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PubMed2026

The efficacy of modified psychodynamic psychotherapy for patients with schizophrenia-spectrum disorders in Germany: a prospective, single-centre, assessor-blinded, parallel-group, randomised controlled trial.

BACKGROUND: People with schizophrenia-spectrum disorders have difficulties in interpersonal functioning that remain insufficiently addressed by standard care. Despite long-standing clinical use, psychodynamic psychotherapy has little empirical support compared with other psychosocial treatments for people with schizophrenia-spectrum disorders. We evaluated the efficacy of Modified Psychodynamic Psychotherapy for Schizophrenia (MPP-S), a manualised treatment tailored to the interpersonal vulnerability characteristic of this population, plus treatment as usual (TAU), compared with TAU alone. METHODS: This prospective, single-centre, assessor-blinded, parallel-group, randomised controlled trial was conducted at the Psychiatric University Hospital of the Charité at St Hedwig Hospital in Berlin, Germany. Participants were outpatients aged 18-64 years who were diagnosed with schizophrenia or schizoaffective disorder and exclusion criteria included organic brain disorder, somatic illness affecting cerebral function, and current or past alcohol or illicit drug misuse requiring addiction-specific treatment. Participants were randomly assigned 1:1 in blocks of ten to MPP-S (minimum 30 sessions) plus TAU or TAU alone. Outcome assessors were masked, but participants and therapists were not. The primary outcome was psychosocial functioning, measured using the Mini International Classification of Functioning, Disability and Health Rating for Limitations of Activities and Participation in Psychological Disorders (Mini-ICF-APP) and evaluated at baseline and prespecified post-treatment (24 months) and follow-up (36 months) assessments. Analyses followed the intention-to-treat principle. Linear mixed models were used to analyse incomplete longitudinal data under a missing-at-random assumption. People with lived experience were not formally involved in the design, conduct, or reporting of this study. This trial was preregistered at ClinicalTrials.gov (NCT02576613) and is complete. FINDINGS: From Oct 12, 2015, to Dec 7, 2021, 130 participants (57 [44%] female and 73 [56%] male) were randomly assigned to either MPP-S plus TAU (n=65) or TAU alone (n=64). One participant withdrew consent to data analysis. Regarding the primary outcome of psychosocial functioning, linear mixed models showed significant group-by-time interactions favouring the intervention: estimated marginal means indicated adjusted between-group differences in Mini-ICF-APP scores of -3·45 (95% CI -5·51 to -1·40; p=0·0011) at 24 months and -4·07 (-6·19 to -1·94; p=0·0002) at 36 months. The frequency of adverse events was similar between groups. There were three serious adverse events: two participants died by suicide (one in the MPP-S plus TAU group who did not start psychotherapy and one in the TAU alone group) and one participant in the MPP-S plus TAU group was admitted to a forensic hospital. INTERPRETATION: MPP-S added to TAU could improve psychosocial functioning compared with TAU alone. Our findings suggest efficacy and possible long-term benefits of psychodynamic psychotherapy for schizophrenia-spectrum disorders and indicate its potential role alongside other psychotherapeutic and psychosocial treatments. FUNDING: Berlin Institute of Health, Deutsche Gesellschaft für Psychoanalyse, Psychotherapie, Psychosomatik und Tiefenpsychologie, International Psychoanalytic University Berlin, and Köhler-Stiftung.

Humans↗
PubMed2026

A child and young person focused systematic review of scrotal ultrasound with Mitigants to identify missed torsion.

BACKGROUND: Diagnostic accuracy of ultrasound for adults is stated as excellent. Paediatric and adult acute scrotal diseases are different. Findings in adults may not apply in children. The authors have seen overconfidence and interpretation with adult disease in mind in children with scrotal pain and have seen testicular loss as a result. OBJECTIVES: To interrogate the literature methodologically to report diagnostic accuracy of ultrasound (US) for the acute scrotum specifically in CYP with a follow-up methodology which allows identification of missed torsion. STUDY DESIGN: We performed systematic review and meta-analysis of studies reporting true diagnostic accuracy of ultrasound for testicular torsion (TT). PubMed, MEDLINE, Scopus, and Web of Science databases were searched from platform start until September 2023 using MeSH terms with protocol as detailed on PROSPERO. Multiple author search was undertaken. Two authors extracted data for included studies. Study quality was reported through QUADAS-2 methodology. Surgical findings or 12 months follow up in non-operative cases would be the gold standard to identify late atrophy due to missed torsion. Studies with methodology to identify missed torsion outwith the initial consult were included for meta-analysis. RESULTS: A total of 6790 cases were reported from the 38 papers identified. Studies were often flawed with poor definition of outcomes and short follow-up duration. Meta-analysis of the 10 high-quality studies revealed pooled sensitivity and specificity of 0.93 and 0.99. Doppler US by trained individuals demonstrated excellent diagnostic accuracy. Nonetheless, on extrapolation of the data, especially where flow was preserved, 5.6% of torsions were missed. DISCUSSION/CONCLUSION: Our review confirms a high diagnostic accuracy of US for TT in CYP. However, a 5.6% missed torsion rate was found if flow alone was considered diagnostic. The authors suggest US should be used as an adjunct in ambiguous cases, ensuring that clinically obvious torsion goes to theatre immediately and is not delayed by ultrasound. TRIAL REGISTRATION: PROSPERO: CRD42023412619.

Humans↗
PubMed2026

Dual Transcranial Direct Current Stimulation Modulates Hierarchical Functional Network Organization in Post-Stroke Cognitive Impairment: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the clinical efficacy of dual transcranial direct current stimulation (tDCS) in patients with post-stroke cognitive impairment (PSCI) and to explore the effects on the hierarchical organization of functional brain networks, ranging from regional synchronization to inter-regional connectivity and global network topology. METHODS: In this randomized, double-blind, sham-controlled trial, 74 PSCI patients received conventional therapy alongside either active dual-tDCS (n&#x2009;=&#x2009;38) or sham stimulation (n&#x2009;=&#x2009;36). Active tDCS targeted the dorsolateral prefrontal cortex (DLPFC) via anodal-left/cathodal-right nodes (2.0&#x2009;mA, 20&#x2009;min/day, 20 sessions). The primary outcome was the Montreal Cognitive Assessment (MoCA). Secondary outcomes included the Mini-Mental Status Examination (MMSE), Stroop Test (ST), Trail Making Test (TMT), Wechsler Memory Scale (WMS), and Barthel Index (BI). A subgroup of 36 participants (18 per group) underwent resting-state functional magnetic resonance imaging (rs-fMRI) to analyze regional homogeneity (ReHo), functional connectivity (FC), and network topology. Partial correlations assessed the association between neuroimaging alterations and clinical improvements. RESULTS: The tDCS group showed significantly greater improvements in MoCA scores (tDCS: 5.74&#x2009;&#xb1;&#x2009;2.76 vs. sham: 2.69&#x2009;&#xb1;&#x2009;2.69; t&#x2009;=&#x2009;4.799, p&#x2009;<&#x2009;0.001) as well as in attention and memory domains compared to the sham group. The rs-fMRI changes included increased ReHo in the right middle temporal gyrus (MTG) and the left inferior frontal gyrus (IFG), and reduced FC between the right MTG-left superior frontal gyrus and left IFG-cerebellum (p&#x2009;<&#x2009;0.05, FWE-corrected). Additionally, small-worldness and global efficiency increased (p&#x2009;<&#x2009;0.05) with these alterations correlating with clinical recovery. Adverse events were rare and self-limiting. CONCLUSION: Dual-tDCS over bilateral DLPFC safely improves cognitive recovery in PSCI. These clinical gains are associated with rs-fMRI alterations, specifically in regional synchronization, inter-regional connectivity, and global topology, which suggest a potential biomarker for monitoring tDCS efficacy, offering a rationale for precision neuromodulation in stroke rehabilitation.

Humans↗
PubMed2026

Surgical management of esophageal atresia with tracheoesophageal fistula in extremely low birth weight neonates: A systematic review.

BACKGROUND: Surgical management of esophageal atresia/tracheoesophageal fistula (EA/TEF) in extremely low birth weight (ELBW) neonates remains challenging and controversial. This study systematically reviews surgical strategies and outcomes in this population. METHODS: Following PRISMA guidelines, Cochrane, Embase, MEDLINE, Scopus, and Web of Science (2004-2024) were searched in February 2025 for studies on surgical management of ELBW neonates with EA/TEF (PROSPERO CRD42025636228). Fatal chromosomal abnormalities were excluded. Demographics, comorbidities, surgical techniques, and complications were analyzed descriptively. Risk of bias was assessed. RESULTS: Eleven publications (five case reports and six case series) comprising 30 patients (Gross type B/C = 1/29) met the eligibility criteria. Mean gestational age was 28.1 (23-34) weeks, and mean birth weight was 760.4 (422-995) g. Twelve primary repairs (PR) and 18 delayed primary repairs (DPR) were performed, including staged repair (n = 11), lower esophageal banding (n = 4), and other techniques (n = 3). Postoperatively, four anastomotic leaks were managed conservatively, six strictures and one recurrent TEF required endoscopic intervention, three fundoplications and two aortopexies were reported (follow-up: 1-198 months, n = 19). Overall mortality was 30% (PR: 8.3%; DPR: 44.4%). Mortality was 60% among neonates with major congenital heart defects (CHD) and 40% among those with VACTERL association. EA/TEF-related complications contributed to 33.3% of deaths. CONCLUSIONS: Mortality in this cohort remains high, particularly with major CHD, and is largely unrelated to EA/TEF-specific complications. In selected cases, PR appears feasible as an alternative to DPR, although conclusions are limited by the small sample size and heterogeneous studies.

Humans↗
PubMed2025

The impact of the COVID-19 pandemic on osteoporotic fractures: a systematic review and meta-analysis.

BACKGROUND: Recent reports suggest that the COVID-19 pandemic and associated lockdowns may have influenced the epidemiology of osteoporotic fractures, but results vary across regions and fracture types. The aim of this study was to provide evidence-based insights into the impact of the pandemic on osteoporotic fracture incidence. METHODS: We searched four databases (PubMed, Embase, Cochrane Library, and Web of Science) up to August 2025 for observational or retrospective studies comparing osteoporotic fracture incidence during the COVID-19 pandemic (2020) with the pre-pandemic period (2019). The primary outcome of interest was the change in fracture incidence, analysed using risk ratios (RR) with 95% confidence intervals (CI) in Review Manager 5.4. Subgroup analyses were performed by sex, geographic region, and fracture type. RESULTS: Nine studies meeting the inclusion criteria were analysed. Overall, "all types" of osteoporotic fractures showed a significant decrease during the pandemic (RR = 0.85, 95% CI 0.80-0.91, p&#x2009;<&#x2009;0.0001). Specifically, forearm fractures decreased significantly (RR = 0.87, 95% CI 0.79-0.96, p&#x2009;=&#x2009;0.002). However, for the most clinically significant fractures, no statistically significant global change was found for hip fractures (RR = 0.93, 95% CI 0.76-1.15, p&#x2009;=&#x2009;0.14) or vertebral fractures (RR = 1.35, 95% CI 0.85-2.15, p&#x2009;=&#x2009;0.20). In regional subgroup analysis, hip fracture incidence decreased significantly in South America (RR = 0.79, p&#x2009;=&#x2009;0.0004) and in both males and females, but no significant change was observed in Europe (RR = 0.92, 95% CI 0.81-1.04, p&#x2009;=&#x2009;0.17). CONCLUSION: During the COVID-19 pandemic, there was a decrease in the incidence of minor fractures, such as those of the forearm, likely due to reduced outdoor activity. However, the incidence of major osteoporotic fractures (hip and vertebral) remained stable globally, with significant reductions observed only in specific regions like South America.

Humans↗
PubMed2026

Contact tracing for hepatitis C: perspectives of people with experience of substance use and hepatitis C on intervention acceptability.

INTRODUCTION: Chronic hepatitis C (HCV) is a major cause of cirrhosis and hepatocellular carcinoma. In the UK, the principal risk factor for HCV is injecting drug use. The introduction of direct acting anti-virals (DAA's) have transformed HCV care, with cure rates of over 95%. However, HCV is often asymptomatic, and reinfection is a concern. Modelling and real-life studies demonstrate the potential effectiveness of a contact tracing approach for finding people who have acquired HCV through injecting drug use. However, it is not used routinely in the UK. This qualitative study was undertaken to assess the acceptability of a contact tracing approach to identify people who have injected drugs with an index patient recently diagnosed with HCV. METHODS: Twelve people with lived or living experience of injecting drug use and an HCV diagnosis were interviewed using semi-structured interview topic guides. Participants were purposefully selected according to the inclusion criteria and to ensure there was an even spread of male and female participants. Sekhon's Theoretical Framework of Acceptability, incorporating seven components (affective attitude, burden, ethicality, intervention coherence, opportunity cost, perceived effectiveness, and self-efficacy) was used to analyse data from interview transcripts. RESULTS: A sample of 12 people who inject drugs in the UK indicated that a contact tracing approach was acceptable across two components of Sekhon's acceptability framework: affective attitude and ethicality. Participants broadly found the idea of tracing people who may be at risk of contracting HCV acceptable, and the approach aligned with their value systems. A contact tracing approach would help alleviate concerns about putting other people's lives at risk through HCV transmission and was seen as a 'sensible' way of finding people at risk. However, there were caveats to this acceptability. Contact tracing approaches delivered by mainstream health, or governmental organisations increased burden, opportunity costs and perceived effectiveness of a contact tracing approach for HCV, particularly within contexts of exclusion and criminalisation of people who inject drugs. Burden and opportunity costs were also affected by individual experiences and risks of violence, sexual violence and abuse. There was a lack of knowledge of contact tracing approaches amongst respondents, leading to a lack of intervention coherence and misunderstandings of what contact tracing was and how it would work. Trusted relationships with NGOs and HCV specialist nurses reduced burden and increased confidence and ability (self-efficacy) to engage with a contact tracing approach. CONCLUSION: People who inject drugs broadly perceive contact tracing as an acceptable method of finding people who are at risk of HCV. However, this acceptability is based on specific modes of delivery through trusted organisations. Findings further highlight the importance of naming and describing contact tracing approaches appropriately, as well as assessing and mitigating against potential risk to index patients, to increase self-efficacy and capacity to engage. Considering these findings, the potential for expanding existing contact tracing approaches should be explored to ensure the UK reaches and maintains its elimination targets.

Humans↗
PubMed2026

Efficacy and safety of thulium fiber laser versus conventional holmium:YAG laser in anatomical endoscopic enucleation of the prostate: a systematic review and pairwise meta-analysis.

PURPOSE: Anatomical endoscopic enucleation is an established treatment for benign prostatic obstruction. Whether thulium fiber laser enucleation (ThuFLEP) improves outcomes over conventional holmium:YAG laser enucleation (HoLEP) remains uncertain. We compared the efficacy and safety of ThuFLEP versus non-MOSES-modulated HoLEP. METHODS: We performed a PRISMA-compliant systematic review and pairwise meta-analysis of randomised and comparative cohort studies comparing ThuFLEP and conventional HoLEP in adult men. Six databases were searched. Outcomes included International Prostate Symptom Score (IPSS), IPSS quality-of-life score, maximum urinary flow rate (Qmax), post-void residual volume, hospital stay, and complications. Risk of bias and certainty of evidence were assessed with RoB 2/ROBINS-I and GRADE. RESULTS: Seven non-overlapping comparative populations in eight publications included 3,509 patients. ThuFLEP was associated with a small statistically significant reduction in IPSS at 3&#xa0;months (mean difference [MD] -1.04 points, 95% confidence interval [CI] -1.81 to -0.28) of uncertain clinical relevance. Qmax differences were small and directionally inconsistent across follow-up (favouring HoLEP at 3&#xa0;months and ThuFLEP at 6 and 12&#xa0;months) and derived mainly from retrospective cohorts, with neutral randomised subgroups. Stress and urge urinary incontinence were less frequent overall (RR 0.75, 95% CI 0.58 to 0.96, and RR 0.39, 95% CI 0.22 to 0.68), but both estimates depended on one large registry cohort and were not robust to its exclusion. Most other complications and hospital stay showed no clear between-group difference. Limitations include few studies per outcome, heterogeneity, sparse safety events, inconsistent prostate-specific antigen reporting, and mostly low/very low certainty evidence. CONCLUSION: ThuFLEP and conventional HoLEP are clinically comparable with no definitive superiority of either laser. Platform selection should be individualised according to surgeon expertise, institutional resources, and patient characteristics. Future trials should standardise cost-effectiveness outcomes and investigate whether the distinct laser-tissue interactions impact adenoma clearance, PSA reduction, enucleation completeness, and long-term durability.

Humans↗
PubMed2026

Application of SPI-guided analgesia in laparoscopic gynecologic surgery: a randomized controlled trial evaluating the remifentanil-sparing effect and predictive value of time-weighted SPI.

This study aimed to achieve two primary objectives: (1) to evaluate the opioid-sparing effect of Surgical Pleth Index (SPI)-directed analgesia during surgery via a randomized controlled trial (RCT), and (2) to propose and preliminarily assess a novel dynamic metric, Threshold-based Time-Weighted SPI (Tb-TW-SPI), which integrates stimulus intensity and duration, for its predictive efficacy regarding postoperative moderate-to-severe pain. Employing an RCT combined with exploratory analysis, 61 patients undergoing elective laparoscopic gynecologic surgery were randomized into an SPI-directed analgesia group or a conventional analgesia group. The primary outcome was total intraoperative remifentanil consumption. Postoperatively, an exploratory analysis of the control group data evaluated the correlation between Tb-TW-SPI and Numeric Rating Scale (NRS) pain scores in the post-anesthesia care unit (PACU), calculating its predictive value for moderate-to-severe pain (NRS&#x2009;&#x2265;&#x2009;4). Results: The SPI-directed group required significantly less intraoperative remifentanil than the conventional group [median (IQR): 5.84(5.02,6.62)vs. 6.96(5.81,8.19)&#xb5;g/kg/h; P&#x2009;=&#x2009;0.016]. Postoperative pain scores did not differ significantly between groups (P&#x2009;>&#x2009;0.05). Exploratory analysis of the conventional analgesia group revealed that Tb-TW-SPI values were significantly higher in patients with moderate-to-severe postoperative pain (NRS&#x2009;&#x2265;&#x2009;4) compared to those without (P&#x2009;=&#x2009;0.0417).The area under the ROC curve for Tb-TW-SPI predicting this pain was 0.74 (95% CI: 0.52-0.96), with 67% sensitivity and 76% specificity at an optimal cutoff of 1210. This RCT suggests that SPI-directed analgesia can safely and moderately reduce intraoperative remifentanil consumption. Furthermore, the proposed Tb-TW-SPI metric, in this exploratory analysis, suggests potential for predicting postoperative pain, though this finding requires validation in larger cohorts with higher-frequency SPI sampling, offering a new direction for SPI interpretation. Large-scale, multicenter trials are warranted to validate the predictive utility of Tb-TW-SPI. Clinical Trial Registration, China Clinical Trial Registry: ChiCTR2400088444.

Humans↗
PubMed2026

Surgical management and outcomes of total colonic aganglionosis in children: A systematic review and meta-analysis.

AIM: Total colonic aganglionosis (TCA) is a rare form of Hirschsprung disease, and there is no consensus regarding its optimal surgical management. This systematic review and meta-analysis aimed to evaluate different surgical approaches and outcomes in children with TCA. METHODS: A systematic search of PubMed/MEDLINE and Embase was performed for studies published between January 2000 and December 2025. The review followed PRISMA guidelines and was prospectively registered in PROSPERO (CRD420251078401). Eligible studies included patients aged &#x2264;18 years with TCA who underwent conventional pull-through procedures (CPT; Duhamel, Soave, Swenson, Rehbein, and Ikeda-Soper) or non-conventional techniques (NCPT; STATE procedure, J-pouch, right- or left-sided colonic patch pull-through, and ileocecal patch). A subgroup analysis comparing Duhamel and ileoanal pull-through procedures (IAPT) was also performed. Outcomes included fecal incontinence, Hirschsprung-associated enterocolitis (HAEC), requirement for additional interventions, postoperative intestinal obstruction, and mortality. Meta-analysis was performed using jamovi software, version 2.3.28, with p < 0.05 considered statistically significant. RESULTS: Seven studies including 134 patients compared CPT (n = 85) with NCPT (n = 49), and ten studies including 274 patients compared Duhamel (n = 143) with IAPT (n = 131). Across both comparisons, pooled odds ratios (ORs) showed no statistically significant differences in fecal incontinence, HAEC, requirement for additional interventions, postoperative intestinal obstruction (Duhamel vs IAPT only), or mortality. For CPT versus NCPT, the pooled ORs were 1.1 for fecal incontinence (95% CI, 0.44-2.73; p = 0.837), 1.1 for HAEC (95% CI, 0.49-2.71; p = 0.743), 4.3 for requirement for additional interventions (95% CI, 0.86-22.1; p = 0.074), and 3.4 for mortality (95% CI, 0.52-21.5; p = 0.198). For Duhamel versus IAPT, the pooled ORs were 1.4 for fecal incontinence (95% CI, 0.60-3.36; p = 0.423), 0.6 for HAEC (95% CI, 0.22-2.06; p = 0.503), 1.8 for requirement for additional interventions (95% CI, 0.62-5.50; p = 0.262), 1.1 for postoperative intestinal obstruction (95% CI, 0.21-6.01; p = 0.875), and 1.03 for mortality (95% CI, 0.25-4.20; p = 0.965). CONCLUSION: No statistically significant differences were identified between CPT and NCPT or between Duhamel and IAPT for the evaluated outcomes in children with TCA. However, the absence of statistically significant differences should not be interpreted as evidence of equivalence, particularly given the small sample sizes, wide confidence intervals, and clinical and methodological heterogeneity of the studies included. The choice of surgical approach should be individualized according to disease extent, patient-specific factors, institutional experience, and surgical expertise. TYPE OF STUDY: Meta-analysis. LEVEL OF EVIDENCE: III.

Humans↗
PubMed2026

Impact of PerioperAtive LidocAine Infusions on Enhanced Recovery After Noncardiac Surgery (IMPALA-ERAS) in an inpatient setting: rationale, design and protocol for a sequential, repeated crossover trial.

INTRODUCTION: Multimodal analgesic strategies designed to minimise perioperative opioid exposure are fundamental components of enhanced recovery after surgery (ERAS) pathways. Despite widespread implementation of ERAS protocols, the optimal analgesic regimen remains undefined, as the individual contributions of specific agents to overall analgesic efficacy and opioid-sparing effects are not fully elucidated. Intravenous lidocaine, a widely utilised local anaesthetic, possesses both analgesic and anti-inflammatory properties and has been associated with improved gastrointestinal recovery. This study seeks to pragmatically evaluate the impact of incorporating perioperative intravenous lidocaine infusion into established ERAS pathways on postoperative functional recovery. METHODS AND ANALYSIS: The Impact of PerioperAtive LidocAine Infusions (IMPALA) on ERAS trial is a single-centre, pragmatic, cluster-randomised, double-blinded, placebo-controlled study. A total of 2290 patients undergoing elective colorectal surgery, emergency general surgery, urology, ventral hernia repair, surgical oncology or spine surgery will be randomly assigned to receive either intraoperative and postoperative intravenous lidocaine infusions (administered for up to 48 hours) or placebo as part of a standardised multimodal analgesic regimen integrated into established ERAS pathways. The primary outcome is case mix index-adjusted resource length of stay, defined as the time interval from surgical initiation to hospital discharge adjusted for case mix index. The primary outcome is total inpatient opioid consumption within the first 72 hours, reported in oral morphine milligram equivalents. Secondary outcomes include various in-hospital clinical endpoints derived from the electronic health record. ETHICS AND DISSEMINATION: This protocol and accompanying statistical analysis plan outline the study design, primary and secondary endpoints and analytic methodology. The IMPALA-ERAS trial has received ethical approval from the Vanderbilt University Institutional Review Board (IRB: 250617). The findings will be disseminated via peer-reviewed publications and presentations at national conferences. Results from this trial are expected to inform evidence-based practices regarding perioperative lidocaine infusion and its potential contributions to enhanced postoperative recovery in surgical patients. TRIAL REGISTRATION NUMBER: NCT07224711.

Humans↗
PubMed2026

Beyond antigen matching: compatibility intelligence theory for transfusion as an emergent biological system.

BACKGROUND: Despite major advances in serologic testing, extended phenotyping, and blood group genomics, clinically similar transfusion exposures may result in markedly different immune and clinical outcomes. Existing compatibility strategies do not fully explain this biological variability. OBJECTIVES: To examine transfusion compatibility as an emergent donor-recipient biological state and propose a systems-level conceptual framework that integrates established biological determinants into a testable model for future precision transfusion medicine. METHODS: This narrative review critically synthesizes current evidence from blood group genomics, recipient immunobiology, inflammation, disease-specific biology, transfusion medicine, and computational prediction. The proposed framework distinguishes Compatibility Intelligence Theory (CIT) as a biological interpretation from Precision Transfusion Intelligence (PTI) as its potential clinician-supervised translational application. RESULTS: The review argues that transfusion compatibility is shaped by interactions among donor genetics, recipient immune biology, inflammatory physiology, disease context, transfusion history, and longitudinal adaptation rather than by antigen matching alone. CIT provides an organizational framework for integrating these determinants, whereas PTI describes a possible clinician-supervised translation. To address current feasibility, the revised framework separates variables into routinely measurable, contextually available but incompletely standardized, and research-stage domains, and proposes a staged strategy for deriving rather than assuming their quantitative weights. Any clinical implementation would require comparative validation against current serologic, phenotypic, and genotype-based practice. CONCLUSIONS: Compatibility Intelligence Theory offers a testable systems-level framework for understanding transfusion compatibility without replacing established transfusion practices. The framework is not presented as a ready-to-use score: currently measurable variables can be organized for structured risk review, whereas inflammatory, immunogenetic, and multi-omic inputs require prospective standardization and validation. If future studies demonstrate incremental predictive and patient-centered benefit, CIT-informed PTI could support an adaptive, evidence-based extension of current precision transfusion practice.

Humans↗
PubMed2026

Precision targeting of teacher burnout using network-informed ecological momentary interventions.

Teacher well-being affects classroom functioning and workforce stability, yet generic digital programs rarely use person-specific affect dynamics to select support. This cluster-randomised trial evaluated whether micro-interventions selected from high expected influence (EI) nodes in teachers' contemporaneous affect networks produced larger changes in burnout-related EI and everyday happiness than content-matched random allocation. The objectives were to estimate allocation effects on changes in estimated network summaries and happiness, evaluate network change as a statistical mediator, examine personality moderation, and benchmark simpler allocation rules. A two-arm cluster randomised platform trial was conducted in 84 public schools across four urban districts in H Province. After a 14&#xa0;day baseline of ecological momentary assessment (EMA), person specific partial correlation networks were estimated for happiness, exhaustion, detachment, efficacy and rumination. An optimisation engine prioritised three brief micro-intervention types per teacher according to baseline EI, while the active control received the same library without network information. EMA continued for 8&#xa0;weeks; Bayesian multilevel models, permutation-based mediation, and benchmarking analyses were applied. EI-based targeting produced larger reductions in the composite EI-change index than active control (mean difference 0.11, 95% credible interval 0.08 to 0.14) and higher week 7 EMA happiness (4.4 points on a 0 to 100 scale, 95% credible interval 2.7 to 6.0), with a positive arm by week slope difference of 0.62 points per week (95% credible interval 0.39 to 0.85). Model-based mediation estimates were consistent with approximately one half of the happiness difference being statistically associated with change in the composite EI-change index (average conditional mediation estimate 3.5 points, 95% credible interval 2.0 to 5.2). Benchmarking showed smaller gains under severity, threshold, or group-level centrality rules. Effects were stronger among teachers higher in conscientiousness. The findings indicate that integrating EMA, network modelling, and EI-driven optimisation yields measurable gains beyond content-matched exposure, providing a proof of concept for district-scale precision mental health that requires prospective implementation testing. Replication in additional regions, expanded node sets, and longer follow up are warranted to assess durability and generalisability.

Female↗
PubMed2026

Genome-wide identification and expression profiling of HSD3B and SDR42E1 genes in the Pacific oyster (Crassostrea gigas): potential associations with gonadal development.

Sex steroids are lipid-soluble signaling molecules that regulate sex differentiation, reproductive development and physiological homeostasis in animals. 3&#x3b2;-Hydroxysteroid dehydrogenase/&#x394;5-&#x394;4 isomerase (3&#x3b2;-HSD) is a key steroidogenic enzyme, whereas SDR42E1, an extended short-chain dehydrogenase/reductase, has been implicated in sterol- and steroid-related metabolism. However, the composition, evolutionary relationships and expression patterns of the HSD3B- and SDR42E1-related genes in bivalve gonadal development remain poorly characterized. In this study, five PF01073-containing genes, comprising three CgHsd3b and two CgSdr42e1 genes, were identified in the Pacific oyster Crassostrea gigas. Phylogenetic analysis separated the proteins into HSD3B-related and SDR42E1-related groups, and gene-structure and motif analyses indicated subfamily-level divergence. All five proteins retained the SDR domain but differed in exon-intron structure and motif composition. Each contained the extended-SDR TGxxGxxG motif, whereas exact classical [ST]GxxxGxG and NNAG motifs were absent. Tyr- and Lys-equivalent residues were conserved, while the HSD3B1 Ser-equivalent position contained Thr in two C. gigas proteins and Ser in one. These features support their classification as extended-SDR proteins but do not establish enzymatic activity or substrate specificity. The three CgHsd3b genes were dispersed on one chromosome, whereas CgSdr42e1-1 and CgSdr42e1-2 were adjacent on another chromosome, suggesting a possible local duplication event for the CgSdr42e1 pair. Public RNA-seq data showed distinct tissue- and gonadal-stage expression patterns, with several genes displaying gonad-biased or female-stage-associated expression. Independent RT-qPCR profiling of the representative genes CgHsd3b-3 and CgSdr42e1-1 detected stage-dependent expression, although tissue rankings differed from those in the public RNA-seq datasets. These differences may reflect the use of independent biological samples, tissue composition, normalization procedures, and platform-specific measurements. Because enzymatic assays, metabolite measurements, cellular localization, and functional perturbation were not performed, the results identify candidate genes whose expression is associated with gonadal development rather than demonstrating regulatory roles. This study provides a comparative framework for future functional investigation of sterol- and steroid-related metabolism in bivalves.

Animals↗
PubMed2026

Substance use and co-occurring mental health conditions among adolescents and young adults in North America: a systematic review.

BACKGROUND: Substance use and co-occurring mental health conditions are common among adolescents and young adults and represent an important clinical and public health concern in North America. Trauma exposure, psychiatric symptoms, and social adversity frequently co-occur with substance-related problems in this population. This systematic review aimed to synthesize evidence on prevalence patterns, associated clinical and psychosocial factors, and care-related implications described in the literature on adolescents and young adults with substance use and co-occurring mental health conditions. METHODS: This systematic review followed PRISMA guidelines and was preregistered in PROSPERO (CRD42024581685). A systematic search was conducted in MEDLINE (Ovid), Embase, PsycINFO, and Google Scholar. Eligible studies examined adolescents and young adults (&#x2264;&#x2009;25 years) in North America. A combination of subject headings, keywords, and synonyms for the concepts "adolescents," "young adults," "substance use disorders," and "co-occurring mental health conditions" was used. Of 1,882 records identified, 29 studies met the inclusion criteria. Given the heterogeneity of the literature, findings were synthesized narratively. RESULTS: The included studies showed heterogeneity in population, setting, denominator, and ascertainment method. Across the literature, depressive, anxiety-related, trauma-related, and externalizing mental health presentations were frequently reported alongside substance-related problems in adolescents and young adults. Trauma exposure, adverse childhood experiences, and broader social adversity were also commonly reported in association with substance-related problems across studies. Care-related implications were more limited and were largely derived as future directions mentioned across studies rather than direct evaluations of youth-specific service models. CONCLUSION: Co-occurring mental health and substance-related problems were frequently reported among adolescents and young adults in high-risk and service-engaged populations in North America. Trauma and social adversity were prominent across the reviewed literature, while direct evidence for evaluated, integrated, youth-specific care models remains limited. These findings support the relevance of developmentally appropriate, integrated, and trauma-informed approaches to care and highlight the need for further research directly evaluating improved service delivery models for this population. CLINICAL TRIAL NUMBER: Not applicable.

Humans↗
PubMed2026

Intravenous Ketamine reduces psychological pain in suicidal inpatients: A secondary analysis of a six-week randomized placebo-controlled trial.

BACKGROUND: Psychological pain has been conceptualized as an unbearable inner experience and a possible precondition for suicidal ideation. No randomized placebo-controlled study has specifically investigated psychological pain as a treatment target in psychiatric populations. We examined ketamine's effect on psychological pain in suicidal psychiatric inpatients. METHODS: This secondary analysis used KETIS, a 6-week randomized, double-blind, placebo-controlled trial. Participants received two 40-minute intravenous infusions of ketamine (0.5&#xa0;mg/kg) or placebo (0.9% saline) 24&#xa0;h apart, alongside usual care and medication. Psychological and physical pain were assessed at baseline, repeatedly during 96&#xa0;h, and at weeks 2, 4, and 6 using the self-rated PPP-VAS. Longitudinal mixed models compared pain trajectories. RESULTS: The trial randomized suicidal inpatients to ketamine (n&#xa0;=&#xa0;73) or placebo (n&#xa0;=&#xa0;83). Psychological pain decreased in both groups but was lower with ketamine during the first 96&#xa0;h. Pointwise scores were lower with ketamine from 40&#xa0;min to 96&#xa0;h, largest at 40&#xa0;min, 2&#xa0;h, 4&#xa0;h, and 24&#xa0;h (all p&#xa0;<&#xa0;0.001), but not at weeks 2, 4, or 6. This early difference remained significant after adjustment for depressive symptoms and hopelessness. The early reduction appeared more pronounced in the bipolar subgroup. No robust baseline predictors of outcome were identified. CONCLUSIONS: Intravenous ketamine was associated with a greater reduction in psychological pain than placebo in suicidal inpatients, with the clearest effects emerging within the first hours after treatment and remaining evident through the first 96&#xa0;h. Ketamine may represent a clinically relevant option as a psychological pain reliever in psychiatric patients.

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&#x202f;=&#x202f;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&#x202f;=&#x202f;0.017) in CD4 cells. Our findings highlight distinct immune cell and biomarker signatures in PTB and EPTB.

Humans↗
PubMed2026

Perspectives of participating neurologists and study nurses - Mixed-methods process evaluation of a web-based program for relapse management in multiple sclerosis (POWER@M2).

BACKGROUND: Relapsing-remitting multiple sclerosis is a chronic inflammatory disease of the central nervous system and the leading cause of disability in young adults. In Germany, 90% of relapses are treated with high-dose intravenous glucocorticoids, despite limited evidence for long-term benefit and international preference for oral administration. Time constraints often hinder informed decision-making. The multicentre Randomized Controlled Trial (RCT) POWER@MS2 (N&#x202f;=&#x202f;160, 2020-2023), conducted at 18 German MS-centres, aimed to promote self-determined relapse management through a complex intervention (dialogue-based decision aid, nurse-led webinar, online-chat). OBJECTIVE: While RCTs demonstrate effectiveness, process evaluations are essential to understand implementation, mechanisms of impact and contextual factors. This study explored healthcare professionals' experiences and attitudes toward implementing relapse self-management and self-medication in clinical practice. METHODS: A mixed-methods process evaluation followed the UK Medical Research Council- framework. Quantitative data were collected via validated questionnaires at up to three time points and analysed descriptively. Interview guides were developed based on these results. Qualitative data from neurologist and study nurse interviews were thematically analysed. Results were triangulated using a joint display. RESULTS: Data were collected from 55 neurologists and 17 study nurses (quantitative) and from 7 neurologists and 4 nurses (qualitative) (2020-2024). Most neurologists opposed routine steroid use, reserving it for severe relapses. Some voiced concerns about self-management, but informed patients were generally viewed as capable of safe self-medication. Study nurses gave mixed feedback on the intervention, citing overload and improved guidance. CONCLUSION: Clinicians showed openness toward implementing the intervention. Enhancing accessibility and addressing specific concerns may support broader adoption.

Humans↗
PubMed2026

Early mobilization within 24 to 48&#xa0;h improves postoperative clinical outcomes in older adults with hip fracture: A systematic review and meta-analysis.

BACKGROUND: Hip fracture is a major public health concern among older adults, often resulting in prolonged disability, institutionalization, and increased healthcare burden. Early mobilization has been widely recommended to enhance postoperative recovery; however, there is a lack of consolidated evidence quantifying its impact on clinical and functional outcomes. This study aimed to synthesize and evaluate the impact of early mobilization following hip fracture surgery in older adults and to explore potential sources of heterogeneity to better inform clinical and nursing practice. METHODS: A comprehensive literature search was conducted across seven databases (PubMed, Embase, Scopus, Web of Science, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, and Emcare) from inception to June 15, 2025. Eligible studies included randomized controlled trials and observational cohort studies comparing early mobilization (defined as ambulation within 24 to 48&#xa0;h postoperatively) to delayed or usual mobilization in patients undergoing hip fracture surgery. Primary outcomes included mortality, discharge destination, and length of hospital stay. Secondary outcomes included postoperative complications, functional recovery, and readmission. Risk of bias was assessed using funnel plots and Egger's test. RESULTS: Twenty-six studies involving 297,435 patients were included. Compared with delayed mobilization, early mobilization significantly reduced 30-day mortality (relative risk&#xa0;=&#xa0;0.40, 95% confidence interval: 0.25-0.64) and 1-year mortality (relative risk&#xa0;=&#xa0;0.57, 95% confidence interval: 0.40-0.80) (both p&#xa0;<&#xa0;0.05). In regional analyses of pooled mortality, similar reductions were observed across Asia-Pacific, North America, and Europe. Patients receiving early mobilization were more likely to be discharged home and had shorter hospital stays. Early mobilization also resulted in a reduced risk of postoperative complications (relative risk&#xa0;=&#xa0;0.79, 95% confidence interval: 0.74-0.84, p&#xa0;<&#xa0;0.05), with specific improvements in pneumonia and thromboembolism rates. Functional independence was significantly improved, as shown by higher Barthel Index scores and increased odds of achieving Functional Independence Measure &#x2265;5 at discharge. No significant difference was observed in readmission rates. CONCLUSIONS: lization within 24 to 48&#xa0;h following hip fracture surgery was associated with favorable outcomes, including reduced mortality, improved functional independence, higher rates of discharge to home, shorter hospital length of stay, and fewer postoperative complications. Although heterogeneity across studies and the predominance of observational evidence warrant cautious interpretation, these findings support current recommendations for early mobilization and highight the potential value of structured and standardized mobilization protocols in routine postoperative hip fracture care.

Humans↗