Parenteral support and micronutrient deficiencies in children with short bowel syndrome: A comprehensive retrospective study.

BACKGROUND & AIMS: Short bowel syndrome (SBS) is the leading cause of chronic intestinal failure. The duration of parenteral support (PS) and the long-term micronutrient needs in children with SBS vary, based on their clinical and anatomical characteristics. Our study aimed to review the clinical course and identify high risk patient groups for prolonged PS and long-term micronutrient supplementation. METHODS: A retrospective review was conducted on electronic medical records of children with SBS and chronic intestinal failure who were enrolled in the multidisciplinary intestinal rehabilitation program at Manchester Children's Hospital, UK. Children were included in the review if they required PN for more than 60 days out of 74 consecutive days and had at least 3 years of follow-up. Statistical analysis was performed using IBM SPSS Statistics 24.0. RESULTS: 40 children with SBS achieved enteral autonomy (EA) and 14 remained dependent on PS after 36 months of follow up. Necrotizing enterocolitis was the most common cause for intestinal resection (38.9%) followed by gastroschisis (22.2%), malrotation with volvulus (20.4%), segmental volvulus (9.3%) and long segment Hirschsprung disease (1.9%). Those who achieved EA had significantly longer intestinal length 27.5% (15.0-39.3) than those who remained on PS 6.0% (1.5-12.5) (p < 0.001). Type I SBS was only found in the PS cohort. Median PN dependence was 10.82 months [IQR 5.73-20.78]. Congenital diagnosis was associated with longer PN dependence (21.0 ± 20.0) than acquired (8.7 ± 7.8 months), (p = 0.02). The need for micronutrient supplementation was assessed after the transition to EA; 87.5% children had at least one micronutrient depletion, most commonly Vitamin D (64.1%), followed by iron (48.7%), Vitamin B12 (34.2%), and vitamin E (28.6%). Iron deficiency and vitamin A depletion were correlated with longer PS after multivariate analysis (OR: 1.103, 1.006-1.210, p = 0.037 and OR: 1.048, 0.998-1.102, p = 0.062 respectively). CONCLUSION: In our cohort, small bowel length was the main predictor for EA. Children on longer PS, had more often a congenital cause of resection and were at risk for micronutrient deficiencies in EA.

Intestinal Failure-Associated Liver Disease and Growth Pre- and Post-Transition to a Composite Lipid Emulsion.

OBJECTIVES: Infants with intestinal failure have an increased risk of intestinal failure-associated liver disease (IFALD). Composite intravenous lipid emulsion (ILE) may reduce the risk of cholestasis. The primary outcome was to compare IFALD rates in infants with intestinal failure, between those receiving a composite ILE versus soybean oil ILE. The secondary outcome compared growth between these 2 groups. METHODS: At our 2 tertiary neonatal/pediatric hospitals, we identified all patients (≤1 year old) who received ≥6 weeks parenteral nutrition (PN) from 2010 to 2018. Data included liver and growth parameters. IFALD was defined as serum conjugated bilirubin (CB) >33 µmol/L (≥2 mg/dL). Nonparametric tests were used for all comparisons. RESULTS: Fifty infants (35 composite ILE, 15 soybean oil ILE) were included. Those on composite ILE received PN for longer (10.1 vs 7.6 weeks; P = 0.001) and had higher baseline CB (29 vs 6.5 µmol/L; P = 0.001). No differences were found by 6 weeks (14.5 vs 5 µmol/L; P = 0.54) and by PN cessation (4 vs 4 µmol/L; P = 0.33). The proportion of patients with IFALD decreased from 54% to 20% for composite ILE, while stable given soybean oil ILE (7%). There were no differences in weight, length, or head circumference z scores ( P > 0.05). CONCLUSIONS: In our institutions, over 8 years, chronic intestinal failure was rare. Composite ILE was the predominant lipid choice for infants who needed longer courses of PN or had developed cholestasis. Despite longer PN duration, and higher baseline CB, overall rates of IFALD decreased with composite ILE. Regardless of parenteral lipid used, there were no differences in growth.

Management of long-term home parenteral nutrition: Historical perspective, common complications, and patient education and training.

Intestinal failure (IF) is a rare disease that requires ongoing intravenous supplementation to sustain growth and health. Advancements in parenteral nutrition (PN) and central venous access in the 1960s and 1970s transformed a life-limiting disease to a chronic one in which patients are able to administer hydration, electrolytes, micronutrients, and macronutrients in the comfort of their home. However, despite ongoing advancements in the field of home PN (HPN), complications-whether related to central venous catheters or PN itself-remain common and can be associated with significant morbidity and mortality. Central venous access can be associated with thrombosis, central line-associated bloodstream infection, or damage and can result in loss of access over time. PN can be associated with IF-associated liver disease or hyperglycemia. The key to preserving central venous access and quality of life and maintaining health for patients with chronic IF (CIF) is education focused on prevention and prompt management of CIF complications as they arise. This education typically takes place at the time of initiation of HPN, either in the hospital setting or in the patient's home. The present manuscript describes the historical progression of HPN, prevalence and characteristics of CIF, and an in-depth discussion of the most common catheter-related and PN-related complications and their management, along with a discussion of our education and training process.

Omega-3 fatty acids impair miR-1-3p-dependent Notch3 down-regulation and alleviate sepsis-induced intestinal injury.

BACKGROUND: Sepsis is a troublesome syndrome that can cause intestinal injury and even high mortality rates. Omega-3 fatty acids (FAs) are known to protect against intestinal damage. Accordingly, the current study set out to explore if omega-3 FAs could affect sepsis-induced intestinal injury with the involvement of the microRNA (miR)-1-3p/Notch3-Smad axis. METHODS: First, cecal ligation and perforation (CLP) was performed to establish septic mouse models in C57BL/6J mice, and mouse intestinal epithelial MODE-K cells were induced by lipopolysaccharide (LPS) to establish sepsis cell models. The CLP-induced septic mice or LPS-exposed cells were subjected to treatment with Omega-3 FAs and activin (Smad signaling activator), miR-1-3p inhibitor and over-expressed/short hairpin RNA (oe-/sh)-Notch3 to explore their roles in inflammation, intestinal oxidative stress and cell apoptosis. A dual-luciferase reporter gene assay was further performed to verify the regulatory relationship between miR-1-3p and Notch3. RESULTS: Omega-3 FAs inhibited CLP-induced intestinal injury and ameliorated LPS-induced intestinal epithelial cell injury by down-regulating miR-1-3p, as evidenced by decreased levels of tumor necrosis factor-α, interleukin-1ß (IL-1ß) and IL-6, in addition to diminished levels of reactive oxygen species, malondialdehyde levels and superoxide dismutase activity. Furthermore, miR-1-3p could down-regulate Notch3, which inactivated the Smad pathway. CONCLUSION: Collectively, our findings indicated that omega-3 FAs elevate the expression of Notch3 by down-regulating miR-1-3p, and then blocking the Smad pathway to alleviate intestinal epithelial inflammation and oxidative stress injury caused by sepsis.

Effects of Bovine Colostrum with or without Egg on In Vitro Bacterial-Induced Intestinal Damage with Relevance for SIBO and Infectious Diarrhea.

Small intestinal bacterial overgrowth (SIBO) occurs commonly, is difficult to treat, and frequently recurs. Bovine colostrum (BC) and chicken eggs contain immunoglobulins and other components that possess antimicrobial, immunoregulatory, and growth factor activities; however, it is not known if they have the ability to reduce injury caused by the presence of bacteria associated with SIBO (Streptococcus, Escherichia coli, Staphylococcus, Bacteroides, Klebsiella, Enterococcus, and Proteus) and infectious diarrhea (enteropathogenic Escherichia coli, Salmonella). We examined the effects of BC, egg, or the combination, on bacterial growth and bacteria-induced changes in transepithelial electrical resistance (TEER) and bacterial translocation across confluent Caco-2 monolayers. BC, egg, or the combination did not affect bacterial growth. Adding bacteria to monolayers reduced TEER and (with minor variations among species) increased bacterial translocation, increased monolayer apoptosis (increased caspase-3 and Baxα, reduced Bcl2), increased intercellular adhesion molecule 1 (ICAM-1), and reduced cell adhesion molecules zonulin1 (ZO1) and claudin-1. BC, egg, or the combination reduced these effects (all p < 0.01) and caused additional increases in vascular endothelial growth factor (VEGF) and Heat Shock Protein 70 (Hsp70) expression. We conclude that BC ± egg strengthens mucosal integrity against a battery of bacteria relevant for SIBO and for infectious diarrhea. Oral BC ± egg may have clinical value for these conditions, especially SIBO where eradication of precipitating organisms may be difficult to achieve.

The Effect of Sacral Neuromodulation in Ambulatory Spina Bifida Patients with Neurogenic Bladder and Bowel Dysfunction.

OBJECTIVE: To assess the effect of sacral neuromodulation (SNM) in ambulatory spina bifida patients with neurogenic bladder and bowel dysfunction. MATERIALS AND METHODS: We retrospectively reviewed the records of 29 ambulatory spina bifida patients with neurogenic bladder and bowel dysfunction who underwent SNM testing from July 2012 to January 2020. Clinical data and video-urodynamic parameters were collected and compared using the t-test and the chi-square test. The potential risk factors were considered by logistic regression analysis. P < .05 was considered significant. RESULTS: In the test phase, 21 patients (72.4%) achieved successful improvement of at least 1 symptom. The success rate for chronic urinary retention (26.09%) was significantly lower (P <.05) than that for urgency-frequency syndrome (58.82%) and urinary incontinence (56.25%). The mean neurogenic bowel dysfunction score decreased from 13.3±6.29 to 6.9±5.09 (P <.0001). The urodynamic evaluation showed a significant improvement in the mean maximum cystometric capacity, compliance, and maximum detrusor pressure (P <.05). Implantation was performed in 16 cases (55.17%). The analysis of the risk factors showed that chronic urinary retention was a statistically significant variable (P <.05). No complications were reported in the test phase. The average follow-up time was 41.19±33.06 months. Two patients changed to intermittent catheterization, and 2 patients changed to augmentation cystoplasty. CONCLUSION: SNM is effective for neurogenic bladder and bowel dysfunction in patients with ambulatory spina bifida, especially in those without chronic urinary retention. And SNM can also significantly improve the urodynamic parameters of these patients during the storage period.

[A real-world study to evaluate a peptidic oral supplement in adults with altered intestinal function after parenteral nutrition]. / Un estudio en la vida real para evaluar un suplemento oral peptídico en adultos con alteración de la función intestinal tras la nutrición parenteral.

INTRODUCTION: Objectives: in routine clinical practice many disorders are found that can disrupt the sequence of reactions in digestion and absorption, leading to malnutrition and requiring the use of oral nutritional supplements (ONS). The objective of our study was to evaluate in a real world setting the use of and compliance with a peptide-based ONS in malnourished adult patients with intestinal compromise after more than 14 days of parenteral nutrition. Material and methods: the study was carried out in 44 malnourished patients who required total parenteral nutrition for at least 14 days without using the oral route during their hospital stay. All patients were administered, on an outpatient basis, 1 brick per day of Vital 1.5® for 12 weeks. At the beginning of treatment and after the intervention period evaluated, the following variables were collected: weight, height, body mass index (BMI), global subjective assessment test, nutritional biochemistry, 3-day nutritional survey, adverse effects generated by the formula, and completion rate. Results: 44 patients were enrolled. Mean age was 70.4 ± 10.4 years (20 women & 24 men). After the intervention the following parameters had increased: BMI (0.51 ± 0.1 kg/m2; p = 0.02), weight (1.4 ± 0.3 kg; p = 0.03), prealbumin (3.5 ± 4.1 mg/dl; p = 0.01), albumin (1.3 ± 0.1 mg/dl; p = 0.03), and transferrin (71.5 ± 24.1 mg/dl; p = 0.02). Dietary intake of the ONS represented 14.4 % of the diet's total caloric intake at 3 months, 17.5 % of carbohydrates, 12.9 % of proteins, and 12.3 % of fats. Mean compliance was 87.7 ± 7.2 % of the prescribed intakes. In relation to the nutritional situation, at the beginning of the study, 52.3 % (n = 23) of patients were in the global subjective assessment test in category B (moderate malnutrition or nutritional risk), and 47.7 % (n = 21) in category C (severe malnutrition). After the intervention, 75 % of patients were in category A (n = 33), 13.6 % (n = 6) in category B, and 11.4 % (n = 5) in category C. Conclusions: the use of a peptide-based ONS with short-chain triglycerides in outpatients showed a beneficial effect on biochemical and anthropometric parameters, and improved the nutritional status of patients with high compliance and good tolerance rates.

INTRODUCCIÓN: Objetivos: en la práctica clínica habitual existen multitud de situaciones y patologías que pueden interrumpir la digestión y la absorción intestinal, cursando con desnutrición y requiriendo el uso de suplementos orales nutricionales (SON). El objetivo de nuestro estudio fue evaluar, en el contexto de la vida real, el uso de un SON basado en péptidos, y el cumplimiento con el mismo, en pacientes adultos desnutridos con compromiso intestinal tras más de 14 días de nutrición parenteral. Material y métodos: el estudio se realizó en 44 pacientes desnutridos que requirieron nutrición parenteral total al menos 14 días, sin utilización de la vía oral durante el ingreso hospitalario. Se les administró de manera ambulatoria 1 brik al día de Vital 1.5® para su consumo durante 12 semanas. Al inicio del tratamiento y tras el periodo de intervención se les recogieron las variables siguientes: peso, talla, IMC, test de valoración subjetiva global, bioquímica nutricional, encuesta nutricional, efectos adversos generados por la fórmula y cumplimentación. Resultados: se incluyeron 44 pacientes con una edad media de 70,4 ± 10,4 años (20 mujeres/24 hombres). Tras la intervención aumentaron el IMC (0,51 ± 0,1 kg/m2; p = 0,02), el peso (1,4 ± 0,3 kg; p = 0,03), la prealbúmina (3,5 ± 4,1 mg/dl; p = 0,01), la albúmina (1,3 ± 0,1 mg/dl; p = 0,03) y la transferrina (71,5 ± 24,1 mg/dl; p = 0,02). La toma del SON represento a los 3 meses un 14,4 % del aporte calórico total de la dieta, un 17,5 % de los hidratos de carbono, un 12,9 % de las proteínas y un 12,3 % de las grasas. La cumplimentación media del grupo fue del 87,7 ± 7,2 % de las tomas prescritas. En relacion a la situacion nutricional, a la entrada del estudio un 52,3 % (n = 23) de los pacientes presentaban en el test de valoración subjetiva global la categoría B (malnutrición moderada o riesgo nutricional) y un 47,7 % (n = 21) la categoría C (desnutrición severa). Tras la intervención, un 75 % de los pacientes presentaban la categoría A (buena situación nutricional (n = 33), un 13,6 % (n = 6) de los pacientes presentaban la categoría B y un 11,4 % (n = 5) la categoría C. Conclusiones: la utilización de un suplemento peptídico con triglicéridos de cadena corta en pacientes ambulatorios tras haber recibido una nutrición parenteral total muestra un efecto beneficioso sobre los parametros bioquímicos y antropométricos, y la situación nutricional, con una alta cumplimentación y buena tolerancia.

Mixed Oil-Based Lipid Emulsions vs Soybean Oil-Based Lipid Emulsions on Incidence and Severity of Intestinal Failure-Associated Liver Disease in a Neonatal Intensive Care Unit.

BACKGROUND: Neonates requiring long-term parenteral nutrition (PN) are at risk for developing intestinal failure-associated liver disease (IFALD). The purpose of this study was to compare the incidence and severity of IFALD in a highly surgical neonatal population receiving mixed oil-based lipid emulsions (MOLEs) vs soybean oil-based lipid emulsions (SOLEs) for long-term PN. METHODS: This retrospective cohort study evaluated patients admitted to a neonatal intensive care nursery that received PN for ≥14 days. Patients were separated into 2 cohorts; those who received SOLE and those who received MOLE. The primary outcome of this study was the occurrence of IFALD. Secondary outcomes included time to IFALD, peak bilirubin level during therapy, incidence of hypertriglyceridemia, bronchopulmonary dysplasia, and retinopathy of prematurity. RESULTS: A total of 107 patients were included in the study, IFALD occurred in 44.8% of patients receiving SOLE compared with 30% of patients receiving MOLE (relative risk, 0.67; 95% CI, 0.39-1.15). In the multivariable analysis, adjusting for the known confounders (prematurity, necrotizing enterocolitis, presence of ostomy, and duration of PN and lipids), the type of lipids was not a significant predictor for development of IFALD. Duration of PN and duration of lipids were determined to be significant risk factors for IFALD, regardless of type of lipid emulsion (odds ratio, 1.03; 95% CI, 1.01-1.05). CONCLUSIONS: Use of MOLE resulted in no significant difference in the outcomes studied when compared with SOLE. Duration of PN and duration of lipids were significant risk factors for development of IFALD.

Ghrelin reverts intestinal stem cell loss associated with radiation-induced enteropathy by activating Notch signaling.

BACKGROUD: Exposure to high-dose radiation, such as after a nuclear accident or radiotherapy, elicits severe intestinal damage and is associated with a high mortality rate. In treating patients exhibiting radiation-induced intestinal dysfunction, countermeasures to radiation are required. In principle, the cellular event underlying radiation-induced gastrointestinal syndrome is intestinal stem cell (ISC) apoptosis in the crypts. High-dose irradiation induces the loss of ISCs and impairs intestinal barrier function, including epithelial regeneration and integrity. Notch signaling plays a critical role in the maintenance of the intestinal epithelium and regulates ISC self-renewal. Ghrelin, a hormone produced mainly by enteroendocrine cells in the gastrointestinal tract, has diverse physiological and biological functions. PURPOSE: We investigate whether ghrelin mitigates radiation-induced enteropathy, focusing on its role in maintaining epithelial function. METHODS: To investigate the effect of ghrelin in radiation-induced epithelial damage, we analyzed proliferation and Notch signaling in human intestinal epithelial cell. And we performed histological analysis, inflammatory response, barrier functional assays, and expression of notch related gene and epithelial stem cell using a mouse model of radiation-induced enteritis. RESULTS: In this study, we found that ghrelin treatment accelerated the reversal of radiation-induced epithelial damage including barrier dysfunction and defective self-renewing property of ISCs by activating Notch signaling. Exogenous injection of ghrelin also attenuated the severity of radiation-induced intestinal injury in a mouse model. CONCLUSION: These data suggest that ghrelin may be used as a potential therapeutic agent for radiation-induced enteropathy.

Branch-like gas in a commercial diver's liver: a case report.

We report the case of a 42-year-old commercial diver who presented with palpitations, arthralgia, tachypnea and vomiting after three hours of repetitive dives to 25-30 meters below sea level (msw). He was diagnosed with severe decompression sickness (Type II DCS) based on his dive history, his abrupt ascent to the surface within minutes, and systemic symptoms with mild hypovolemic shock. Besides remarkable cutis marmorata on the torso, the patient was also found positive for diffuse branch-like pneumatosis in the liver, mesentery and intestines on an abdominal computed tomography (CT). His vitals were relatively stable, with a soft distended abdomen and mild tenderness over the right upper quadrant. He was treated with hyperbaric oxygen (HBO2) treatment in addition to essential crystalloid resuscitation. The abdominal pneumatosis resolved completely after two HBO2 sessions. Post-diving intra-abdominal pneumatosis is a rare complication of DCS. In our case it was difficult for dive doctors to diagnose promptly because an emergency abdominal CT was not a routine for potential DCS cases. We propose that a contrast-enhanced abdominal CT, which usually involves a intravenous injection of imaging agent, should be considered in emergency management of these patients, especially when they present with gastrointestinal symptoms.

Composite Lipid Emulsion for the Infant at Risk of Intestinal Failure-associated Liver Disease: The Canadian Perspective.

Currently, in North America we are fortunate to have a number of available options for lipid emulsions to be used in the parenteral nutrition regimens for infants and children, including for long-term parenteral nutrition given intestinal failure. Neonates and infants in particular are at risk for intestinal failure-associated liver disease (IFALD). The choice of parenteral lipid emulsion will influence the risk and severity of IFALD. The purpose of this review is to discuss the rationale for the composite lipid emulsion SMOFlipid that includes soybean, medium-chain triglycerides, olive and fish oils for IFALD, with focus on the Canadian practice and experience.

Phytosterolaemia associated with parenteral nutrition administration in adult patients.

Vegetable lipid emulsions (LE) contain non-declared phytosterols (PS). We aimed to determine PS content depending on the brand and LE batch, and in adult hospitalised patients treated with parenteral nutrition (PN), to establish the association between plasma and administered PS. Part I was the LE study: totals and fractions of PS in three to four non-consecutive batches from six LE were analysed. Part II was the patient study: patients with at least 7 previous days of PN with 0·8 g/kg per d of an olive/soyabean (O/S) LE were randomised (day 0) 1:1 to O/S or 100 % fish oil (FO) at a dose of 0·4 g/kg per d for 7 d (day 7). Plasma PS, its fractions, total cholesterol on days 0 and 7, their clearance and their association with PS administered by LE were studied. In part I, LE study: differences were found in the total PS, their fractions and cholesterol among different LE brands and batches. Exclusive soyabean LE had the highest content of PS (422·36 (sd 130·46) µg/ml). In part II, patient study: nineteen patients were included. In the O/S group, PS levels were maintained (1·11 (sd 6·98) µg/ml) from day 0 to 7, while in the FO group, significant decreases were seen in total PS (-6·21 (sd 4·73) µg/ml) and their fractions, except for campesterol and stigmasterol. Plasma PS on day 7 were significantly associated with PS administered (R2 0·443). PS content in different LE brands had great variability. PS administered during PN resulted in accumulation and could be prevented with the exclusive administration of FO LE.

Laminarin-rich extract improves growth performance, small intestinal morphology, gene expression of nutrient transporters and the large intestinal microbial composition of piglets during the critical post-weaning period.

The identification of natural bioactive compounds which can prevent the post-weaning growth check and enhance gastrointestinal health in the absence of in-feed medications is an urgent priority for the swine industry. The objective of this experiment was to determine the effects of increasing dietary inclusion levels of laminarin in the first 14 d post-weaning on pig growth performance and weaning associated intestinal dysfunction. At weaning, ninety-six pigs (8·4 (sd 1·09) kg) (meatline boars × (large white × landrace sows)) were blocked by live weight, litter and sex and randomly assigned to: (1) basal diet; (2) basal + 100 parts per million (ppm) laminarin; (3) basal + 200 ppm laminarin and (4) basal + 300 ppm laminarin (three pigs/pen). The appropriate quantity of a laminarin-rich extract (65 % laminarin) was added to the basal diet to achieve the above dietary inclusion levels of laminarin. After 14 d of supplementation, eight pigs from the basal group and the best-performing laminarin group were euthanised for sample collection. The 300 ppm laminarin group was selected as this group had higher ADFI compared with all other groups and higher ADG than the basal group (P < 0·05). Laminarin supplementation increased villus height in the duodenum and jejunum (P < 0·05). Laminarin supplementation increased the expression of SLC2A8/GLUT8 in the duodenum, SLC2A2/GLUT2, SLC2A7/GLUT7, SLC15A1/PEPT1 and FABP2 in the jejunum and SLC16A1/MCT1 in the colon. Laminarin supplementation reduced Enterobacteriaceae numbers in the caecum (P < 0·05) and increased lactobacilli numbers (P < 0·05), total volatile fatty acid concentrations and the molar proportions of butyrate (P < 0·01) in the colon. In conclusion, 300 ppm laminarin from a laminarin-rich extract has potential, as a dietary supplement, to improve performance and prevent post-weaning intestinal dysfunction.

Early intravenous administration of tranexamic acid ameliorates intestinal barrier injury induced by neutrophil extracellular traps in a rat model of trauma/hemorrhagic shock.

BACKGROUND: Early intravenous administration of tranexamic acid has been shown to protect the intestinal barrier after a model of trauma-hemorrhagic shock in the rat, but the potential mechanism remains unclear. Our previous studies have demonstrated that neutrophil extracellular traps contribute to the intestinal barrier dysfunction during sepsis and other critical conditions. Meanwhile, there are high levels of neutrophil infiltration in the intestine during trauma-hemorrhagic shock. Here, we hypothesized that neutrophil extracellular trap formation played a vital role during trauma-hemorrhagic shock-induced intestinal injury and that tranexamic acid, a serine protease inhibitor, may inhibit neutrophil extracellular trap formation and protect intestinal barrier function in trauma-hemorrhagic shock. METHODS: A model of trauma-hemorrhagic shock in male rats was established. The rats were divided into 6 groups: (1) sham group; (2) trauma-hemorrhagic shock group; (3) trauma-hemorrhagic shock + DNase I group; (4) trauma-hemorrhagic shock + tranexamic acid group; (5) trauma-hemorrhagic shock + tranexamic acid (different time) group; and (6) trauma-hemorrhagic shock + tranexamic acid (different doses) group. The DNase I solution was injected intravenously to disrupt neutrophil extracellular traps immediately after the trauma-hemorrhagic shock model was completed. After 24 hours, the small intestine and blood were collected for analysis. Human neutrophils were harvested and incubated with phorbol-12-myristate-13-acetate or tranexamic acid, generation of reactive oxygen species, and key proteins expression were detected. RESULTS: Trauma-hemorrhagic shock induced the formation of intestinal neutrophil extracellular traps and disrupted the intestinal tight junction proteins. Clearing of neutrophil extracellular traps by DNase I resulted in increased expression of tight junction proteins and alleviated the intestinal injury. Early intravenous tranexamic acid administration (1 hour after trauma-hemorrhagic shock) decreased neutrophil extracellular trap formation and prevented tight junction protein disruption compared to the non-tranexamic acid group; however, after delayed administration of tranexamic acid (6 hours), there were no changes in neutrophil extracellular trap formation and intestinal injuries compared to the non-tranexamic acid group. Furthermore, tranexamic acid inhibited neutrophil extracellular trap formation and protected the intestinal barrier in a dose-dependent manner and high-dose (20 mg/kg) treatment of tranexamic acid showed a better effect compared with the therapeutic dose (10 mg/kg). The results of thromboelastography demonstrated that the R and K values in the high-dose group decreased (R, 1.85 ± 0.14 vs 3.87 ± 0.16 minutes, P < .001; K, 0.95 ± 0.04 vs 1.48 ± 0.07 minutes, P < .001), accompanied by a decrease in LY30, indicating that treatment with a high dose of tranexamic acid may cause hypercoagulability and shutdown of fibrinolysis. In addition, less neutrophil extracellular trap formation was detected in neutrophils incubated with neutrophils via an reactive oxygen species-dependent pathway. CONCLUSION: We first demonstrated a novel role of neutrophil extracellular traps in the pathophysiology of intestinal barrier dysfunction during trauma-hemorrhagic shock. Notably, early but not delayed intravenous administration of tranexamic acid effectively inhibits neutrophil extracellular trap formation and protects intestinal barrier function. Therefore, these results suggested a potential theoretic intervention for the protection of the intestinal barrier during trauma-hemorrhagic shock. In such a process, tranexamic acid appears to regulate neutrophil extracellular trap formation via the classic reactive oxygen species/mitogen-activated protein kinase pathway.

Mechanisms of Parenteral Nutrition-Associated Liver and Gut Injury.

Parenteral nutrition (PN) has revolutionized the care of patients with intestinal failure by providing nutrition intravenously. Worldwide, PN remains a standard tool of nutrition delivery in neonatal, pediatric, and adult patients. Though the benefits are evident, patients receiving PN can suffer serious cholestasis due to lack of enteral feeding and sometimes have fatal complications from liver injury and gut atrophy, including PN-associated liver disease or intestinal failure-associated liver disease. Recent studies into gut-systemic cross talk via the bile acid-regulated farnesoid X receptor (FXR)-fibroblast growth factor 19 (FGF19) axis, gut microbial control of the TGR5-glucagon-like peptide (GLP) axis, sepsis, and role of prematurity of hepatobiliary receptors are greatly broadening our understanding of PN-associated injury. It has also been shown that the composition of ω-6/ω-3 polyunsaturated fatty acids given parenterally as lipid emulsions can variably drive damage to hepatocytes and cell integrity. This manuscript reviews the mechanisms for the multifactorial pathogenesis of liver disease and gut injury with PN and discusses novel ameliorative strategies.

Pyruvate Protects Against Intestinal Injury by Inhibiting the JAK/STAT Signaling Pathway in Rats With Hemorrhagic Shock.

BACKGROUND: This study aimed to investigate the role of Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway in protection by peritoneal resuscitation (PR) using pyruvate-peritoneal dialysis solution (PY-PDS) against intestinal injury from hemorrhagic shock (HS) in rats. MATERIALS AND METHODS: Sixty-four rats were assigned to eight groups: group SHAM; group intravenous resuscitation (VR); groups NS, LA, and PY in which the rats were subjected to HS and PR with normal saline (NS), lactate-peritoneal dialysis solution (LA-PDS), and PY-PDS, respectively, combined with VR; and groups DMSO, RPM, and AG490 in which the rats were subjected to HS and VR with pretreatment of dimethyl sulfoxide (DMSO), rapamycin (RPM), and tyrphostin B42 (AG490). RESULTS: At 2 h after HS and resuscitation, the levels of diamine oxidase, 15-F2t-isoprostane, thromboxane B2, and endothelin-1, in the blood and the intestinal mucosal apoptotic index and caspase-3 were lower in groups PY, RPM, and AG490 than in groups VR, NS, LA, and DMSO. Group PY showed lower levels of malondialdehyde and myeloperoxidase and a higher level of superoxide dismutase than groups VR, NS, and LA. Phosphorylated JAK2 and phosphorylated STAT3 levels were lower in groups PY, RPM, AG490, and LA than in groups VR, NS, and DMSO. CONCLUSIONS: The protection mechanism of PR with PY-PDS combined with VR was related to the inhibition of the JAK/STAT signaling pathway during HS and resuscitation. The process might include suppression of oxidative stress, reduction of neutrophil infiltration, regulation of microcirculation, and inhibition of apoptosis.

Falla intestinal. Artículo de revisión / Intestinal failure Review article

La falla intestinal (FI) se define como la disminución de la función del intestino por debajo de lo mínimo necesario para la absorción de los macronutrientes y / o agua y electrolitos, de tal manera que se requiere de la suplementación intravenosa (SIV) para mantener la salud y el crecimiento. Desde el punto de vista funcional se clasifica en tres tipos. FI tipo I: condición aguda, de corto duración y generalmente auto limitada, FI tipo II: estado agudo prolongado, a menudo en pacientes metabólicamente inestables, que requieren cuidado multidisciplinario y SIV durante períodos de una semana o meses, acompañada de complicaciones sépticas, metabólicas y nutricionales y FI tipo III: condición crónica, en pacientes metabólicamente estables, que requieren SIV durante meses o años. Su manejo requiere de terapia nutricional y en casos seleccionados cirugía autóloga de reconstrucción(AU)

Intestinal failure (FI) is defined as the decrease in intestinal function below the minimum necessary for the absorption of macronutrients and / or water and electrolytes, in such a way that intravenous supplementation (IVS) is required to maintain health and growth. From a functional point of view, it is classified into three types. FI type I: acute condition, of short duration and generally self-limited, FI type II: prolonged acute state, often in metabolically unstable patients, requiring multidisciplinary care and SIV for periods of a week or months, accompanied by septic, metabolic and nutrition and FI type III: chronic condition, in metabolically stable patients, who require SIV for months or years. Its management requires nutritional therapy and in selected cases autologous reconstruction surgery(AU)

[Standardized treatment of chronic radiation-induced bowel injury].

Radiation-induced bowel injury is a common complication of radiation therapy for pelvic malignancy. Given the huge number of patients diagnosed with pelvic malignancy, the number of patients diagnosed with radiation-induced bowel injury increased year by year, which put a great burden on the clinical diagnosis and treatment of radiation-induced bowel injury. In particular, chronic radiation-induced bowel injury, which is manifested in the process of prolonged, repeated and progressive aggravation, seriously affects the physical and mental health of patients and makes clinical diagnosis and treatment difficult. However, due to insufficient attention and understanding from doctors and patients, standardized diagnosis and treatment of radiation-induced bowel injury still have a long way to go. Radiation-induced bowel injury is self-limited but irreversible. During diagnosis, we should pay attention to overall evaluation of the stage of disease based on clinical symptoms, endoscopic examination, imaging examination, pathology and nutritional risk. The treatment methods include health education, drug therapy, enema therapy, formalin local treatment, endoscopic treatment and surgical treatment, etc. The treatment decision-making should be based on clinical symptoms, endoscopic or imaging findings to alleviate the clinical symptoms of patients as the primary goal and to improve the long-term quality of life of patients as the ultimate goal.

TAME trial: a multi-arm phase II randomised trial of four novel interventions for malnutrition enteropathy in Zambia and Zimbabwe - a study protocol.

INTRODUCTION: Severe acute malnutrition (SAM) in children in many countries still carries unacceptably high mortality, especially when complicated by secondary infection or metabolic derangements. New therapies are urgently needed and we have identified mucosal healing in the intestine as a potential target for novel treatment approaches. METHODS AND ANALYSIS: The TAME trial (Therapeutic Approaches for Malnutrition Enteropathy) will evaluate four novel treatments in an efficient multi-arm single-blind phase II design. In three hospitals in Zambia and Zimbabwe, 225 children with SAM will be randomised to one of these treatments or to standard care, once their inpatient treatment has reached the point of transition from stabilisation to increased nutritional intake. The four interventions are budesonide, bovine colostrum or N-acetyl glucosamine given orally or via nasogastric tube, or teduglutide given by subcutaneous injection. The primary endpoint will be a composite score of faecal inflammatory markers, and a range of secondary endpoints include clinical and laboratory endpoints. Treatments will be given daily for 14 days, and evaluation of the major endpoints will be at 14 to 18 days, with a final clinical evaluation at 28 days. In a subset of children in Zambia, endoscopic biopsies will be used to evaluate the effect of interventions in detail. ETHICS AND DISSEMINATION: The study has been approved by the University of Zambia Biomedical Research Ethics Committee (006-09-17, dated 9th July, 2018), and the Joint Research Ethics Committee of the University of Zimbabwe (24th July, 2019). Caregivers will provide written informed consent for each participant. Findings will be disseminated through peer-reviewed journals, conference presentations and to caregivers at face-to-face meetings. TRIAL REGISTRATION NUMBER: NCT03716115; Pre-results.

The effects of vitamins and selenium mixture or ranitidine against small intestinal injury induced by indomethacin in adult rats.

This study was aimed at investigating morphological and biochemical efficacies of antioxidants on indomethacin-induced small intestinal damage in rats. Group I: control animals (negative control) given only placebo, Group II: (positive control) are animals orally given combination of antioxidants [vitamin C (Vit C), vitamin E (Vit E), ß-carotene and sodium selenite (Se)] daily for 3 days, Group III: Rats were given only indomethacin, Group IV: animals were given of antioxidants combination for 3 days, last dose was given 2 hr before the administration of indomethacin. Group V: Animals receiving ranitidine for 3 days (second positive control). Group VI: Animals received ranitidine for 3 days, last dose was given 2 hr before to indomethacin administration. Indomethacin caused degenerative morphological and biochemical changes, which were reversed on antioxidants administration. As a result, we propose that antioxidants combination would be therapeutically beneficial for treating indomethacin-induced lesions of small intestine. PRACTICAL APPLICATIONS: Indomethacin is a widely preferred nonsteroidal anti-inflammatory drug (NSAID) but its side effects on gastrointestinal system are well known. Indomethacin also causes production of reactive oxygen species. Antioxidants and selenium has protective effects. According to the results of this study, antioxidants and selenium can be used as a food supplement for preventing NSAID-induced side effects and toxicity.