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Anti-inflammatory agents after hip and shoulder arthroplasty: A systematic review and meta-analysis.

BACKGROUND: Postoperative inflammation after arthroplasty contributes to pain, delayed mobilization and prolonged hospitalization. Recent randomized trials have evaluated pharmacological anti-inflammatory strategies within contemporary enhanced recovery pathways, but evidence after hip and shoulder arthroplasty remains scattered across different drug classes and perioperative regimens. OBJECTIVES: To synthesize recent randomized controlled trial (RCT) evidence on perioperative anti-inflammatory agents after hip and shoulder arthroplasty. METHODS: PubMed, Embase, Cochrane Library and Web of Science were searched for English-language RCTs published from January 2020 to March 2026. The 2020-2026 window was selected to update evidence generated under modern arthroplasty, anesthesia, multimodal analgesia and enhanced recovery after surgery (ERAS) pathways. Eligible trials included adults undergoing hip or shoulder arthroplasty and compared corticosteroids, cyclooxygenase-2 (COX-2) inhibitors, nonsteroidal anti-inflammatory drug (NSAID)-based/local anti-inflammatory regimens, or related anti-inflammatory interventions with placebo, saline, no treatment, or the same regimen without the target component. Weighted mean differences (WMDs) were pooled using random-effects models. RESULTS: Nine RCTs involving 800 patients were included. Anti-inflammatory interventions significantly reduced postoperative C-reactive protein (CRP) [WMD=-32.18, 95% confidence interval (CI) (-41.16, -23.21), P<0.001], interleukin-6 (IL-6) [WMD=-31.25, 95% CI (-41.79, -20.77), P<0.001], rest pain [WMD=-0.41, 95% CI (-0.58, -0.23), P<0.001], activity pain [WMD=-0.56, 95% CI (-0.83, -0.29), P<0.001] and hospital stay [WMD=-0.54, 95% CI (-0.92, -0.15), P=0.006]. CONCLUSION: Recent RCT evidence suggests that perioperative anti-inflammatory interventions can attenuate early inflammatory responses and improve short-term pain and recovery after hip and shoulder arthroplasty. Because data were limited and clinically heterogeneous, the findings should not be interpreted as evidence favoring a specific drug class, dose, route, or timing.

Humans

Impact of smoking on structural failure after arthroscopic rotator cuff repair: a systematic review and meta-analysis.

BACKGROUND: Rotator cuff tears cause significant shoulder pain and functional limitation. Arthroscopic rotator cuff repair improves symptoms, yet structural failure rates remain substantial. Smoking may impair tendon-to-bone healing, but clinical studies report mixed findings due to heterogeneous methodology. Therefore, a systematic synthesis of imaging-confirmed outcomes is needed to clarify the association between smoking and structural failure after arthroscopic rotator cuff repair. METHODS: This review followed PRISMA 2020 and was registered in PROSPERO (CRD420251246197). PubMed, Embase, Scopus, Web of Science, and the Cochrane Library were searched from inception to 12 December 2025. Comparative clinical studies of adults undergoing arthroscopic rotator cuff repair that reported imaging-confirmed structural integrity (magnetic resonance imaging or ultrasonography) at &#x2265;6 months were included. Two reviewers independently screened studies, extracted data, and assessed quality using the Newcastle-Ottawa Scale. The primary outcome (structural failure) was pooled as risk ratios using a random-effects model with the restricted maximum likelihood estimator and Hartung-Knapp adjustment. Secondary continuous outcomes were synthesized using Bayesian random-effects models; subgroup, sensitivity, and meta-regression analyses explored heterogeneity. RESULTS: Ten cohort studies (1,683 shoulders) were included. Smoking was associated with a higher risk of imaging-confirmed structural failure (risk ratio 1.53; 95% confidence interval 1.13-2.08; P = .011) with low heterogeneity (I2 = 24.7%). Subgroup and sensitivity analyses supported robustness, with no evidence of effect modification by region, follow-up duration, tear size, or smoking definition. Meta-regression showed no significant influence of age, smoking prevalence, or diabetes prevalence on the pooled effect. Secondary outcomes (3 studies) suggested slightly lower postoperative American Shoulder and Elbow Surgeons scores among smokers, while visual analog scale pain scores and forward flexion showed no clear between-group differences. No publication-bias signals were detected for the primary outcome. CONCLUSION: Smoking is associated with a higher risk of imaging-confirmed structural failure after arthroscopic rotator cuff repair. Functional outcomes were broadly similar between groups, with only a small, likely clinically negligible reduction in American Shoulder and Elbow Surgeons scores among smokers. These findings support careful smoking history assessment and perioperative risk modification, including smoking cessation strategies.

Humans

Open repairs with biceps rerouting does not impact retears in large to massive rotator cuff tears compared to conventional open repair: a randomized clinical trial.

BACKGROUND: The treatment of large to massive rotator cuff tears leads to a high failure rate and several techniques have been proposed to improve these results. Rerouting the long head of the biceps tendon (LHBT) appears to be a biological reinforcement to increase tendon healing. Therefore, this study aimed to compare the clinical and radiological outcomes of open repair for large and massive rotator cuff tears reinforced with the LHBT to conventional open repair. METHODS: A prospective randomized study was conducted with patients diagnosed with large to massive rotator posterosuperior rotator cuff tear and intact LHBT, randomized into 2 groups: biceps rerouting and conventional open repair. The functional outcomes were assessed by the American Shoulder and Elbow Surgeon score, University of California at Los Angeles score, and SF-12 questionnaire preoperatively and at 6, 12, and 24 months postoperatively. Pain level was also assessed by the visual analog scale including the first day and 2 weeks postoperatively. Structural outcomes were rotator cuff and LHBT healing with magnetic resonance imaging and acromiohumeral distance (AHD) through radiography. RESULTS: We evaluated 58 patients, 29 in each group. At the end of the follow-up there were no statistically significant differences between groups in American Shoulder and Elbow Surgeon (76.1 vs. 80.4, P = .761), University of California at Los Angeles (27.1 vs. 29.1, P = .634), or visual analog scale scores (1.3 vs. 1.1, P = .781). Additionally, rotator cuff healing rates (48.3% vs. 44.8%, P = .402) and LHBT healing rates (79.3% vs. 82.7%, P = .738) were similar. AHD increased in both groups, with no significant difference in delta AHD (P = .513). Both groups showed significant clinical improvement over time in all evaluated outcomes (P < 0,01). No postoperative complications were reported. CONCLUSIONS: We could not identify an advantage of open repair with LHBT rerouting as reinforcement over conventional open repair. Nonetheless, all clinical scores improved at the end of the 24 months of follow-up in both groups.

Humans

Impact on analgesia, diaphragmatic function, and recovery between erector spinae plane block versus superior trunk block in arthroscopic shoulder surgery: a randomized controlled trial.

BACKGROUND: Effective analgesia and preservation of diaphragmatic function are key considerations in analgesia for shoulder surgery. The superior trunk block provides analgesia with reduced phrenic nerve involvement, while the erector spinae plane block offers minimal impact on diaphragm motion. This randomized controlled trial compared the analgesic efficacy, impact on diaphragmatic motion, and postoperative recovery between the two blocks. METHODS: Sixty patients undergoing arthroscopic shoulder surgery were randomized to receive either erector spinae plane block or superior trunk block. Primary outcomes were postoperative VAS and changes in diaphragmatic excursion. Secondary outcomes included Quality of Recovery-15 (QoR-15) scores, morphine-equivalent consumption, and the handgrip strength motor blockade. RESULTS: The superior trunk block resulted in significantly lower dynamic VAS at 1-h postoperatively (0.1 [0.0, 0.2] vs. 5.7 [4.0, 7.6]; p&#x2009;<&#x2009;0.001) and reduced 24-h morphine consumption (7.8 [2.5, 15.0] mg vs. 12.7 [7.5, 17.3] mg; p&#x2009;=&#x2009;0.038) compared to the erector spinae plane block. However, diaphragmatic excursion was better preserved in the erector spinae plane block group (8.37% &#xb1; 20.7% vs. -20.09% &#xb1; 22.2%; p&#x2009;<&#x2009;0.001), with a lower incidence of partial hemidiaphragm paresis (3.3% vs. 46.7%; p&#x2009;<&#x2009;0.001). At 24&#x2009;h postoperatively, QoR-15 scores were higher in the superior trunk block group (p&#x2009;=&#x2009;0.047), and no patient in either group developed handgrip motor blockade. CONCLUSIONS: Superior trunk block offers superior early postoperative analgesia and better overall recovery, while erector spinae plane block minimizes diaphragmatic impairment. However, the erector spinae plane block may represent an option only in carefully selected patients at high respiratory risk, acknowledging its significantly poorer early analgesic profile.

Humans

All-inside repair is an effective treatment for medial meniscus posterior root tears: a systematic review and meta-analysis of biomechanical and clinical evidence.

BACKGROUND: Medial meniscus posterior root tears (MMPRTs) reproduce the biomechanics of subtotal meniscectomy. Repair is favored, but the role of all-inside repair (AR) remains unclear relative to transtibial pull-out (TP). This study aimed to review the biomechanical and clinical evidence on AR for MMPRTs. METHODS: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered in the International Prospective Register of Systematic Reviews (PROSPERO). MEDLINE, Embase, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched. Outcomes included patient-reported outcome measures (PROMs), magnetic resonance imaging (MRI), and biomechanical performance. When available, random-effects meta-analysis was performed. RESULTS: Thirteen studies were included. AR restored contact mechanics and showed load to failure comparable to TP, with lower stiffness. Meta-analysis showed lower conversion to total knee arthroplasty with AR versus non-repair (RR 0.18, 95% CI 0.05-0.58), and no significant PROM differences between AR and TP. CONCLUSIONS: AR showed favorable biomechanical properties and improved outcomes versus non-repair. Compared with TP, no significant clinical differences were observed. AR may represent a reasonable option in selected scenarios.

Humans

Webcam-Based Real-Time Visual Feedback During Baduanjin Practice in Older Adults: 6-Week Pilot Randomized Study.

BACKGROUND: Baduanjin qigong is a traditional mind-body exercise used to support balance and physical health in older adults. Age-related changes in proprioception may make accurate self-directed performance difficult without external guidance. OBJECTIVE: The aim of this study is to explore whether webcam-based real-time visual feedback delivered during supervised laboratory sessions was associated with differences in webcam-derived 2D pose discrepancy and movement consistency during Baduanjin practice in older adults. METHODS: A total of 31 older adults were enrolled, and 28 participants with complete analyzable records were included in this complete-case dataset (feedback group, n=14; nonfeedback group, n=14). All sessions were conducted face-to-face in a supervised motion-analysis laboratory. Weekly 2D pose-discrepancy values were analyzed using a linear mixed-effects model with fixed effects for group, categorical week, and the group-by-week interaction and a participant-specific random intercept. Joint- and movement-specific participant-level 6-week means were analyzed exploratorily using Welch independent-samples t tests. Holm correction was applied across 24 exploratory contrasts (6 week-specific, 8 joint-specific, and 10 movement-specific comparisons), and Hedges g and 95% CIs were reported. Participant-specific weekly slopes and within-participant variability were additionally examined to directly assess longitudinal error drift. RESULTS: The linear mixed-effects model showed no significant group-by-week interaction (Wald &#x3c7;25=1.09; P=.96) and no significant overall week effect (Wald &#x3c7;25=6.40; P=.27). Averaged across 6 weeks, the feedback group had an estimated mean 2D pose discrepancy 1.20&#xb0; lower than the nonfeedback group (95% CI -2.38&#xb0; to -0.02&#xb0;; P=.046), although this marginal pilot finding was sensitive to an analytic approach. No week-specific contrast remained significant after Holm adjustment. Nominal right elbow, right shoulder, and right knee differences did not survive global Holm correction. Form 3 showed a lower mean discrepancy in the feedback group (mean difference -3.70&#xb0;, 95% CI -5.86&#xb0; to -1.54&#xb0;; Hedges g=-1.30; unadjusted P=.002; Holm-adjusted P=.04). Direct analyses of participant-specific slopes and within-participant SDs did not support a significant between-group difference in longitudinal error drift. CONCLUSIONS: In this small exploratory pilot study conducted under supervised laboratory conditions, the 6-week trajectories did not differ significantly between groups. A marginally lower average 2D pose discrepancy was observed in the feedback group across the 6 weeks, but no individual week- or joint-specific comparison remained significant after multiplicity adjustment. Form 3 was the only exploratory contrast that remained significant after global Holm correction. Direct longitudinal analyses did not demonstrate prevention of error drift. Larger studies using validated reference measurements, prespecified outcomes, and adequately powered longitudinal designs are required.

Humans

Effect of different liposomal bupivacaine concentrations in ultrasound-guided superior trunk block on postoperative analgesia and mobility: a randomized double-blind controlled trial protocol for shoulder arthroscopy.

BACKGROUND: Shoulder arthroscopy frequently causes severe postoperative pain that may impede recovery. Liposomal bupivacaine provides prolonged analgesia, and ultrasound-guided superior trunk block (STB) offers comparable analgesia to interscalene block with a lower risk of hemidiaphragmatic paralysis. However, the optimal concentration of liposomal bupivacaine for STB remains unknown. METHODS: This randomized, double-blind, controlled trial will enrol 282 adult patients scheduled for elective arthroscopic rotator cuff repair. Patients will be randomly allocated (1:1:1) to receive ultrasound-guided STB with liposomal bupivacaine 66&#x2009;mg (Group A), 44&#x2009;mg (Group B) or 33&#x2009;mg (Group C), each diluted to 10&#x2009;mL. The co-primary outcomes are (1) rest pain Numeric Rating Scale (NRS) score at 48&#x2009;h post-surgery and (2) cumulative oral morphine milligram equivalents (MME) consumption within 0-48&#x2009;h after surgery. Secondary outcomes include rest pain NRS scores at 6, 24 and 72&#x2009;h; motor function assessed by Muscle Balance Scale, Bromage score and American Shoulder and Elbow Surgeons (ASES) score at 6, 24, 48 and 72&#x2009;h; and Quality of Recovery-15 (QoR-15) score at 24 and 48&#x2009;h. DISCUSSION: This study will provide evidence on the optimal concentration of liposomal bupivacaine for STB in arthroscopic shoulder surgery, aiming to achieve effective and prolonged analgesia without compromising shoulder mobility.

Humans

Hip Arthroscopy-Assisted Management of Pipkin Types I and II Femoral Head Fracture-Dislocations: Mid-Term Clinical and Radiographic Outcomes.

OBJECTIVES: Hip arthroscopy-assisted surgery has been proposed as a minimally invasive option for femoral head fractures; however, evidence with mid-term follow-up remains limited. This study aimed to evaluate the clinical and radiographic outcomes of arthroscopy-assisted management for Pipkin Types I and II femoral head fracture-dislocations with a minimum follow-up of 5&#x2009;years. METHODS: This retrospective study included 23 consecutive adults (19 Pipkin I and 4 Pipkin II) treated with hip arthroscopy-assisted fragment excision or internal fixation between March 2013 and January 2020. Preoperative computed tomography was used for surgical planning, and fixation was placed with arthroscopic headless screws. Clinical outcomes were assessed using the Harris Hip Score (HHS) and Thompson-Epstein (T-E) criteria. Radiographic evaluation included avascular necrosis (AVN), heterotopic ossification (HO; Brooker), osteoarthritis (OA; T&#xf6;nnis), and fracture reduction quality (Matta's criteria). Group comparisons were evaluated using independent samples t-tests, Mann-Whitney U tests, and Fisher's exact test. The mean follow-up was 86.2&#x2009;&#xb1;&#x2009;21.2&#x2009;months. RESULTS: The cohort consisted of 19 males and 4 females with a mean age of 28.7&#x2009;&#xb1;&#x2009;9.9&#x2009;years. Fifteen patients underwent fixation and eight underwent excision. The final mean HHS was 98.3&#x2009;&#xb1;&#x2009;1.9, with 21 patients (91%) achieving excellent and 2 (9%) good T-E criteria. There were no significant differences between the fixation and excision groups in demographic characteristics, operative time, or functional outcomes (all p&#x2009;>&#x2009;0.05); however, hospital stay was significantly shorter in the excision group (2.9&#x2009;&#xb1;&#x2009;0.6 vs. 5.5&#x2009;&#xb1;&#x2009;4.6&#x2009;days, p&#x2009;=&#x2009;0.028). In the fixation group, mean maximal displacement improved from 7.6&#x2009;mm preoperatively to 2.6&#x2009;mm postoperatively, with anatomic reduction achieved in 6 cases (40%), imperfect in 6 (40%), and poor in 3 (20%). Patients with Pipkin Type I fractures had significantly higher HHS than those with Type II fractures (98.7&#x2009;&#xb1;&#x2009;1.7 vs. 96.0&#x2009;&#xb1;&#x2009;0.8, p&#x2009;=&#x2009;0.018). Complications were rare, with one case of Brooker Grade I HO and one case of mild OA. No AVN or total hip arthroplasty occurred during the follow-up. CONCLUSIONS: Hip arthroscopy-assisted management of selected Pipkin Type I and II femoral head fractures yields excellent mid-term clinical outcomes with acceptable radiographic reduction and a low complication rate. This minimally invasive technique represents a viable alternative in appropriately selected patients when fragment characteristics and surgical expertise permit.

Humans

Preoperative Patient Education on Opioid Use and Pain After Surgery: A Randomized Trial.

OBJECTIVE: To evaluate the impact of preoperative analgesic education on postoperative opioid consumption, pain scores, and patient satisfaction with analgesia. BACKGROUND: Effective postoperative pain management is crucial for patient recovery and satisfaction, yet opioid use poses risks of tolerance and addiction. Preoperative patient education offers a potential avenue to mitigate opioid reliance and improve pain management outcomes. METHODS: This single-center randomized trial was conducted at the Cleveland Clinic Main Campus between October 2021 and October 2023. Adult patients scheduled for hip arthroplasty or laparoscopic-assisted abdominal surgery with an ASA physical status of 1 to 4 were eligible. Patients with a history of prolonged opioid use, planned regional block or epidural analgesia, or limited English fluency were excluded. Participants were randomized 1:1 to receive either an analgesic educational video or a generic video about surgery and hospitalization. The primary outcome was opioid consumption during the initial 72 postoperative hours. Secondary outcomes included time-weighted average pain scores and patient satisfaction with analgesia. RESULTS: Among 957 analyzed patients, preoperative analgesic education did not significantly reduce opioid consumption (adjusted ratio of geometric means, 1.01; 95% CI, 0.86-1.18; P =0.890) or improve pain scores (adjusted mean difference, -0.1; 95% CI, -0.3 to 0.2; P =0.617). Patient satisfaction scores also did not differ significantly between groups (adjusted mean difference, -0.1; 95% CI, -0.3 to 0.2; P = 0.611). CONCLUSIONS: Preoperative analgesic education did not result in clinically meaningful reductions in opioid consumption or improvements in pain management outcomes. Further research may explore more intensive educational interventions to optimize postoperative pain management strategies.

Humans

Isometric Exercises for Tendinopathies: A Systematic Literature Review.

PURPOSE: Musculoskeletal disorders are among the most common reasons for medical consultation, with tendinopathies accounting for up to 30% of such presentations. Although exercise remains the cornerstone of management, the most effective modality continues to be debated. Eccentric exercise has long been the mainstay, but the role of isometric exercise in pain modulation and functional recovery remains unclear. This systematic review aims to evaluate the current evidence on the efficacy of isometric exercises in the management of tendinopathies across various anatomic sites. METHODS: A systematic search was conducted in PubMed, MEDLINE, Embase, and the Cochrane Library from inception to August 1, 2025. Eligible studies included randomized controlled trials and prospective or retrospective cohort studies assessing isometric exercise interventions for tendinopathy, with or without comparator groups. Case series and case reports were excluded. Data extracted included participant demographic characteristics, site of tendinopathy, symptom duration, treatment duration, adherence, and outcome measures such as Victorian Institute of Sports Assessment (A, P, or G), visual analog scale, Patient-Specific Functional Scale, 36 item short form health survey (SF-36), and EuroQol 5-Dimension questionnaires. Imaging outcomes (ultrasound or magnetic resonance imaging) were recorded where available. Methodological quality and risk of bias were assessed using the Cochrane Risk of Bias tool in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. FINDINGS: The search identified 304 articles, of which 13 randomized controlled trials met the inclusion criteria, encompassing 336 participants (40% female). Tendinopathy sites included the patellar (n = 4), Achilles (n = 3), lateral elbow (n = 2), rotator cuff (n = 2), wrist extensor (n = 1), and gluteal (n = 1) tendons. Median symptom duration was 23 months (interquartile range, 3-51 months). Intervention periods ranged from a single 45-minute session to 4-month exercise programs. Treatment adherence was high initially (nearly 100%) but declined over time, with 70% of participants in the isometric and 58% in the control (isotonic) groups completing &#x2265;80% of sessions. Pain reduction and functional improvement were statistically significant in only 3 studies. Imaging-based outcomes were inconsistently reported, and study heterogeneity precluded meta-analysis. Overall methodological quality was rated as good in 3 studies and poor in 10. IMPLICATIONS: Current evidence provides limited support for the superiority of isometric exercise in tendinopathy management. Although isometric regimens appear tolerable and may confer short-term analgesic benefits, their long-term efficacy relative to eccentric or isotonic protocols remains uncertain. Future research should prioritize standardized outcome measures, longer follow-up, and uniform diagnostic criteria to strengthen the evidence base for exercise prescription in tendinopathies.

Humans

Outcomes of Response-Based Watch-and-Wait and Surgical Management After Total Neoadjuvant Therapy for Rectal Cancer: A Systematic Review and Meta-analysis.

BackgroundTotal neoadjuvant therapy (TNT) increases clinical complete response rates in locally advanced rectal cancer (RC), allowing response-based management strategies such as watch-and-wait (WW) as an alternative to total mesorectal excision (TME). Outcomes associated with WW after TNT remain incompletely defined. This study aimed to compare oncologic and organ-preservation outcomes between WW and surgical management following TNT.MethodsA systematic search was conducted in PubMed, Scopus, and Cochrane Central up to April 2025. Observational studies comparing WW and TME following TNT were included. Pooled odds ratios (ORs), hazard ratios (HRs), and 95% confidence intervals (CIs) were calculated using a random-effects model. Heterogeneity was assessed with I2 statistics. Secondary outcomes included tumor regrowth, salvage surgery, and permanent stoma. Risk of bias was evaluated using ROBINS-I.ResultsSix studies comprising 793 patients were analyzed. WW showed no significant difference compared with TME regarding local recurrence (OR 1.36, 95% CI 0.07-26.17; I2 = 80%), distant metastases (OR 0.62, 95% CI 0.29-1.33; I2 = 49%), 5-year disease-free survival (HR 0.97, 95% CI 0.71-1.31; I2 = 51.7%), or overall survival (HR 1.03, 95% CI 0.81-1.30; I2 = 27.9%). Permanent stoma rates were lower with WW (OR 0.12, 95% CI 0.01-1.23; I2 = 71%), becoming significant after sensitivity analysis (OR 0.04, 95% CI 0.01-0.19).ConclusionWW after TNT offers oncologic outcomes comparable to TME, with high organ preservation and reduced surgical morbidity in highly selected patients.

Humans

A smartphone-integrated Pt@Cu-HCF nanozyme-based paper sensor for on-site determination of total antioxidant capacity in marine oils.

Total antioxidant capacity (TAC) serves as a key indicator for evaluating the nutritional quality of foods. In this study, we designed a platinum-embedded copper hexacyanoferrate (denoted as Pt@Cu-HCF) nanozyme that exhibits high oxidase-like activity, efficiently catalyzing the oxidation of chromogenic substrates to generate robust colorimetric signals. Antioxidants quench hydroxyl radicals (&#x2219;OH) produced during the catalytic process, leading to a concentration-dependent suppression of the color signal. Leveraging this mechanism, a smartphone-integrated, colorimetric paper sensor for on-site TAC quantification was developed, using vitamin E as the calibration standard. The sensor was applied to determine TAC in fish oil, algal oil, and krill oil, demonstrating a linear response range of 9.78-312.5&#xa0;&#x3bc;M and a limit of detection (LOD) of 6.41&#xa0;&#x3bc;M. Validation using real-world marine oil samples showed excellent agreement with a commercial assay kit, confirming the reliability and practical applicability of this portable sensor for TAC measurement in complex biological matrices.

Antioxidants

Comparison of opioid-free versus opioid-based total intravenous anaesthesia in elderly patients undergoing short-duration surgery: a randomized controlled trial.

INTRODUCTION: Older adults who undergo short-duration surgery are vulnerable to opioid-related complications. It is uncertain whether an opioid-free total intravenous anaesthesia (OFA) can reduce these events. We aimed to determine whether OFA reduces the incidence of major postoperative adverse events compared with standard opioid-based total intravenous anaesthesia (OBA). PATIENTS AND METHODS: This single-center randomized clinical trial was conducted in China. From May to August 2025, 400 patients aged &#x2265;60&#x2009;years undergoing elective, short-duration surgery (anticipated duration of less than 90&#x2009;min) were randomized 1:1 to receive either OFA (n&#x2009;=&#x2009;200) or OBA (n&#x2009;=&#x2009;200). The primary outcome was a composite of postoperative hypoxemia, delirium, or nausea and vomiting (PONV) within 48&#x2009;h. RESULTS: A total of 400 randomized patients (mean [SD] age, 69.5 [7.0] years; 125 [31.3%] women). The primary composite outcome occurred in 50 patients (25.0%) in the OFA group and 87 patients (43.5%) in the OBA group (adjusted odds ratio, 0.40; 95% CI, 0.25 to 0.62; p < .001). Among the OFA group had a lower incidence of hypoxemia (15.0% vs 32.0%) and PONV (8.0% vs 16.0%). Intraoperative hemodynamic stability was greater in the OFA group. However, the OFA group had a higher incidence of intraoperative bradycardia (10.0% vs 3.0%; p = .005) and longer extubation times (mean, 9.5 vs 7.2&#x2009;min; p < .001). CONCLUSION: These findings suggest that OFA is a viable alternative to opioid-based anesthesia for improving postoperative outcomes by reducing the incidence of hypoxemia and PONV in this population, while warranting careful management of its associated side effects. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2500102550.

Humans

Antegrade dissection and re-entry vs retrograde strategy in chronic total occlusion percutaneous coronary intervention: Rationale and design of the ADRENALINE randomized study.

RATIONALE: While antegrade wiring (AW) is the most common initial strategy for chronic total occlusion (CTO) percutaneous coronary intervention (PCI), difficult CTO lesions frequently require either antegrade dissection and re-entry (ADR) or a retrograde strategy. Comparative data between ADR and the retrograde approach remain limited. DESIGN: The Antegrade Dissection vs Retrograde re-ENtry And Load of Interventionalist Effort (ADRENALINE) is a prospective, multicenter randomized study with a superiority design. It is planned to enroll 121 patients with difficult coronary CTO (J-CTO score &#x2265;2) referred for CTO-PCI in accordance with the hybrid algorithm. Subjects undergoing successful AW will be included in the observational arm. Patients with failed or unattempted AW will be randomized 1:1 to ADR or retrograde CTO crossing strategy (n = 74). All patients will undergo pre- and postprocedural laboratory testing (including cardiac troponin T and creatine kinase-MB), cardiac magnetic resonance (CMR) for late gadolinium enhancement, and health status assessment by the Seattle Angina Questionnaire and the Rose Dyspnea Scale. The co-primary endpoints are total procedure time and successful guidewire crossing. Additionally, the relationship between different recanalization strategies and stress among interventional cardiologists will be explored. CONCLUSION: ADRENALINE is the first randomized study of ADR vs retrograde strategy for difficult CTO PCI, assessing procedural outcomes, CMR-detected myocardial infarction, and 3-month quality of life. ENROLMENT STATUS: The first patient was enrolled on July 29, 2025. As of June 14, 2026, 45 patients (26 randomized, 19 observational) of the planned 121 patients have been enrolled. TRIALS REGISTRATION: Clinicaltrials.gov: Identifier, NCT06878729.

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

Impact of estimated total blood volume on NT-proBNP response to angiotensin receptor-neprilysin inhibition in acute heart failure: Insights from the PREMIER study.

BACKGROUND: Sacubitril/valsartan (Sac/Val) reduces N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in acute heart failure (AHF), particularly in patients with reduced ejection fraction. However, whether estimated total blood volume (TBV), calculated using anthropometric equations, is associated with heterogeneity in biomarker response remains uncertain. METHODS: This post hoc exploratory sub-analysis of the PREMIER randomized trial evaluated whether baseline estimated TBV was associated with heterogeneity in NT-proBNP reduction after Sac/Val compared with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) therapy. Estimated TBV was calculated using validated anthropometric equations and dichotomized at the median (4.05 L). Patients were further stratified by left ventricular ejection fraction (LVEF <40% vs &#x2265;40%). The primary endpoint was the proportional change in NT-proBNP from baseline to Week 8. RESULTS: Among 376 patients, 372 with baseline estimated TBV data were analyzed. In the high TBV group, Sac/Val was associated with greater NT-proBNP reduction than ACEI/ARB (-56% vs -32%; ratio of change, 0.67; 95% confidence interval, 0.53-0.84; P = .001), whereas no significant difference was observed in the low TBV group (P for heterogeneity = 0.063). In patients with LVEF <40%, Sac/Val was associated with greater NT-proBNP reduction in both TBV groups. In patients with LVEF &#x2265;40%, Sac/Val was associated with greater NT-proBNP reduction in the high TBV group, whereas the point estimate in the low TBV group numerically favored ACEI/ARB. CONCLUSIONS: In this exploratory post hoc analysis, higher estimated TBV was associated with greater NT-proBNP reduction after Sac/Val, particularly among patients with LVEF &#x2265;40%. These findings are hypothesis-generating and require external validation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05164653; Japan Registry of Clinical Trials, jRCTs021210046.

Humans

Desmodium styracifolium Total Flavone Capsules for Urolithiasis: A Phase 3 Randomized Clinical Trial.

IMPORTANCE: No oral medication is currently approved for the management of urolithiasis. Guang Jing Qian Cao (Desmodium styracifolium total flavone capsules; hereinafter, Guang Jing), a traditional Chinese herbal extract, has shown clinical benefits for urolithiasis, but randomized clinical trials are needed to assess its effectiveness. OBJECTIVE: To evaluate whether Guang Jing improves stone passage rates (SPRs) compared with placebo in adults with urolithiasis. DESIGN, SETTING, AND PARTICIPANTS: This double-blind, placebo-controlled, phase 3 randomized clinical trial was conducted at 34 sites in China from December 2017 to April 2020. Participants included adults (aged 18-70 years) with diagnosed ureteral stones. Data analysis was conducted on November 4, 2020. INTERVENTION: Participants were randomized 3:1 to receive oral Guang Jing (0.6 g) or matching placebo 3 times daily for 28 days, in addition to investigator-prescribed background medication. MAIN OUTCOMES AND MEASURES: The primary outcome was SPR by day 28, confirmed by computed tomography. Secondary outcomes included SPR by day 14, stone migration rate, and stone migration distance. Between-group comparisons were performed using the Cochran-Mantel-Haenszel test for categorical outcomes and t tests for continuous outcomes. RESULTS: A total of 606 participants were randomly assigned to receive Guang Jing (n&#x2009;=&#x2009;458) or placebo (n&#x2009;=&#x2009;148). Their mean (SD) age was 43.0 (12.0) years, 474 (78.2%) were male, and the mean (SD) stone size was 0.6 (0.1) cm. The SPR by day 28 was significantly higher for the Guang Jing group compared with the placebo group (204 of 457 [44.6%] vs 50 of 148 [33.8%]; relative risk, 1.32 [95% CI, 1.03-1.69]; P&#x2009;=&#x2009;.03), with an absolute risk difference of 10.9 (95% CI, 2.0-19.7) percentage points. No significant between-group differences in SPR by day 14 (Guang Jing vs placebo: 133 [29.1%] vs 33 [22.3%]; P&#x2009;=&#x2009;.14) or stone migration distance (mean [SD], 29.5 [51.8] mm vs 29.7 [43.8] mm; P&#x2009;=&#x2009;.11) were observed. Adverse event rates were similar for the Guang Jing and placebo groups (88 [19.3%] vs 27 [18.2%]). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, treatment with Guang Jing significantly increased the expulsion of 5- to 10-mm ureteral stones by day 28, with a favorable safety profile. These findings suggest that Guang Jing may be an additional medical expulsive therapy option for appropriately selected patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry Identifier: ChiCTR-IIR-17013275.

Humans

Pretreatment EBV-DNA/TLG-Based Risk Stratification Is Associated With Survival Outcomes in Nonmetastatic Nasopharyngeal Carcinoma: An Exploratory Study.

Whether combining pretreatment plasma Epstein-Barr virus DNA (EBV-DNA) with 18F-FDG PET/CT-derived total lesion glycolysis (TLG) improves prognostic stratification in nonmetastatic nasopharyngeal carcinoma (NPC) is unclear, particularly in nonendemic populations. We retrospectively analyzed 86 eligible nonmetastatic NPC patients treated with definitive radiotherapy (2010-2024) at a single nonendemic-region institution. EBV-DNA (prespecified cutoff 3500 copies/mL) and TLG (cutoff 200, ROC-derived within this cohort) were dichotomized. Both were available in 59/86 patients (68.6%), who differed from the rest in nodal and overall stage and in RT technique. Baseline PET/CT was in-house in 57 of 86 patients, and a robustness analysis in that subgroup is reported. Given limited events (13 PFS, 9 OS), Cox analyses are exploratory and were supplemented with penalized regression and bootstrap validation. At a median follow-up of 75.5&#x2009;months, 5-year PFS and OS for the whole cohort (n&#x2009;=&#x2009;86) were 81.1% and 85.9%. The EBV-DNAhigh/TLGhigh subgroup remained associated with inferior PFS after adjustment in an exploratory model (adjusted HR&#x2009;=&#x2009;3.97, 95% CI: 1.32-11.93) and, in a single-variable model, with inferior OS (HR&#x2009;=&#x2009;4.13, 95% CI: 1.10-15.52). Discrimination was comparable to the individual-biomarker model for PFS and lower for OS. Five-year PFS fell monotonically across the four risk groups in the complete-case cohort (n&#x2009;=&#x2009;59; 89.7%-58.3%). OS differed across groups (log-rank p&#x2009;=&#x2009;0.044) but was not strictly monotonic, with wide, overlapping confidence intervals. This two-biomarker model is hypothesis-generating and needs prospective, multicenter validation before any consideration of risk-adapted treatment.

Epstein&#x2013;Barr virus DNA