Trial Sequential Analysis Research Articles

A novel developed DGS can be used to identify gene loci that may be associated with osteoporosis

Abstract Purpose Previous meta-analyses only examined the association between single gene polymorphisms and osteoporosis; there is no compilation of all gene loci that correlate with osteoporosis in the literature. In this study, we develop a new literature-based approach, a decisive gene strategy (DGS), to examine the sufficiency of the cumulative sample size for each gene locus and to assess whether a definite conclusion of the association between the gene locus and osteoporosis can be drawn. Methods The DGS was used to search PubMed, Embase, and Cochrane databases for all meta-analyses that correlated gene polymorphisms with osteoporosis. Trial sequential analysis was employed to examine the sufficiency of the cumulative sample size. Finally, we assessed the importance of gene loci in osteoporosis based on whether there were enough sample sizes and the heterogeneity of the literature with the I2 value. Results After excluding 169 irrelevant publications, 39 meta-analysis papers were obtained. Among Caucasians, in 17 gene loci, there were eight gene loci (e.g., vitamin D Receptor ApaI rs7975232) with sufficient cumulative sample size to confirm that they were unrelated to the disease. Among Asians, in 15 gene loci, four gene loci that had sufficient sample sizes were risk factors: VDR FokI rs2228570 (odds ratio (OR) = 1.44, 95% confidence interval (CI) = 1.22-1.70), TGF β1 rs1800470 (OR = 1.35, 95% CI = 1.10-1.65), IGF1 rs2288377 (OR = 1.44, 95% CI = 1.28-1.62), and IGF1 rs35767 (OR = 1.20, 95% CI = 1.06-1.36), respectively, whereas one gene locus, ESR2 RsaI rs1256049 (OR = 0.69, 95% CI = 0.59-0.81), was a protective factor. Conclusions The DGS successfully identified five gene loci in osteoporosis that will apply to other diseases to find causal genes, which may apply disease-related genes in clinical practice, and to provide appropriate disease prevention policies. Key messages • The DGS that will apply to other diseases to find causal genes. • The DGS, which may apply disease-related genes in clinical practice, and to provide appropriate disease prevention policies.

Intermittent levosimendan infusions for advanced heart failure: a systematic review and meta-analysis of randomized controlled trials

Abstract Background Intermittent intravenous infusions of levosimendan have been shown to provide benefits in patients with advanced heart failure (AHF), preventing HF rehospitalization and mortality. Purpose We aim to investigate the efficacy of intermittent intravenous levosimendan infusion in patients with AHF. Methods A systematic review and meta-analysis synthesizing evidence from randomized controlled trials (RCTs) obtained from PubMed, Embase Cochrane, Scopus, and WOS until September 2023. We used the random-effects model to report dichotomous outcomes using risk ratio (RR) and continuous outcomes using mean difference (MD), with a 95% confidence interval (CI). Finally, we implemented a trial sequential analysis (TSA) to improve the reliability of our results. Results We included 15 RCTs with 1,181 patients. Intermittent levosimendan was significantly associated with an improved left ventricular ejection fraction (LVEF) compared to placebo (MD: 6,39, 95% CI [3.04, 9.73], P= 0.002; I2=75, P=0.0005), with cumulative Z-score of change after ≤ 1 week passing the monitoring boundaries favors the levosimendan but did not cross the required information size. Additionally, there was a significant improvement in the all-cause mortality rate favoring levosimendan (RR: 0.60, 95% CI [0.40, 0.90], P= 0.01; I2=9, P=0.36). However, There was no difference between intermittent levosimendan and placebo in all-cause rehospitalization rate (RR: 0.75, 95% CI [0.46, 1.22], P= 0.25; I2=70, P=0.04) or event-free survival rate (RR: 0.97, 95% CI [0.72, 1.30], P= 0.84; I2=63, P=0.03). Conclusion In patients with AHF, intermittent levosimendan significantly improved LVEF and all-cause mortality rate. However, there was no effect on rehospitalization or event-free survival.Figure 1.LVEF and TSAFigure 2.Mortality, Rehospital, Surviva

Videolaryngoscopy vs. direct laryngoscopy for tracheal intubation by experienced anaesthetists: a meta-analysis and trial sequential analysis of randomised controlled trials.

Videolaryngoscopy vs. direct laryngoscopy for tracheal intubation by experienced anaesthetists: a meta-analysis and trial sequential analysis of randomised controlled trials.

Irrigation with fibrinolytic agents versus saline for percutaneous drainage of abdominal abscesses: A meta-analysis with trial sequential analysis of randomized trials.

Fibrinolytic agents (FA) activate the fibrinolytic system, converting plasminogen into plasmin to break down fibrin. Their use for irrigation of abdominal abscesses is debated, and this meta-analysis evaluates their efficacy. We searched PubMed, Embase, and Cochrane Central for randomized controlled trials (RCTs) comparing FA and saline in percutaneous drainage of abdominal abscesses. Outcomes included length of hospitalization, duration of drainage, and drainage volume. We pooled mean differences (MD) and 95% confidence intervals (CI) using a random-effects model. We also performed a trial sequential analysis (TSA). We included six RCTs encompassing 299 patients. In the overall analysis, FA increased drainage volume (MD 104.25mL; 95% CI 35.72-172.77mL; p=0.003; I2=0%). In children, saline reduced hospitalization duration (MD -1.26days; 95% CI -1.98 to -0.55days; p=0.0006; I2=0%), whereas FA increased drainage volume (MD 84.66mL; 95% CI 5.77-153.54mL; p=0.04; I2=0%). In adults, FA significantly reduced hospitalization duration (MD -11.12days; 95% CI -15.16 to -7.08days; p<0.00001; I2=0%) and duration of drainage (MD -6.53days; 95% CI -9.25 to -3.81days; p<0.00001; I2=0%) while increasing drainage volume (MD 164.47mL; 95% CI 26.16-302.78mL; p=0.02; I2=0%). On TSA, the required information size was achieved only for the adult subgroup's hospitalization and drainage duration. In adults, FA reduce hospitalization and drainage duration and increase drainage volume. In children, saline seems more effective in reducing hospitalization duration, while FA increase drainage volume. These findings underscore the need for age-specific treatments and further research, especially in the pediatric population.

Anterior quadratus lumborum blocks for postoperative pain treatment following intra-abdominal surgery: A systematic review with meta-analyses and trial sequential analyses.

The anterior quadratus lumborum (QL) block may be used for postoperative pain management for intra-abdominal surgeries, but the evidence is uncertain. We aimed to investigate the benefit and harm of the anterior QL block compared to placebo/no block for intra-abdominal surgery. We searched Medline, Embase, and CENTRAL for randomized controlled trials investigating anterior QL block for postoperative pain management for adult patients undergoing any intra-abdominal surgery. The two co-primary outcomes were cumulative 24-h opioid consumption and serious adverse events. We performed meta-analysis, trial sequential analysis (TSA), assessed the risk of bias, and present the certainty of evidence with the Grading of Recommendations, Assessment, Development and Evaluation approach. Thirty-five trials randomizing 2418 patients were included in the meta-analyses. Anterior QL block may reduce cumulative 24-h intravenous opioid consumption compared to placebo/no block (MD -10.42 mg, 96.7% CI -14.83 to -6.01, TSA-adjusted CI -17.03 to -3.82, p < .01). Two trials reported on SAEs. Anterior QL block may have little to no effect on the number of serious adverse events compared to placebo (RR 1.49, 96.7% CI 0.19 to 11.47, p = .68), but the evidence is very uncertain. All trial results were assessed as being high risk of bias. The anterior QL block may reduce cumulative 24-h opioid consumption. Reported serious adverse events were few and the anterior QL block may have little to no effect on the number of SAEs, but the evidence was very uncertain.

Meta-analysis of RCTs on the safety of non-fixation of mesh in TAPP inguinal hernia repair: an updated meta-analysis

ObjectiveThis meta-analysis aims to compare the clinical efficacy of mesh non-fixation and fixation in laparoscopic transabdominal preperitoneal (TAPP) inguinal hernia repair, systematically evaluating the application value of the mesh non-fixation technique in clinical settings.MethodsA computerized search of PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov databases was conducted to identify randomized controlled trials (RCTs) comparing mesh non-fixation and fixation in TAPP inguinal hernia repair. Meta-analysis was performed using RevMan 5.3 software, and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) evidence grading system was employed for outcome quality assessment. Publication bias analysis was performed using Begg’s test. A trial sequential analysis (TSA) was performed using TSA 0.9.5.10 Beta software.ResultsA total of nine RCTs involving 1,879 inguinal hernia patients were included. Meta-analysis results demonstrated that, compared to the fixation group, the non-fixation group exhibited significantly lower seroma occurrence rate [RR = 0.43, 95% CI (0.20, 0.89), P = 0.02, heterogeneity P = 0.28, I²=22%], Visual Analog Scale (VAS) pain score at 6 months postoperatively [MD=-0.21, 95% CI (-0.29, -0.12), P < 0.00001, heterogeneity P = 0.34, I²=0%], and cost [MD=-3.23 thousand yuan, 95% CI (-4.26, -2.19), P < 0.00001, heterogeneity P = 0.0003, I²=92%]. There were no statistically significant differences in overall complication rate [RR = 0.88, 95% CI (0.62, 1.23), P = 0.45, heterogeneity P = 0.11, I²=44%], overall infection event rate [RR = 0.96, 95% CI (0.36, 2.56), P = 0.93, heterogeneity P = 0.62, I²=0%] and recurrence rate [RR = 0.75, 95% CI (0.28, 1.99), P = 0.56, heterogeneity P = 0.44, I²=0%] between the two groups. The results of the TSA indicated that the observed lower seroma occurrence rate in the non-fixation group compared to the fixation group requires further validation through the inclusion of additional RCTs.ConclusionMesh non-fixation in TAPP inguinal hernia repair is deemed safe and does not elevate the risk of hernia recurrence. However, given certain limitations in this study, future comprehensive and reliable validation will require further multicenter, high-quality, large-sample double-blind RCTs.

Perioperative Analgesic Interventions for Reduction of Persistent Postsurgical Pain After Total Hip and Knee Arthroplasty: A Systematic Review and Meta-analysis.

High pain levels immediately after surgery have been associated with persistent postsurgical pain. Still, it is uncertain if analgesic treatment of immediate postsurgical pain prevents the development of persistent postsurgical pain. We searched MEDLINE, CENTRAL, and Embase up to September 12, 2023, for randomized controlled trials investigating perioperative analgesic interventions and with reported pain levels 3 to 24 months after total hip or knee arthroplasty in patients with osteoarthritis. The primary outcome was pain score 3 to 24 months after surgery, assessed at rest and during movement separately. Two authors independently screened, extracted data, and assessed risk of bias using the Cochrane Risk of Bias 2 tool. We conducted meta-analyses and tested their robustness with trial sequential analyses and worst-best and best-worst case analyses. We included 49 trials with 68 intervention arms. All but 4 trials were at high risk of bias for the primary outcome. Moreover, the included trials were heterogeneous in terms of exclusion criteria, baseline pain severity, and which cointerventions the participants were offered. For pain at rest, no interventions demonstrated a statistically significant difference between intervention and control. For pain during movement, perioperative treatment with duloxetine (7 trials with 641 participants) reduced pain scores at 3 to 24 months after surgery (mean difference -4.9 mm [95% confidence interval {CI}, -6.5 to -3.4] on the 0-100 visual analog scale) compared to placebo. This difference was lower than our predefined threshold for clinical importance of 10 mm. We found no perioperative analgesic interventions that reduced pain 3 to 24 months after total hip or knee arthroplasty for osteoarthritis. The literature on perioperative analgesia focused little on potential long-term effects. We encourage the assessment of long-term pain outcomes.

Subcutaneous fast-acting insulin analogues ± long-acting insulin vs IV insulin infusion in DKA: updated meta-analysis of randomised trials.

Diabetic ketoacidosis (DKA) is often treated with intravenous regular insulin infusion (IVRII). Subcutaneous fast-acting insulin analogues (FAIAs); either alone or combined with subcutaneous long-acting insulin (LAI); might be useful to treat DKA. Our meta-analysis updated on their benefits and safety in DKA. We searched major electronic databases for randomised trials on subcutaneous FAIAs ± subcutaneous LAI vs IVRII in DKA. Primary outcomes were all-cause in-hospital mortality, time to resolution of DKA and hyperglycemia, in-hospital DKA recurrence and hospital readmission for DKA post-discharge. Secondary outcomes included resource utilisation and patient satisfaction. Safety outcomes were adverse events. Reviewers assessed risk of bias and quality of evidence using GRADE. We performed a priori subgroup and trial sequential analyses on primary outcomes. Seven trials enrolled 351 mainly adult patients (255/351) with mild to moderate DKA. No trials studied subcutaneous FAIA and subcutaneous LAI. Their risk of bias was high or unclear in several domains. No all-cause in-hospital mortality and DKA recurrence were reported. No trial investigated hospital readmission for DKA post-discharge. There was no difference in mean time to resolution of DKA (mean difference = -0.70, 95% CI -2.18 to 0.79 h, p = 0.36) or hyperglycemia [blood glucose < 250 mg/dL (13.9 mmol/L)] (mean difference = -0.17, 95% CI -1.10 to 0.76 h, p = 0.72) between subcutaneous FAIA and IVRII groups. There were largely no subgroup effects. Both groups had similar secondary outcomes. Hypoglycemia was the most common adverse event. Quality of evidence was low to very-low for all outcomes. The only possible trial sequential analysis for time to resolution of DKA was inconclusive. There was low- to very-low quality evidence that subcutaneous FAIA did not affect patient-centered outcomes in mainly adult patients with mild to moderate DKA compared to IVRII.

Polymorphisms of Estrogen receptor alpha (ESR1) rs9340799, rs2234693, rs1801132, and rs2228480 and their association with migraine risk: a meta-analysis with meta-regression and trial sequential analysis

Polymorphisms of Estrogen receptor alpha (ESR1) rs9340799, rs2234693, rs1801132, and rs2228480 and their association with migraine risk: a meta-analysis with meta-regression and trial sequential analysis

Efficacy and safety of warm needle acupuncture for allergic rhinitis: A systematic review and meta-analysis with trial sequential analysis

BackgroundsWarm needle acupuncture is a distinct form of acupuncture therapy in which, after the needle is inserted into the acupoint, a lit moxa stick is placed on the needle's handle. ObjectiveThis research aims to provide evidence for efficacy and safety of warm needle acupuncture for allergic rhinitis. Search strategiesSeven online databases were searched for study collection, which were published up to March 15th, 2022. Keywords of searching included “AR”, “allergic rhinitis”, “anaphylactic rhinitis”, “warming needle”, “warming needle acupuncture”, “needle warming moxibustion”, “warm needle”, “warm needling method” and “warmed needle”. The quality of the included trials was assessed using the Cochrane risk of bias tool. InterventionsAmong the included trials, warm needle acupuncture—either alone or in combination with Western medicine or other acupoint-based therapies—served as the primary intervention for the experimental groups. In contrast, the control groups received treatments such as Western medicine alone, manual acupuncture alone, or a combination of electro and manual acupuncture. Systematic reviews and meta-analyses were conducted using RevMan 5.3, following the Cochrane systematic review methodology, while trial sequential analysis was performed with TSA 0.9. The quality of the findings was assessed using GRADEpro. ResultsFinally, 23 studies involving 2230 participants were covered. Results of this study revealed that warm needle acupuncture only, or with western medicine, or with other acupoint-based interventions were significantly superior to western medicine alone, manual acupuncture alone, or electro plus manual acupuncture for allergic rhinitis. Adverse events associated with warm needle acupuncture included sensations of chest tightness, throat itching, and allergic reactions to moxa smoke; however, these occurrences were not more frequent than those observed with Western medicine. There is need for RCTs of high quality with placebo or waitlist controls of the intervention for allergic rhinitis. ConclusionWarm needle acupuncture is with potential efficacy and is safe for patients with allergic rhinitis, but more trials are need for further confirmation of the evidence.

The efficacy of ciprofol versus propofol on anesthesia in patients undergoing endoscopy: a systematic review and meta-analysis of randomized controlled trials.

Ciprofol is a new intravenous anesthetic with a similar chemical structure to propofol. We aimed to compare the incidence of adverse actions like injection pain and time indexes of ciprofol versus propofol on anesthesia in patients undergoing endoscopy. We also compared anesthetists' satisfaction during the procedure. Two independent researchers (Liu and Zeng) searched the Cochrane Library, Embase databases, and PubMed for controlled clinical trials. This meta-analysis of randomized controlled trials (RCTs) was performed with the Review Manager, Stata and the Cochrane Risk-of-Bias 2 tool to evaluate methodological quality. Relative risks with 95% confidence interval (CI) were calculated for outcomes. Ten trials, including 1545 patients, were examined in the current meta-analysis. During anesthesia in patients undergoing endoscopy, the incidence of injection pain was significantly reduced in the research group. Compared with propofol, the pooled risk difference (RD) with the use of ciprofol for injection pain for all the procedures was - 0.34 (95% confidence interval [CI], -0.48 to 0.19), and RR for hypotension was 0.73(95% CI:0.58 to 0.92). GRADE showed this meta-analysis has moderate or low confidence. Trial sequential analysis for mortality indicated insufficient sample size for a definitive judgment for lower incidence of hypotension. In painless endoscopy, compared with propofol, ciprofol exhibited non-inferiority anesthesia/sedation in patients, and had a good safety profile with a lower incidence of pain on injection and may reduce the chance of hypotension. Trial sequential analysis suggested the need for more cases, and GRADE highlighted moderate certainty, emphasizing the necessity for further targeted RCTs. PROSPERO, CRD42023433627.

Laparoscopic versus open repair for peptic ulcer perforation: a systematic review, meta-analysis and trial sequential analysis of randomised controlled trials. Time to conclude!

The aim of this study was to investigate comparative outcomes of laparoscopic and open repair for peptic ulcer perforation (PUP). A PRISMA-compliant systematic review with a PROSPERO-registered protocol (registration number CRD42024529286) was conducted. All randomised controlled trials (RCTs) involving PUP patients managed by laparoscopic or open repair were identified and their risk of bias assessed. Outcome syntheses for perioperative mortality and morbidities, need for reoperation, procedure time and length of hospital stay were conducted using random-effects modelling to calculate risk ratios (RR) or mean difference (MD) with 95% confidence intervals (CI). Nine RCTs met the inclusion criteria, enrolling 670 patients of whom 317 were randomised to receive laparoscopic surgery and 353 were managed with open surgery. Laparoscopic repair of PUP significantly reduced mortality (RR 0.37, p = 0.03), total complications (RR 0.57, p = 0.0009), ileus (RR 0.43, p = 0.04), wound complications (RR 0.36, p < 0.0001) and length of hospital stay (MD -2.37, p = 0.0003) compared with the open approach. There were no significant differences in rate of postoperative leak (RR 2.00, 95% CI 0.74-5.41, p = 0.17), abdominal collection (RR 1.19, 95% CI 0.46-3.07, p = 0.72), sepsis (RR 1.17, 95% CI 0.39-3.52, p = 0.65), respiratory complications (RR 0.68, 95% CI 0.32-1.46, p = 0.32), reoperation (RR 1.74, 95% CI 0.57-5.30, p = 0.33) and operating time (MD 15.31, 95% CI -4.86 to 35.47, p = 0.14) between the two groups. Laparoscopic repair of PUP is associated with significantly lower mortality and morbidity and shorter length of stay compared with the open approach. The laparoscopic approach should be the management of choice subject to the existence of laparoscopic expertise.

Non-invasive positive pressure ventilation for acute asthma in children.

Asthma is one of the most common reasons for hospital admission among children, with significant economic burden and impact on quality of life. Non-invasive positive pressure ventilation (NPPV) is increasingly used in the care of children with acute asthma, although the evidence supporting it is weak, and clinical guidelines do not offer any recommendations on its routine use. However, NPPV might be an effective way to improve outcomes for some children with asthma. A previous review did not demonstrate a clear benefit, but was limited by few studies with small sample sizes. This is an update of the previous review. To assess the benefits and harms of NPPV as an add-on therapy to usual care (e.g. bronchodilators and corticosteroids) in children (< 18 years) with acute asthma. We searched the Cochrane Airways Group Specialised Register, CENTRAL, MEDLINE, and Embase. We also conducted a search of ClinicalTrials.gov and the WHO ICTRP. We searched all databases from their inception to March 2023, with no restrictions on language of publication. We included randomised clinical trials (RCTs) assessing NPPV as add-on therapy to usual care versus usual care for children hospitalised for acute asthma exacerbations. We used standard Cochrane methods. We included three RCTs randomising 60 children with acute asthma to NPPV and 60 children to control. All included trials assessed the effects of bilevel positive airway pressure (BiPAP) for acute asthma in a paediatric intensive care unit (PICU) setting. None of the trials used continuous positive airway pressure (CPAP). The controls received standard care. The median age of children ranged from three to six years, and asthma severity ranged from moderate to severe. Our primary outcome measures were all-cause mortality, serious adverse events, and asthma symptom score. Secondary outcomes were non-serious adverse events, health-related quality of life, arterial blood gases and pH, pneumonia, cost, and PICU length of stay. None of the trials reported any deaths or serious adverse events (except one trial that reported intubation rate). Two trials reported asthma symptom score, each demonstrating reductions in asthma symptoms in the BiPAP group. In one trial, the asthma symptom score was (mean difference (MD) -2.50, 95% confidence interval (CI) -4.70 to -0.30, P = 0.03; 19 children) lower in the BiPAP group. In the other trial, a cross-over trial, BiPAP was associated with a lower mean asthma symptom score (MD -3.7; 16 children; very low certainty evidence) before cross-over, but investigators did not report a standard deviation, and it could not be estimated from the first phase of the trial before cross-over. The reduction in both trials was above our predefined minimal important difference. Overall, NPPV with standard care may reduce asthma symptom score compared to standard care alone, but the evidence is very uncertain. The only reported serious adverse event was intubation rate in one trial. The trial had an intubation rate of 40% and showed that BiPAP may result in a large reduction in intubation rate (risk ratio 0.47, 95% CI 0.23 to 0.95; 78 children), but the evidence is very uncertain. Post hoc analysis showed that BiPAP may result in a slight decrease in length of PICU stay (MD -0.87 day, 95% CI -1.52 to -0.22; 100 children), but the evidence is very uncertain. Meta-analysis or Trial Sequential Analysis was not possible because of insufficient reporting and different scoring systems. All three trials had high risk of bias with serious imprecision of results, leading to very low certainty of evidence. The currently available evidence for NNPV is uncertain. NPPV may lead to an improvement in asthma symptom score, decreased intubation rate, and slightly shorter PICU stay; however, the evidence is of very low certainty. Larger RCTs with low risk of bias are warranted.

Is Thrombectomy Effective for Large Vessel Occlusion Stroke Patients with Mild Symptoms? Meta-Analysis and Trial Sequential Analysis

Background: Endovascular treatment (EVT) is an established method for managing large vessel occlusion (LVO), but its efficacy in patients with mild stroke (National Institutes of Health Stroke Scale [NIHSS] score &lt; 6) remains debated. Given the clinical problem of early neurological deterioration in approximately 10% of mild stroke patients, understanding the role of EVT in managing these patients is crucial. Our objective was to perform a meta-analysis with trial sequential analysis (TSA) focusing on mild stroke patients with LVO to determine whether EVT offers better outcomes than best medical therapy alone. Methods: A comprehensive search of PubMed, Cochrane, and Embase databases up to 12 December 2023 identified 14 retrospective and prospective cohort studies, including a total of 4436 patients with NIHSS scores less than 6 and presenting with LVO. Studies were categorized into crossover and non-crossover groups to prevent overestimation of the treatment effect. In the crossover group, patients initially treated with BMT were moved to EVT upon clinical deterioration. In the non-crossover group, patients remained in their initially assigned treatment. Meta-analysis and data extraction followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The primary outcome was achieving an excellent functional outcome, defined as a modified Rankin scale (mRS) score of 0–1 at 3 months. Secondary outcomes included good (mRS 0–2) and favorable (mRS 0–3) functional outcomes. Safety outcomes were symptomatic intracerebral hemorrhage (sICH) and mortality at 3 months. Results: In the crossover group, EVT did not significantly improve excellent functional outcomes, and TSA results were inconclusive. Conversely, in the non-crossover group, EVT significantly improved the excellent functional outcome rates at 3 months (65.0% vs. 53.7%; OR 1.62; 95% CI 1.13 to 2.32), supported by TSA. EVT increased the risk of sICH in both crossover and non-crossover groups, while mortality rates did not significantly differ between EVT and BMT groups. Conclusions: Our research indicates that thrombectomy may not significantly help mild stroke patients in recovering functional status and could increase the risk of sICH. The disparity in results between crossover and non-crossover studies highlights the critical need for the prompt identification of patients at risk of early neurological deterioration to minimize negative outcomes. Additional randomized controlled trials are essential to optimize the application of EVT in this patient population.

TCT-758 Safety and Efficacy of Transcatheter Aortic Valve Replacement (TAVR) With Self-Expanding Valves (SEV) Versus Surgical Aortic Valve Replacement (SAVR): A Meta-Analysis and Trial Sequential Analysis (TSA) of Randomized Controlled Trials

TCT-758 Safety and Efficacy of Transcatheter Aortic Valve Replacement (TAVR) With Self-Expanding Valves (SEV) Versus Surgical Aortic Valve Replacement (SAVR): A Meta-Analysis and Trial Sequential Analysis (TSA) of Randomized Controlled Trials

Natural and bio-engineered stem cell-derived extracellular vesicles for spinal cord injury repair: A meta-analysis with trial sequential analysis

BackgroundStem-cell derived extracellular vesicles (EVs) have shown promise in preclinical spinal cord injury (SCI) models but lack a comprehensive literature review for clinical translation guidance. MethodsThis meta-analysis with trial sequential analysis systematically search PubMed, Web of Science, Embase, and Cochrane Library databases. Prespecified inclusion criteria were studies reporting on measurable outcomes relevant to SCI repair. Risk of bias and quality of reporting were assessed. Random-effects meta-analyses and subgroup analyses comparing natural and bio-engineered EVs were performed. The study was registered with PROSPERO (CRD42024512122). FindingsThe search identified 3935 records, of which 39 studies were included, totaling 1801 animals. Administration of EVs significantly improved locomotor function as measured by Basso-Beattie-Bresnahan or Basso-Mouse-Scale scores at 1 week (natural EVs: SMD 1.50, 95 % CI 1.06–1.95; bio-engineered EVs: SMD 1.93, 95 % CI 1.34–2.52) and 3 weeks (natural EVs: SMD 2.57, 95 % CI 1.96–3.17; bio-engineered EVs: SMD 3.16, 95 % CI 2.29–4.02) post-injury. Subgroup analyses indicated surface modification approaches were most effective among bio-engineered EV strategies. EVs also promoted nerve growth (SMD 2.95, 95 % CI 2.12–3.78), enhanced neuron conductivity (MD 0.75, 95 %CI 0.59–0.90), alleviated inflammation (SMD −3.12, 95 % CI −4.15--2.10), and reduced lesion size (SMD −2.90, 95 % CI −3.87--1.93). ConclusionsBoth natural and bio-engineered EVs improve functional and pathological outcomes in animal models of SCI. The enhanced benefits observed with bio-engineered EVs, particularly those utilizing surface modification approaches, highlight the importance of continued exploration into bio-engineering techniques to optimize EVs’ therapeutic efficacy for SCI repair.Protocol RegistrationCRD42024512122.

S704 Robotic-Assisted Versus Video-Assisted Minimally Invasive Surgery for Esophageal Cancer: An Updated Systematic Review, Meta-Analysis and Trial Sequential Analysis

S704 Robotic-Assisted Versus Video-Assisted Minimally Invasive Surgery for Esophageal Cancer: An Updated Systematic Review, Meta-Analysis and Trial Sequential Analysis

Correction: Comparison of cefiderocol and colistin-based regimens for the treatment of severe infections caused by carbapenem-resistant Acinetobacter baumannii: a systematic review with meta-analysis and trial sequential analysis

Correction: Comparison of cefiderocol and colistin-based regimens for the treatment of severe infections caused by carbapenem-resistant Acinetobacter baumannii: a systematic review with meta-analysis and trial sequential analysis

Meta-analysis of the Selected Genetic Variants in Immune-Related Genes and Multiple Sclerosis Risk.

Previous studies have suggested that certain variants in immune-related genes may participate in the pathogenesis of multiple sclerosis (MS), including rs17824933 in the CD6 gene, rs1883832 in the CD40 gene, rs2300747 in the CD58 gene, rs763361 in the CD226 gene, rs16944 in the IL-1β gene, rs2243250 in the IL-4 gene, and rs12722489 and rs2104286 in the IL-2Rα gene. However, the results remained inconclusive and conflicting. In view of this, a comprehensive meta-analysis including all eligible studies was conducted to investigate the association between these 8 selected genetic variants and MS risk. Up to June 2023, 64 related studies were finally included in this meta-analysis. The odds ratios (ORs) and corresponding 95% confidence intervals (CIs) calculated by the random-effects model were used to evaluate the strength of association. Publication bias test, sensitivity analyses, and trial sequential analysis (TSA) were conducted to examine the reliability of statistical results. Our results indicated that rs17824933 in the CD6 gene, rs1883832 in the CD40 gene, rs2300747 in the CD58 gene, rs763361 in the CD226 gene, and rs12722489 and rs2104286 in the IL-2Rα gene may serve as the susceptible factors for MS pathogenesis, while rs16944 in the IL-1β gene and rs2243250 in the IL-4 gene may not be associated with MS risk. However, the present findings need to be confirmed and reinforced in future studies.

Could Hypertonic Saline Improve Clinical Outcomes in Traumatic Brain Injury? A Trial Sequential Analysis.

Could Hypertonic Saline Improve Clinical Outcomes in Traumatic Brain Injury? A Trial Sequential Analysis.