Impact of body composition, grip strength, and physical performance on clinical outcomes for locally advanced gastric cancer during neoadjuvant chemotherapy: A prospective cohort study.

OBJECTIVE: Neoadjuvant chemotherapy (NC) is critical in treating locally advanced gastric cancer (LAGC). However, the effect of body composition, grip strength, and physical performance during neoadjuvant chemotherapy remains uncertain. This study aimed to investigate the impact of these factors on perioperative clinical outcomes in LAGC patients undergoing NC. METHODS: A total of 162 consecutive patients receiving NC at two centers were prospectively registered between June 2022 and September 2023. The data on body composition parameters, grip strength, and physical performance during NC were collected, compared, and analyzed. The primary outcome was the tumor response after completion of NC. RESULTS: Overall, we included 92 LAGC patients. No significant changes were observed in body composition, grip strength, and physical performance after NC. The change in skeletal muscle index and grip strength were both significantly lower in the patients with poor tumor response. According to the Youden index, the cutoff values of △SMI and △grip strength were -2.0 and -2.8, respectively. Based on these two parameters, the area under the curve to predict tumor response was 0.817 (P < 0.001). Furthermore, visceral fat index (VFI) loss >6.9 and 5-time chair stand test increase >2.4 independently predicted postoperative complication (OR: 3.82, 95% CI: 1.138-12.815, P = 0.030; OR: 5.01, 95% CI: 1.086-23.131, P = 0.039, respectively). CONCLUSIONS: For LAGC patients receiving NC, changes in SMI, VFI, grip strength, and physical status can predict perioperative clinical outcomes. These patients should be given special nutritional intervention.

Comparison of bioelectrical impedance analysis and computed tomography for the assessment of muscle mass in patients with gastric cancer.

BACKGROUND: Low muscle mass was significantly correlated with poor clinical outcomes in cancer patients. This study aimed to compare the differences between bioelectrical impedance analysis (BIA) and computed tomography (CT) in measuring skeletal muscle mass and detecting low muscle mass in patients with gastric cancer (GC). METHOD: This cross-sectional study included a total of 302 consecutive patients diagnosed with GC at our institution from October 2021 to March 2023. CT images were analyzed at the L3 level to obtain the cross-sectional area of skeletal muscle, which was subsequently used for calculating whole-body skeletal muscle mass via the Shen equation and skeletal muscle tissue density. BIA was utilized to measure skeletal muscle mass using the manufacturer's proprietary algorithms. Skeletal muscle mass (kg) was divided by height squared (m2) to obtain skeletal muscle index (SMI, kg/m2). Pearson's correlation coefficient was performed to assess the correlation between SMI measured by BIA and CT. The agreement between the two methods was assessed using Bland-Altman analyses. The clinically acceptable agreement was defined as the 95% limits of agreement (LOA) for the percentage bias falling within ± 10%. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of BIA in identifying low muscle mass. RESULTS: A total of 59 patients (19.5%) were identified as having low muscle mass based on CT analysis, whereas only 19 patients (6.3%) met the criteria for low muscle mass according to BIA analysis. BIA-measured SMI showed a strong positive correlation with CT-measured SMI in all patients (r = 0.715, P < 0.001). With Bland-Altman analysis, there was a significant mean bias of 1.18 ± 0.96 kg/m2 (95% CI 1.07-1.29, P < 0.001) between SMI measured by BIA and CT. The 95% LOA for the percentage bias ranged from -7.98 to 33.92%, which exceeded the clinically acceptable range of ± 10%. A significant difference was observed in the mean bias of SMI measured by BIA and CT between patients with and without GLIM malnutrition (1.42 ± 0.91 kg/m2 versus 0.98 ± 0.96 kg/m2, P < 0.001). The cut-off values for BIA-measured SMI in identifying low muscle mass using CT as the reference were 10.11 kg/m2 for males and 8.71 kg/m2 for females (male: AUC = 0.840, 95% CI: 0.772-0.908; female: AUC = 0.721, 95% CI: 0.598-0.843). CONCLUSIONS: Despite a significant correlation, the values of skeletal muscle mass obtained BIA and CT cannot be used interchangeably. The BIA method may overestimate skeletal muscle mass in GC patients compared to CT, especially among those with GLIM malnutrition, leading to an underestimation of low muscle mass prevalence.

Dietary Provision, GLIM-Defined Malnutrition and Their Association with Clinical Outcome: Results from the First Decade of nutritionDay in China.

Malnutrition is a common and serious issue that worsens patient outcomes. The effects of dietary provision on the clinical outcomes of patients of different nutritional status needs to be verified. This study aimed to identify dietary provision in patients with eaten quantities of meal consumption and investigate the effects of dietary provision and different nutritional statuses defined by the GLIM criteria on clinical outcomes based on data from the nutritionDay surveys in China. A total of 5821 adult in-patients from 2010 to 2020 were included in this study's descriptive and Cox regression analyses. Rehabilitation and home discharge of 30-day outcomes were considered a good outcome. The prevalence of malnutrition defined by the GLIM criteria was 22.8%. On nutritionDay, 51.8% of all patients received dietary provisions, including hospital food and a special diet. In multivariable models adjusting for other variables, the patients receiving dietary provision had a nearly 1.5 higher chance of a good 30-day outcome than those who did not. Malnourished patients receiving dietary provision had a 1.58 (95% CI [1.36-1.83], p < 0.001) higher chance of having a good 30-day outcome and had a shortened length of hospital stay after nutritionDay (median: 7 days, 95% CI [6-8]) compared to those not receiving dietary provision (median: 11 days, 95% CI [10-13]). These results highlight the potential impacts of the dietary provision and nutritional status of in-patients on follow-up outcomes and provide knowledge on implementing targeted nutrition care.

Early enteral nutrition versus early supplemental parenteral nutrition in patients undergoing major abdominal surgery: a secondary analysis of 2 randomized clinical trials.

BACKGROUND: The effect of early isoenergetic feeding routes [early enteral nutrition (E-EN) or early supplemental parenteral nutrition (E-SPN)] on the outcome of patients undergoing major abdominal surgery is controversial. OBJECTIVES: The aim of this study was to investigate the impact of early isoenergetic EN compared with early isoenergetic SPN on nosocomial infections in patients undergoing major abdominal surgery. METHODS: This study is a secondary, post hoc analysis of data from 2 open-label randomized clinical trials. Participants were recruited from the general surgery department of 11 academic hospitals in China undergoing major abdominal surgery and with Nutritional Risk Screening 2002 score ≥3. All eligible patients were categorized into 2 groups based on their achievement of the 100% energy target on postoperative day (POD) 3: the E-EN group (n = 199) and the E-SPN group (n = 115). The primary outcome was the incidence of nosocomial infections between POD 3 and hospital discharge. RESULTS: In total, 314 patients [mean (SD) age, 59.2 (11.4) y; 113 (36.0%) females] were included. Patients in the E-EN group showed no significant difference in nosocomial infections compared with those in the E-SPN group {17/199 [8.5%] compared with 10/115 [8.7%], risk difference, 0.2% [95% confidence interval (CI): -6.3, 6.6]}. The hematological nutritional status of the E-EN group showed a significant improvement at discharge compared with the E-SPN group (albumin: 38.0 ± 6.0 g/L compared with 35.5 ± 7.6 g/L; mean difference, -2.5 g/L; 95% CI: -4.0, -1.0 g/L; prealbumin: 200.0 ± 8.0 mg/L compared with 158.4 ± 38.1 mg/L; mean difference, -41.6 mg/L; 95% CI: -41.7, -36.1 mg/L). Other indicators were comparable between groups. CONCLUSION: E-EN compared with isoenergetic SPN may not be associated with a reduced rate of nosocomial infection in patients undergoing major abdominal surgery, but may be associated with improved hematological nutritional status. TRIAL REGISTRATION NUMBER: This trial was registered at clinicaltrials.gov as NCT03115957 (https://clinicaltrials.gov/ct2/show/NCT03115957) and NCT03117348 (https://clinicaltrials.gov/ct2/show/NCT03117348).

Phase angle - A screening tool for malnutrition, sarcopenia, and complications in gastric cancer.

BACKGROUND: Patients with gastric cancer (GC) are more likely to experience malnutrition and muscle wasting. This study aims to investigate the potential of phase angle (PhA) as a screening tool for identifying malnutrition and sarcopenia in GC patients, as well as its association with short-term outcomes after radical gastrectomy. METHODS: This cross-sectional study enrolled patients diagnosed with GC at The Affiliated People's Hospital of Jiangsu University from October 2021 to September 2022. PhA was measured using bioelectrical impedance analysis. Computed tomography scan images were analyzed for body composition at the level of the third lumbar vertebra. Malnutrition was diagnosed using Global Leadership Initiative on Malnutrition (GLIM) criteria. Sarcopenia diagnosis was based on the Asian Working Group for Sarcopenia (AWGS) 2019 criteria. RESULTS: A total of 248 patients with GC were analyzed, including 188 patients who underwent radical gastrectomy. Of these, 71.4 % (n = 177) were male and 28.6 % (n = 71) were female and the median overall age was 68 years (IQR: 61-72 years). According to GLIM criteria, 49.2 % (n = 122) of patients were malnourished and 19.8 % (n = 49) had sarcopenia based on AWGS criteria. A one-degree decrease in PhA was significantly associated with GLIM malnutrition (Odds Ratio [OR] = 8.108, 95 % CI:3.181-20.665) and sarcopenia (OR = 2.903, 95 % CI:1.170-7.206). PhA exhibited fair to good diagnostic accuracy in identifying GLIM malnutrition (male: AUC = 0.797; female: AUC = 0.816) and sarcopenia (male: AUC = 0.814; female: AUC = 0.710). Low PhA (OR = 3.632, 95 % CI: 1.686-7.824) and operation time (OR = 2.434, 95 % CI:1.120-5.293) were independently associated with the risk of postoperative complications. CONCLUSIONS: PhA can serve as a reliable screening tool for identifying patients at risk of malnutrition, sarcopenia, and postoperative complications in GC.

Predictive value of serum fibroblast growth factor 19 and liver stiffness for intestinal failure associated liver disease-cholestasis.

BACKGROUND: Intestinal failure associated liver disease (IFALD)-cholestasis is a common complication of long-term parenteral nutrition (PN) in patients with intestinal failure (IF). The lack of effective early identification indicators often results in poor clinical outcomes. The objective of this study was to evaluate the predictive value of serum FGF19 and liver stiffness in IFALD-cholestasis. METHODS: Eligible adults diagnosed with IF were identified from Jinling Hospital in China. Diagnostic criteria for IFALD-cholestasis: total bilirubin >1 mg/dL and conjugated bilirubin >0.3 mg/dL for ≥6 months. Fasting blood specimens were prospectively collected and serum FGF19 concentrations were determined using ELISA and liver stiffness was measured by Two-dimensional shear wave elastography. Binary logistic regression analysis identified predictors of IFALD-cholestasis. Receiver operating characteristic (ROC) curves and areas under the ROC curves (AUROC) were used to evaluate the accuracy of serum FGF19 and liver stiffness in identifying IFALD-cholestasis. RESULTS: Of 203 study patients with IF, 70 (34.5%) were diagnosed with IFALD-cholestasis. The serum FGF19 levels in those with IFALD-cholestasis were significantly decreased compared with those in patients without, and liver stiffness was significantly increased (p < 0.001). Multivariate logistic regression analyses suggested that intestinal discontinuity, dependence on PN, liver stiffness >6.5 kPa, and serum FGF19 ≤107 pg/mL were independent risk factors for IFALD-cholestasis. The AUROC for serum FGF19 and liver stiffness, which indicate the occurrence of IFALD-cholestasis, were 0.810 and 0.714, respectively. Serum FGF19 had a superior predictive performance than liver stiffness (p < 0.05). CONCLUSION: Both low circulating serum FGF19 concentration and increased liver stiffness are excellent predictors of IFALD-cholestasis, but serum FGF19 is superior to increased liver stiffness in predicting IFALD-cholestasis.

Impact of malnutrition and sarcopenia on quality of life in patients with inflammatory bowel disease: A multicentre study.

BACKGROUND: Malnutrition and subsequent alterations in body composition (BC), particularly sarcopenia, are common but not yet elucidated in patients with inflammatory bowel disease (IBD); we aimed to detail the changes in BC and the characteristics of co-occurrence of malnutrition and sarcopenia in IBD patients and to investigate its effect on quality of life. METHODS: This study was a multicentre, prospective, observational study involving four tertiary referral hospitals in China. The following data were collected from consecutive IBD inpatients: demographic information, medical history, recent weight change, handgrip strength (HGS) and BC parameters by bioelectrical impedance analysis (BIA). Nutritional assessments were performed through stepwise screening (Nutritional Risk Screening 2002) and diagnosis (World Health Organization-related body mass index [BMI], subjective global assessment, European Society for Clinical Nutrition and Metabolism 2015 and Global Leadership Initiative on Malnutrition [GLIM] criteria). The quality of life was assessed by the Inflammatory Bowel Disease Questionnaire. IBD patients were compared with 1:1 sex-, age- and BMI-matched healthy controls (MHC). RESULTS: A total of 238 IBD patients (177 Crohn's disease [CD] and 61 ulcerative colitis [UC]), 68.5% male, with a mean age of 38.5 ± 14.0 years and a mean BMI of 19.8 ± 3.5 kg/m2 , were recruited. Compared with MHC (n = 122), IBD patients showed significant deterioration in BC and physical function, characterized by muscle depletion (appendicular skeletal muscle mass index [ASMI], 8.0 ± 1.3 vs. 6.7 ± 1.2 kg/m2 , Δ% -15.0% [-22.0%, -10.0%], P < 0.001) and fat accumulation (visceral fat area, 32.9 ± 22.6 vs. 66.5 ± 35.8, Δ% 110.0% [35.0%, 201.0%], P < 0.001). The prevalence of GLIM-defined malnutrition and sarcopenia in IBD patients was 60.1% and 25.2%, respectively. The nutritional status of patients with CD was worse than that of patients with UC. The activity phase of IBD significantly and negatively affected BC, while the lesion location did not. The co-occurrence of sarcopenia and malnutrition was not optimistic; 16.4-21.8% of patients suffer from sarcopenia and malnutrition based on different criteria at the same time, which was accompanied by a reduction in quality of life. HGS was correlated with various BC parameters (body cell mass, r = 0.76; ASMI, r = 0.70; fat-free mass, r = 0.73, all P < 0.001). CONCLUSIONS: GLIM-defined malnutrition and sarcopenia were prevalent in IBD patients and kept a high rate of co-occurrence, which was accompanied with impaired quality of life. The alteration of BC in IBD patients was characterized by muscle depletion and fat accumulation. The strong correlation between HGS and BIA-derived BC suggested its hopeful evaluation in nutritional status and sarcopenia in IBD patients.

Developing Strategies to Improve the Efficacy of CAR-T Therapy for Acute Myeloid Leukemia.

OPINION STATEMENT: Acute myeloid leukemia (AML) is a fatal blood malignancy. With the development of immunotherapy, particularly chimeric antigen receptor T cells (CAR-T), the treatment of AML has undergone a significant change. Despite its advantages, CAR-T still faces a number of limitations and challenges while treating AML. Finding novel targets, altering the structure of CAR to increase efficacy while lowering side effects, and using double-target CAR and logic circuits are typical examples of key to answer these problems. With the advancement of gene editing technology, gene editing of tumor cells or normal cells to create therapeutic effects has grown in popularity. Additionally, the combination of multiple drugs is routinely used to address some of the obstacles and difficulties associated with CAR-T therapy. The review's primary goal was to summarize recent strategies and developments of CAR-T therapy for AML.

Serum ferritin is associated with sarcopenia and predicts long-term survival for gastric cancer undergoing radical gastrectomy.

BACKGROUND: Gastric cancer (GC) is one of the most common malignant tumors, and its long-term overall survival (OS) still needs to be improved. This study aimed to elucidate the relationship between serum ferritin (SF) and sarcopenia and its ability to predict long-term OS for GC patients. METHODS: Clinicopathological data from GC patients who underwent radical gastrectomy were reviewed and received 3 years of follow-up after surgery. The correlation between SF and sarcopenia was determined by Spearman analysis. Factors used to establish a nomogram to predict the 3-year OS for GC were identified by multivariate Cox hazard analysis. RESULTS: We retrospectively identified 372 GC patients after surgery and randomly divided (3:1) into a training cohort and a validation cohort. The correlation coefficient between SF and sarcopenia was 0.323. GC patients with SF < 151.5 µg/L had a significantly longer 3-year OS. The variables of the nomogram include SF, sarcopenia, TNM stage system, and neoadjuvant chemotherapy. In the training cohort and validation cohort, the area under the time-dependent ROC curve was 0.81 and 0.791, respectively. The calibration curve and decision curve in different cohorts have good consistency. 3-year OS was significantly different among the three groups (log-rank P  < 0.001) divided by calculating the nomogram score. CONCLUSION: SF was positively correlated with sarcopenia, and the nomogram was a practical tool for predicting 3-year OS after radical gastrectomy, furthermore could be used to stratify the risk of 3-year OS in patients with GC.

Alliance between titans: combination strategies of CAR-T cell therapy and oncolytic virus for the treatment of hematological malignancies.

There have been several clinical studies using chimeric antigen receptor (CAR)-T cell therapy for different hematological malignancies. It has transformed the therapy landscape for hematologic malignancies dramatically. Nonetheless, in acute myeloid leukemia (AML) and T cell malignancies, it still has a dismal prognosis. Even in the most promising locations, recurrence with CAR-T treatment remains a big concern. Oncolytic viruses (OVs) can directly lyse tumor cells or cause immune responses, and they can be manipulated to create therapeutic proteins, increasing anticancer efficacy. Oncolytic viruses have been proven in a rising number of studies to be beneficial in hematological malignancies. There are limitations that cannot be avoided by using either treatment alone, and the combination of CAR-T cell therapy and oncolytic virus therapy may complement the disadvantages of individual application, enhance the advantages of their respective treatment methods and improve the treatment effect. The alternatives for combining two therapies in hematological malignancies are discussed in this article.

Impact of sarcopenia on the survival of patients undergoing liver transplantation for decompensated liver cirrhosis.

BACKGROUND: Patients with decompensated cirrhosis (DC) are prone to skeletal muscle loss, namely, sarcopenia, before liver transplantation (LT). While sarcopenia is reportedly associated with adverse outcomes after LT, these findings are limited owing to mixed diseases and retrospective data. We investigated the association between sarcopenia and 1-year overall survival (OS) in patients with DC after LT and established and validated a prediction model for postoperative OS based on sarcopenia. METHODS: Overall, 222 consecutive patients who underwent LT at our centre were registered between September 2020 and June 2022. Third lumbar spine skeletal muscle mass index was measured using computed tomography. Patients were divided into sarcopenia and non-sarcopenia groups according to the skeletal muscle mass index, and baseline data and postoperative outcomes were collected, compared and analysed. The primary outcome was the 1-year OS after LT. We established a dynamic nomogram of the OS predictive model. RESULTS: We included 177 DC patients [mean (standard deviation) age, 50.2 ± 9.3 years; 52 women (29.4%)]; 73 (41.2%) had sarcopenia. The mean (standard deviation) body mass index was 22.6 ± 4.5 kg/m2 , 28 (15.8%) patients had weight loss ≥5% within 6 months before admission, and the mean (standard deviation) model for end-stage liver disease (MELD) score was 18.4 ± 7.9. Patients with sarcopenia had a longer duration of intensive care unit stay (4.1 ± 2.2 vs. 3.1 ± 1.1 days, P = 0.008), higher rate of major complications (45.2% vs. 22.1%, P = 0.001) and higher postoperative mortality (15.1% vs. 2.9%, P = 0.003) than those without sarcopenia. The median 1-year OS after surgery was shorter in patients with sarcopenia than in those without (P < 0.001). Sarcopenia [hazard ratio (HR), 2.54; 95% confidence interval (CI), 1.54-5.63; P = 0.022], weight loss ≥5% (HR, 2.46; 95% CI, 1.39-5.09; P = 0.015) and MELD score (HR, 1.05; 95% CI, 1.01-1.09; P = 0.009) were independent risk factors associated with 1-year OS. The area under the curve of the established dynamic nomogram was 0.774, the calibration curve showed good consistency, and analysis of the decision curve showed more clinical benefits than the MELD score alone. High-risk patients (>102.9 points calculated using the nomogram) had a significantly reduced survival rate. CONCLUSIONS: Sarcopenia is associated with adverse outcomes after LT in patients with DC. High-risk patients should be classified by dynamic nomogram upon admission.

Rapid assessment of malnutrition based on GLIM diagnosis in Crohn's disease.

Background and aims: Malnutrition is strongly linked to adverse outcomes in patients with Crohn's disease (CD). In this study, our objective was to validate the Global Leadership Initiative on Malnutrition (GLIM) criteria and develop a fast and accurate diagnostic approach for identifying malnutrition in CD patients. Methods: This study assessed 177 CD patients from four general hospitals. The efficacy of the GLIM criteria for the diagnosis of CD malnutrition was compared. By analyzing the independent factors, a nomogram model was derived and internally validated to predict the diagnosis of malnutrition in patients with CD. Model performance was assessed using discrimination and calibration, decision curves, and net benefit analyses. Results: Compared with the SGA criteria, the GLIM criteria was consistent in sensitivity (88.89%) and specificity (78.43%) [AUC = 0.84; 95% Confidence Interval (CI): 0.77-0.89]. The Harvey-Bradshaw index(HBI) score (OR: 1.58; 95% CI: 1.15-2.18), body mass index (OR: 0.41; 95% CI: 0.27-0.64), and mid-upper arm circumference (OR: 0.68; 95% CI: 0.47-0.9) were independent factors associated with malnutrition. The nomogram was developed based on these indicators showing good discrimination in malnutrition diagnosis (AUC = 0.953; 95% CI: 0.922-0.984), with agreement after calibration curve and decision curve analysis. Conclusion: The GLIM criteria are appropriate for diagnosing malnutrition in CD patients. The HBI score may be used to diagnose malnutrition in patients with CD and become a possible selection for the GLIM etiologic criteria of inflammation. The HBM nomogram could be a simple, rapid, and efficient method for diagnosing malnutrition in CD patients.

Effects of resistance training on sarcopenia in patients with intestinal failure: A randomized controlled trial.

BACKGROUND: The potential effects of resistance training on sarcopenia in patients with intestinal failure (IF) are not fully elucidated. This study aimed to explore the efficacy of a resistance training program on appendicular skeletal muscle index (ASMI), physical performance, body composition, biochemical parameters, and health-related quality of life (HRQOL) in patients with IF exhibiting sarcopenia. METHODS: A single-center randomized controlled trial was conducted in a Chinese tertiary teaching hospital. Patients with IF exhibiting sarcopenia were randomly assigned to the exercise group or control group. Participants in the exercise group incorporated four sets of resistance training involving the limbs and abdominal and lower back muscles, six times weekly for 4 weeks. The control group received no specific intervention. The primary outcome was the between-group difference in ASMI 4 weeks after intervention. Secondary outcomes included handgrip strength, 6-m gait speed, body composition, biochemical parameters, and HRQOL. RESULTS: A total of 60 participants (control group 30, age 51.2 ± 12.9 years, women 43.3%; exercise group 30, age 53.9 ± 14.5 years, women 56.7%) completed the 4-week intervention trial. For the primary outcome, significant intervention effects were found in ASMI between the exercise group and the control group (mean difference 0.72, 95% CI, 0.56-0.89, P < 0.001). There were notable differences in handgrip strength (mean difference 2.7, 95% CI, 1.7-3.6, P < 0.001), 6-m gait speed (mean difference 0.08, 95% CI, 0.01-0.35, P = 0.034), body composition (including total cell mass, bone mineral content, skeletal muscle mass, lean mass, visceral fat area, total body water, intracellular water, extracellular water, and segmental water-legs), and biochemical parameters (including IGF-1, prealbumin, and hemoglobin) between the two groups (P < 0.05). No significant intervention benefits were observed for other secondary outcomes, including biochemical parameters (including albumin, total bilirubin, etc.) and HRQOL (P > 0.05). CONCLUSIONS: In this randomized clinical trial, we observed that 4 weeks of resistance training was associated with improved ASMI, physical performance, biochemical parameters (including IGF-1, prealbumin, and hemoglobin), and body composition in IF patients with sarcopenia. Resistance training can be recommended as a simple and effective method to improve sarcopenia in patients with IF. CLINICAL TRIAL REGISTRATION: www.chictr.org.cn, identifier: ChiCTR2100051727.

Effect of early achievement of energy target by different nutritional support strategies on nosocomial infections in patients undergoing major abdominal surgery: a secondary analysis of two randomized clinical trials.

BACKGROUND: The effect of early achievement of energy targets (EAETs) using different nutritional support strategies in patients undergoing major abdominal surgery is unclear. This study determined the impact of EAETs on the incidence of nosocomial infections in patients undergoing major abdominal surgery. METHODS: This was a secondary analysis of two open-label randomized clinical trials. Patients from the general surgery department of 11 academic hospitals in China undergoing major abdominal surgery and at nutritional risk (Nutritional risk screening 2002≥3) were divided into two groups based on whether they met the 70% energy targets, the EAET (521 EAET and non-achievement of energy target (114 NAET) groups. The primary outcome was the incidence of nosocomial infections between postoperative day 3 and discharge, and the secondary outcomes were actual energy and protein intake, postoperative noninfectious complications, intensive care unit admission, mechanical ventilation, and hospital stay. RESULTS: Overall, 635 patients [mean (SD) age, 59.5 (11.3) years] were included. The EAET group received more mean energy between days 3 and 7 than the NAET group (22.7±5.0 vs. 15.1±4.8 kcal/kg/d; P <0.001). The EAET group had significantly fewer nosocomial infections than the NAET group [46/521(8.8%) vs. 21/114(18.4%); risk difference, 9.6%; 95% CI, 2.1-17.1%; P =0.004]. A significant difference was found in the mean (SD) number of noninfectious complications between the EAET and NAET groups [121/521(23.2%) vs. 38/114(33.3%); risk difference, 10.1%; 95% CI, 0.7-19.5%; P =0.024]. The nutritional status of the EAET group was significantly improved at discharge compared with the NAET group ( P <0.001), and other indicators were comparable between groups. CONCLUSION: EAETs was associated with fewer nosocomial infections and improved clinical outcomes, regardless of the nutritional support strategy (early enteral nutrition alone or combined with early supplemental parenteral nutrition).

Decentralized adaptively weighted stacked autoencoder-based incipient fault detection for nonlinear industrial processes.

Modern industrial processes often exhibit large-scale and nonlinear characteristics. Incipient fault detection for industrial processes is a big challenge because of the faint fault signature. To improve the performance of incipient fault detection for large-scale nonlinear industrial processes, a decentralized adaptively weighted stacked autoencoder (DAWSAE) -based fault detection method is proposed. First, the industrial process is divided into several sub-blocks and local adaptively weighted stacked autoencoder (AWSAE) is established for each sub-block to mine local information and obtain local adaptively weighted feature vectors and residual vectors. Second, the global AWSAE is established for the whole process to mine global information and obtain global adaptively weighted feature vectors and residual vectors. Finally, local statistics and global statistics are constructed based on local and global adaptively weighted feature vectors and residual vectors to detect the sub-blocks and the whole process, respectively. The advantages of proposed method are verified by a numerical example and Tennessee Eastman process (TEP).

Effects of oral immunonutritional supplement on 3-year disease-free survival in gastric cancer patients with pathological stage III after total gastrectomy (CRUCIAL): study protocol of a multicentre, randomised clinical trial.

INTRODUCTION: The nutritional status of patients with gastric cancer (GC) after total gastrectomy continues to deteriorate and lasts a long time after discharge, which is an independent risk factor for mortality. Recent guidelines have recommended appropriate nutritional support after discharge for cancer surgery patients with malnutrition or nutritional risk. The evidence on the efficacy of oral immunonutritional supplement (INS) and its effect on long-term disease-free survival (DFS) in patients with GC is limited. This study was designed to test the hypothesis that oral INS compared to diet alone may improve 3-year DFS of GC patients with pathological stage III after total gastrectomy (Nutrition Risk Screening 2002 score ≥3 at discharge). METHODS AND ANALYSIS: This is a pragmatic, open-label, multicentre, randomised controlled study. 696 eligible GC patients with pathological stage III after total gastrectomy will be randomised in a 1:1 ratio to oral INS group or normal diet group for 6 months. The primary endpoint is 3-year DFS after discharge. The following secondary endpoints will be evaluated: 3-year overall survival; unplanned readmission rate at 3 and 6 months after discharge; quality of life, body mass index and haematological index at 3, 6 and 12 months after discharge; incidence of sarcopenia at 6 and 12 months after discharge; and the tolerance to chemotherapy. The adverse events of oral INS will also be evaluated during the intervention. ETHICS AND DISSEMINATION: This study was approved by the ethics committee of Jinling Hospital, Nanjing University (number 2021NZKY-069-01). The present study may validate the effectiveness of oral immunonutritional therapy in improving 3-year DFS for GC patients with pathological stage III after total gastrectomy for the first time. The results of this trial will be disseminated in peer-reviewed journals and at scientific conferences. TRIAL REGISTRATION NUMBER: NCT05253716.

Total parenteral nutrition impairs glucose metabolism by modifying the gut microbiome.

Total parenteral nutrition (TPN) can lead to complications, such as glucose metabolism disorders. While TPN is associated with impairments in intestinal function, the gut barrier and mucosal immunity, the relationship between the gut microbiome and TPN-related glucose metabolism disorders remains to be explored. In a cohort of 256 participants with type 2 intestinal failure, we show that parenteral nutrition providing >80% of total energy induces insulin resistance and a higher risk of complications. Using various male mouse models, we demonstrate that changes in Lactobacillaceae and indole-3-acetic acid (IAA) levels underlie these complications. Lactobacillaceae and IAA levels decrease in TPN-treated mice and participants, while their abundances in the latter are negatively correlated with insulin resistance and serum lipopolysaccharide levels. Furthermore, IAA activates the aryl hydrocarbon receptor and increases glucagon-like peptide-1 secretion through upregulation of Gcg expression and increased stem cell differentiation towards L cells. Finally, liraglutide, a glucagon-like peptide-1 receptor agonist, completely prevents TPN-induced glucose metabolism disorders in mice. Thus, TPN induces glucose metabolism disorders by altering the gut microbiota and its metabolites.

Down regulation of NDUFS1 is involved in the progression of parenteral-nutrition-associated liver disease by increasing Oxidative stress.

Parenteral nutrition (PN)-associated liver disease (PNALD) is a common and life-threatening complication of patients receiving PN. However, its definitive pathology remains unclear. Ubiquinone oxidoreductase core subunit S1 (NDUFS1), which is the largest core subunit of mitochondrial complex I, could alter the mitochondrial reactive oxygen species (ROS) formation. The purpose of this study was to investigate the role of NDUFS1 in the pathogenesis of PNALD and its underlying mechanism. We performed hepatic proteomics analysis of PNALD patients, and established a PNALD rat model to verify the role of oxidative stress, NDUFS1, pyrin inflammasome, and IL-1ß in the progression of PNALD. Proteomics analysis revealed the NDUFS1 expression was decreased in PNALD patients, and the differentially espressed proteins were involved in mitochondrial respiratory chain complex Ⅰ. Treatment with MitoQ or overexpression of NDUFS1 can alleviate the progression of PNALD by reducing oxidative stress. The expression of pyrin, caspase-1, and IL-1ß was increased in PN rats. Pharmacological antagonism of pyrin by colchicine can alleviate liver injury and hepatic steatosis. NDUFS1 prevents PNALD pathogenesis by regulating oxidative stress. Pyrin inflammasome and IL-1ß may participate in the process of PNALD development by suppressing the transcription of MTTP and impairing the secretion of VLDL. Oxidative stress reduction may be employed as a strategy in the prevention and treatment of PNALD.