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.

Iron overload is related to muscle wasting in patients with cachexia of gastric cancer: using quantitative proteome analysis.

The incidence of gastric cancer cachexia is high and the clinical management is poor, so the study aimed to clarify the mechanism of muscle wasting to better screen patients with gastric cancer cachexia. Gastric cancer patients undergoing radical gastrectomy were divided into cachexia with sarcopenia (CS, n = 13) and normal (N, n = 10) two groups. The possible mechanism of skeletal muscle reduction was explored through Tandem Mass Tag (TMT) technique, Perls staining, Western blot analysis and measurement of oxidative stress indicators. The preoperative weight, weight loss, body mass index, calorie intake and skeletal muscle index values of the CS group were significantly lower than those of the N group (P < 0.05). We identified 114 differentially expressed proteins (DEP) in the muscles of two groups using TMT analysis. Bioinformatics analysis of DEP revealed that ferritin, iron and oxidative stress may be related to skeletal muscle consumption. Following Perls staining and measurement iron concentration in skeletal muscles, we found that the iron in the muscles of the CS group was significantly increased, and at the same time, western blot analysis showed that the expression of ferritin in the CS group was significantly increased and regulated by hepcidin-ferroportin axis. Finally, the CS group showed increased oxidative stress and weakened antioxidant stress systems in the muscles compared with the N group when oxidative stress indicators were analyzed. In conclusion, iron overload may be related to muscle loss in patients with gastric cancer cachexia. Gastric cancer patients with elevated ferritin are more likely to have muscle wasting.

Differential Metabolomic Analysis of Liver Tissues from Rat Models of Parenteral Nutrition-Associated Liver Disease.

Parenteral nutrition (PN) is a life-saving therapy for patients with intestinal failure, but parenteral nutrition-associated liver disease (PNALD) limits its long-term use. The present study is aimed at determining which pathways are altered most notably in a rat model of PNALD. We randomly assigned male Sprague-Dawley (SD) rats into two different groups, whereby they received either enteral nutrition (EN) or PN. Liver tissues were harvested from all rats 7 days later for metabolomic profiling. The composition of primary conjugated bile acids was altered, the synthesis of polyunsaturated fatty acids was reduced, the conversion of pyruvate to acetyl-CoA was blocked, and the synthesis of phosphatidylcholine was inhibited in rats with PNALD. Riboflavin, which is involved in the electron transfer process in the mitochondrial electron transport chain, was remarkably decreased in PNALD rats. A deficiency of polyunsaturated fatty acids, riboflavin, choline, and taurine might be involved in the progression of PNALD. The implications of these findings for the field of medicine are that supplementation with polyunsaturated fatty acids, riboflavin, choline, and taurine might have potential as therapeutic strategies for PNALD and also shed light on the mechanisms of PNALD.

Prolonged Parenteral Nutrition Is One of the Most Significant Risk Factors for Nosocomial Infections in Adult Patients With Intestinal Failure.

BACKGROUND: Intestinal failure (IF) and its management are associated with an increased likelihood of infectious complications. This study aimed to evaluate the prevalence and potential risk factors for nosocomial infections (NIs) in hospitalized adult patients with IF. METHODS: In total, 259 eligible patients with IF admitted to a single clinical nutrition center in a tertiary referral hospital from January 1, 2012, to January 1, 2019, were retrospectively identified. NIs were defined according to the 2008 Centers for Disease Control and Prevention criteria. Univariate and multivariate analyses were performed to identify independent risk factors for NIs. RESULTS: The mean age of the study population was 47.0 ± 17.7 years, and 158 (61.0%) were men. The mean body mass index was 16.2 ± 2.9 kg/m2 , and 219 (84.6%) were diagnosed with malnutrition. The prevalence of NIs was 25.5% (113 NIs in 66 patients). The most common NIs were pneumonia (14.3%), bacteremia of unknown origin (13.5%), catheter-related bloodstream infection (5.0%), lower respiratory tract infection (5.0%), surgical site infection (3.9%), and urinary tract infection (1.9%). Multivariate analysis revealed that decreased serum albumin level (odds ratio [OR], 0.884; 95% CI, 0.883-0.978, P < .05), presence of gallbladder stones or cholestasis (OR, 3.144; 95% CI, 1.044-9.464; P < .05), and prolonged parenteral nutrition (PN) use (OR, 1.072; 95% CI, 1.039-1.105; P < .001) were independent predictors for NIs. CONCLUSIONS: NIs remain prevalent in hospitalized adult patients with IF. Prolonged PN use was one of the most significant predictors for NIs.

Risk Factors for Nephrolithiasis in Adults with Short Bowel Syndrome.

INTRODUCTION: Patients with short bowel syndrome (SBS) commonly develop nephrolithiasis. However, the risk factors for nephrolithiasis in patients with SBS remain unclarified. The present study aimed to identify the risk factors for nephrolithiasis in adults with SBS. METHODS: All eligible adults diagnosed with SBS and admitted to a tertiary referral center from December 2008 to 2018 were retrospectively identified from a prospectively maintained database. Patients' demographic and clinical characteristics were analyzed using univariate and multivariate analyses to identify the risk factors for nephrolithiasis. RESULTS: Of 231 adults with SBS, 42 (18.2%) developed nephrolithiasis. The mean age was 46.4 ± 17.8 years, the mean body mass index was 18.2 ± 3.8 kg/m2, and median duration of SBS was 11 months (range 2-324 months). Multivariate binary logistic regression analysis revealed that the independent risk factors for nephrolithiasis in adults with SBS were jejuno-ileal anastomosis and colon-in-continuity (OR 4.335; 95% CI 1.175-16.002; p = 0.028), prolonged duration of SBS (OR 1.008; 95% CI 1.002-1.014; p = 0.010), and increased serum creatinine concentration (OR 1.005; 95% CI 1.001-1.009; p = 0.012). CONCLUSIONS: Nephrolithiasis is common in adults with SBS. As nephrolithiasis can have adverse clinical consequences, patients with SBS should be closely monitored, and prophylactic interventions should be considered.