender-based violence, with significant consequences. This study analyzes non-lethal IPV cases reported to a medico-legal unit of Casablanca between 2018 and 2023. Data from 4,784 female victims were reviewed, focusing on socio-demographics, violence types, perpetrator relationships, and judicial involvement across the pre-COVID, peak COVID-19, and post-COVID periods. Married women represented 59.2% of victims. Physical violence predominated (83.1%), while sexual violence was underreported (14.7%). The year 2020 marked a sharp increase in reported non-lethal IPV cases (n = 1,005), correlating with pandemic confinement. Among married women, judicial requisition (legal request for forensic examination) and medico-legal certification (medical documentation for judicial use) rates were high (81.5% and 81.0%, respectively). Post-pandemic years declined moderately but remained above pre-COVID levels. International comparison confirmed a global rise in IPV during COVID-19, with Morocco displaying comparatively higher rates of medico-legal documentation and judicial involvement. IPV in Morocco is entrenched and intensified by COVID-19. While the medico-legal system is robust in documentation, the system must evolve by integrating systematic psychological assessment into medico-legal evaluations, standardizing certification and referral protocols, and strengthening coordination between medico-legal, health, and social support services to improve victim protection.

Humans↗

PubMed2026

Divergent trajectories of genome architecture and chromosome evolution in ferns and angiosperms.

Ferns and angiosperms represent the two largest vascular plant lineages but exhibit striking genomic and ecological contrasts. We investigated whether differences in genome size, chromosome architecture, GC content, and stomatal traits reveal divergent evolutionary trajectories between these lineages. We assembled the most comprehensive dataset to date, integrating genome size, chromosome number and size, GC content, and stomatal traits for over 1100 fern species and compared it with an extensive angiosperm dataset. Ferns exhibited markedly lower variability and c. 16-fold slower rates of chromosome size evolution than angiosperms. A persistent positive relationship between genome size and chromosome number in ferns suggests limited cytological post-polyploid diploidization. While ferns generally possess larger stomata, this difference disappears after accounting for genome size, indicating that nucleotypic constraints, rather than lineage-specific physiology, dictate stomatal dimensions. Both groups share a unimodal GC-genome size relationship peaking at c. 14 Gbp. Larger fern chromosomes imply lower genome-wide recombination rates, potentially limiting genetic reshuffling and adaptive potential. Our results highlight fundamentally divergent evolutionary trajectories, likely shaped by meiotic symmetry in ferns and meiotic asymmetry, possibly centromere drive, and post-polyploid diploidization in angiosperms, defining the functional and genomic landscapes of these lineages across deep evolutionary timescales.

Genome, Plant↗

PubMed2026

RNA dysregulation as a determinant of aging and neurodegenerative vulnerability.

In the nervous system, aging causes deterioration of cellular and molecular processes that are associated with declines in cognition, sensory perception, and motor coordination. Aging is also the strongest risk factor for neurodegenerative disease, yet the mechanisms by which aging predisposes neurons to dysfunction remain incompletely understood. While genomic instability, proteostasis decline, mitochondrial dysfunction, and chronic inflammation have dominated prevailing models, recent evidence highlights RNA dysregulation as a central component of age-associated decline. In this review, we summarize recent findings suggesting that aging progressively erodes RNA regulatory fidelity through alterations in RNA-binding protein abundance, localization, biophysical behavior, and RNA interactions. We argue that age-dependent RNA dysregulation represents an important mechanism that converges with genetic risk to drive neuronal vulnerability and neurodegeneration.

RNA dysregulation↗

PubMed2026

Approaches to observational study designs and analytical options to evaluate the safety of multi-dose vaccines: a systematic review.

INTRODUCTION: Observational studies require careful considerations when evaluating the safety of multidose vaccines. We reviewed design and analytical approaches in observational studies evaluating the safety of multidose vaccines in the post-licensure phase. METHODS: EMBASE, MEDLINE, Web of Science, and Scopus (2018-2022) were searched for hypothesis-testing studies evaluating the safety of multidose vaccines. Key features from frequently used designs were extracted. RESULTS: Among 123 eligible studies, cohort (46%) and self-controlled case series (SCCS)/self-controlled risk interval (SCRI) (40%) followed by case-control (12%) were the most common designs, and 15% of studies used multiple designs. Among cohort studies evaluating multiple doses, vaccination date (36%) and cohort entry with time-updated exposure status (32%) were frequent approaches used to define time zero. Twenty-eight percent of cohort studies did not report time zero; all but one evaluated COVID-19 vaccine effect on post-delivery and fertility-related outcomes. For SCCS/SCRI, 64% of studies accounted for event-dependent exposures, mainly by including pre-exposure periods (53%) and modified SCCS model (48%), while 20% employed multiple correction strategies. Among studies using multiple designs, 68% reached consistent conclusions. CONCLUSIONS: SCCS/SCRI and cohort designs dominate multidose vaccine safety studies. Clear reporting on time zero in pregnancy and fertility-related cohort studies, and on addressing event-dependent exposures in SCCS/SCRI studies is needed, along with guidance on interpreting results from multiple designs.

Humans↗