Sphingosine 1-phosphate (S1P) receptor modulators as an induction and maintenance therapy for ulcerative colitis: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVE: One sphingosine-1-phosphate (S1P) receptor modulator is approved (ozanimod) and another (etrasimod) is under investigation for the induction and maintenance of remission of ulcerative colitis (UC). We aim to evaluate the efficacy and safety of S1P modulators in patients with active UC. METHODS: We conducted a systematic review and meta-analysis synthesizing randomized controlled trials (RCTs), which were retrieved by systematically searching: PubMed, Web of Science, SCOPUS, and Cochrane through May 13th, 2023. We used the fixed-effect model to pool dichotomous data using risk ratio (RR) with a 95% confidence interval (CI). RESULTS: Five RCTs with a total of 1990 patients were included. S1P receptor modulators were significantly associated with increased clinical response during both the induction (RR 1.71 with 95% CI [1.50, 1.94], P = 0.00001) and maintenance phases (RR 1.89 with 95% CI [1.33, 2.69], P = 0.0004); clinical remission rates during both induction (RR 2.76 with 95% CI [1.88, 4.05], P = 0.00001) and maintenance phases (RR 3.34 with 95% CI [1.41, 7.94], P = 0.006); endoscopic improvement during both induction (RR 2.15 with 95% CI [1.71, 2.70], P = 0.00001) and maintenance phases (RR 2.41 with 95% CI [1.15, 5.05], P = 0.02); and histologic remission during both induction (RR 2.60 with 95% CI [1.89, 3.57] [1.17, 2.10], P = 0.00001) and maintenance phases (RR 2.52 with 95% CI [1.89, 3.37], P = 0.00001). Finally, there was no difference regarding safety outcomes as compared to placebo in both the induction and maintenance phases. CONCLUSION: S1P receptor modulators are effective in inducing and maintaining remission in patients with moderate to severe UC.

Protective efficacy and safety of radiation-attenuated and chemo-attenuated Plasmodium Falciparum sporozoite vaccines against controlled and natural malaria infection: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVE: Despite the significant burden of Plasmodium falciparum (Pf) malaria and the licensure of two vaccines for use in infants and young children that are partially effective in preventing clinical malaria caused by Pf, a highly effective vaccine against Pf infection is still lacking. Live attenuated vaccines using Pf sporozoites as the immunogen (PfSPZ Vaccines) hold promise for addressing this gap. Here we review the safety and efficacy of two of the most promising PfSPZ approaches: PfSPZ Vaccine (radiation attenuated PfSPZ) and PfSPZ-CVac (chemo-attenuated PfSPZ). METHODS: We conducted a systematic review and meta-analysis by searching PubMed, EMBASE, SCOPUS, CENTRAL, and WOS until 22nd December 2021. We included randomized controlled trials (RCTs) of these two vaccine approaches that measured protection against parasitaemia following controlled human malaria infection (CHMI) in malaria-naive and malaria-exposed adults or following exposure to naturally transmitted Pf malaria in African adults and children (primary outcome) and that also measured the incidence of solicited and unsolicited adverse events as indicators of safety and tolerability after vaccination (secondary outcome). We included randomized controlled trials (RCTs) that measured the detected parasitaemia after vaccination (primary outcome) and the incidence of various solicited and unsolicited adverse events (secondary outcome). The quality of the included RCTs using the Cochrane ROB 1 tool and the quality of evidence using the GRADE system were evaluated. We pooled dichotomous data using the risk ratio (RR) for development of parasitemia in vaccinees relative to controls as a measure of vaccine efficacy (VE), including the corresponding confidence interval (CI). This study was registered with PROSPERO (CRD42022308057). RESULTS: We included 19 RCTs. Pooled RR favoured PfSPZ Vaccine (RR: 0.65 with 95% CI [0.53, 0.79], P = 0.0001) and PfSPZ-table (RR: 0.42 with 95% CI [0.27, 0.67], P = 0.0002) for preventing parasitaemia, relative to normal saline placebo. Pooled RR showed no difference between PfSPZ Vaccine and the control in the occurrence of any solicited adverse event (RR: 1.00 with 95% CI [0.82, 1.23], P = 0.98), any local solicited adverse events (RR: 0.73 with 95% CI [0.49, 1.08], P = 0.11), any systemic solicited adverse events (RR: 0.94 with 95% CI [0.75, 1.17], P = 0.58), and any unsolicited adverse event (RR: 0.93 with 95% CI [0.78, 1.10], P = 0.37). CONCLUSION: PfSPZ and PfSPZ-CVacs showed comparable efficacy. Therefore, they can introduce a promising strategy for malaria prophylaxis, but more large-scale field trials are required to sustain efficacy and yield clinically applicable findings.

Safety and Efficacy of Camostat Mesylate for Covid-19: a systematic review and Meta-analysis of Randomized controlled trials.

BACKGROUND: Camostat mesylate, an oral serine protease inhibitor, is a powerful TMPRSS2 inhibitor and has been reported as a possible antiviral treatment against COVID-19. Therefore, we aim to assess the safety and efficacy of camostat mesylate for COVID-19 treatment. METHODS: A systematic review and meta-analysis synthesizing randomized controlled trials from PubMed, Scopus, Embase, Cochrane, Web of Science, clinical trials.gov, and medrxiv until June 2023. The outcomes were pooled using Mean difference (MD) for continuous outcomes and risk ratio (RR) for dichotomous outcomes. The protocol is registered in PROSPERO with ID CRD42023439633. RESULTS: Nine RCTs, including 1,623 patients, were included in this analysis. There was no difference between camostat mesylate and placebo in producing negative PCR test results at 1-7 days (RR: 0.76, 95% CI: [0.54, 1.06] P = 0.1), 8-14 days (RR: 1.02, 95% CI: [0.84, 1.23] P = 0.87), or 15-21 days (RR: 0.99, 95% CI: [0.82, 1.19] P = 0.90); clinical resolution of symptoms at 1-7 days (RR: 0.94 (95% CI: 0.58, 1.53) P = 0.81), 8-14 days (RR: 0.91, 95% CI: [0.74, 1.11] P = 0.33, ), or 15-21 days (RR: 0.77, 95% CI: [0.40, 1.51] P = 0.45); and time to symptom improvement (MD:-0.38 weeks (95% CI: [-1.42, 0.66] P = 0.47, I2 = 85%). CONCLUSION: Camostat mesylate did not improve clinical outcomes in patients with COVID-19, compared to placebo.

Clinical decision support systems to optimize adherence to anticoagulant guidelines in patients with atrial fibrillation: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Clinical decision support systems (CDSS) have been utilized as a low-cost intervention to improve healthcare process measures. Thus, we aim to estimate CDSS efficacy to optimize adherence to oral anticoagulant guidelines in eligible patients with atrial fibrillation (AF). METHODS: A systematic review and meta-analysis of randomized controlled trials (RCTs) retrieved from PubMed, WOS, SCOPUS, EMBASE, and CENTRAL through August 2023. We used RevMan V. 5.4 to pool dichotomous data using risk ratio (RR) with a 95% confidence interval (CI). PROSPERO ID: CRD42023471806. RESULTS: We included nine RCTs with a total of 25,573 patients. There was no significant difference, with the use of CDSS compared to routine care, in the number of patients prescribed anticoagulants (RR: 1.06, 95% CI [0.98, 1.14], P = 0.16), the number of patients prescribed antiplatelets (RR: 1.01 with 95% CI [0.97, 1.06], P = 0.59), all-cause mortality (RR: 1.19, 95% CI [0.31, 4.50], P = 0.80), major bleeding (RR: 0.84, 95% CI [0.21, 3.45], P = 0.81), and clinically relevant non-major bleeding (RR: 1.05, 95% CI [0.52, 2.16], P = 0.88). However, CDSS was significantly associated with reduced incidence of myocardial infarction (RR: 0.18, 95% CI [0.06, 0.54], P = 0.002) and cerebral or systemic embolic event (RR: 0.11, 95% CI [0.01, 0.83], P = 0.03). CONCLUSION: We report no significant difference with the use of CDSS compared to routine care in anticoagulant or antiplatelet prescription in eligible patients with AF. CDSS was associated with a reduced incidence of myocardial infarction and cerebral or systemic embolic events.

Efficacy of tacrolimus versus cyclosporine after lung transplantation: an updated systematic review, meta-analysis, and trial sequential analysis of randomized controlled trials.

BACKGROUND: Little data supports using tacrolimus versus cyclosporin for immunosuppression concerning acute rejection and bronchiolitis obliterans syndrome/Chronic Lung Allograft Dysfunction CLAD complications following lung transplantation (LTx). Our goal was to evaluate the use of tacrolimus versus cyclosporine in preventing these complications after LTx. METHODS: We included randomized controlled trials (RCTs) by searching PubMed, Web of Science, SCOPUS, and Cochrane through January 10th, 2024. We pooled dichotomous data using the risk ratio (RR) and continuous data using the mean difference (MD) with a 95% confidence interval (CI). RESULTS: We included Four RCTs with a total of 677 patients. Tacrolimus was significantly associated with decreased risk of acute rejection (RR: 1.21, 95% CI [1.03, 1.42], I2 = 25%, P = 0.02) compared with cyclosporine, bronchiolitis obliterans syndrome/CLAD (RR: 1.87, 95% CI [1.26, 2.77], I2 = 52%, P = 0.002), and treatment withdrawal (RR: 3.11, 95% CI [2.06, 4.70], I2 = 0%, P = < 0.00001). However, tacrolimus significantly increased the risk of new-onset diabetes (RR: 0.33, 95% CI [0.12, 0.91], I2 = 0%, P = 0.03), and kidney dysfunction (RR: 0.79, 95% CI [0.66, 0.93], I2 = 0%, P = 0.006). In contrast, there was no difference in the incidence of all-cause mortality (RR: 91, 95% CI [0.68, 1.22], I2 = 0%, P = 0.53), arterial hypertension (RR: 2.40, 95% CI [0.41, 14.21], I2 = 92%, P = 0.33), and new cancer (RR: 1.57, 95% CI [0.79, 3.10], I2 = 4%, P = 0.20). CONCLUSION: Tacrolimus has decreased acute rejection episodes and CLAD rate than cyclosporine, but it increased the risk of new-onset diabetes and kidney dysfunction.

Efficacy and safety of extracorporeal membrane oxygenation for cardiogenic shock complicating myocardial infarction: a systematic review and meta-analysis.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been presented as a potential therapeutic option for patients with cardiogenic shock complicating myocardial infarction (CS-MI). We aimed to investigate the efficacy and safety of ECMO in CS-MI. METHODS: A systematic review and meta-analysis synthesizing evidence from randomized controlled trials obtained from PubMed, Embase, Cochrane, Scopus, and Web of Science until September 2023. We used the random-effects model to report dichotomous outcomes using risk ratio and continuous outcomes using mean difference with a 95% confidence interval. Finally, we implemented a trial sequential analysis to evaluate the reliability of our results. RESULTS: We included four trials with 611 patients. No significant difference was observed between ECMO and standard care groups in 30-day mortality with pooled RR of 0.96 (95% CI: 0.81-1.13, p = 0.60), acute kidney injury (RR: 0.65, 95% CI: 0.41-1.03, p = 0.07), stroke (RR: 1.16, 95% CI: 0.38-3.57, p = 0.80), sepsis (RR: 1.06, 95% CI: 0.77-1.47, p = 0.71), pneumonia (RR: 0.99, 95% CI: 0.58-1.68, p = 0.96), and 30-day reinfarction (RR: 0.95, 95% CI: 0.25-3.60, p = 0.94). However, the ECMO group had higher bleeding events (RR: 2.07, 95% CI: 1.44-2.97, p < 0.0001). CONCLUSION: ECMO did not improve clinical outcomes compared to the standard of care in patients with CS-MI but increased the bleeding risk.

Intravascular imaging-guided versus angiography-guided percutaneous coronary intervention: a systematic review and bayesian network meta-analysis of randomized controlled trials.

BACKGROUND: Percutaneous coronary intervention (PCI) has become one of the most commonly performed interventional life-saving procedures worldwide. Intravascular Imaging (intravascular ultrasound (IVUS) and optical coherence tomography (OCT)) have initially evolved to guide PCI compared with angiography. However, this technology is not universally employed in all PCI procedures, and there is ongoing controversy regarding its additional benefits to patient outcomes. We aim to estimate the efficacy and safety of imaging modalities during PCI, allowing pre-, per, and post-intervention assessment of coronary vascularization. METHODS: A systematic review and Bayesian network meta-analysis of randomized controlled trials (RCTs), which were retrieved from PubMed, WOS, SCOPUS, EMBASE, and CENTRAL through September 2023. We used R, version 4.2.0. Effect sizes will be presented as odds ratios with accompanying 95% credible intervals. PROSPERO ID: CRD42024507821. RESULTS: Our study, encompassing 36 RCTs with a total of 17,572 patients, revelead that compared to conventional angiography, IVUS significantly reduced the risk of major adverse cardiovascular events (MACE) (OR: 0.71 [95% CrI: 0.56 to 0.87]) but not OCT (OR: 0.91 [95% CrI: 0.62 to 1.39]), IVUS and OCT significantly reduced the risk of cardiac death (OR: 0.50 [95% CrI: 0.33 to 0.76]) and (OR: 0.55 [95% CrI: 0.31 to 0.98]), respectively, IVUS significantly reduced the risk of target vessel-related revascularization (OR: 0.60 [95% CrI: 0.48 to 0.75]) but not OCT (OR: 0.86 [95% CrI: 0.60 to 1.19]), IVUS and OCT significantly reduced the risk of stent thrombosis (OR: 0.50 [95% CrI: 0.28 to 0.92]) and (OR: 0.48 [95% CrI: 0.22 to 0.98]), respectively, IVUS significantly reduced the risk of re-stenosis (OR: 0.65 [95% CrI: 0.46 to 0.88]) but not OCT (OR: 0.55 [95% CrI: 0.15 to 1.99]), neither IVUS (OR: 0.97 [95% CrI: 0.71 to 1.38]) nor OCT (OR: 0.75 [95% CrI: 0.49 to 1.22]) were associated with statistically significant reductions in all-cause mortality, neither IVUS (OR: 0.70 [95% CrI: 0.45 to 1.32]) nor OCT (OR: 0.81 [95% CrI: 0.47 to 1.59]) were associated with statistically significant reductions in target vessel failure, neither IVUS (OR: 0.88 [95% CrI: 0.43 to 2.44]) nor OCT (OR: 0.81 [95% CrI: 0.37 to 2.04]) were associated with statistically significant reductions in target lesion failure, and neither IVUS (OR: 0.82 [95% CrI: 0.60 to 1.06]) nor OCT (OR: 0.84 [95% CrI: 0.59 to 1.19]) were associated with statistically significant reductions in myocardial infarction. CONCLUSION: Intravascular imaging-guided, including IVUS and OCT, improved the postinterventional outcomes of PCI, notably suggesting their advantage over traditional angiography with no significant difference between IVUS and OCT.

Adjunctive left atrial posterior wall isolation for atrial fibrillation: An updated systematic review and meta-analysis.

OBJECTIVE: Posterior left atrial wall isolation (PWI) plus traditional pulmonary vein isolation (PVI) has been proposed as a promising intervention to decrease atrial fibrillation (AF) recurrence. We aim to investigate the efficacy and safety of adding PWI to the traditional PVI in patients with AF. METHODS: A systematic review and meta-analysis was conducted using synthesizing randomized controlled trials (RCTs) retrieved by systematically searching PubMed, Web of Science, SCOPUS, EMBASE, and Cochrane through June 14, 2023. We used Stata version 17 to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD), with a 95% confidence interval (CI) (PROSPERO ID: CRD42023446227). RESULTS: We included 11 RCTs with a total number of 1534 patients. Combined ablation with PWI + PVI was not associated with any significant difference over PVI only regarding the recurrence of clinical AF (RR: 0.86 with 95% CI [0.70-1.06]), all atrial arrhythmia (RR: 0.93 with 95% CI [0.82-1.07]), nonatrial fibrillation arrhythmia (RR: 1.22 with 95% CI [0.97-1.53]), early AF (RR: 0.89 with 95% CI [0.62-1.27]), and antiarrhythmic drugs at discharge (RR: 0.83 with 95% CI [0.67-1.04]). However, it was associated with increased total ablation duration (minutes) (MD: 12.58 with 95% CI [6.80-18.37]) and total procedure duration (minutes) (MD: 16.77 with 95% CI [9.63-23.91]), without any significant difference regarding adverse events (RR: 1.05 with 95% CI [0.63-1.74]). CONCLUSION: While the pooled data from PWI + PVI using point-by-point radiofrequency did not suggest a benefit in the recurrence of various atrial arrhythmias compared to PVI alone, PWI+PVI using direct posterior wall ablation, especially with cryoballoon, demonstrated a significant reduction in recurrence of AF/atrial arrhythmias. Also, PWI + PVI significantly increased the ablation and total procedure durations.

Efficacy and Safety of Endoscopic Stricturotomy in Inflammatory Bowel Disease-Related Strictures: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIM: Luminal strictures, common in inflammatory bowel disease (IBD), especially Crohn's disease (CD), are typically treated with endoscopic balloon dilatation (EBD). The newer endoscopic stricturotomy (ESt) approach shows promise, but data is limited. This systematic review and meta-analysis assess the effectiveness and safety of ESt in IBD-related strictures. METHODS: A comprehensive literature search was conducted until November 2023 for studies assessing ESt efficacy and safety in IBD. Primary outcomes were clinical and technical success, with secondary endpoints covering adverse events, subsequent stricture surgery, additional endoscopic treatments (ESt or EBD), medication escalation, disease-related emergency department visits, and hospitalization post-ESt. Technical success was defined as passing the scope through the stricture, and clinical success was defined as symptom improvement. Single-arm meta-analysis (CMA version 3) calculated the event rate per patient with a 95% confidence interval (CI). Heterogeneity was evaluated using I2. RESULTS: Nine studies were included, involving 640 ESt procedures on 287 IBD patients (169 CD, 118 ulcerative colitis). Of these, 53.3% were men, with a mean age of 43.3 ± 14.3 years and a mean stricture length of 1.68 ± 0.84 cm. The technical success rate was 96.4% (95% CI 92.5-98.3, p-value < 0.0001), and the clinical success rate was 62% (95% CI 52.2-70.9, p-value = 0.017, I2 = 34.670). The bleeding rate was 10.5% per patient, and the perforation rate was 3.5%. After an average follow-up of 0.95 ± 1.1 years, 16.4% required surgery for strictures post-ESt, while 44.2% needed additional endoscopic treatment. The medication escalation rate after ESt was 14.7%. The disease-related emergency department visit rate was 14.7%, and the disease-related hospitalization rate post-procedure was 21.3%. CONCLUSION: Our analysis shows that ESt is safe and effective for managing IBD-related strictures, making it a valuable addition to the armamentarium of endoscopists. Formal training efforts should focus on ensuring its widespread adoption.

Ultrasound-Guided Versus Palpation-Guided Techniques to Achieve Vascular Access in Children Undergoing Cardiac Surgery: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Pediatric heart surgery is a vital therapeutic option for congenital heart disease, which is one of the most prevalent causes of death in children. Arterial cannulation (AC) and central venous catheter (CVC) are required in pediatric cardiac surgery for continuous monitoring of the central venous pressure (CVP), replacement of fluid or blood products, close hemodynamic monitoring, and frequent sampling for arterial blood gases (ABG). A systematic review and meta-analysis synthesizing evidence from randomized controlled trials (RCTs) retrieved from PubMed, Embase Cochrane, Scopus, and WOS until February 2024. Risk ratio (RR) was used to report dichotomous outcomes, and mean difference (MD) was used to report continuous outcomes, both with a 95% confidence interval (CI) using the random-effects model. Thirteen RCTs with 1060 children were included. Regarding arterial cannulation, the ultrasound-guided technique (US) was associated with a statistically significant increase in successful cannulation [RR: 1.31 with 95% CI (1.10, 1.56), P < 0.0001], and first-attempt success [RR: 1.88 with 95% CI (1.35, 2.63), P < 0.0001]. However, US was not associated with any statistically significant difference in venous cannulation in both outcomes with [RR: 1.13 with 95% CI (0.98, 1.30), P = 0.10], [RR: 1.53 with 95% CI (0.86, 2.71), P = 0.15] respectively. Moreover, US was associated with a statistically significant decrease in the number of attempts either in arterial cannulation with [MD: - 0.73 with 95% CI (- 1.00, - 0.46), P < 0.0001] or in venous cannulation with [MD: - 1.34 with 95% CI (- 2.55, - 0.12), P = 0.03], and the time of attempted cannulation also either in arterial cannulation with [MD: - 2.27 with 95% CI (- 3.38, - 1.16), P < 0.0001] or in venous cannulation with [MD: - 4.13 with 95% CI (- 7.06, - 1.19), P < 0.0001]. US guidance improves successful cannulation rates and first-attempt success in arterial access and reduces the number of attempts and procedural time for arterial and venous access. It was also associated with a lower incidence of complications and procedure failure, particularly in arterial access. However, it was associated with a higher incidence of venous puncture.

The effect of clinical decision support systems on clinical outcomes in acute kidney injury: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: To determine whether clinical decision support systems (CDSS) for acute kidney injury (AKI) would enhance patient outcomes in terms of mortality, dialysis, and acute kidney damage progression. METHODS: The systematic review and meta-analysis included the relevant randomized controlled trials (RCTs) retrieved from PubMed, EMBASE, Web of Science, Cochrane, and SCOPUS databases until 21st January 2024. The meta-analysis was done using (RevMan 5.4.1). PROSPERO ID: CRD42024517399. RESULTS: Our meta-analysis included ten RCTs with 18,355 patients. There was no significant difference between CDSS and usual care in all-cause mortality (RR: 1.00 with 95% CI [0.93, 1.07], p = 0.91) and renal replacement therapy (RR: 1.11 with 95% CI [0.99, 1.24], p = 0.07). However, CDSS was significantly associated with a decreased incidence of hyperkalemia (RR: 0.27 with 95% CI [0.10, 0.73], p = 0.01) and increased eGFR change (MD: 1.97 with 95% CI [0.47, 3.48], p = 0.01). CONCLUSIONS: CDSS were not associated with clinical benefit in patients with AKI, with no effect on all-cause mortality or the need for renal replacement therapy. However, CDSS reduced the incidence of hyperkalemia and improved eGFR change in AKI patients.

The efficacy and safety of difelikefalin for pruritus in hemodialysis patients: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Chronic kidney disease-associated pruritus (CKD-ap) is a common complication that negatively affects the quality of life. Difelikefalin has emerged as a novel FDA-approved drug to manage CKD-ap. This systematic review and meta-analysis will assess the efficacy and safety of Difelikefalin versus placebo to manage CKD-ap. METHODS: PubMed, Scopus, WOS, Central, and Embase were systematically searched until November 2023. RevMan was used to perform meta-analysis. Quality assessment was conducted using the Cochrane RoB 2.0 tool. Results were reported as risk ratio (RR) and mean difference (MD) with a 95% confidence interval (CI). PROSPERO ID: (CRD42023485979). RESULTS: Five RCTs with a total of 896 participants were included. Difelikefalin significantly decreased the weekly mean WI-NRS score (MD: -0.99 [-1.22, -0.75], p ˂ .00001), 5-D itch scale total score (MD: -1.51 [-2.26, -0.76], p > .0001), and Skindex-10 total score (MD: -7.39 [-12.51, -2.28], p = .005), but showed significantly higher adverse events (RR: 1.26 [1.03, 1.55], p = .03), versus placebo. However, there was no significant difference between both groups in serious adverse events (RR: 1.42 [0.78, 2.57], p = .25) or death (RR: 0.81 [0.19, 3.34], p = .77). CONCLUSION: Difelikefalin appears to be a promising agent for the management of CKD-induced pruritus in patients with end-stage renal disease. However, evidence is still underpowered due to the paucity of the current data; therefore, more robust RCTs are required to confirm the benefit of Difelikefalin.

Navigating the Proteomic Landscape of Menopause: A Review.

Background and Objectives: Proteomics encompasses the exploration of protein composition, regulation, function, and pathways. Its influence spans diverse clinical fields and holds promise in addressing various women's health conditions, including cancers, osteoporosis, and cardiovascular disorders. However, no comprehensive summary of proteomics and menopausal health exists. Our objective was to summarize proteomic profiles associated with diseases and disorders in peri- and postmenopausal women. Materials and Methods: We conducted a comprehensive search of databases including PubMed, Google Scholar, the Cochrane database, Elsevier, and ScienceDirect until 2022. A total of 253 studies were identified, and 41 studies met the inclusion criteria to identify data of interest. These included the study design, disease, and proteomics/proteins of significance, as described by the authors. Results: The 41 studies covered diverse areas, including bone disorders (10 studies), cardiovascular diseases (5 studies), oncological malignancies (10 studies), and various conditions, such as obesity, nonalcoholic liver disease, the effects of hormone replacement therapy, and neurological diseases (16 studies). The results of our study indicate that proteomic profiles correlate with heart disease in peri- and postmenopausal women, with distinct sex differences. Furthermore, proteomic profiles significantly differ between women with and without osteoporosis. Additionally, patients with breast, ovarian, and endometrial cancer exhibit notable variations in proteomic profiles compared to those without these conditions. Conclusions: Proteomics has the potential to enhance risk assessment and disease monitoring in peri- and postmenopausal women. By analyzing unique protein profiles, clinicians can identify individuals with heightened susceptibility to specific diseases or those already affected by established conditions. This review suggests that there is sufficient preliminary data related to proteomics in peri- and postmenopausal women for early identification of cardiovascular disease, osteoporosis, and cancers, disease monitoring, and tailoring individualized therapies. Rigorous validation studies involving large populations are essential before drawing definitive conclusions regarding the clinical applicability of proteomic findings.

Cold Versus Hot Snare Polypectomy for Colorectal Polyps: An Updated Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND AND OBJECTIVE: Endoscopic polypectomy is an excellent tool for colon cancer prevention. With the innovation of novel resection techniques, the best method is still being investigated. Hence, we aim to evaluate the efficacy and safety of cold snare polypectomy (CSP) versus hot snare polypectomy (HSP) for colorectal polyp resection. METHODS: A systematic review and meta-analysis synthesizing evidence from randomized controlled trials retrieved from PubMed, EMBASE, WOS, SCOPUS, and CENTRAL until July 16, 2022. We pooled dichotomous outcomes using risk ratio (RR) with the corresponding CI. This review's protocol was prospectively registered in PROSPERO with ID: CRD42022347496. RESULTS: We included 18 randomized controlled trials with a total of 4317 patients and 7509 polyps. Pooled RR favored HSP regarding the complete resection rate (RR: 0.96 with 95% CI: 0.95, 1, P = 0.03) and local recurrence incidence (RR: 5.74 with 95% CI: 1.27, 25.8, P = 0.02). Pooled RR favored CSP regarding the colonoscopy time (mean difference: -6.50 with 95% CI: -7.55, -5.44, P = 0.00001) and polypectomy time (mean difference: -57.36 with 95% CI: -81.74, -32.98, P = 0.00001). There was no difference regarding the incidence of immediate bleeding ( P = 0.06) and perforation ( P = 0.39); however, HSP was associated with more incidence of delayed bleeding ( P = 0.01), abdominal pain ( P = 0.007), and postresection syndrome ( P = 0.02). DISCUSSION: HSP is associated with a higher complete resection and lower recurrence rates; however, HSP is also associated with a higher incidence of adverse events. Therefore, improving the complete resection rate with CSP still warrants more innovation, giving the technique safety and shorter procedure duration.

The efficacy of vitamin D supplementation for irritable bowel syndrome: narrow scope and GRADE miss-interpretation.

We read the article by Haung et al. that pooled the effects of vitamin D on irritable bowel syndrome symptoms and associated quality of life. However, the current review suffers from some methodological errors: inadequate search strategy; the grading of recommendations assessment, development, and evaluation (GRADE) miss-assessment; and miss-interpretation. Accordingly, addressing the emphasized limitations will lead to more robust findings and conclusions.

The efficacy and safety of tenecteplase versus alteplase for acute ischemic stroke: an updated systematic review, pairwise, and network meta-analysis of randomized controlled trials.

Tenecteplase (TNK) is a promising candidate to replace alteplase as the standard of care for acute ischemic stroke (AIS); however, the optimal dosage is still to be investigated. Therefore, we aim to evaluate the safety and efficacy of TNK versus alteplase and to investigate the optimal TNK dosage. A systematic review, pairwise, and network meta-analysis synthesizing randomized controlled trials (RCTs) from WOS, SCOPUS, EMBASE, and PubMed until July 26th, 2022. We used the risk ratio (RR) for dichotomous outcomes presented with the corresponding 95% confidence interval (CI). We registered our protocol in PROSPERO with ID: CRD42022352038. Nine RCTs with a total of 3,707 patients were included. TNK significantly led to complete recanalization (RR: 1.27 with 95% CI [1.02, 1.57], P = 0.03); however, we found no difference regarding early neurological improvement (RR: 1.07 with 95% CI [0.94, 1.21], P = 0.33) and excellent neurological recovery (RR: 1.03 with 95% CI [0.96, 1.10], P = 0.42). Also, TNK was similar to alteplase regarding mortality (RR: 0.99 with 95% CI [0.82, 1.18], P = 0.88), intracranial haemorrhage (RR: 1.00 with 95% CI [0.85, 1.18], P = 0.99), and parenchymal hematoma (RR: 1.13 with 95% CI [0.83, 1.54], P = 0.44). TNK in the dose of 0.25 mg is a viable candidate to displace alteplase as the standard of care in patients with an AIS within 4.5 h of presentation due to its better rate of early neurological recovery and non-inferiority in terms of safety outcomes. However, the evidence regarding TNK's role in AIS presenting after 4.5 h from symptoms onset, wake-up stroke, and minor stroke/TIA is still lacking, necessitating further double-blinded pragmatic RCTs in this regard.

Defibrillation strategies for refractory ventricular fibrillation out-of-hospital cardiac arrest: A systematic review and network meta-analysis.

BACKGROUND AND OBJECTIVE: Double sequential external defibrillation (DSED) and vector-change defibrillation (VCD) have been suggested to enhance clinical outcomes for patients with ventricular fibrillation (VF) refractory of standard defibrillation (SD). Therefore, this network meta-analysis aims to evaluate the comparative efficacy of DSED, VCD, and SD for refractory VF. METHODS: A systematic review and network meta-analysis synthesizing randomized controlled trials (RCTs) and comparative observational studies retrieved from PubMed, EMBASE, WOS, SCOPUS, and Cochrane through November 15th, 2022. R software netmeta and netrank package (R version 4.2.0) and meta-insight software were used to pool dichotomous outcomes using odds ratio (OR) presented with the corresponding confidence interval (CI). Our protocol was prospectively published in PROSPERO with ID: CRD42022378533. RESULTS: We included seven studies with a total of 1632 participants. DSED was similar to SD in survival to hospital discharge (OR: 1.14 with 95% CI [0.55, 2.83]), favorable neurological outcome (modified Rankin scale ≤2 or cerebral performance category ≤2) (OR: 1.35 with 95% CI [0.46, 3.99]), and return of spontaneous circulation (ROSC) (OR: 0.81 with 95% CI [0.43; 1.5]). In addition, VCD was similar to SD in survival to hospital discharge (OR: 1.12 with 95% CI [0.27, 4.57]), favorable neurological outcome (OR: 1.01 with 95% CI [0.18, 5.75]), and ROSC (OR: 0.88 with 95% CI [0.24; 3.15]). CONCLUSION: Double sequential external defibrillation and VCD were not associated with enhanced outcomes in patients with refractory VF out-of-hospital cardiac arrest, compared to SD. However, the current evidence is still inconclusive, warranting further large-scale RCTs.

The effects of transcranial direct current stimulation on cognitive function for mild cognitive impairment: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Transcranial direct current stimulation (tDCS) emerged as a potential modality for enhancing cognitive functions in patients with cognitive decline, including mild cognitive impairment (MCI). Our systematic review and meta-analysis aim to synthesize the available randomized controlled trials (RCTs) on the effects of tDCS on cognitive functions in patients with MCI. METHODS: Our review protocol was registered on PROSPERO with ID: CRD42022360587. We conducted a systematic database search until September 2022. Standardized mean difference (SMD) and pooled effect size (ES) for robust variance estimation (RVE) method were used as effect estimates for our meta-analysis. RESULTS: We included 11 RCTs with a total of 429 participants. The meta-analysis showed that, compared to sham groups, tDCS did not improve global functioning (measured by MOCA) (SMD = 0.02, CI = - 0.30 to 0.35; p = 0.88), memory domain (ES = 0.681, CI = - 2.15 to 3.51, p = 0.576), sustained attention (measured by TMT-A) (SMD = - 0.21, CI = - 0.52 to 0.10, p = 0.19), and executive function (measured by TMT-B) (SMD = - 0.53, CI = - 1.56 to 0.50, p = 0.20). CONCLUSION: Our meta-analysis found no significant effect of tDCS on cognitive functions in MCI patients, including effects on global functioning, memory, sustained attention, and executive function. Therefore, an important change to be tested in future studies is to look for a better combination with tDCS for patients with MCI.

Otolaryngologic manifestations among MPOX patients: A systematic review and meta-analysis.

PURPOSE: MPOX has numerous otolaryngologic presentations that have been recognized as clinically important, especially with the onset of the 2022 outbreak. However, how these features vary across region and outbreak have yet to be elucidated or supported by meta-analysis. The objective of this study is to identify the otolaryngologic manifestations of MPOX across previous and current outbreaks and among endemic and non-endemic regions. BASIC PROCEDURES: Data sources of MEDLINE (PubMed), the Cochrane Library, Scopus, Embase, Web of Science, Google Scholar, and OpenGrey were searched through August 2022. All observational studies reporting data on laboratory-confirmed MPOX patients with otolaryngologic symptoms were included. Two authors independently performed the screening process while a third resolved disagreements. Data were extracted into a structured form by two authors independently. We performed a meta-analysis of the prevalence of otorhinolaryngologic symptoms using MetaXL software (version 5.3) under a random-effects model. MAIN FINDINGS: 38 studies with 5952 patients were included. The four most prevalent manifestations were headache at 31 % (95 % CI [0.16-0.49], I 2  = 99 %), sore throat at 22 % (95 % CI [0.09-0.37], I 2  = 99 %), cough at 16 % (95 % CI [0.05-0.30], I 2  = 99 %), and cervical lymphadenopathy at 10 % (95 % CI [0.01-0.26], I 2  = 100 %). Otolaryngologic features were more prevalent in previous outbreaks as compared to the 2022 outbreak including 37 % prevalence of headache (95 % CI [0.11-0.66], I 2  = 100 %), 33 % prevalence of cough (95 % CI [0.21-0.47], I 2  = 98 %), 27 % prevalence of sore throat (95 % CI [0.07-0.53], I 2  = 99 %), 15 % prevalence of cervical lymphadenopathy (95 % CI [0.00-0.428], I 2  = 100 %), 13 % prevalence of oral ulcers (95 % CI [0.02-0.30], I 2  = 99 %), 6 % prevalence of oral exanthem (95 % CI [0.00-0.17], I 2  = 99 %), 5 % prevalence of dysphagia (95 % CI [0.00-0.18], I 2  = 99 %), and 5 % prevalence of tonsillar signs (95 % CI [0.00-0.13], I 2  = 99 %). Features that were more prevalent in endemic areas versus non-endemic areas include 27 % prevalence of cough (95 % CI [0.14-0.41], I 2  = 99 %), 15 % prevalence of oral ulcers (95 % CI [0.02-0.36], I 2  = 99 %), 6 % prevalence of tonsillar signs (95 % CI [0.00-0.18], I 2  = 99 %), and 19 % prevalence of cervical lymphadenopathy (95 % CI [0.00-0.48], I 2  = 100 %), while the only feature more prevalent in non-endemic areas was headache with a prevalence of 36 % (95 % CI [0.24-0.47], I 2  = 96 %). PRINCIPAL CONCLUSIONS: In this systematic review and meta-analysis, four symptoms - headache, sore throat, cough, and cervical lymphadenopathy - were found to be the most prevalent otolaryngologic features of MPOX. Otolaryngologic manifestations of MPOX were more pronounced in prior outbreaks and in endemic areas as compared to the 2022 outbreak and non-endemic areas. These findings may aid MPOX recognition in an otolaryngology setting.

Efficacy and safety of triple therapy versus dual therapy for lymphatic filariasis: A systematic review and meta-analysis.

OBJECTIVE: Lymphatic filariasis is a serious public health issue. Recent studies showed that a single dosage of triple therapy (Ivermectin, Diethylcarbamazepine, and Albendazole) is more effective than dual therapy (Ivermectin plus Albendazole or Diethylcarbamazepine plus Albendazole) for clearing microfilaria from the blood. We aimed to evaluate the efficacy and safety of triple therapy versus dual therapy in patients infected with microfilaria and communities endemic to lymphatic filariasis. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, EMBASE, SCOPUS, Cochrane Central Register of Controlled Trials, and Web of Science until 24th June 2021. We included randomized control trials that compared triple with dual therapy given to patients with lymphatic filariasis or endemic communities. This study was registered with PROSPERO (CRD42021266724). RESULTS: We included eight articles after the screening process. Triple therapy caused more clearance of microfilaria in the blood (RR: 1.52; 95% CI: 1.15, 2.02; p = 0.003), while dual therapy caused more clearance of the circulating filariae antigen in the blood (RR: 0.76; 95% CI: 0.65, 0.88; p = 0.0003), both 12 months after drug administration. The triple therapy had a similar adverse effect compared with the dual therapy group. CONCLUSION: Based on the greater efficacy in the clearance of microfilaria and the safety of triple therapy, it constitutes a better strategy for the eradication programs of lymphatic filariasis in endemic regions. However, further studies are needed to confirm our results.