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.

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 diagnosis and treatment of Helicobacter pylori infection.

BACKGROUND: To systematically evaluate the quality of the guidelines for the diagnosis and treatment of Helicobacter pylori infection and to analyze the differences and reasons for the key recommendations in the guidelines. METHODS: Databases and websites were systematically searched to obtain guidelines for the diagnosis and treatment of Helicobacter pylori infection. Four independent reviewers used the Guideline Evaluation Tool (AGREE II) to evaluate the included guidelines. The intraclass correlation coefficient (ICC) and Fleiss' kappa coefficient were used to measure the consistency of evaluation guidelines between guide reviewers. Differences between guidelines and the reasons for the differences were analyzed by comparing the recommendations of different guidelines and the evidence supporting the recommendations. RESULTS: A total of 17 guidelines for Helicobacter pylori infection were included in this study. The AGREE II scores of these guidelines were low overall, with 4 of them had a score of over 60%, which indicates that the guidelines are recommended, and 13 of them having a score ranging from 30 to 60%, which indicates that the guidelines are recommended but need to be revised, while no guideline had a score of 30% or less, which indicates that they were not recommended. The analysis of these guidelines found that there were some differences in the main recommendations. Not all guidelines recommend sequential therapy as the recommended therapy. Whether bismuth quadruple therapy should be used as the recommended first-line therapy is unclear. The antibiotic resistance rate is different in different regions. Combined with the local antibiotic sensitivity test, the eradication rate of Helicobacter pylori can be improved. CONCLUSION: There are significant differences in the quality of Helicobacter pylori infection guidelines and the key recommendations. Improving the deficiencies of existing guidelines is an effective way to develop high-quality guidelines and make reasonable recommendations for the treatment of Helicobacter pylori infection in the future.

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.

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.

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.

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.

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.

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.

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.

Early oral nutrition improves postoperative ileus through the TRPA1/CCK1-R-mediated mast cell-nerve axis.

BACKGROUND: The mechanism of early oral nutrition that regulates the mast cell-nerve axis to improve postoperative ileus (POI) remains unclear. This study aims to investigate whether early oral nutrition can improve POI through Transient receptor potential ankyrin-1 (TRPA1)/cholecystokinin 1 receptor (CCK1-R) in the mast cell-nerve axis. METHODS: Experiment 1: Male Sprague-Dawley (SD) rats were randomly divided into the TRPA1 inhibitor + oral nutrition group (TI + ON + POI), oral nutrition group (ON + POI), POI group (POI) and sham surgery group (Sham). Nine rats in each group were treated. Experiment 2: Primary cultures of mast cells and dorsal root ganglion cells were created, and a non-contact co-culture system was established. The cells were divided into the dorsal root ganglion (DRG) group, mast cell group, DRG + mast cell group, TRPA1 inhibitor or enhancer group, mast cell stabilizer or enhancer group, CCK1-R inhibitor or enhancer group. The results of expression of TRPA1, CCK1-R and histamine in colon tissue, portal vein blood, supernatant or dorsal root ganglia, intestinal transport test and mast cell morphology were analysed. RESULTS: In experiment 1, Early oral nutrition could alleviate the degranulation and activation of mast cells and alleviate the inflammatory reaction of intestinal wall muscles (P<0.05). Early oral nutrition improved POI by stabilizing mast cells with TRPA1. TRPA1 inhibitor decreased CCK1-R concentrations in portal vein blood and CCK1-R expression in colonic smooth muscle (P<0.05). In experiment 2, the change in mast cell function regulated the secretion of CCK1-R by neurons, CCK1-R negatively regulated the degranulation and activation of mast cells (P<0.05), and mast cells positively regulated the expression of TRPA1 protein in DRG (P<0.05). CONCLUSIONS: Early enteral nutrition can improve POI through the TRPA1/CCK1-R-mediated mast cell-nerve axis. TRPA1 positively regulates CCK1-R to stabilize mast cells, but TRPA1 is not the target of the downstream CCK1-R pathway.

Heterogeneity of nutrition care procedures in nutrition guidelines for cancer patients.

OBJECTIVES: The aim of this study was to systematically assess the nutrition care procedures in nutrition guidelines for cancer patients and identify gaps limiting evidence-based practise. METHODS: A systematic search of databases and websites was conducted to identify nutrition guidelines for cancer patients. The quality of the eligible guidelines was evaluated by using the Appraisal of Guidelines for Research and Evaluation (AGREE II). The Measurement Scale of Rate of Agreement (MSRA) was used to assess the scientific agreement of formulated recommendations for nutrition care procedures in the guidelines (2017-2019), and evidence supporting these recommendations was extracted and analysed. RESULTS: Seventeen nutrition guidelines for cancer patients were identified. Only European Society for Clinical Nutrition and Metabolism (ESPEN) and Australian guidelines have a total quality score of more than 60%, which is worthy of clinical recommendation. Twelve guidelines (2017-2019) were included to further analyse the heterogeneity and causes of nutrition care procedures, and we found that the content and tools of nutrition screening and assessment, the application of immune nutrients, and the selection of nutritional support pathways were heterogeneous. The main reasons for the heterogeneity of nutrition care procedures were insufficient attention to nutrition risk screening, differences in recommendations for nutrition assessment, immune nutrients and nutritional support, unreasonable citation of screening and assessment evidence, preference of developers, and lack of evidence of high-quality research on energy and nitrogen demand. In addition, the fairness and propensity of the guidelines for the selection of evidence for different cancer patients are also potential reasons for the heterogeneity of nutritional care procedures. CONCLUSIONS: The quality of the nutrition guidelines for cancer patients was highly variable. The nutrition care procedures were heterogeneous among the different guidelines in the last 3 years. Specific improvement of the factors leading to the heterogeneity of nutrition care procedures will be a reasonable and effective way for developers to upgrade the nutrition care procedures in the guidelines for cancer patients.

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.

Comparison of multi-modal early oral nutrition for the tolerance of oral nutrition with conventional care after major abdominal surgery: a prospective, randomized, single-blind trial.

BACKGROUND & AIMS: Early oral nutrition (EON) has been shown to improve recovery of gastrointestinal function, length of stay and mortality after abdominal surgery; however, early oral nutrition often fails during the first week after surgery. Here, a multi-modal early oral nutrition program is introduced to promote recovery of gastrointestinal function and tolerance of oral nutrition. METHODS: Consecutive patients scheduled for abdominal surgery were randomized to the multimodal EON group or a group receiving conventional care. The primary endpoint was the time of first defecation. The secondary endpoints were outcomes and the cost-effectiveness ratio in treating infectious complications. The rate of infectious-free patients was regarded as the index of effectiveness. RESULTS: One hundred seven patients were randomly assigned to groups. Baseline characteristics were similar for both groups. In intention-to-treat analysis, the success rate of oral nutrition during the first week after surgery in the multimodal EON group was 44 (83.0%) versus 31 (57.4%) in the conventional care group (P = 0.004). Time to first defecation, time to flatus, recovery time of bowel sounds, and prolonged postoperative ileus were all less in the multimodal EON group (P < 0.05). The median postoperative length of stay in the multimodal EON group was 8 days (6, 12) versus 10 days (7, 18) in the conventional care group (P < 0.001). The total cost of treatment and nutritional support were also less in the multi-modal early oral nutrition group (P < 0.001). The effectiveness was 84.9 and 79.9% in the multimodal EON and conventional care group, respectively (P = 0.475). However, the cost-effectiveness ratio was USD 537.6 (506.1, 589.3) and USD 637.8 (593.9, 710.3), respectively (P < 0.001). CONCLUSION: The multi-modal early oral nutrition program was an effective way to improve tolerance of oral nutrition during the first week after surgery, decrease the length of stay and improve cost-effectiveness after abdominal surgery. TRIAL REGISTRATION: Registration number: ChiCTR-TRC-14004395 . Registered 15 March 2014.

Impact of nutritional support that does and does not meet guideline standards on clinical outcome in surgical patients at nutritional risk: a prospective cohort study.

OBJECTIVE: To investigate the impact of nutritional support on clinical outcomes in patients at nutritional risk who receive nutritional support that meets guideline standards and those who do not. METHODS: This prospective cohort study enrolled hospitalized patients from the Second Affiliated Hospital of Kunming Medical University from February 2010 to June 2012. The research protocols were approved by the university's ethics committee, and the patients signed informed consent forms. The clinical data were collected based on nutritional risk screening, administration of enteral and parenteral nutrition, surgical information, complications, and length of hospital stay. RESULTS: During the study period, 525 patients at nutritional risk were enrolled in the cohorts. Among patients who received nutritional support that met the guideline standards (Cohort 1), the incidence of infectious complications was lower than that in patients who did not meet guideline standards (Cohort 2) (17.1 % vs. 26.9 %, P = 0.01). Subgroup analysis showed that individuals who received a combination of parenteral nutrition (PN) and enteral nutrition (EN) for 7 or more days had a significantly lower incidence of infectious complications (P = 0.001) than those who received only PN for 7 or more days or those who received nutritional support for less than 7 days or at less than 10 kcal/kg/d. Binary logistic regression analysis showed that, after adjusting for confounding factors, nutritional support that met guideline standards for patients with nutritional risk was a protective factor for complications (OR: 0.870, P < 0.002). CONCLUSIONS: In patients at nutritional risk after abdominal surgery, nutritional support that meets recommended nutrient guidelines (especially regimens involving PN + EN ≥ 7 days) might decrease the incidence of infectious complications and is worth recommending; however, well-designed trials are needed to confirm our findings. Nutritional support that does not meet the guideline standards is considered clinically undesirable.