Management of pediatric intestinal failure related to short bowel syndrome.

Intestinal failure (IF) secondary to short bowel syndrome is a challenging and complex medical condition with significant risk for surgical and medical complications. Significant advancements in the care of this patient population have led to improved survival rates. Due to their intensive medical needs children with IF are at risk for long-term complications that require comprehensive management and close monitoring. The purpose of this paper is to review the available literature emphasizing the surgical aspects of care for children with IF secondary to short bowel syndrome. A key priority in the surgical care of this patient population includes strategies to preserve available bowel and maximize its function. Utilization of novel surgical techniques and autologous bowel reconstruction can have a significant impact on children with IF secondary to short bowel syndrome related to the function of their bowel and ability to achieve enteral autonomy. It is also important to understand the potential long-term complications to ensure strategies are put in place to mitigate risk with early detection to improve long-term outcomes.

Estudio epidemiológico de la prevalencia del síndrome de intestino corto en España / Epidemiological study of the prevalence of short bowel syndrome in Spain

Introducción: El síndrome de intestino corto (SIC) es una alteración de la absorción de los nutrientes causado, frecuentemente, por la resección quirúrgica del intestino delgado. El espectro de las manifestaciones clínicas varía ampliamente, según la longitud remanente del intestino delgado.Objetivo:Conocer la prevalencia de los casos de SIC en España en el año 2018.Método:Estudio observacional transversal multicéntrico, de base poblacional, mediante cuestionario telemático en el que se recogen los datos de los pacientes diagnosticados de SIC en 2018.Resultados:De un total de 541 centros sanitarios seleccionados, del Catálogo Nacional de Hospitales del Ministerio de Sanidad, participaron 101 hospitales. Con los datos obtenidos, la prevalencia de SIC en España se estimaría en 4,18 pacientes por millón de habitantes durante ese año.Conclusiones:La falta de participación dificulta obtener resultados concluyentes, lo que resulta mucho más importante cuando se trata de problemas de salud poco prevalentes. (AU)

Introduction: Short bowel syndrome (SBS) is a disturbance in nutrient absorption often caused by surgical resection of the small intestine. The spectrum of clinical manifestations varies widely, depending on the remaining length of the small intestine.Objective:To estimate the prevalence of cases of SBS cases in Spain in 2018.Method:A population-based, multicenter cross-sectional study, using an online survey, that collects data from patients diagnosed with SBS in 2018.Results:From a total of 541 health centers selected, of the National Catalog of Hospitals of the Ministry of Health, 101 hospitals took part in. With the data obtained, the prevalence of SIC in Spain would be estimated at 4.18 patients per million inhabitants during that year.Conclusions:Lack of participation makes it difficult to obtain conclusive results, which is much more important when it comes to low prevalence health topics. (AU)

Hospital-based delays to revascularization increase risk of postoperative mortality and short bowel syndrome in acute mesenteric ischemia.

OBJECTIVE: Acute mesenteric ischemia (AMI) is a surgical emergency for which delays in treatment have been closely associated with high morbidity and mortality. Although the duration of ischemia as a determinant of outcomes for AMI is well known, the objective of this study was to identify hospital-based determinants of delayed revascularization and their effects on postoperative morbidity and mortality in AMI. METHODS: All patients who underwent any surgery for AMI from a multi-center hospital system between 2010 and 2020 were divided into two groups based on timeliness of mesenteric revascularization after presentation. Early revascularization (ER) was defined as having both vascular consultation ≤12 hours of presentation and vascular surgery performed at the patient's initial operation. Delayed revascularization (DR) was defined as having either delays to vascular consultation or vascular surgery. A retrospective review of demographic and postoperative data was performed. The effect of DR on major postoperative outcomes, including 30-day and 2-year mortality, total length of bowel resection, and development of short bowel syndrome, were analyzed. Effects of delayed vascular consultation alone, delayed vascular surgery alone, no revascularization during admission, and admitting service on outcomes were also examined on subgroup analyses. RESULTS: A total of 212 patients were analyzed. Ninety-nine patients received ER, whereas the remaining 113 patients experienced a DR after hospital presentation. Among the DR group, 55 patients (25.9%) had delayed vascular consultation, whereas vascular surgery was deferred until after the initial operation in 37 patients (17.4%). Fifty-one patients (24.0%) were never revascularized during admission. DR was a significant predictor of 30-day (odds ratio [OR], 2.09; 95% confidence interval [CI], 1.4-4.9; P = .03) and 2-year mortality (hazard ratio, 1.55, 95% CI, 1.0-2.3; P = .04). DR was also independently associated with increased bowel resection length (OR, 7.47; P < .01) and postoperative short bowel syndrome (OR, 2.4; P = .03) on multivariate analyses. When examined separately on subgroup analysis, both delayed vascular consultation (OR, 3.38; P = .03) and vascular surgery (OR, 4.31; P < .01) independently increased risk of 30-day mortality. Hospital discharge after AMI without mesenteric revascularization was associated with increased risk of short bowel syndrome (OR, 2.94; P < .01) and late mortality (hazard ratio, 1.60; P = .04). CONCLUSIONS: Delayed vascular consultation and vascular surgery are both significant hospital-based determinants of postoperative mortality and short bowel syndrome in patients with AMI. Timing-based management protocols that emphasize routine evaluation by a vascular surgeon and early, definitive mesenteric revascularization should be established and widely adopted for all patients with clinically suspected AMI at presentation.

Approach to Intestinal Failure in Children.

PURPOSE OF REVIEW: Pediatric intestinal failure is a complex condition requiring specialized care to prevent potential complications. In this article, we review the available evidence supporting recent advances in care for children with intestinal failure. RECENT FINDINGS: Multidisciplinary intestinal rehabilitation teams utilize medical and surgical management techniques to help patients achieve enteral autonomy (EA) while preventing and treating the complications associated with intestinal failure. Recent advances in lipid management strategies, minimization of intestinal failure associated liver disease, prevention of central line-associated blood stream infections, and loss of access, as well as development of promising new hormone analogue therapy have allowed promotion of intestinal adaptation. These advances have decreased the need for intestinal transplant. There have been recent advances in the care of children with intestinal failure decreasing morbidity, mortality, and need for intestinal transplantation. The most promising new therapies involve replacement of enteroendocrine hormones.

D-lactic acidosis - a rare complication of short bowel syndrome.

D-lactic acidosis represents a rare form of metabolic acidosis that occurs most commonly in patients with short bowel syndrome. This is a serious, sometimes life-threatening complication. The cause is the accumulation of D-lactate in the body, which is formed in excessive amounts by fermentation of unabsorbed carbohydrates by the intestinal microbiota. The nervous system is predominantly affected, which also results in clinical manifestations. The clinical picture is dominated by a wide range of non-specific neurological symptoms. The disease can sometimes manifest as somnolence to coma. From the aspect of laboratory diagnostics, the disease is characterized by severe metabolic acidosis with an increased anion gap. In this case report, we present a unique case of a 54-year-old woman with Crohns disease and short bowel syndrome who in a short time was repeatedly hospitalized for recurrence of severe metabolic acidosis with severe impaired consciousness. Based on the evaluation of anamnestic data, clinical picture and laboratory tests, the patient was diagnosed with D-lactic acidosis. In the discussion we discuss the individual steps that led to this diagnosis and compare our experience with data in the world literature.

Antibiotic Stewardship Through Standardized Diagnosis and Treatment of Small Bowel Bacterial Overgrowth in Pediatric Patients With Short Bowel Syndrome Reduces Antibiotic Exposure and Improves Cost of Health Care.

BACKGROUND: Small bowel bacterial overgrowth (SBBO) is difficult to diagnose in pediatric patients with short bowel syndrome due to the invasive nature of the gold standard testing. Alternative testing methods also have barriers leaving providers to diagnose clinically. This has led to antibiotic overprescribing in this population. An algorithm for SBBO identification and standardized treatment is proposed. OBJECTIVE: Standardize SBBO identification and treatment in pediatric short bowel syndrome. METHODS: 1-year retrospective chart review and literature review. RESULTS: Final analysis of 146 admissions revealed diagnostic and antibiotic prescribing inconsistencies. In total, 28% (n = 41) received antibiotics for SBBO including those who continued home antibiotic (n = 27), those prescribed an antibiotic based on clinical suspicion (n = 12), and those prescribed an antibiotic based on duodenal aspirate (n = 2). In 10.2% (n = 15) patients, antibiotics were prescribed without clear clinical indication resulting in 342 antibiotic exposed days and $24,000 in prescription costs. CONCLUSION: Clinical research is greatly needed as it relates to SBBO. In the meantime, the proposed algorithm guides providers through diagnosis and treatment decision-making. Thoughtful antibiotic prescribing is key to optimizing outcomes while minimizing adverse effects of antibiotics. IMPLICATIONS FOR NURSING: The algorithm empowers nursing to minimize antibiotic overuse through collaborative teamwork.

[An acidosis not so basic]. / Une acidose pas si basique.

We present the case of a four-year-old girl, who was hospitalized in intensive care unit for a coma resulting from metabolic acidosis with increased anion gap. The patient was treated for short bowel syndrome, following necrotising enterocolitis, which occurred 51 days after birth. In our initial evaluation of the patient's metabolic acidosis, we were unable to identify the cause of the increased anion gap. Urinary organic acids chromatography identified a large peak of lactate (quantified at 15 mmol/mol of creatiniuria), as well as its metabolites. The discrepancy between normal blood lactate concentration assayed by enzymatic assay, and the large amount of lactate found by gas-chromatography/mass spectrometry (GC/MS) in urine highlights the limit of the stereospecificity of enzymatic assays. Indeed, most lactates assay use enzymatic assays that are specific for L-lactate, whereas organic acids chromatography, whose column is mostly achiral, can detect both stereoisomers, D- and L-lactate. Organic acids in urine analysis, in addition to the clinical context, suggested a diagnosis of D-lactic acidosis. Following a review of the physiopathology and treatment of short bowel syndrome, we will discuss the mechanism and diagnosis of the D-lactic acidosis in our patient. This case highlights the need to perform an organic acid profile in urine in the presence of any unexplained increased anion gap to determine its cause.

Advances in chronic intestinal failure management and therapies.

PURPOSE OF REVIEW: To summarize changes and recent advances in therapies for chronic intestinal failure (CIF). RECENT FINDINGS: In the last few years, the management of CIF has significantly improved through better prevention and treatment of catheter-related bloodstream infections (CRBSIs) and intestinal failure-associated liver disease (IFALD), as well as improved enteral autonomy by using small bowel growth factors in selected patients. This may have been reflected by a recent reduction in small bowel transplantations. SUMMARY: Although CIF management has become more established and effective, the long-term implications of parenteral nutrition still place substantial burden on patients such that further work is required to improve patients' quality of life as well as continued efforts to reduce complications relating to CIF management.

Colon polyps in patients with short bowel syndrome before and after teduglutide: Post hoc analysis of the STEPS study series.

BACKGROUND & AIMS: Teduglutide promotes intestinal growth and is approved for the treatment of short bowel syndrome and intestinal failure (SBS-IF). Based on the pharmacologic activity and preclinical findings, teduglutide can potentially induce proliferative colonic mucosal changes. The aim of this study is to report the occurrence of colorectal polyps in adult patients with SBS-IF who received teduglutide in clinical studies conducted to date. METHODS: A post hoc analysis of the completed Study of Teduglutide Effectiveness in Parenteral Nutrition-Dependent Short Bowel Syndrome Subjects (STEPS) clinical study series (NCT00798967, EudraCT 2008-006193-15; NCT00930644, EudraCT 2009-011679-65; NCT01560403) evaluated electronic case report form data for baseline colonoscopies (performed before treatment) and for surveillance or end-of-study (performed after treatment with teduglutide 0.05 mg/kg/day for 24 and 36 months) post-exposure procedures. RESULTS: In the STEPS studies, 73 patients treated with teduglutide had a baseline colonoscopy. No post-exposure colonoscopy was scheduled in STEPS. In STEPS-2/3, 50 of 65 patients with remnant colon (77%) underwent a protocol-mandated post-exposure colonoscopy. Colon polyps were reported at baseline in 12% (9/73) of patients and post-exposure in 18% (9/50) of patients. Two had polyps both at baseline and post-exposure. On histology, available for 7 patients, 5 had adenomas (1 serrated, 4 tubular) and none had malignancy or high-grade dysplasia. CONCLUSION: These data support recommendations for colonoscopic screening before teduglutide therapy and subsequent on-therapy colonoscopic surveillance for patients with SBS-IF. Further studies are required to assess the risk of polyp formation in patients with SBS-IF and the most appropriate colon polyp surveillance strategies.

[Resected bowel syndrome: clinical course and treatment options].

The current concepts of the short bowel syndrome and malabsorption after intestinal surgery are generally accepted, but do not fully reflect the patients condition, making it difficult to diagnose and treat it. AIM: The purpose of the study is to analyze the clinical course of the patients after bowel resection, to create a classification based on the variants identified to allow for a differentiated treatment and to introduce the concept of the resected bowel syndrome. MATERIALS AND METHODS: We observed 239 patients (96 men and 143 women) aged 18 to 80 who underwent intestinal resection for 1 month to 16 years (from 2002 to 2018). The 1st group included 96 patients with small bowel resection (40 men and 56 women). The 2nd group included 39 men and 58 women with small bowel resection, including the resection of the ileocecal valve and the right-hand side of the colon (n=97). The 3rd group included 17 men and 29 women with the resection of the right-hand side of the colon or colectomy (n=46). The survey included the NRS-2002 (Nutritional Risk Screening 2002) screening test to identify nutritional risk, a clinical assessment of the symptoms that occurred after the surgery, instrumental methods (esophagogastroduodenoscopy, colonoscopy with biopsy, ultrasound of the abdominal cavity organs and the kidneys, a plain radiography of the abdominal cavity organs, an X-ray examination of the small intestine and the intestinal passage), serum citrulline and short-chain fatty acids in faeces. RESULTS: Based on the analysis of the clinical symptoms and the nutritional status of the patients, a new concept is proposed the resected bowel syndrome with two variants of its progression: either with or without the development of nutritional insufficiency of three types: the dehydration type, the protein-energy insufficiency type and a mixed type. Type 1 requires the use of antimicrobials with the control of SCFA concentrations in faeces. Type 2 requires the introduction of an optimal amount of easily digestible protein to correct protein-energy deficit. The 3rd (most severe) mixed type requires prescription of a parenteral nutrition component with the control of citrulline concentration in the blood serum. CONCLUSION: The proposed concept the resected bowel syndrome makes it possible to improve its diagnosis, take into account the variants of its progression and allow for a differentiated treatment.

Night Blindness in Cystic Fibrosis: The Key Role of Vitamin A in the Digestive System.

Vitamin A is a fundamental micronutrient that regulates various cellular patterns. Vitamin A deficiency (VAT) is a worldwide problem and the primary cause of nocturnal blindness especially in low income countries. Cystic fibrosis (CF) is a known risk factor of VAD because of liposoluble vitamin malabsorption due to pancreatic insufficiency. We describe a case of a 9-year-old girl who experienced recurrent episodes of nocturnal blindness due to profound VAD. This little girl is paradigmatic for the explanation of the key role of the gut-liver axis in vitamin A metabolism. She presents with meconium ileus at birth, requiring intestinal resection that led to a transient intestinal failure with parenteral nutrition need. In addition, she suffered from cholestatic liver disease due to CF and intestinal failure-associated liver disease. The interaction of pancreatic function, intestinal absorption and liver storage is fundamental for the correct metabolism of vitamin A.

Increased intestinal permeability in patients with short bowel syndrome is not affected by parenteral nutrition.

The aim of our study was to assess the presence and degree of intestinal leakage in subjects suffering from short bowel syndrome (SBS) and its modification by parenteral nutrition. To this end we assessed circulating levels of selected makers of intestinal permeability including zonulin, fatty acid binding protein 2 (FABP-2), citrulline and glucagon-like peptide 2 (GLP-2). We also measured lipopolysaccharide binding protein (LBP) as a marker of circulating levels of lipopolysaccharide acting through the CD14 molecule. Eleven SBS and 10 age- and BMI-matched control subjects were included into the study. The effect of parenteral nutrition was assessed after 14 days, 6 and 12 months from its initiation, respectively. At baseline, SBS patients had increased gut permeability as measured by zonulin (47.24+/-2.14 vs. 39.48+/-1.20 ng/ml, p=0.006) and LBP (30.32+/-13.25 vs. 9.77+/-0.71 microg/ml, p<0.001) compared to healthy controls. Furthermore, SBS subjects had reduced FABP-2, unchanged citrulline and increased sCD14 and GLP-2 relative to control group. Throughout the whole study period the administered parenteral nutrition had no significant effect on any of the studied parameters. Taken together, our data show that patients with short bowel syndrome have increased intestinal permeability that is not affected by parenteral nutrition.

Effects of glepaglutide, a novel long-acting glucagon-like peptide-2 analogue, on markers of liver status in patients with short bowel syndrome: findings from a randomised phase 2 trial.

BACKGROUND: With the introduction of glucagon-like peptide-2 (GLP-2) in the treatment of short bowel syndrome (SBS), there is emerging evidence that GLP-2 may play a role in the restoration of the disturbed homeostatic feedback in the gut-liver axis and may ameliorate SBS-associated liver damage. We have previously presented that daily subcutaneous injections with 1 and 10 mg of glepaglutide improved intestinal function in patients with SBS. As exploratory endpoints, we here assessed the effect of glepaglutide on liver function. METHODS: Liver tests, transient elastography (TE) with controlled attenuation parameter (CAP), indocyanine green (ICG) kinetics, soluble CD163 (sCD163), soluble mannose receptor (sMR), and lipopolysaccharide binding protein (LBP) were assessed in 18 patients with SBS in a randomised, cross-over, dose-finding phase 2 trial before and after three weeks of treatment with glepaglutide. This trial is completed and registered at ClinicalTrials.gov: NCT02690025. FINDINGS: Between Feb 2016 and Jan 2017, 22 patients with SBS were screened. Of these, 18 patients were randomised and treated with glepaglutide; 16 patients completed the trial. Treatment with glepaglutide was associated with increase in TE and ICG-elimination. In the 10 mg dose group, glepaglutide increased sCD163 by 0·44 mg/mL (P = 0·0498), and alkaline phosphatase (ALP) decreased in the 1 mg dose group by 33 U/L (P = 0·032). CAP, sMR, LBP, liver transaminases, and INR were not affected. INTERPRETATION: Glepaglutide may improve hepatic excretory function, but at the same time activate resident liver macrophages and increase liver stiffness. The excretory and the stiffness findings may to some extent relate to increased splanchnic blood flow which would not influence the marker of macrophage activation. Thus, glepaglutide exerted diverse effects on liver status that call for attention in future studies. FUNDING: Zealand Pharma.

Emerging treatments for short bowel syndrome in adult patients.

INTRODUCTION: Short bowel syndrome (SBS) is the major cause of chronic intestinal failure (IF), defined as 'the reduction of gut function below the minimum necessary for the absorption of macronutrients and/or water and electrolytes, such that intravenous supplementation is required to maintain health and/or growth'. Areas covered: Spontaneous intestinal adaptation, including increased hormonal secretion, development of hyperphagia and gut microbiota dysbiosis, occurs 2 years after resection, improving intestinal absorption and decreasing PN dependency. Hormonal treatments, promoting intestinal hyperadaptation, have been proposed in patients with SBS with chronic IF. Clinical studies showed teduglutide to increase urine production and reduce the need for parenteral support volume in these patients. According to the latest ESPEN Guidelines, if a growth factor treatment is considered, the GPL2 analog, teduglutide, should be the first-choice treatment. Expert opinion: These therapies underline the importance of patient monitoring at home and the complexity for HPN adaptation. A multidisciplinary approach should be a gold standard.

Ultra-short bowel syndrome during infancy: improving outcomes and novel therapies.

PURPOSE OF REVIEW: Ultra-short bowel syndrome is relatively rare and has not yet been extensively reported. In ultra-short bowel syndrome, poor absorption of nutrients and dysmotility, interfere with fluid, energy, electrolyte and micronutrient balance. Patients with this disorder are managed through prolonged parenteral nutrition with the ultimate goal of achieving enteral autonomy. Overall outcomes of these patients are dependent on postsurgical bowel anatomy (residual length, intact colon, ostomy closure timing), incidence of sepsis, and care by a multidisciplinary specialized team. RECENT FINDINGS: Over the years, standardization of management has improved outcomes. This includes central line care, lipid alternatives, enteral therapy, medications (antidiarrheal agents, acid suppression medications, bile acid binding salts, and enteral antibiotics) including Teduglutide. Bowel lengthening procedures have also proven beneficial, and finally bowel transplant does remain an option for a patient in whom rehabilitation has failed. SUMMARY: Although there are many factors that influence outcomes of ultra-short bowel patients, novel therapies such as Teduglutide have been introduced with the aim of improving intestinal adaptation. Surgical lengthening and transplant are viable options in the setting of failed rehabilitation.

Treatment in a Tertiary Intestinal Rehabilitation Center Improves Outcome for Children With Short Bowel Syndrome.

The aim of this study was to determine prognostic factors in pediatric patients with short bowel syndrome and very short bowel syndrome (defined as less than 25 cm of the bowel with or without colon). This was a retrospective, single-center, observational study that included patients with intestinal failure. Thirty-eight children with short bowel syndrome were included in the study (mean age at diagnosis = 8.4 [range = 0-48] months; female/male = 20/18); 12 children (31.6%) had very short bowel syndrome. Weaning from parenteral nutrition was achieved in 29 (74.5%) of children with short bowel syndrome but only in 4 (33%) in the very short bowel syndrome group. Positive prognostic factors associated with successful weaning from parenteral nutrition were an absolute higher length of the residual intestine, a remnant of at least some part of the colon, and treatment in an experienced center from the diagnosis. Patients with short bowel syndrome and very short bowel syndrome should be treated in a center experienced in intestinal rehabilitation.