Updated Meta-analysis Research Articles

Urgent Versus Elective Laparoscopic Cholecystectomy Following Percutaneous Transhepatic Gallbladder Drainage for Moderate Acute Cholecystitis: A Meta-Analysis

Background There is still controversy regarding the treatment strategy for moderate acute cholecystitis (AC). Percutaneous transhepatic gallbladder drainage (PTGBD) followed laparoscopic cholecystectomy (LC) has shown advantages compared to emergency LC (ELC). However, the results are controversial. Therefore, we conducted this updated meta-analysis to clarify this issue. Materials and Methods A comprehensive literature search for relevant studies comparing the PTGBD + LC and ELC for moderate AC was performed. The statistical analysis was conducted using Stata. Results A total of 14 studies were included. The pooled analysis revealed that PTGBD + LC group had a shorter operation time (SMD = −1.07, 95%CI = −1.19 to −0.95), lower amount of intraoperative bleeding (SMD = −0.93, 95%CI = −1.07 to −0.79), lower conversion rate (OR = 0.28, 95% CI = 0.17-0.44), lower postoperative complications (OR = 0.45, 95% CI = 0.23-0.88) shorter postoperative hospital stay (SMD = −1.20, 95%CI = −1.33 to −1.07), lower wound infection rate (OR = 0.41, 95%CI = 0.23-0.74) and higher hospitalization expenses (SMD = 1.13, 95%CI = 0.96 to 1.29) compared with ELC group. There was no significant difference in the incidence of bile leak, bile duct injury and total hospital stay. Conclusion This meta-analysis suggested that PTGBD + LC has significant advantages over ELC for moderate AC patients, including lower surgical difficulty, lower conversion rate, fewer postoperative complications, and shorter hospital stay.

Preventive effects of nitric oxide donors in contrast-induced nephropathy in patients undergoing coronary artery angiography: an updated systematic review and meta-analysis of 13 randomized controlled trials.

Contrast-induced nephropathy (CIN) is associated with increased mortality and morbidity in patients undergoing coronary angiography (CAG) and percutaneous coronary intervention (PCI). We aimed to assess the latest evidence on the preventive effects of nitric oxide (NO) donors in CIN patients undergoing CAG/PCI. We conducted a comprehensive systematic review and meta-analysis of RCTs from PubMed, Web of Science, Scopus, Embase, and Cochrane searches until May 5th, 2024. Dichotomous data were pooled using risk ratio (RR), and continuous data were pooled using mean difference (MD), both with a 95% confidence interval (CI), using (R version 4.3). Our analysis included 13 RCTs encompassing 3,550 patients. NO donors were significantly associated with a decreased incidence of CIN compared to placebo either as an oral administration (RR: 0.33 with 95% CI [0.26, 0.42], P < 0.01) or IV infusions (RR: 0.56 with 95% CI [0.40, 0.78], P < 0.01). Moreover, NO donors were significantly associated with decreased serum creatinine levels compared to placebo either as an oral administration (MD: - 0.07 with 95% CI [- 0.10, - 0.04], P < 0.01) or IV infusions (MD: - 0.07 with 95% CI [- 0.09, - 0.04], P < 0.01). In terms of safety, NO donors were significantly associated with a decreased incidence of major adverse cardiac events (MACE) compared to placebo as an oral administration (RR: 0.64 with 95% CI [0.45, 0.89], P < 0.01). However, there was no significant difference between NO donors as IV infusions and placebo in MACE (RR: 0.68 with 95% CI [0.38, 1.21], P = 0.18). Finally, NO donors were significantly associated with a decreased incidence of all-cause mortality compared to placebo as an oral administration (RR: 0.58 with 95% CI [0.36, 0.94], P = 0.03). Nevertheless, there was no statistically significant difference in all-cause mortality between IV infusions of NO donors and placebo (RR: 1.84 with 95% CI [0.40, 8.52], P = 0.44). NO donors as adjunct therapy are associated with reduced incidence of CIN and decreased serum creatinine levels, either as an oral or IV administration. They were also associated with reduced incidence of MACE, all-cause mortality, and recurrent myocardial infarction as an oral administration, which makes this simple, low-cost intervention an important therapeutic option in patients undergoing CAG/PCI.

Perioperative direct oral anticoagulant management during cardiac implantable electronic device surgery: an updated systematic review and meta-analysis.

Patients undergoing cardiovascular implantable electronic device (CIED) implantation are often on direct oral anticoagulation (DOAC). However, the evidence on whether to continue or temporarily discontinue DOAC therapy during the perioperative period in these patients is unclear. We conducted a comprehensive literature review using PubMed, Embase, and Cochrane databases through July 2024. We included studies comparing uninterrupted versus interrupted perioperative DOAC therapy in patients undergoing CIED procedure- primary implants, pulse generator replacement, and device upgrades. Primary outcomes were clinically significant device-pocket hematoma and thromboembolic events. Secondary outcomes included any device-pocket hematoma, all-cause mortality, major bleeding, and any bleeding. A total of 1,607 patients from 8 studies were included. The mean age was 73.2years, with atrial fibrillation as the indication for DOAC therapy in most patients. The mean CHA2DS2-VASc was 3.4. Among the included studies, 2 were randomized control trials (RCTs), while the others were observational cohort studies, including one that was propensity score matched. Our meta-analysis found both strategies to be similar in terms of clinically significant pocket hematoma (RR 1.70; 95%CI 0.84-3.45; p = 0.14; I2 = 0%), thromboembolic complications (RR 0.35; 95%CI 0.04-3.32; p = 0.36; I2 = 19%), any pocket hematoma, all-cause mortality and any bleeding with a higher risk of major bleeding with uninterrupted anticoagulation. This meta-analysis shows that uninterrupted DOAC therapy is comparable to interrupted therapy for CIED procedures, with a potential increase in major bleeding risk but low overall complication rates. Further research is needed to confirm the best approach of periprocedural anticoagulation in these patients.

Viscoelastic haemostatic assays to guide therapy in elective surgery: an updated systematic review and meta-analysis.

Patients undergoing major surgery frequently experience major uncontrolled bleeding. The aim of this systematic review and meta-analysis was to evaluate the clinical efficacy of using viscoelastic haemostatic assays to manage peri-operative bleeding in elective surgery. We searched PubMed/MEDLINE and Embase databases for randomised controlled trials according to pre-determined criteria. The primary outcomes were blood product requirements; duration of stay in the operating theatre or ICU; and surgical reintervention rate. We included 20 randomised controlled trials. The overall risk of bias was low to moderate. Twelve studies used thromboelastography-based transfusion algorithms, while eight used thromboelastometry. Viscoelastic haemostatic assay-guided therapy was associated with a statistically significant reduction in transfusion of red blood cells (standardised mean difference (95%CI) 0.16 (-0.29 to 0.02)), platelets (standardised mean difference (95%CI) -0.33 (-0.56 to -0.10)) and fresh frozen plasma (standardised mean difference (95%CI) -0.64 (-1.01 to -0.28)). There was no evidence of an effect of viscoelastic haemostatic assay-guided therapy on surgical reintervention (relative risk (95%CI) 1.09 (0.70-1.69)). Viscoelastic haemostatic assay-guided therapy was associated with lower blood loss and shorter ICU duration of stay. There was no evidence of any effect on total duration of stay and all-cause mortality. Viscoelastic haemostatic assay-guided therapy may reduce peri-operative blood product transfusion requirements and blood loss during major elective surgery, with no discernible effect on patient-centred outcomes. The overall quality of evidence was modest.

Adjuvant Immune Checkpoint Inhibitors for Muscle-Invasive Urothelial Carcinoma: An Updated Systematic Review, Meta-analysis, and Network Meta-analysis.

Adjuvant immune checkpoint inhibitors (ICIs) have recently emerged as guideline-recommended treatments of high-risk muscle-invasive urothelial carcinoma (MIUC). However, there is limited evidence regarding the optimal candidates and the differential efficacy of adjuvant ICI regimens. To synthesize and compare the efficacy and safety of adjuvant ICIs for high-risk MIUC using updated data from phase III randomized controlled trials. In April 2024, three databases were searched for eligible randomized controlled trials that evaluated oncologic outcomes in patients with MIUC treated with adjuvant ICIs. Pairwise meta-analysis (MA) and network meta-analyses were performed to compare the hazard ratios of oncological outcomes, including disease-free survival (DFS), overall survival (OS), and adverse events. Subgroup analyses were conducted on the basis of predefined clinicopathological features. Three randomized controlled trials that assessed the efficacy of adjuvant nivolumab, pembrolizumab, and atezolizumab were included in the MAs and network meta-analyses groups. Pairwise MAs showed that treatment with adjuvant ICIs significantly improved DFS [hazards ratio: 0.77, 95% confidence interval (CI): 0.66-0.90] as well as OS (hazards ratio: 0.87, 95% CI 0.76-1.00) in patients with MIUC compared with in the placebo/observation group. The DFS benefit was prominent in patients who underwent neoadjuvant chemotherapy (P = 0.041) and in those with bladder cancer (P = 0.013) but did not differ across programmed death-ligand 1 and lymph node status. Adjuvant ICI therapy was associated with increased risk of any (OR: 2.98, 95% CI 2.06-4.33) and severe adverse events (OR: 1.78, 95% CI 1.49-2.13). The treatment rankings revealed that pembrolizumab for DFS (84%) and nivolumab for OS (93%) had the highest likelihood of improving survival. Our analyses demonstrated the DFS and OS benefits of adjuvant ICIs for high-risk MIUC. Furthermore, patients with bladder cancer who underwent neoadjuvant chemotherapy appeared to be the optimal candidates for adjuvant ICIs regarding prolonged DFS. Adjuvant ICIs are the standard of care for high-risk MIUC, and differential clinical behaviors and efficacy will enrich clinical decision-making.

Safety and efficacy of IL-17 inhibitors in hidradenitis suppurativa: an updated systematic review and meta-analysis including the BE-HEARD trials.

Safety and efficacy of IL-17 inhibitors in hidradenitis suppurativa: an updated systematic review and meta-analysis including the BE-HEARD trials.

Efficacy and safety of transcranial direct current stimulation (tDCS) in treatment of refractory epilepsy: an updated systematic review and meta-analysis of randomized sham-controlled trials.

Despite the currently available treatment, one-third of epilepsy patients continue to experience seizures. Transcranial direct current stimulation (tDCS) has emerged as a potential neuromodulation approach for the non-invasive treatment of refractory epilepsy. This study aims to provide a comprehensive investigation of the efficacy and safety of tDCS in patients with drug-resistant epilepsy. The following databases were searched from inception until June 2023; PubMed, Scopus, Embase, WOS, EBSCO, Cochrane Central, and Ovid MEDLINE. Pooled mean difference was calculated for change in seizure frequency (SF), and number of Interictal epileptiform discharges (IEDs) at different follow-up intervals. We included nine parallel randomized sham-controlled trials with a total of 267 patients. Active tDCS patients had a significantly lower SF per month at 4 and 8 weeks (MD = -4.06, 95% CI [-6.01 to -2.12], p < 0.0001), and (MD = -2.66, 95% CI [-5.09 to -0.23], p = 0.03), respectively. However, weekly SF showed no statistically significant results at 4 weeks of follow-up. The IEDs were observed to significantly decline at 2, 4, and 8 weeks of follow-up. The reported adverse events were mild including mild itching and erythematous rash that resolved spontaneously. In conclusion, tDCS significantly reduced monthly SF and the number of IEDs. Future large RCTs with standard clear informed parameters are still required.

Tenecteplase vs Alteplase in Acute Ischemic Stroke Within 4.5 Hours: A Systematic Review and Meta-Analysis of Randomized Trials.

The current European Stroke Organisation expedited recommendation on tenecteplase (TNK) for acute ischemic stroke (AIS) advocates that TNK 0.25 mg/kg can be used alternatively to alteplase (tissue plasminogen activator [TPA]) for AIS of <4.5 hours duration, based on a meta-analytical approach establishing noninferiority. Since the publication of these guidelines, 4 additional randomized controlled clinical trials (RCTs) have provided further insight. We conducted an updated systematic review and meta-analysis including all available RCTs that investigated efficacy and safety of TNK 0.25 mg/kg compared with TPA for the treatment of AIS within 4.5 hours of onset. The primary outcome was defined as the excellent functional outcome at 3 months (modified Rankin Scale [mRS] score 0-1), whereas good functional outcome (mRS score 0-2), reduced disability at 3 months (≥1-point reduction across all mRS scores), symptomatic intracranial hemorrhage (sICH), and 3-month mortality were evaluated as secondary outcomes. Pooled estimates were calculated with random-effects model. A prespecified subgroup analysis was performed stratifying for TNK formulation, that is, original TNK vs biocopy: recombinant human TNK tissue-type plasminogen activator that is available in China and has a different production process. Eleven RCTs were included comprising a total of 3,788 patients treated with TNK vs 3,757 patients treated with TPA. TNK was associated with higher likelihood of excellent functional outcome (risk ratio [RR] 1.05, 95% CI 1.01-1.10; p = 0.012; I2 = 0%; risk difference 2.95%; 95% CI 0.76%-5.14%; p = 0.008; I2 = 0%) and reduced disability at 3 months (common odds ratio 1.10, 95% CI 1.01-1.19; p = 0.034; I2 = 0%) compared with TPA while good functional outcome (RR 1.03, 95% CI 0.99-1.07; p = 0.142; I2 = 28%) was similar between the groups. Regarding safety outcomes, similar rates of sICH (RR 1.12, 95% CI 0.83-1.53; p = 0.456; I2 = 0%) and 3-month mortality (RR 0.97, 95% CI 0.82-1.15; p = 0.727; I2 = 12%) were observed. When stratified for TNK regimen (original vs biocopy), statistical significance in achieving an excellent functional outcome at 3 months was retained for the original TNK (RR 1.05, 95% CI 1.00-1.10; p = 0.044; I2 = 0%). The updated meta-analysis confirms similar safety between TNK 0.25 mg/kg and TPA, while showing that TNK is superior to TPA regarding excellent functional outcome and reduced disability at 3 months. These findings support transitioning to TNK in clinical practice.

Abstract 4138662: Mineralocorticoid receptor antagonist in patients with acute myocardial infarction: An updated systematic review and meta-analysis of randomized trials

Background: While mineralocorticoid antagonists (MRA) reduce mortality in patients developing heart failure post myocardial infarction (MI), it is unclear whether they are beneficial in an unselected post-MI population. Aims: Using a systematic review and meta-analysis, we aim to determine the effect of MRA treatment versus no MRA treatment on all-cause mortality in unselected post-MI patients from randomized data, simultaneously with the presentation of the largest randomized controlled trial on the topic, the CLEAR SYNERGY trial. Methods/Approach: We completed a systematic review of all randomized controlled trials comparing MRA treatment to no MRA treatment in post-MI patients. We will perform our primary analysis using fixed effects with the Peto odds ratio method and use random effects as a sensitivity analysis. The primary outcome will be all-cause mortality, and secondary outcomes will include cardiovascular mortality, new or worsening heart failure, recurrent myocardial infarction and stroke. Results/Data: Our systematic review of Pubmed, Embase, and CENTRAL from inception until April 30, 2024, yielded 456 records. A total of 11,199 participants from 11 randomized clinical trials will be included in addition to the late-breaking CLEAR SYNERGY trial. The CLEAR SYNERGY trial is a 2 x 2 factorial randomized controlled trial of low-dose colchicine 0.5mg daily versus placebo and spironolactone 25mg daily versus placebo in 7,062 post-MI patients who were within 72h of the index percutaneous coronary intervention. The results of the spironolactone factorial will be presented in the fall of 2024 with an expected median follow-up of 3.5 years. As the investigators of the CLEAR SYNERGY trial, we will combine our data with the other 11 trials for a total of 12 trials and 18,261 participants. Conclusions: CLEAR SYNERGY is the largest randomized controlled trial with the longest follow-up of spironolactone in the post-MI population. Our meta-analysis will provide updated effect estimates of post-MI MRA treatment, leveraging the late-breaking CLEAR SYNERGY data to reflect the totality of the evidence.

Abstract 4117922: The Role of Combined Renin Angiotensin Aldosterone System Inhibitors (RAASi) Plus Beta Blocker Therapy For Cardiotoxicity Prevention In Patients Under Chemotherapy For Breast Cancer: A Meta-Analysis of Randomized Controlled Trials

Introduction: Anti-neoplastic agents, including anthracyclines and trastuzumab, frequently employed in breast cancer treatment carry on considerable cardiotoxic effects impairing both cardiac chamber and cardiac fiber parameters leading to incident heart failure. In response to this challenging side effect, numerous randomized controlled trials (RCTs) have investigated the cardioprotective efficacy of RAASi and beta-blockers (BBs) in patients undergoing anthracycline and trastuzumab chemotherapy. We aim to perform an updated meta-analysis to elucidate the potential cardioprotective properties of these medications in patients undergoing chemotherapy for breast cancer. Methods: A comprehensive search of the literature was performed through April 2024 on PubMed, EMBASE and Clinicaltrials.gov. In total, data from 4 randomized studies were extracted and analyzed. The primary analysis was the effect of RAASi and BBs on LVEF as well as global longitudinal strain (GLS). Data were analyzed using a random-effects model to derive weighted mean differences (WMDs) and 95% confidence intervals for both LVEF and GLS. Data was analyzed using Review Manager 5.3 (RevMan 5.3) software. Results: In total, data from 248 patients (N = 124 on cardioprotection; N = 124 without cardioprotection) undergoing treatment with anti-neoplastic agents for breast cancer were included. At the end of treatment, patients undergoing cardioprotective therapy demonstrated improved LVEF preservation compared to the control group, (mean difference 2.14 [0.03, 4.25]; P=0.05; I2 = 79%). In addition, patients undergoing dual RAASi + BB therapy showed better GLS preservation compared to control group (mean difference –1.37 [-2.01, -0.72]; P &lt; 0.0001; I2 = 0%). Conclusion: In breast cancer patients undergoing anti-neoplastic regimens comprising anthracycline and trastuzumab, the concomitant administration of RAASi and BBs demonstrated better LVEF as well as GLS preservation upon completion of treatment over those without cardioprotective therapy. These findings shed light on the potential benefit derived from the synergistic effects of RAASi and BBs therapy in safeguarding both cardiac chamber and fiber functions amidst aggressive anti-cancer regimens, although further investigations still need to be conducted.

Abstract 4120957: Endovascular Thrombectomy Versus Medical Management for Acute Ischemic Stroke with Large Infarct: An Updated Meta-Analysis of Randomized Controlled Trials

Background: Endovascular therapy (EVT) has revolutionized the treatment of acute ischemic stroke due to large vessel occlusions. Despite the increasing evidence for EVT, its efficacy remains understudied in patients with acute ischemic stroke with large infarcts. Patients with large-volume ischemic strokes are excluded from major randomized controlled trials (RCTs) despite contributing up to 25% of all acute ischemic strokes. Aim: This study aimed to compare clinical outcomes with endovascular thrombectomy versus medical management in patients with acute ischemic stroke with large infarct. Methods: We conducted a systematic literature review on PubMed, Embase, Scopus and Cochrane Library from inception to 15th May 2024 for RCTs. The inverse-variance random-effects model was used to pool odds ratio (OR) and risk ratio (RR) with 95% confidence intervals. The statistical significance was set at p&lt;0.05. Results: 6 RCTs with 1887 patients (945: EVT and 942: medical management) were included. The mean age in both EVT and medical management groups was 70 ± 11.4 years. EVT was associated with a better modified Rankin Score (mRS) at 90 days [OR: 1.68; 95% CI: 1.38, 2.04; p&lt;0.00001], mRS at 90 days (0-2) [OR: 2.47; 95% CI: 1.87, 3.27; p&lt;0.00001], mRS at 90 days (0-3) [OR: 1.96; 95% CI: 1.56, 2.46; p&lt;0.00001], and early neurological improvement [RR: 2.35; 95% CI: 1.79, 3.10; p&lt;0.00001] compared to medical management. EVT was also associated with a higher risk of symptomatic intracranial hemorrhage [RR: 1.71; 95% CI: 1.09, 2.66; p=0.02]. The 90-day mortality [RR: 0.86; 95% CI: 0.72, 1.02; p=0.08] was comparable between the two groups. Conclusion: Patients with acute ischemic stroke with large infarct had superior functional outcomes with EVT as compared to medical management alone. However, EVT was associated with higher risks of symptomatic intracranial hemorrhage, with comparable 90-day mortality risk. Further large RCTs are warranted to evaluate the outcomes with EVT in acute ischemic stroke with large infarct.

Knee pain improvement after genicular artery embolization for the management of knee osteoarthritis: an updated systematic review and meta-analysis of 21 studies.

Knee osteoarthritis is aprogressive inflammatory musculoskeletal disease with aprevalence of approximately 15-23% and limited treatment options. In recent years, transcatheter genicular artery embolization (GAE) has been proposed due to promising results concerning symptomatic knee pain relief and mobility. This systematic review and meta-analysis aimed to evaluate the aggregated data on the safety and efficacy of GAE for pain reduction in the treatment of knee osteoarthritis. Asystematic search of the three major databases (MEDLINE, Embase, and CENTRAL) from inception to 27February 2024 was conducted according to the PRISMA guidelines. Studies reporting pain reduction according to the Visual Analogue Scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)-Total, WOMAC-Pain, and Knee Injury and Osteoarthritis Outcome Score (KOOS)-Pain scales and adverse event rates were included. Meta-analysis was performed by estimating the mean differences and by fitting random-effect models. Overall, 21studies were included, comprising of 633 patients and 758 knees treated. The combined data analysis showed that patients who underwent GAE demonstrated mean declines in the VAS score of -38.5 points (95% confidence interval [CI]: -44.9, -32.0) at 1month, -36.2 points (95%CI -43.0, -29.5) at 3months, -40.3 points (95%CI: -49.0, -31.7) at 6months, and -40.5 points (95%CI: -54.5, -26.6) at 12months. Similarly, significant differences at all time points were also found for the WOMAC-Total, WOMAC-Pain, and KOOS-Pain scores. No difference between permanent and non-permanent embolic material was found in the subgroup analysis for all time points. Genicular artery embolization is safe and effective for the treatment of painful knee osteoarthritis. This result was not affected by the type of embolic material used (permanent vs. non-permanent).

The Effect of Spirulina Supplementation on Blood Pressure in Adults: A GRADE-Assessed Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Previous studies have yielded controversial results regarding the effect of spirulina on blood pressure (BP), which need updating. So, this updated systematic review and meta-analysis of randomized controlled trials (RCTs) carry out a more accurate estimation of the effect of spirulina on BP in adults. This systematic searches (in PubMed/Medline, Scopus, and ISI Web of Science) until April 1, 2024, to identify related RCTs based on PICOS guidelines (population (individuals > 18 years old), the intervention (spirulina), the comparison (control or placebo group), the outcomes (systolic BP (SBP) and diastolic BP (DBP)), the study design (RCTs)), and PRISMA-checklist (Supporting Information, data S2). We evaluated the impact of spirulina on DBP and SBP. Conventional procedures were employed for analyzing publication bias, heterogeneity, and sensitivity. The GRADE criteria and the Cochrane assessment method were employed to evaluate the risk of bias (ROB) and certainty of evidence across the studies, respectively. The result shows spirulina consumption decreases SBP (WMD: -4.41 mmHg, 95% CI: -6.74 to -2.07, I2 = 66.1%) and DBP (WMD: -2.84 mmHg, 95% CI: -4.65 to -1.03, I2 = 62.3%). Subgroup analysis demonstrated SBP and DBP were still lower in individuals with ≥ 120 and ≥ 80 mmHg, hypertension (HTN) individuals, overweight individuals, age > 50 years, and > 8 weeks of intervention. Indeed, we do not observe publication bias, ROB, or interference studies in the overall results of BPs, and based on GRADE, our outcomes have moderate quality. Because of the low number of studies and participants, the dose-response and meta-regression are not significant. His study demonstrated spirulina intervention decreased SBP and DBP in HTN and overweight individuals, age > 50 years, and > 8 weeks of intervention. So, spirulina intake decreases BP and could be used in clinical practice. Furthermore, more and high-quality RCTs are needed to establish the clinical efficacy of the spirulina and determine cutoff spirulina interventions based on dose and duration. Trial Registration: PROSPERO: CRD42024534608.

Direct Oral Anticoagulants Versus Aspirin for Stroke Prevention After Embolic Stroke of Undetermined Source: An Updated Meta-Analysis of Randomized Controlled Trials

Background: Four randomized controlled trials (RCTs) did not show a benefit of direct oral anticoagulant (DOAC) treatment compared with antiplatelet therapy for the prevention of recurrent strokes in patients with embolic stroke of undetermined source (ESUS). However, the balance between efficacy and safety in subgroups needs to be better defined. We aimed to assess the relative benefits of DOACs in key subgroups of adult patients with ESUS. Methods: We searched major databases (PubMed, Embase, CENTRAL, and Web of Science) for RCTs published from inception to 16 June 2024. The primary outcome was recurrent stroke, and the main safety outcomes were major bleeding and clinically relevant non-major bleeding (CRNB). We assessed the risk of bias using the Cochrane Risk of Bias tool 2. Results: We identified four RCTs, involving a total of 13,970 patients with ESUS. Compared to antiplatelet therapy, treatment with DOAC did not reduce the risk of recurrent stroke (RR 0.95, 95% CI 0.83–1.08, p = 0.45) or ischemic stroke (RR 0.92, 95% CI 0.80–1.05, p = 0.22) or increase major bleeding (RR 1.57, 95% CI 0.87–2.83; p = 0.14). DOAC treatment was associated with a significantly higher risk of CRNMB compared to aspirin (RR 1.52, 95% CI: 1.22–1.90; p = 0.0002). The subgroup analysis demonstrated that use of DOACs was associated with a significant protective effect in patients aged 75 or older (RR 0.76, 95% CI 0.60–0.97, p = 0.03) and when the time from index stroke to randomization was ≥8 days (RR 0.80, 95% CI 0.66–0.97, p = 0.02) in preventing recurrency of any type of stroke. Conclusions: Our meta-analysis showed lack of overall benefit of anticoagulation with DOAC compared to antiplatelet therapy for recurrent stroke prevention in adult patients with ESUS. However, the subgroup analyses suggest the possibility of interactions between age and timing of randomization since stroke and treatment with an DOAC in terms of recurrent stroke prevention. Further research toward tailoring the antithrombotic strategy according to patient characteristics is needed.

Complete versus culprit-only coronary revascularization in patients with myocardial infarction and multivessel disease undergoing percutaneous coronary intervention: an updated meta-analysis.

Recently, the FFR-Guidance for Complete Nonculprit Revascularization (FULL REVASC) trial in ST elevation myocardial infarction (STEMI) patients with multiple vessel disease (MVD) did not show differences in the composite endpoint of death from any cause, myocardial infarction, or unplanned revascularization than culprit-lesion-only percutaneous coronary intervention (PCI) at 4.8 years, although complete revascularization is a recommendation IA in current guidelines. We want to determine through an updated meta-analysis whether complete revascularization is associated with decreased mortality and hard clinical endpoints compared to culprit lesion only PCI. We searched MEDLINE, Embase, ISI Web of Science, and Cochrane Central Register of Controlled Trials) from January 1990 to April 2024 using the terms "percutaneous coronary intervention" combined with "non culprit lesions" or "culprit lesion" or "complete revascularization" or "incomplete revascularization." Additionally, a "snowball search" was conducted. Only randomized clinical trials (RCT) reporting mortality, re-infarction or new revascularization after at least 12 months and using predominantly drug eluting stents were included. The summary effect of different revascularization strategies on cardiovascular endpoints was estimated and measures of effect size were expressed as odds ratios (ORs). Eight RCT involving 9515 patients were included, with a follow-up range between 12 months and 4.8 years. Main findings show that culprit lesion revascularization was associated with an increased risk of MI (OR: 1.38; 95% CI: 1.05 to 1.81, I2 42%) and ischemia-guided revascularization (OR: 2.81; 95% CI: 1.86 to 4.26, I2 80%) compared to complete revascularization, without differences in overall mortality (OR: 1.15; 95% CI: 0.98 to 1.36, I2 2%). In patients with STEMI and MVD without cardiogenic shock, our metanalysis showed that complete revascularization with PCI significantly reduced the risk of non-fatal myocardial reinfarction and ischemic-driven revascularization compared to culprit vessel-only revascularization, without differences in overall mortality.

Letter: Hypertonic Saline Solution Versus Mannitol for Brain Relaxation During Craniotomies: A Systematic Review and Updated Meta-Analysis.

Letter: Hypertonic Saline Solution Versus Mannitol for Brain Relaxation During Craniotomies: A Systematic Review and Updated Meta-Analysis.

Genetic Association of the Ins/Del Variant of ACE and Risk of Cardiomyopathy: A Case-Control Study and Updated Meta-Analysis.

Cardiomyopathy, is a complex condition influenced by multiple genes and environmental factors. It has been suspected that cardiomyopathy is affected by the ACE gene's I/D polymorphism. Our study aimed to evaluate the association between this polymorphism and cardiomyopathy risk in the Jammu population of North India, alongside a meta-analysis to determine the specific risks associated with different types of cardiomyopathy. In the case-control study, we opted for a convenient sampling technique to gather patients from hospitals. Meanwhile, for the meta-analysis registered under PROSPERO with CRD42024519763, and in line with PRISMA guidelines, we accessed online databases and applied predefined inclusion criteria. Data extraction and quality assessment were performed using the Newcastle-Ottawa scale. Statistical analysis included genotypic frequencies, Hardy-Weinberg equilibrium testing, logistic regression models, and assessments for heterogeneity and publication bias. The case-control study revealed a significant association between the ACE I/D risk variant and cardiomyopathy risk in the Jammu population (OR: 1.30, CI [1.04-1.63], p-value=0.021). Furthermore, a total of 34 studies were fund-eligible for the meta-analysis and demonstrated a significant association between the risk variant and both dilated (OR: 1.25, CI [1.03-1.50], p-value=0.022) and hypertrophic (OR: 1.31, CI [1.0876-1.5776], p-value = 0.004446) cardiomyopathy. Our study found a significant association between the I/D polymorphism and cardiomyopathy risk in the Jammu population. Further, the meta-analysis strengthens the findings by consistently linking the ACE I/D polymorphism to both dilated and hypertrophic cardiomyopathy. These results underscore the importance of genetic factors in cardiomyopathy risk assessment and further research is needed to understand the underlying mechanisms and potential therapeutic implications.

The Optimal Dosage and Duration of Metformin for Prevention and Treatment of Antipsychotic-Induced Weight Gain: An Updated Systematic Review and Meta-Analysis.

Weight gain and metabolic complications are substantial adverse effects associated with second-generation antipsychotics. However, comprehensive guidelines for managing antipsychotic-induced weight gain are lacking. This review included all double-blind, placebo-controlled studies investigating metformin's effectiveness in addressing antipsychotic-related weight gain. We systematically searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, Google Scholar, and ClinicalTrials.gov for relevant studies from the inception to 2024. A random-effects model was used for the meta-analysis. This meta-analysis, including 20 studies with 1070 patients, revealed that metformin significantly surpassed placebo in attenuating weight gain in patients receiving antipsychotics. The mean weight change with metformin was -3.32kg [95% confidence interval (CI): -4.57 to -2.07]. Additionally, metformin use resulted in a marked decrease in body mass index [-1.24kg/m2 (95% CI: -1.70 to -0.77)]. Metformin could maintain the effects from 12 to 24 weeks. This updated meta-analysis investigated the durations and dosages of metformin use in patients with schizophrenia experiencing antipsychotic-induced weight gain. The findings highlight the need for additional large-scale research to validate our findings.

In Reply: Hypertonic Saline Solution Versus Mannitol for Brain Relaxation During Craniotomies: A Systematic Review and Updated Meta-Analysis.

In Reply: Hypertonic Saline Solution Versus Mannitol for Brain Relaxation During Craniotomies: A Systematic Review and Updated Meta-Analysis.

Association between nickel exposure and diabetes risk: an updated meta-analysis of observational studies

ObjectiveThe results of epidemiological studies on the association between nickel exposure and diabetes remain controversial. Therefore, an update meta-analysis was conducted to examine the association between urinary nickel levels and diabetes risk, and to focus on whether there is an association between blood nickel levels and diabetes risk.MethodsRelevant studies were comprehensively searched from PubMed, Web of Science, and Wanfang databases from their inception to July 2024. The random-effects model was utilized to determine pooled Standard Mean Difference (SMD) and 95% confidence intervals (CIs), with stratified and sensitivity analyses also performed. Heterogeneity between studies was assessed using I2 statistic, while publication bias was evaluated using Egger's and Begg's tests. The quality of the included studies was assessed using the Newcastle-Ottawa Scale.ResultsA total of 19 studies involving 46,071 participants were included in this meta-analysis. The random-effects model indicated that the pooled SMD for nickel exposure levels in diabetic patients and non-diabetic controls were 0.16 (95% CI 0.07–0.2) for urine and 0.03 (95% CI −0.20 to 0.27) for blood, respectively.ConclusionIt was discovered that diabetes risk was positively correlated with urinary nickel levels, whereas there was no significant correlation with blood nickel levels. Furthermore, it appeared that the association between nickel exposure and diabetes risk differ in individuals with diabetes compared to those with pre-diabetes, and that the direction of the correlation may even be reversed. In conclusion, more high-quality prospective studies are needed in order to validate these findings in future research endeavors.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO, registration number: CRD42024534139.