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Comparison of Adult Tracheostomy Outcomes Before and After Implementation of a Dedicated Tracheostomy Team.

OBJECTIVE: (A) Determine patient and institutional factors associated with increased length of stay (LOS) and complications of tracheostomy, (B) Develop data-driven quality improvement in tracheostomy care. DESIGN: Mixed methods protocol used cross-sectional survey assessing institutional trends in tracheostomy-specific care. Retrospective chart review compared tracheostomy patient outcomes prior to and during implementation of a multidisciplinary tracheostomy care team and standardized guidelines. PARTICIPANTS: Patients undergoing tracheostomy from January 2019 to December 2021 at a tertiary hospital. METHODS: Patient factors, procedure type and indication, tracheostomy tube size, management timeline, insurance, and disease severity using Acute Physiology and Chronic Health Evaluation II (APACHE II) score were analyzed for associations with LOS and adverse events. Multivariate analyses controlled for APACHE II score and payer source. LOS and complications were compared between patients before and during implementation of multidisciplinary tracheostomy care team and standardized guidelines. RESULTS: Three-hundred and eighteen patients met criteria with a 21.7% complication rate, average LOS of 24 days (SD&#x2009;=&#x2009;28.523), and median LOS post-tracheostomy of 14 days (IQR 7, 29). Departments without standardized protocols had greater LOS (F[1,316]&#x2009;=&#x2009;28.706, P&#x2009;<&#x2009;.001]) and complication odds (OR&#x2009;=&#x2009;2.92, P&#x2009;=&#x2009;.015, 95% CI[1.231, 6.930]). Larger tracheostomy tube size was linked to increased LOS (&#x3b2;&#x2009;=&#x2009;.253, t(314)&#x2009;=&#x2009;4.741, P&#x2009;<&#x2009;.001, 95% CI[4.137, 10.081]). Delays from ventilation discontinuation to cuffless tube exchange and decannulation correlated with increased LOS (&#x3b2;&#x2009;=&#x2009;.406, t(184)&#x2009;=&#x2009;6.321, P&#x2009;<&#x2009;.001, 95% CI[.928, 1.771]); (&#x3b2;&#x2009;=&#x2009;.554, t(129)&#x2009;=&#x2009;7.625, P&#x2009;<&#x2009;.001, 95% CI[1.008, 1.715]). When focusing on a single department, comparing 2019 patients to 2021 patients (pre- and post-guideline and care team), overall, LOS decreased from 33.08 to 30.83 days (P&#x2009;=&#x2009;.586). When excluding patients discharged on a ventilator, the 2019 group had average LOS of 37.938 days versus 33.41 days in 2021 (P&#x2009;=&#x2009;.344). CONCLUSIONS: Standardized tracheostomy care guidelines and multidisciplinary care teams are critical to improving institutional outcomes. Data-driven approaches to quality improvement ensure efficient and targeted methods to improving patient care. LEVEL OF EVIDENCE: 4.

Humans

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

Evaluation of the clinical and mechanistic role of MCM2 expression in the prediction of meningioma recurrence after radiotherapy.

OBJECTIVE: Postoperative radiotherapy is an effective treatment for meningiomas; however, treatment response varies among patients. In addition, practical methods for predicting tumor recurrence after radiotherapy have not been well established. Minichromosome maintenance protein 2 (MCM2), a key regulator of DNA replication licensing, was recently implicated in highly proliferative molecular subtypes of meningioma. In this study, the authors evaluated whether MCM2 immunohistochemical expression predicts response to radiotherapy in patients with meningiomas. METHODS: The authors retrospectively analyzed the records of patients with WHO grade 1-3 meningiomas treated with resection followed by radiotherapy at a single institution between July 2003 and November 2023. The MCM2 labeling index was assessed immunohistochemically, and patients were stratified into MCM2-high and -low groups using a cutoff of 35%. Progression-free survival (PFS) was defined as the interval from the completion of radiation therapy to postoperative radiological tumor recurrence or regrowth. Patients who showed no progression were censored at their last follow-up. PFS was estimated using Kaplan-Meier analysis and subsequently evaluated with Cox proportional hazards models. To further investigate the biological mechanisms associated with MCM2 expression, comprehensive transcriptomic analyses, including gene set enrichment analysis, was performed to elucidate the molecular processes that occur within MCM2-high tumors. RESULTS: The study population included 15 men (42%) and 21 women (58%), with a mean age of 63 years. Ten tumors (28%) were classified as MCM2-high meningiomas and 26 (72%) as MCM2-low meningiomas. High MCM2 expression was significantly associated with WHO grades 2-3 histology and higher Ki-67 labeling indices. During a median follow-up of 2.52 years, tumor progression after radiotherapy occurred in 47% of the patients. High MCM2 expression (HR 8.34, p = 0.03) was significantly associated with shorter PFS and remained an independent predictor of recurrence after adjustment for WHO grade, tumor size, and Ki-67 labeling index. Transcriptomic analyses of MCM2-high tumors revealed upregulation of cell proliferation-related pathways, accompanied by increased signaling through the E2F8-CHEK1 axis associated with radiation resistance and suppression of the TNF-&#x3b1; signaling pathway implicated in radiosensitivity. CONCLUSIONS: In meningiomas, high MCM2 expression is associated with early recurrence following radiotherapy. The study findings suggest that this association is driven by diverse biological mechanisms related to cell cycle regulation and radioresistance. Immunohistochemical assessment of MCM2 expression may serve as a practical and accessible biomarker for risk stratification and may support the future development of individualized postoperative radiotherapy strategies.

Humans

Prognostic value of the Island sign for hematoma expansion and functional outcome after intracerebral hemorrhage: a systematic review and meta-analysis.

PURPOSE: The Island Sign (IS) is a radiological finding observed in patients with intracerebral hemorrhage (ICH). This meta-analysis aimed to evaluate the association between IS and both hematoma expansion (HE) and functional outcomes by comparing ICH patients with and without IS. METHODS: We searched PubMed, Embase and Cochrane Library for studies of intracerebral hemorrhage reporting the IS. The primary outcomes were functional status and hematoma expansion, secondary outcome was mortality. Statistical analysis was performed using RStudio, effect sizes were calculated as odds ratios (ORs) with 95% confidence interval (95% CIs), and heterogeneity was assessed with I2 statistics. In addition, meta-regression and sensitivity analyses were performed, and publication bias was assessed through funnel plots and Egger's regression test. RESULTS: We included 21 observational studies with a total of 9,459 patients with spontaneous ICH, 1,769 of them had IS, while 7,690 did not. The mean age was 63.5&#xa0;&#xb1;&#xa0;13.2 and 5,835 (61.7%) were male. Poor functional outcomes (OR 2.77, 95% CI: 2.14-3.58, p&#xa0;<&#xa0;0.0001, I2&#xa0;=&#xa0;4.9%) and hematoma expansion (OR 2.75, 95% CI: 1.87-4.03, p&#xa0;<&#xa0;0.0001, I2&#xa0;=&#xa0;77.4%) were substantially higher in patients with IS, as well as the overall mortality rate (OR 2.54, 95% CI: 1.55-4.17, p&#xa0;=&#xa0;0.0002, I2&#xa0;=&#xa0;0%). Meta-regression analysis showed no statistically significant association between imaging-related timing variables and hematoma expansion. Furthermore, the leave-one-out sensitivity analyses showed that no single study exerted a disproportionate influence on the overall effect for the examined outcomes, and Egger's linear regression tests were not statistically significant for both outcomes. CONCLUSION: Patients with the Island Sign are associated with higher rates of poor functional outcomes and hematoma expansion. Thus, IS is a relevant radiological finding with potential to support early risk stratification and optimize patient management and treatment selection.

Humans

Efficacy, acceptability, and related outcomes of pharmacological interventions for acute bipolar mania: a systematic review and dose-related network meta-analysis across different age groups.

BACKGROUND: Acute bipolar mania carries negative social and economic consequences. We investigated the comparative efficacy/response/acceptability of pharmacological interventions for acute bipolar mania, considering dose effects across different age groups. METHODS: We conducted a network meta-analysis (NMA) to search for randomized controlled trials (RCTs) comparing pharmacological interventions with one another or placebo in acute bipolar mania patients, indexed in PubMed/MEDLINE, Embase, Web of Science, and Scopus (from inception through 2025.12.24). Co-primary outcomes were change in manic symptoms/response/and acceptability. Tolerability/remission and rate of adverse events were secondary outcomes. Confidence-In-Network-Meta-Analysis was likewise appraised. RESULTS: 113 RCTs, encompassing 49 distinct treatment combinations, included 20,666 participants. Sensitivity analysis retaining only low-risk-of-bias studies and excluding outliers for possible effect modifiers indicated that risperidone 3&#xa0;mg/day(SMD&#xa0;=&#xa0;-7.57;95%C.I.&#xa0;=&#xa0;-8.25;-5.85); tamoxifen 160&#xa0;mg/day(SMD&#xa0;=&#xa0;-1.73;95%C.I.&#xa0;=&#xa0;-2.32;-1.13); rivastigmine 3&#xa0;mg/day(SMD&#xa0;=&#xa0;-1.13;95%C.I.&#xa0;=&#xa0;-1.06;-0.58); haloperidol 30&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.96;95%C.I.&#xa0;=&#xa0;-1.25;-0.75); valproate 750&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.76;95%C.I.&#xa0;=&#xa0;-1.48;-0.58); tamoxifen 40&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.75;95%C.I.&#xa0;=&#xa0;-1.41;-0.59); celecoxib 400&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.74;95%C.I.&#xa0;=&#xa0;-1.20;-0.38); paliperidone extended-release 12&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.62; 95%C.I.&#xa0;=&#xa0;-0.91;-0.32); olanzapine 15&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.59;95%C.I.&#xa0;=&#xa0;-0.60;-0.38); olanzapine 20&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.52;95%C.I.&#xa0;=&#xa0;-0.66;-0.38); risperidone 4&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.53;95%C.I.&#xa0;=&#xa0;-0.76;-0.29); allopurinol 600&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.54;95%C.I.&#xa0;=&#xa0;-0.67;-0.22); cariprazine 12&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.49;95%C.I.&#xa0;=&#xa0;-0.66;-0.33); risperidone 4.2&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.46;95%C.I.&#xa0;=&#xa0;-0.75;-0.17); lithium 1500&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.42;95%C.I.&#xa0;=&#xa0;-0.57;-0.28); ziprasidone 160&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.49;95%C.I.&#xa0;=&#xa0;-0.68;-0.31); asenapine 20&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.38;95%C.I.&#xa0;=&#xa0;-0.53;-0.22); haloperidol 8&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.34;95%C.I.&#xa0;=&#xa0;-0.63;-0.05); aripiprazole 15&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.33;95%C.I.&#xa0;=&#xa0;-0.61;-0.06) outperformed placebo. Ziprasidone 160&#xa0;mg/day, celecoxib 200&#xa0;mg/day, asenapine 20&#xa0;mg/day, and asenapine 10&#xa0;mg/day proved more efficacious than placebo in children. No statistically significant differences were reported between treatments and placebo for response/remission/acceptability/tolerability, and manic/hypomanic switch. A meta-regression of efficacy effect sizes against the adapted AMSTAR-Plus content scores showed that larger SMDs were associated with lower AMSTAR scores, indicating lower study quality, warranting further caution for such large efficacy estimates. CONCLUSIONS: Our findings are consistent with previous NMAs and current guidelines, expanding the current knowledge base while concurrently appraising different drugs, doses, and age groups.

Humans

Matching-adjusted indirect comparison of fruquintinib versus ramucirumab in advanced gastric or gastroesophageal junction adenocarcinoma.

Aim: Fruquintinib (Fruq), a selective VEGFR 1/2/3 inhibitor, showed a significant progression-free survival (PFS) benefit in the Phase III FRUTIGA trial for advanced gastric/gastroesophageal junction (G/GEJ) adenocarcinoma. Ramucirumab (RAM), an anti-VEGFR2 antibody, demonstrated efficacy in the RAINBOW-Asia trial. This anchored matching-adjusted indirect comparison (MAIC) evaluated Fruq plus paclitaxel versus RAM plus paclitaxel as second-line therapy for G/GEJ adenocarcinoma in the absence of head-to-head trials. Materials & methods: Data from individual patients in the FRUTIGA study (N&#xa0;=&#xa0;703) and aggregated data from the RAINBOW-Asia study (N&#xa0;=&#xa0;440) were analyzed. Baseline characteristics were balanced using entropy balancing. The placebo plus paclitaxel (PBO&#xa0;+&#xa0;PTX) groups served as the common comparators. The primary outcome was PFS; secondary outcomes included overall survival, objective response rate (ORR) and disease control rate (DCR). Rates of treatment-emergent adverse events (TEAEs) were also compared as an exploratory outcome using an adjusted indirect risk difference. Sensitivity analyses included restricted mean survival time and simulated treatment comparison. Results: After weighting (effective sample size&#xa0;=&#xa0;564), baseline covariates were balanced. The anchored MAIC demonstrated that Fruq&#xa0;+&#xa0;PTX significantly improved PFS compared with RAM&#xa0;+&#xa0;PTX (HR: 0.70; 95% CI: 0.51-0.96; p&#xa0;=&#xa0;0.0280), corresponding to a 30% reduction in progression risk, with a significant restricted mean survival time benefit of 1.18&#xa0;months at 20&#xa0;months (95% CI: 0.08-2.27; p&#xa0;=&#xa0;0.024). Fruq achieved significantly higher ORR (OR: 1.76, 95% CI: 1.16-2.68; p&#xa0;=&#xa0;0.008) and DCR (OR: 1.94, 95% CI: 1.33-2.83; p&#xa0;<&#xa0;0.001). Overall survival was similar (0.97; 95% CI: 0.73-1.30; p = 0.8640). Subgroup analyses showed PFS benefits with Fruq in patients with ECOG PS 1, peritoneal metastases and two or fewer metastatic sites. In sensitivity analysis, the simulated treatment comparison also suggested a PFS benefit for Fruq&#xa0;+&#xa0;PTX (HR: 0.40, 95% CI: 0.32-0.50; p&#xa0;<&#xa0;0.0001). For any-grade TEAEs, the indirect comparison showed higher adjusted relative incidences of increased bilirubin with Fruq&#xa0;+&#xa0;PTX than with RAM&#xa0;+&#xa0;PTX (RD: 12.3%; 95% CI: 2.3-22.4%, p&#xa0;<&#xa0;0.05) and of hypokalemia (RD: 9.0%; 95% CI: 1.5-16.4%, p&#xa0;<&#xa0;0.05). For grade &#x2265;3 TEAEs, the adjusted relative incidence of decreased body weight was higher with Fruq&#xa0;+&#xa0;PTX than with RAM&#xa0;+&#xa0;PTX (RD: 2.9%; 95% CI: 0.6-5.2%, p&#xa0;<&#xa0;0.05). The adjusted relative incidences of increased AST, ALT and hypocalcemia were numerically lower in the fruquintinib group than in the RAM group. Conclusion: This MAIC indicates that Fruq&#xa0;+&#xa0;PTX may be more effective than RAM&#xa0;+&#xa0;PTX in second-line advanced G/GEJ adenocarcinoma, with potentially improved PFS, ORR and DCR, and similar overall survival. Safety analyses suggested generally comparable safety profiles across the two regimens. Fruq&#xa0;+&#xa0;PTX remains a valuable treatment option, offering important comparative evidence for clinical and health technology assessment decisions. Trial Registration: Clinicaltrials.gov identifiers: NCT07144995.

Adult

Fracture-related infection following open forefoot fractures caused by dropped objects.

INTRODUCTION: This study evaluated the rate of fracture-related infection (FRI) of open forefoot fractures caused by dropped objects, and examined associations of treatment characteristics, including intravenous and oral antibiotics and operative debridement, with FRI. METHODS: Patients aged 18-80 years who sustained an open metatarsal or phalanx fracture caused by a dropped object between January 2021 and June 2024 were retrospectively identified from two Level 1 trauma centers. The primary outcome was FRI, determined based on the FRI consensus criteria. FRI rates were compared between those who underwent irrigation and debridement (I&D) at bedside versus in the operating room, and between those who received oral versus intravenous (IV) antibiotics. Patient characteristics were also analyzed to determine host factors associated with FRI. RESULTS: A total of 86 patients (median age 41 years [IQR: 29-56], 58% male) were included. Eighty-five patients (99%) received antibiotics, 31 (36%) of whom received intravenous antibiotics. Sixty-six patients (77%) received an I&D at presentation, 57 (66%) at bedside and 9 (10%) in the operating room. Thirteen patients (15%, 95% CI: 8.3%-24%) developed FRI. No significant difference in FRI rate was found between patients who underwent I&D at bedside versus in the operating room (12% versus 11%, p&#x202f;>&#x202f;0.99). Among patients who did not undergo I&D in the operating room, no significant difference in FRI rate was found between patients who received oral versus IV antibiotics (17% versus 13%, p&#x202f;=&#x202f;0.74). Insulin-dependent diabetes was associated with an increased risk of FRI (60% versus 12%, p&#x202f;=&#x202f;0.02). CONCLUSIONS: In this cohort, one in seven patients developed FRI. No statistically significant differences in FRI rates were observed by I&D setting (bedside versus operative) or antibiotic route (oral versus IV), including in a subgroup analysis excluding patients treated with operating room I&D. These findings are limited by sample size and potential treatment selection bias and should not be interpreted as evidence of equivalence. Management should be individualized based on clinical judgement, resource availability, and patient factors. These findings can help guide the management protocols for "dropped objects" open forefoot fractures presenting to urgent care and the emergency department. LEVEL OF EVIDENCE: Therapeutic Level III.

Humans

Beyond Glycaemia: Fear of Hypoglycaemia, Cognition and Functional Mobility After Advanced Hybrid Closed-Loop Therapy in Older Adults With Type 1 Diabetes: A Prespecified Secondary Analysis of a Randomised, Single-Centre Study.

BACKGROUND: Evidence on psychological, cognitive and functional outcomes of advanced diabetes technologies in older adults with long-standing type 1 diabetes (T1D) remains limited. We evaluated whether initiation of advanced hybrid closed-loop (AHCL) therapy was associated with changes in fear of hypoglycaemia, diabetes distress, psychological well-being, cognition, frailty-related measures and mobility-related function in adults aged &#x2265;&#x2009;65&#x2009;years with T1D. METHODS: This prespecified, exploratory secondary analysis was conducted within a single-centre, open-label, randomised, controlled, parallel-group trial including adults aged &#x2265;&#x2009;65&#x2009;years with long-standing T1D. Participants were randomly assigned (1:1) to initiate AHCL therapy using the MiniMed 780G system or to continue standard diabetes treatment. The secondary outcomes included WHO-5, the 17-item Diabetes Distress Scale (DDS), Hypoglycemia Fear Survey-II (HFS-II), Montreal Cognitive Assessment, Digit Symbol Substitution Test, Fried frailty phenotype and performance-based functional measures. No formal sample-size calculation was performed for these secondary outcomes. RESULTS: Thirty-one participants were randomised and 29 completed 12&#x2009;months of follow-up and were included in the treatment-effect analyses. In the baseline-adjusted primary analysis, AHCL therapy was associated with a lower HFS-II score than standard treatment (adjusted mean difference -18.9; 95% CI: -32.4 to -5.4; nominal p&#x2009;=&#x2009;0.008), although this finding did not remain statistically significant after Holm correction (adjusted p&#x2009;=&#x2009;0.104) or in an exploratory model additionally adjusted for sex (difference -13.6; 95% CI: -32.2 to 5.0; p&#x2009;=&#x2009;0.145). Diabetes distress, psychological well-being, global cognition and processing speed did not differ between groups. In sex-adjusted sensitivity analyses, the between-group differences remained statistically significant for 6-min walk distance (92.6&#x2009;m; 95% CI: 36.8 to 148.3; p&#x2009;=&#x2009;0.002) and Timed Up and Go performance (-2.27&#x2009;s; 95% CI: -4.28 to -0.27; p&#x2009;=&#x2009;0.028), but not for gait speed (0.27&#x2009;m/s; 95% CI: -0.05 to 0.59; p&#x2009;=&#x2009;0.099). At 12&#x2009;months, 12 of 14 AHCL participants were robust and 2 were pre-frail; in the control group, 11 of 15 were robust and 4 were pre-frail. No participant was classified as frail at follow-up. CONCLUSIONS: In this small, selected cohort, AHCL therapy was associated with a nominally lower fear-of-hypoglycaemia score and better performance on selected mobility-related tests over 12&#x2009;months. The fear-of-hypoglycaemia finding did not remain statistically significant after correction for multiple comparisons or additional adjustment for sex. Six-minute walk distance and Timed Up and Go remained statistically significant in the exploratory sex-adjusted sensitivity analyses, whereas the gait-speed difference did not. No measurable between-group deterioration in global cognition or processing speed was observed. These exploratory findings require confirmation in larger studies with balanced representation by sex and direct measurement of physical activity. These findings also support a person-centred clinical message: older age alone should not be regarded as a barrier to AHCL when treatment is introduced with individualised education and appropriate ongoing support.

Humans

The hidden threat from food-derived carbon dots: Formation, biodistribution, and potential health risks.

Food-derived carbon dots (CDs) are a new class of carbon-based nanoparticles generated during the thermal processing of food matrices. These nanomaterials have been extensively studied for their unique fluorescence, good biocompatibility, and tunable surface chemistry in food detection, intelligent packaging, and biomedical applications. However, their nanoscale size and high surface activity have raised safety concerns regarding biological interactions, in vivo biodistribution, and potential long-term health hazards. Although CDs have traditionally been regarded as low-toxicity materials due to their favorable biocompatibility, the potential hidden risks of CDs have not received sufficient attention. CDs exhibit dose-dependent toxicity, not only accumulating in various tissues and organs but also potentially inducing oxidative stress and interfering with cellular metabolic functions. Therefore, this review summarizes the advances in sources, synthetic strategies, and core properties of CDs, with a special focus on in vivo biological interactions, fates, and potential safety challenges. In addition, it is proposed that the standardized detection and risk assessment system should be established to further explore the long-term health effects of CDs under real dietary exposure, thereby ensuring their safety and sustainable application.

Carbon Quantum Dots

Adaptive Sports Exposure Across Physical Medicine and Rehabilitation Residency and Sports Medicine Fellowship Programs: A National Cross-Sectional Website Analysis.

Adaptive sports improve health and quality of life for people with disabilities, yet the extent of adaptive sports exposure in physical medicine and rehabilitation (PM&R) training is unclear. This cross-sectional study reviewed the public websites of 115 accredited physical medicine and rehabilitation residency programs and 26 sports medicine fellowship programs for any mention of adaptive sports, characterizing exposure type, target populations, and associated program characteristics. Adaptive sports were mentioned by 32 residency programs (27.8%) and 8 fellowship programs (30.8%). Mention varied significantly by geographic region in both cohorts (residency, West 64% vs. South 19%, P=.017; fellowship, Midwest 80% vs. South 0%, P=.035) and, among residencies, was associated with larger program size and a greater number of associated subspecialty fellowships. Residency exposure was predominantly volunteer-based, whereas fellowship exposure was exclusively clinical or undisclosed; target populations served were frequently unspecified. Programs have an opportunity to expand structured adaptive sports training and to clearly convey these opportunities to applicants and patients.

Adaptive sports

Clinical Utility of Ultra-Widefield Swept-Source OCT for Intraocular Tumors: Comparison With Ultrasonography, SD-OCT, and MRI.

PURPOSE: To evaluate the clinical performance of ultra-widefield swept-source optical coherence tomography (UWF-OCT) in the assessment of choroidal tumors and to compare it with ultrasonography (US), spectral-domain (SD)-OCT, and magnetic resonance imaging (MRI). DESIGN: Retrospective diagnostic comparison. SUBJECTS: Thirty-nine eyes from 39 patients diagnosed with choroidal tumors at a single tertiary referral center. METHODS: This retrospective diagnostic comparison evaluated patients diagnosed with choroidal tumors at a single tertiary referral center between January 2023 and August 2025. All patients underwent UWF-OCT imaging at diagnosis. Tumor measurements obtained with UWF-OCT were compared with US, SD-OCT, and MRI. Comparative analysis among imaging modalities and predictors affecting UWF-OCT applicability was performed. MAIN OUTCOME MEASURES: Tumor thickness (mm) and largest basal diameter (LBD, mm) measurements, and complete measurability rate across different tumor size categories. RESULTS: Thirty-nine eyes from 39 patients (mean age 59.2 &#xb1; 16.9 years) were analyzed, including 27 choroidal melanomas (69.2%), 5 metastatic tumors (12.8%), 4 hemangiomas (10.3%), 2 osteomas (5.1%), and 1 (2.6%) indeterminate choroidal melanocytic lesion. UWF-OCT successfully measured both tumor thickness and largest basal diameter (LBD) in 100% (31/31) of small and medium choroidal tumors, substantially outperforming SD-OCT (complete measurement achieved in 63.6% of small tumors, and 0% of medium or large tumors). UWF-OCT measurements were systematically smaller than ultrasonography (thickness: -32.3%, P < .01; LBD: -11.1%, P < .01) and MRI (thickness: -29.2%, P < .01). Mushroom-shaped tumor morphology was the strongest negative predictor of UWF-OCT quality (OR = 0.015, 95% CI 0.001-0.196, P < .01). UWF-OCT's complete measurability was limited in large tumors (12.5%, 1/8). CONCLUSIONS: UWF-OCT provides precise, noninvasive, single-scan assessment of small-to-medium choroidal tumors with detailed structural visualization. It may be particularly useful for dome-shaped tumors, while multimodal imaging with US and MRI remains optimal for complex morphologies. Overall, UWF-OCT represents a valuable tool for diagnosis and treatment planning, with potential utility for longitudinal follow-up in choroidal tumor management.

Humans

Virtual, Augmented, and Mixed Reality Technologies in Neurosurgical Training: Enhancing Skills and Surgical Outcomes: A Systematic Review.

OBJECTIVE: To systematically review the role of virtual reality (VR), augmented reality (AR), and mixed reality (MR) in neurosurgical education and training. DESIGN: Systematic review conducted in accordance with the PRISMA guidelines. SETTING: A comprehensive search was performed across PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar for English-language studies published between 1 January 2020 and 30 April 2026. PARTICIPANTS: Studies involving neurosurgeons, fellows, residents, and medical students (maximum sample size: n = 48) were included. RESULTS: Of 7,204 initially identified studies, 25 met the inclusion criteria. VR was primarily used for surgical simulation (100% of VR studies) and anatomical education (62.5%). AR demonstrated broader applications, including preoperative planning (40%) and intraoperative support (30%). MR was evenly distributed across simulation, planning, and intraoperative support (40% each). The most frequently improved outcomes were training effectiveness (52%) and technical proficiency (44%). Methodological quality scores, assessed using the Modified Medical Education Research Study Quality Instrument (MMERSQI), ranged from 39.5 to 84.5, indicating varied rigor. CONCLUSION: VR, AR, and MR technologies show potential to enhance surgical precision, technical skills, and educational outcomes in neurosurgical training. However, standardization of methodologies and cost-effective solutions remain essential. Future research should focus on long-term clinical impact and integration of AI-driven training models.

Virtual Reality

Long-term glycemic variability and risk of peripheral artery disease: a systematic review and meta-analysis of cohort studies.

BACKGROUND: A systematic review and meta-analysis to evaluate the impact of long-term glucose variability (GV) on the risk of developing peripheral artery disease (PAD). METHODS: The protocol was prospectively registered in PROSPERO (ID: CRD420251148763). Relevant longitudinal studies were identified through comprehensive searches of PubMed, Embase, and Web of Science. The primary outcome was the risk ratio (RR) of PAD comparing participants with high versus low GV. Summary effect sizes were calculated using a random-effects model to account for between-study heterogeneity. RESULTS: Eleven cohorts were included. Higher GV showed a positive association with PAD risk (RR: 1.42; 95% CI [1.21-1.66] p&#xa0;<&#xa0;0.001), although substantial heterogeneity was present (I 2&#xa0;=&#xa0;91%). This association was consistent across subgroups defined by region (Asian vs. Western), study design, diabetic status, GV metrics, PAD diagnostic methods, and adjustment for HbA1c (all p for subgroup differences > 0.05), except for follow-up duration. Studies with follow-up < 8 years showed a stronger association than those with &#x2265; 8 years (RR: 1.64 vs. 1.19; p for subgroup difference = 0.006). CONCLUSIONS: Elevated long-term GV appears to be associated with an increased risk of PAD. However, substantial heterogeneity across studies suggests that the magnitude of this association should be interpreted with caution.

Humans

Association between seminal and serum iron parameters and male infertility: a systematic review and meta-analysis.

BACKGROUND: Iron is an essential trace element for normal spermatogenesis, yet excessive iron accumulation may impair male fertility. Preliminary studies imply a link between elevated iron levels and male infertility, but evidence remains limited without systematic quantitative synthesis. This metaanalysis assessed the association between iron concentrations and male infertility. METHODS: We systematically searched PubMed, CBM, CNKI and Cochrane Library. RevMan, Stata and R were used for data analysis. Randomeffects models pooled effect sizes, with forest and funnel plots generated to evaluate seminal and serum iron levels in male infertility. RESULTS: After screening studies published up to April 2025, a total of ten eligible articles involving 985 participants were finally included in this meta-analysis. Pooled results revealed that seminal and serum iron concentrations were notably higher in infertile males compared with fertile controls. Specifically, infertile men presented higher seminal iron levels (SMD&#x2009;=&#x2009;0.44, 95% CI: 0.12-0.76, P&#x2009;<&#x2009;0.05), as well as elevated serum iron levels (SMD&#x2009;=&#x2009;3.77, 95% CI: 1.68-5.87, P&#x2009;<&#x2009;0.05). The present results suggest that increased seminal and serum iron concentrations may be potentially correlated with male infertility risk.

Humans

Primary ACL Repair and Reconstruction in Isolated ACL Ruptures: Forgotten Joint Scores and the Association Between Residual Laxity and Joint Awareness.

BACKGROUND: Primary anterior cruciate ligament (ACL) repair has recently reemerged as a treatment option for carefully selected proximal ACL tears. However, evidence regarding patient-reported joint awareness and the relationship between postoperative laxity and joint awareness remains limited. PURPOSE: To compare joint awareness, clinical outcomes, and postoperative laxity between primary ACL repair and hamstring tendon autograft reconstruction in carefully selected patients with isolated ACL rupture, and to explore the association between residual laxity and postoperative joint awareness. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: This retrospective cohort study included 85 patients with isolated ACL rupture treated with either primary ACL repair (n = 26) or hamstring autograft reconstruction (n = 59), with a minimum follow-up of 24 months. Clinical outcomes, including visual analog scale score, Lysholm score, International Knee Documentation Committee (IKDC) score, Tegner activity scale score, postoperative knee laxity, return to sport, and rerupture rates, were evaluated. The authors also used the Forgotten Joint Score-12 (FJS-12), a measure of joint awareness, to evaluate patients. A higher score reflects lower joint awareness, suggesting function more similar to a native knee. Multivariable regression analyses were performed to evaluate variables associated with postoperative FJS-12 values. RESULTS: No differences were observed between groups in postoperative Lysholm, IKDC, and Tegner activity scale scores; Lachman- and pivot-shift-assessed postoperative laxity; and return-to-sport rates. However, postoperative FJS-12 values were significantly higher in the repair group compared with the reconstruction group (87.0 &#xb1; 15.0 vs 77.5 &#xb1; 14.2; mean difference, 9.5 points [95% CI, 2.8-16.3]; P = .006), corresponding to a moderate effect size (Cohen d = 0.66). Secondary exploratory regression analyses demonstrated that residual postoperative laxity was associated with lower postoperative FJS-12 values in both Lachman- and pivot-shift-based models (R2 = 0.649 and 0.680, respectively; P < .001 for both). CONCLUSION: In carefully selected patients with proximal ACL tears and adequate tissue quality, no significant between-group differences were detected in conventional clinical outcomes, postoperative laxity, return-to-sport rates, or rerupture rates between primary ACL repair and reconstruction. Primary ACL repair was associated with higher postoperative FJS-12 values at short- to midterm follow-up, suggesting function more similar to that of a native knee. Residual postoperative laxity was associated with lower FJS-12 values in secondary exploratory analyses.

Humans

The asymmetry of working memory training transfer: A systematic review and meta-analysis.

Working memory (WM) training is widely used to enhance cognitive performance; however, its transfer to untrained tasks remains controversial. Traditional theories emphasize task similarity as the primary determinant of training transfer, but they cannot fully explain emerging evidence of asymmetric transfer across tasks. Two directional transfer hypotheses are proposed here to explain this asymmetry: the resource-based transfer advantage hypothesis predicts stronger transfer from more to less cognitively demanding tasks, whereas the ability-based transfer advantage hypothesis predicts stronger transfer from tasks engaging broader task-general abilities to tasks engaging task-specific narrower abilities. The contrast between span and updating paradigms provides an informative framework for distinguishing these accounts, because updating tasks are generally more cognitively demanding, whereas span tasks involve broader abilities. Accordingly, we conducted a three-level meta-analysis of 55 studies (208 effect sizes; N = 3,492). The results showed that updating training transferred reliably to span tasks (g = 0.176, p < .001), whereas span training did not reliably transfer to updating tasks (g = 0.048, p = .453), supporting the resource-based account. This advantage of updating training also extended to non-WM outcomes and was more pronounced at lower training doses, in non-adult samples, and with verbal stimuli. Together, these findings extend WM transfer theory beyond task similarity by highlighting the importance of cognitive demand and offer guidance for WM training design.

Humans

An Assessment of Reliability Estimation Methods for Binomial Health Care Quality Measures.

We evaluated the performance of commonly used methods for estimating the reliability of binomial health care quality measures using simulated datasets spanning a range of performance score means and variances, numbers of entities, and patient sample sizes. For each simulation, reliability was estimated for all selected methods and compared with the known true reliability derived from the simulation parameters, with methods assessed on their accuracy and precision. Logistic regression with reliability estimated on the outcome scale demonstrated the highest accuracy and precision among all methods evaluated. The widely used Adams beta-binomial method performed poorly, although a modification recommended by Nieser and Harris substantially improved its performance. These approaches are applicable only to binomial measures. Among methods that can be applied to both binomial and continuous measures, permutation resampling of the Spearman rank correlation coefficient was the most accurate and precise, outperforming other commonly used approaches. Overall, for binomial quality measures, logistic regression on the outcome scale is the preferred method for reliability estimation, followed closely by the modified beta-binomial approach, while for non-binomial measures, permutation-based Spearman rank correlation appears to be the most suitable method.

Reproducibility of Results

Game-Based Intervention for Bullying: Assessing the Efficacy of the REThink Therapeutic Game in Primary School Children.

Children's mental health issues can have a lasting effect into adulthood, including enhanced risks for their social and emotional development, as well as their academic performance and overall behavior. Worldwide nearly 1 billion children are affected by the bullying phenomenon, with social, emotional, and economic consequences. In this vein, our study aimed to analyze the effect of the therapeutic game REThink on the improvement of emotion regulation abilities and the reduction of both bullying behavior and victimization in primary school children. Our sample consisted of 75 children who were voluntarily enrolled by their parents, and randomly assigned to the intervention group (n&#x2009;=&#x2009;38) or to the control group (n&#x2009;=&#x2009;37). They completed the baseline assessment consisting of emotion regulation, irrationality, bullying and victimization behavior measurements, then the children from the intervention group played the therapeutic game REThink. Four&#x2009;weeks later, after completing each level twice, every participant had completed the same questionnaires at the post-test assessment. The results indicated significant changes across victimization for children who were exposed to verbal, physical or social bullying, increased emotional control and lower levels of irrationality, low frustration tolerance to work and demandingness, with small to medium effect size improvements for the REThink game group compared to the control group. The REThink therapeutic game proved to be a promising intervention tool for reducing victimization effects and irrationality, and improving emotion regulation abilities in primary school children. Future research could improve on these results by addressing the timeline stability limit.

Humans