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Dexamethasone as an adjuvant to continuous erector spinae plane block for postoperative analgesia after video-assisted thoracoscopic surgery for pulmonary nodule surgery: a randomized controlled trial.

BACKGROUND: While dexamethasone is proven to enhance single-shot erector spinae plane block (ESPB), its role as an adjuvant in continuous ESPB catheters is unclear. This randomised controlled trial evaluated whether adding dexamethasone to ropivacaine improves analgesia after video-assisted thoracoscopic surgery (VATS). METHODS: 85 patients undergoing VATS with continuous ESPB were randomised to receive postoperative infusion of either 0.2% ropivacaine(C-ESPB group) or ropivacaine with 10&#x2009;mg dexamethasone(D&#x2009;+&#x2009;C-ESPB group). The primary outcome was resting pain visual analog scale (VAS)at 12&#x2009;h postoperatively, while secondary outcomes included QoR-15 scores, tramadol consumption, time to first analgesic requirement, postoperative adverse events, 3-month incidence of chronic pain, catheter-related complications, pain intensity at other times, and hospital stay. RESULTS: The D&#x2009;+&#x2009;C-ESPB group had significantly lower resting pain at 12&#x2009;h [2.56 (1.03) vs 3.24 (1.21), mean difference -0.680, p&#x2009;=&#x2009;0.006]; and lower coughing pain at 12&#x2009;h [4.60 (1.48) vs 5.69 (1.35), mean difference 1.086, p&#x2009;<&#x2009;0.001], with analgesic superiority sustained through 72&#x2009;h. Quality of Recovery-15 scores were higher at 12&#x2009;h [124.70 (12.48) vs 117.26 (12.24); mean difference -7.436, p&#x2009;=&#x2009;0.007] and 48&#x2009;h [141.60 (5.51) vs 138.98 (6.64); mean difference -2.628, p&#x2009;=&#x2009;0.050]; Total tramadol consumption over 72&#x2009;h was markedly reduce [0 (0,100) vs 100 (75,100), z&#xa0;=&#xa0;-3.807, p&#x2009;<&#x2009;0.001], and hospital stay was shorter [Mean (SD) 6.09 (1.34)&#xa0;d vs 6.93 (1.55)d, p&#x2009;<&#x2009;0.001]. The intervention did not, however, alter the 3-month incidence of chronic postsurgical pain (31% vs 34%, p&#x2009;=&#x2009;0.756). CONCLUSION: Dexamethasone significantly enhances the analgesic efficacy of continuous ESPB, improving early pain control, recovery quality, and opioid-sparing after VATS, but does not reduce the incidence of chronic persistent surgical pain.

Humans

Randomized phase-II trial of surufatinib plus FOLFOX/FOLFIRI versus FOLFOXIRI as second-line therapy for metastatic colorectal cancer.

BACKGROUND: Second-line treatment for metastatic colorectal cancer (mCRC) typically involves oxaliplatin- or irinotecan-based doublet chemotherapy with or without anti-angiogenic antibodies. Triplet regimens such as FOLFOXIRI have demonstrated synergy and improved efficacy as first-line therapy. Surufatinib, an oral multi-kinase inhibitor targeting VEGFR1-3, FGFR1, and CSF-1R, may enhance chemotherapy efficacy. We evaluated surufatinib combined with doublet (FOLFOX/FOLFIRI) versus triplet (FOLFOXIRI) chemotherapy as second-line treatment for mCRC. PATIENTS AND METHODS: This multicentre, open-label, randomized phase-II trial used Simon's minimax two-stage design. Eligible patients had mCRC progressing on or within 6&#x2009;months after first-line doublet chemotherapy. Patients were randomized 1:1 to surufatinib 250&#x2009;mg once daily plus either mFOLFOX6/FOLFIRI (doublet cohort, selected based on prior regimen) or FOLFOXIRI (triplet cohort). The primary endpoint was objective response rate (ORR). RESULTS: From September 2021 to November 2023, 57 patients were randomized (28 per cohort after one withdrawal). In the doublet cohort, ORR was 35.7% (95% CI: 18.6-55.9), median progression-free survival (PFS) was 5.4&#x2009;months (95% CI: 3.8-7.0), and median overall survival (OS) was 19.0&#x2009;months (95% CI: 9.2-28.8). In the triplet cohort, ORR was 39.3% (95% CI: 21.5-59.4), median PFS was 5.8&#x2009;months (95% CI: 3.3-8.2), and median OS was 10.9&#x2009;months (95% CI: 6.0-15.8). Grade &#x2265;3 treatment-emergent adverse events occurred more frequently in the triplet (71.4%) versus doublet (57.1%) cohort, with higher rates of treatment delays (89.3% versus 72.0%) and discontinuations (25.0% versus 14.3%). CONCLUSIONS: Surufatinib plus doublet chemotherapy showed encouraging antitumor activity and acceptable tolerability in second-line mCRC, warranting further evaluation in a larger randomized trial. In contrast, surufatinib plus triplet chemotherapy was associated with increased toxicity, more frequent treatment delays or discontinuations, and shorter overall survival; this combination is not recommended for further investigation in this setting.ClinicalTrials.gov: NCT04734249Date of registration: January 31, 2021.

Humans

Prevalence and risk factors of red blood cell alloimmunization among sickle cell disease patients in resource-limited countries: A systematic review and meta-analysis.

BACKGROUND: Sickle cell disease (SCD) is an inherited hemoglobinopathy characterized by hemoglobin S production, in which homozygous individuals (HbSS) develop a broad range of acute and chronic complications. While disease-modifying and curative therapies are increasingly available in high-income settings, red blood cell (RBC) transfusion remains the mainstay of treatment in resource-limited countries and is associated with high rates of alloimmunization. This systematic review and meta-analysis aimed to estimate the prevalence of alloimmunization and identify associated risk factors among patients with SCD living in resource-limited settings. METHODS: Africa Journals Online (AJOL), Embase, PubMed, Scopus, and Web of Science were searched for original studies published from inception to December 15, 2025. Only studies conducted in low- and lower-middle-income countries (LMICs) were included. Eligible studies evaluated the prevalence of alloimmunization in patients with SCD receiving RBC transfusions. A random-effects meta-analysis of proportions was performed to pool quantitative data, while qualitative findings were systematically summarized in tabular form. Statistical heterogeneity was assessed using the I&#xb2; statistic and further explored using Baujat plots, leave-one-out analyses, and meta-regression. RESULTS: Our analysis included 27 studies conducted in Africa (n&#x202f;=&#x202f;23) and Asia (n&#x202f;=&#x202f;4), predominantly from lower-middle-income countries (n&#x202f;=&#x202f;19) and mainly employing a cross-sectional design (n&#x202f;=&#x202f;20), comprising 3128 previously transfused patients with SCD. The pooled prevalence of RBC alloimmunization was 8.76% (95% CI: 6.71-11.37%; I&#xb2; = 75%). Higher alloimmunization rates were observed in West and North Africa, particularly in C&#xf4;te d'Ivoire, Egypt, and Nigeria, whereas lower rates were reported in Asia and East Africa. The most frequently identified antibodies belonged to the Rh blood group system (n&#x202f;=&#x202f;153), followed by the Kell system (n&#x202f;=&#x202f;65). CONCLUSION: In resource-limited settings, RBC alloimmunization is a frequent and clinically significant complication in patients with SCD, contributing to increased morbidity and potential mortality. Targeted and economically viable antigen matching may reduce alloimmunization rates and improve transfusion safety in LMICs.

Humans

The effect of dexmedetomidine in mechanically ventilated patients with sepsis and septic shock: a meta-analysis of randomized controlled trials.

PURPOSE: Dexmedetomidine (DEX) is a central sympatholytic with sedative properties widely used in critically ill patients. However, its effects in patients with sepsis and septic shock remain controversial. This meta-analysis evaluated the efficacy and safety of DEX compared to other sedatives in mechanically ventilated patients with sepsis and septic shock. METHODS: A systematic search was conducted across PubMed, Embase, Scopus, and Cochrane Library from inception through May 1, 2025 for randomized controlled trials comparing DEX with other sedatives or placebo in mechanically ventilated patients with sepsis and septic shock. Primary outcomes included overall mortality and Sequential Organ Failure Assessment (SOFA) scores. Secondary outcomes encompassed duration of mechanical ventilation (MV), length of stay in Intensive Care Unit (ICU), incidence of hypotension and bradycardia. RESULTS: Fifteen studies involving 3,882 patients (1,945 in the DEX group, 1,937 in the control group) were included. DEX was demonstrated no significant differences compared to other sedatives or placebo in overall mortality (Risk Ratio [RR] 0.98, 95% Confidence Interval [CI] 0.90 to 1.07, p&#x2009;=&#x2009;0.71, I2&#x2009;=&#x2009;0%), SOFA scores (Mean Difference [MD]&#x2009;-&#x2009;0.14, 95% CI -0.81 to 0.52, p&#x2009;=&#x2009;0.67, I2&#x2009;=&#x2009;0%), length of stay in ICU (MD -0.32, 95% CI -1.69 to 1.06, p&#x2009;=&#x2009;0.65, I2&#x2009;=&#x2009;77%), or incidence of hypotension (RR 1.15, 95% CI 0.81 to 1.62, p&#x2009;=&#x2009;0.44, I2&#x2009;=&#x2009;14%). However, DEX significantly reduced the duration of MV (MD -0.54, 95% CI -0.98 to -0.10, p&#x2009;=&#x2009;0.02, I2&#x2009;=&#x2009;25%) but was associated with an increased incidence of bradycardia (RR 1.67, 95% CI 1.22 to 2.28, p&#x2009;=&#x2009;0.001, I2&#x2009;=&#x2009;0%). CONCLUSIONS: In mechanically ventilated patients with sepsis and septic shock, DEX shortened duration of MV but was associated increased bradycardia risk. No mortality or organ dysfunction benefits were observed. These findings suggest DEX is a reasonable therapeutic option to facilitate earlier ventilator weaning in selected patients (particularly those without shock), but careful monitoring for cardiovascular adverse effects is warranted.

Humans

The Effectiveness of Passive Half-Time Interventions on Simulated Second-Half Performance in Elite Youth Soccer Players.

The half-time period in soccer provides a potentially important window to implement short-duration interventions aimed at maintaining second-half performance. However, passive rest has been associated with a decline in subsequent physical and technical performance. While re-warm-up strategies are well studied, little is known about the efficacy of technology-based, passive recovery modalities, device-supported interventions that require minimal active movement or physical exertion from the athlete, during half-time intervals. This study examined whether percussive therapy, electrical muscle stimulation, and pneumatic compression can mitigate second-half performance decline in male adolescent soccer players. Forty-three academy-level players (17.5 &#xb1; 0.6 years) completed a simulated soccer protocol including the Loughborough Soccer Pass Test (LSPT), repeated 20-meter sprints, and completed Total Quality of Recovery (TQR) assessments before and after half-time. Participants were randomized into one of four intervention groups during the 15-minute half-time interval: Passive Rest (CON), Percussive Therapy (Theragun Pro; TG), EMS (PowerDot; PD), and Pneumatic Compression (RecoveryAir; COMP). Linear mixed-effects models assessed Time &#xd7; Condition interactions for performance and recovery outcomes. Passive half-time rest led to significant deterioration in technical skill, sprint performance, and perceived recovery (p < .05) for the control group. TG and PD significantly improved technical performance (LSPT scores) compared to the control group (d = 0.65 and 0.72, respectively; p < .01). Furthermore, TG and COMP were effective at maintaining 20-meter sprint times (d = 0.58 and 0.49; p < .01), whereas the control group experienced significant slowing. Perceived recovery (TQR) scores significantly declined in the CON group from First Half to Second Half (16.5 &#xb1; 2.2 to 11.1 &#xb1; 2.3. However, this decline was significantly attenuated in all intervention groups: TG (17.5 &#xb1; 1.9 to 14.2 &#xb1; 1.9), PD (17.3 &#xb1; 1.9 to 15.1 &#xb1; 1.9), and COMP (17.6 &#xb1; 1.9 to 15.9 &#xb1; 2.0). Short-duration passive interventions during half-time can mitigate performance decline in adolescent soccer players. TG and EMS appear most effective for preserving technical skills, while COMP may support perceived recovery. These findings highlight practical strategies for optimizing in-game performance and inform evidence-based half-time protocols.

Humans

Esketamine vs. sufentanil for quality of recovery after outpatient gynecological surgery: a randomized clinical trial.

BACKGROUND: Perioperative administration of esketamine has been reported to improve early quality of recovery (QoR). However, data on its effects in outpatient surgery are limited. This study aimed to assess the impact of esketamine on QoR in patients undergoing outpatient gynecological procedures. METHODS: In this investigator-initiated, double-blind, randomized clinical trial, patients aged 18-65&#x2009;years scheduled for outpatient gynecological surgery under sedation were allocated to receive esketamine (0.2&#x2009;mg/kg) or sufentanil (0.1&#x2009;&#x3bc;g/kg) combined with propofol (1.5-3&#x2009;mg/kg). The primary outcome was quality of recovery on postoperative day (POD) 1. Secondary outcomes included quality of recovery on POD2, sedation success rate, length of post-anesthesia care unit (PACU) stay, injection pain, postoperative pain, nausea and vomiting, fatigue, patient and clinician satisfaction, sleep quality, and anxiety and depression. RESULTS: A total of 126 patients were randomized, with 63 assigned to the esketamine group and 63 to the sufentanil group. Of these, 125 patients were included in the final analysis (62 in the esketamine group and 63 in the sufentanil group), as one patient lacked follow-up data. The mean (SD) QoR-15 score on POD1 was 137.9 (14.5) in the esketamine group and 137.8 (10.7) in the sufentanil group, with no significant difference between groups (absolute difference, 0.2; 95% CI, -4.2 to 4.6; p&#x2009;=&#x2009;0.93). For secondary outcomes, the esketamine group had a longer PACU stay (median, 28.0 vs. 23.0&#x2009;min; p&#x2009;<&#x2009;0.001), a lower incidence of severe injection pain (22.6% vs. 50.8%; p&#x2009;=&#x2009;0.002), a higher proportion of patients with pain scores &#x2265; 4 at 30&#x2009;min postoperatively (30.6% vs. 6.3%; p&#x2009;=&#x2009;0.001), and higher fatigue scores (median, 3.0 vs. 2.0; p&#x2009;=&#x2009;0.01). Other secondary outcomes did not differ significantly between groups. CONCLUSION: Among patients undergoing sedation for outpatient gynecological procedures, esketamine did not significantly improve quality of recovery on POD1 compared to sufentanil. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2500098466.

Humans

Complete Revascularization Guided by Functional Coronary Angiography in STEMI.

BACKGROUND: Complete coronary-artery revascularization is recommended in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease, but the preferred strategy for identifying nonculprit lesions that warrant treatment remains uncertain. METHODS: In this international, randomized trial, we assigned patients with STEMI and multivessel disease in whom the culprit lesion had been successfully treated to undergo complete coronary-artery revascularization guided by functional coronary angiography (physiology-guided group) or by conventional angiography (angiography-guided group). The primary outcome was a composite of death from any cause, myocardial infarction, cerebrovascular accident (stroke or transient ischemic attack), or ischemia-driven revascularization, assessed in a time-to-event analysis. The primary safety outcome was a composite of contrast-associated acute kidney injury or major bleeding. RESULTS: A total of 1823 patients underwent randomization; 913 were assigned to the physiology-guided group and 910 assigned to the angiography-guided group. The median age of the patients was 66 years (interquartile range, 58 to 76), and 24% were women. At a median follow-up of 17.9 months, a primary-outcome event had occurred in 81 patients (8.9%) in the physiology-guided group and in 125 patients (13.7%) in the angiography-guided group (hazard ratio, 0.62; 95% confidence interval [CI], 0.47 to 0.83; P<0.001). A primary-safety-outcome event occurred in 42 patients (4.6%) in the physiology-guided group and in 65 patients (7.1%) in the angiography-guided group (hazard ratio, 0.63; 95% CI, 0.43 to 0.93; P&#x2009;=&#x2009;0.02). CONCLUSIONS: In patients with STEMI and multivessel coronary artery disease, a strategy of complete coronary-artery revascularization guided by functional coronary angiography resulted in a lower risk of a primary-outcome event (death, myocardial infarction, cerebrovascular accident, or ischemia-driven revascularization) than a strategy guided by conventional angiography. (Funded by the Italian Health Ministry and others; AIR-STEMI ClinicalTrials.gov number, NCT05818475.).

Aged

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

Impact of stromal maturity and proportion on prognosis and immune landscape in colorectal cancer.

BACKGROUND: Tumour microenvironment and cancer cells have constant interaction affecting cancer progression. Tumour-stroma ratio (TSR) in the tumour centre and desmoplastic reaction (DR) classification at the invasive margin are prognostic factors based on stroma evaluation on H&E slides. However, their combined value and immunological associations remain poorly defined. This study examines the prognostic and immunological value of TSR, DR, and their combination in two large colorectal cancer cohorts. METHODS: Two colorectal cancer cohorts (N&#x2009;=&#x2009;1,876) were analyzed. We introduced a three-tiered Stromal Maturity and Proportion Score (SMAPS) based on the presence of high (>50%) TSR and myxoid stroma (immature DR classification). Alcian blue staining was used to further quantify myxoid stroma. Multiplex immunohistochemistry combined with digital image analyses, was utilized to study immune cell densities associated with SMAPS, TSR, DR, and Alcian blue intensity. RESULTS: In the study cohort (N&#x2009;=&#x2009;1,100), SMAPS was a stronger predictor of cancer-specific mortality [HR for high (vs. low) SMAPS 2.01 (95% CI 1.47-2.75), p&#x2009;<&#x2009;0.0001] compared to TSR [HR for stroma-high (vs. stroma-low) 1.49 (95% CI 1.15-1.93), p&#x2009;=&#x2009;0.003] and DR classification [HR for immature (vs. mature) 1.84 (95% CI 1.39-2.45), p&#x2009;<&#x2009;0.0001]. High SMAPS, stroma-high TSR, and immature DR correlated with lower densities of CD3+ T cells, B cells, M1-like macrophages, CD66B+ granulocytes, and mast cells. Alcian blue staining was associated with immature DR and corresponding immune cells. The validation cohort (N&#x2009;=&#x2009;776) confirmed the association of SMAPS with survival and T cell densities. CONCLUSIONS: TSR and DR are independent prognostic factors for cancer-specific survival. SMAPS is a promising prognostic tool that integrates stromal maturity at the invasive margin and stromal proportion in the tumour centre. SMAPS has stronger prognostic value compared to TSR and DR classifications alone. A high stromal proportion and myxoid content are associated with an immunosuppressive microenvironment characterized by lower densities of antitumourigenic immune cells.

Humans

Obinutuzumab or Tacrolimus in Primary Membranous Nephropathy.

BACKGROUND: Studies of obinutuzumab, a type II anti-CD20 antibody, have shown efficacy in the treatment of hematologic cancers and autoimmune diseases. An evaluation of the efficacy and safety of obinutuzumab in patients with primary membranous nephropathy is needed. METHODS: In a phase 3 trial, we randomly assigned adults with primary membranous nephropathy in a 1:1 ratio to receive intravenous obinutuzumab or oral tacrolimus. The primary end point was complete remission (defined as a urinary protein-to-creatinine ratio of 0.3 or lower and a stable estimated glomerular filtration rate [eGFR]) at week 104. Key secondary end points were complete or partial remission at week 104, complete remission at week 76, a sustained reduction in the eGFR of at least 30%, duration of complete remission, and change in the Patient-Reported Outcomes Measurement Information System Fatigue T score from baseline to week 104. Fixed-sequence hierarchical testing was performed. Safety was assessed. RESULTS: A total of 142 patients underwent randomization. At week 104, complete remission was observed in 26 of 71 patients in the obinutuzumab group and in 4 of 70 patients in the tacrolimus group (37% vs. 6% with multiple imputation for missing data; adjusted difference, 31 percentage points; 95% CI, 18 to 44; P<0.001). The analyses of complete or partial remission at week 104 and complete remission at week 76 also showed a significant treatment effect. The analysis of a sustained eGFR reduction did not show a significant treatment effect; thus, subsequent end points in the hierarchy were not formally tested for significance. Adverse events of grade 3 or higher were reported in 16 patients (22%) in the obinutuzumab group and in 13 patients (19%) in the tacrolimus group; serious adverse events occurred in 12 (17%) and 10 (14%), respectively. There were 61 and 57 infections per 100 patient-years in the obinutuzumab and tacrolimus groups, respectively; 3 and 4 serious infections per 100 patient-years; and 11 and 14 serious adverse events per 100 patient-years. Adverse drug reactions with obinutuzumab included infusion-related reactions, respiratory tract infections, and neutropenia. One patient in each group died during escape therapy. CONCLUSIONS: Obinutuzumab was superior to tacrolimus in inducing complete remission in patients with primary membranous nephropathy. (Funded by F. Hoffmann-La Roche; MAJESTY ClinicalTrials.gov number, NCT04629248.).

Adult

Structured robotic colorectal training in a non-tertiary NHS hospital: a 502-case consecutive cohort implementation study.

Robotic-assisted colorectal surgery has expanded rapidly across NHS practice in the UK. Structured unit-wide training pathways are essential for safe technology adoption, yet published outcome data from non-tertiary hospitals remain limited. This study describes the implementation and feasibility of a unit-wide robotic colorectal program at a high-volume non-tertiary hospital, reporting outcomes across 502 consecutive resections performed by eight consultant surgeons and presenting these in the context of nationally published benchmarks. A retrospective cohort study of 502 consecutive robotic colorectal resections performed at York Teaching Hospital between May 2022 and December 2025. Eight consultant surgeons (A-H) participated in a structured four-phase training pathway incorporating simulation training, proctored cases, complexity-based case progression, and formal credentialing. Primary outcomes were 30-day mortality, unplanned return to theatre (RTT), and anastomotic leak (AL). Anastomotic leak was calculated using only patients who underwent anastomosis as the denominator. Procedure-stratified and individual surgeon outcomes with 95% confidence intervals were reported. Risk-adjusted cumulative sum (RA-CUSUM) analysis was performed to evaluate learning curves. Outcomes are presented descriptively alongside nationally published reference data; no formal statistical comparison against national benchmarks was performed. 502 robotic colorectal resections were performed. Mean patient age was 70.0 &#xb1; 11.3&#xa0;years; 58.4% were male. Median ASA grade was III. The indication was malignancy in 89.2% of cases. Length of stay was non-normally distributed and is therefore reported using median and interquartile range in the revised analysis. Key outcomes: - 30-day mortality: 1.0% (5/502; 95% CI 0.4-2.3%) - Unplanned return to theatre (RTT): 5.2% (26/502; 95% CI 3.6-7.5%) - Anastomotic leak (AL): 3.3% (15/450; 95% CI 2.0-5.5%; denominator = patients with anastomosis) - 30-day unplanned readmission: 5.0% (25/502; 95% CI 3.4-7.2%) - Conversion to open surgery: 3.6% (18/502; 95% CI 2.3-5.6%) - Lymph node yield &#x2265;12: 91.3% of cancer resections - R0 resection rate: 95.1% of cancer resections All primary outcomes fell within or below the published reference ranges used for descriptive context. RA-CUSUM trajectories were heterogeneous: no surgeon crossed the predefined upper control limit, but several curves showed later upward movement. Accordingly, the analysis is interpreted as safety surveillance rather than evidence of uniform performance improvement. RA-CUSUM monitoring showed that no surgeon crossed the predefined upper control limit; however, heterogeneous trajectories precluded a claim of uniform performance improvement.

Humans

Targeted Nrf2 activation improves vascular endothelial function with aging and prevents vascular dysfunction following disuse in younger and older adults.

Aging and physical inactivity/disuse contribute to cardiovascular disease, which is attributable, in part, to vascular endothelial dysfunction associated with impaired nuclear-factor erythroid 2-related factor 2 (Nrf2) signaling. However, the ability to augment Nrf2 activation and its effects on age- and disuse-related vascular dysfunction in humans remains limited. In a double-blind, randomized, placebo-controlled study design 20 younger adults (8M/12F, age 27&#x202f;&#xb1;&#x202f;7&#x202f;y) and 24 older adults (12M/12F, age 67&#x202f;&#xb1;&#x202f;8&#x202f;y) were randomized to receive either placebo or PB125 (200&#x202f;mg/day, Nrf2 activator) across three visits: baseline, 2 weeks of supplementation, and following either 5 days of bed rest (old) or 2 weeks of limb immobilization (young). Brachial and popliteal artery flow-mediated dilation (FMD), passive leg movement-induced (PLM) leg blood flow (LBF) and vascular conductance (LVC) and serum antioxidant status (superoxide dismutase, SOD) were assessed at each timepoint. Compared to placebo, 2 weeks of PB125 increased brachial (PB125: 2.8&#x202f;&#xb1;&#x202f;1.5 to 3.8&#x202f;&#xb1;&#x202f;1.3%, p&#x202f;<&#x202f;0.0001) and popliteal FMD (PB125: 1.5&#x202f;&#xb1;&#x202f;1.5 to 2.3&#x202f;&#xb1;&#x202f;1.4%, p&#x202f;=&#x202f;0.033) in older, but not younger adults (both, p&#x202f;>&#x202f;0.27). During bed rest, PB125 preserved brachial (3.8&#x202f;&#xb1;&#x202f;1.3 to 3.6&#x202f;&#xb1;&#x202f;1.4%, p&#x202f;=&#x202f;0.543) and popliteal FMD (2.3&#x202f;&#xb1;&#x202f;1.4 to 2.7&#x202f;&#xb1;&#x202f;1.4%, p&#x202f;=&#x202f;0.269), LVC (1.1&#x202f;&#xb1;&#x202f;0.8 to 1.1&#x202f;&#xb1;&#x202f;1.5 AUC, p&#x202f;=&#x202f;0.530) and circulating SOD concentrations (28.3&#x202f;&#xb1;&#x202f;7.2 to 28.6&#x202f;&#xb1;&#x202f;8.6 U/mL, p&#x202f;=&#x202f;0.888) in older adults compared to placebo (all, p&#x202f;<&#x202f;0.05). Following limb immobilization, PB125 preserved popliteal FMD (4.4&#x202f;&#xb1;&#x202f;2.8 to 3.4&#x202f;&#xb1;&#x202f;1.8%, p&#x202f;=&#x202f;0.302) in younger adults compared to placebo (p&#x202f;<&#x202f;0.05). These findings demonstrate targeted Nrf2 activation with PB125 improves age-related vascular endothelial dysfunction while preserving vascular function and antioxidant capacity following periods of disuse.

Humans

Preoperative Proximal Migration of the Radial Head as an Independent Predictor of Suboptimal Outcomes After Osteochondral Autograft Transplantation for Capitellar Osteochondritis Dissecans: A Retrospective Cohort Study.

BACKGROUND: Osteochondral autograft transplantation (OAT) is widely performed for capitellar osteochondritis dissecans (OCD). However, preoperative predictors of suboptimal postoperative outcomes remain unclear. PURPOSE/HYPOTHESIS: The authors aimed to evaluate clinical outcomes after OAT for capitellar OCD and identify preoperative risk factors associated with suboptimal outcomes. They hypothesized that radiographic indicators of disease severity, including preoperative proximal migration of the radial head, lesion size, and lateral wall disruption, would be associated with suboptimal postoperative clinical outcomes. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: The records of adolescent athletes who underwent OAT for capitellar OCD with a minimum 2-year follow-up were retrospectively reviewed. Clinical outcomes included elbow range of motion (ROM) and Timmerman-Andrews (T-A) score. A suboptimal outcome was defined as a postoperative T-A score <160. Preoperative radiographs were used to measure proximal migration of the radial head relative to the coronoid process, hypertrophy of the radial head, OCD lesion area, and a 5-grade lateral wall disruption classification; measurement reliability was assessed. Multivariate logistic regression analysis was performed to identify independent predictors of a suboptimal outcome, and receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff value for proximal migration. RESULTS: A total of 69 elbows (mean age, 13.6 years; mean follow-up, 48 months) were included. ROM and T-A scores improved significantly after OAT, and all athletes returned to any sports. Of these, 50 elbows (72%) achieved good outcomes, whereas 19 (28%) had suboptimal outcomes. Preoperative proximal migration was significantly greater in the suboptimal outcome group compared with the good outcome group (mean, 2.1 &#xb1; 2.3 vs 0.5 &#xb1; 1.7 mm; P = .002), as were lesion area (mean, 70 &#xb1; 16 vs 58 &#xb1; 20 mm2; P = .02) and lateral wall disruption grade (median, 5 vs 3; P = .01). On multivariate analysis, proximal migration of the radial head was the only independent predictor of a suboptimal outcome (adjusted OR, 1.47 per 1-mm increase; 95% CI, 1.03-2.09; P = .033). ROC analysis showed an area under the curve of 0.72 with an optimal cutoff of 2.2 mm (sensitivity, 56%; specificity, 84%). CONCLUSION: OAT resulted in significant clinical improvement in adolescents with capitellar OCD; however, 28% of patients were classified as having suboptimal outcomes. Preoperative proximal migration of the radial head is an independent predictor of a suboptimal postoperative outcome. A value >2.2 mm may indicate advanced radiocapitellar incongruity, a condition in which OAT may be less effective.

Humans

Phase 3 Trial of Oral Infigratinib in Children with Achondroplasia.

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

Adolescent

Comparative Effectiveness of Exercise Interventions for Hamstring Injury Prevention in Football Players: A Systematic Review and Network Meta-analysis.

BACKGROUND: Hamstring strain injury is a leading time-loss injury in football, yet trials have evaluated diverse exercise-based prevention programs with limited direct head-to-head evidence. This systematic review and network meta-analysis aimed to compare the effectiveness of exercise-based interventions for preventing hamstring injuries in football players using exposure-adjusted incidence rate ratios. METHODS: We conducted a PRISMA-aligned systematic review and random-effects network meta-analysis of randomized controlled trials in football players comparing exercise-based interventions to prevent hamstring injuries. Searches covered PubMed, Cochrane Library, Embase and Web of Science from inception to January 5, 2026. Interventions were modeled as separate nodes (Nordic hamstring exercise [NHE], FIFA 11, FIFA 11&#x2009;+&#x2009;, FIFA 11&#x2009;+&#x2009;Kids, bounding exercise program [BEP], usual training). The primary effect measure was incidence rate ratio (IRR) versus usual training, with ranking by P-scores; exploratory subgroup analyses were conducted by sex-restricted male-only evidence and age group. RESULTS: Eleven randomized controlled trials involving 9,282 participants were included. The network was connected but largely star-shaped, with most evidence comparing active interventions against usual training and no direct active-active comparisons. FIFA 11&#x2009;+&#x2009;showed the most consistent exposure-adjusted association with reduced hamstring injury incidence versus usual training (IRR&#x2009;=&#x2009;0.55, 95% CI 0.31-0.98; P-score&#x2009;=&#x2009;0.84). FIFA 11&#x2009;+&#x2009;Kids showed a favorable but imprecise estimate, whereas NHE showed a modest non-significant reduction and FIFA 11 and BEP showed no clear benefit. Male-only findings were broadly consistent with the primary analysis. Age-stratified analyses suggested that the apparent hierarchy was not fully identical across age strata, but subgroup networks were sparse and exploratory. RoB 2 judged three studies as high risk and eight as having some concerns; no trial was judged as overall low risk. Between-study heterogeneity was substantial, and treatment rankings were, therefore, interpreted cautiously. CONCLUSIONS: In this IRR-based network meta-analysis, FIFA 11&#x2009;+&#x2009;showed the most consistent exposure-adjusted association with reduced hamstring injury incidence compared with usual training. However, certainty across the primary comparisons ranged from low to very low because of clinical and methodological heterogeneity, sparse direct evidence for several nodes, reliance on indirect active-active comparisons, substantial between-study heterogeneity, and moderate-to-high risk of bias across the included studies. The treatment hierarchy should, therefore, be interpreted as a low-to-very-low-certainty, population-level summary rather than as a basis for firm recommendations. Further well-reported, age- and population-specific head-to-head trials with consistent exposure, injury-definition, adherence, and intervention-dose reporting are needed. Registration Systematic review registration PROSPERO (CRD420251243576).

FIFA 11&#x2009;+&#x2009;

Assessing time to symptomatic progression, a patient-relevant efficacy endpoint, in the MARIPOSA study in non-small cell lung cancer.

INTRODUCTION: In the phase 3 randomized MARIPOSA study, amivantamab and lazertinib combination therapy demonstrated improved progression-free survival (PFS) and overall survival (OS) versus osimertinib in participants with previously untreated, epidermal growth factor receptor-mutated advanced non-small cell lung cancer. Time to symptomatic progression (TTSP) was introduced to assess clinical worsening and complement endpoints that investigate radiographic disease progression and patient-reported outcomes. TTSP provides an easily interpretable measure of disease-specific symptom worsening to further support patient experience. METHODS: In MARIPOSA, TTSP was quantitatively assessed as a secondary efficacy endpoint and defined as the time from randomization until participants experience disease-specific symptom worsening requiring a clinical intervention or treatment change, or death. To evaluate the impact of amivantamab and lazertinib on TTSP considering its established OS benefit against osimertinib, an exploratory analysis censoring death events was performed. RESULTS: At the final protocol-specified OS analysis (median follow up: 37.8 months), median TTSP was 43.6 months with amivantamab and lazertinib versus 29.3 months with osimertinib (hazard ratio [HR]: 0.69; 95% confidence interval [CI]: 0.57-0.83; p&#x202f;<&#x202f;0.0001). Amivantamab and lazertinib reduced deaths following a TTSP event compared to osimertinib. A strong correlation between TTSP and PFS or OS was observed. CONCLUSIONS: Amivantamab and lazertinib significantly delayed TTSP versus osimertinib. TTSP offers a clinician-validated measurement of disease-specific symptom worsening, capturing symptoms perceived by patients that prompt clinical action. TTSP is highly correlated with PFS and OS, providing complementary insights alongside traditional endpoints. TTSP enhances understanding of treatment benefit and supports informed clinical decision-making by integrating patient experience.

Humans

Effects of an actuated ankle exoskeleton on walking stability in healthy adults: a controlled laboratory study.

BACKGROUND: Ankle exoskeletons are widely used to reduce the metabolic cost of walking, yet their effects on walking stability during unperturbed gait remain insufficiently understood. Walking stability can be characterized using complementary measures that capture stride-to-stride variability, global temporal organization, and local dynamic stability. Understanding how walking with an actuated ankle exoskeleton system influences these different aspects of gait stability is essential for the safe design and control of wearable robotic devices. METHODS: Eighteen healthy adults walked on a treadmill at a constant speed (1.1&#xa0;m/s) with and without an actuated bilateral ankle exoskeleton in a randomized crossover design. Spatiotemporal variability was quantified using coefficients of variation (CoV) of stride length, step width, and stance ratio. Global gait stability was assessed using detrended fluctuation analysis of stride time. Local dynamic stability was evaluated using maximum Lyapunov exponent calculated for the trunk, hip, upper leg, lower leg, and foot. Paired-samples two-sided t-tests were used to compare conditions. RESULTS: Walking with the ankle exoskeleton resulted in increased stride-to-stride spatiotemporal variability, reflected by higher CoV values for stride length (p&#x2009;<&#x2009;0.001) and stance ratio (p&#x2009;=&#x2009;0.005), while mean stride length and step width remained unchanged. Mean stance ratio was reduced in the exoskeleton condition (p&#x2009;<&#x2009;0.001). Global gait stability did not differ between conditions, indicating preserved long-range temporal gait organization. Local dynamic stability increased at the lower leg (p&#x2009;<&#x2009;0.001) and foot (p&#x2009;=&#x2009;0.019) when walking with the exoskeleton. CONCLUSIONS: Walking with the actuated ankle exoskeleton alters gait control across multiple levels during steady walking. While stride-to-stride variability in stride length and stance ratio increased, global gait stability remained unchanged. Local dynamic stability was increased at the lower leg and foot, suggesting segment-specific effects of ankle-level assistance close to the assisted joint. However, these findings should be interpreted as the combined effect of wearing the exoskeleton and receiving active assistance, rather than the isolated effect of plantarflexion assistance. These&#xa0;results provide insight for the design and control of ankle exoskeletons with respect to stability-related effects during walking.

Humans

Diffusion MRI radiomics in meningiomas: imaging correlates of tumor grade and intraoperative consistency.

OBJECTIVE: Despite advancements in imaging studies, the preoperative prediction of the biological behavior and intraoperative consistency of intracranial meningiomas remains limited. This study evaluated the association of volumetric diffusion-based and texture-derived radiomic features extracted from routine MRI with histopathological aggressiveness and intraoperative tumor consistency. METHODS: Ninety-seven intracranial meningiomas resected at two tertiary centers were retrospectively analyzed. Volumetric segmentation was performed on contrast-enhanced T1-weighted MRI and coregistered to apparent diffusion coefficient (ADC) maps. Data on first-order diffusion metrics and selected texture features were collected. The associations between World Health Organization (WHO) grade and Ki-67 index were assessed using nonparametric tests and Spearman correlation analysis. Independent factors associated with intraoperative tumor consistency (Zada grades 1-5) were evaluated via multivariate ordinal logistic regression analysis that adjusted for tumor volume, skull base location, calcification status, and WHO grade. Secondary receiver operating characteristic (ROC) curve analyses were performed to differentiate solid (Zada grades 4-5) from soft (Zada grades 1-2) tumors. ROC analyses were performed within the study cohort and were intended as exploratory assessments of discriminative performance. RESULTS: The mean ADC (ADCmean) and the 10th percentile of the ADC decreased significantly with increasing WHO grade (p < 0.001). ADCmean had a moderate inverse correlation with the Ki-67 index (r = -0.42, p < 0.001) and intraoperative tumor consistency (r = -0.45, p < 0.001). In the multivariate analysis, the ADCmean remained independently associated with increasing tumor firmness. Each 0.1 &#xd7; 10-3 mm2/sec increase corresponded to a 38% reduction in the odds of belonging to a higher consistency category (OR 0.62, 95% CI 0.51-0.74, p < 0.001). The ROC analysis showed good discrimination for solid tumors (area under the curve 0.847, 95% CI 0.742-0.953) and soft tumors (area under the curve 0.824, 95% CI 0.714-0.935). Texture features had weaker associations with intraoperative tumor consistency. CONCLUSIONS: Volumetric diffusion-derived metrics, particularly ADCmean, are associated with both histopathological aggressiveness and intraoperative tumor firmness in meningiomas. Diffusion imaging may reflect a graded microstructural continuum rather than a purely dichotomous property, providing complementary preoperative insights into surgical complexity.

Humans