Cystathionine gamma-lyase (Cth) induces efferocytosis in macrophages via ERK1/2 to modulate intestinal barrier repair.

BACKGROUND: The inflammatory response induced by intestinal ischaemia‒reperfusion injury (I/R) is closely associated with infectious complications and mortality in critically ill patients, and the timely and effective clearance of apoptotic cells is an important part of reducing the inflammatory response. Studies have shown that the efferocytosis by phagocytes plays an important role. Recently, studies using small intestine organoid models showed that macrophage efferocytosis could promote the repair capacity of the intestinal epithelium. However, no studies have reported efferocytosis in the repair of I/R in animal models. RESULTS: We used an in vivo efferocytosis assay and discovered that macrophage efferocytosis played an indispensable role in repairing and maintaining intestinal barrier function after I/R. In addition, the specific molecular mechanism that induced macrophage efferocytosis was Cth-ERK1/2 dependent. We found that Cth drove macrophage efferocytosis in vivo and in vitro. Overexpression/silencing Cth promoted/inhibited the ERK1/2 pathway, respectively, which in turn affected efferocytosis and mediated intestinal barrier recovery. In addition, we found that the levels of Cth and macrophage efferocytosis were positively correlated with the recovery of intestinal function in clinical patients. CONCLUSION: Cth can activate the ERK1/2 signalling pathway, induce macrophage efferocytosis, and thus promote intestinal barrier repair. Video Abstract.

Systematic evaluation of the diagnostic approach of inflammatory bowel disease guidelines.

OBJECTIVE: To collect and evaluate the diagnostic approach of inflammatory bowel disease (IBD) guidelines and provide useful feedback for guideline developers and evidence-based clinical information to help physicians make decisions. METHODS: Diagnostic guidelines for IBD were retrieved by performing systemic and manual searches. Qualified clinical practice guidelines (CPGs) were included and then evaluated by four well-trained evaluators using the AGREE II instrument. To reduce the bias generated in this process, we used the Measurement Scale of Rate of Agreement (MSRA) tool to interpret the results. Guidelines with good recommendation distributions among the diagnostic field were further reclassified and evaluated. RESULTS: Fifteen diagnostic CPGs for IBD were identified and evaluated, and 70.3% (11/15) of the CPGs were above the recommended level. We observed heterogeneity among the diagnostic CPGs for IBD and discrepancies among different domains in one specific guideline. Potential improvements were identified in the fields of stakeholder involvement, rigour of development and applicability. By further analysing the heterogeneity of the recommendations and evidence in 5 UC-CPGs, we found the following issues: no discussion of diagnosing severe complications of UC, disputed significance of serologic and genetic diagnoses of UC, insufficient attention towards medical histories/physical examinations/differential diagnoses and discrepancy in classification criteria. CONCLUSION: The included diagnostic CPGs for IBD were generally of good quality, but heterogeneity was identified. Addressing these issues will provide useful feedback for the guideline updating process, and it will also benefit current clinical practice and eventually patient outcome.

Evaluation of pharmacotherapy recommendations in guidelines for inflammatory bowel disease.

WHAT IS KNOWN AND OBJECTIVE: The aim of this study was to systematically assess drug therapy in the guidelines for inflammatory bowel disease and to provide recommendations for the development of such guidelines. STUDY DESIGN: A systematic search was conducted in databases and on websites to identify guidelines for the treatment of inflammatory bowel disease. Qualified guidelines were assessed through the Appraisal of Guidelines for Research and Evaluation (AGREE II). Evidence from the guidelines was extracted from the guidelines themselves. The Oxford Centre for Evidence-based Medicine (OCEBM) evidence grading system was used to regrade and assess this evidence. RESULTS: A total of 11 guidelines for the medical treatment of inflammatory bowel disease (Crohn's disease and ulcerative colitis) (2015-2019) were finally included, and after scoring using the AGREE II tool, the median scores in each domain were as follows: Ⅰ. scope and purpose (median score=88.9%, range: 76.4%-91.7%), Ⅱ. stakeholder involvement (median =38.9%, range: 18.1%-61.1%), Ⅲ. rigour of development (median =69.3%, range: 39.6%-77.6%), Ⅳ. clarity and presentation (median =97.2%, range: 91.7%-100%), Ⅴ. applicability (median =45.8%, range: 24%-68.8%) and Ⅵ. editorial independence (median =94.0%, range: 0-100%). Most of the guidelines scored over 60%, which is worthy of clinical recommendation, but different guidelines suggest that there is a great difference in drug therapy, mainly due to various populations, diverse focuses of attention, distinct efficacy of drugs between Crohn's disease and ulcerative colitis, and the preference of guiding developers for select evidence. WHAT IS NEW AND CONCLUSION: The quality of medical treatment guidelines for inflammatory bowel disease varies considerably. Over the past 5 years, medical treatment has been heterogeneous among different guidelines. Consideration of factors leading to heterogeneity of recommendations for drug treatment, especially preferences for evidence selection, will help upgrade the guidelines.

Quality assessment of the guidelines for the management of malignant pleural effusions and ascites.

OBJECTIVES: To fully assess the quality of the guidelines for the management of malignant pleural effusions (MPE) and ascites and reveal the heterogeneity of recommendations and possible reasons among guidelines. METHODS: A systematic search was performed in the database to obtain guidelines for the management of MPE and ascites. The AGREE IIGtool was used to assess the quality of these guidelines. The Measurement Scale of Rate of Agreement (MSRA) was introduced to assess the scientific agreement of formulated recommendations for the management of MPE and ascites among guidelines, and evidence supporting these recommendations was extracted and analyzed. RESULTS: Nine guidelines were identified. Only 4 guidelines scored more than 60% and are worth recommending. Recommendations were also heterogeneous among guidelines for the management of MPE, and the main reasons were the different emphases of the recommendations for the treatment of MPE, the contradictions in recommendations, and the unreasonably cited evidence for MPE. CONCLUSIONS: The quality of the management guidelines for patients with MPE and malignant ascites was highly variable. Specific improvement of the factors leading to the heterogeneity of recommendations will be a reasonable and effective way for developers to upgrade the recommendations in the guidelines for MPE.

Quality evaluation of guidelines for the diagnosis and treatment of radiation enteritis.

OBJECTIVE: To systematically evaluate the guidelines for the diagnosis and treatment of radioactive enteritis, compare their differences and reasons and provide some reference for updating them. METHODS: This study used guidelines related to radiation enteritis by searching a database. Four independent reviewers used the AGREE II evaluation tool to evaluate the quality of the included guidelines, collate their main recommendations, and analyze the highest evidence supporting the main recommendations. RESULTS: Six diagnostic and therapeutic guidelines for radiation enteritis were included in this study, one of which, the American Society for Gastrointestinal Endoscopy guidelines, had an overall score of over 60%, which is worthy of clinical recommendation. In the diagnosis and treatment of radioactive rectal injury, the recommendations for hemorrhagic endoscopic treatment are mature and mainly include (I) argon plasma coagulation; (II) formalin treatment; (III) bipolar electrocoagulation; (IV) heater probe; (V) radiofrequency ablation; and (VI) cryoablation. CONCLUSION: The methodological quality of radioactive enteritis guidelines is unequal; even in the same guidelines, different domains have a large difference. For radioactive rectal damage diagnosis, a type of endoscopic treatment recommendation is more mature, but the overall diagnosis and treatment of radioactive enteritis still lacks high-quality research evidence.

Integrative analysis reveals marker genes for intestinal mucosa barrier repairing in clinical patients.

This study aims to identify biomarkers of intestinal repair and provide potential therapeutic clues for improving functional recovery and prognostic performance after intestinal inflammation or injury. Here, we conducted a large-scale screening of multiple transcriptomic and scRNA-seq datasets of patients with inflammatory bowel disease (IBD), and identified 10 marker genes that potentially contribute to intestinal barrier repairing: AQP8, SULT1A1, HSD17B2, PADI2, SLC26A2, SELENBP1, FAM162A, TNNC2, ACADS, and TST. Analysis of a published scRNA-seq dataset revealed that expression of these healing markers were specific to absorptive cell types in intestinal epithelium. Furthermore, we conducted a clinical study where 11 patients underwent ileum resection demonstrating that upregulation of post-operative AQP8 and SULT1A1 expression were associated with improved recovery of bowel functions after surgery-induced intestinal injury, making them confident biomarkers of intestinal healing as well as potential prognostic markers and therapeutic targets for patients with impaired intestinal barrier functions.

Quality evaluation of metabolic and bariatric surgical guidelines.

Objective: To evaluate the quality of surgical guidelines on bariatric/metabolic surgery. Methods: Four independent reviewers used the AGREE II (The Appraisal of Guidelines for Research and Evaluation II) tool to assess the methodological quality of the included guidelines and conducted a comparative analysis of the main recommendations for surgical methods of these guidelines. Results: Nine surgical guidelines were included in this study. Five articles with AGREE II scores over 60% are worthy of clinical recommendation. The field of rigor of development was relatively low, with an average score of 50.82%. Among 15 key recommendations and the corresponding best evidence in the guidelines, only 4 key recommendations were grade A recommendations. Conclusions: The quality of metabolic and bariatric guidelines is uneven, and there is much room for improvement.

Systematic appraisal of guidelines for the diagnosis of pancreatic cancer.

This review aimed at assessing current guidelines' methodological quality systematically for pancreatic cancer's diagnosis and to reveal the heterogeneity of the recommendations among the evaluated guidelines. A systematic search was conducted to find the latest guidelines for pancreatic cancer's diagnosis. The Appraisal of Guidelines for Research and Evaluation (AGREE II) tool was used to assess the qualified guidelines' feature. We extracted the main recommendations for the diagnosis of pancreatic cancer from the guidelines and performed a heterogeneity evaluation. The highest-level evidence that supported these recommendations was further extracted and analysed. Nine guidelines for the diagnosis of pancreatic cancer were included in this study. Four of the guidelines had an overall score of more than 60% and thus are recommended for clinical use. Further analysis of the heterogeneity of the main recommendations for the diagnosis of pancreatic cancer in the guidelines revealed that the recommendations vary greatly among the different guidelines. The main reasons for the great differences include the neglect of symptoms and signs, great differences in the items involved in recommendations for the diagnosis of pancreatic cancer, inconsistent recommendations for some indicators (carbohydrate antigen 19-9 and ERCP), the unreasonable citation of evidence, and the failure of some recommendations to provide evidence supporting the recommendations. For most recommendations, there was a low level of evidence and a dearth of high-quality study evidence. Recommendations for pancreatic cancer diagnosis have been significantly inconsistent over the past five years. The quality of the guidelines for diagnosing pancreatic cancer also varies. The improvement by the guideline creators of the factors that contribute to the differences mentioned above will be a shortcut to update the guidelines for the diagnosis of pancreatic cancer.

Appraisal of the diagnostic procedures of acute pancreatitis in the guidelines.

OBJECTIVES: The purpose of this study was to comprehensively assess the heterogeneity of procedures in the diagnostic guidelines for acute pancreatitis and to identify gaps limiting knowledge in diagnosing this disease. METHODS: A systematic search of a number of databases was performed to determine the guidelines for the diagnosis of acute pancreatitis in patients with severe pancreatitis. The guidelines for the diagnosis of severe pancreatitis were evaluated by AGREE II. The Measurement Scale of Rate of Agreement (MSRA) was used to assess the guidelines (2015-2020) and extract evidence supporting these recommendations for analysis. RESULTS: Seven diagnostic guidelines for acute pancreatitis were included. Only the 2019 WSES Guidelines for the Management of Severe Acute Pancreatitis and the Japanese Guidelines for the Management of Acute Pancreatitis: Japanese Guidelines 2015 had a total score of more than 60%, which is worthy of clinical recommendation. The average scores of the Scope and Purpose domain and the Clarity and Expression domain were the highest at 71.62% and 75.59%, respectively, while the average score of the Applicability area was the lowest at 16.67%. The included guidelines were further analyzed to determine the heterogeneity of the diagnosis of acute pancreatitis. The main reasons for the heterogeneity were the citation of low-quality evidence, the presence of far too many indicators for the classification of acute pancreatitis, unclear depictions of the standard, and poorly comprehensive recommendations for the diagnosis of the aetiology in the primary diagnosis of acute pancreatitis, the severity classification, the aetiological diagnosis, and the diagnosis of comorbidities. CONCLUSIONS: The quality of different diagnostic guidelines for severe pancreatitis is uneven. The recommendations are largely based on low-quality evidence, and the guidelines still have much room for improvement to reach a high level of quality. The diagnostic procedures for acute pancreatitis vary widely in different guidelines. There are large differences between them, and resolving the abovementioned reasons would be a very wise choice for guideline developers to revise and upgrade the guidelines in the future.

Consensus and controversy among severe pancreatitis surgery guidelines: a guideline evaluation based on the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool.

The purpose of this study was to systematically evaluate guidelines for surgery in patients with severe pancreatitis and to identify gaps limiting evidence-based medicine practice. A systematic search of databases and related websites was conducted to identify surgical guidelines for patients with severe pancreatitis. The quality of the included guidelines was assessed using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. The similarities among key recommendations were compared, and the evidence supporting them was extracted and analysed. Seven surgical guidelines for patients with severe pancreatitis were included. Only two guidelines, those of the World Society of Emergency Surgery (WSES) and the European Society of Gastrointestinal Endoscopy (ESGE), scored more than 60% for overall quality and were worthy of clinical recommendation. We found that the quality of the severe acute pancreatitis surgical guidelines have much room for improvement, especially in the field of application, the participation of stakeholders and editorial independence. The heterogeneity and causes of surgical recommendations were further analysed, and the latest evidence was retrieved. It was found that the surgical guidelines for severe pancreatitis lacked high-quality evidence, some of the recommendations were controversial, and evidence citation was unreasonable. The quality of surgical guidelines for patients with severe pancreatitis varies widely. In the past 5 years, the key recommendations of the surgical guidelines for severe pancreatitis have been somewhat consistent and controversial, and improvement in these existing problems and controversies will be an effective way for developers to upgrade the surgical guidelines for severe pancreatitis.

The relationship between pistachio (Pistacia vera L) intake and adiposity: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The aim of the study was to conduct a systematic review to comprehensively evaluate the relationship between pistachio intake and obesity. METHODS: We searched 6 databases and acquired parameters from randomized controlled trials regarding obesity, including body weight, body mass index (BMI), and waist circumference. A fixed-effect model was applied to the meta-analysis for the weighted mean difference (WMD) between a diet with pistachios and a control diet. RESULTS: Eleven trials including a total of 1593 subjects met the inclusion criteria. Compared to the group on a control diet, the pistachio diet group showed lower BMI values (WMD: -0.18 kg/m; 95% confidence interval [CI]: -0.26, -0.11 kg/m; I = 29.8%) and no differences in body weight (WMD: -0.22 kg; 95% CI: -0.50, 0.07 kg; I = 0.0%) or waist circumference (WMD: 0.76 cm; 95% CI: -0.11, 1.63 cm; I = 7.0%). CONCLUSION: A diet with pistachios reduced BMI and had no significant effects on body weight and waist circumference.

Evaluation of guidelines for the management of perianal fistulas in Crohn's disease.

INTRODUCTION: The occurrence of perineal fistula is a significant evesnt in the evolution of Crohn's disease. Approximately 21% to 23% of patients develop perineal fistula at least once in their lifetime, approximately 30% of patients have cases of recurrence, and the refractory and recurrent perineal lesions of Crohn's disease impose a great economic burden on patients. The main purpose of this review was to investigate the quality of guidelines for perineal fistula in Crohn's disease. AREA COVERED: Relevant websites and databases were systematically searched to identify and select clinical guidelines related to perineal fistulas in Crohn's disease. Four independent reviewers assessed the eligible guidelines using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) and used intraclass correlation coefficients (ICC) to measure the agreement among the guideline reviewers. CONCLUSION: There is much room for improvement in the quality of guidelines for the management of perineal fistulas in Crohn's disease. The recommendations and evidence for guidelines for the management of perineal fistulas in Crohn's disease are quite heterogeneous, and guideline-developers would be well advised to address the above issues during future guideline development.

Accuracy of using serum D-dimer for diagnosis of acute intestinal ischemia: A meta-analysis.

OBJECTIVE: The purpose of this meta-analysis is to comprehensively assess the accuracy of serum D-dimer for the diagnosis of acute intestinal ischemia. METHODS: Diagnostic studies of D-dimer for accurate diagnosis of acute intestinal ischemia were extracted from 6 databases, and prospective and retrospective studies that provided adequate data on sensitivity and specificity were included here. Sensitivity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were calculated. The overall diagnostic performance of D-dimer was assessed by plotting a summary receiver operating characteristic curve (SROC) and calculating the area under the curve (AUC). RESULTS: A total of 1300 patients with suspected acute intestinal ischemia from 12 studies met the inclusion criteria. The combined sensitivity, specificity, PLR, NLR, and DOR were 0.94 (95% CI: 0.87-0.97), 0.50 (95% CI: 0.40-0.61), 1.9 (95% CI: 1.5-2.3), 0.12 (95% CI: 0.05-0.26), and 16 (95% CI: 7-39), respectively. The AUC was 0.81 (95% CI: 0.78-0.84). CONCLUSION: The results of this meta-analysis suggested that plasma D-dimer detection might be a useful means of identifying patients with acute intestinal ischemia of the abdomen.