Effect of Anterograde Lavage via Temporary Loop Ileostoma on the Recovery of Bowel Function in Patients Receiving Stoma Closure: A Retrospective Cohort Study.

BACKGROUND: The effect of anterograde lavage in patients with rectal cancer who underwent anterior resection and plan to receive stoma closure is unclear. OBJECTIVE: This study aimed to investigate the effect of anterograde lavage on postoperative bowel function recovery in patients who underwent temporary loop ileostomy and stoma closure. DESIGN: This was a hospital-based retrospective cohort study. SETTINGS: This study was conducted at a tertiary referral center. PATIENTS: All consecutive patients who underwent anterior resection for rectal cancer and were planning to receive stoma closure from March through December 2019 were included. INTERVENTIONS: The enrolled patients were divided into 2 groups according to whether they received anterograde lavage before stoma closure. MAIN OUTCOME MEASURES: Short-term functional outcomes, including time to first passing of flatus, first defecation time, and recovery time to first meal, were compared between the groups. Secondary outcomes included length of hospital stay, total cost of hospitalization, and postoperative complications. RESULTS: A total of 222 eligible participants were included in the analysis, including 114 in the lavage group and 108 in the nonlavage group. No statistically significant differences were found in age, sex ratio, or distance between the anastomotic line and dentate line. In the lavage group, patients' time to first passing of flatus (38 vs 42 h; p = 0.006), first defecation time (42 vs 48 h; p < 0.001), recovery time to first meal (48 vs 55.5 h; p < 0.001), and length of hospital stay (5 vs 7 d; p < 0.001) were significantly shorter than those in the nonlavage group, and the total cost of hospitalization was significantly lower than that of the nonlavage group (25,000 vs 28,000 RMB; p < 0.001). No significant difference was found in the incidence of postoperative complications between the 2 groups (p = 0.067). LIMITATIONS: This study is limited by its relatively small sample size and retrospective design with single-center participants. CONCLUSIONS: Anterograde lavage before stoma closure is safe and noninvasive. For patients receiving anterior resection and planning to have stoma closure, this procedure can potentially help recover bowel function more rapidly. See Video Abstract at http://links.lww.com/DCR/C51. EFECTO DEL LAVADO ANTERGRADO MEDIANTE ILEOSTOMA TEMPORAL EN ASA SOBRE LA RECUPERACIN DE LA FUNCIN INTESTINAL EN PACIENTES QUE RECIBEN CIERRE DE ESTOMA UN ESTUDIO DE COHORTE RETROSPECTIVO: ANTECEDENTES:No está claro el efecto del lavado anterógrado en pacientes con cáncer de recto con resección anterior que planean recibir el cierre del estoma.OBJETIVO:Investigar el efecto del lavado anterógrado en la recuperación de la función intestinal posoperatoria en pacientes que se sometieron a ileostomía en asa temporal y cierre de estoma.DISEÑO:Estudio de cohorte retrospectivo basado en el hospital.AJUSTES:Centro de referencia terciario.PACIENTES:Todos los pacientes que se sometieron a una resección anterior por cáncer de recto y que planeaban recibir el cierre del estoma desde marzo hasta diciembre de 2019.INTERVENCIONES:Los pacientes inscritos se dividieron en dos grupos según si recibieron lavado anterógrado antes del cierre del estoma.PRINCIPALES MEDIDAS DE RESULTADO:Los resultados funcionales a corto plazo, incluido el tiempo de la primera evacuación de flatos, tiempo de la primera defecación y tiempo de recuperación hasta la primera comida, se compararon entre los grupos. Resultados secundarios incluyeron duración de la estancia hospitalaria, costo total de la hospitalización y complicaciones posoperatorias.RESULTADOS:Se incluyeron en el análisis un total de 222 participantes elegibles, incluidos 114 en el grupo de lavado y 108 en el grupo de no lavado. No hubo diferencias estadísticamente significativas en la edad, la proporción de sexos o la distancia entre la línea de anastomosis y la línea dentada. En el grupo de lavado, el tiempo de la primera evacuación de flatos de los pacientes (38 vs 42 h; p = 0,006), el tiempo de la primera defecación (42 vs 48 h; p < 0,001), el tiempo de recuperación hasta la primera comida (48 vs 55,5 h; p < 0,001) y la duración de la estancia hospitalaria (5 vs 7 días; p < 0,001) fueron significativamente más cortos que los del grupo de no lavado, y el costo total de la hospitalización fue significativamente menor que el del grupo de no lavado (25000 vs 28000 RMB; p < 0,001). No hubo diferencia significativa en la incidencia de complicaciones postoperatorias entre los dos grupos (p = 0,067).LIMITACIONES:Este estudio está limitado por su tamaño de muestra relativamente pequeño y su diseño retrospectivo con participantes de un solo centro.CONCLUSIONES:El lavado anterógrado antes del cierre del estoma es seguro y no invasivo. Para los pacientes que se someten a una resección anterior y planean cerrar el estoma, este procedimiento puede ayudar potencialmente a recuperar la función intestinal más rápidamente. Consulte Video Resumen en http://links.lww.com/DCR/C51. (Traducción-Dr. Francisco M. Abarca-Rendon).

Metformin and the risk of neurodegenerative diseases in patients with diabetes: A meta-analysis of population-based cohort studies.

AIMS: The association between metformin use and neurodegenerative disease (ND) onset remains controversial. In this systematic review and meta-analysis, we aimed to determine the relationship between metformin use and ND risk based on data from population-based cohort studies. METHODS: Articles were systematically searched in PubMed, EMBASE and Cochrane Library databases. Pooled relative risks (RRs) with 95% CIs were obtained using a random-effects model. Subgroup analyses, sensitivity analyses and meta-regression were performed to identify the sources of heterogeneity and strengthen the results. RESULTS: Twelve population-based cohort studies involving 194,792 participants (94,462 metformin users and 100,330 metformin non-users) were eligible for inclusion in this meta-analysis. The pooled RR of NDs reached 0.77 (95% CI 0.67-0.88) when comparing metformin users with non-users. The effects were more prominent in long-term metformin users (≥4 years) (RR 0.29, 95% CI 0.13-0.44) and studies from Asian countries (RR 0.69, 95% CI 0.64-0.74). The effect estimates were stable when stratified by subtypes of NDs, study designs, and control definitions (p for interaction >0.05). Meta-regression did not identify the coefficients as the sources of heterogeneity (all p > 0.05). CONCLUSIONS: This systematic review and meta-analysis found that metformin use, especially long-term use, was associated with lower ND risk. However, because there was substantial heterogeneity among studies, high-quality randomized controlled trials are still needed to confirm this finding.

The use of acupuncture for advanced cancer care: Protocol for a systematic review and meta-analysis.

AIM: To assess the up-to-date evidence of acupuncture for the management of cancer-related and cancer treatment-related outcomes among people with advanced cancer. DESIGN: Systematic review with meta-analyses involving multidimensional outcomes. METHODS: The protocol of this systematic review has been registered in PROSPERO with the registration number CRD42020212982. Six databases (including Pubmed, EMBASE, Cochrane Library, SinoMed, ClinicalTrials.gov and Chinese Clinical Trial Registry) will be searched from inception through November 2020 to identify relevant interventional trials examining acupuncture management on multidimensional outcomes in patients with advanced cancer. Main outcomes will include cancer and treatment-related symptoms, quality of life, sleep quality and adverse events. DerSimonian & Laird random-effects meta-analysis will be applied to calculate pooled relative risks for binary data and pooled weighted mean differences (WMDs) or standardized mean differences (SMDs) for continuous data. Trial quality ratings and risk of bias will be evaluated using the Cochrane Risk of Bias Tool and the Grading of Recommendations Assessment, Development and Evaluation approach. DISCUSSION: The efficacy of acupuncture on advanced cancer care and outcomes has not yet been determined. Palliative care for patients with advanced cancer may involve multiple challenges that include physical and mental health care. This systematic review will offer updated and comprehensive evidence of acupuncture on specific outcomes induced by advanced cancer and cancer-related treatment, which can give high level clinical recommendations to improve patient care and clinical outcomes.

Effects of statin exposure and lung cancer survival: A meta-analysis of observational studies.

Statin exposure has been reported to improve survival in several cancers. However, studies evaluating the association between statins and prognostic outcomes in patients with lung cancer are conflicting and heterogeneous. Pubmed, EMBASE and reference lists of included studies were searched to identify studies investigating the association between statin exposure and lung cancer prognosis. The primary outcome measure was overall survival (OS) and secondary ones included cancer-specific survival (CSS) and recurrence-free survival (RFS). Hazard ratios (HRs) with 95% confidence intervals (95% CIs) of these outcomes were pooled using random-effects models. Thirteen studies with data from 99,297 individuals satisfying the inclusion criteria were identified. Studies were ranked to be at low to moderate risk of bias. Meta-analysis showed that statin exposure was significantly associated with improved OS (pooled HR 0.79, 95% CI 0.72-0.86), CSS (pooled HR 0.83, 95% CI 0.77-0.89) and RFS (pooled HR 0.85, 95% CI 0.81-0.89). Subgroup analyses showed that statin users after diagnosis of lung cancer had more survival benefit for OS (HR 0.68, 95% CI 0.51-0.92) than those before diagnosis (HR 0.86, 95% CI 0.81-0.90) and current users (HR 0.79, 95% CI 0.62-1.02) (P for interaction <0.001). Besides, statin users were likely to have more survival benefits in stage IV lung cancer patients (HR 0.77, 95% CI 0.74-0.79) than in mixed stage (I-IV or I-III) patients (P for interaction = 0.004). Statin exposure is associated with significantly improved survival in patients with lung cancer. Future studies are warranted to further demonstrate the therapeutic role of statins in specific lung cancer patients.

Effects of statins on cancer mortality and progression: A systematic review and meta-analysis of 95 cohorts including 1,111,407 individuals.

Statins have been implicated in the regulation of cell proliferation, apoptosis and tumor progression in cancer patients and statin use at the time of cancer diagnosis has been reported to be associated with reduced cancer risk and improved survival, irrespective of concomitant anti-cancer therapy. A systematic literature search of relevant databases through May 2015 was conducted to identify studies assessing the prognostic impact of statin use on prognostic outcomes in cancer patients. Literature search identified 95 cohort studies that met the inclusion criteria. A meta-analysis of 55 articles showed that statin use was significantly associated with decreased risk of all-cause mortality (HR 0.70, 95% Cl 0.66 to 0.74) compared with nonusers. The observed pooled estimates were retained for cancer-specific mortality (HR 0.60, 95% Cl 0.47 to 0.77), progression-free survival (HR 0.67, 95% Cl 0.56 to 0.81), recurrence-free survial (HR 0.74, 95% Cl 0.65 to 0.83) and disease-free survival (HR 0.53, 95% Cl 0.40 to 0.72). These associations almost remained consistent across those outcomes when stratified by publication type, tumour location, study design, sample size, initiation of statins, disease stage, research country, follow-up duration or research hospital involved. Subgroup analyses according to initiation of statins showed postdiagnosis statin users (HR 0.65, 95% Cl 0.54 to 0.79) gained significantly more recurrence-free survival benefit than prediagnosis statin users (HR 0.86, 95% Cl 0.77 to 0.96) (p for interaction = 0.018). Statin therapy has potential survival benefit for patients with malignancy. Further large-scale prospective studies emphasising survival outcomes of individual cancer type are strongly encouraged.

Interleukin 22 protects colorectal cancer cells from chemotherapy by activating the STAT3 pathway and inducing autocrine expression of interleukin 8.

Resistance to chemotherapy is the major cause of colorectal cancer (CRC) treatment failure. The cytokine IL-22, which is produced by T cells and NK cells, is associated with tumorigenesis and tumor progression in cancers. However, the role of IL-22 in chemoresistance has not been investigated. We found that IL-22 levels in tumor tissues and peripheral blood were associated with chemoresistance and indicate poor prognosis for patients who received FOLFOX chemotherapy. In CRC cells, IL-22 was able to attenuate the cytotoxic and apoptosis-inducing effects of 5-FU and OXA by activating the STAT3 pathway and subsequently increasing the expression of anti-apoptotic genes. In addition, IL-22 conferred resistance to 5-FU and OXA by inducing IL-8 autocrine expression through STAT3 activation. Our findings identify IL-22 as a novel chemoresistance cytokine and may be a useful prognostic biomarker for CRC patients receiving FOLFOX chemotherapy.

Effects of a nurse-led eHealth programme on functional outcomes and quality of life of patients with stroke: a pooled analysis of randomized controlled trials.

Background: Stroke remains a leading cause of disability worldwide. Nurse-led eHealth programs have emerged as a potentially effective strategy to improve functional outcomes and quality of life in stroke survivors. However, the variability of study designs and outcomes measured across trials necessitates a pooled analysis to comprehensively assess the efficacy of these interventions. This protocol outlines the methodology for a pooled analysis that aims to synthesize evidence from randomized controlled trials (RCTs) evaluating nurse-led eHealth interventions for stroke patients. Methods and analysis: This pooled analysis will be conducted according to the PRISMA guidelines. We will include RCTs that evaluate nurse-led eHealth programs and report on functional outcomes or quality of life in stroke patients. Comprehensive searches of electronic databases including Pubmed, EMBASE, the Cochrane Library, CINAHL, and PsycINFO will be conducted with a predefined search strategy. Study selection will involve screening titles and abstracts, followed by full-text review using explicit inclusion and exclusion criteria. Data extraction will be undertaken independently by two reviewers. The risk of bias will be assessed through the Cochrane Risk of Bias tool. Additionally, the quality of evidence for each outcome will be evaluated using the GRADE approach. Meta-analyses will be performed using random-effects models, and heterogeneity will be quantified using the I2 statistic. Subgroup and sensitivity analyses will explore potential sources of heterogeneity. Discussion and conclusions: This pooled analysis is poised to provide a nuanced understanding of the effectiveness of nurse-led eHealth programs in stroke rehabilitation, leveraging a thorough methodological framework and GRADE tool to ensure robustness and reliability of evidence. The investigation anticipates diverse improvements in patient outcomes, underscoring the potential of personalized, accessible eHealth interventions to enhance patient engagement and treatment adherence. Despite the challenges posed by the heterogeneity of interventions and rapid technological advancements, the findings stand to influence clinical pathways by integrating eHealth into standard care, if substantiated by the evidence. Our study's depth and methodological rigor possess the potential to initiate changes in healthcare policy, advocating for the adoption of eHealth and subsequent investigations into its cost-efficiency. Ultimately, we aim to contribute rich, evidence-based insights into the burgeoning field of digital health, offering a foundational assessment of its applications in stroke care. Our data is expected to have a lasting impact, not only guiding immediate clinical decisions but also shaping the trajectory of future healthcare strategies in stroke recovery. Systematic review registration: Identifier (CRD42024520100: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=520100).

Impact of hormone replacement therapy on all-cause and cancer-specific mortality in colorectal cancer: A systematic review and dose‒response meta-analysis of observational studies.

OBJECTIVE: The effect of hormone replacement therapy (HRT) on colorectal cancer (CRC) mortality and all-cause mortality remains unclear. We conducted a systematic review and dose-response meta-analysis to determine the effects of HRT on CRC mortality and all-cause mortality. METHODS: We searched the electronic databases of PubMed, Embase, and The Cochrane Library for all relevant studies published until January 2024 to investigate the effects of HRT exposure on survival rates for patients with CRC. Two reviewers independently extracted individual study data and evaluated the risk of bias between the studies using the Newcastle‒Ottawa Scale. We performed a two-stage random-effects dose-response meta-analysis to examine a possible nonlinear relationship between the year of HRT use and CRC mortality. RESULTS: Ten cohort studies with 480,628 individuals were included. HRT was inversely associated with the risk of CRC mortality (hazard ratios (HR) = 0.77, 95% CI (0.68, 0.87), I2 = 69.5%, p < 0.05). The pooled results of seven cohort studies revealed a significant association between HRT and the risk of all-cause mortality (HR = 0.71, 95% CI (0.54, 0.92), I2 = 89.6%, p < 0.05). A linear dose-response analysis (p for nonlinearity = 0.34) showed a 3% decrease in the risk of CRC for each additional year of HRT use; this decrease was significant (HR = 0.97, 95% CI (0.94, 0.99), p < 0.05). An additional linear (p for nonlinearity = 0.88) dose-response analysis showed a nonsignificant decrease in the risk of all-cause mortality for each additional year of HRT use. CONCLUSIONS: This study suggests that the use of HRT is inversely associated with all-cause and colorectal cancer mortality, thus causing a significant decrease in mortality rates over time. More studies are warranted to confirm this association.

Predictors associated with successful weaning of veno-venous extracorporeal membrane oxygenation and mortality in adult patients with severe acute lung failure: Protocol of a pooled data analysis of cohort studies.

BACKGROUND: Severe acute lung failure (ALF) often necessitates veno-venous extracorporeal membrane oxygenation (VV-ECMO), where identifying predictors of weaning success and mortality remains crucial yet challenging. The study aims to identify predictors of weaning success and mortality in adults undergoing VV-ECMO for severe ALF, a gap in current clinical knowledge. METHODS AND ANALYSIS: PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials will be searched for cohort studies examining the predictive factors of successful weaning and mortality in adult patients on VV-ECMO due to severe ALF. Risk of bias assessment will be conducted using the Newcastle-Ottawa scale for each included study. The primary outcomes will be successful weaning from VV-ECMO and all-cause mortality. Between-study heterogeneity will be evaluated using the I2 statistic. Sensitivity, subgroup, and meta-regression analyses will be performed to ascertain potential sources of heterogeneity and assess the robustness of our results. We will use the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) tool to recommend the level of evidence. DISCUSSION: This study seeks to provide clinically significant insights into predictors for weaning and mortality during VV-ECMO treatment for ALF, aiming to support clinical decisions and potentially influence health policy, thereby improving patient outcomes. ETHICS AND DISSEMINATION: Given the absence of direct engagement with human subjects or access to personal medical records, ethical approval for this study is deemed unnecessary. The study findings will be shared at a scientific conference either at the global or national level. Alternatively, the results will be presented for publication in a rigorously peer-reviewed journal regarding critical care medicine.

Risk factors of postoperative delirium following spine surgery: A meta-analysis of 50 cohort studies with 1.1 million participants.

Objectives: Postoperative delirium (POD) is considered to be a common complication of spine surgery. Although many studies have reported the risk factors associated with POD, the results remain unclear. Therefore, we performed a meta-analysis to identify risk factors for POD among patients following spinal surgery. Methods: We systematically searched the PubMed, Embase and the Cochrane Library for relevant articles published from 2006 to February 1, 2023 that reported risk factors associated with the incidence of POD among patients undergoing spinal surgery. The Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed, and random effects models were used to estimate pooled odds ratio (OR) estimates with 95 % confidence intervals (CIs) for each factor. The evidence from observational studies was classified according to Egger's P value, total sample size, and heterogeneity between studies. Results: Of 11,329 citations screened, 50 cohort studies involving 1,182,719 participants met the inclusion criteria. High-quality evidence indicated that POD was associated with hypertension, diabetes mellitus, cardiovascular disease, pulmonary disease, older age (>65 years), patients experiencing substance use disorder (take drug ≥1 month), cerebrovascular disease, kidney disease, neurological disorder, parkinsonism, cervical surgery, surgical site infection, postoperative fever, postoperative urinary tract infection, and admission to the intensive care unit (ICU). Moderate-quality evidence indicated that POD was associated with depression, American Society of Anesthesiologists (ASA) fitness grade (>II), blood transfusion, abnormal potassium, electrolyte disorder, length of stay, inability to ambulate and intravenous fluid volume. Conclusions: Conspicuous risk factors for POD were mainly patient- and surgery-related. These findings help clinicians identify high-risk patients with POD following spinal surgery and recognize the importance of early intervention.

Comparison of efficacy and tolerability of adjuvant therapy for resected high-risk stage III-IV cutaneous melanoma: a systemic review and Bayesian network meta-analysis.

Background: Although immune checkpoint inhibitors (ICIs) and targeted therapies have been widely used as adjuvant treatment for resected melanoma, the optimal therapy remains controversial. Therefore, we conducted this updated network meta-analysis (NMA) to assess the efficacy and tolerability of adjuvant therapies for cutaneous melanoma. Methods: PubMed, Embase, Cochrane library, and Web of Science were systematically searched for relevant literatures published in the last 30 years. Disease-free survival (DFS), overall survival (OS), and serious adverse events were considered as the efficacy and tolerability outcomes. Results: In all, 27 randomized controlled trials (RCTs) including 16,709 stage III-IV melanoma patients were enrolled in this NMA. For BRAF wild-type melanoma, our analysis showed that both nivolumab and pembrolizumab demonstrated significantly better DFS and tolerability than ipilimumab (10 mg/kg). Nivolumab, pembrolizumab, ipilimumab (3 mg/kg), and ipilimumab (10 mg/kg) all appeared to be effective in prolonging OS, but no therapy demonstrated significantly better OS than ipilimumab (10 mg/kg). Nivolumab + ipilimumab showed the best DFS, but did not appear to be effective in improving OS and ranked only seventh in tolerability. Vaccines and granulocyte-macrophage colony-stimulating factor therapies were well tolerated, but all failed to improve the DFS or OS in stage III melanoma patients. In terms of BRAF mutation-positive melanoma, ICIs (nivolumab + ipilimumab, nivolumab, pembrolizumab, ipilimumab; 10 mg/kg) exhibited comparable efficacy to dabrafenib + trametinib, and all these therapies showed significantly better DFS than placebo. Conclusion: Considering efficacy and tolerability, nivolumab and pembrolizumab seem to be preferable adjuvant therapies for patients with stage III-IV melanoma. For BRAF mutation-positive patients, more RCTs are still required to determine which is better between ICIs and targeted therapy.

The bared external anal sphincter (BEAS), a new technique for high horseshoe anal fistula: a hospital-based cohort study.

The aim of this study was to introduce a new technique, the bared external anal sphincter technique, and to evaluate its effectiveness and safety for primary or recurrent high horseshoe anal fistula (HHAF). We used data from a tertiary referral hospital's prospective database of a hospital-based cohort. All the patients underwent the bared external anal sphincter procedure. The main outcomes were short-term clinical outcomes including the 6-month cure rate, Visual Analog Scale pain score (VAS-PS) and Cleveland Clinic Florida incontinence score (CCF-IS). The secondary outcomes included the Quality of Life in Patients with Anal Fistula Questionnaire score (QoLAF-QS), Bristol stool chart and postoperative complications. A total of 48 HHAF patients (39 males) with a mean age of 34.2 years (SD 9.04; range, 21-54) were analyzed in this retrospective study. At the 6-month follow-up, the average VAS-PS and CCF-IS were 0.81 (SD 2.28; range, 0-10) and 1.29 (SD 2.87; range, 0-13), respectively. QoLAF-QS showed that the bared external anal sphincter procedure had no impact over their quality of life in 45 patients (93.75%), limited impact in 2 patients (4.16%), and moderate impact in one patient (2.08%). The Bristol stool scale showed that all patients had normal stool characteristics. The 6-month cure rate was 93.75%. Three patients (6.25%) experienced recurrent symptoms but recovered after surgical management. Urinary retention occurred in 1 case (2.78%). No other postoperative complications were reported. No patient had anal incontinence. The bared external anal sphincter procedure is a safe, effective and sphincter-sparing approach for patients with primary or recurrent HHAF in terms of short-term results.

Value of ctDNA methylation biomarkers in diagnosis of colorectal tumors.

Tweetable abstract DNA methylation alterations have been identified as promising biological markers for early-stage colorectal cancer detection. Here, the authors highlight some recent advances in DNA methylation and its role in the early diagnosis and overall disease course management of colorectal tumors. New insights into DNA methylation biomarkers for colorectal cancer early diagnosis and management are discussed.

Immune checkpoint inhibitors for patients with microsatellite instability-high colorectal cancer: protocol of a pooled analysis of clinical trials.

Introduction: Colorectal cancer (CRC) is the third most common cause of cancer and the second leading cause of cancer-related deaths worldwide. Microsatellite instability-high (MSI-H) is a distinct molecular subtype of CRC that occurs in approximately 15% of all cases. Recently, immune checkpoint inhibitors (ICIs) have emerged as a promising therapeutic approach for patients with MSI-H colorectal cancer, exhibiting higher response rates than standard chemotherapies. To assess the effectiveness and safety of ICIs for the treatment of patients with MSI-H CRC, we propose a comprehensive pooled analysis of clinical trial data. Methods and analysis: A systematic search of multiple electronic databases, including PubMed, EMBASE, Cochrane Library, and Clinicaltrials.gov, will be conducted from their inception until September, 2023 to identify eligible randomized controlled trials (RCTs) and non-randomized studies. Inclusion criteria comprise studies of adult patients with histologically confirmed MSI-H CRC treated with immune checkpoint inhibitors, with a comparison to a control group receiving conventional therapies. Outcomes of interest will be overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and incidence of treatment-related adverse events (AEs). The Cochrane Risk of Bias tool and the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tool will be employed to evaluate the methodological quality of included studies. A random-effects model using the DerSimonian and Laird method will be applied for pooling the effect estimates, calculating hazard ratios (HRs) or risk ratios (RRs) with their corresponding 95% confidence intervals (CIs). Heterogeneity will be assessed using I² statistics, and subgroup analysis and meta-regression will be performed to explore potential effect modifiers in case of substantial heterogeneity. Publication bias will be evaluated with funnel plots and Egger's test. Sensitivity analysis will be conducted to assess the robustness of the results. Discussion: This meta-analysis will synthesize available evidence from clinical trials on immune checkpoint inhibitors in treating MSI-H colorectal cancer. The findings will offer valuable information about the effectiveness and safety of ICIs in this patient population, contributing to the refinement of clinical guidelines and enhancing the decision-making process for healthcare providers, policy-makers, and patients. The comprehensive analysis of subgroups and sensitivity allows for an in-depth understanding of potential effect modification, providing essential directions for future research. Ethics and dissemination: This study will involve the use of published data; hence, ethical approval is not required. The results of the study will be disseminated through publications in peer-reviewed journals and presentations at relevant conferences. The findings will potentially impact clinical decision-making and contribute to the development of evidence-based treatment recommendations for patients with MSI-H colorectal cancer. Clinical trial registration: Open Science Framework identifier, 10.17605/OSF.IO/ZHJ85.

Surgical laser therapy for cryptoglandular anal fistula: Protocol of a systematic review and meta-analysis.

INTRODUCTION: Anal fistula is the natural evolution of perianal abscess and one of the most common perianal diseases for adults. For complex fistula, it is still very challenging for anorectal surgeons to manage. With the introduction of laser technique in surgery, it is becoming more and more widely used for the treatment of cryptoglandular anal fistula. During the past decade, numerous studies have reported the clinical effectiveness and postoperative outcomes of different forms of laser treatment for anal fistula. However, as these studies were varied in terms of baseline characteristics, the evidence for the true clinical effectiveness of laser treatment for anal fistula need further critical appraisal. Therefore, the purpose of this study is to evaluate the outcomes of surgical laser therapy for cryptoglandular anal fistula stratified by laser type and Parks' classification through a synthesis of quantitative and qualitative evidence. METHODS AND ANALYSIS: This study will be carried out with adherence to the Cochrane Handbook. We will search PubMed, Cochrane Library, and Embase until June, 2022 to identify all relevant interventional and observational studies examining the effects of laser therapy on the clinical outcomes for cryptoglandular anal fistula. Data extraction from eligible studies will be performed independently by two unblinded authors using standardized extraction forms. Risk of bias assessment for each study will be conducted using Cochrane tool for randomized controlled trials (RCTs) and the Newcastle-Ottawa scale (NOS) tool for observational studies. The DerSimonian-Laird random-effects model will be used to calculate the pooled estimates. Heterogeneity will be examined by subgroup analysis stratified by laser type and Parks' classification and other study characteristics. Potential publication bias will be assessed by funnel plot symmetrical and Egger's regression tests. CONCLUSIONS: The synthesis of quantitative and qualitative evidence of this systemic review will yield updated and comprehensive evidence of laser treatment on specific outcomes, which can provide anorectal surgeons with high level evidence-based recommendations to improve patient care and clinical outcomes. OSF registration number: DOI 10.17605/OSF.IO/36ADW.

Scalp Nerve Block, Local Anesthetic Infiltration, and Postoperative Pain After Craniotomy: A Systematic Review and Network Meta-analysis of Randomized Trials.

The most efficacious methods for controlling postoperative pain in craniotomy remain unknown. A systematic review and network meta-analysis were performed to compare the efficacies of different strategies of scalp nerve block (SNB), scalp infiltration (SI), and control in patients undergoing craniotomy. MEDLINE, Embase, and CENTRAL databases were searched for randomized controlled trials. The primary outcome was postoperative 24-hour pain score, and the secondary outcome was opioid consumption within the first 24 hour after surgery. The effect was estimated using the between-group mean difference and ranked using the surface under the cumulative ranking curve (SUCRA) score. Twenty-four randomized trials were identified for inclusion. SNB using ropivacaine reduced postoperative 24-hour pain score when compared with control (mean difference [95% credible interval], -2.04 [-3.13, -0.94]; low quality), and when compared with SI using ropivacaine (-1.77 [-3.04, -0.51]; low quality) or bupivacaine (-1.96 [-3.65, -0.22]; low quality). SNB using ropivacaine was likely the most efficacious method for pain control (SUCRA, 91%), and also reduced opioid consumption within the first postoperative 24 hours as compared with control (mean difference [95% credible interval], -11.91 [-22.42, -1.4]; low quality). SNB using bupivacaine, lidocaine, and epinephrine combined, and SNB using ropivacaine, were likely the most efficacious methods for opioid consumption reduction (SUCRA, 88% and 80%, respectively). In summary, different methods of SNB / SI seem to have different efficacies after craniotomy. SNB using ropivacaine may be superior to other methods for postcraniotomy pain control; however, the overall quality of evidence was low.