Quality Evaluation of Guidelines for the Diagnosis and Treatment of Liver Failure.

OBJECTIVES: This study aimed to systematically assess the methodological quality and key recommendations of the guidelines for the diagnosis and treatment of liver failure (LF), furnishing constructive insights for guideline developers and equipping clinicians with evidence-based information to facilitate informed decision-making. DATA SOURCES: Electronic databases and manual searches from January 2011 to August 2023. STUDY SELECTION: Two reviewers independently screened titles and abstracts, then full texts for eligibility. Fourteen guidelines were included. DATA EXTRACTION AND SYNTHESIS: Two reviewers extracted data and checked by two others. Methodological quality of the guidelines was appraised using the Appraisal of Guidelines for Research and Evaluation II tool. Of the 14 guidelines, only the guidelines established by the Society of Critical Care Medicine and the American College of Gastroenterology (2023) achieved an aggregate quality score exceeding 60%, thereby meriting clinical recommendations. It emerged that there remains ample room for enhancement in the quality of the guidelines, particularly within the domains of stakeholder engagement, rigor, and applicability. Furthermore, an in-depth scrutiny of common recommendations and supporting evidence drawn from the 10 adult LF guidelines unveiled several key issues: controversy exists in the recommendation, the absence of supporting evidence and confusing use of evidence for recommendations, and a preference in evidence selection. CONCLUSIONS: There are high differences in methodological quality and recommendations among LF guidelines. Improving these existing problems and controversies will benefit existing clinical practice and will be an effective way for developers to upgrade the guidelines.

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.

Evaluation of guidelines for the diagnosis and treatment of achalasia.

Due to the unclear quality of the current guidelines, users may be confused about how to diagnose and treat achalasia. The objective of this work is to systematically evaluate the methodological quality of the current guidelines for diagnosing and treating achalasia and to determine the heterogeneity among recommendations. We systematically searched literature databases to retrieve relevant guidelines for the diagnosis and treatment of achalasia. The Appraisal of Guidelines for Research and Evaluation II tool was used to evaluate the quality of the included guidelines. Key recommendations in the guidelines were extracted, and the reasons for the heterogeneity of the key recommendations between different guidelines were further analyzed. Seven guidelines on the diagnosis and treatment of achalasia are included in this study. The overall score of three guidelines exceeded 60%. The average score in domain 5 was the lowest, at 41.8%. The average scores in domain 2, domain 3, and domain 6 were also low, at 45.4%, 57.1% and 56.9%, respectively. The main recommendations and quality of evidence for different guidelines vary greatly, mainly due to the different emphases among different guidelines, the lack of systematic retrieval, or the unfairness of evidence use in some guidelines. There are considerable differences in the methodological quality of diagnosis and treatment guidelines for achalasia. Additionally, the differences in the main recommendations and evidence support among guidelines are also obvious. Guideline developers should improve the above related factors to decrease the heterogeneity, and they should further formulate or update the guidelines for the diagnosis and treatment of achalasia.

Pd-catalyzed 5-exo-dig cyclization/etherification cascade of N-propargyl arylamines for the synthesis of polysubstituted furans.

A method for the synthesis of furans bearing indoline skeletons was developed via an intramolecular palladium-catalyzed 5-exo-dig cyclization/etherification cascade of N-propargyl arylamines containing a 1,3-dicarbonyl side chain. This method realized the first capture of vinyl carbopalladiums by ketones as O-nucleophiles and showed a wide range of substrate tolerability affording trisubstituted furans in various yields. The enantioselective version for this domino process and diverse derivatizations of the reaction products were also studied.

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.

Reduced Popdc3 expression correlates with high risk and poor survival in patients with gastric cancer.

AIM: To investigate the expression of Popeye domain containing 3 (Popdc3) and its correlation with clinicopathological features and prognosis of gastric cancer. METHODS: The method of immunohistochemistry was used to investigate the expression of Popdc3 in 306 cases of human gastric cancer and 84 noncancerous gastric tissues. Simultaneously, the relationship between Popdc3 expression and the survival of the patients was retrospectively analyzed. RESULTS: Popdc3 was detected in 72 (85.71%) of 84 human nontumor mucosa. High expression of Popdc3 protein was detected in 78 (25.49%) of 306 human gastric cancer cases, and low expression was detected in 228 (74.51%). Low expression of Popdc3 correlated with depth of invasion (P < 0.0001), regional lymph nodes (P < 0.0001) and distant metastasis (P = 0.02), and tumor, nodes, metastasis (TNM) stages (P < 0.0001). On multivariate analysis, only the patient's gender, regional lymph node metastasis, distant metastasis, TNM stages, and the expression of Popdc3 were independent prognostic factors in patients with gastric cancer. The Kaplan-Meier plot showed that low Popdc3 expression had a much more significant effect on the survival of those patients with early-stage tumors (χ² = 104.741, P < 0.0001), with a > 51.9% reduction in the three-year survival compared with high Popdc3 expression. In late stages, the difference was also significant (χ² = 5.930, P = 0.015), with a 32.6% reduction in the three-year survival. CONCLUSION: Reduced expression of Popdc3 may play a significant role in the carcinogenesis and progression of gastric cancer. Popdc3 may be an independent prognostic factor.

Abnormal expression of adhesion protein Bves is associated with gastric cancer progression and poor survival.

Although many molecular and biological studies have shown risk factors for gastric cancer, the available knowledge is still insufficient to unveil the exact mechanism of gastric cancer. To investigate the relationships between Bves expression and the clinicopathologic features of gastric cancer and whether Bves can act as prognostic indicators in gastric cancer. Tissues were obtained from the gastrectomy specimens of 306 human gastric cancer and 78 noncancerous gastric tissue at the Department of Surgery and Pathology, the Second Affiliated Hospital of Kunming Medical University from February 1996 to March 2007. The method of immunohistochemistry was used to investigate the expression of Bves in them. The relationship between Bves expression and the survival times of the patients was retrospectively analysed. Reduced expression of Bves frequently occurred in gastric cancer tissue. Low expression of Bves correlated with histologic differentiation, depth of invasion, regional lymph nodes and distant metastasis, and TNM stages (P < 0.05). Bves expression did not correlate with age, gender, location of tumor, size of tumor and histologic type (P > 0.05); Further multivariate analysis revealed that lymph node metastasis (P < 0.0001), distant metastasis (P < 0.0001), surgical treatment (P < 0.0001), and the expression of Bves (P < 0.0001) were independent prognostic factors in patients with gastric cancer; The Kaplan-Meier plot showed that survival times of patients with low Bves expression was significantly lower than those in patients with high Bves expression. Besides, low Bves expression had a much more significant effect on the survival of those patients with early stage tumors (χ2 = 131.216,P < 0.0001), highlighted by a >51.3% reduction in 3-year survival compared with that of patients with high Bves expression. In late stages, the difference was also significant (χ2 = 5.818,P = 0.016), with a 34.8% reduction in 3-year survival. Reduced expression of Bves in gastric cancer is associated with tumor progression and the patient's poor survival. This study showed that the studied protein has further provided a basis for the development of potential biomarker for gastric cancer prognosis.

Ectopic expression of RASSF2 and its prognostic role for gastric adenocarcinoma patients.

RASSF2 has recently been identified as a potential tumor suppressor that serves as a Ras effector in various types of human cancers. However, there have been few reports detailing this in gastric cancer. Samples of gastric adenocarcinoma from 276 Chinese patients with follow-up were analyzed for RASSF2 protein expression by immunohistochemistry. RASSF2 was expressed in up to 31.2% (86/276) of this group of gastric carcinoma. The expression of RASSF2 was significantly lower in carcinomas than in normal mucosas (P<0.05). RASSF2 corresponded positively with patient age, histological differentiation, depth of tumor invasion, regional lymph node and distant metastasis, and TNM stage (all P<0.05). Further multivariate analysis revealed that patient gender, depth of tumor invasion, distant metastasis, TNM stage and the expression of RASSF2 were independent prognostic factors for patients with gastric cancer. The Kaplan-Meier plot showed that the overall mean survival time of the patients with RASSF2-negative expression was shorter than that of patients with positive expression (χ(2)=156.874, P<0.0001). Moreover, RASSF2-negative expression had a much more significant effect on the survival of those patients with early stage tumors (χ(2)=127.167, P<0.0001), highlighted by a >50.9% reduction in 3-year survival compared to that of patients with RASSF2-positive expression. In late stages, the difference was also significant (χ(2)=6.246, P=0.019), with a 35.5% reduction in 3-year survival. It is suggested that RASSF2 plays an important role in the evolution of gastric adenocarcinoma and should be considered as a potential marker for its prognosis.