With shorter window periods than serologic point-of-care (POC) tests and faster turnaround than laboratory-based nucleic acid tests (NAT), POC NATs could improve early detection of HIV. Furthermore, semiquantitative POC NAT may provide real-time monitoring for persons with HIV. There have been limited evaluations of POC NAT implementation in the United States. This paper describes the protocols and procedures used to evaluate the acceptability and feasibility of POC NAT implementation and test performance in clinical and community settings in Seattle, Washington. The Greater Access and Impact through POC NAT (GAIN) study was a Centers for Disease Control and Prevention-funded study that enrolled participants at a Ryan White-funded, hospital-based clinic (Madison Clinic) and a community site (Seattle's LGBTQ+ Center [the Center]). Persons seeking HIV testing, nonoccupational postexposure prophylaxis, or pre-exposure prophylaxis (PrEP) enrolled at either site received the standard of care plus the SAMBA II HIV-1 Qualitative Whole Blood Test (SAMBA Qual) and pooled laboratory HIV NAT, and persons with HIV enrolled at the Center received standard-of-care sexually transmitted infection testing plus the SAMBA II HIV-1 Semiquantitative Whole Blood Test (SAMBA Semi-Q) and laboratory viral load testing. Persons with HIV from Madison Clinic were recruited into a randomized clinical trial (RCT) to compare the clinical standard of care with the addition of the SAMBA Semi-Q (backed up by Food and Drug Administration-approved laboratory NAT). All participants completed a demographic survey during their study visit and contributed prospective data via electronic medical records. Subsets of participants from each group were invited to complete a postvisit acceptability survey and participate in an individual interview. Patient flow was observed at Madison Clinic to assess the impact of POC testing on clinic visit timing. From January 2022 to December 2024, 733 participants completed 753 GAIN research visits. Of those, 491 visits were completed by 489 participants seeking HIV testing and/or PrEP at the Center, and 61 visits were completed by 43 participants seeking HIV testing, nonoccupational postexposure prophylaxis, and/or PrEP at Madison Clinic. Test result data will assess test performance, with analyses anticipated in 2027. Seven people with HIV were enrolled at the Center, and 194 people with HIV were enrolled in the Madison Clinic RCT. Data from patients with HIV at Madison Clinic will be used to conduct a survival analysis evaluating the impact of POC NAT on time to viral suppression and to assess test performance, with analyses anticipated in 2026. In-depth acceptability surveys were completed by 193 participants, and 41 interviews were conducted. These data will contribute to qualitative and mixed methods analyses, which are anticipated in 2026. Time-and-motion observations conducted in 2021 and 2023 included 47 patients; results are anticipated in 2026. The GAIN study is an important evaluation of POC NAT implementation in the United States in community and clinical care settings for HIV diagnosis and viral load monitoring. Results will be reported in future publications.
Surgical site infections represent a significant complication after emergency laparotomy, contributing to increased morbidity, mortality, and healthcare costs. Negative pressure wound therapy (NPWT) may reduce the incidence of surgical site infections; however, evidence from randomized controlled trials remains inconsistent. To present a systematic review and meta-analysis, comparing NPWT with conventional dressings in emergency laparotomies. Systematic searches were conducted according to the Cochrane Handbook and reported according to the PRISMA 2020 guidelines. The PubMed, Embase, and Cochrane CENTRAL databases were searched since their inception, using terms related to emergency laparotomy, NPWT, and conventional dressings. The reference lists of included studies were manually examined to identify additional eligible trials. Only randomized controlled trials that compared NPWT with conventional dressings in emergency abdominal surgeries and that reported surgical site infection rates or other clinical outcomes were included. The primary outcome was the incidence of surgical site infection. Secondary outcomes included wound dehiscence, seroma formation, length of hospital stay, and 30-day mortality. Eight randomized controlled trials, totaling 1,377 patients (707 in the NPWT group and 670 in the conventional dressing group), were included. NPWT significantly reduced the risk of surgical site infection (risk ratio [RR] 0.43; 95% confidence interval [CI] 0.26-0.73; p=0.002; heterogeneity [I2]=76%) and wound dehiscence (RR 0.32; 95%CI 0.18-0.58; p=0.0002). No significant differences were observed regarding seroma formation (RR 0.59; 95%CI 0.34-1.01; p=0.05), length of hospital stay (mean difference [MD] -0.39 days; 95%CI -1.15- 0.36; p=0.92) or mortality (RR 0.96; 95%CI 0.55-1.68; p=0.88). This systematic review and meta-analysis of randomized clinical trials suggests that NPWT reduces the incidence of surgical site infection and wound dehiscence after emergency laparotomy, supporting its use in high-risk patients. Surgical site infections are a major postoperative complication after emergency laparotomies, contributing substantially to morbidity, mortality, and healthcare costs. Strategies to reduce postoperative complications have increasingly focused on perioperative optimization through evidence-based, multimodal protocols. Retrospective analyses have demonstrated the efficacy of intermittent negative pressure wound therapy in diminishing the incidence of surgical site infections following laparotomy in patients undergoing gynecological and general surgical procedures. Nonetheless, the findings derived from randomized controlled trials have yielded inconsistent results. This original systematic review and meta-analysis of randomized controlled trials demonstrated the efficacy of negative pressure wound therapy in reducing the incidence of surgical site infections and wound dehiscence among patients undergoing emergency laparotomy when compared to conventional dressings. As infecções do sítio cirúrgico representam uma complicação relevante após laparotomia de emergência, contribuindo para o aumento da morbidade, da mortalidade e dos custos em saúde. A terapia por pressão negativa em feridas (TPNF) pode reduzir a incidência de infecções do sítio cirúrgico; entretanto, as evidências provenientes de ensaios clínicos randomizados permanecem inconsistentes. Apresentar uma revisão sistemática e metanálise, comparando a TPNF com curativos convencionais em laparotomias de emergência. Foram realizadas buscas sistemáticas de acordo com o Cochrane Handbook e relatadas conforme as diretrizes PRISMA 2020. As bases PubMed, Embase e Cochrane CENTRAL foram pesquisadas desde a sua criação, utilizando termos relacionados à laparotomia de emergência, TPNF e curativos convencionais. As listas de referências dos estudos incluídos foram examinadas manualmente para a identificação de ensaios adicionais elegíveis. Foram incluídos apenas ensaios clínicos randomizados que compararam a TPNF com curativos convencionais em cirurgias abdominais de emergência e que relataram taxas de infecção do sítio cirúrgico ou outros desfechos clínicos. O desfecho primário foi a incidência de infecção do sítio cirúrgico. Os desfechos secundários incluíram deiscência da ferida, formação de seroma, tempo de internação hospitalar e mortalidade em 30 dias. Oito ensaios clínicos randomizados, totalizando 1.377 pacientes (707 no grupo TPNF e 670 no grupo curativo convencional), foram incluídos. A TPNF reduziu significativamente o risco de infecção do sítio cirúrgico (razão de risco [RR] 0,43; intervalo de confiança [IC] 95% 0,26–0,73; p=0,002; heterogeneidade [I2]=76%) e de deiscência da ferida (RR 0,32; IC95% 0,18–0,58; p=0,0002). Não foram observadas diferenças significativas quanto à formação de seroma (RR 0,59; IC95% 0,34–1,01; p=0,05), ao tempo de internação hospitalar (diferença de médias [DM] -0,39 dias; IC95% -1,15–0,36; p=0,92) ou à mortalidade (RR 0,96; IC95% 0,55–1,68; p=0,88). Esta revisão sistemática e metanálise de ensaios clínicos randomizados sugere que a TPNF reduz a incidência de infecção do sítio cirúrgico e de deiscência da ferida após laparotomia de emergência, apoiando seu uso em pacientes de alto risco.
Nanobodies are small but specific heavy chain-only antibody fragments. Their small size, relative stability, and ability to access difficult to reach deep-tissue antigens makes them valuable research, diagnostic, and therapeutic tools. Nanobodies are derived from the variable heavy (VH) domain of heavy chain-only antibodies that are unique to camelids, including alpacas, llamas, and camels. The approaches employed to produce nanobodies, have been evolving and expanding since the initial discovery of heavy chain-only antibodies 30 years ago. Traditional nanobody development involves camelid immunization with a soluble, purified protein, followed by blood collection and processing, enrichment for potent nanobody sequences, and eventual expression and purification of candidate nanobodies for testing and validation. Alternative nanobody generation strategies aim to identify novel nanobodies utilizing synthetic or animal-derived naïve nanobody libraries in combination with phage-, yeast surface-, or ribosome displays for nanobody selection. This article outlines a novel protocol series for nanobody production using a commercially available transgenic "nanomouse", engineered to produce heavy chain-only antibodies containing camelid VH domains from alpacas, dromedaries, and Bactrian camels. These protocols will cover the following aspects: (1) Nanomouse breeding, genotyping, and colony establishment; (2) Nanomouse immunization and tissue collection; (3) RNA extraction from nanomouse immune cells isolated from blood and tissues; (4) Generation and amplification of VHH DNA from nanomouse cDNA; (5) Digestion of VHH DNA and ligation into a phagemid expression vector; (6) Preparation of a screenable Escherichia coli TG1-based phagemid library; (7) Antigen-driven VHH selection using phage display; (8) Single colony VHH ELISA screening; (9) Sequencing of ELISA hits and candidate VHH sequence identification; (10) Geneblock design of candidate VHH and Gibson Assembly into a nanobody expression vector; and (11) Nanobody over-expression and purification. We provide a comprehensive toolkit to facilitate nanobody development and make it more accessible to the greater research community. © 2026 The Author(s). Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Nanomouse breeding, genotyping, and colony establishment Basic Protocol 2: Nanomouse immunization and tissue collection Basic Protocol 3: RNA extraction from nanomouse immune cells isolated from blood and tissues Basic Protocol 4: Generation and amplification of VHH DNA from nanomouse cDNA Basic Protocol 5: Digestion of VHH DNA and ligation into a phagemid expression vector Basic Protocol 6: Preparation of a screenable E. coli TG1-based phagemid library Basic Protocol 7: Antigen-driven VHH selection using phage display Basic Protocol 8: Single colony VHH enzyme-linked immunosorbent assay (ELISA) screening Basic Protocol 9: Sequencing of ELISA hits and candidate VHH sequence identification Basic Protocol 10: Geneblock design of candidate VHH and Gibson Assembly into a nanobody expression vector Basic Protocol 11: Nanobody over-expression and purification.
Perinatal mental health concerns are common and may be heightened among immigrant populations because of migration-related stressors, social isolation, stigma, language barriers, and limited access to culturally safe care. Although previous reviews have examined perinatal mental health among immigrants broadly, evidence focused specifically on South Asian immigrant women in Canada across pregnancy and the postpartum period has not been comprehensively mapped. South Asian women represent one of the largest and fastest-growing immigrant populations in Canada and may experience unique cultural, familial, linguistic, and migration-related factors that shape perinatal mental health experiences and access to care. This scoping review will map the extent, range, and nature of evidence on perinatal mental health among South Asian immigrant women in Canada by examining reported mental health outcomes, associated risk and protective factors, help-seeking experiences, and barriers and facilitators to accessing support services, and identify gaps to inform future research, practice, and policy. This protocol was developed in accordance with Joanna Briggs Institute guidance for scoping review protocols and reported using the PRISMA-P checklist, where applicable (see S2 Checklist). The completed scoping review will be reported according to the PRISMA-ScR checklist. MEDLINE, Embase, PsycINFO, CINAHL, and Scopus will be searched for literature published from January 2000 to the date of the final search. Grey literature will be identified through targeted searches of government, public health, professional, and community organization websites. Eligible sources will include qualitative, quantitative, mixed-methods, and relevant grey literature addressing perinatal mental health during pregnancy and up to 12 months postpartum among South Asian immigrant women residing in Canada. Inclusion criteria are immigrant women of South Asian origin from counties such as India, Pakistan, Bangladesh, Sri Lanka, Afghanistan, Nepal, Bhutan, and Maldives residing in Canada during the perinatal period. Two reviewers will independently screen titles, abstracts with disagreements resolved through discussion or third-reviewer adjudication. Data will be extracted using a standardized charting form and summarized using descriptive mapping and narrative synthesis. Protocols and planned studies will be charted separately from completed studies. Consistent with scoping review methodology, formal exclusion of studies based on methodological quality will not be undertaken; however, study characteristics and reported methodological limitations will be charted to support interpretation of the evidence base. Ethics approval is not required because the review will use publicly available sources only. Findings will be disseminated through a dissertation, peer-reviewed publication, and conference presentations. The review will provide a comprehensive overview of existing evidence and knowledge gaps to support culturally responsive perinatal mental health research, policy development, and healthcare practice for South Asian immigrant women in Canada. This protocol has been preregistered on the Open Science Framework:10.17605/OSF.IO/FZN4S.
Neoadjuvant cisplatin-based chemotherapy is a standard therapy for muscle-invasive bladder cancer. The efficacy and safety of neoadjuvant and adjuvant (perioperative) enfortumab vedotin-pembrolizumab as compared with neoadjuvant cisplatin-based chemotherapy in persons with this cancer are unclear. We conducted a phase 3, open-label, randomized trial involving adults with muscle-invasive bladder cancer eligible for cisplatin-based chemotherapy and radical cystectomy with pelvic lymph-node dissection (cystectomy). Participants were assigned to receive neoadjuvant enfortumab vedotin-pembrolizumab (4 cycles; enfortumab vedotin [1.25 mg per kilogram of body weight on days 1 and 8] and pembrolizumab [200 mg on day 1] every 3 weeks), cystectomy, and 5 cycles of enfortumab vedotin and 13 cycles of pembrolizumab as adjuvant therapy or to receive neoadjuvant cisplatin-gemcitabine (4 cycles; cisplatin [70 mg per square meter of body-surface area on day 1] plus gemcitabine [1000 mg per square meter on days 1 and 8] every 3 weeks) and cystectomy. The primary end point was event-free survival; key secondary end points were overall survival and pathological complete response. Safety was assessed. A total of 405 participants were assigned to receive enfortumab vedotin-pembrolizumab and 403 to receive cisplatin-gemcitabine. The median time from randomization to the data-cutoff date was 33.6 months (range, 22.5 to 53.6). A total of 86.7% of the participants in the enfortumab vedotin-pembrolizumab group and 89.6% of those in the cisplatin-gemcitabine group underwent cystectomy. At 2 years, estimated event-free survival was 79.4% with enfortumab vedotin-pembrolizumab and 66.2% with cisplatin-gemcitabine (hazard ratio for an event or death, 0.53; 95% confidence interval [CI], 0.41 to 0.70; P<0.001); estimated overall survival was 86.9% and 81.3%, respectively (hazard ratio for death, 0.65; 95% CI, 0.48 to 0.89; two-sided P = 0.006). A pathological complete response occurred in 55.8% and 32.5% of the participants (P<0.001). The incidence of grade 3 or higher adverse events of any cause was 75.7% with enfortumab vedotin-pembrolizumab and 67.2% with cisplatin-gemcitabine. Among participants with muscle-invasive bladder cancer eligible for cisplatin-based chemotherapy, perioperative enfortumab vedotin-pembrolizumab led to significantly better event-free and overall survival outcomes and a significantly higher incidence of pathological complete response than neoadjuvant cisplatin-gemcitabine, but with more adverse events of grade 3 or higher. (Funded by Merck Sharp and Dohme and others; KEYNOTE-B15/EV-304 ClinicalTrials.gov number, NCT04700124.).
Despite global progress in reducing HIV incidence, adolescent girls and young women in sub-Saharan Africa remain disproportionately affected. Biomedical HIV prevention tools such as pre-exposure prophylaxis, condoms and HIV testing are effective but underutilized, especially within facility-based models. Schools represent consistent and scalable contact points for reaching adolescent girls and young women, yet evidence on the feasibility, accessibility and effectiveness of school-based biomedical HIV prevention interventions remains limited. This systematic review aims to synthesize evidence on how school-based programs implement, deliver and achieve outcomes in HIV prevention interventions involving pre-exposure prophylaxis, condom and HIV testing for adolescent girls and young women in sub-Saharan Africa. This review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines. Eligible studies will include randomized and non-randomized trials and qualitative research published between January 2015 and December 2025. Databases to be searched include PubMed, Embase, PsycINFO, CINAHL and the African Index Medicus, together with relevant grey literature sources (WHO, UNAIDS, UNICEF and PEPFAR). Two reviewers will independently screen titles, abstracts, and full texts, extract data, and assess risk of bias using appropriate tools. Quantitative data will be synthesized using meta-analysis where feasible, while qualitative findings will undergo thematic synthesis. Outcomes of interest include the feasibility, accessibility, and effectiveness of school-based HIV prevention interventions. This review will provide a comprehensive synthesis of evidence on biomedical HIV prevention interventions delivered in school settings for adolescent girls and young women in sub-Saharan Africa. Findings will highlight implementation process, barriers, facilitators and equity considerations. Trial registration number: PROSPERO CRD420251249595.
The dysregulation of both reduced (IL-33red) and oxidised (IL-33ox) interleukin (IL)-33 has been implicated in chronic obstructive pulmonary disease (COPD) inflammation and remodelling processes. Tozorakimab, an anti-IL-33 monoclonal antibody, inhibits both IL-33red and IL-33ox activity. The tozorakimab LUNA programme comprises four ongoing, multicentre, randomised, double-blind, parallel-group, placebo-controlled, phase III studies evaluating the efficacy and safety of tozorakimab in participants with symptomatic COPD and a history of exacerbations receiving optimised inhaled therapy. In OBERON (NCT05166889) and TITANIA (NCT05158387), 1132 and 1172 participants, respectively, were randomised to receive tozorakimab 300 mg every 4 or 8 weeks or placebo for 52 weeks. In MIRANDA (NCT06040086), 1454 participants were randomised 3:2 to tozorakimab 300 mg every 2 weeks or placebo for ≥52 weeks. In PROSPERO (NCT05742802), participants who completed treatment with tozorakimab in OBERON or TITANIA will continue treatment for an additional 28 weeks or 52 weeks; participants recruited from the placebo arm will be re-randomised 1:1 to tozorakimab or placebo. The primary endpoint in OBERON, TITANIA and MIRANDA is the annualised rate of moderate-to-severe COPD exacerbations; the primary endpoint in PROSPERO is the annualised rate of severe COPD exacerbations. For all studies, the primary endpoint will be first assessed in former smokers, then in current and former smokers. Secondary key endpoints include measures of lung function, respiratory symptoms, health status and safety. The tozorakimab LUNA programme is assessing the efficacy and safety of tozorakimab in participants with COPD. It is the largest pivotal programme of any biologic therapy in COPD to date. The protocols were approved by independent ethics committees and institutional review boards. Results of the studies will be submitted to the EU Clinical Trials Information System within a year from the global end of trial data in all participating countries and will be published or presented at scientific meetings. OBERON: NCT05166889; TITANIA: NCT05158387; MIRANDA: NCT06040086; PROSPERO: NCT05742802.
This study aimed to examine the perceived challenges and attitudes toward home-based treatment for hematology and hemato-oncology patients among physicians and nurses. A qualitative study was conducted based on 23 semistructured interviews with physicians (n = 11) and nurses (n = 12) from eight hospitals across Israel. The participants were recruited using opportunistic sampling, and the interviews were analyzed thematically using an inductive reflexive thematic analysis approach. Data saturation was achieved. Three overarching themes emerged: (1) the hospital as a safe haven: the conflict between hospital safety and the benefits of home treatment; participants emphasized the importance of hospital-based monitoring and expressed concerns about patient safety in home settings; (2) building a well-functioning home treatment system vs. fearing loss of control; while envisioning an organized, hospital-led model, participants stressed the need for trained staff, dedicated coordination, and clinical oversight; and (3) balancing costs, risks, and institutional support; participants highlighted financial disincentives, infrastructure gaps, and the role of professional trust in promoting patient acceptance. Although healthcare professionals recognize the potential benefits of home-based treatment, their support is contingent upon robust clinical protocols, institutional alignment, and clear coordination mechanisms. These findings underscore the central role of provider engagement in advancing safe and sustainable models of home care for hematology and hemato-oncology patients. The study offers practical insights that will assist in implementing health policies, developing clinical programs, and organizational planning for the safe and sustainable implementation of nonpalliative home care in hematology and hemato-oncology.
Metastatic castration-resistant prostate cancer (mCRPC) is among the leading causes of cancer-related mortality in men worldwide. Treatment options for mCRPC typically include chemotherapy and androgen receptor pathway inhibitors. Immune checkpoint inhibitors (ICIs) have demonstrated a limited effect in mCRPC. We hypothesized that the addition of stereotactic body radiation therapy (SBRT) could enhance immune responses and improve treatment outcomes. Patients with mCRPC who had received at least two prior lines of therapy were randomized 1:1 to receive SBRT with nivolumab and ipilimumab (arm A) or nivolumab and ipilimumab (arm B). The dual primary endpoints in the study were prostate-specific antigen (PSA) response rate and objective response rate (ORR). Secondary endpoints included overall survival (OS), PSA, radiologic progression-free survival, and toxicity. We enrolled 91 patients, and 81 patients received at least one treatment with ICIs and were eligible for evaluation of the efficacy and safety endpoints. Of the evaluable patient population, the confirmed PSA response rate was 21.6% (95% CI 9.8% to 38.2%) in arm A, and 20.5% (95% CI 9.8% to 35.3%) in arm B. ORR was 16.7% (95% CI 4.7% to 37.4%) and 22.2% (95% CI 10.1% to 39.2%) in arms A and B, respectively. Median OS was 10.2 months (95% CI 7.1 to 15.2) in arm A and 9.2 months (95% CI 7.1 to 14.4) in arm B. Treatment-related adverse events grade 3-4 were observed in 27 patients (33.3%). The addition of SBRT to nivolumab and ipilimumab did not improve outcomes; however, a fraction of the patients had a response to the treatment combination of nivolumab and ipilimumab. Explorative translational research is needed to identify possible biomarkers of response to immunotherapy with ICIs in mCRPC. European Union Clinical Trial Registry (https://www.clinicaltrialsregister.eu) EudraCT number: 2018-003461-34 and on https://clinicaltrials.gov (NCT05655715).
Background: Short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) is used for locally advanced rectal cancer (LARC). However, the pathological complete response (pCR) rate still hovers around 30%. Radiotherapy and immune checkpoint inhibitors have been shown to exert synergistic anticancer effects. This phase II randomized clinical trial aimed to evaluate the efficacy and safety of SCRT followed by capecitabine plus oxaliplatin (CAPOX) and tislelizumab versus SCRT followed by CAPOX alone in LARC. Methods: Patients initially diagnosed with clinical tumor stage 1 to 2, with node involvement and no distant metastasis (cT1-2N+M0) or clinical tumor stage 3 to 4, with any node status and no distant metastasis (cT3-4NanyM0) rectal adenocarcinoma were randomly assigned to receive SCRT (25 Gy in 5 fractions [25 Gy/5F]), followed by 4 cycles of CAPOX combined with tislelizumab (SCRT-TNT-ICI) or CAPOX alone (SCRT-TNT). After total mesorectal excision, 2 cycles of postoperative chemotherapy were administered according to the patient's preference. The primary end point was the pCR rate, and secondary end points included major pathological response (tumor regression grade 0 or 1), 3-year progression-free survival, 3-year overall survival, and adverse events. Results: Between September 2021 and March 2024, 118 patients were randomized, of whom 111 started the allocated treatment, with 53 and 58 in SCRT-TNT-ICI and SCRT-TNT groups, respectively. Of those, 89 patients had surgical resection, including 45 in the SCRT-TNT-ICI group and 44 in the SCRT-TNT group. The pCR rate was 45.3% (95% confidence interval [CI], 31.5% to 59.8%) in the SCRT-TNT-ICI group compared to 27.6% (95% CI, 16.6% to 40.8%) in the SCRT-TNT group (odds ratio = 2.17; 95% CI, 0.99 to 4.79; P = 0.052). The major pathological response rates were 50.9% (95% CI, 36.6% to 65.2%) and 31.0% (95% CI, 19.5% to 44.6%), respectively (odds ratio = 2.31; 95% CI, 1.06 to 5.01; P = 0.033). During the neoadjuvant treatment period, the incidence of grade 3 to 4 adverse events was comparable between the SCRT-TNT-ICI and SCRT-TNT groups, with anemia being the most common in both groups. Conclusion: This phase II study provides preliminary evidence of promising tumor regression with SCRT-TNT combined with tislelizumab in LARC, warranting further validation in phase III trials. Trial registration: This trial was registered at clinicaltrials.gov (Identifier: NCT05086627).
Postoperative recurrence of Crohn's disease (CD) is common and may occur without symptoms. Ileocolonoscopy is the reference standard for detecting endoscopic recurrence, but its invasiveness limits repeated use. Intestinal ultrasound (IUS) is a non-invasive monitoring tool, although diagnostic criteria and ultrasound modalities vary across studies. We conducted a systematic review and diagnostic test accuracy meta-analysis to evaluate the performance of IUS for detecting postoperative recurrence. PubMed/MEDLINE, EMBASE, Scopus, and the Cochrane Library were searched from inception to April 2025. Eligible studies evaluated IUS for postoperative recurrence in CD using ileocolonoscopy as the reference standard. Data were extracted to reconstruct independent 2 × 2 diagnostic tables. The primary synthesis used hierarchical bivariate binomial random-effects models to jointly estimate summary sensitivity and specificity. Heterogeneity was explored through subgroup analyses by ultrasound modality, Doppler use, contrast route, bowel wall thickness threshold, diagnostic definition, data collection period, and recurrence severity. Twelve studies were included in the systematic review and narrative synthesis; 11 provided reconstructable independent 2 × 2 data and were included in the bivariate meta-analysis. IUS showed high summary sensitivity of 87.6% (95% CI, 81.0%-92.1%; P < .001) and good summary specificity of 80.2% (95% CI, 60.6%-91.5%; P < .001). The false negative rate was 12.4% (95% CI, 7.9%-19.0%), the false positive rate was 19.8% (95% CI, 8.5%-39.4%), positive likelihood ratio was 4.436 (95% CI, 2.070-9.505), negative likelihood ratio was 0.154 (95% CI, 0.101-0.236), and diagnostic odds ratio was 28.8 (95% CI, 11.0-75.4). Diagnostic performance was generally consistent across studies, although differences in ultrasound protocols and bowel wall thickness thresholds, most commonly ≥3 or ≥5 mm, appeared to contribute to between-study variability. IUS shows high sensitivity and good specificity for postoperative recurrence surveillance in CD. Its interpretation should remain linked to ultrasound protocol, threshold, recurrence definition, and clinical context.
Background: Walking is a dynamic activity that relies on inputs from the multisensory system, i.e., somatosensory, vision, and vestibular. These inputs are processed and integrated in the central nervous system to produce motor impulses for efficient walking balance. The Sensory Organization Test (SOT) is established as the gold standard for assessing sensory contributions to standing balance. However, no comparable assessments have been developed for the clinical evaluation of balance during gait. This study evaluated the Gait Sensory Interaction Test (GaitSIT), a novel virtual reality (VR)-based assessment for characterizing sensory-condition-specific changes in walking balance. Methods: The GaitSIT comprises a VR environment with a physical compliant foam walking surface that evaluates gait-balance by systematically manipulating and evaluating the sensory systems. Twenty-nine healthy young adults (mean age 24.9 ± 6.4 years) were instructed to complete 6 m walking trials under six standardized conditions (C): eyes open, eyes closed/dark scene, and rotating visual scenes on a firm surface, then repeated on a foam surface. Wearing an Oculus VR headset, participants were instructed to walk in a straight line at their preferred speed, as naturally as possible, in two test sessions on the same day, followed by a third test session 24 h later. Headset-derived sway measures, including position, velocity, and acceleration data, were recorded, and the continuous trajectory deviation angle (i.e., directional control) and sensory ratios were calculated. Linear mixed-effects models included trial-level walking speed as a covariate. Additionally, participants completed the modified Clinical Test of Sensory Interaction on Balance (mCTSIB) as a clinical standing-balance reference measure; its concurrent-validity findings will be reported separately. Results: Significant condition effects were observed for position, velocity, acceleration, and CTDA after adjustment for trial-level walking speed (all p<0.001), indicating that the six sensory conditions elicited distinct gait-balance responses. Significant differences relative to the baseline condition (C1) were observed across conditions C2-C6 for position, C3-C6 for velocity, and C2 and C5 for acceleration. Session effects were not significant for any primary kinematic outcome after speed adjustment. A significant condition × session interaction was observed for position (p<0.001), whereas velocity, acceleration, and CTDA demonstrated no significant interactions. Walking speed was significantly associated with position, acceleration, and CTDA, but not velocity. Sensory-ratio analyses revealed larger visual and vestibular ratios relative to somatosensory ratios, with the visual and vestibular ratios generally decreasing across sessions. Conclusions: GaitSIT successfully manipulated sensory conditions during overground walking and produced significant changes in gait-related sway, directional control, and sensory-ratio measures. These findings support the feasibility of GaitSIT as a portable, low-cost, and immersive assessment framework for characterizing sensory-condition-specific gait-balance responses after accounting for walking speed and providing indirect behavioral indices related to sensory reweighting.
Inferior alveolar nerve (IAN) dissection and repositioning is critical for preventing iatrogenic IAN injury during combined mandibular border resection and sagittal split ramus osteotomy (SSRO) in patients with severe hemimandibular hyperplasia (HH). Traditional IAN repositioning includes two-stage and concurrent one-stage procedures. This study introduces a modified one-stage technique and compares the respective advantages and disadvantages of these three surgical protocols. Four patients with HH were enrolled and treated with three different surgical protocols: one two-stage procedure, one conventional one-stage procedure, and two modified one-stage procedures. The modified technique features a vertical osteotomy placed 5 mm anterior to the mental foramen to protect the anterior loop of the IAN. All patients achieved satisfactory facial symmetry and aesthetic improvement postoperatively. Neurosensory assessment at 6-month follow-up confirmed complete recovery of lower lip sensation without persistent numbness. Compared with the two-stage and conventional one-stage approaches, the modified technique effectively preserved the IAN anterior loop, simplified surgical procedures, and minimized bony defects by maintaining buccal cortical bone integrity. The modified one-stage approach is a simplified and effective technique that provides reliable neuroprotection for the anterior loop of the IAN while minimizing bony defects during SSRO in HH patients. Given the limited sample size of this case series, further large-sample and long-term studies are required to fully validate tits efficacy, long-term stability, and complication profile.
To systematically evaluate and quantitatively synthesize the effects of Tai Chi interventions on the mental health of college students. This study was conducted in accordance with the PRISMA 2020 guidelines for systematic reviews and meta-analyses and was registered in PROSPERO (CRD420261329121). PubMed, Web of Science, Scopus, Cochrane Library, EBSCO, CNKI, Wanfang Database, and the China Science and Technology Journal Database were systematically searched from database inception to February 1, 2026. Randomized controlled trials (RCTs) investigating the effects of Tai Chi interventions on the mental health of college students were included. Statistical analyses were performed using Review Manager 5.4. For continuous outcomes, standardized mean differences (SMDs) or mean differences (MDs) with 95% confidence intervals (CIs) were calculated. A random-effects model was used to pool the effect sizes. Between-study heterogeneity was assessed using Cochran's Q test and the I 2 statistic. Sensitivity analyses and subgroup analyses were also conducted. A total of 12 randomized controlled trials involving 1,057 college students were included (554 in the intervention group and 503 in the control group). The meta-analysis showed that Tai Chi intervention significantly reduced depression symptoms among college students (SMD = -0.67, 95% CI [-0.90, -0.43], p < 0.00001). Tai Chi also demonstrated significant effects in alleviating anxiety (SMD = -0.79, 95% CI [-1.42, -0.15], p = 0.02) and stress (SMD = -0.40, 95% CI [-0.65, -0.14], p = 0.002). In addition, Tai Chi significantly improved sleep quality among college students (MD = -2.14, 95% CI [-4.13, -0.15], p = 0.03), although substantial heterogeneity was observed across studies. The present meta-analysis provides quantitative evidence that Tai Chi interventions have beneficial effects on improving mental health among college students, particularly in reducing depression, anxiety, and stress. Although Tai Chi also appears to improve sleep quality, the relatively high heterogeneity across studies indicates that further high-quality randomized controlled trials are needed to confirm these findings and to determine optimal intervention protocols. PROSPERO: CRD420261329121, https://www.crd.york.ac.uk/PROSPERO/view/CRD420261329121.
Point-of-care ultrasound (POCUS) improves patient care by expedited diagnosis and safer procedures. Despite POCUS benefits, some clinicians, including emergency physicians, do not readily use POCUS. The study objective identified barriers and facilitators to clinical POCUS use and performed an intervention to address these barriers. A prospective cohort study at a single academic hospital included emergency department attendings, residents and advanced practice providers (APPs). Participants were surveyed on perceived POCUS use barriers and facilitators (primary outcome). A multifaceted intervention from December 2023 to January 2024 addressed identified barriers and involved: in-person POCUS education during shift by ultrasound faculty, clinical POCUS workflow demonstration during resident conference/faculty meetings and QR code reference files on machines. 42/99 participants (42.4%) responded to surveys preintervention and 28 postintervention (28.3%). 56 physicians and APPs participated in the in-person POCUS intervention (17 attendings, 34 residents, 5 APPs). Perceived POCUS barriers were time constraints on shift; internet/connectivity problems and losing saved images; forgetting to finish exam worksheets online; images not uploading into Butterfly cloud by the end of shift and residents performing 'phantom scans'. Perceived POCUS facilitators included clear documentation protocols, hands-on teaching sessions and incentives for completing scans. Comfort in teaching diagnostic and procedural POCUS improved pre to postintervention but did not change for performing POCUS. Identified barriers and facilitators were incorporated into a multifaceted intervention to improve clinical POCUS workflow processes. Future individualised interventions for low POCUS users and institutional initiatives with POCUS champions can be studied for improved patient care.
Microplastics (MPs) act as reactive surfaces and carriers in aquatic systems, influencing the mobility, bioavailability, and toxicity of heavy metals. Recent research has clarified how heavy metals adsorb onto MPs, focusing on adsorption pathways, physicochemical factors, analytical methods, toxicological impacts, and remediation strategies. Metal binding to MPs depends on factors such as polymer type, particle size, aging, surface properties, zeta potential, pH, salinity, dissolved organic matter, temperature, and the presence of biofilms. Adsorption occurs through mechanisms including electrostatic interactions, surface complexation, ion exchange, pore filling, hydrogen bonding, van der Waals forces, cation-π interactions, surface precipitation, and biofilm-mediated binding. MP-metal interactions vary with environmental conditions; for example, salinity and dissolved organic matter can enhance or reduce adsorption, depending on metal speciation, polymer characteristics, and experimental conditions. Toxicological studies show that MPs carrying heavy metals can increase bioaccumulation and combined toxicity by promoting transport and cellular uptake. However, strong adsorption and limited desorption may sometimes reduce the bioavailability of dissolved metals. The Mediterranean Sea is a key case study due to its semi-enclosed nature, high urbanization, maritime activity, wastewater discharge, and significant plastic pollution, all of which heighten the importance of MP-metal interactions. There is an urgent need for standardized adsorption protocols, thorough in situ and ex situ characterization, ecologically relevant toxicological studies, and integrated remediation strategies addressing both MPs and associated heavy metals.
Ensuring viral safety is a critical aspect of biopharmaceutical production, requiring sensitive and reliable methods for detecting adventitious agents. In this study, we systematically evaluated the performance of selected cell line-virus combinations to identify optimal models for in vitro viral detection assays. Three cell lines (Vero, MRC-5 and BHK-21 [C-13]) and representative model viruses (Reovirus type 3, Adenovirus type 5, Human parainfluenza virus type 3, and Herpes simplex virus) were analyzed in terms of cytopathic effect (CPE) kinetics, morphology, and detection sensitivity. All tested systems demonstrated high analytical sensitivity, with limits of quantification (LOQ) reaching 0.01 TCID50/mL for selected viruses. However, substantial differences were observed in infection dynamics and CPE morphology depending on the cell line-virus combination. BHK-21 [C-13] cells exhibited the most rapid and pronounced CPE for Reovirus type 3, enabling early and unambiguous detection. Vero cells provided robust and reproducible detection of Adenovirus type 5, characterized by well-defined cytopathic progression. MRC-5 cells showed controlled and consistent infection kinetics for both Human parainfluenza virus type 3 and Herpes simplex virus, allowing improved temporal resolution and interpretability. These findings demonstrate that assay performance depends not only on sensitivity but also on the kinetics and morphology of infection. Based on combined evaluation criteria, the following optimal cell line-virus pairs were identified: BHK-21 [C-13]/Reovirus type 3, Vero/Adenovirus type 5, and MRC-5/Human parainfluenza virus type 3 and Herpes simplex virus. The proposed approach supports rational selection of detection models and provides a preliminary descriptive framework for the development of routine visual screening assays in biopharmaceutical quality control.
Age is frequently considered a major determinant of postoperative recovery after colorectal surgery and is often perceived as a limiting factor for an enhanced recovery after surgery (ERAS®) pathway. The integration of ERAS® with a robotic surgical approach (RERAS-concept) may be associated with synergistic effects especially for this group of patients. However, real-world-data evaluating age-related differences in postoperative recovery under RERAS conditions remain limited. This retrospective analysis of a prospectively maintained database included all elective robotic colorectal resections performed between January 2019 and April 2024 under a fully standardized ERAS®-protocol. Patients were categorized into younger (≤ 69 years) and older (≥ 70 years) adults. The primary endpoint was the comparison of short-term perioperative outcomes. Secondary endpoints comprised functional recovery parameters and perioperative ERAS® compliance. 344 robotic colorectal resections were analyzed (219 colon and 125 rectal resections). Older adults presented with increased frailty levels across both colon and rectal resections (mFI-5 all p = < 0.0001). In colon resections, this was accompanied by significantly higher preoperative risk profiles, reflected by a greater proportion of ASA III patients (72.1% vs. 40.7%; p < 0.0001), while intraoperative characteristics, postoperative morbidity and length of hospital stay were comparable between age groups. Older adults achieved oral pain control earlier (1 vs. 2 days; p = 0.0410), reported lower postoperative pain scores from the day of surgery through postoperative day 3 (all p < 0.05) and demonstrated greater mobilization on postoperative day 3 (6 vs. 5 h; p = 0.0298). In rectal resections, younger patients more frequently received neoadjuvant therapy (59.1% vs. 39%; p = 0.0248). Duration of surgery was shorter in older adults (229 vs. 245 min; p = 0.0176), while the other endpoints were comparable between cohorts. In this real-world cohort, robotic colorectal surgery within a standardized ERAS® pathway resulted in comparable postoperative recovery across age groups, with statistically significant advantages in pain control and mobilization favoring older adults, supporting age-independent implementation of the RERAS concept.
Large language models (LLMs) have demonstrated expert-level performance on medical licensing examinations, but most benchmarks focus on final accuracy. Critical gaps remain in understanding model efficiency (latency), the efficacy of tiered "rescue" protocols for error correction, and the systematic correlation between performance and human-rated question difficulty. The German M2 examination, paired with the AMBOSS platform's user data-driven difficulty ratings, provides an opportunity to map AI performance against human cognitive load. This study aimed to move beyond singular accuracy scores by (1) evaluating and comparing the baseline (tier 1; T1) accuracy and response latency of next-generation rapid-response LLMs, (2) analyzing the efficacy of a 2-tiered rescue (tier 2; T2) protocol in correcting initial errors, and (3) correlating model performance with the user data-driven AMBOSS difficulty rating. We evaluated 4 LLMs (Gemini 2.5 Flash, Gemini 2.5 Pro, GPT-5 Instant, and GPT-5 Thinking) on the complete 316-item German M2 (Fall 2024) medical examination, including all multimodal (image-based) questions. A zero-shot copy-paste prompting strategy was used, and outputs were evaluated against ground-truth answers using a strict exact-match criterion. A 2-tiered protocol was used: T1 (Gemini Flash and GPT-5 Instant) provided baseline responses. If incorrect, a T2 (Gemini Pro and GPT-5 Thinking) model was deployed as a "rescue." Performance was analyzed using the McNemar test, the Wilcoxon signed-rank test, the Fisher exact test, and logistic regression. Baseline (T1) accuracy was identical at 91.5% (289/316; 95% CI 87.85%-94.06%) for both Gemini 2.5 Flash and GPT-5 Instant, with 27 errors each. However, Gemini Flash (mean 1.57, SD 1.06 s) was significantly faster than GPT-5 Instant (mean 2.07, SD 1.89 s; P<.001). Additionally, GPT-5 Instant expended significantly more time on incorrect answers compared with correct ones (P=.002), whereas Gemini Flash showed no such hesitation (P=.81). The T2 rescue rate for GPT-5 Thinking (13/27, 48.2%; 95% CI 30.74%-66.01%) was higher, though not statistically significant (P=.41), than that for Gemini 2.5 Pro (9/27, 33.3%; 95% CI 18.64%-52.18%). This rescue protocol elevated final accuracy to 94.3% (298/316; 95% CI 91.18%-96.37%) for the Gemini system and 95.6% (302/316; 95% CI 92.70%-97.34%) for the GPT-5 system (P=.48). A strong, inverse relationship with difficulty was found: for every 1-point increase in difficulty, the odds of a correct T1 response decreased by 42.1% (odds ratio 0.579, 95% CI 0.425-0.788; P<.001) for Gemini Flash and 47.7% (odds ratio 0.523, 95% CI 0.379-0.720; P<.001) for GPT-5 Instant. This negative correlation persisted even after the rescue (P=.01 and P=.006, respectively). Expert-level LLM performance on the German M2 examination masks a critical vulnerability: a decrease in accuracy correlated with increased question difficulty. A 2-tiered "rescue" system is an effective strategy to mitigate these difficulty-based failures and achieve >95% accuracy.
Structured exercise is a key component of cardiac rehabilitation (CR) for patients with heart failure (HF), but access to center-based cardiac rehabilitation (CBCR) is often limited. Mobile health (mHealth) platforms enable remote, virtual, or hybrid cardiac rehabilitation (RVH-CR) delivery. This study aimed to evaluate the effectiveness and safety of structured, exercise-focused RVH-CR supported by mHealth compared with usual care or CBCR in patients with heart failure with reduced ejection fraction (HFrEF) or in HF populations predominantly comprising patients with HFrEF. We searched PubMed, Web of Science, MEDLINE via Ovid, Cochrane CENTRAL, and CINAHL Complete from inception to April 27, 2026. Randomized controlled trials comparing mHealth-supported RVH-CR with usual care or CBCR were included. The primary outcome was exercise capacity, assessed by peak oxygen uptake (VO2 peak) and 6-minute walk distance (6MWD). Secondary outcomes included health-related quality of life and safety. Data were pooled using random-effects meta-analysis stratified by comparator. Risk of bias was assessed with the Cochrane Risk of Bias Tool version 2, and evidence certainty was evaluated using GRADE (Grading of Recommendations Assessment, Development, and Evaluation). Eight randomized controlled trials with 1368 patients were included. In the CBCR comparison, mHealth-supported RVH-CR showed a statistically significant greater improvement in VO2 peak than CBCR (mean difference [MD] 0.82, 95% CI 0.06-1.57; P=.03), although this finding was based on a limited number of trials. Compared with usual care, mHealth-supported RVH-CR was associated with improved 6MWD (MD 22.99, 95% CI 1.15-44.82; P=.04). Single-trial estimates suggested improvements in VO2 peak (MD 2.50, 95% CI 0.88-4.12) and Minnesota Living with Heart Failure Questionnaire scores (standardized MD -0.57, 95% CI -0.98 to -0.17; P<.01) versus usual care. The certainty of evidence ranged from low to moderate. No intervention-related deaths or serious adverse events were reported, but sparse events and short follow-up limited conclusions regarding safety. The effects of structured RVH-CR supported by mHealth differed according to comparator type, but the certainty of evidence ranged from low to moderate. Compared with usual care, mHealth-supported RVH-CR was associated with improved 6MWD. Compared with CBCR, mHealth-supported RVH-CR showed a significantly greater improvement in VO2 peak in a limited number of trials, but superiority, equivalence, or noninferiority to CBCR cannot be concluded. Because usual care and CBCR are clinically distinct comparators, no single overall effect across comparator types should be inferred. Future studies should assess long-term outcomes and standardize structured exercise protocols across RVH-CR models.