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New Insights Into Intestinal Failure-Associated Liver Disease in Children.
Khalaf, RT, Sokol, RJ
Hepatology (Baltimore, Md.). 2020;(4):1486-1498
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Development of intestinal failure-associated liver disease (IFALD) is a common complication of long-term parenteral nutrition (PN) in children and adults. The molecular and cellular mechanisms and the phases of IFALD are now being delineated. Components of PN lipid emulsions, including plant sterols, interact with hepatic innate immune activation promoted by products of gut bacterial overgrowth/dysbiosis and altered intestinal barrier function (gut-liver axis) and by episodes of sepsis to cause cholestasis and IFALD. New therapeutic strategies, including modifications of intravenous lipid emulsions to reduce pro-inflammatory fatty acids and plant sterol content, can lower the risk of IFALD, reverse cholestasis, and reduce complications, although the significance of persisting hepatic fibrosis is unknown. This review will provide an update on advances in the pathogenesis of IFALD, newer therapeutic and preventative strategies, and challenges that confront managing patients with IFALD.
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Role of heat shock protein and cytokine expression as markers of clinical outcomes with glutamine-supplemented parenteral nutrition in surgical ICU patients.
Wischmeyer, PE, Mintz-Cole, RA, Baird, CH, Easley, KA, May, AK, Sax, HC, Kudsk, KA, Hao, L, Tran, PH, Jones, DP, et al
Clinical nutrition (Edinburgh, Scotland). 2020;(2):563-573
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BACKGROUND Nutrients, such as glutamine (GLN), have been shown to effect levels of a family of protective proteins termed heat shock proteins (HSPs) in experimental and clinical critical illness. HSPs are believed to serve as extracellular inflammatory messengers and intracellular cytoprotective molecules. Extracellular HSP70 (eHSP70) has been termed a chaperokine due to ability to modulate the immune response. Altered levels of eHSP70 are associated with various disease states. Larger clinical trial data on GLN effect on eHSP expression and eHSP70's association with inflammatory mediators and clinical outcomes in critical illness are limited. OBJECTIVE Explore effect of longitudinal change in serum eHSP70, eHSP27 and inflammatory cytokine levels on clinical outcomes such as pneumonia and mortality in adult surgical intensive care unit (SICU) patients. Further, evaluate effect of parenteral nutrition (PN) supplemented with GLN (GLN-PN) versus GLN-free, standard PN (STD-PN) on serum eHSP70 and eHSP27 concentrations. METHODS Secondary observational analysis of a multicenter clinical trial in 150 adults after cardiac, vascular, or gastrointestinal surgery requiring PN support and SICU care conducted at five academic medical centers. Patients received isocaloric, isonitrogenous PN, with or without GLN dipeptide. Serum eHSP70 and eHSP27, interleukin-6 (IL-6), and 8 (IL-8) concentrations were analyzed in patient serum at baseline (prior to study PN) and over 28 days of follow up. RESULTS eHSP70 declined over time in survivors during 28 days follow-up, but non-survivors had significantly higher eHSP70 concentrations compared to survivors. In patients developing pneumonia, eHSP70, eHSP27, IL-8, and IL-6 were significantly elevated. Adjusted relative risk for hospital mortality was reduced 75% (RR = 0.25, p = 0.001) for SICU patients with a faster decline in eHSP70. The area under the receiver operating characteristic curve was 0.85 (95% CI: 0.76 to 0.94) for the final model suggesting excellent discrimination between SICU survivors and non-survivors. GLN-PN did not alter eHSP70 or eHSP27 serum concentrations over time compared to STD-PN. CONCLUSION Our results suggest that serum HSP70 concentration may be an important marker for severity of illness and likelihood of recovery in the SICU. GLN-supplemented-PN did not increase eHSP70.
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Effects of parenteral ω-3 fatty acid supplementation in postoperative gastrointestinal cancer on immune function and length of hospital stay: a systematic review and meta-analysis.
Bai, H, Li, Z, Meng, Y, Yu, Y, Zhang, H, Shen, D, Chen, L
Asia Pacific journal of clinical nutrition. 2018;(1):121-128
Abstract
BACKGROUND AND OBJECTIVES Omega-3 fatty acids are widely used in nutritional support. However, whether parenteral supplementation with ω-3 fatty acids is effective for gastrointestinal cancer patients remains uncertain. This study assessed the effects of this form of parenteral nutrition on immune function and clinical outcomes in postoperative gastrointestinal cancer patients. METHODS AND STUDY DESIGN We searched Medline, Embase, Scopus, and the reference lists of selected studies to identify randomized controlled trials that compared ω-3 fatty acids with a control, and that included immune indices, infectious complications, or length of hospital stay in the final outcomes. The odds ratio and weighted mean difference with 95% confidence intervals were calculated and the I2 statistic was used to assess heterogeneity. RESULTS Seven trials with a total of 457 participants were included in the meta-analysis. Five pooled trials with 373 participants indicated that the incidence of infectious complications was significantly different between the intervention and control groups (odds ratio: 0.36; 95% confidence interval: 0.18, 0.74, p<0.05). Five trials involving 385 participants indicated that parenteral ω-3 fatty acid supplementation significantly shortened the length of hospital stay (weighted mean difference: -2.29, 95% confidence interval: -3.64, -0.93; p<0.05). Meta-analysis also indicated that ω-3 fatty acids increased the level of CD4+ and CD4+/CD8+ ratio. CONCLUSIONS The results of this study suggest that parenteral ω-3 fatty acid supplementation is beneficial for gastrointestinal cancer patients, and is accompanied by improved postoperative immune function and satisfactory clinical outcomes.
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The intensive care medicine research agenda in nutrition and metabolism.
Arabi, YM, Casaer, MP, Chapman, M, Heyland, DK, Ichai, C, Marik, PE, Martindale, RG, McClave, SA, Preiser, JC, Reignier, J, et al
Intensive care medicine. 2017;(9):1239-1256
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PURPOSE The objectives of this review are to summarize the current practices and major recent advances in critical care nutrition and metabolism, review common beliefs that have been contradicted by recent trials, highlight key remaining areas of uncertainty, and suggest recommendations for the top 10 studies/trials to be done in the next 10 years. METHODS Recent literature was reviewed and developments and knowledge gaps were summarized. The panel identified candidate topics for future trials in critical care nutrition and metabolism. Then, members of the panel rated each one of the topics using a grading system (0-4). Potential studies were ranked on the basis of average score. RESULTS Recent randomized controlled trials (RCTs) have challenged several concepts, including the notion that energy expenditure must be met universally in all critically ill patients during the acute phase of critical illness, the routine monitoring of gastric residual volume, and the value of immune-modulating nutrition. The optimal protein dose combined with standardized active and passive mobilization during the acute phase and post-acute phase of critical illness were the top ranked studies for the next 10 years. Nutritional assessment, nutritional strategies in critically obese patients, and the effects of continuous versus intermittent enteral nutrition were also among the highest-ranking studies. CONCLUSIONS Priorities for clinical research in the field of nutritional management of critically ill patients were suggested, with the prospect that different nutritional interventions targeted to the appropriate patient population will be examined for their effect on facilitating recovery and improving survival in adequately powered and properly designed studies, probably in conjunction with physical activity.
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Perioperative immunonutrition in surgical cancer patients: a summary of a decade of research.
Klek, S, Szybinski, P, Szczepanek, K
World journal of surgery. 2014;(4):803-12
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BACKGROUND Immunonutrition is assumed to enhance immune system function. In surgical patients, it is supposed to reduce postoperative complications. However, results of recent clinical trials have been puzzling and have not supported this theory. AIM: The aim of our study was to evaluate the value of enteral and parenteral postoperative immunonutrition. METHODS After initial evaluation of 969 patients, the intent-to-treat analysis included 776 patients (female 407, male 466, mean age 61.1 years) undergoing gastric or pancreatic resections between 2001 and 2009. All patients were randomly assigned after surgery to one of the following groups: standard enteral nutrition (SEN), immunomodulating enteral nutrition (IMEN), standard parenteral nutrition (SPN), or immunomodulating parenteral nutrition (IMPN). All malnourished patients received preoperative parenteral nutrition. Number and type of postoperative complications, length of hospitalization (length of stay [LOS]), and vital organ function were assessed. RESULTS No statistically significant differences were observed in well-nourished patients, during either enteral or parenteral intervention, independent of the type of intervention (standard or immunomodulating). However, analysis of the malnourished group revealed the positive impact of enteral immunonutrition on reduction of postoperative complications (28.3 vs. 39.2 %, respectively; p = 0.043) and LOS (17.1 and 13.1 days, respectively; p < 0.05) compared with a standard enteral diet. The cross-analysis of SEN, IMEN, SPN, and IMPN was insignificant. CONCLUSIONS The type of postoperative nutrition was of no importance in well-nourished patients. However, in malnourished patients, enteral immunonutrition helped to improve treatment outcome. These findings suggest its use as a method of choice during the postoperative period.
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A double-blind, randomized clinical trial comparing soybean oil-based versus olive oil-based lipid emulsions in adult medical-surgical intensive care unit patients requiring parenteral nutrition.
Umpierrez, GE, Spiegelman, R, Zhao, V, Smiley, DD, Pinzon, I, Griffith, DP, Peng, L, Morris, T, Luo, M, Garcia, H, et al
Critical care medicine. 2012;(6):1792-8
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OBJECTIVE Parenteral nutrition has been associated with metabolic and infectious complications in intensive care unit patients. The underlying mechanism for the high risk of complications is not known but may relate to the proinflammatory effects of soybean oil-based lipid emulsions, the only Food and Drug Administration-approved lipid formulation for clinical use. DESIGN Prospective, double-blind, randomized, controlled trial. SETTING Medical-surgical intensive care units from a major urban teaching hospital and a tertiary referral university hospital. PATIENTS Adult medical-surgical intensive care unit patients. INTERVENTION Parenteral nutrition containing soybean oil-based (Intralipid) or olive oil-based (ClinOleic) lipid emulsions. MEASUREMENTS Differences in hospital clinical outcomes (nosocomial infections and noninfectious complications), hospital length of stay, glycemic control, inflammatory and oxidative stress markers, and granulocyte and monocyte functions between study groups. RESULTS A total of 100 patients were randomized to either soybean oil-based parenteral nutrition or olive oil-based parenteral nutrition for up to 28 days. A total of 49 patients received soybean oil-based parenteral nutrition (age 51 ± 15 yrs, body mass index 27 ± 6 kg/m2, and Acute Physiology and Chronic Health Evaluation II score 15.5 ± 7 [±SD]), and a total of 51 patients received olive oil-based lipid emulsion in parenteral nutrition (age 46 ± 19 yrs, body mass index 27 ± 8 kg/m2, and Acute Physiology and Chronic Health Evaluation II score 15.1 ± 6 [±SD]) for a mean duration of 12.9 ± 8 days. The mean hospital blood glucose concentration during parenteral nutrition was 129 ± 14 mg/dL, without differences between groups. Patients treated with soybean oil-based and olive oil-based parenteral nutrition had a similar length of stay (47 ± 47 days and 41 ± 36 days, p = .49), mortality (16.3% and 9.8%, p = .38), nosocomial infections (43% vs. 57%, p = .16), and acute renal failure (26% vs. 18%, p = .34). In addition, there were no differences in inflammatory and oxidative stress markers or in granulocyte and monocyte functions between groups. CONCLUSION The administration of parenteral nutrition containing soybean oil-based and olive oil-based lipid emulsion resulted in similar rates of infectious and noninfectious complications and no differences in glycemic control, inflammatory and oxidative stress markers, and immune function in critically ill adults.
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Continuous enteral and parenteral feeding each reduces heart rate variability but differentially influences monocyte gene expression in humans.
Gale, SC, Shanker, BA, Coyle, SM, Macor, MA, Choi, CW, Calvano, SE, Corbett, SA, Lowry, SF
Shock (Augusta, Ga.). 2012;(3):255-61
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Enteral (EN) or parenteral (PN) nutrition is used to support critically ill patients until oral feeding resumes. Enteral nutrition is assumed preferable to PN, but the differential influence on immune function is not well defined. Autonomic nervous activity is known to influence innate immune responses, and we hypothesized that EN and PN could influence both autonomic signaling and gene activation in peripheral blood monocytes (PBMs). Ten subjects (aged 18-36 years) received continuous EN or PN for 72 h. Peripheral blood monocytes were isolated from whole blood before and after continuous feeding and were analyzed for gene expression using a microarray platform. Gene expression after feeding was compared from baseline and between groups. To measure autonomic outflow, subjects also underwent heart rate variability (HRV) monitoring during feeding. Time and frequency domain HRV data were compared between groups and five orally fed subjects for changes from baseline and changes over time. During continuous EN and PN, subjects exhibited declines in both time and frequency domain HRV parameters compared with baseline and with PO subjects, indicating a loss of vagal/parasympathetic tone. However, PN feeding had a much greater influence on PBM gene expression compared with baseline than EN, including genes important to innate immunity. Continuous EN and PN are both associated with decreasing vagal tone over time, yet contribute differently to PBM gene expression, in humans. These preliminary findings support assumptions that PN imposes a systemic inflammatory risk but also imply that continuous feeding, independent of route, may impart additional risk through different mechanisms.