Short Bowel Syndrome Patients Research Articles

The Epidemiology and Clinical Management of Short Bowel Syndrome and Chronic Intestinal Failure in Crohn's Disease in Italy: An IG-IBD Survey.

Limited data exist on the epidemiology and clinical management of short bowel syndrome (SBS) and chronic intestinal failure (CIF) in Crohn's disease (CD). This study aimed to evaluate these aspects in Italy. Members of the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD) were invited to complete a cross-sectional web survey. A subgroup analysis examined the influence of different clinical settings on SBS and CIF management in CD. A total of 47/128 (36.7%) IG-IBD centers participated. Among them, 31.9% were teduglutide (TED) prescribers, and 48.9% were academic centers. The median estimated prevalence of CIF among small bowel CD patients was 1%, and it was significantly higher in academic centers (2.0% [IQR 1-5%] vs. 0.13% [IQR 0-1%], p = 0.02). Seventy-eight percent of centers managed fewer than 10 SBS and CD patients. Routine small bowel measurement and nutritional assessment were performed in only 15% and 42.6% of centers, respectively. TED was prescribed by 12 centers to 35 patients, with a treatment success rate exceeding 50% in 81.8% of centers. The estimated prevalence of CIF in CD patients with small bowel involvement in Italy is 1%. The diagnosis and management practices for SBS and CIF are suboptimal, and TED use is limited.

Successful weaning from parenteral nutrition in a short bowel syndrome patient with high-output stoma through restricted oral diet: a case report.

A restricted oral diet plays a significant role in the nutritional management of patients with Short Bowel Syndrome (SBS). SBS patients often experience increased intestinal output, especially if they are classified as net "secretors" (typically having less than 100 cm of residual jejunum). This means they lose more water and sodium from their stoma than they take in by mouth. In this report, we present the case of an SBS patient with 80 cm of remaining bowel, no colon in continuity, and a high-output stoma. The patient was managed with a restrictive oral diet in combination with parenteral nutrition, pharmacological treatment, and high patient compliance. Following this regimen, the patient's condition improved significantly, leading to a reduction in stoma output and an improvement in nutritional status, including stabilization and weight gain. Upon discharge from the hospital, the patient was maintaining an oral diet with specific nutritional recommendations and receiving parenteral saline. This case report suggests that the combined use of restricted oral intake and parenteral nutrition (PN), alongside appropriate pharmacological management and high patient compliance, can effectively manage high-output stomas and improve nutritional status, even in cases where the small bowel is less than 100 cm in length.

Textbook outcome in short bowel syndrome

BackgroundTextbook outcome (TO) is a single composite score representing ideal care for a procedure or medical condition. Short bowel syndrome (SBS) patients are at high risk for complications and death. Our aim was to determine the incidence of and predictive factors for a TO in SBS patients. Methods515 adults with SBS were followed for 12 months after initial hospital discharge for SBS. TO was defined based on eight outcome parameters. Demographic data, intestinal anatomy, and nutritional outcome were compared in patients with and without TO. Results78 (15 ​%) patients had a TO. The frequency of the different components of TO were: PN ​< ​1 year (39 ​%), BMI >18.5 ​kg/m2 (89 ​%), no stoma (59 ​%), no surgical intervention (71 ​%), no hospital readmission (56 ​%), no vascular access infection (62 ​%), absence of end stage liver disease (96 ​%), and survival (97 ​%). Intestinal remnant length and anatomy type were predictive of a TO. ConclusionsA TO is achieved in 15 ​% SBS patients using the selected criteria. This is largely attributable to continued need for PN. Intestinal length and anatomy were independent predictors of TO.

Impaired intestinal FXR signaling is involved in aberrant stem cell function leading to intestinal failure-associated liver disease in pediatric patients with short bowel syndrome.

Intestinal failure-associated liver disease (IFALD) is a serious complication of long-term parenteral nutrition in patients with short bowel syndrome (SBS), and is the main cause of death in SBS patients. Prevention of IFALD is one of the major challenges in the treatment of SBS. Impairment of intestinal barrier function is a key factor in triggering IFALD, therefore promoting intestinal repair is particularly important. Intestinal repair mainly relies on the function of intestinal stem cells (ISC), which require robust mitochondrial fatty acid oxidation (FAO) for self-renewal. Herein, we report that aberrant LGR5+ ISC function in IFALD may be attributed to impaired farnesoid X receptor (FXR) signaling, a transcriptional factor activated by steroids and bile acids. In both surgical biopsies and patient-derived organoids (PDOs), SBS patients with IFALD represented lower population of LGR5+ cells and decreased FXR expression. Moreover, treatment with T-βMCA in PDOs (an antagonist for FXR) dose-dependently reduced the population of LGR5+ cells and the proliferation rate of enterocytes, concomitant with decreased key genes involved in FAO including CPT1a. Interestingly, however, treatment with Tropifexor in PDOs (an agonist for FXR) only enhanced FAO capacity, without improvement in ISC function and enterocyte proliferation. In conclusion, these findings suggested that impaired FXR may accelerate the depletion of LGR5 + ISC population through disrupted FAO processes, which may serve as a new potential target of preventive interventions against IFALD for SBS patients.

Translating plasma citrulline concentration in clinical practice: Role of cross-sectional assessment in adult patients with short bowel syndrome

BackgroundCross-sectional plasma citrulline concentration (CIT) is considered a marker of enterocyte mass. The role of CIT in clinical practice in patients with short bowel syndrome (SBS) is not clearly defined. AimTo assess the accuracy of CIT to discriminate SBS from healthy controls (HC) and SBS with intestinal failure (SBS-IF), requiring intravenous supplementation (IVS), from SBS with intestinal insufficiency (SBS-II). MethodsCross-sectional study on unselected outpatients (31 SBS-II, 113 SBS-IF) and 19 healthy controls (HC). Demographic data, SBS characteristics, nutritional status, oral intake, intestinal fat absorption, renal function and IF severity, categorized by the volume of the required IVS, were collected at time of CIT evaluation (µmol/L). Data as mean±SD. ResultsCIT was 36.6 ± 6.0 in HC, 30.2 ± 14.0 in SBS-II and 18.8 ± 12.3 in SBS-IF (p < 0.001). CIT cutoff was 31 for the diagnosis of SBS (sensitivity 79 %, specificity 89 %), and 14 for the discrimination between SBS-IF and SBS-II (sensitivity 100 %, specificity 51 %). Wide ranges of CIT were observed in all SBS-IF severity categories. ConclusionsIn unselected SBS patients, CIT was accurate to diagnose SBS, had high sensitivity to diagnose SBS-IF but showed low specificity for SBS-II. In SBS-IF, CIT was not an accurate marker of IF severity.

#1964 Diagnosis performance of urine oxalate/creatinine ratio for hyperoxaluria screening

Abstract Background and Aims Primary and secondary hyperoxaluria is characterized by significantly elevated urinary oxalate levels, increased risk of kidney stones, nephrocalcinosis, and chronic kidney disease. Patients with enteric hyperoxaluria are especially at high-risk populations. However, identifying hyperoxaluric individuals within these populations remains challenging due to difficulties in obtaining complete urine collections. This study aims to evaluate the diagnostic performance of the urine oxalate/creatinine ratio to improve the screening of hyperoxaluria. Method We pooled data from an adult tertiary renal exploration center, including living donors, short bowel syndrome patients, bariatric surgery patients, and individuals with nephrolithiasis or other nephrological issues undergoing 24-hour urine analysis. We assessed the relationship between the urine oxalate/creatinine ratio and 24-hour oxalate excretion. The diagnostic performance of the ratio was analyzed using ROC curves, and an optimal diagnostic threshold was established. Results Of the 1485 initially included adult patients reported in Table 1, 37% lacked complete urine collections, resulting in a study population of 974 individuals (453 females, 521 males, median age 48 years, median renal function 97 ml/min/1.73 m²). Nineteen percent had hyperoxaluria, with a higher prevalence in females (25% vs. 13% in males). Median 24-hour oxaluria was 548 (432,740) µmol/d in the diseased group and 244 (188,309) µmol/d in the healthy group. A strong correlation (Spearman's rank correlation rho= 0.8, p &amp;lt; 0.001) was found between the urine oxalate/creatinine ratio and 24-hour oxalate excretion. ROC curves for both genders exhibited similar performance, with an optimal threshold for the entire population yielding an AUC of 0.97 (0.962-0.981). The diagnostic threshold for maximum sensitivity was an oxalate/creatinine ratio of 0.025 mmol/mmol (Sensitivity = 1, Specificity = 0.65, PPV = 0.4, NPV = 1), while for maximum specificity, it was an oxalate/creatinine 0.074 mmol/mmol (Sensitivity= 0.31, Specificity = 1, PPV = 1, NPV = 0.862). The optimal diagnostic threshold chosen by the minimum distance from the left-upper corner was an oxalate/creatinine 0.034 mmol/mmol (Sensitivity= 0.92, Specificity = 0.91, PPV = 0.69, NPV = 0.98) (Fig. 1). Conclusion The urine oxalate/creatinine ratio demonstrates excellent diagnostic performance and is efficient in screening hyperoxaluric patients within high-risk populations. However, the positive predictive value is insufficient to be a standalone reliable diagnostic test. Therefore, 24-hour urine oxalate measurement remains necessary for diagnosis.

Quality of Life of Children with Short Bowel Syndrome from Patients' and Parents' Points of View.

Despite limited research, existing studies using generic quality of life (QOL) tools indicate decreased physical health and compromised emotional functioning in children with IF. This study investigates QOL in children with short bowel syndrome (SBS) and its determinants. The study included 57 pediatric patients with SBS treated at Mannheim's University Hospital between 1998 and 2014. To evaluate QOL, the KINDL questionnaire was used. Three age-specific questionnaire variants were employed, and parental proxy reports were collected. Most patients underwent intestinal lengthening procedures, with varying primary diagnoses. A comparison with healthy children from the patient's perspective revealed no difference but from the parent's perspective showed lower QOL in SBS patients, especially regarding physical and mental well-being. QOL varied with age, with 7-10-year-olds reporting the lowest scores. Several factors, including independence from parenteral nutrition and the presence of a complete colon, positively influenced QOL. The independence of parenteral nutrition and the presence of a complete colon positively influenced QOL. The Bianchi technique for intestinal lengthening has also shown promise but needs further research. The observation sample in this study is too small to generalize about the whole population of SBS patients. However, this study shows that many health and treatment factors affect QOL, and a large multicenter study is necessary. Our findings underline the importance of appropriate psychological support for children with SBS and their families.

Prevalence of eosinophilic gastrointestinal diseases in children with short bowel syndrome: A single center study.

Patients with short bowel syndrome (SBS) have multiple risk factors for eosinophilic gastrointestinal diseases (EGIDs) including increased risk for intestinal dysbiosis and food allergy compared to their counterparts with normal anatomy. However, there is limited data on the prevalence of EGIDs in children with SBS. We aimed to define the prevalence of EGIDs in an SBS cohort and its association with different risk factors via a retrospective chart review of patients with SBSat Children's National Hospital. The prevalence of eosinophilic esophagitis in our SBS cohort was 10%, eosinophilic gastritis was 4.9%, and eosinophilic enteritis was 4.9%. SBS patients with history of allergy or atopy were more likely to have esophageal and intestinal eosinophilia on biopsy than patients without allergy. The prevalence of EGIDs in our SBS cohort is significantly higher than in the general population and may be associated with allergic polarization.

Important issues in proposing autonomy training in home parenteral nutrition for short bowel syndrome patients: a qualitative insight from the patients' perspectives.

The standard treatment for short bowel syndrome is home parenteral nutrition. Patients' strict adherence to protocols is essential to decrease the risk of complications such as infection or catheter thrombosis. Patient training can even result in complete autonomy in daily care. However, some patients cannot or do not want too much responsibility. However, doctors often encourage them to acquire these skills. Based on qualitative investigations with patients, we wanted to document issues of importance concerning perceptions of autonomy in daily care. Semistructured interviews were conducted with 13 adult patients treated by home parenteral nutrition using a maximum variation sampling strategy. We proceeded to a thematic analysis following an inductive approach. After achieving clinical management of symptoms, a good quality of life is within the realm of possibility for short bowel syndrome patients with home parenteral nutrition. In this context, achieving autonomy in home parenteral nutrition could be a lever to sustain patients' quality of life by providing better life control. However, counterintuitively, not all patients aim at reducing constraints by reaching autonomy in home parenteral nutrition. First, they appreciate the social contact with the nurses, which is particularly true among patients who live alone. Second, they can feel safer with the nurse's visits. Regaining freedom was the main motivation for patients in the training program and the main benefit for those who were already autonomous. Medical teams should consider patients' health locus of control (internal or external) for disease management to support them concerning the choice of autonomy in daily care for parenteral nutrition.

A case report of anemia associated with short bowel syndrome corrected by EPO during nutrition therapy

Many study showed long-term parenteral treatment often couple with iron-deficiency anemia. This case was a short bowel syndrome (SBS) patient with remaining 15 centimeters intestine and intact ileocecal valve.

A Systematic Review of Quality of Life in Patients with Short Bowel Syndrome and Their Caregivers.

Understanding the quality of life and the factors that influence it for patients with short bowel syndrome (SBS) and their caregivers is of utmost importance in order to enhance their well-being. Therefore, This study aimed to provide a comprehensive understanding of the impact of SBS on patients and their caregivers, as well as its associated factors, by synthesizing the available evidence. A systematic review of the literature was done using PubMed, Embase databases, CNKI, and ISPOR conference papers. Included articles were manually searched to identify any other relevant studies. Quality was assessed using appropriate Joanna Briggs Institute critical appraisal tools. This review included 16 studies, comprising 15 observational studies and 1 randomized controlled trial. The findings revealed that the QoL of patients with SBS was lower than that of the general population regarding physical functioning and psychological domain. Meanwhile, caregivers experienced challenges in maintaining their QoL. The QoL of SBS patients was found to be influenced by various factors such as treatment, age, sex, stoma, and small intestine length. Among them, the treatment is the most noteworthy factor that can be effectively improved through external interventions. While numerous studies have provided insights into the compromised QoL experienced by individuals with SBS and their caregivers, there remains a scarcity of large-sample quantitative investigations examining the determinants of QoL. The existing body of literature on caregivers is also notably deficient.

Circulating Oxalate Levels in Short Bowel Syndrome as a Severity Marker of CKD

BackgroundPatients with short bowel syndrome (SBS) may exhibit enteric hyperoxaluria (EH), and the prevalence of oxalate nephropathy in SBS is likely underestimated. Plasma oxalate (POx) is a surrogate of systemic oxalate deposition and, consequently, may increase the risk of developing chronic kidney disease (CKD). The main objective was to explore the distribution of plasma oxalate levels in SBS patients. MethodsPatients followed for SBS were recruited prospectively in the OXAGO study (NCT04119765) to assess POx during their annual renal follow-up including iohexol clearance. Inclusion criteria were age ≥ 18 years, and SBS type II and type III for more than 6 months. ResultsForty-seven patients were included but only 45 patients has a measured Pox (55 % males, 80 % SBS type 2, 66 % parenteral nutrition, 61% kidney stone history). POx levels were 6.8±4.4 μmol/L, 29 % of patients had POx ≥5 μmol/L. In the whole cohort, mean urinary oxalate (UOx) was 648 ± 415 and 54 % were > 500 μmol/24hrs. In the group of patients with high POx levels (HPO), 24hr-urine oxalate was significantly higher than in the group with normal POx levels (NPO): 919±566 vs 526±257 μmol/L, p=0.003.GFR was 66±22 mL/min/1.73m2, 91% had CKD. GFR was significantly lower in the HPO than in the NPO group: 49±23 vs 73±18 mL/min/1.73m2, p=0.0005. ConclusionPatients with SBS can display increased POx levels even with GFR > 30 mL/min per 1.73m2. POx may be an interesting biomarker to assess the severity of enteric hyperoxaluria.

Glepaglutide efficacy and safety in short bowel syndrome patients without or with colon-in-continuity: Results of ease sbs 1 phase 3 trial

Glepaglutide efficacy and safety in short bowel syndrome patients without or with colon-in-continuity: Results of ease sbs 1 phase 3 trial

Determinants of parenteral nutrition (PN) weaning in a pediatric cohort of short bowel syndrome (SBS) patients in the era of GLP-2 analogue treatment

Determinants of parenteral nutrition (PN) weaning in a pediatric cohort of short bowel syndrome (SBS) patients in the era of GLP-2 analogue treatment

High frequency of tyg index in adult short Bowel syndrome patients weaned from parenteral nutrition

High frequency of tyg index in adult short Bowel syndrome patients weaned from parenteral nutrition

Featuring molecular regulation of bile acid homeostasis in pediatric short bowel syndrome.

Disturbed bile acid homeostasis may foster development of short bowel syndrome (SBS) associated liver disease during and after weaning off parenteral nutrition (PN). Our aim was to study hepatic molecular regulation of bile acid homeostasis in relation to serum and fecal bile acid profiles in pediatric SBS. Liver histopathology and mRNA expression of genes regulating synthesis, uptake and export of bile acids, and cellular receptors involved in bile acid signaling were measured in SBS patients (n=33, median age 3.2 years). Simultaneously, serum (n=24) and fecal (n=10) bile acid profiles were assessed. Sixteen patients were currently on PN. Results of patients were compared to healthy control subjects. Nine of ten (90%) patients with histological cholestasis received current PN, while portal inflammation was present in 60% (6/10) of patients with cholestasis compared to 13% (3/23) without cholestasis (P=0.01). In all SBS patients, hepatic synthesis and uptake of bile acids was increased. Patients on current PN showed widespread repression of hepatic FXR target genes, including downregulated canalicular (BSEP, MDR3) and basolateral (MRP3) bile acid exporters. Serum and fecal primary bile acids were increased both during and after weaning off PN. Bile acid homeostasis in SBS is characterized by interrupted enterohepatic circulation promoting increased hepatic synthesis and conservation of bile acids. In PN dependent SBS patients with hepatic cholestasis and inflammation, the molecular fingerprint of downregulated hepatocyte canalicular and basolateral bile acid export with simultaneously increased synthesis and uptake of bile acids could favor their accumulation in hepatocytes and predispose to liver disease.

Predictive Potential of Biomarkers of Intestinal Barrier Function for Therapeutic Management with Teduglutide in Patients with Short Bowel Syndrome.

The human intestinal tract reacts to extensive resection with spontaneous intestinal adaptation. We analyzed whether gene expression analyses or intestinal permeability (IP) testing could provide biomarkers to describe regulation mechanisms in the intestinal barrier in short bowel syndrome (SBS) patients during adaptive response or treatment with the glucagon-like peptide-2 analog teduglutide. Relevant regions of the GLP-2 receptor gene were sequenced. Gene expression analyses and immunohistochemistry were performed from mucosal biopsies. IP was assessed using a carbohydrate oral ingestion test. The study includes 59 SBS patients and 19 controls. Increases in gene expression with teduglutide were received for sucrase-isomaltase, sodium/glucose cotransporter 1, and calcium/calmodulin serine protein kinase. Mannitol recovery was decreased in SBS but elevated with teduglutide (Δ 40%), showed a positive correlation with remnant small bowel and an inverse correlation with parenteral support. Biomarkers predicting clinical and functional features in human SBS are very limited. Altered specific gene expression was shown for genes involved in nutrient transport but not for genes controlling tight junctions. However, mannitol recovery proved useful in describing the absorptive capacity of the gut during adaptation and treatment with teduglutide.

Intestinal microbiome in short bowel syndrome: diagnostic and therapeutic opportunities.

The intestinal microbiome plays a strong, complementary role in the development and integrity of the intestinal epithelium. This biology is crucial for intestinal adaptation, particularly after the mucosal insults that lead to short bowel syndrome (SBS). The purpose of this review is to discuss relationships between the intestinal microbiota and the physiology of intestinal adaptation. We will address interactions between the intestinal microbiome and nutritional metabolism, factors leading to dysbiosis in SBS, and common compositional differences of the gut microbiome in SBS patients as compared to healthy controls. We will also discuss novel opportunities to expand diagnostic and therapeutic interventions in this population, by using our knowledge of the microbiome to manipulate luminal bacteria and study their resultant metabolites. As microbial therapeutics advance across so many fields of medicine, this review is timely in its advocacy for ongoing research that focuses on the SBS population.Our review will discuss 4 key areas: 1) physiology of the intestinal microbiome in SBS, 2) clinical and therapeutic insults that lead to a state of dysbiosis, 3) currently available evidence on microbiome-based approaches to SBS management, and 4) opportunities and innovations to inspire future research. The clinical implications of this review are both current, and potential. Understanding how the microbiome impacts intestinal adaptation and host physiology may enhance our understanding of why we experience such clinical variability in SBS patients' outcomes. This review may also expand clinicians' understanding of what 'personalized medicine' can mean for this patient population, and how we may someday consider our nutritional, therapeutic, and prognostic recommendations based on our patients' host, and microbial physiology.

Cutoffs and Characteristics of Abnormal Bowel Dilatation in Pediatric Short Bowel Syndrome.

Although excessive intestinal dilatation associates with worsened outcomes in pediatric short bowel syndrome (SBS), little is known about the natural history and definition of pathological dilatation. We addressed fore-, mid-, and hind-gut dilatation in children with SBS, who had not undergone autologous intestinal reconstructive (AIR) surgery, in relation to controls. SBS children without history of AIR surgery (n = 59) and age-matched controls without any disclosed intestinal pathology (n = 140) were included. Maximum diameter of duodenum, small bowel (SB), and colon were measured in each intestinal contrast series during 2002 to 2020 and expressed as diameter ratio (DR) to L5 vertebrae height. Predictive ability of DR for weaning off parenteral nutrition (PN) was analyzed with Cox proportional hazards regression models using multiple cutoffs. Duodenum (DDR), SB (SBDR), and colon (CDR) DR were 53%, 183%, and 23% higher in SBS patients compared to controls ( P < 0.01 for all). The maximal DDR and SBDR measured during follow-up is associated with current PN dependence and young age. DDR correlated with SBDR ( r = 0.586, P < 0.01). Patients with maximal DDR less than 1.5, which was also the 99th percentile for controls, were 2.5-fold more likely to wean off PN ( P = 0.005), whereas SBDR and CDR were not predictive for PN duration. All segments of remaining bowel, especially SB, dilate above normal levels in children with SBS. In SBS children without AIR surgery, PN dependence and young age is associated with duodenal and small intestinal dilatation, while duodenal dilatation also predicted prolonged PN.

Oral antimicrobial agents in patients with short bowel syndrome: worth a try!

The use of oral antimicrobial agents in patients with short bowel syndrome (SBS) is challenging due to the changes in gastrointestinal anatomy that may result in diminished absorption and altered drug bioavailability. Prospective studies evaluating bioavailability of antimicrobial agents after oral administration in SBS patients are lacking. To determine the bioavailability of orally administered antimicrobial agents commonly used for treatment in SBS patients to guide clinical decision making when faced with infections. We performed an explorative, clinical study investigating the pharmacokinetics (PK) of clindamycin, ciprofloxacin, flucloxacillin and fluconazole in SBS patients with intestinal failure. Participants received a combination of two antimicrobial agents simultaneously. To determine the oral bioavailability, participants received a single oral and IV dose of both agents on two occasions, after which they underwent intensive PK sampling on six predefined time points up to 12 hours after administration. Primary outcome was the oral bioavailability of these antimicrobial agents. Secondary outcomes were intravenous PK characteristics following non-compartmental analysis. Eighteen SBS patients were included: the mean (SD) age was 59 (17) years and 61% of participants were female. The median observed (IQR) bioavailability of ciprofloxacin, clindamycin, flucloxacillin and fluconazole were 36% (24-50), 93% (56-106), 50% (32-76) and 98% (61-107), respectively. The bioavailability of selected antimicrobial agents in certain patients with SBS appeared to be better than expected, providing a feasible treatment option. Due to the large observed differences between patients, therapeutic drug monitoring should be part of the treatment to safeguard adequate exposure in all patients. Registered in the Dutch Trial Register (NL7796) and EudraCT number 2019-002587-28.