Evidence-based recommendations of the Andalusian Group for Nutrition Reflection and Investigation (GARIN) for the management of adult patients with short bowel syndrome

Nutrición Hospitalaria Revisión ISSN (electrónico): 1699-5198 - ISSN (papel): 0212-1611 - CODEN NUHOEQ S.V.R. 318 Evidence-based recommendations of the Andalusian Group for Nutrition Reflection and Investigation (GARIN) for the management of adult patients with short bowel syndrome Recomendaciones basadas en la evidencia del Grupo Andaluz para la Reflexión e Investigación en Nutrición (GARIN) para el manejo del paciente con síndrome de intestino corto Francisco J. Vílchez-López1,2, Laura Larrán-Escandón1,2, José M. García-Almeida3,4, Carmen Arraiza-Irigoyen5, José A. Irles Rocamora6, María J. Molina-Puerta7,8, Juan B. Molina Soria9, José L. Pereira-Cunill10,11, Juana M. Rabat-Restrepo12, María I. Rebollo-Pérez13, María P. Serrano-Aguayo10,11, Carmen Tenorio-Jiménez14, Gabriel Olveira4,15,16, and Pedro P. García-Luna10,11,17 1Endocrinology and Nutrition Clinical Management Unit. Hospital Universitario Puerta del Mar. Cádiz, Spain. 2Instituto de Investigación Biomédica de Cádiz (INIBICA). Cádiz, Spain. 3Endocrinology and Nutrition Clinical Management Unit. Hospital Universitario Virgen de la Victoria. Málaga, Spain. 4Instituto de Investigación Biomédica de Málaga (IBIMA). Málaga, Spain. 5Department of Endocrinology and Nutrition. Complejo Hospitalario de Jaén. Jaén, Spain. 6Endocrinology and Nutrition Clinical Management Unit. Hospital Universitario de Valme. Seville, Spain. 7Endocrinology and Nutrition Clinical Management Unit. Hospital Universitario Reina Sofía. Córdoba, Spain. 8Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC). Córdoba, Spain. 9Nutrition and Dietetics Unit. Hospital General de Linares. Linares, Jaén. Spain. 10Endocrinology and Nutrition Clinical Management Unit. Hospital Universitario Virgen del Rocío. Seville, Spain. 11Endocrine Diseases Research Group. Instituto de Biomedicina de Sevilla (IBiS). Seville, Spain. 12Department of Endocrinology and Nutrition. Hospital Universitario Virgen Macarena. Seville, Spain. 13Department of Endocrinology and Nutrition. Hospital Juan Ramón Jiménez. Huelva, Spain. 14Endocrinology and Nutrition Clinical Management Unit. Hospital Universitario Virgen de las Nieves. Granada, Spain. 15Endocrinology and Nutrition Clinical Management Unit. Hospital Regional Universitario de Málaga. Universidad de Málaga. Málaga, Spain. 16CIBERDEM (CB07/08/0019). Instituto de Salud Carlos III. Madrid, Spain. 17GARIN Group. Seville, Spain Keywords: Short bowel syndrome. Home parenteral nutrition. Teduglutide. Abstract In order to develop evidence-based recommendations and expert consensus for the nutritional management of patients with short bowel syndrome (SBS), we conducted a systematic literature search using the PRISMA methodology plus a critical appraisal following the GRADE scale procedures. Pharmacological treatment with antisecretory drugs, antidiarrheal drugs, and somatostatin contributes to reducing intestinal losses. Nutritional support is based on parenteral nutrition; however, oral intake and/or enteral nutrition should be introduced as soon as possible. In the chronic phase, the diet should have as few restrictions as possible, and be adapted to the SBS type. Home parenteral nutrition (HPN) should be individualized. Single-lumen catheters are recommended and taurolidine should be used for locking the catheter. The HPN’s lipid content must be greater than 1 g/kg per week but not exceed 1 g/kg per day, and omega-6 fatty acids (ω6 FAs) should be reduced. Trace element vials with low doses of manganese should be used. Patients with chronic SBS who require long-term HPN/fluid therapy despite optimized treatment should be considered for teduglutide treatment. All patients require a multidisciplinary approach and specialized follow-up. These recommendations and suggestions regarding nutritional management in SBS patients have direct clinical applicability. Correspondence: Gabriel Olveira. Unidad de Gestión Clínica de Endocrinología y Nutrición. Hospital Regional Universitario de Málaga. Universidad de Málaga. 29010 Málaga, Spain e-mail: [email protected] ©Copyright 2021 SENPE y ©Arán Ediciones S.L. Este es un artículo Open Access bajo la licencia CC BY-NC-SA (http://creativecommons.org/licenses/by-nc-sa/4.0/). Received: 19/05/2021 • Accepted: 22/06/2021 Vílchez-López FJ, Larrán-Escandón L, García-Almeida JM, Arraiza-Irigoyen C, Irles Rocamora JA, MolinaPuerta MJ, Molina Soria JB, Pereira-Cunill JL, Rabat-Restrepo JM, Rebollo-Pérez MI, Serrano-Aguayo MP, Tenorio-Jiménez C, Olveira G, García-Luna PP. Evidence-based recommendations of the Andalusian Group for Nutrition Reflection and Investigation (GARIN) for the management of adult patients with short bowel syndrome. Nutr Hosp 2021;38(6):1287-1303 Author contributions: conceptualization, FJVL, LLE, GOF, PPGL; methodology, all authors; writing, original draft preparation, FJVL, LLE; writing, review and editing, FJVL, LLE, GOF, PPGL; all authors read and agreed to the published version of the manuscript. Funding: funding for the face-to-face meeting and the translation into English was provided by NESTLE HEALTHCARE. This entity did not participate at any time in the choice of topic to be discussed, nor in the choice of authors or in any scientific aspect of the article. Only in its official translation. Conflicts of interest: the authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; inthe writing of the manuscript, or in the decision to publish the results. Data availability statement: data sharing is not applicable to this article. DOI: http://dx.doi.org/10.20960/nh.03705 1288 F. J. Vílchez-López et al. [Nutr Hosp 2021;38(6):1287-1303] INTRODUCTION Short bowel syndrome (SBS) is one of the most important causes of acute intestinal failure (IF) and the most frequent cause of chronic IF (75 % of cases). SBS is defined as a reduction in small bowel length, which leaves less than 200 cm or less than 50% of the initial length. The main causes of SBS are mesenteric ischemia and Crohn’s disease. SBS is classified according to the type of anastomoses, i.e., type I (end jejunostomy or ileostomy), type II (jejuno-colic anastomosis), and type III (jejuno-ileal anastomosis) (1,2). From the clinical point of view, acute SBS frequently develops abdominal sepsis and fluid and electrolyte disorders (3). In chronic SBS, the patient’s clinical and metabolic situation will also depend on the intestinal segment affected, the functionality of the remaining intestine, and the presence or absence of terminal ileum, ileocecal valve, and colon (4). Intestinal adaptation is a process that may take up to 24 months after intestinal resection. Different mechanisms are involved, such as the development of compensatory hyperphagia, structural changes that increase the absorption surface, functional changes that slow transit time, and changes in the gut microbiota (4,5). HPN is required indefinitely unless total intestinal adaptation is attained. SBS is a rare disease and the scientific quality of evidence regarding treatment is generally low, with the exception of specific aspects. Questions about nutritional therapy and pharmacological treatment, among others, still do not have clear answers. The Andalusian Group for Nutrition Reflection and Investigation (GARIN) aims to answer these questions in an attempt to try and improve care for these patients, and standardize routine clinical practice. MATERIALS AND METHODS The GARIN group members held a virtual meeting to propose and select questions related to the clinical practice and management of patients with SBS. Nine questions were considered to be of interest either because clinical practice guidelines (CPGs) do not answer them or because the response provided is not clear. Once selected, on May 1, 2020 a systematic bibliographic search was carried out in PUBMED, which was narrowed down to published systematic review articles, meta-analyses, controlled clinical trials, case series, and clinical practice guidelines (CPGs) published in the last 10 years. The search formula used was: “Short Bowel Syndrome” AND (“Diagnosis” OR “Therapeutics” OR “Nutrition Therapy” OR “Citrulline” OR “Nutritional Support” OR “Drug Therapy” OR “Diet” OR “Enteral Nutrition” OR “Parenteral Nutrition, Home” OR “Nutrition Assessment” OR “quality of life” OR “Fat Emulsions, Intravenous” OR “Fatty Acids, Omega-3” OR “Probiotics” OR “Bacterial Overgrowth Syndrome” OR “bioelectrical impedance analysis”), with limits: “From 01-01-2010 to 01-05-2020”, “Adults over 19 y”, “Spanish and English” and “human beings”. The evaluation of the eligibility of the different works was carried out independently by two reviewers (FJVL and LLE). Disagreements between reviewers were resolved by consensus. After the initial reading of the title and Abstract, we excluded case reports, works referred to pediatric populations, and papers not directly related to the topic. The rest of articles required a full reading by both reviewers to assess their eligibility and decide which articles should be included or excluded. A total of 262 results were obtained, of which 130 articles were reviewed that met the search criteria. Of the 132 articles that wereexcluded, 15 referred to a pediatric population and 79 were case reports. Another 37 articles were also excluded, since they made reference specifically to the underlying disease of SBS, surgical treatment, etc., rather than aspects related to the diagnosis and medical treatment. Figure 1 specifies the process according to the PRISMA methodology (6). The quality assessment of each original study was carried out using the grade-pro methodology (https://gradepro.org/). In a second virtual meeting, in which an updated Summary of the literature available on short bowel syndrome was presented, the members of the GARIN group discussed those aspects rela ted to the considered questions that were more controversial, or those in which there was less scientific evidence available. Aspects in which, therefore, our opinion as a group of experts could have added value. The various proposals were debated and agreed. The evaluation of grading the evidence of each proposal was performed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) scale (7); finally, they were drafted according to the criteria set out in table I. A consensus was reached regarding the responses to the questions previously selected, taking the available evidence into conPalabras clave: Síndrome del intestino corto. Nutrición parenteral domiciliaria. Teduglutida. Resumen Con el fin de desarrollar recomendaciones basadas en la evidencia y el consenso de expertos para el manejo nutricional de los pacientes con síndrome de intestino corto (SIC), realizamos una búsqueda bibliográfica sistemática utilizando la metodología PRISMA junto a una valoración crítica siguiendo los procedimientos de la escala GRADE. El tratamiento farmacológico con fármacos antisecretores, antidiarreicos y somatostatina contribuye a reducir las pérdidas intestinales. El apoyo nutricional se basa en la nutrición parenteral; sin embargo, la ingesta oral y/o la nutrición enteral deben introducirse lo antes posible. En la fase crónica, la dieta debe tener las menores restricciones posibles y adaptarse al tipo de SIC. La nutrición parenteral domiciliaria (NPD) debe individualizarse. Se recomiendan catéteres de un solo lumen y se debe utilizar taurolidina para bloquear el catéter. El contenido de lípidos de la HPN debe ser superior a 1 g/kg por semana, pero no debe exceder 1 g/kg por día, y debe reducirse el ácido graso omega-6 (AG ω6). Deben utilizarse viales de oligoelementos con dosis bajas de manganeso. Los pacientes con SIC crónico que requieren NPD/fluidoterapia a largo plazo a pesar del tratamiento optimizado deben considerarse para el tratamiento con teduglutida. Todos los pacientes requieren un abordaje multidisciplinar y un seguimiento especializado. Estas recomendaciones y sugerencias con respecto al manejo nutricional de los pacientes con SIC tienen aplicabilidad clínica directa. 1289EVIDENCE-BASED RECOMMENDATIONS OF THE ANDALUSIAN GROUP FOR NUTRITION REFLECTION AND INVESTIGATION (GARIN) FOR THE MANAGEMENT OF ADULT PATIENTS WITH SHORT BOWEL SYNDROME [Nutr Hosp 2021;38(6):1287-1303] Table I. Grades of recommendation according to the GRADE-ASPEN scale Quality of evidence Weighing risks vs benefits Grade recommendation Statement High to very low Net benefits outweigh the risks Strong We recommend High to very low Benefits compensate the risks Weak We suggest High to very low Uncertain if the benefits compensate the risks Further research needed We cannot make a recommendation at this time / As expert consensus our proposal is… Adapted from Druyam et al. (7). IDENTIFICATIONSCREENINGELEGIBILITYINCLUDED Full-text articles assesed for eligibility (n = 262) Studies included (n =130) Full-text articles excluded (n = 132): – Pediatric population (n = 15) – Case reports (n = 79) – Not related to the topic (n = 36) – Animals (n = 1) Records identified through database searching (PubMed) (n = 262) Records after duplicated removed (n = 262) Records screened (n = 262) sideration. After the discussion, the group members electronically evaluated the consensus using a Likert-type scale (8). The evaluation form had five possible answers to evaluate each recommendation (“totally disagree” with an assigned value of 1, “disagree” with an assigned value of 2, “neither agree nor disagree” with an assigned value of 3, “agree” with an assigned value of 4, and “totally agree” with an assigned value of 5). The consensus level of each recommendation was calculated by adding the total value resulting from the responses obtained, dividing it by the maximum value, and then multiplying it by 100. RESULTS This article includes the responses to 9 questions, obtained from the process described above. After each question, the di fferent proposals suggested by GARIN and the supporting scientific evidence were collected. All the GARIN group members responded to the surveys. The questions and the level of consensus reached after responding to the Likert scale are specified in table II. Figure 1. Flow diagram following the PRISMA methodology that reflects the selection and evaluation process of the analyzed papers. Adapted from Liberati et al. (7). Table II. GARIN group proposals and level of consensus reached after evaluation using the Likert scale GARIN Group proposals Consensus level Which therapeutic measures should be implemented in acute IF secondary to SBS? We recommend strict fluid balance in all patients 95.38% As a consensus of experts our proposal is to maintain a minimum diuresis of 1 mL/kg/h (or 25/mL/kg/day) 98.46 % As a consensus of experts our proposal is to determine the concentration of electrolytes in the urine and to maintain Na concentrations above 20 mmol/L or 50 mmol/24 h, together with a Na/K ratio in the urine>1 87.69 % As a consensus of experts, our proposal is the use of the bioelectric impedance analysis as an additional method to assess hydration status, in comparison with other pathologies 76.92 % We recommend the monitoring and replacement of electrolytes (mainly magnesium, sodium, and potassium) 100 % As a consensus of experts, our proposal is to maintain electrolyte levels at the high limit of normality, in the case of postoperative ileus 75.38 % What is the optimal symptomatic drug treatment for SBS? For SBS patients, especially those with high fecal production, we suggest PPI treatment for the first 6 months, followed by individualized treatment 95.38 % We are unable to make a recommendation to propose a PPI drug of choice 92.3 % (Continues on the next page) 1290 F. J. Vílchez-López et al. [Nutr Hosp 2021;38(6):1287-1303] Table II (Cont.). GARIN group proposals and level of consensus reached after evaluation using the Likert scale GARIN Group proposals Consensus level What is the optimal symptomatic drug treatment for SBS? As a consensus of experts, our proposal is to replace PPI treatment with an H2 receptor antagonist (H2RA) in patients who develop hypomagnesemia when under PPI treatment 96.92 % We suggest the use of loperamide as a first-line antidiarrheal agent to reduce water and electrolyte loss (after ruling out gastrointestinal tract infection). If losses are not controlled with loperamide, then add codeine 98.56 % In order to ensure adequate therapeutic adherence, coupled with clinical results, we suggest ease of access to these drugs with this therapeutic indication 96.92 % As a consensus of experts our proposal is to associate octreotide soon after intestinal resection in patients whose intestinal output is not controlled with the abovementioned drugs, especially if the ostomy is high output 87.69 % As a consensus of experts our proposal is to associate bile salt chelating resin with antisecretory and antidiarrheal agents in patients with intestinal resection (less than 100 cm of remaining small bowel) and colon in continuity, and non-controlled diarrhea 93.84 % As a consensus of experts our proposal is use pancreatic enzyme therapy in the case of steatorrhea despite adequate compliance with the dietary recommendations 87.69 % As a consensus of experts our proposal is to use empirical antibiotic treatment in patients with clinical suspicion of bacterial overgrowth, with rifaximin as the first choice, and in the case of requiring several cycles, different antibiotic regimens should be used in a cyclical way, to avoid the appearance of bacterial resistance 89.23 % We suggest monitoring the efficacy of other concomitant drugs, mindful that there may be a need for dose increase or alternative route administration 95.38 % What is the ideal nutritional assessment method for SBS? We recommend repeated screening and nutritional assessments for all patients in all the phases of the disease 100 % As a consensus of experts our proposal is to apply GLIM criteria to establish the diagnosis of malnutrition and grade its severity, with the objective of its validation in the coming years 87.69 % As a consensus of experts our proposal is to use BIA, in addition to analytical and anthropometric parameters, to detect changes in nutritional status and evaluate the nutritional interventions carried out 84.61 % What are the recommended nutritional requirements with SBS? In the acute phase, we suggest using indirect calorimetry where available 81.53 % As a consensus of experts our proposal for an alternative is to establish the energy and protein requirements according to the following calculations: – In acute phase: caloric requirements: 25-35 kcal/kg/day; protein requirements: 1.5 g/kg real weight/day – In chronic phase: caloric requirements: 25-35 kcal/kg/day. Use usual weight in case of edema and adjusted weight in case of obesity. As a consensus of experts our proposal is to calculate the caloric requirements using Johnstone’s equation if the impedance measurement is available; protein requirements: 1-1.4 g/kg/day 80 % We recommend adjusting the requirements to the clinical and analytical changes, and to always consider the potential loss of nutrients through the stoma 98.46 % What recommendations can we establish in oral feeding and enteral nutrition in SBS? Acute phase We suggest starting an ad libitum oral diet as soon as possible 89.23 % We suggest reducing the supply of hypotonic fluids (less than 500 mL/day) and administering oral glucosaline solutions with at least 90 mmol/L of Na and 300 mosm/L osmolarity in patients with ostomies 96.62 % As a consensus of experts our proposal is to supplement with enteral nutrition/enteroclysis if oral intake is not possible or is insufficient 92.3 % As a consensus of experts our proposal is continuous EN feeding at a low speed, as long as it is a consensual decision made by the therapeutic team and the patient 80.0 % As a consensus of experts our proposal is the use of polymeric formulations for nasoenteric enteral nutrition, and to resort to oligomeric formulations if there is intolerance 83.07 % (Continues on the next page) 1291EVIDENCE-BASED RECOMMENDATIONS OF THE ANDALUSIAN GROUP FOR NUTRITION REFLECTION AND INVESTIGATION (GARIN) FOR THE MANAGEMENT OF ADULT PATIENTS WITH SHORT BOWEL SYNDROME [Nutr Hosp 2021;38(6):1287-1303] Table II (Cont.). GARIN group proposals and level of consensus reached after evaluation using the Likert scale GARIN Group proposals Consensus level Chronic phase: general measures As a consensus of experts our proposal is that the diet be as restriction-free as possible, but adapted to the general and specific recommendations of each type of SBS, according to the patient’s clinical condition 91.66 % As a consensus of experts our proposal is to supply oral nutritional supplements to SBS patients with a low level of parenteral nutrition dependence 90.77 % As a consensus of experts our proposal is for several small meals to be ingested throughout the day, to avoid drinking liquids with meals and to minimise the consumption of simple sugars 90.76 % Currently, we are unable to make a recommendation about the addition of glutamine or other specific nutrients 89.23 % Chronic phase: symptomatic colon patients As a consensus of experts our proposal is to reduce lipid intake to 20% of the total calorie value (TCV), although this percentage may be raised slightly in a stable patient so as to increase the total intake 89.23 % As a consensus of experts our proposal is to increase the intake of complex carbohydrates (60% TCV) 89.23 % As a consensus of experts our proposal is not to add soluble fibre in a systematic way, although it may be considered in selected cases 87.69 % As a consensus of experts our proposal is not to exclude lactose in a systematic way 92.3 % As a consensus of experts our proposal is to reduce the intake of oxalate 95.38 % Currently, we are unable to make a recommendation about the use of probiotics in these patients 93.84 % Chronic phase: patients without colon in continuity We suggest using salt liberally 92.3 % We suggest oral rehydration formulas, and for hypotonic and hypertonic fluids to be avoided when there is a fluid imbalance 95.38 % As a consensus of experts our proposal is a hypercaloric diet, with protein supplying 20% of the TCV. The fat/carbohydrate ratio is less relevant and it can be increased 93.84 % As a consensus of experts our proposal is not to add soluble fibre in a systematic way, although in selected cases it may have benefits 84.61 % As a consensus of experts our proposal is not to exclude lactose in a systematic way 96.92 % Home parenteral nutrition What is the catheter of choice for HPN in patients with SBS? As a consensus of experts our proposal is to individualise the choice of access based on the patient’s characteristics and the site’s experience 95.38 % We recommend using single-lumen catheters or using a lumen exclusively for PN when using multiple-lumen catheters 100 % What is the ideal catheter lock? We recommend locking the catheter with taurolidine in all cases 98.46 % What method of administration should we use? We suggest administering the HPN cyclically 98.46 % What should be the formulation composition for macro and micronutrients? As a consensus of experts our proposal is to distribute non-protein calories between CH 60-70% and lipids 30-40%, once the caloric and protein requirements have been calculated 93.84 % We suggest that the lipid content be greater than 1 g/kg/week but not greater than 1 g/kg/day 87.69 % We suggest reducing the supply of ω6 FAs by using the new lipid emulsions (MCT, olive oil, fish oil) 92.3 % We suggest limiting glucose intake to less than 5-7 mg/kg/min or 3-6 g/kg/day 96.92 % We suggest a total volume of 25-35 mL/kg/day, individualized according to fluid losses and in cases such as kidney failure or heart failure 93.84 % We suggest administering electrolytes based on the recommended daily needs, adjusted in order to normalise plasma levels 93.84 % As a consensus of experts our proposal is a daily intake of intravenous vitamins based on the recommended daily needs, individualised in accordance with regular monitoring to maintain levels within normality 95.38 % As a consensus of experts our proposal is a supply of intravenous trace elements based on the recommended daily needs, individualised according to regular monitoring 92.31 % We suggest an extra dose of zinc (12-17 mg/L of intestinal fluid lost) in case of abundant intestinal losses 87.69 % We suggest using vials of trace elements with low manganese doses 84.61 % (Continues on the next page) 1292 F. J. Vílchez-López et al. [Nutr Hosp 2021;38(6):1287-1303] DISCUSSION INITIAL ACUTE PHASE MANAGEMENT What are the therapeutic measures to implement in acute IF secondary to SBS? GARIN proposal: We recommend strict fluid balance in all patients (consensus level: 95.38%) (moderate quality of evidence; net benefits outweigh the risks). As a consensus of experts, our proposal is to maintain a minimum diuresis of 1 mL/kg/h (or 25/mL/kg/day) (consensus level: 98.46%). As a consensus of experts, our proposal is to determine the concentration of electrolytes in the urine and to maintain Na concentrations above 20 mmol/L or 50 mmol/24 h, together with a Na/K ratio in urine>1 (consensus level: 87.69%). As a consensus of experts, our proposal is the use of the bioelectric impedance analysis as an additional method to assess the hydration status, in comparison with other pathologies (consensus level: 76.92%). We recommend the monitoring and replacement of electrolytes (mainly magnesium, sodium, and potassium) (consensus level: 100%) (low quality of evidence; net benefits outweigh the risks). As a consensus of experts, our proposal is to maintain electrolyte levels at the high limit of normality in the case of postoperative ileus (consensus level: 75.38%). The management of acute IF secondary to massive intestinal resections should be multidisciplinary and based on the SOWATS approach, proposed by the Maastricht group and endorsed by ESPEN: (S) Sepsis control, (O) Optimization of nutritional care, (W) Table II (Cont.). GARIN group proposals and level of consensus reached after evaluation using the Likert scale GARIN Group proposals Consensus level Teduglutide What is the role of teduglutide in the treatment of SBS? We suggest initiating treatment with teduglutide in chronic SBS patients who require ongoing HPN/fluid therapy despite optimised treatment, and with an acceptable nutritional status and fluid and electrolyte balance, who meet the following requirements: non-obstructive and non-malignant underlying disease; clinical stability after the intestinal adaptation period after intestinal resection (estimated at 12 months after extensive bowel resection or 6 months after minor reoperation on a long-standing SBS) 81.82 % We suggest performing colonoscopy in patients with colon prior to starting treatment 96.36 % What do we need to consider in patients who are candidates for teduglutide treatment? We suggest close monitoring of the water balance, weight, physical examination, biochemical parameters, and intake changes, to adjust nutritional and volume requirements 90.91 % We suggest a colonoscopy every year for the first two years and then every 5 years 89.01 % We suggest a six-monthly check-up of biliary and pancreatic parameters 92.73 % We suggest evaluating the effectiveness of the treatment on a regular basis. In the absence of clinical improvement after 12 months, consider if treatment should be stopped 90.91 % Wound care, (A) Assessment of intestine and fistula anatomy, (T) Timing of surgery, and (S) Surgical strategy (3). Fluid and electrolyte replacement should be started immediately, before any nutritional intervention. Fluid and electrolyte losses are greater in the initial post-resection period, especially in patients with end-jejunostomy or proximal ileostomy. Therefore, hemodynamic stabilization and prevention/treatment of dehydration and electrolyte deficiencies (especially magnesium, po tassium, and sodium) is essential. It is essential to monitor the fluid balance (including intestinal or nasogastric tube drainage losses), kidney function, acid-base balance, and electrolyte levels(3). A minimum diuresis of 1 mL/kg/h (or 25 mL/kg/day) should be maintained. In general, the water requirements tend to exceed 30-40 mL/kg/day. Urine sodium concentration is a gauge of hydration status. Concentrations below 20 mmol/L or 50mmol/24h, together with a Na/K ratio in urine<1, indicate early fluid and sodium depletion and precede any elevation in urea and creatinine (3). Bioelectrical impedance analysis (BIA) is a simple, non-invasive, and low-cost method that, in addition to evaluating body composition, allows assessing the hydration status in patients with kidney disease or heart failure, although there are currently no studies in patients with SBS. Hyperhydration assessed by BIA has been associated with an increase in mortality (9). Electrolyte replacement is crucial. Loss depends on the affected intestinal segment, although often it is not predictable. Hypokalemia, hypomagnesemia, and hypophosphatemia are common and associated with paralytic ileus and refeeding syndrome. Restoring levels to high-normal could be beneficial for treating the ileus, but evidence to support this recommendation is lacking (10). 1293EVIDENCE-BASED RECOMMENDATIONS OF THE ANDALUSIAN GROUP FOR NUTRITION REFLECTION AND INVESTIGATION (GARIN) FOR THE MANAGEMENT OF ADULT PATIENTS WITH SHORT BOWEL SYNDROME [Nutr Hosp 2021;38(6):1287-1303] PHARMACOTHERAPY (Table III) What is the optimal symptomatic drug treatment for SBS? GARIN proposal: For SBS patients, especially those with high fecal production, we suggest PPI treatment for the first 6 months, followed by individualized treatment (consensus level: 95.38 %) (low quality of evidence; benefits compensate the risks). Currently, we are unable to make a recommendation to propose a PPI drug of choice (consensus level: 92.3%). As a consensus of experts, our proposal is to replace PPI treatment with an H2 receptor antagonist (H2RA) in patients who develop hypomagnesemia when under PPI treatment (consensus level: 96.92%). We suggest the use of loperamide as first-line antidiarrheal agent to reduce water and electrolyte loss (after ruling out gastrointestinal tract infection). If losses are not controlled with loperamide, then add codeine (consensus level: 98.56%) (low quality of evidence; benefits compensate the risks). In order to ensure adequate therapeutic adherence, coupled with clinical results, we suggest ease of access to these drugswith this therapeutic indication (consensus level: 96.92%) (low quality of evidence; benefits compensate the risks). As a consensus of experts our proposal is to associate octreotide soon after intestinal resection in patients whose intestinal output is not controlled with the above-mentioned drugs, especially if the ostomy is high output (consensus level: 87.69%). As a consensus of experts our proposal is to associate a bile salt-chelating resin with antisecretory and antidiarrheal agents in patients with intestinal resection (less than 100 cm of remaining small bowel) and colon in continuity, and non-controlled diarrhea (consensus level: 93.84%). As a consensus of experts our proposal is to use pancreatic enzyme therapy in the case of steatorrhea despite adequate compliance with the dietary recommendations (consensus level: 87.69%). As a consensus of experts our proposal is to use empirical antibiotic treatment in patients with clinical suspicion of bacterialovergrowth, with rifaximin as the first choice. In the case of requiring several cycles, different antibiotic regimens should be used in a cyclical way, to avoid the appearance of bacterial resistance (consensus level: 89.23%). We suggest monitoring the efficacy of other concomitant drugs, mindful that there may be a need for dose increase or alternative route administration (consensus level: 95.38%) (low quality of evidence; net benefits outweigh the risks). Table III. Pharmacological treatment of SBS (3,4,11,12,14,27) Therapeutic group Mechanism of action Active ingredient (via) Dose (maximum) Antidiarrheal agents: slowing of intestinal transit Peripheral opioid agonist Loperamide (vo) 2-6 mg QID (24 mg/d) Central and peripheral opioid agonist Codeine (vo) 15-30 mg QID (240 mg/d) Antisecretory agents: inhibition of gastric secretion Proton pump inhibitors Omeprazole (vo/iv) 20-40 mg/12 h Lansoprazole (vo) 15-30 mg/12 h Pantoprazole (vo/iv) 20-40 mg/12 h Esomeprazole (vo/iv) 20-40 mg/12 h Rabeprazole (vo) 20 mg/12 h H2 antagonists Famotidine (vo/iv) 20-40 mg/12 h Cimetidine (vo/iv) 200-400 mg/12 h Mixed: inhibits gastric secretion, gastric and colonic motility, and intestinal secretion Alpha-2 adrenergic agonist Clonidine (vo) 0.1-0.2 mg/12 h Mixed: inhibits gastric, biliopancreatic and intestinal secretion, and decreases intestinal motility Somatostatin analogue Octreotid (sc) 50-250 mcg/6-12 h Antibiotics: bacterial overgrowth treatment Microbiota modification Amoxicillin-clavulanate (vo) 500 mg-125 mg/8 h Ciprofloxacin (vo) 500 mg/12 h Rifaximin (vo) 550 mg/8 h Metronidazole (vo) 500 mg/8 h Trimethoprim-sulfamethoxazole (vo) 160-800 mg/12 h Pancreatic enzymes Fat malabsorption Pancreatic lipase (vo) 500 u/kg/meal (2,500 u/kg/ meal or 10,000 u/kg/d) vo: orally; iv: intravenously; sc: subcutaneously; QID: 4 times per day. 1294 F. J. Vílchez-López et al. [Nutr Hosp 2021;38(6):1287-1303] Pharmacotherapy is a symptomatic treatment used for the many SBS-associated pathophysiological mechanisms. The indications and proposed doses are based on those published in the literature; however, many of these drugs are prescribed off-label. The low prevalence of SBS means that clinical trials are practically non-existent and, in many cases, the therapeutic plan is based on the drug response witnessed in other pathologies such as chronic diarrhea or malabsorption. Antisecretory drugs Hypergastrinemia secondary to intestinal resection is a cause of gastric hypersecretion, which accelerates transit and neutralizes pancreatic enzymes and bile salts, making digestion difficult. Therefore, the use of antisecretory drugs is useful, initially intravenously and later orally/enterally. PPIs are of choice because they contribute to reducing stool wet weight and sodium excretion (upto 25%), especially during the first 6 months after surgery and when fecal production exceeds 2 L/day. Long-term maintenance may be considered in individual cases. The effects on energy and macronutrient absorption are less pronounced. All (100%) of the GARIN group experts use omeprazole as a first-line PPI at varying dosages (between 40 and 80 mg per day) (3,4,11,12). The use of PPIs has been associated with the development of hypomagnesemia, and this is possibly a dose-dependent effect, so it is essential to monitor magnesium and calcium levels, and to exercise greater caution in high-risk patients such as those with high-output ostomies. In the event of PPI-associated hypomagnesemia, the use of H2RAs should be considered (13). Seventy-five percent of the GARIN group experts use famotidine as an alternative to PPIs in hypomagnesemia cases. Anti-diarrheal agents An intestinal resection, especially if it affects the distal small bowel, causes a decrease in PYY, GLP1 and GLP2, which accelerates intestinal transit and reduces the contact time of nutrients with the intestinal mucosa. Antidiarrheal agents help to slow down the gastrointestinal transit. Loperamide reduces the loss of water and electrolytes, helps to reduce the need for intravenous fluid therapy, and facilitates stoma management. It has no central effects and, since it participates in the enterohepatic circulation, it can be administered at high doses safely and effectively in patients with terminal ileum resection. Its effectiveness should be evaluated regularly. One hundred percent (100%) of the GARIN group experts use loperamide at varying dosages as first-choice antidiarrheal agent. If loperamide is not sufficient, codeine should be added, which has a longer lasting effect; however, it crosses the blood-brain barrier and may cause side effects on the central nervous system. Since they have different mechanisms of action, both drugs can be administered together, 30 to 60 minutes before meals (to compensate for the gastrocolic reflex) and before sleeping. Treatment adjustments should be made every 3-5 days, until either an adequate clinical response is observed, adverse effects appear, or the maximum dose is reached. Diarrhea associated with Clostridium difficile or gastrointestinal infection should be exclu ded before initiating treatment with antidiarrheals (3,4,11,12). Octreotide A somatostatin analogue. It reduces digestive secretions, promotes fluid and electrolyte absorption, and slows transit. It is useful in patients with high-output ostomies refractory to conventional treatment, especially in the short term after intestinal resection. Gallstones appear in 20-50% of treated patients, so this should be monitored. It may delay intestinal adaptation (3,4,11,12). Resins (cholestyramine and colestipol) These are useful in patients whose colon is in continuity. In patients with a residual ileum of less than 100 cm and colon incontinuity, they can help prevent unabsorbed bile salts in the ileum spilling over into the colon and inducing osmotic diarrhea. However, they should be avoided in patients with more than 100cm of ileum because they can induce steatorrhea (3,11,12). Antibiotics Antibiotics are recommended in patients with SBS and bacterial overgrowth. Although there are no specific diagnostic criteria for its definition, this therapeutic plan in the event of clinical suspicion is justifiable. Different regimens should be administered cyclically, to avoid the appearance of bacterial resistance (4,12,14). They should be handled with caution in patients with colon because they can alter the gut microbiota and, thereby, inhibit the energy salvage achieved by the absorption of short-chain fatty acids, and increase the risk of lactic acidosis. Although there are no conclusive data in favor of a specific drug as the first choice, rifaximin seems to have better efficacy and tolerability (15). Pancreatic enzymes These can be useful in patients with steatorrhea despite ha ving complied with dietary recommendations, in relation to the persistence of rapid transit (12). Concomitant drugs SBS patients not only need drugs for symptomatic control but they often have concomitant diseases that require pharmacological treatment. This can be compromised by factors such as acid hypersecretion, rapid gastric emptying, reduced absorption 1295EVIDENCE-BASED RECOMMENDATIONS OF THE ANDALUSIAN GROUP FOR NUTRITION REFLECTION AND INVESTIGATION (GARIN) FOR THE MANAGEMENT OF ADULT PATIENTS WITH SHORT BOWEL SYNDROME [Nutr Hosp 2021;38(6):1287-1303] surface area, accelerated intestinal motility, interruption of enterohepatic circulation, and intestinal microbiota disorders. For this reason, it is essential to monitor the efficacy of the concomitant drugs, since they may require dose titration and, on occasions, alternative administration routes (subcutaneous, parenteral, rectal,etc.) (4). NUTRITIONAL ASSESSMENT AND NUTRITIONAL REQUIREMENTS What is the ideal nutritional assessment method for SBS? GARIN proposal: We recommend repeated screening and nutritional assessments for all patients in all the phases of the disease (consensus level: 100%) (low quality of evidence; net benefits outweigh the risks). As a consensus of experts our proposal is to apply GLIM criteria to establish the diagnosis of malnutrition and grade its severity, with the objective of its validation in the coming years. (Consensus level: 87.69%) As a consensus of experts our proposal is to use BIA, in addition to analytical and anthropometric parameters, to detect changes in nutritional status and evaluate the nutritional interventions carried out (consensus level: 84.61%). A complete nutritional assessment must be performed in all patients. A consensus was recently reached regarding the diagnosis of nutritional status by a group of experts from the main scientific societies (GLIM Criteria: Global Leadership Initiative on Malnutrition) (3,16). Bioelectrical impedance (BIA) is a non-invasive tool to measure body composition and nutritional status. The phase angle is considered a marker of cell integrity and, in various pathologies, it has been correlated with other nutritional parameters and/or muscle mass. There are no specific studies involving SBS, but it has been proposed as a prognostic marker in different clinical situations including HIV, cancer, surgery, and chronic liver disease (17,18). Bioelectrical impedance vector analysis (BIVA) is a vectorial approach of BIA, which could represent an alternative method that avoids errors derived from the BIA equation, and provides an improved estimation of body compartments. Fassini et al. concluded that BIVA may represent a better predictor of nutritional status for the analysis and interpretation of body composition in patients with short bowel syndrome (19). What are the recommended nutritional requirements in the SBS? GARIN proposal: In the acute phase, we suggest using indirect calorimetry where available (consensus level: 81.53%) (low quality of evidence; benefits compensate the risks). As a consensus of experts our proposal for an alternative is to establish the energy and protein requirements according to the following calculations (consensus level: 80%): – In the acute phase: caloric requirements: 25-35 kcal/kg/day; protein requirements: 1.5 g/kg real weight/day. – In the chronic phase: caloric requirements: 25-35 kcal/kg/ day. Use usual weight in case of edema and adjusted weight in case of obesity. As a consensus of experts our proposal is to calculate the caloric requirements using Johnstone’s equation if the impedance measurement is available. Protein requirements: 1-1.4 g/kg/day. We recommend adjusting these requirements to clinical and laboratory changes, and to always consider the potential loss of nutrients through the stoma (consensus level: 98.46%) (low quality of evidence; net benefits outweigh the risks). Indirect calorimetry is the gold-standard technique for estimating caloric needs, and it should be repeated periodically to detect changes in energy requirements. However, this technique is not always avai lable and, frequently, it is necessary to resort to predictive equations. The latest ASPEN (2016) and ESPEN (2019) recommendations for acute-phase patients in the intensive care unit are 25-30kcal/ kg/day (providing 70% of the estimated requirements during the first week, with progressive increases from then on) and 1.22g/kg/day and 1.3 g/kg/day of proteins, respectively (20,21). The ESPEN recommendations for acute IF are 25-35 kcal/kg/day (depending on whether the patient is in the early catabolic phase or in the later anabolic phase), and up to 1.5 g/kg real weight/ day of proteins (3). Most scientific societies recommend 20-35 kcal/kg in chronic IF (4). The usual weight should be used in the presence of edema, and the adjusted weight in the case of obesity (BMI>30kg/m2). In a situation of severe malnutrition, the calorie goal can be 30-35 kcal/kg/day (22). Some authors have compared the results of indirect calorimetry with those of various predictive equations (23). Skallerup et al. concluded that the best approximations are obtained with the Harris-Benedict equation (with anthropometric parameters) or with the Johnstone equation (with impedance measurement), despite the fact that the BMR is overestimated or underestimated in approximately 35% of the patients with both of them (24). This may mean that formulas are necessary that estimate the BMR using body composition parameters such as fat-free mass or muscle mass index. All these recommendations should be adapted to the clinical situation of the patient, the presence ofcatabolic stress, body composition (if possible), the presenceof comorbidities, and the level of physical activity. The recommended protein requirements in this phase range between 0.8 and 1.4 g/kg/day (4). In patients with normal renal function the goal would be 0.8-1 g/kg/day, increasing this figure to 1.5 g/kg/day in the presence of metabolic stress (22). Additionally, none of these recommendations takes into account the sometimes significant fecal losses of nutrients, which results in the calculated requirements being frequently underestimated, as suggested by Fassini et al. (25). 1302 F. J. Vílchez-López et al. [Nutr Hosp 2021;38(6):1287-1303] by bioelectrical impedance analysis and mortality in patients with different medical conditions: Systematic review and meta-analyses. Clin Nutr ESPEN 2018;28:12-20. DOI: 10.1016/j.clnesp.2018.08.022 10. Pironi L, Corcos O, Forbes A, Holst M, Joly F, Jonkers C, et al. Intestinal failure in adults: Recommendations from the ESPEN expert groups. Clin Nutr 2018;37:1798-809. DOI: 10.1016/j.clnu.2018.07.036 11. Buchman AL. Intestinal Failure and Rehabilitation. Gastroenterol Clin North Am 2018;47:327-40. DOI: 10.1016/j.gtc.2018.01.006 12. Kumpf VJ. Pharmacologic management of diarrhea in patients with short bowel syndrome. JPEN J Parenter Enteral Nutr 2014;38:38S-44S. DOI: 10.1177/0148607113520618 13. Srinutta T, Chewcharat A, Takkavatakarn K, Praditpornsilpa K, Eiam-Ong S, Jaber BL, et al. Proton pump inhibitors and hypomagnesemia: A meta-analysis of observational studies. Medicine (Baltimore) 2019;98:e17788. DOI: 10.1097/MD.0000000000017788 14. Johnson E, Vu L, Matarese LE. Bacteria, Bones, and Stones: Managing Complications of Short Bowel Syndrome. Nutr Clin Pract 2018;33:454-66. DOI: 10.1002/ncp.10113 15. Rao SSC, Bhagatwala J. Small Intestinal Bacterial Overgrowth: Clinical Features and Therapeutic Management. Clin Transl Gastroenterol 2019;10:e00078. DOI: 10.14309/ctg.0000000000000078 16. Cederholm T, Jensen GL, Correia MITD, Gonzalez MC, Fukushima R, Higashiguchi T, et al. GLIM criteria for the diagnosis of malnutrition - A consensus report from the global clinical nutrition community. Clin Nutr 2019;38:1-9. DOI: 10.1016/j.clnu.2018.08.002 17. Lukaski HC, Kyle UG, Kondrup J. Assessment of adult malnutrition and prognosis with bioelectrical impedance analysis: phase angle and impedance ratio. Curr Opin Clin Nutr Metab Care 2017;20:330-9. DOI: 10.1097/ MCO.0000000000000387 18. Rinaldi S, Gilliland J, O’Connor C, Chesworth B, Madill J. Is phase angle an appropriate indicator of malnutrition in different disease states? A systematic review. Clin Nutr ESPEN 2019;29:1-14. DOI: 10.1016/j. clnesp.2018.10.010 19. Fassini PG, Nicoletti CF, Pfrimer K, Nonino CB, Marchini JS, Ferriolli E. Bioelectrical impedance vector analysis as a useful predictor of nutritional status in patients with short bowel syndrome. Clin Nutr 2017;36:1117-21. DOI: 10.1016/j.clnu.2016.07.011 20. Taylor BE, McClave, SA, Martindale RG, Warren M.M, Johnson DR, Braunschweig C, et al. Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). Crit Care Med 2016;44:390-438. DOI: 10.1097/ CCM.0000000000001525 21. Singer P, Blaser AR, Berger MM, Alhazzani W, Calder PC, Casaer MP, et al. ESPEN guideline on clinical nutrition in the intensive care unit. Clin Nutr 2019;38:48-79. DOI: 10.1016/j.clnu.2018.08.037 22. Bielawska B, Allard JP. Parenteral Nutrition and Intestinal Failure. Nutrients 2017;9(5):466. DOI: 10.3390/nu9050466 23. Ławiński M, Singer P, Gradowski Ł, Gradowska A, Bzikowska A, Majewska K. Predicted versus measured resting energy expenditure in patients requiring home parenteral nutrition. Nutrition 2015;31:1328-32. DOI: 10.1016/j. nut.2015.05.002 24. Skallerup A, Nygaard L, Olesen SS, Vinter-Jensen L, Køhler M, Rasmussen HH. Can We Rely on Predicted Basal Metabolic Rate in Patients With Intestinal Failure on Home Parenteral Nutrition? JPEN J Parenter Enteral Nutr 2017;41:1139-45. DOI: 10.1177/0148607116657648 25. Fassini PG, Das SK, Pfrimer K, Suen VMM, Sérgio Marchini J, Ferriolli E. Energy intake in short bowel syndrome: assessment by 24-h dietary recalls compared with the doubly labelled water method. Br J Nutr 2018;119:196201. DOI: 10.1017/S0007114517003373 26. Jategaonkar PA, Yadav SP. A Simple Bed-side Method of Enteral Feeding through Distal Mucous Fistula in Patients with Short Bowel Syndrome to overcome Parenteral Dependency: The Jategaonkar Technique. J Coll Physicians Surg Pak 2019;29:1212-4. DOI: 10.29271/jcpsp.2019.12.1212 27. Jeppesen PB, Fuglsang KA. Nutritional Therapy in Adult Short Bowel Syndrome Patients with Chronic Intestinal Failure. Gastroenterol Clin North Am 2018;47:61-75. DOI: 10.1016/j.gtc.2017.10.004 28. Atia A, Girard-Pipau F, Hébuterne X, Spies WG, Guardiola A, Ahn CW, et al. Macronutrient absorption characteristics in humans with short bowel syndrome and jejunocolonic anastomosis: starch is the most important carbohydrate substrate, although pectin supplementation may modestly enhance short chain fatty acid production and fluid absorption. JPEN J Parenter Enteral Nutr 2011;35:229-40. DOI: 10.1177/0148607110378410 29. Hurt RT, Vallumsetla N, Edakkanambeth Varayil J, Bonnes SL, Nanda S, Nadeau J, et al. Pilot Study Comparing 2 Oral Rehydration Solutions in Patients With Short Bowel Syndrome Receiving Home Parenteral Nutrition: A Prospective Double-Blind Randomized Controlled Trial. Nutr Clin Pract 2017;32:814-9. DOI: 10.1177/0884533617714975 30. Pironi L, Boeykens K, Bozzetti F, Joly F, Klek S, Lal S, et al. ESPEN guideline on home parenteral nutrition. Clin Nutr 2020;39(6):1645-666. DOI: 10.1016/j. clnu.2020.03.005 31. Wanden-Berghe Lozano C, Pereira Cunill JL, Cuerda Compes C, Ramos Boluda E, Maiz Jiménez MI, Gómez Candela C, et al. Home and Ambulatory Artificial Nutrition (NADYA) Report. Home Parenteral Nutrition in Spain, 2017. Nutr Hosp 2018;35:1491-6. DOI: 10.20960/nh.2364 32. Hortencio TDR, Arendt BM, Teterina A, Jeejeebhoy KN, Gramlich LM, Whittaker JS, et al. Changes in Home Parenteral Nutrition Practice Based on the Canadian Home Parenteral Nutrition Patient Registry. JPEN J Parenter Enteral Nutr 2017;41:830-6. DOI: 10.1177/0148607115609289 33. Winkler MF, DiMaria-Ghalili RA, Guenter P, Resnick HE, Robinson L, Lyman B, et al. Characteristics of a Cohort of Home Parenteral Nutrition Patients at the Time of Enrollment in the Sustain Registry. JPEN J Parenter Enteral Nutr 2016;40:1140-9. DOI: 10.1177/0148607115586575 34. Hon K, Bihari S, Holt A, Bersten A, Kulkarni H. Rate of Catheter-Related Bloodstream Infections Between Tunneled Central Venous Catheters Versus Peripherally Inserted Central Catheters in Adult Home Parenteral Nutrition: A Meta-analysis. JPEN J Parenter Enteral Nutr 2019;43:41-53. DOI: 10.1002/ jpen.1421 35. Mateo-Lobo R, Riveiro J, Vega-Piñero B, Botella-Carretero JI. Infectious Complications in Home Parenteral Nutrition: A Systematic Review and Meta-Analysis Comparing Peripherally-Inserted Central Catheters with Other Central Catheters. Nutrients 2019;11(9):2083. DOI: 10.3390/nu11092083 36. Bond A, Chadwick P, Smith TR, Nightingale JMD, Lal S. Diagnosis and management of catheter-related bloodstream infections in patients on home parenteral nutrition. Frontline Gastroenterol 2020;11:48-54. DOI: 10.1136/ flgastro-2018-101094 37. Wouters Y, Causevic E, Klek S, Groenewoud H, Wanten GJA. Use of Catheter Lock Solutions in Patients Receiving Home Parenteral Nutrition: A Systematic Review and Individual-Patient Data Meta-analysis. JPEN J Parenter Enteral Nutr 2020;44(3). DOI: 10.1002/jpen.1761 38. Saqui O, Fernandes G, Allard JP. Quality of life analysis during transition from stationary to portable infusion pump in home parenteral nutrition patients: a Canadian experience. Nutr Clin Pract 2014;29:131-41. DOI: 10.1177/0884533613516129 39. Winkler MF, Hagan E, Wetle T, Smith C, Maillet JO, Touger-Decker R. An exploration of quality of life and the experience of living with home parenteral nutrition. JPEN J Parenter Enteral Nutr 2010;34:395-407. DOI: 10.1177/0148607110362582 40. Iacone R, Scanzano C, Santarpia L, Alfonsi L, Marra M, Pagano MC, et al. Essential Amino Acid Profile in Parenteral Nutrition Mixtures: Does It Meet Needs? Nutrients 2018;10(12):1937. DOI: 10.3390/nu10121937 41. Lal S, Pironi L, Wanten G, Arends J, Bozzetti F, Cuerda C, et al. Clinical approach to the management of Intestinal Failure Associated Liver Disease (IFALD) in adults: A position paper from the Home Artificial Nutrition and Chronic Intestinal Failure Special Interest Group of ESPEN. Clin Nutr 2018;37:1794-7. DOI: 10.1016/j.clnu.2018.07.006 42. Pironi L, Sasdelli AS. Intestinal Failure-Associated Liver Disease. Clin Liver Dis 2019;23:279-91. DOI: 10.1016/j.cld.2018.12.009 43. Xu Z, Li Y, Wang J, Wu B, Li J. Effect of omega-3 polyunsaturated fatty acids to reverse biopsy-proven parenteral nutrition-associated liver disease in adults. Clin Nutr 2012;31:217-23. DOI: 10.1016/j.clnu.2011.10.001 44. Jurewitsch B, Gardiner G, Naccarato M, Jeejeebhoy KN. Omega-3-enriched lipid emulsion for liver salvage in parenteral nutrition-induced cholestasis in the adult patient. JPEN J Parenter Enteral Nutr 2011;35:386-90. DOI: 10.1177/0148607110382023 45. Uzzan M, Kirchgesner J, Poupon J, Corcos O, Pingenot I, Joly F. Antioxidant trace elements serum levels in long-term parenteral nutrition (PN): Prevalence and infectious risk associated with deficiencies, a retrospective study from a tertiary home-PN center. Clin Nutr 2017;36:812-7. DOI: 10.1016/j. clnu.2016.05.008 46. Btaiche IF, Carver PL, Welch KB. Dosing and monitoring of trace elements in long-term home parenteral nutrition patients. JPEN J Parenter Enteral Nutr 2011;35:736-47. DOI: 10.1177/0148607111413902 47. Dastych M, Šenkyřík M, Novák F, Wohl P, Maňák J, Kohout P. Trace Element Status (Zinc, Copper, Selenium, Iron, Manganese) in Patients with Long- 1303EVIDENCE-BASED RECOMMENDATIONS OF THE ANDALUSIAN GROUP FOR NUTRITION REFLECTION AND INVESTIGATION (GARIN) FOR THE MANAGEMENT OF ADULT PATIENTS WITH SHORT BOWEL SYNDROME [Nutr Hosp 2021;38(6):1287-1303] Term Home Parenteral Nutrition. Ann Nutr Metab 2016;69:120-4. DOI: 10.1159/000450763 48. Dastych M, Senkyrík M. Manganese in Whole Blood and Hair in Patients with Long-Term Home Parenteral Nutrition. Clin Lab 2016;62:173-7. 49. Vanek VW, Borum P, Buchman A, Fessler TA, Howard L, Jeejeebhoy K, et al. A.S.P.E.N. position paper: recommendations for changes in commercially available parenteral multivitamin and multi-trace element products. Nutr Clin Pract 2012;27:440-91. DOI: 10.1177/0884533612446706 50. Austin K, Markovic MA, Brubaker PL. Current and potential therapeutic targets of glucagon-like peptide-2. Curr Opin Pharmacol 2016;31:13-8. DOI: 10.1016/j.coph.2016.08.008 51. Pironi L. Translation of Evidence Into Practice With Teduglutide in the Management of Adults With Intestinal Failure due to Short-Bowel Syndrome: A Review of Recent Literature. JPEN J Parenter Enteral Nutr 2020;44(6):968-78. DOI: 10.1002/jpen.1757 52. Jeppesen PB, Pertkiewicz M, Messing B, Iyer K, Seidner DL, O’keefe SJ, et al. Teduglutide reduces need for parenteral support among patients with short bowel syndrome with intestinal failure. Gastroenterology 2012;143:1473-81. e1473. DOI: 10.1053/j.gastro.2012.09.007 53. Schwartz LK, O’Keefe SJ, Fujioka K, Gabe SM, Lamprecht G, Pape UF, et al. Long-Term Teduglutide for the Treatment of Patients With Intestinal Failure Associated With Short Bowel Syndrome. Clin Transl Gastroenterol 2016;7:e142. DOI: 10.1038/ctg.2015.69 54. Seidner DL, Fujioka K, Boullata JI, Iyer K, Lee HM, Ziegler TR. Reduction of Parenteral Nutrition and Hydration Support and Safety With Long-Term Teduglutide Treatment in Patients With Short Bowel Syndrome-Associated Intestinal Failure: STEPS-3 Study. Nutr Clin Pract 2018;33:520-7. DOI: 10.1002/ncp.10092 55. Iyer KR, Kunecki M, Boullata JI, Fujioka K, Joly F, Gabe S, et al. Independence From Parenteral Nutrition and Intravenous Fluid Support During Treatment With Teduglutide Among Patients With Intestinal Failure Associated With Short Bowel Syndrome. JPEN J Parenter Enteral Nutr 2017;41:946-51. DOI: 10.1177/0148607116680791 56. Jeppesen PB, Gabe SM, Seidner DL, Lee HM, Olivier C. Factors Associated With Response to Teduglutide in Patients With Short-Bowel Syndrome and Intestinal Failure. Gastroenterology 2018;154:874-85. DOI: 10.1053/j.gastro.2017.11.023 57. Chen KS, Xie J, Tang W, Zhao J, Jeppesen PB, Signorovitch JE. Identifying a subpopulation with higher likelihoods of early response to treatment in a heterogeneous rare disease: a post hoc study of response to teduglutide for short bowel syndrome. Ther Clin Risk Manag 2018;14:1267-77. DOI: 10.2147/TCRM.S166081 58. Seidner DL, Gabe SM, Lee HM, Olivier C, Jeppesen PB. Enteral Autonomy and Days Off Parenteral Support With Teduglutide Treatment for Short Bowel Syndrome in the STEPS Trials. JPEN J Parenter Enteral Nutr 2020;44(4):697702. DOI: 10.1002/jpen.1687 59. Kochar B, Herfarth HH. Teduglutide for the treatment of short bowel syndrome - a safety evaluation. Expert Opin Drug Saf 2018;17:733-9. DOI: 10.1080/14740338.2018.1483332 60. Ring LL, Nerup N, Jeppesen PB, Svendsen LB, Achiam MP. Glucagon like peptide-2 and neoplasia; a systematic review. Expert Rev Gastroenterol Hepatol 2018;12:257-64. DOI: 10.1080/17474124.2018.1417032