Patients' and caregivers' perspective on challenges and outcomes with tube feeding: Analysis of home enteral nutrition survey data.

BACKGROUND: Given the growing use of home enteral nutrition (HEN), assessing the experience of consumers and caregivers is crucial to understanding the real-world subjective and objective challenges of administering HEN. METHODS: After obtaining institutional review board approval, a survey was distributed to HEN consumers and caregivers between January 16, 2020, and July 16, 2021. Data collected included information regarding demographics, primary diagnosis, tube and connectors, HEN regimen, and overall HEN experience. RESULTS: A total of 884 individuals responded to the survey: 673 (76.1%) responses by caregivers and 211 (23.9%) responses by patients. The study cohort included 566 (64%) children and 318 (36%) adults. The leading primary diagnosis of participants was developmental delay and motility disorder for children and adults, respectively. Low-profile gastric tubes were the most used (75.7% of children and 30.3% of adults). Notably, legacy connectors were utilized for more patients (46.7% children, 52.6% adults) compared to ISO-80369-3 connectors (38.9% children, 29.7% adults). HEN complications were prevalent, including enteral tube site infections and other tube-related complications, including clogging and kinking. CONCLUSION: This real-world data reveals that HEN complications remain prevalent. Additionally, despite introducing ISO-80369-3 connectors many years ago, most patients continue to use legacy tubes with a significant lack of knowledge about ISO-80369-3 connectors. The survey results guide HEN providers to focus on several areas to reduce complications.

Liver cirrhosis and antibiotic therapy but not TIPS application leads to a shift of the intestinal bacterial communities: A controlled, prospective study.

OBJECTIVES: The gut-liver axis is discussed to play an important role in hepatic cirrhosis. Decompensated liver cirrhosis is associated with portal hypertension, which can lead to a variety of complications. Transjugular intrahepatic portosystemic shunt (TIPS) is an established treatment option for the complications of portal hypertension. In this study we focused on the effect of TIPS on intestinal microbial composition in cirrhotic patients. METHODS: Thirty patients with liver cirrhosis were compared to 18 healthy adults. Seventeen patients with cirrhosis and portal hypertension received a TIPS. Clinical characteristics, including age, sex, and liver function measured with a Child-Pugh score and model for end-stage liver disease score, were obtained. Intestinal microbial composition was assessed via 16S rRNA gene amplicon sequencing from stool probes before and after TIPS. RESULTS: TIPS led to a reduction of hepatic venous pressure gradient. However, TIPS did not cause a shift in the intestinal bacterial communities. Independent from the application of TIPS, antibiotic therapy was associated with a significant difference in the intestinal bacterial microbiota and also a reduced α-diversity. In addition, a significant difference was observed in the intestinal bacterial composition between patients with liver cirrhosis and healthy controls. CONCLUSION: The presence of liver cirrhosis and the use of antibiotic therapy, but not the application of TIPS, were associated with a significant shift of the intestinal bacterial communities, showing a high impact on the microbiota of patients with liver cirrhosis.

Urinary acid-base excretion deciphers high acid load from colonic bicarbonate loss in intestinal failure patients with ileocolonic anastomosis - Guidance for composition of parenteral support.

BACKGROUND & AIMS: Acid-base disturbances are common in short bowel (SB) patients due to increased intestinal bicarbonate loss. However, the resulting systemic acid load has not been quantified. Base excess is used to monitor metabolic acid-base disturbances but inadequately reflects the acid load. Our aim was to investigate the systemic acid/base load in SB-patients to obtain quantitative estimates to guide the composition of parenteral support. METHODS: We calculated total acid load in SB patients by summing 24-h urinary net acid excretion (NAE) and the provision of base equivalents in parenteral support. We then compared differences among anatomical SB-types: jejunostomy (SB-J), jejunocolostomy (SB-JC), and jejunoileostomy (SB-JIC). 47 urine samples from 34 SB patients were analyzed for bicarbonate (HCO3-), ammonium (NH4+), and titratable acid (TA) concentrations. NAE was calculated as (TA + NH4+) - HCO3-. Mixed-effects repeated-measures models were used to statistically examine differences between SB-types and associations with parenteral nutrition and NAE. A healthy cohort served as control. RESULTS: In comparison to SB-J, SB-JC patients had a 4.1 mmoL/l lower base excess (95% CI: -6.3 to -1.8) and an 84.5 mmol/day higher total acid load (CI: 41.3 to 127.7). There were no significant differences between SB-JIC and SB-J regarding base excess, NAE, or total acid load. Higher amounts of infused acetate, sodium, and chloride, but not the acetate/chloride ratio, were associated with lower NAE and higher base excess. CONCLUSIONS: Due to increased colonic bicarbonate loss, patients with SB-JC have a ∼4.4-fold higher acid load than healthy controls. The ion transport mechanisms mediating this bicarbonate loss from the remaining colon need further experimental investigation. NAE could be a useful tool to adjust base infusion in SB.

Retroperitoneal cecal volvulus: a complication of a rare internal hernia - a case report.

Introduction and importance: The foramen of Winslow hernia (FWH) is a rare type of internal hernia. In one-third of cases, the cecum was found in the lesser sac. More rarely, the herniated cecum might be volvulated, which represents 1-1.5% of the causes of intestinal obstruction. Once diagnosed, surgical reduction and/or resection of the nonviable herniated bowel is crucial for a positive outcome. Case presentation: The authors report a case of retroperitoneal cecal volvulus that complicated FWH in a patient with a history of laparoscopic cholecystectomy. Clinical discussion: A delay in the diagnosis is associated with high morbidity and even higher mortality. Because of lacking a consensus, the treatment of FWH depends on the team's surgical experience. Conclusion: Reporting this case will help us to keep in mind this differential diagnosis while treating patients in our daily practice.

Nutritional status in patients with chronic pancreatitis and liver cirrhosis is related to disease conditions and not dietary habits.

Malnutrition is a common complication of chronic pancreatitis (CP) and liver cirrhosis (LC). Inadequate food intake is considered a relevant driver of malnutrition in both entities. However, the contribution of habitual diet to impaired nutritional status is unclear. In a prospective, multicenter cross-sectional study, we recruited patients with confirmed CP or LC and healthy volunteers as a control group. Malnutrition was diagnosed according to the Global Leadership Initiative on Malnutrition criteria. We comprehensively investigated habitual dietary intake on nutrient, food group, and dietary pattern level applying two validated food frequency questionnaires. We included 144 patients (CP: n = 66; LC: n = 78) and 94 control subjects. Malnutrition was prevalent in 64% and 62% of patients with CP or LC, respectively. In both CP and LC, despite slightly altered food group consumption in malnourished and non-malnourished patients there were no differences in energy or nutrient intake as well as dietary quality. Compared to controls patients showed distinct dietary food group habits. Patients consumed less alcohol but also lower quantities of fruits and vegetables as well as whole grain products (p < 0.001, respectively). Nevertheless, overall dietary quality was comparable between patients and healthy controls. Nutritional status in CP and LC patients is rather related to disease than habitual dietary intake supporting the relevance of other etiologic factors for malnutrition such as malassimilation or chronic inflammation. Despite distinct disease-related differences, overall dietary quality in patients with CP or LC was comparable to healthy subjects, which suggests susceptibility to dietary counselling and the benefits of nutrition therapy in these entities.

A multi-national survey of experience and attitudes towards managing catheter related blood stream infections for home parenteral nutrition.

BACKGROUND AND AIMS: Catheter-related bloodstream infection (CRBSI) is the most common complication of home parenteral nutrition (HPN) in patients with chronic intestinal failure (CIF). The aim of this study was to assess the broad range of practices of international multi-disciplinary teams involved in the care of this complication occurring in CIF patients. DESIGN: An online questionnaire was designed and distributed to members of the European Society for Clinical Nutrition and Metabolism (ESPEN) and distributed to colleagues involved in managing patients with CIF. RESULTS: A total of 47 responses were included from centers across 21 countries. The centers had been delivering HPN for a median 21 years (IQR 11-35) and were actively following a median 58 patients (27-120) per center for benign CIF in 80% of cases (67-95). Tunneled catheters were the most common type of central venous catheters (CVC), representing 70% (47-86) of all CVC in use. For the management of CRBSI, written procedures were provided in 87% of centers. First measures included simultaneous central and peripheral blood cultures (90%), stopping HPN infusion (74%), and administrating an antibiotic lock and systemic antibiotics (44%). Immediate removal of the CVC was more likely in case of fungal infection (78%), Staphylococcus aureus (53%), or in case of PICC catheter (52%) (all p < 0.01). After the first CRBSI, 80% of centers used preventive CVC locks (taurolidine in 84% of cases, p < 0.001). We observed a large heterogeneity in practices regarding preparation, duration, reaspiration, and volume of CVC locks, and monitoring of CRBSI (timing of blood cultures, radiological work-up). CONCLUSION: In this international survey of HPN expert centers, we observed a significant consensus regarding the initial management of CRBSI and the use of secondary preventive CVC locks, while areas of variation exist. Management of CRBSI may be improved with clearer recommendations based on the micro-organism and the type of CVC, including PICC lines which are increasingly used yet insufficiently studied in HPN patients.

ESPEN guideline on chronic intestinal failure in adults - Update 2023.

BACKGROUND & AIMS: In 2016, ESPEN published the guideline for Chronic Intestinal Failure (CIF) in adults. An updated version of ESPEN guidelines on CIF due to benign disease in adults was devised in order to incorporate new evidence since the publication of the previous ESPEN guidelines. METHODS: The grading system of the Scottish Intercollegiate Guidelines Network (SIGN) was used to grade the literature. Recommendations were graded according to the levels of evidence available as A (strong), B (conditional), 0 (weak) and Good practice points (GPP). The recommendations of the 2016 guideline (graded using the GRADE system) which were still valid, because no studies supporting an update were retrieved, were reworded and re-graded accordingly. RESULTS: The recommendations of the 2016 guideline were reviewed, particularly focusing on definitions, and new chapters were included to devise recommendations on IF centers, chronic enterocutaneous fistulas, costs of IF, caring for CIF patients during pregnancy, transition of patients from pediatric to adult centers. The new guideline consist of 149 recommendations and 16 statements which were voted for consensus by ESPEN members, online in July 2022 and at conference during the annual Congress in September 2022. The Grade of recommendation is GPP for 96 (64.4%) of the recommendations, 0 for 29 (19.5%), B for 19 (12.7%), and A for only five (3.4%). The grade of consensus is "strong consensus" for 148 (99.3%) and "consensus" for one (0.7%) recommendation. The grade of consensus for the statements is "strong consensus" for 14 (87.5%) and "consensus" for two (12.5%). CONCLUSIONS: It is confirmed that CIF management requires complex technologies, multidisciplinary and multiprofessional activity, and expertise to care for the underlying gastrointestinal disease and to provide HPN support. Most of the recommendations were graded as GPP, but almost all received a strong consensus.

Experience and opinions relating to pregnancy in patients with chronic intestinal failure: an international survey.

Introduction: Pregnancy in patients with chronic intestinal failure (CIF) is a relatively rare occurrence but is an important contemporary topic given both the increasing use of home parenteral nutrition (HPN) and the demographics of patients with CIF. Method: An opinion-based survey was produced in a multidisciplinary manner, which was then distributed internationally, via the European Society for Clinical Nutrition and Metabolism network, using a web-based survey tool for healthcare professionals with a specialist interest in the management of CIF. Results: Seventy specialists from 11 countries completed the survey. Fifty-four per cent of the respondents reported some experience of managing pregnancy in patients with CIF. However, 60% stated that they did not feel that it was their role to discuss the topic of pregnancy with their patients, with fewer than 10% stating that they routinely did so. Respondents felt that an individualised approach was required when considering alterations to parenteral support prior to conception, during pregnancy and in the postnatal period. Most respondents also felt there was no increased risk of catheter-related blood stream infections, while catheter-related thrombosis was deemed to be the most significant HPN-related complication for pregnant women. Conclusion: This study reports a variable experience, knowledge and confidence of healthcare professionals when considering pregnancy in patients with CIF. The risk of HPN-related complication was felt to be greater during pregnancy, with an individualised approach being the preferred route for most aspects of care. The findings support the need for an international registry and subsequent consensus guidelines for the management of pregnancy in CIF.

C. perfringens Blood Stream Infection due to Nontransmural Ischemia of the Esophagus, Stomach, and Left Colon: Case Report.

We report the case of a 74-year-old female with abdominal pain, tarry stools, and tachycardia. Previous history included diabetes mellitus with micro- and macroangiopathy. Imaging revealed portal gas, left sided colitis, and emphysematous gastritis, besides severe atherosclerosis with subtotal celiac trunk occlusion and moderate stenosis of the inferior mesenteric artery. Upper endoscopy revealed findings consistent with focal necrotizing gastritis at the greater curvature and acute esophageal necrosis. Blood cultures immediately grew Clostridium perfringens. The patient was treated with broad spectrum antibiotics and was discharged after 21 days in the hospital. This case demonstrates the rare coincident occurrence of nontransmural ischemia of the left colon, the esophagus, and the stomach as a result of low-flow circulatory compromise, which then precipitated C. perfringens associated emphysematous gastritis and blood stream infection.

Randomized, controlled clinical trial of the DIALIVE liver dialysis device versus standard of care in patients with acute-on- chronic liver failure.

BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) is characterized by severe systemic inflammation, multi-organ failure and high mortality rates. Its treatment is an urgent unmet need. DIALIVE is a novel liver dialysis device that aims to exchange dysfunctional albumin and remove damage- and pathogen-associated molecular patterns. This first-in-man randomized-controlled trial was performed with the primary aim of assessing the safety of DIALIVE in patients with ACLF, with secondary aims of evaluating its clinical effects, device performance and effect on pathophysiologically relevant biomarkers. METHODS: Thirty-two patients with alcohol-related ACLF were included. Patients were treated with DIALIVE for up to 5 days and end points were assessed at Day 10. Safety was assessed in all patients (n = 32). The secondary aims were assessed in a pre-specified subgroup that had at least three treatment sessions with DIALIVE (n = 30). RESULTS: There were no significant differences in 28-day mortality or occurrence of serious adverse events between the groups. Significant reduction in the severity of endotoxemia and improvement in albumin function was observed in the DIALIVE group, which translated into a significant reduction in the CLIF-C (Chronic Liver Failure consortium) organ failure (p = 0.018) and CLIF-C ACLF scores (p = 0.042) at Day 10. Time to resolution of ACLF was significantly faster in DIALIVE group (p = 0.036). Biomarkers of systemic inflammation such as IL-8 (p = 0.006), cell death [cytokeratin-18: M30 (p = 0.005) and M65 (p = 0.029)], endothelial function [asymmetric dimethylarginine (p = 0.002)] and, ligands for Toll-like receptor 4 (p = 0.030) and inflammasome (p = 0.002) improved significantly in the DIALIVE group. CONCLUSIONS: These data indicate that DIALIVE appears to be safe and impacts positively on prognostic scores and pathophysiologically relevant biomarkers in patients with ACLF. Larger, adequately powered studies are warranted to further confirm its safety and efficacy. IMPACT AND IMPLICATIONS: This is the first-in-man clinical trial which tested DIALIVE, a novel liver dialysis device for the treatment of cirrhosis and acute-on-chronic liver failure, a condition associated with severe inflammation, organ failures and a high risk of death. The study met the primary endpoint, confirming the safety of the DIALIVE system. Additionally, DIALIVE reduced inflammation and improved clinical parameters. However, it did not reduce mortality in this small study and further larger clinical trials are required to re-confirm its safety and to evaluate efficacy. CLINICAL TRIAL NUMBER: NCT03065699.

Orally compensated short bowel patients are thin, potentially malnourished but rarely sarcopenic.

BACKGROUND AND AIM: In short bowel syndrome, insufficient absorptive capacity of the remnant bowel may lead to metabolic and nutritional consequences including electrolyte disturbances, severe diarrhea and malnutrition. While intestinal failure requires parenteral nutrition, short bowel patients with intestinal insufficiency (SB/II) have achieved oral autonomy. The aim of this exploratory study was to assess the nutritional, muscular and functional status of orally compensated SB/II patients. METHODS: 28 orally compensated SB/II patients with a mean of 46 months after termination of parenteral nutrition and 56 age- and sex-matched healthy controls (HC) were compared regarding anthropometric parameters, body composition using bioelectrical impedance analysis, handgrip strength and gait speed, blood parameters as well as nutritional intake and physical activity using validated questionnaires. Malnutrition and sarcopenia were diagnosed according to the criteria of the GLIM or EWGSOP2. RESULTS: SB/II patients had lower body mass index (BMI) and anthropometric parameters than HC but were within the normal weight range. The GLIM algorithm operationally diagnosed malnutrition in 39% (n = 11) of SB/II patients. Reduced skeletal muscle mass index and phase angle were rarely accompanied by a reduction of handgrip strength below cut-off values and the subsequent diagnosis of sarcopenia in SB/II patients (15%, n = 4). Compared to 11% of HC, 37% of SB/II patients had low physical activity level. Female SB/II patients had higher caloric and macronutrient intake. Caloric intake negatively correlated with body weight indicating compensatory hyperphagia in patients with lower body weight. Some of the SB/II patients showed signs of dehydration. CONCLUSIONS: Orally compensated SB/II patients are thinner than HC but have mostly normal BMI. Malnutrition is frequently diagnosed but may be overestimated due to the underlying malabsorption and its interplay with hyperphagia. Muscle mass is often reduced but is rarely accompanied by functional impairment leading to sarcopenia diagnosis. Thus, SB/II patients long term after termination of parenteral support may be malnourished but usually do not develop sarcopenia.

Ileocolonic Healing after Small Ileocecal Resection in Mice: NOD2 Deficiency Impairs Anastomotic Healing by Local Mechanisms.

Ileocecal resection (ICR) is frequently performed in Crohn's disease (CD). NOD2 mutations are risk factors for CD. Nod2 knockout (ko) mice show impaired anastomotic healing after extended ICR. We further investigated the role of NOD2 after limited ICR. C57B16/J (wt) and Nod2 ko littermates underwent limited ICR including 1-2 cm terminal ileum and were randomly assigned to vehicle or MDP treatment. Bursting pressure was measured on POD 5, and the anastomosis was analyzed for matrix turn-over and granulation tissue. Wound fibroblasts from subcutaneously implanted sponges were used for comparison. The M1/M2 macrophage plasma cytokines were analyzed. Mortality was not different between groups. Bursting pressure was significantly decreased in ko mice. This was associated with less granulation tissue but was not affected by MDP. However, anastomotic leak (AL) rate tended to be lower in MDP-treated ko mice (29% vs. 11%, p = 0.07). mRNA expression of collagen-1α (col1 α), collagen-3α (col3 α), matrix metalloproteinase (mmp)2 and mmp9 was increased in ko mice, indicating increased matrix turn-over, specifically in the anastomosis. Systemic TNF-α expression was significantly lower in ko mice. Ileocolonic healing is impaired in Nod2 ko mice after limited ICR by local mechanisms maybe including local dysbiosis.

COVID-19 infection in patients on long-term home parenteral nutrition for chronic intestinal failure.

BACKGROUND AND AIMS: To investigate the incidence and the severity of COVID-19 infection in patients enrolled in the database for home parenteral nutrition (HPN) for chronic intestinal failure (CIF) of the European Society for Clinical Nutrition and Metabolism (ESPEN). METHODS: Period of observation: March 1st, 2020 March 1st, 2021. INCLUSION CRITERIA: patients included in the database since 2015 and still receiving HPN on March 1st, 2020 as well as new patients included in the database during the period of observation. Data related to the previous 12 months and recorded on March 1st 2021: 1) occurrence of COVID-19 infection since the beginning of the pandemic (yes, no, unknown); 2) infection severity (asymptomatic; mild, no-hospitalization; moderate, hospitalization no-ICU; severe, hospitalization in ICU); 3) vaccinated against COVID-19 (yes, no, unknown); 4) patient outcome on March 1st 2021: still on HPN, weaned off HPN, deceased, lost to follow up. RESULTS: Sixty-eight centres from 23 countries included 4680 patients. Data on COVID-19 were available for 55.1% of patients. The cumulative incidence of infection was 9.6% in the total group and ranged from 0% to 21.9% in the cohorts of individual countries. Infection severity was reported as: asymptomatic 26.7%, mild 32.0%, moderate 36.0%, severe 5.3%. Vaccination status was unknown in 62.0% of patients, non-vaccinated 25.2%, vaccinated 12.8%. Patient outcome was reported as: still on HPN 78.6%, weaned off HPN 10.6%, deceased 9.7%, lost to follow up 1.1%. A higher incidence of infection (p = 0.04), greater severity of infection (p < 0.001) and a lower vaccination percentage (p = 0.01) were observed in deceased patients. In COVID-19 infected patients, deaths due to infection accounted for 42.8% of total deaths. CONCLUSIONS: In patients on HPN for CIF, the incidence of COVID-19 infection differed greatly among countries. Although the majority of cases were reported to be asymptomatic or have mild symptoms only, COVID-19 was reported to be fatal in a significant proportion of infected patients. Lack of vaccination was associated with a higher risk of death.

Analysis of ESPEN and GLIM algorithms reveals specific drivers for the diagnosis of malnutrition in patients with chronic gastrointestinal diseases.

OBJECTIVES: Disease-related malnutrition (MN) is common in patients with liver cirrhosis (LC), short bowel syndrome (SBS), and chronic pancreatitis (CP). Different MN risk screening tools and diagnostic criteria of the European Society for Clinical Nutrition and Metabolism (ESPEN) and Global Leadership Initiative on Malnutrition (GLIM) algorithms were analyzed for their diagnostic accuracy and role as specific drivers to diagnose MN in patients with LC, SBS, and CP. METHODS: A total of 187 patients with LC, SBS, and CP, as well as control patients were prospectively recruited in a multicenter cross-sectional study. MN risk was screened using Nutritional Risk Screening 2002 (NRS-2002), the Malnutrition Universal Screening Tool (MUST), and the Royal Free Hospital Nutritional Prioritizing Tool (RFH-NPT), and diagnosed using the ESPEN, GLIM, and GLIMCRP+ (GLIM incorporating C-reactive protein [CRP] >5 mg/L) algorithms. For each of the individual diagnostic criteria, relative frequency, sensitivity, specificity, as well as positive and negative predictive values were calculated. RESULTS: NRS-2002 was only sensitive in conjunction with ESPEN, while MUST was sensitive additionally with the GLIM algorithm. RFH-NPT worked the best for LC. GLIM and GLIMCRP+ diagnosed MN more frequently than the ESPEN algorithm. Diagnostic criteria were detected at remarkably different relative frequencies starting with reduced food intake/malabsorption and chronic disease/inflammation, followed by weight loss, reduced fat-free mass index, low body mass index, and body mass index <18.5 kg/m². Relative frequencies differed between LC, SBS, and CP. Weight loss in LC and CP and reduced fat-free mass index and food intake in SBS had good diagnostic accuracy, suggesting that these criteria act as specific drivers for MN. CONCLUSIONS: RFH-NPT and MUST performed better in conjunction with the GLIM algorithm than NRS-2002. MN was diagnosed more frequently by GLIM than the ESPEN algorithm in LC, SBS, and CP. Individual criteria acted as specific drivers in MN in chronic gastrointestinal diseases.

Dysbiosis and reduced small intestinal function are required to induce intestinal insufficiency in mice.

Extensive bowel resection can lead to short bowel syndrome and intestinal failure. Resection-induced dysbiosis may be related to the specific anatomic site of resection and influences the disease progression. Although patients with end-jejunostomy are at high risk for intestinal failure, preservation of the ileocecal valve and colon counteracts this risk. The present study investigated the role of the cecum in maintaining microbial homeostasis after different types of small bowel resection. Male C57BL6/J mice were anesthetized by intraperitoneal injection of ketamine-xylazine and received extended ileocecal resection (extended ICR), limited ileocecal resection (limited ICR), or mid-small bowel resection (SBR). Stool samples were collected before surgery and between postoperative days 2-7, for 16S rRNA gene sequencing. Only extended ICR, but neither limited ICR nor SBR, induced intestinal insufficiency. α-Diversity was reduced in both ICR variants but not after SBR. All resections resulted in an increase in Proteobacteria. Pathobionts, such as Clostridia, Shigella, and Enterococcus, increased after SBR while Muribaculaceae, Lactobacillus, and Lachnospiraceae decreased. Limited ICR resulted in an increase of members of the Clostridium sensu stricto group, Terrisporobacter and Enterococcus and a decrease of Muribaculaceae. The increase of Enterococcus was even more pronounced after extended ICR while Muribaculaceae and Akkermansia were dramatically reduced. Both ICR variants caused a decrease in steroid biosynthesis and glycosaminoglycan degradation-associated pathways, suggesting altered bile acid transformation and mucus utilization.NEW & NOTEWORTHY Resection-induced dysbiosis affects disease progression in patients with short bowel syndrome. Severe dysbiosis occurs after removal of the ileocecal valve, even in the absence of short bowel conditions, and is associated with the loss of Muribaculaceae and Akkermansia and an increase of Clostridium and Enterococcus. The preservation of the cecum should be considered in surgical therapy, and dysbiosis should be targeted based on its specific anatomical signature to improve postoperative bacterial colonization.

Effects of Bile Duct Ligation and Ghrelin Treatment on the Colonic Barrier and Microbiome of Mice.

INTRODUCTION: Cholestatic liver disease (CLD) is associated with intestinal barrier dysfunction. The peptide hormone ghrelin may exert both hepatoprotective and barrier-strengthening effects. Here, we have evaluated these effects under the conditions of experimental cholestasis. METHODS: C57BL/6J mice with bile duct ligation (BDL) or sham surgery were treated with ghrelin or solvent for 9 days. Liver injury was assessed by histological and laboratory analyses. Paracellular macromolecule permeability and transmural electrical resistance (TMER) of colonic tissues were measured using a Ussing chamber. Expression of tight junction (TJ) genes was quantified by real-time PCR. Amplicon metagenomic sequencing was employed to analyze bacterial 16S rRNA from colonic stool samples. RESULTS: Mice with BDL exhibited weight loss and signs of severe liver injury. These changes were unaffected by ghrelin treatment. FITC-4-kDa-dextran flux was increased and TMER decreased after BDL. Treatment with ghrelin tended to reduce these effects. Furthermore, application of ghrelin was associated with higher mRNA levels of claudin-4, occludin, and ZO-1 in colonic tissues of mice with BDL. Reduced alpha-diversity of the microbiome was observed in solvent-treated mice with BDL but not in ghrelin-treated animals. CONCLUSION: Ghrelin treatment did not improve weight loss and liver damage but increased gene expression of colonic TJ proteins and restored the alpha-diversity of the microbiome. Since protective effects of ghrelin might be masked by the severity of the model, we suggest follow-up studies in models of milder CLD.

Transjugular intrahepatic portosystemic shunt vs conservative treatment for recurrent ascites: A propensity score matched comparison.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) placement is an effective intervention for recurrent tense ascites. Some studies show an increased risk of acute on chronic liver failure (ACLF) associated with TIPS placement. It is not clear whether ACLF in this context is a consequence of TIPS or of the pre-existing liver disease. AIM: To better understand the risks of TIPS in this challenging setting and to compare them with those of conservative therapy. METHODS: Two hundred and fourteen patients undergoing their first TIPS placement for recurrent tense ascites at our tertiary-care center between 2007 and 2017 were identified (TIPS group). Three hundred and ninety-eight patients of the same time interval with liver cirrhosis and recurrent tense ascites not undergoing TIPS placement (No TIPS group) were analyzed as a control group. TIPS indication, diagnosis of recurrent ascites, further diagnoses and clinical findings were obtained from a database search and patient records. The in-hospital mortality and ACLF incidence of both groups were compared using 1:1 propensity score matching and multivariate logistic regressions. RESULTS: After propensity score matching, the TIPS and No TIPS groups were comparable in terms of laboratory values and ACLF incidence at hospital admission. There was no detectable difference in mortality (TIPS: 11/214, No TIPS 13/214). During the hospital stay, ACLF occurred more frequently in the TIPS group than in the No TIPS group (TIPS: 70/214, No TIPS: 57/214, P = 0.04). This effect was confined to patients with severely impaired liver function at hospital admission as indicated by a significant interaction term of Child score and TIPS placement in multivariate logistic regression. The TIPS group had a lower ACLF incidence at Child scores < 8 points and a higher ACLF incidence at ≥ 11 points. No significant difference was found between groups in patients with Child scores of 8 to 10 points. CONCLUSION: TIPS placement for recurrent tense ascites is associated with an increased rate of ACLF in patients with severely impaired liver function but does not result in higher in-hospital mortality.

In silico investigation of molecular networks linking gastrointestinal diseases, malnutrition, and sarcopenia.

Malnutrition (MN) is a common primary or secondary complication in gastrointestinal diseases. The patient's nutritional status also influences muscle mass and function, which can be impaired up to the degree of sarcopenia. The molecular interactions in diseases leading to sarcopenia are complex and multifaceted, affecting muscle physiology, the intestine (nutrition), and the liver at different levels. Although extensive knowledge of individual molecular factors is available, their regulatory interplay is not yet fully understood. A comprehensive overall picture of pathological mechanisms and resulting phenotypes is lacking. In silico approaches that convert existing knowledge into computationally readable formats can help unravel mechanisms, underlying such complex molecular processes. From public literature, we manually compiled experimental evidence for molecular interactions involved in the development of sarcopenia into a knowledge base, referred to as the Sarcopenia Map. We integrated two diseases, namely liver cirrhosis (LC), and intestinal dysfunction, by considering their effects on nutrition and blood secretome. We demonstrate the performance of our model by successfully simulating the impact of changing dietary frequency, glycogen storage capacity, and disease severity on the carbohydrate and muscle systems. We present the Sarcopenia Map as a publicly available, open-source, and interactive online resource, that links gastrointestinal diseases, MN, and sarcopenia. The map provides tools that allow users to explore the information on the map and perform in silico simulations.

Long-term results of teduglutide treatment for chronic intestinal failure - Insights from a national, multi-centric patient home-care service program.

BACKGROUND & AIMS: Teduglutide is a Glucagon-like peptide-2 (GLP-2) agonist indicated for the treatment of patients with parenteral support (PS) dependent short bowel syndrome (SBS) with chronic intestinal failure (cIF). Its application is accompanied by a structured nation-wide home-care service program in Germany. We investigated care characteristics and outcome parameters in a clinical real-world observational setting. METHODS: Data generated within a therapy-accompanying home-care service program for adult SBS-cIF patients were analyzed retrospectively for patients treated up to 1 year (data cut: April 2020). RESULTS: In total, 52 teduglutide-treated patients were included by 6 German cIF centers. At teduglutide administration start, 49/52 patients were on PS, 3 of them without macronutrients. The majority of patients received individualized parenteral nutrition (PN) (n = 32/46), while 13/46 were on commercial premixed bags. PS application was done by patients themselves (37%), home-care nurses (19%), relatives (8%) or by a combination of those (16%). In patients with PS dependency at baseline and available follow-up data (n = 40-44), teduglutide treatment resulted in significantly reduced PN days, caloric needs, infusion time, and infusion volume after 6 and 12 months. After 1 year, reduction of infusion time was positively correlated with a reduction of PN calories and volume; 30 patients (68%) were responders (PS-volume reduction ≥20%), and 6 patients (14%) were completely weaned off PS. Sleep disturbances per night were significantly reduced after 3 months of treatment and stool characteristics improved in consistency and significantly in frequency, while meal frequency remained stable. CONCLUSIONS: Teduglutide treatment associated reduction in PS volume and calories was accompanied by reduced infusion days, infusion times, sleep disturbances, stable oral intake surrogates, and improved stool characteristics, all of these potential parameters for improving quality of life. Furthermore, analyzed care characteristics reflect SBS-cIF treatment as a complex, resource-intensive and demanding task for both, healthcare system and patients.