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.

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.

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.

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).

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.

The application value of preoperative fat-free mass index within Global Leadership Initiative on Malnutrition-defined malnutrition criteria for postoperative outcomes in patients with esophagogastric cancer.

OBJECTIVE: The present study aimed to investigate the prognostic value of the preoperative fat-free mass index (FFMI) for postoperative outcomes in patients undergoing esophagogastric cancer surgery and to explore the role of the FFMI in the Global Leadership Initiative on Malnutrition (GLIM) criteria. METHODS: This multicenter retrospective observational study took place in four teaching tertiary hospitals in China from September 2015 to June 2018. Malnutrition was diagnosed following the GLIM criteria. The evaluation of muscle mass (ie, the FFMI) as one of the constituents contained in the GLIM consensus was measured by bioelectrical impedance analysis. According to their FFMI per the GLIM criteria, patients with esophagogastric cancer were divided into a normal-FFMI group and a low-FFMI group. The observation indicators were postoperative complications, length of stay, wound healing time, postoperative antibiotic time, and nutritional status in the two groups. RESULTS: Of the 205 total patients with esophagogastric cancer, 76 (37.1%) were diagnosed with malnutrition. The normal-FFMI group had a significantly lower rate of postoperative complications (43 [33.3%] of 129 patients versus 37 [48.7%] of 76 patients; P = 0.038) and a shorter postoperative length of stay (12.6 ± 3.1 d versus 14.3 ± 3.2 d; P = 0.034), postoperative antibiotic time (5.3 ± 2.9 d versus 6.4 ± 2.1 d; P = 0.031), and wound healing time (10.9 ± 2.5 d versus 11.9 ± 3.1 d; P = 0.005) compared with the low-FFMI group. There were no significant differences between the groups in rates of other clinical outcomes. The body mass index (BMI) and FFMI were generally consistent in the diagnosis of malnutrition based on GLIM criteria (kappa, 0.464; P < 0.001). The linear correlation between BMI and FFMI (correlation coefficient, 0.659; P < 0.001) was moderate in patients with esophagogastric cancer who were at nutritional risk. CONCLUSIONS: The FFMI has an important role in the diagnosis of malnutrition using the GLIM criteria. In this study, a decreased preoperative FFMI was closely associated with postoperative complications in patients with esophagogastric cancer.

Liver PP2A-Cα Protects From Parenteral Nutrition-associated Hepatic Steatosis.

BACKGROUND & AIMS: Parenteral nutrition (PN) is a lifesaving therapy for patients with intestinal failure. Hepatic steatosis is a potentially fatal complication of long-term PN, but the involved pathological mechanisms are incompletely unclarified. Herein, we identify the role of protein phosphatase 2A (PP2A) in the pathogenesis of parenteral nutrition-associated hepatic steatosis (PNAHS). METHODS: Proteomic/phosphoproteomic analyses of liver samples from patients with PNAHS were applied to identify the mechanism of PNAHS. Total parenteral nutrition (TPN) mice model, in vivo, and in vitro experiments were used to assess the effect of PP2A-Cα on liver fatty acid metabolism. RESULTS: Reduced expression of PP2A-Cα (catalytic subunit) enhanced activation of serine/threonine kinase Akt2 and decreased activation of adenosine monophosphate-activated protein kinase (AMPK) were associated with hepatic steatosis in patients with PNAHS. Mice given PN for 14 days developed hepatic steatosis, down-regulation of PP2A-Cα, activation of Akt2, and inhibition of AMPK. Hepatocyte-specific deletion of PP2A-Cα in mice given PN exacerbated Akt2 activation, AMPK inhibition, and hepatic steatosis through an effect on fatty acid degradation, whereas hepatocyte-specific PP2A-Cα overexpression significantly ameliorated hepatic steatosis accompanied with Akt2 suppression and AMPK activation. Additionally, pharmacological activation of Akt2 in mice overexpressing PP2A-Cα led to the aggravation of hepatic steatosis. CONCLUSIONS: Our findings demonstrate that hepatic PP2A-Cα serves as a protective factor of PNAHS due to ameliorating hepatic steatosis and improving liver function. Our study provides a strong rationale that PP2A-Cα may be involved in the pathogenesis of PNAHS.

Poor Pre-operative Nutritional Status Is a Risk Factor of Post-operative Infections in Patients With Gastrointestinal Cancer-A Multicenter Prospective Cohort Study.

Objective: This study aimed to assess the prognostic value of the Nutritional Risk Score 2002 (NRS2002) and patient-generated subjective global assessment (PG-SGA) for post-operative infections in patients with gastric cancer (GC) and colorectal cancer (CRC) who underwent curative surgery. Methods: This prospective study included 1,493 GC patients and 879 CRC patients who underwent curative surgery at 18 hospitals in China between April 2017 and March 2020. The NRS2002 and PG-SGA were performed on the day of admission. The relationship between the nutritional status of patients before surgery and post-surgical incidence of infection was analyzed using univariate and multiple logistic regression analyses. Results: According to NRS2002, the prevalence of nutritional risk was 51.1% in GC patients and 63.9% in CRC patients. According to the PG-SGA, 38.9% of GC patients and 54.2% of CRC patients had malnutrition. Approximately 4.4% of the GC patients and 9.9% of the CRC patients developed infectious complications after surgery. The univariate and multiple logistic regression analyses showed that the risk of infections was significantly higher in GC patients with a high nutritional risk score (NRS2002 ≥5) than in those with a low score (NRS2002 <3), and the PG-SGA score was identified as a predictor of post-operative infection complications of CRC. Conclusion: The pre-operative nutritional status of patients with GC or CRC has an impact on post-operative infection occurrence. NRS2002 ≥5 was a risk factor for post-operative infection in patients with GC, and the PG-SGA B/C was a predictor of infections in patients with CRC.

Validation of the GLIM criteria for diagnosis of malnutrition and quality of life in patients with inflammatory bowel disease: A multicenter, prospective, observational study.

BACKGROUND & AIMS: The Global Leadership Initiative on Malnutrition (GLIM) has recently been proposed as a consensus criterion for identifying malnutrition. However, data on the application of GLIM criteria in patients with inflammatory bowel disease (IBD) are limited. Therefore, this study aimed to explore the validity of this neoteric criterion for identifying malnutrition and investigate the association between malnutrition and quality of life (QoL) in patients with IBD. METHODS: This multicenter, prospective, observational study assessed hospitalized patients with IBD at four general hospitals. Nutritional status was evaluated using criteria from the World Health Organization (WHO) related body mass index (BMI) cut-off value, Subjective Global Assessment (SGA), European Society for Clinical Nutrition and Metabolism (ESPEN) criteria of malnutrition in 2015, and GLIM criteria. Kappa (K) values were calculated to determine interrater validity and consistency among different prevalence of malnutrition. Patients' QoL was assessed by the Inflammatory Bowel Disease Questionnaire (IBDQ). RESULTS: A total of 238 hospitalized patients with IBD were enrolled, with a mean age of 38.5 ± 14.0 years, 68.5% of them were male, and 177 with Crohn's disease (CD). Among all patients, 39.5% were underweight (BMI < 18.5 kg/m2), and the prevalence of malnutrition was 66.0%, 47.5%, and 60.1% according to SGA, ESPEN, and GLIM criteria, respectively. Moreover, the prevalence of malnutrition was significantly higher among patients with CD than those with ulcerative colitis (UC), according to GLIM criteria (69.5% vs. 32.8%, p < 0.001). The GLIM criteria showed a substantial concordance with ESPEN criteria (K = 0.67, 95% confidence interval [CI] 0.58-0.76, p < 0.001), and a fair concordance with the SGA (K = 0.57, 95% CI 0.46-0.68, p < 0.001) and WHO criteria (K = 0.52, 95% CI 0.43-0.62, p < 0.001). An impairment in the nutritional status was accompanied by a progressive reduction in the patients' QoL. CONCLUSIONS: The prevalence of malnutrition is high in patients with IBD. The GLIM criteria may be an appropriate and effective tool to identify malnutrition in the IBD populations due to its substantial concordance with ESPEN and a fair concordance with SGA and WHO-related BMI. GLIM-defined malnutrition showed an enormous adverse impact on patients' QoL.

Effect of Early vs Late Supplemental Parenteral Nutrition in Patients Undergoing Abdominal Surgery: A Randomized Clinical Trial.

Importance: The effect of and optimal timing for initiating supplemental parenteral nutrition (SPN) remain unclear after major abdominal surgery for patients in whom energy targets cannot be met by enteral nutrition (EN) alone. Objective: To examine the effect of early supplemental parenteral nutrition (E-SPN) (day 3 after surgery) or late supplemental parenteral nutrition (L-SPN) (day 8 after surgery) on the incidence of nosocomial infections in patients undergoing major abdominal surgery who are at high nutritional risk and have poor tolerance to EN. Design, Setting, and Participants: A multicenter randomized clinical trial was conducted from April 1, 2017, to December 31, 2018, in the general surgery department of 11 tertiary hospitals in China. Participants were those undergoing major abdominal surgery with high nutritional risk and poor tolerance to EN (≤30% of energy targets from EN on postoperative day 2, calculated as 25 and 30 kcal/kg of ideal body weight daily for women and men, respectively) and an expected postoperative hospital stay longer than 7 days. Data analysis was performed from February 1 to October 31, 2020. Interventions: Random allocation to E-SPN (starting on day 3 after surgery) or L-SPN (starting on day 8 after surgery). Main Outcomes and Measures: The primary outcome was the incidence of nosocomial infections between postoperative day 3 and hospital discharge. Results: A total of 230 patients (mean [SD] age, 60.1 [11.2] years; 140 men [61.1%]; all patients were of Han race and Asian ethnicity) were randomized (115 to the E-SPN group and 115 to the L-SPN group). One patient in the L-SPN group withdrew informed consent before the intervention. The E-SPN group received more mean (SD) energy delivery between days 3 and 7 compared with the L-SPN group (26.5 [7.4] vs 15.1 [4.8] kcal/kg daily; P < .001). The E-SPN group had significantly fewer nosocomial infections compared with the L-SPN group (10/115 [8.7%] vs 21/114 [18.4%]; risk difference, 9.7%; 95% CI, 0.9%-18.5%; P = .04). No significant differences were found between the E-SPN group and the L-SPN group in the mean (SD) number of noninfectious complications (31/115 [27.0%] vs 38/114 [33.3%]; risk difference, 6.4%; 95% CI, -5.5% to 18.2%; P = .32), total adverse events (75/115 [65.2%] vs 82/114 [71.9%]; risk difference, 6.7%; 95% CI, -5.3% to 18.7%; P = .32), and rates of other secondary outcomes. A significant difference was found in the mean (SD) number of therapeutic antibiotic days between the E-SPN group and the L-SPN group (6.0 [0.8] vs 7.0 [1.1] days; mean difference, 1.0 days; 95% CI, 0.2-1.9 days; P = .01). Conclusion and Relevance: In this randomized clinical trial, E-SPN was associated with reduced nosocomial infections in patients undergoing abdominal surgery and seems to be a favorable strategy for patients with high nutritional risk and poor tolerance to EN after major abdominal surgery. Trial Registration: ClinicalTrials.gov Identifier: NCT03115957.

Immediate vs. gradual advancement to goal of enteral nutrition after elective abdominal surgery: A multicenter non-inferiority randomized trial.

BACKGROUND & AIMS: The strategy of increasing the postoperative enteral nutrition dose to the target goal has not yet been clarified. This study aimed to determine whether an immediate goal-dose enteral nutrition (IGEN) strategy is non-inferior to a gradual goal-dose enteral nutrition (GGEN) strategy in reducing infections in patients undergoing abdominal surgery involving the organs of the digestive system. METHODS: This randomized controlled trial enrolled postoperative patients with nutritional risk screening 2002 scores ≥3 from 11 Chinese hospitals. Energy targets were calculated as 25 kcal/kg and 30 kcal/kg of ideal body weight for women and men, respectively. Patients were randomly assigned 1:1 to IGEN or GGEN group after enteral tolerance was confirmed (30% of the target on day 2). The IGEN group immediately started receiving 100% of the caloric requirements on day 3, while the GGEN group received 40% progressing to 80% of target on day 7. The primary endpoint was the infection rate until discharge, based on the intention-to-treat population. RESULTS: A total of 411 patients were enrolled and randomized to the IGEN and GGEN groups, and five patients did not receive the allocated intervention. A total of 406 patients were included in the primary analysis, with 199 and 207 in the IGEN and GGEN groups, respectively. Infection was observed in 17/199 (8.5%) in the IGEN group and 19/207 (9.2%) in the GGEN group, respectively (difference, -0.6%; [95% confidence interval (CI), -6.2%-4.9%]; P = 0.009 for non-inferiority test). There were significantly more gastrointestinal intolerance events with IGEN than with GGEN (58/199 [29.1%] vs. 32/207 [15.5%], P < 0.001). All other secondary endpoints were non-significant. CONCLUSIONS: Among postoperative patients at nutritional risk, IGEN was non-inferior to GGEN in regards to infectious complications. IGEN was associated with more gastrointestinal intolerance events. It showed that IGEN cannot be considered to be clinically directive. ClinicalTrials.gov (#NCT03117348).

Long-Term Outcome in Gastric Cancer Patients with Different Body Composition Score Assessed via Computed Tomography.

BACKGROUND: The purpose of this study was to assess the body composition score (BCS) impact on 3-year survival after radical gastrectomy in patients with gastric cancer. METHODS: This retrospective study included patients with gastric cancer from September 2015 to June 2017. The patients were divided into three groups: BCS0 (having normal skeletal muscle or adipose mass), BCS1 (having low skeletal muscle mass only), and BCS2 (having low skeletal muscle and adipose mass) according to their third lumbar vertebra skeletal muscle index and fat index calculated using abdominal computed tomography. The clinicopathological indicators, postoperative complications, 3-year over survival (OS) rate after radical gastrectomy, and cause of death among the three groups were compared. RESULTS: A total of 187 patients were enrolled in the study, in which 102 patients (54.6%) had BCS0, 76 (40.6%) had BCS1 and 9 (4.8%) had BCS2. There was no significant difference in postoperative complications among the groups. 3-year OS was significantly shortened with each 1-score increase in BCS (Log-rank p < 0.001). Multivariate Cox regression analyses showed that no neoadjuvant chemotherapy, tumor stage III, BCS1, and BCS2 were independent prognostic factors for 3-year OS after radical gastrectomy. The main cause of death was cancer-related. CONCLUSION: We demonstrated that BCS1 and BCS2 were strongly associated with poor 3-year survival for patients with gastric cancer who underwent radical gastrectomy, suggesting that special attention may be required for nutritional support while determining therapeutic strategies.

Autophagy suppression plays a role in parenteral nutrition-associated lung injury.

BACKGROUND & AIMS: The long-term usage of parenteral nutrition (PN) is associated with the increased incidence of pneumonia. Few studies have focused on the pathogenesis of PN-associated lung injury (PNLI). Previous studies have found that autophagy suppression may be an important mechanism for PN-associated complications. The present study aimed to investigate the effect of PN on lung barrier impairment and its association with autophagy. METHODS: We retrospectively identified intestinal failure patients admitted to a clinical nutrition service center to determine the morbidity of hospital-acquired pneumonia (HAP) and its association with PN. In animal studies, we established the PNLI mouse model to measure severity of lung injury, lung barrier, pulmonary microbiota in bronchoalveolar fluid (BALF), levels of autophagy and apoptosis, and the inflammatory signaling pathway. RESULT: Among the 259 patients, 37 (14.3%) patients developed HAP. Multivariate analysis revealed that prolonged PN was an independent predictor for HAP. In animal studies, we found that PN impaired the lung barrier and disturbed pulmonary microbiota homeostasis. The abundance of Actinomycetes and Firmicutes phyla in BALF were significantly increased, while the Bacteroidetes phylum decreased. Bacterial translocations in the lung were observed by fluorescence in situ hybridization. PN caused autophagy suppression and activated the apoptosis level and inflammatory HMGB1/RAGE/NF-kB signaling pathway. The intervention of exogenous rapamycin can attenuate the impairment of the lung barrier, reduce apoptosis and inhibit inflammatory signaling by upregulation of autophagy. CONCLUSION: PN had a damaging effect on the lung barrier, disturbed pulmonary microbiota homeostasis, and induced bacterial translocation. Autophagy suppression might be a crucial mechanism in inducing PNLI.