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2.
Ann Palliat Med ; 12(5): 1072-1080, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37691334

ABSTRACT

The use of total parenteral nutrition (TPN) in patients with gastrointestinal cancers is a well-established practice, yet there is substantial variability in its use across institutions. Decision-making around the initiation of TPN is complex. An interdisciplinary team can help identify patient factors and clinical situations that influence whether a patient is likely to benefit from parenteral nutrition. We present the case of a woman with a gastrointestinal cancer who benefited from the initiation of TPN as a bridge therapy to further cancer treatment. This case highlights the importance of establishing a plan for nutrition with specific goals in mind, such as optimizing patients for more cancer-directed therapy. Although patients with gastrointestinal cancers may be candidates for TPN, many patient-specific factors, such as functional status and opportunities for future treatments, must be considered prior to the initiation of parenteral nutrition. An interdisciplinary approach should be used to make recommendations based on patient goals, with a focus on patient and cancer characteristics that are associated with positive outcomes after initiation of TPN. These characteristics include functional status, nutritional status, degree of symptom control, and ability to safely administer nutrition. It is important to continually assess whether parenteral nutrition is beneficial in respect to a patient's preferences and prognosis.


Subject(s)
Gastrointestinal Neoplasms , Parenteral Nutrition, Total , Female , Humans , Gastrointestinal Neoplasms/therapy , Nutritional Status , Parenteral Nutrition, Total/methods
3.
Ann Med ; 54(1): 1701-1713, 2022 12.
Article in English | MEDLINE | ID: mdl-35706376

ABSTRACT

BACKGROUND: Total Parenteral Nutrition (TPN) provides lifesaving nutritional support to patients unable to maintain regular enteral nutrition (EN). Unfortunately, cholestasis is a significant side effect affecting 20-40% of paediatric patients. While the aetiology of TPN-associated injury remains ill-defined, an altered enterohepatic circulation in the absence of gut luminal nutrient content during TPN results in major gut microbial clonal shifts, resulting in metabolic endotoxemia and systemic inflammation driving liver injury and cholestasis. HYPOTHESIS: To interrogate the role of gut microbiota, using our novel ambulatory TPN piglet model, we hypothesized that clonal reduction of bacteria in Firmicutes phylum (predominant in EN) and an increase in pathogenic Gram-negative bacteria during TPN correlates with an increase in serum lipopolysaccharide and systemic inflammatory cytokines, driving liver injury. METHODS: Upon institutional approval, 16 animals were allocated to receive either TPN (n = 7) or EN only (n = 9). The TPN group was subdivided into a low systemic inflammation (TPN-LSI) and high systemic inflammation (TPN-HSI) based on the level of serum lipopolysaccharide. Culture-independent identification of faecal bacterial populations was determined by 16S rRNA. RESULTS: Piglets on TPN, in the TPN-HSI group, noted a loss of enterocyte protective Firmicutes bacteria and clonal proliferation of potent inflammatory and lipopolysaccharide containing pathogens: Fusobacterium, Bacteroidetes and Campylobacter compared to EN animals. Within the TPN group, the proportion of Firmicutes phylum correlated with lower portal lipopolysaccharide levels (r = -0.89). The TPN-LSI had a significantly lower level of serum bile acids compared to the TPN-HSI group (7.3 vs. 60.4 mg/dL; p = .018), increased day 14 weight (5.67 vs. 5.07 kg; p = .017) as well as a 13.7-fold decrease in serum conjugated bilirubin. CONCLUSION: We demonstrate a novel relationship between the gut microbiota and systemic inflammation in a TPN animal model. Pertinently, the degree of gut dysbiosis correlated with the severity of systemic inflammation. This study underscores the role of gut microbiota in driving liver injury mechanisms during TPN and supports a paradigm change in therapeutic targeting of the gut microbiota to mitigate TPN-related injury. KEY MESSAGESThis study identified a differential link between gut microbiota and inflammation-the higher the dysbiosis, the worse the systemic inflammatory markers.Higher levels of Firmicutes species correlated with reduced inflammation.


Subject(s)
Cholestasis , Dysbiosis , Animals , Child , Cholestasis/etiology , Dysbiosis/complications , Firmicutes , Humans , Inflammation/complications , Lipopolysaccharides , Liver , Parenteral Nutrition/adverse effects , Parenteral Nutrition, Total/adverse effects , Parenteral Nutrition, Total/methods , RNA, Ribosomal, 16S , Swine
4.
Medicine (Baltimore) ; 101(1): e28434, 2022 Jan 07.
Article in English | MEDLINE | ID: mdl-35029889

ABSTRACT

RATIONALE: Fetal brain hemorrhage is rare. It is caused mainly by maternal trauma or fetal coagulation disorder, but in some cases, vitamin K deficiency may be the cause. PATIENT CONCERNS: We describe the case of a pregnant woman with bowel obstruction who was susceptible to vitamin K deficiency due to oral diet restriction, decreased intestinal absorption, and limited intravenous vitamin K supplementation. DIAGNOSIS: After 18 days of intermittent total parenteral nutrition, acute onset of severe fetal brain hemorrhage developed. INTERVENTIONS: After acute onset of fetal brain hemorrhage, the patient underwent an emergency cesarean section at 25 + 3 weeks of gestation due to fetal non-reassuring fetal monitoring. OUTCOMES: The Apgar score at birth was 0/0, and despite cardiopulmonary resuscitation, neonatal death was confirmed. After the baby was delivered, we checked the maternal upper abdominal cavity and found a massive adhesion in the small bowel to the abdominal wall near the liver and stomach with an adhesion band. The adhesion band, presumably a complication of previous hepatobiliary surgery, appeared to have caused small bowel obstruction. Adhesiolysis between the small bowel and abdominal wall was performed. LESSONS: This case demonstrates that even relatively short-term total parenteral nutrition can cause severe fetal brain hemorrhage. Vitamin K supplementation is required for mothers who are expected to be vitamin K deficient, especially if they are on total parenteral nutrition for more than 3 weeks.


Subject(s)
Intestinal Obstruction/etiology , Intracranial Hemorrhages/etiology , Parenteral Nutrition, Total/adverse effects , Vitamin K Deficiency/complications , Adult , Cesarean Section/adverse effects , Female , Fetal Diseases , Humans , Infant, Newborn , Parenteral Nutrition, Total/methods , Pregnancy , Vitamin K/administration & dosage
5.
Eur J Surg Oncol ; 48(1): 204-210, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34462143

ABSTRACT

AIM: This study was aimed to analyze the incidence, risk factors, and management of chylous ascites (CA) after radical D3 resection for colorectal cancer, and to construct a predicting nomogram for prolonged resolution of CA. METHOD: Consecutive colorectal cancer patients who underwent radical D3 resection were included. Logistic analysis was used to identify risk factors of postoperative CA, as well as prolonged CA resolution. A predictive nomogram for prolonged resolution of CA was developed and validated internally. RESULTS: Among 7167 patients included, 277 (3.8%) patients developed CA. Logistic regression analysis demonstrated that laparoscopic operation (OR 1.507; P = 0.017) and tumors fed by the superior mesenteric artery (SMA, OR 2.456; P < 0.001) were independent risk factors of postoperative CA following radical D3 surgery for colorectal cancer. Open operation (OR 0.422; P = 0.027), drainage output on the first day of treatment (OR 1.004; P = 0.016), time to oral intake (OR 1.273; P = 0.042), and time to onset (OR 1.231; P = 0.024) were independently associated with prolonged resolution of postoperative CA (≥7 days). A predictive nomogram for prolonged CA resolution was developed with a C-index of 0.725. CONCLUSION: The incidence of CA after radical D3 surgery of colorectal cancer was 3.8%. Open operation, drainage output on the first day of treatment, time to oral intake, and time to onset were independently associated with prolonged resolution of postoperative CA. A nomogram may assist in tailored treatment decision-making and counseling patient with treatment strategies.


Subject(s)
Adenocarcinoma/surgery , Chylous Ascites/epidemiology , Colectomy , Colorectal Neoplasms/surgery , Lymph Node Excision , Postoperative Complications/epidemiology , Aged , Chylous Ascites/physiopathology , Chylous Ascites/therapy , Dietary Fats/therapeutic use , Female , Hospitals, High-Volume , Humans , Incidence , Male , Middle Aged , Parenteral Nutrition, Total/methods , Postoperative Complications/physiopathology , Postoperative Complications/therapy , Risk Assessment , Somatostatin/therapeutic use
6.
Anticancer Res ; 41(12): 6237-6246, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34848479

ABSTRACT

BACKGROUND/AIM: Surgical stress significantly decreases serum diamine oxidase (DAO), a marker of intestinal mucosal maturation and integrity. This study aimed to determine the effects of postoperative enteral and total parenteral nutrition (EN and TPN, respectively) in patients with esophageal cancer. PATIENTS AND METHODS: This prospective randomized trial compared serum DAO activities, nutritional states, trace elements and complications between patients who underwent esophagectomy and received EN or TPN for seven days thereafter. RESULTS: Fifty-one patients were randomized to receive EN or TPN. The rates of change in serum DAO activity from the day before surgery were 0.79, 0.89 and 0.91 on postoperative days (POD) 1, 3 and 7, respectively, in the EN group, and 0.64, 0.76 and 1.06, respectively, in the TPN group, with no significant differences. Furthermore, the rates of changes in indicators of nutritional status, namely total protein, albumin, total cholesterol, trace element concentrations and infectious and non-infectious complications did not significantly differ between the groups. CONCLUSION: EN and/or TPN can be administered for early nutritional management until resumption of oral intake after esophagectomy according to the postoperative status of individual patients with esophageal cancer.


Subject(s)
Enteral Nutrition/methods , Esophageal Neoplasms/therapy , Parenteral Nutrition, Total/methods , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Postoperative Care , Prospective Studies , Young Adult
7.
Sci Rep ; 11(1): 20897, 2021 10 22.
Article in English | MEDLINE | ID: mdl-34686686

ABSTRACT

We aimed to analyze the risk factors of positive peripherally inserted central catheter (PICC)-related fungal colonization in preterm infants. This retrospective study collected data from 2018 to 2020. The enrolled infants who underwent PICC insertion were born at < 32 weeks' gestation or birth weight < 1500 g. The demographics, PICC-related characteristics, and treatment information were collected. Univariate and multivariate analyses were performed to investigate risk factors for PICC-related fungal colonization. The receiver operating characteristic (ROC) curve was used to determine the optimal cut-off values for the duration of antibiotics and parenteral nutrition. In total, 124 premature infants underwent PICC insertion. Among them, 19 patients had positive results of fungi on the PICC tips. The duration of antibiotics (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.02-1.31), parenteral nutrition infusion (OR 1.27, 95% CI 1.05-1.54), and postnatal glucocorticoid exposure (OR 9.48, 95% CI 1.06-84.98) were independent risk factors for fungal colonization in PICCs. The ROC curves showed that the risk increased after 15 days of antibiotic use and 28 days of parenteral nutrition infusion. Appropriate clinical management should be used to prevent fungal colonization and fungemia.


Subject(s)
Catheter-Related Infections/etiology , Catheter-Related Infections/microbiology , Catheterization, Central Venous/adverse effects , Catheterization, Peripheral/adverse effects , Catheters, Indwelling/adverse effects , Infant, Premature, Diseases/etiology , Infant, Premature, Diseases/microbiology , Birth Weight/physiology , Female , Gestational Age , Humans , Infant, Newborn , Infant, Premature , Male , Odds Ratio , Parenteral Nutrition/methods , Parenteral Nutrition, Total/methods , Risk Factors
8.
Nat Rev Gastroenterol Hepatol ; 18(12): 903-911, 2021 12.
Article in English | MEDLINE | ID: mdl-34594028

ABSTRACT

Trends in nutritional science are rapidly shifting as information regarding the value of eating unprocessed foods and its salutary effect on the human microbiome emerge. Unravelling the evolution and ecology by which humans have harboured a microbiome that participates in every facet of health and disease is daunting. Most strikingly, the host habitat has sought out naturally occurring foodstuff that can fulfil its own metabolic needs and also the needs of its microbiota, each of which remain inexorably connected to one another. With the introduction of modern medicine and complexities of critical care, came the assumption that the best way to feed a critically ill patient is by delivering fibre-free chemically defined sterile liquid foods (that is, total enteral nutrition). In this Perspective, we uncover the potential flaws in this assumption and discuss how emerging technology in microbiome sciences might inform the best method of feeding malnourished and critically ill patients.


Subject(s)
Critical Care/history , Diet/history , Food, Formulated/history , Gastrointestinal Microbiome , Nutritional Support/history , Perioperative Care/history , Critical Care/methods , Critical Illness/therapy , Diet/adverse effects , Diet/methods , Dietary Fiber/microbiology , Dietary Fiber/therapeutic use , Food, Formulated/adverse effects , History, 20th Century , Humans , Malnutrition/diet therapy , Malnutrition/history , Malnutrition/microbiology , Nutritional Support/methods , Parenteral Nutrition, Total/adverse effects , Parenteral Nutrition, Total/history , Parenteral Nutrition, Total/methods , Perioperative Care/adverse effects , Perioperative Care/methods , United States
9.
Int J Med Sci ; 18(14): 3106-3111, 2021.
Article in English | MEDLINE | ID: mdl-34400881

ABSTRACT

Background: We investigated the extent of growth of microorganisms with simultaneous administration of lipid emulsions with infusions for Total Parenteral Nutrition (TPN), assuming that the lipid emulsions contaminated with microorganisms are stagnant in a closed-type infusion device. We also investigated if bacterial growth can be prevented in the infusion device by flushing the inside of the infusion device with saline solution after the administration of lipid emulsion from the side tube in vitro setting. Methods: We made a preparation by adding Escherichia coli to the lipid emulsion and started the infusion simultaneously with the infusion solution for TPN and lipid emulsion with the piggyback method. Immediately after the completion of lipid emulsion infusion, we conducted flushing with saline solution. The volume of saline solution was none, 5, 10, or 20 mL at a flow rate of 1 mL/s. Infusion solution that was stagnant in the infusion device was collected immediately before completing the lipid emulsion infusion and 20 h after flushing, i.e., 24 h after starting the infusion for TPN, and the number of viable bacteria was determined. Results: The number of viable E. coli increased in the infusion device of all three species used in this experiment 24 h after starting the lipid emulsion infusion without flushing. We found that bacterial growth could be prevented through flushing with saline solution after the completion of lipid emulsion infusion and flushing out the stagnant infusion solution in the closed-type infusion device. Conclusions: We found that if E. coli was present in the closed-type infusion device, it would multiply. We also found that the number of viable bacteria varied according to the variety and internal structure of the closed-type infusion device as well as the liquid volume used for flushing, although flushing can prevent the growth of microorganisms. Proper management and manipulation of infusion is required to prevent infection.


Subject(s)
Equipment Contamination/prevention & control , Escherichia coli/isolation & purification , Fat Emulsions, Intravenous/administration & dosage , Infusions, Intravenous/instrumentation , Parenteral Nutrition, Total/instrumentation , Escherichia coli/growth & development , Parenteral Nutrition, Total/methods
10.
BMC Cancer ; 21(1): 799, 2021 Jul 10.
Article in English | MEDLINE | ID: mdl-34246241

ABSTRACT

BACKGROUND: Ovarian cancer is a common cancer type in women and is often associated with onset of malnutrition. Total parenteral nutrition (TPN) is a nutritional intervention method that has been reported to have controversial effect on cancer patients. In the present retrospective study, we sought to explore the prevalence of malnutrition assessed by the Nutritional Risk Index (NRI) and its association with survival in advanced stage ovarian cancer patients. We also compared the post-operative outcome of the malnourished patients treated with either TPN or conservative management. RESULTS: A total of 415 patients with advanced stage ovarian cancer were separated into 4 nutrition groups based on the NRI scores. We found that a number of factors were significantly different among the 4 nutrition groups, including age, serum albumin level, BMI and NRI; among which serum albumin level and NRI were identified to be independent predictors of progression-free and overall survival. In the moderately and severely malnourished patients, those who were treated with TPN had significantly shorter hospitalization period, lower serum albumin level and lower BMI after surgery. In addition, serum albumin level, use of TPN and number of patients with complications were closely related to the hospital stay duration. CONCLUSION: Malnutrition status is closely associated with survival of advanced stage ovarian cancer patients. These patients may benefit from TPN treatment for reduced hospitalization, especially with the onset of hypoalbuminemia.


Subject(s)
Malnutrition/etiology , Malnutrition/therapy , Ovarian Neoplasms/therapy , Parenteral Nutrition, Total/methods , Adult , Aged , Female , Humans , Male , Middle Aged , Treatment Outcome
11.
Clin Nutr ; 40(6): 3702-3707, 2021 06.
Article in English | MEDLINE | ID: mdl-34130015

ABSTRACT

INTRODUCTION: Refeeding syndrome occurs with the reintroduction of food after an individual has undergone a substantial period of malnutrition. The development of this condition is not uncommon but is neglected in most cases. OBJECTIVE: To identify the incidence of refeeding syndrome in hospitalized patients undergoing total parenteral nutrition and factors that may be associated with this condition. MATERIALS AND METHODS: Observational retrospective and prospective cohort study. Data collection took place at the Hospital de Clínicas de Porto Alegre, from 2015 to 2018. Data was collected consecutively from patient electronic medical records. All hospitalized individuals aged 18 years or more and having a prescription for total parenteral nutrition were included in the study. Exclusion criteria included patients with diabetic ketoacidosis; receiving renal replacement therapy or chronic kidney disease with a glomerular filtration rate <30 mL/min; severe metabolic acidosis or any disease that could affect serum phosphorus levels. WinPepi software, version 11.65, was used to calculate sample size. Data analysis was performed using SPSS version 20.0. A 5% significance level was considered for the established comparisons. The project was approved by the Research Ethics Committee of Hospital de Clínicas de Porto Alegre (number 17-0313). RESULTS: Data from 97 patients was collected. The incidence of refeeding syndrome in our sample was 43.3% (n = 42). Factors positively associated with the syndrome were use of standard parenteral nutrition (p < 0.01), advancing age (mean 62.8 yr versus 55.1 yr; p = 0.013), and amount of total energy administered, which were 25.6 kcal/kg/day versus 23.6 kcal/kg/day for patients with and without refeeding syndrome, respectively (p < 0.01). CONCLUSION: The incidence of refeeding syndrome in individuals using total parenteral nutrition was high. The supply of a greater quantity of total energy in the first week of nutritional therapy, the absence of electrolytes in the parenteral nutrition solution and advancing age were all factors associated with the emergence of refeeding syndrome.


Subject(s)
Parenteral Nutrition, Total/methods , Refeeding Syndrome/epidemiology , Adult , Age Factors , Aged , Aged, 80 and over , Cohort Studies , Electrolytes , Energy Intake , Female , Hospitals, University , Humans , Incidence , Male , Middle Aged , Nutritional Status
14.
Chest ; 159(6): 2309-2317, 2021 06.
Article in English | MEDLINE | ID: mdl-33561455

ABSTRACT

BACKGROUND: Patients with obesity are at higher risk for community-acquired and nosocomial infections. However, no study has specifically evaluated the relationship between obesity and ventilator-associated pneumonia (VAP). RESEARCH QUESTION: Is obesity associated with an increased incidence of VAP? STUDY DESIGN AND METHODS: This study was a post hoc analysis of the Impact of Early Enteral vs Parenteral Nutrition on Mortality in Patients Requiring Mechanical Ventilation and Catecholamines (NUTRIREA2) open-label, randomized controlled trial performed in 44 French ICUs. Adults receiving invasive mechanical ventilation and vasopressor support for shock and parenteral nutrition or enteral nutrition were included. Obesity was defined as BMI ≥ 30 kg/m2 at ICU admission. VAP diagnosis was adjudicated by an independent blinded committee, based on all available clinical, radiologic, and microbiologic data. Only first VAP episodes were taken into account. Incidence of VAP was analyzed by using the Fine and Gray model, with extubation and death as competing risks. RESULTS: A total of 699 (30%) of the 2,325 included patients had obesity; 224 first VAP episodes were diagnosed (60 and 164 in obese and nonobese groups, respectively). The incidence of VAP at day 28 was 8.6% vs 10.1% in the two groups (hazard ratio, 0.85; 95% CI 0.63-1.14; P = .26). After adjustment on sex, McCabe score, age, antiulcer treatment, and Sequential Organ Failure Assessment at randomization, the incidence of VAP remained nonsignificant between obese and nonobese patients (hazard ratio, 0.893; 95% CI, 0.66-1.2; P = .46). Although no significant difference was found in duration of mechanical ventilation and ICU length of stay, 90-day mortality was significantly lower in obese than in nonobese patients (272 of 692 [39.3%] patients vs 718 of 1,605 [44.7%]; P = .02). In a subgroup of patients (n = 123) with available pepsin and alpha-amylase measurements, no significant difference was found in rate of abundant microaspiration of gastric contents, or oropharyngeal secretions between obese and nonobese patients. INTERPRETATION: Our results suggest that obesity has no significant impact on the incidence of VAP.


Subject(s)
Body Mass Index , Intensive Care Units , Obesity/complications , Pneumonia, Ventilator-Associated/etiology , Respiration, Artificial/adverse effects , Shock/therapy , Aged , Female , France/epidemiology , Humans , Incidence , Male , Middle Aged , Parenteral Nutrition, Total/methods , Pneumonia, Ventilator-Associated/epidemiology , Prevalence , Prognosis , Risk Factors , Survival Rate/trends
15.
Ann Clin Biochem ; 58(3): 220-229, 2021 05.
Article in English | MEDLINE | ID: mdl-33353371

ABSTRACT

BACKGROUND: Lipaemic interference on automated analysers has been widely studied using soy-based emulsion such as Intralipid. Due to the greater adoption of fish oil-based lipid emulsion for total parenteral nutrition in view of improved clinical outcomes, we seek to characterize the optical properties of SMOFlipid 20% (Fresenius Kabi, Bad Homburg, Germany), a fish oil-based emulsion, on the Roche Cobas 6000 chemistry analyser (Roche Diagnostic, Basel, Switzerland). METHOD: Various amounts of SMOFlipid were spiked into pooled serums. We plotted Roche Cobas Serum Index Gen.2 Lipaemia Index (L-index) against the amount of SMOFlipid added. We then studied the interference thresholds for aspartate aminotransferase, alanine aminotransferase, albumin and renal panel analytes using SMOFlipid. We subjected five levels of spiked lipaemia to high-speed centrifugation and analysed the specimens pre- and post-centrifugation. To postulate whether fish oil-based lipid emulsion interferes with laboratory results in the clinical setting, we calculated concentrations of SMOFlipid post-lipid rescue therapy and steady-state concentration of a typical total parenteral nutrition regime using pharmacokinetic principles. RESULTS: SMOFlipid optical behaviour is similar to Intralipid using the Serum Index Gen.2 L-index, with 1 mg/dL of SMOFlipid representing 1 unit of L-index. Manufacturer-stated interference thresholds are accurate for alanine aminotransferase, aspartate aminotransferase, albumin, urea and creatinine. High-speed centrifugation at 60 min 21,100g facilitates the removal of fish oil-based SMOFlipid. CONCLUSION: Based on the interference thresholds we verified and pharmacokinetics parameters provided by SMOFlipid manufacturer, total parenteral nutrition may not interfere with chemistry analytes given sufficient clearance, but lipid rescue therapy will interfere. Further studies assessing lipaemic interference on immunoassays are needed.


Subject(s)
Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Fat Emulsions, Intravenous/therapeutic use , Fish Oils/therapeutic use , Olive Oil/therapeutic use , Parenteral Nutrition, Total/methods , Serum Albumin/analysis , Soybean Oil/therapeutic use , Triglycerides/therapeutic use , Clinical Laboratory Techniques/methods , Fat Emulsions, Intravenous/adverse effects , Fish Oils/adverse effects , Humans , Laboratories , Liver/metabolism , Olive Oil/adverse effects , Soybean Oil/adverse effects , Triglycerides/adverse effects , Triglycerides/analysis
16.
Mol Nutr Food Res ; 65(5): e1901270, 2021 03.
Article in English | MEDLINE | ID: mdl-32359213

ABSTRACT

Total parenteral nutrition (TPN) is a life-saving therapy administered to millions of patients. However, it is associated with significant adverse effects, namely liver injury, risk of infections, and metabolic derangements. In this review, the underlying causes of TPN-associated adverse effects, specifically gut atrophy, dysbiosis of the intestinal microbiome, leakage of the epithelial barrier with bacterial invasion, and inflammation are first described. The role of the bile acid receptors farnesoid X receptor and Takeda G protein-coupled receptor, of pleiotropic hormones, and growth factors is highlighted, and the mechanisms of insulin resistance, namely the lack of insulinotropic and insulinomimetic signaling of gut-originating incretins as well as the potentially toxicity of phytosterols and pro-inflammatory fatty acids mainly released from soybean oil-based lipid emulsions, are discussed. Finally, novel approaches in the design of next generation lipid delivery systems are proposed. Propositions include modifying the physicochemical properties of lipid emulsions, the use of lipid emulsions generated from sustainable oils with favorable ratios of anti-inflammatory n-3 to pro-inflammatory n-6 fatty acids, beneficial adjuncts to TPN, and concomitant pharmacotherapies to mitigate TPN-associated adverse effects.


Subject(s)
Drug Delivery Systems/methods , Gastritis/prevention & control , Hepatitis/prevention & control , Lipids/administration & dosage , Parenteral Nutrition, Total/adverse effects , Bile Acids and Salts/metabolism , Dysbiosis/etiology , Emulsions/administration & dosage , Emulsions/chemistry , Gastritis/etiology , Hepatitis/etiology , Humans , Insulin/metabolism , Lipids/pharmacology , Parenteral Nutrition, Total/methods , Receptors, Cytoplasmic and Nuclear/metabolism
17.
Mol Nutr Food Res ; 65(5): e2000412, 2021 03.
Article in English | MEDLINE | ID: mdl-32729969

ABSTRACT

SCOPE: The aim of this study is to test whether the choice of the lipid emulsion in total parenteral nutrition (TPN), that is, n-3 fatty acid-based Omegaven versus n-6 fatty acid-based Intralipid, determines inflammation in the liver, the incretin profile, and insulin resistance. METHODS AND RESULTS: Jugular vein catheters (JVC) are placed in C57BL/6 mice and used for TPN for 7 days. Mice are randomized into a saline group (saline infusion with oral chow), an Intralipid group (IL-TPN, no chow), an Omegaven group (OV-TPN, no chow), or a chow only group (without JVC). Both TPN elicite higher abundance of lipopolysaccharide binding protein in the liver, but only IL-TPN increases interleukin-6 and interferon-γ, while OV-TPN reduces interleukin-4, monocyte chemoattractant protein-1, and interleukin-1α. Insulin plasma concentrations are higher in both TPN, while glucagon and glucagon-like peptide-1 (GLP-1) were higher in IL-TPN. Gluconeogenesis is increased in IL-TPN and the nuclear profile of key metabolic transcription factors shows a liver-protective phenotype in OV-TPN. OV-TPN increases insulin sensitivity in the liver and skeletal muscle. CONCLUSION: OV-TPN as opposed to IL-TPN mitigates inflammation in the liver and reduces the negative metabolic effects of hyperinsulinemia and hyperglucagonemia by "re-sensitizing" the liver and skeletal muscle to insulin.


Subject(s)
Gastritis/etiology , Hepatitis/etiology , Insulin/metabolism , Lipids/administration & dosage , Parenteral Nutrition, Total/methods , Animals , Emulsions/administration & dosage , Emulsions/chemistry , Emulsions/pharmacology , Fatty Acids, Omega-6/pharmacology , Fish Oils/pharmacology , Incretins/metabolism , Insulin/blood , Insulin Resistance , Interferon-gamma/metabolism , Interleukin-6/metabolism , Lipids/chemistry , Malabsorption Syndromes/etiology , Male , Mice, Inbred C57BL , Muscle, Skeletal/drug effects , Muscle, Skeletal/metabolism , Parenteral Nutrition, Total/adverse effects , Phospholipids/administration & dosage , Phospholipids/pharmacology , Soybean Oil/administration & dosage , Soybean Oil/pharmacology , Triglycerides/pharmacology
18.
Oxid Med Cell Longev ; 2020: 8815655, 2020.
Article in English | MEDLINE | ID: mdl-33294125

ABSTRACT

BACKGROUND: The gut was suggested as the driver of critical illness and organ injury. Recently, excessive formation of neutrophil extracellular traps (NETs) was associated with mucosal inflammation. Direct investigation of intestinal mucosa is essential to illuminate the potential mechanism of gut barrier in critically ill patients. We hypothesized that early enteral nutrition (EN) could decrease intestinal NETs and maintain the gut barrier. METHODS: Intestinal biopsies were obtained using biopsy forceps from critically ill surgical patients complicated with enterocutaneous fistula. Expressions of tight junction (TJ) proteins, mucosal inflammation, and apoptosis were evaluated. Moreover, NET-associated proteins were evaluated in intestinal specimens of patients by Western blot and immunofluorescence analysis. RESULTS: The intestinal barrier was significantly impaired in critically ill patients receiving early total parenteral nutrition (TPN), evidenced by intestinal villi atrophy, inflammatory infiltration, increased enterocyte apoptosis, and abnormal TJ expressions. Early EN significantly alleviated these intestinal injuries. In addition, we observed increased formation of the NET structure and elevated expressions of NET-associated proteins in intestines of critically ill surgical patients. Early EN was associated with the diminished presence of NETs and reduced expression of NET-associated proteins. Mechanically, analysis of the TLR4 pathway showed a significant increase in TLR4, NFκB, and MAPK signaling in patients receiving TPN when compared to those receiving early EN. CONCLUSION: The intestinal barrier is disrupted in the human gut during critical illness. Our data suggests that an increased NET structure was showed in the gut of critically ill surgical patients, and early EN treatment was associated with the reduction of NET formation and the preservation of mucosal immunity.


Subject(s)
Enteral Nutrition , Extracellular Traps/metabolism , Intestinal Mucosa/pathology , Neutrophils/metabolism , Tight Junction Proteins/metabolism , Critical Illness/therapy , Humans , Intestinal Mucosa/metabolism , Neutrophils/pathology , Parenteral Nutrition, Total/methods
20.
J Nutr Health Aging ; 24(8): 883-887, 2020.
Article in English | MEDLINE | ID: mdl-33009540

ABSTRACT

OBJECTIVES: Many older patients with pneumonia cannot intake orally after admission and may need nutritional care such as nasogastric tube feeding or total parenteral nutrition. This study sought to compare in-hospital outcomes between patients receiving nasogastric tube feeding and total parenteral nutrition. DESIGN: This is a retrospective cohort study. SETTING: A hospital-based database constructed by the Diagnosis Procedure Combination survey data comprising more than 100 acute-care hospitals. PARTICIPANTS: The study included consecutive older inpatients aged >65 years admitted to participating hospitals with a diagnosis of pneumonia from 2014 through 2017. MEASUREMENTS: We compared patients who received total parenteral nutrition and those who received nasogastric tube feeding in terms of characteristics and outcomes. RESULTS: Among the included inpatients, a total of 336 (73.2%) patients received total parenteral nutrition and 123 (26.8%) patients received nasogastric tube feeding. Patients with nasogastric tube feeding had less in-hospital mortality (13.8% vs 27.1%, p = 0.003) and a smaller number of complications (mean; 0.71 vs 1.44, p <0.001), shorter length of hospital stay (mean; 27.6 vs 48.9, p <0.001), more discharges home (72.4% vs 35.1%, p <0.001), and more discharges without oral intake (65.9% vs 45.8%, p <0.001) than patients with total parenteral nutrition. The same results were obtained in propensity score analysis. CONCLUSIONS: Older patients with pneumonia treated with total parenteral nutrition were significantly more likely to have higher in-hospital mortality than those receiving nasogastric tube feeding.


Subject(s)
Deglutition Disorders/therapy , Enteral Nutrition/methods , Parenteral Nutrition, Total/methods , Pneumonia/therapy , Aged , Cohort Studies , Female , Humans , Male , Retrospective Studies
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