Short Bowel Syndrome Patients Research Articles

S3050 Intestinal Failure-Associated Liver Disease vs Non Alcoholic Fatty Liver Disease in the Setting of Short Bowel Syndrome: A Case of Rapidly Progressive Hepatic Failure

Introduction: Intestinal Failure-Associated Liver Disease (IFALD) is a progressive disease with a high mortality rate in patients dependent on parenteral nutrition (PN). It is a multifactorial entity associated with a spectrum of hepatic manifestations including cholestasis, steatosis, portal hypertension, choline deficiency and manganese toxicity. In patients with Short Bowel Syndrome (SBS), hepatic steatosis occurs in 40-55% and IFALD in 5-15%. Risk factors for IFALD in SBS include chronic PN use and length of remaining bowel. Early IFALD may present similarly to NAFLD, however pathogenic and prognostic differences make distinguishing these diseases crucial. We present a case of rapidly progressive IFALD in an adult SBS patient after PN use. Case Description/Methods: We present a 65 year-old female with massive short bowel resection (< 30cm remaining) and malnutrition with a 12-year history of on-and-off PN use. PN was discontinued 6 months prior and she was gaining weight with enteral feeding and teduglutide. She presented with right upper quadrant pain and nausea. Ultrasound showed cholelithiasis and hepatic steatosis. She was discharged after resolution of symptoms. In two weeks, she returned with jaundice, worsening abdominal pain, weight loss, altered mentation and asterixis. Labs showed total bilirubin 11.4 mg/d L (Direct 6.0mg/d L), ALP 139 IU/L, AST 136 IU/L, ALT 65 IU/L, NH3 182 mg/L and serum carnitine 15 μmol/L. She was treated for hepatic encephalopathy with lactulose, rifaximin and carnitine. Computed tomography showed moderate ascites, mesenteric edema, and edematous bowels. Diagnostic paracentesis revealed portal hypertension. Liver biopsy showed cirrhosis with steatohepatitis and peri-cellular fibrosis consistent with TPN-associated liver disease in the setting of SBS-IF(Image A). Multifocal pneumonia with multi-organ failure led to her death. (Figure) Discussion: This case demonstrates the potentially rapid progression of IFALD, particularly in patients with SBS. Clinicians should exercise high clinical suspicion of IFALD in patients with a history of PN use and SBS that present with hepatic manifestations. Early recognition is important to distinguish the disease from similarly presenting NAFLD (table 1). It is also vital to consider and treat other factors that may exacerbate hepatic disease including nutritional deficiencies. There may be benefit to diagnosis with liver biopsy early in the disease course to initiate prompt treatment or transplant, preventing rapid and fatal progression.Figure 1.: Liver biopsy showing cirrhosis with marked steatohepatitis, mild lobular inflammation, ballooning hepatocyte degeneration nodular and peri-cellular fibrosis stage IV Table 1. - Differentiating features between IFALD vs NAFLD FEATURES IFALD NAFLD Metabolic syndrome No metabolic syndrome ,no insulin resistance, or it is improved after initiating PN, low BMI and low plasma cholesterol levels Metabolic syndrome common with Insulin resistance, hyperlipidemia high BMI Nutritional status and PN dependence Severe malabsorption, mostly dependent on PN No malabsorption, PN mostly not required Plasma choline levels Low plasma free choline concentration Normal to high levels Effect of choline supplementation Reduction of steatosis ,improved liver tests with choline supplementation Minimal difference to choline supplementation Cholestasis Highly evident with hyperbilirubinemia Not typical Steatosis (macro vs micro) Macro and micro steatosis Predominantly macro steatosis Disease progression and cirrhosis development Rapid progression to ESLD, cirrhosis develops within ∼3-5 months after initiating PN Longer duration ∼10-20 years for cirrhosis to develop Zone of steatosis More common in zone -1 (periportal) Mostly involves zone -1(peri-central) Pattern of fibrosis Characteristic "jig-saw" pattern fibrosis Sinusoidal fibrosis with ballooning of hepatocytes Treatment Intestinal transplant is mainstay of treatment to overcome malabsorption and impending liver failure No role of intestinal transplant as no malabsorption. Prognosis Rapid onset of death within 1-4 years Rapid death extremely rare

407.2: Successful Pregnancy in a Small Bowel Syndrome Patient Without Any Nutritional Support. Case Report: GLP-2 Levels in Pregnancy and Breastfeeding

Introduction: Pregnant patients with Short Bowel Syndrome (SBS) and chronic intestinal failure (CIF) can successfully reach to term their pregnancies while on Parenteral Nutrition (PN) but with high rates of complications. The availability of entero-hormones, especially semisynthetic glucagon like peptide 2 (sGLP2) has increased the chances to achieve intestinal sufficiency. Case report: We report the case of a 33-year-old female patient with SBS/CIF (anatomy type 2), weaned off PN using sGLP-2. After 3.7 years of treatment, she became pregnant. The first decision was to interrupt the use of sGLP-2 as pregnancy is a contraindication for its use. She was able to successfully carry out the pregnancy to term without any additional PN support. She had adequate weight gain (59,0 to 66,15 kgs); the newborn weight was 2,450 kgs, and she was able to breastfeed her without complications. Our initial hypothesis was that endogenous fetal GLP-2 (eGLP2) levels could have been a sufficient source to maintain an adequate maternal intestinal absorption, if able to cross the placental barrier. Thus, during the pregnancy, we decided to determine eGLP-2 levels in paired neonatal (cord blood) and maternal plasma samples from pregnant with (n=1) or without SBS (controls, n=2) during the partum and the immediate breastfeeding period (1 and 6 months postpartum); we also aimed to measure and compare eGLP-2 plasma levels between pregnant (n=1) and a non-pregnant SBS patients (Anatomy type 2 (n=7); Anatomy type 3 (n= 5)). Materials and Methods: Blood samples were collected in ice chilled 10 ml tubes containing ethylenediaminetetraacetic acid (EDTA) and a specific dipeptidyl peptidase IV inhibitor. Plasma was immediately separated and stored at −80°C until analyzed. Results: Our results indicated that eGLP-2 levels were significantly lower in neonatal than maternal plasma from our pregnant SBS patient compared to controls (Table 1). During postpartum, eGLP-2 levels increased up to the six-month in both groups (Figure 1). Interestingly, our pregnant SBS patient showed significantly higher GLP-2 levels respect than controls (Figure 1) and non-pregnant SBS patients (Figure 2). Conclusions: We observed that the endogenous neonatal GLP-2 does not represent an extra source of this entero-hormone to improve the adequate intestinal absorption during pregnancy in SBS patients. However, this study suggests that long periods of sGLP-2 treatment in SBS patients could reach an effective intestinal rehabilitation sufficient not only to improve intestinal absorption (to carry out the full pregnancy and to sustain breast feeding), but also to probably increase the eGLP-2 production. This study should be reproduced in experimental models and larger series to validate those results.TAKEDA.

Lacticaseibacillus casei CNCM I-5663 supplementation maintained muscle mass in a model of frail rodents.

The aim of this study was to identify a probiotic-based strategy for maintaining muscle anabolism in the elderly. In previous research, we found that individuals experiencing short bowel syndrome (SBS) after an intestinal resection displayed beneficial metabolic adjustments that were mediated by their gut microbes. Thus, these bacteria could potentially be used to elicit similar positive effects in elderly people, who often have low food intake and thus develop sarcopenia. Gut bacterial strains from an SBS patient were evaluated for their ability to (1) maintain Caenorhabditis elegans survival and muscle structure and (2) promote protein anabolism in a model of frail rodents (18-month-old rats on a food-restricted diet: 75% of ad libitum consumption). We screened a first set of bacteria in C. elegans and selected two Lacticaseibacillus casei strains (62 and 63) for further testing in the rat model. We had four experimental groups: control rats on an ad libitum diet (AL); non-supplemented rats on the food-restricted diet (R); and two sets of food-restricted rats that received a daily supplement of one of the strains (∼109 CFU; R+62 and R+63). We measured lean mass, protein metabolism, insulin resistance, cecal short-chain fatty acids (SCFAs), and SCFA receptor expression in the gut. Food restriction led to decreased muscle mass [−10% vs. AL (p < 0.05)]. Supplementation with strain 63 tempered this effect [−2% vs. AL (p > 0.1)]. The mechanism appeared to be the stimulation of the insulin-sensitive p-S6/S6 and p-eIF2α/eIF2α ratios, which were similar in the R+63 and AL groups (p > 0.1) but lower in the R group (p < 0.05). We hypothesize that greater SCFA receptor sensitivity in the R+63 group promoted gut-muscle cross talk [GPR41: +40% and GPR43: +47% vs. R (p < 0.05)]. Hence, strain 63 could be used in association with other nutritional strategies and exercise regimes to limit sarcopenia in frail elderly people.

Untargeted Metabolomics Reveal Parenteral Nutrition-Associated Alterations in Pediatric Patients with Short Bowel Syndrome.

Short bowel syndrome (SBS) is a major cause of intestinal failure (IF) that may require long-term parenteral nutrition (PN) support. However, long-term PN is accompanied by severe complications such as catheter-related blood stream infection (CRBSI) and intestinal failure-associated liver disease (IFALD), and it is associated with high healthcare costs. In this study, we characterized the plasma metabolomic profile and investigated the role of metabolism in predicting long-term PN in pediatric patients with SBS. Untargeted metabolomics was performed in plasma samples from 20 SBS patients with PN support: 6 patients had IFALD and 14 patients had no liver disease. As controls, 18 subjects without liver or intestinal diseases were included for the analysis. SBS patients had distinct plasma metabolomic signatures compared to controls, and several pathways associated with amino acid metabolism and cell death were significantly changed. The presence of IFALD in SBS was associated with alterations of metabolites mainly classified as “amino acids, peptides, and analogues” and “benzene and derivatives”. Serum direct bilirubin levels were negatively correlated with levels of uridine, skatole, and glabrol. Importantly, SBS patients with long-term PN showed significantly increased levels of glutamine compared to those in the short-term PN group. Finally, using multivariate logistic regression analysis, we developed a prediction model including glutamine and creatinine to identify pediatric SBS patients who need long-term PN support. These findings underscore the potential key role of the metabolome in SBS with IF and suggest that metabolomic profiles could be used in long-term PN assessment.

Severe acute respiratory syndrome coronavirus 2 antibody prevalence in adult patients with short bowel syndrome-A German multicenter cross-sectional study.

BackgroundNot all patients suffer from a severe course of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, demanding a definition of groups at risk. Short bowel syndrome (SBS) has been assumed to be a risk factor, because of the complexity of disease, the need for interdisciplinary care, and frequent contact with caretakers. We aimed to establish data on the course of infection and prevalence of SARS‐CoV‐2 seropositivity in SBS patients in Germany.MethodsFrom January 2021 until January 2022 a total of 119 patients from three different tertiary care centers with SBS were included. All patients received an antibody test against the nucleocapsid (N) antigen and were asked to fill out a questionnaire, which included frequency of contact with medical personnel, risk behavior and worries.ResultsSixty‐seven percent of SBS patients received parenteral nutrition with a median of 6 days per week. The seroprevalence of SARS‐CoV‐2 antibodies was 7.6% (n = 9). Seven patients with positive antibodies had coronavirus disease 2019 (COVID‐19) with a mild course. None of the patients were hospitalized or needed further treatment. There was no difference in willingness to take risks in SARS‐CoV‐2 antibody–positive and –negative patients (P = 0.61). Patients were predominantly worried about the economy (61%) and transmitting COVID‐19 (52%), less frequent (26%) about receiving insufficient medical treatment.ConclusionThese are the first clinical results concerning SARS‐CoV‐2 seropositivity and COVID‐19 disease in patients with SBS. The seropositivity is comparable to national data, which we attribute to increased risk awareness and avoidance. Further studies are warranted to investigate effects of COVID‐19 infection in SBS patients.

Cholecystectomy prior to short bowel syndrome does not alter nutritional prognosis

BackgroundPrevious cholecystectomy is common in patients with short bowel syndrome (SBS). An intact gallbladder is beneficial in preventing cirrhosis in SBS patients, but the nutritional consequences of cholecystectomy are largely unknown. Our aim was to evaluate the effect of pre-SBS cholecystectomy on need for chronic parenteral nutrition (PN). MethodsWe reviewed 485 adults with SBS: 267 underwent cholecystectomy prior to SBS and 218 patients had an intact gallbladder. Demographic data, intestinal anatomy, and nutritional outcome were compared. ResultsPre-SBS cholecystectomy patients were more likely to have had postoperative SBS and BMI >35. Intestinal remnant length and anatomy type and performance of surgical rehabilitation procedures within the first year were similar.Overall, there was no significant difference in the need for PN > 1year between the two groups. There was also no significant difference in the need for PN > 1year in any specific subgroup of intestinal remnant length or intestinal anatomy. ConclusionsCholecystectomy performed prior to the development of SBS does not influence the nutritional prognosis of SBS, regardless of the intestinal remnant length and anatomy type.

Dietary fiber-based regulation of bile salt hydrolase activity in the gut microbiota and its relevance to human disease

ABSTRACT Complications of short bowel syndrome (SBS) include malabsorption and bacterial overgrowth, requiring prolonged dependence on parenteral nutrition (PN). We hypothesized that the intolerance of whole food in some SBS patients might be due to the effect of dietary fiber on the gut microbiome. Shotgun metagenomic sequencing and targeted metabolomics were performed using biospecimens collected from 55 children with SBS and a murine dietary fiber model. Bioinformatic analyses were performed on these datasets as well as from a healthy human dietary intervention study. Compared to healthy controls, the gut microbiota in SBS had lower diversity and increased Proteobacteria, a pattern most pronounced in children on PN and inversely correlated with whole food consumption. Whole food intake correlated with increased glycoside hydrolases (GH) and bile salt hydrolases (BSH) with reduced fecal conjugated bile acids suggesting that dietary fiber regulates BSH activity via GHs. Mechanistic evidence supporting this notion was generated via fecal and plasma bile acid profiling in a healthy human fiber-free dietary intervention study as well as in a dietary fiber mouse experiment. Gaussian mixture modeling of fecal bile acids was used to identify three clinically relevant SBS phenotypes. Dietary fiber is associated with bile acid deconjugation likely via an interaction between gut microbiota BSHs and GHs in the small intestine, which may lead to whole food intolerance in patients with SBS. This mechanism not only has potential utility in clinical phenotyping and targeted therapeutics in SBS based on bile acid metabolism but may have relevance to other intestinal disease states.

Severe Short Bowel Syndrome: Prognosis for Nutritional Independence Through Management by a Multidisciplinary Nutrition Service and Surgery.

Short bowel syndrome (SBS) is a debilitating condition associated with significant morbidity and mortality. Historically, SBS patients require indefinite parenteral nutrition (PN) and endure lifelong nutritional challenges. The purpose of this study was to review the outcomes, specifically nutritional independence, of a multidisciplinary nutrition service. A retrospective analysis of SBS patients followed by our surgical nutrition service was performed. Patients without 1-year follow-up were excluded. Demographics and nutritional parameters were collected at 4 intervals: initial presentation, 1-year, 2-year, and 5-year follow-up. Short bowel syndrome anatomical subtypes identified through operative reports were characterized as end jejunostomy, jejunocolonic, or jejuno-ileocolonic with ileo-cecal valve intact. Intestinal failure was defined by the requirement of PN, while intestinal insufficiency was defined by enteral support requirement. Clinical outcomes examined included mortality, fistula closure, and nutritional independence. The study cohort comprised 89 patients, 50 of whom had ≤ 100cm intestinal length. Mean age was 57 ± 17y, 55 (62%) were female, and median initial intestinal length was 77 [60-120] cm. Short bowel syndrome was complicated by fistulas in 47 (53%) of patients. Overall mortality was 13%, and 67 (75%) were liberated from PN. A total of 58 (65%) underwent operative intervention and fistula closure was achieved in 37 of 47 (79%) patients. Short bowel syndrome patients can experience significant benefit under treatment by a multidisciplinary nutrition service. By incorporating surgical intervention, the majority of patients previously relegated to lifelong PN have the opportunity to become nutritionally independent within 5 years.

How Broad Should Gram-Negative Coverage Be for Febrile Parenteral Nutrition Dependent Short Bowel Syndrome Patients?

Broader spectrum Gram-negative antibiotics are commonly utilized empirically for central line-associated bloodstream infections (CLABSI) in febrile short bowel syndrome (SBS) patients receiving home parenteral nutrition compared to those used empirically for inpatient-acquired CLABSI. This analysis reports 57 CLABSI in 22 patients with SBS admitted from the community and 78 inpatient-acquired CLABSI in 76 patients over a 5-year period. Proportional Gram-negative CLABSI was similar between the SBS and inpatient-acquired cohorts (43.8% vs42.3%, respectively, P = 0.78). 1.8% and 10.3% (P = 0.125) of Gram-negative CLABSI were non-susceptible to ceftriaxone and 0% and 3.8% (P = 0.52) were non-susceptible to ceftazidime in the SBS and inpatient-acquired cohorts, respectively. In the SBS cohort, home ethanol lock therapy and prior culture results impacted Gramnegative pathogen distribution. Broader empiric Gram-negative coverage for CLABSI among SBS patients compared to inpatients is unnecessary. Third-generation cephalosporins represent appropriate empiric Gramnegative agents for febrile SBS patients presenting from the community to our institution.

Enterohormone therapy for short bowel syndrome.

Short bowel syndrome (SBS) patients are at risk to develop intestinal failure when the decreased absorption of macronutrients, water, and electrolytes necessitates parenteral support for survival. The adverse effects of SBS and parenteral support negatively affect the quality of life (QoL) of SBS-intestinal failure patients. However, spontaneous intestinal adaptation along with disease-modifying therapies allow reducing parenteral support, thereby improving QoL. During the first years following extensive surgery, spontaneous structural and functional intestinal changes take place which stimulate a more efficient nutrient and fluid absorption in the remaining bowel. Given their potential role in the ileal braking mechanism, enterohormones, such as glucagon-like peptide (GLP)-2, GLP-1, and peptide YY (PYY), promote an accelerated adaptation or hyperadaptation. While the exact role of GLP-1 and PYY in SBS is still being explored, GLP-2 analogs have clearly shown to be effective in improving outcome in SBS. Whereas spontaneous intestinal adaptation improves the nutritional status of SBS patients to a certain extent, GLP-2 analogs can further decrease parenteral support needs through hyperadaptation. There are, however, other promising candidates on the horizon that - alone or in combination - could possibly establish additional disease-modifying effects.

Managing Home Parenteral Nutrition during Pregnancy in Patient with Short Bowel Syndrome: Case Report of a Successful Experience in Sabah, Malaysia

Short bowel syndrome (SBS) is one of the pathophysiological mechanisms of chronic intestinal failure (IF) which warrants long-term parenteral nutrition (PN). Despite the common use of PN, there has been few literature on PN use for IF patients since before pregnancy. Our patient was diagnosed with gangrenous bowel secondary to congenital malrotation in 2015. Extensive bowel resection resulted in SBS requiring lifelong home PN. In February 2020, patient discovered her pregnancy and PN pharmacists were informed. Energy from PN was increased with addition of multivitamins, trace elements (TEs) and electrolytes tailored to weekly blood results. At gestation week 34, 24-hour urine urea test showed positive nitrogen balance of +3g/day, demonstrating adequate supply from PN. At gestation week 37, a small-for-gestational-age female infant was delivered via spontaneous labour. Apgar score demonstrated excellent condition and the infant managed to thrive subsequently. Patient’s pre-pregnancy underweight status and insufficient weight gain throughout pregnancy are believed to have put her at higher risk for low-birth-weight infant. Vitamins and TEs supplementation generally met the recommendation for pregnancy, which is however established for oral/enteral intake. This case report proved that successful pregnancy is possible in SBS patients on HPN with close monitoring and effective communication with patient.

Acute intestinotrophic effects of short and long-acting glp-2 analogues in rats

Rationale: Short bowel syndrome (SBS) is a debilitating condition where parenteral support often is a prerequisite for patients’ survival. Additional medical therapies with acute and prolonged action are wanted to improve quality of life for patients with SBS. Endogenous glucagon-like-peptide 2 (GLP-2) and synthetic GLP-2 analogues possess remarkable intestinotrophic effects. Teduglutide (Takeda) is a marketed short-acting GLP-2 analogue for SBS patients, requiring daily dosing in man. Glepaglutide (Zealand Pharma) is a novel long-acting GLP-2 analogues currently in phase 3 clinical trial for SBS. The aim of the present study was to investigate the acute intestinotrophic effects of short vs long-acting GLP-2 analogues in rats.

Effect of teduglutide on parenteral support in patients with short bowel syndrome: a cohort study from the canadian home parenteral nutrition registry

Rationale: Teduglutide is a synthetic GLP-2 analog approved for the treatment of adult’s patients with short bowel syndrome (SBS) and has been shown to reduce parenteral support (PS) requirement. The objective of this study was to assess the effect of teduglutide on PS in SBS patients enrolled in the Canadian Home Parenteral Nutrition (HPN) registry.

Teduglutide in short bowel syndrome patients: A way back to normal life?

BackgroundThe glucagon‐like peptide 2 analogue teduglutide is an effective drug for the treatment of short bowel syndrome patients with intestinal failure (SBS‐IF). This intestinotrophic peptide improves intestinal capacity for fluid and nutrient absorption through induction of mucosal growth and reduction of gastrointestinal motility. Clinical trials demonstrated the efficacy of teduglutide in reducing the need for parenteral support (PS). This study describes an SBS‐IF patient population receiving teduglutide therapy in a specialized medical care setting.MethodA retrospective analysis was performed using data of patients experiencing nonmalignant SBS‐IF. They were treated with teduglutide in a multidisciplinary SBS‐IF program at a single university medical center between June 2016 and June 2020.ResultsThirteen patients under teduglutide treatment were included in the final analysis. Mean small bowel length was 82 ± 31 cm, with 77% of patients having their colon in continuity. Over a median follow‐up of 107 weeks, all patients (13 of 13, 100%) responded to the therapy with a clinically significant reduction of PS volume. Mean PS reduction increased with therapy duration and ranged from −82.5% at week 24 (n = 13) to −100% in patients (n = 5) who were treated for 144 weeks. Enteral autonomy was achieved in 12 of 13 (92%) patients. Teduglutide therapy improved stool frequency and consistency, changed dietary habits, and reduced disease‐associated sleep disruptions.ConclusionIntegrating SBS‐IF patients treated with teduglutide in a proactive and tight‐meshed patient care program significantly improves the clinical outcome, leading to an increased proportion of patients reaching enteral autonomy.

S1368 The Pharmacokinetics of Long-Acting GLP-1 Analogue (NM-002) in Patients With Short Bowel Syndrome

Introduction: Glucagon-like peptide-1 (GLP-1) analogues are known to slow down gastric and intestinal motility. NM-002 is a long-acting GLP-1 analogue designed to be used in patients with short bowel syndrome (SBS). The aim of this study was to explore the pharmacokinetic profile of NM-002 in patients with SBS. Methods: Adult patients with SBS were randomized to receive either 50 mg, 100 mg, or 150 mg of NM-002 on Day 1 and Day 15 of the study. Levels of NM-002 were measured with an electrochemiluminescence (ECL) immunoassay, where human anti-Exendin-4 antibody and anti-XTEN biotinylated antibody were used to capture NM-002 molecules and SULFO-TAG Streptavidin bound to the biotinylated NM-002 that was used to generate an electrochemiluminescence signal. This signal was compared to signals generated with known standards of NM-002; the concentration of the NM-002 was back-calculated from the 4-parameter 1/y2 non-linear regression of the standards. The accuracy and precision of this method was validated to be within -3.80% to 12.18%. Results: Nine SBS patients (5m/4f) were recruited to the study; the average age was 51.8 years and an average BMI was 22.1 kg.m-2. Three subjects received 50 mg dose, 4 subjects received 100 mg dose and 2 subjects received 150 mg dose. One of the 50 mg patients did not receive a second dose due to a protocol violation. The mean half-life ranged between 300 and 750 hours and was independent of the dose administered. The pharmacokinetic profile of NM-002 are shown in the table and graph below (Mean + SD). Conclusion: The pharmacokinetic profile of NM-002, a long-acting GLP-1 analogue, shows dose dependent effect with accumulation at Day 15 supporting its extended half-life time. These pharmacokinetic data support twice monthly fixed dosing regimen (or better).Table 1.: The pharmacokinetic profile of NM-002.

S3030 Safety and Efficacy of Teduglutide Therapy for Management of Short Bowel Syndrome After Intestinal Transplantation

Introduction: Intestinal transplantation is a rare surgical procedure performed on patients with severe short bowel syndrome, characterized by inadequate intestinal absorption. Teduglutide, an intestinotrophic drug, increases patients’ intestinal absorption. This case study examines treatment courses of three short bowel syndrome patients beginning teduglutide treatment after intestinal transplantation. Case Description/Methods: 28 data points were collected regarding three intestinal allograft recipients’ teduglutide therapy treatment course. Two patients underwent solitary small intestine transplant, one underwent multivisceral transplant. Biopsy of two patients showed acute and chronic rejection of intestinal allograft; one patient had flattened intestinal villi. Teduglutide aimed to mitigate intestinal insufficiency secondary to rejection or explant-caused short bowel syndrome. All patients were on total parenteral nutrition. Total parenteral nutrition reduction began after a mean of 6.1 (range: 1.4–14.7) months on teduglutide. All patients’ diarrhea improved. Two patients were hospitalized on teduglutide: one for unrelated complications, the other for nausea and vomiting managed by inpatient total parenteral nutrition and ceasing teduglutide. Two patients experienced fluid overload, managed by total parenteral nutrition reduction. No other teduglutide-related complications were reported. Two patients had colonoscopies performed before and after treatment began. No patient was diagnosed with colon polyps, intestinal obstruction, or acute rejection during treatment. One patient developed chronic kidney disease secondary to immunosuppression; teduglutide was stopped upon dialysis initiation and resumed following stabilization. All patients are alive for a mean of 42.6 (range: 4.3–81.0) months since beginning teduglutide. Discussion: Teduglutide was safe and effective in managing our cohort’s short bowel syndrome post-intestine transplant. Teduglutide-linked complications were limited to fluid overload. No evidence of additional complications was found.

Current Surgical Concepts and Indications in the Management of the Short Bowel State: A Call for the Use of Multidisciplinary Intestinal Rehabilitation Programs.

The mainstay of management for short bowel syndrome (SBS) is to promote access to the best quality of care provided by the intestinal rehabilitation program (IRP) in specialized centres. When treating SBS patients, the main goal is to minimize disease-associated complications, as well as achieve enteral autonomy. Surgical strategies should be selected cautiously upon the actual state of the bowel with respect to what it is clinically relevant for that specific patient. To this aim, a personalized and multidisciplinary approach for such a complex syndrome is needed.

Vitamin D Deficiency is Prevalent in Short Bowel Syndrome Patients on Long-Term Parenteral Nutrition Support

Vitamin D Deficiency is Prevalent in Short Bowel Syndrome Patients on Long-Term Parenteral Nutrition Support

Fecal microbiome alterations in pediatric patients with short bowel syndrome receiving a rotating cycle of gastrointestinal prophylactic antibiotics.

Pediatric patients with short bowel syndrome (SBS) are at risk of developing small intestinal bacterial overgrowth (SIBO). Prevention of SIBO using cyclic enteric antibiotics has been implemented to control the balance in microbial ecosystems, although its effectiveness has not been well studied. This study aimed to explore the change in the gut microbial composition in SBS patients during cyclic antibiotic phases and antibiotic-free period, and to compare the microbiota composition between healthy controls and SBS patients. SBS patients taking oral metronidazole alternating with trimethoprim-sulfamethoxazole (TMP-SMT) and antibiotic-free conditions as a '10-day cyclic protocol' were involved in fecal microbiome study using Illumina 16S sequencing. When healthy control possessed the majority of Bacteroidetes spp. (54%) and Firmicutes spp. (33%), the microbial composition in SBS patients especially Firmicutes spp. and Proteobacteria spp. was prominently changed in each phase of treatment. In antibiotic-free period, SBS patients displayed 49% Firmicutes and 36% Proteobacteria. However, higher Proteobacteria than Firmicutes were detected at the commencement of metronidazole (58% versus 33%). Similarly, 56% Proteobacteria and 27% Firmicutes were found during TMP-SMT. Escherichia coli increased prominently during the antibiotic periods. Prophylactic antibiotics change the gut microbiota composition in an unfavorable direction, especially when repeatedly used for a long period. This practice should be reconsidered. III.

P-29: Rapid Progression of Parenteral Nutrition-associated Liver Disease on Liver Biopsies of Pediatric Patients with Short-gut Syndrome: a Case Series

Introduction: The rate of parenteral nutrition-associated liver disease (PNALD) development in short-bowel syndrome (SBS) children on total parenteral nutrition (TPN) is unknown. We present the first case series of pediatric SBS patients on TPN with rapid progression of their PNALD on liver biopsies (LB) obtained <12 months (m) after TPN initiation. Methods: Charts of 81 children with a history of TPN use at a single institution between 2009-2019 were reviewed for inclusion criteria: 1) SBS diagnosis 2) LB obtained <12 m after TPN initiation and 3) No underlying liver disease. Clinical history, nutritional support, and liver function markers (direct bilirubin [Dbili], aspartate aminotransferase [AST], alanine aminotransferase, international normalized ratio, AST to Platelets Ratio Index, ultrasound elastography and LB) were collected via retrospective chart review approved by our institutional review board. Liver pathology was graded by one pathologist. Results: 10 patients fulfilled criteria; the mean duration on TPN prior to LB was 4m (range 1-10.8m) with half on Intralipid, and the other half on an alternative lipid emulsion. Seventy percent also received enteral feeds. Forty percent patients had elevated Dbili. All LBs showed moderate to marked bile ductular reaction associated with a mixed, portal-predominant inflammatory infiltrate of lymphocytes, neutrophils, and occasional eosinophils of mild to moderate severity. Inflammatory infiltration of interlobular bile ducts was a rare finding in a subset of cases; plasma cells were not a prominent feature. Most samples showed some degree of cholestasis, usually canalicular. Lobular inflammation and hepatocyte necrosis were typically mild and nonzonal/spotty though some showed diffuse ballooning hepatocellular injury. No significant steatosis was observed. Fibrosis on trichrome stain was variable, typically portal-predominant; few cases demonstrated pericellular fibrosis. Based on the LB pathology, 70% had a change in medical care such as changing the lipid emulsion. Conclusion: The progression of PNALD in SBS children on LBs <12 months from TPN initiation was more rapid than previously hypothesized. LBs taken at the time of another surgical procedure may be warranted for SBS pediatric patients on TPN.