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Sasson AN, Noelting J, Schwenger KJP, Ghorbani Y, Armstrong D, Raman M, Duerksen DR, Whittaker S, Lu Y, Jurewitsch B, Gramlich L, Ananthakrishnan AN, Allard JP. Clinical outcomes in Crohn's disease patients with short bowel syndrome on home parenteral nutrition are comparable to those with short bowel syndrome from other etiologies. Clin Nutr 2025; 49:149-156. [PMID: 40305998 DOI: 10.1016/j.clnu.2025.04.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Revised: 03/14/2025] [Accepted: 04/12/2025] [Indexed: 05/02/2025]
Abstract
BACKGROUND & AIMS Patients with short bowel syndrome (SBS) and chronic intestinal failure require home parenteral nutrition (PN) support. The main cause of SBS remains Crohn's disease (CD), and complications in this cohort versus SBS from other etiologies remains to be determined. We therefore sought to investigate whether patients with SBS secondary to CD versus SBS secondary to other etiologies, have increased risk of complications and whether there is a difference in overall mortality between groups. METHODS This is a multicentre prospective cohort study using the Canadian Home Parenteral Nutrition (HPN) Registry. Two groups were compared: 1) SBS secondary to CD (SBS-CD) vs. 2) SBS- secondary to other etiologies (SBS-Other) (including trauma, surgical complication, vascular event, volvulus and malignancy). Clinical data for each patient included: number of hospitalizations, number of hospitalizations related to HPN and number of hospitalization days related to HPN, incidence of line sepsis per 1000 catheter days and mortality. Descriptive statistics are presented as median (interquartile range) for continuous variables and as frequency (percentage) for categorical variables as appropriate. Comparison between groups were performed using a 2-sample t-test,Poisson regression analysis or Wilcoxon rank sum test for continuous variables and Chi-square or Fisher exact tests when appropriate for categorical variables. Kaplan-Meir curve and multivariate analysis was performed to assess mortality. Statistical significance is set at a p-value <0.05. RESULTS The study included 383 patients with SBS and intestinal failure: 172 (45 %) SBS-CD and 211 (55 %) SBS-Other; followed for median of 4 (2, 6) years and 2 (2, 4) years respectively (p = 0.027). The groups were comparable at baseline except for younger age, shorter small bowel length and medications with higher use of immunosuppressant therapy (39 % vs. 7 %, p < 0.001) in those with CD. The number of hospitalizations, hospitalization days, and line sepsis per 1000 catheter days were similar amongst the SBS- CD and SBS-Other (p > 0.05 across all primary outcomes). Mortality events were also similar between groups (31 patients (26.72 %) in SBS CD group vs. 37 patients (29.84 %) in SBS- Other group, p = 0.6676). The Kaplan-Meir curve did not show a statistical difference in mortality between groups but a multivariate analysis of the entire patient population showed that age was associated with mortality. In subgroup analysis, patients with SBS- CD taking immunosuppressant therapy were not at higher risk of hospitalizations or line sepsis compared to those not on immunomodulating therapies (0.50 versus 1.57 p = 0.0417). CONCLUSION Individuals with SBS CD do not have increased risk of hospitalizations, central line infections or mortality compared to those with SBS from other causes. In CD, those on immunomodulating therapies do not appear to be at increased risk of complications.
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Affiliation(s)
- Alexa N Sasson
- Department of Medicine, Division of Gastroenterology, Toronto General Hospital, University of Toronto, Toronto, Canada
| | - Jessica Noelting
- Division of Gastroenterology, Essentia Health Duluth and Essentia Health St. Mary's Medical Center, Duluth, MN, USA
| | - Katherine J P Schwenger
- Department of Medicine, Division of Gastroenterology, Toronto General Hospital, University of Toronto, Toronto, Canada
| | - Yasaman Ghorbani
- Department of Medicine, Division of Gastroenterology, Toronto General Hospital, University of Toronto, Toronto, Canada
| | - David Armstrong
- Division of Gastroenterology & Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Maitreyi Raman
- Division of Gastroenterology, University of Calgary, Calgary, Alberta, Canada
| | - Donald R Duerksen
- Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Scott Whittaker
- Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Yidan Lu
- Department of Medicine, McGill University, Montreal, Quebec, Canada
| | - Brian Jurewitsch
- Department of Pharmacy, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Leah Gramlich
- Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - Ashwin N Ananthakrishnan
- Department of Medicine, Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Johane P Allard
- Department of Medicine, Division of Gastroenterology, Toronto General Hospital, University of Toronto, Toronto, Canada.
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Park J, Park S, Chung HJ, Lee DI, Kim JM, Kim SH, Choe EK, Park KJ, Yoon SH. Deep learning for automatic volumetric bowel segmentation on body CT images. Eur Radiol 2025:10.1007/s00330-025-11623-z. [PMID: 40314787 DOI: 10.1007/s00330-025-11623-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Revised: 02/18/2025] [Accepted: 03/31/2025] [Indexed: 05/03/2025]
Abstract
OBJECTIVES To develop a deep neural network for automatic bowel segmentation and assess its applicability for estimating large bowel length (LBL) in individuals with constipation. MATERIALS AND METHODS We utilized contrast-enhanced and non-enhanced abdominal, chest, and whole-body CT images for model development. External testing involved paired pre- and post-contrast abdominal CT images from another hospital. We developed 3D nnU-Net models to segment the gastrointestinal tract and separate it into the esophagus, stomach, small bowel, and large bowel. Segmentation accuracy was evaluated using the Dice similarity coefficient (DSC) based on radiologists' segmentation. We employed the network to estimate LBL in individuals having abdominal CT for health check-ups, and the height-corrected LBL was compared between groups with and without constipation. RESULTS One hundred thirty-three CT scans (88 patients; age, 63.6 ± 10.6 years; 39 men) were used for model development, and 60 for external testing (30 patients; age, 48.9 ± 15.8 years; 16 men). In the external dataset, the mean DSC for the entire gastrointestinal tract was 0.985 ± 0.008. The mean DSCs for four-part separation exceeded 0.95, outperforming TotalSegmentator, except for the esophagus (DSC, 0.807 ± 0.173). For LBL measurements, 100 CT scans from 51 patients were used (age, 67.0 ± 6.9 years; 59 scans from men; 59 with constipation). The height-corrected LBL were significantly longer in the constipation group on both per-exam (79.1 ± 12.4 vs 88.8 ± 15.8 cm/m, p = 0.001) and per-subject basis (77.6 ± 13.6 vs 86.9 ± 17.1 cm/m, p = 0.04). CONCLUSION Our model accurately segmented the entire gastrointestinal tract and its major compartments from CT scans and enabled the noninvasive estimation of LBL in individuals with constipation. KEY POINTS Questions Automated bowel segmentation is a first step for algorithms, including bowel tracing and length measurement, but the complexity of the gastrointestinal tract limits its accuracy. Findings Our 3D nnU-Net model showed high performance in segmentation and four-part separation of the GI tract (DSC > 0.95), except for the esophagus. Clinical relevance Our model accurately segments the gastrointestinal tract and separates it into major compartments. Our model potentially has use in various clinical applications, including semi-automated measurement of LBL in individuals with constipation.
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Affiliation(s)
- Junghoan Park
- Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Sungeun Park
- Department of Radiology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Republic of Korea
| | - Han-Jae Chung
- AI Center, MEDICAL IP Co., Ltd., Seoul, Republic of Korea
| | - Da In Lee
- AI Center, MEDICAL IP Co., Ltd., Seoul, Republic of Korea
| | - Jong-Min Kim
- AI Center, MEDICAL IP Co., Ltd., Seoul, Republic of Korea
| | - Se Hyung Kim
- Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
- Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, Republic of Korea
| | - Eun Kyung Choe
- Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Republic of Korea
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Kyu Joo Park
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Soon Ho Yoon
- Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
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Jeppesen PB, Vanuytsel T, Subramanian S, Joly F, Wanten G, Lamprecht G, Kunecki M, Rahman F, Nielsen TSS, Berner-Hansen M, Pape UF, Mercer DF. Glepaglutide, a Long-Acting Glucagon-like Peptide-2 Analogue, Reduces Parenteral Support in Patients With Short Bowel Syndrome: A Phase 3 Randomized Controlled Trial. Gastroenterology 2025; 168:701-713.e6. [PMID: 39708985 DOI: 10.1053/j.gastro.2024.11.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Revised: 11/20/2024] [Accepted: 11/26/2024] [Indexed: 12/23/2024]
Abstract
BACKGROUND & AIMS Glepaglutide is a long-acting glucagon-like peptide (GLP)-2 analogue developed to improve intestinal absorption in patients with short bowel syndrome (SBS). The authors conducted a trial to establish the efficacy and safety of glepaglutide in reducing parenteral support (PS) needs in patients with SBS with intestinal failure. METHODS In an international, placebo-controlled, randomized, parallel-group, double-blind, phase 3 trial, patients with SBS with intestinal failure requiring PS ≥3 d/wk were randomized 1:1:1 to 24 weeks of glepaglutide 10 mg twice weekly or once weekly or placebo. PS volume was equivalently reduced if mean urine volume of a 48-hour balance period exceeded baseline values by >10%. RESULTS One hundred six patients were randomized and dosed. Glepaglutide twice weekly significantly reduced weekly PS volumes from baseline to week 24 vs placebo (mean change, -5.13 vs -2.85 L/wk; P = .0039; primary end point). Results were similar across major anatomic subgroups. Glepaglutide twice weekly was also superior to placebo for key secondary end points of proportion of patients achieving clinical response, defined as ≥20% PS volume reduction from baseline to weeks 20 and 24 (65.7% vs 38.9%; P = .0243) and patients achieving a reduction in days on PS ≥1 d/wk from baseline to week 24 (51.4% vs 19.4%; P = .0043). Complete PS weaning ("enteral autonomy") was achieved for 5 patients (14%) receiving glepaglutide twice weekly vs 0 for patients receiving placebo. No statistically significant differences were found for glepaglutide once weekly vs placebo for primary or key secondary end points. Significant glepaglutide benefits on patient-reported outcome (Patient Global Impression of Change) were found. Glepaglutide was assessed to be safe and well tolerated. CONCLUSIONS Glepaglutide treatment in patients with SBS with intestinal failure resulted in clinically relevant reductions in PS requirements and was well tolerated. (ClinicalTrials.gov, Number: NCT03690206; ClinicalTrialsRegister.eu, Number: 2017-004394-14.).
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Affiliation(s)
- Palle B Jeppesen
- Department of Medical Gastroenterology and Hepatology, Rigshospitalet, Copenhagen, Denmark.
| | - Tim Vanuytsel
- Department of Gastroenterology and Hepatology, Universitair Ziekenhuis Leuven, Leuven, Belgium
| | | | - Francisca Joly
- Beaujon Hospital, University of Paris, UMR1149, Paris, France
| | - Geert Wanten
- Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
| | | | | | - Farooq Rahman
- University College London Hospitals, London, United Kingdom
| | | | - Mark Berner-Hansen
- Zealand Pharma, Søborg, Denmark; Digestive Disease Center, Bispebjerg University Hospital, Copenhagen, Denmark
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Van Berkel M, Beurskens-Meijerink J, Buters-Ambrosius N, Van Der Hagen E, Huisman-De Waal G, Wanten G. Accurate urine sodium measurements at home using point of care testing in patients with short bowel syndrome. Clin Nutr ESPEN 2025; 66:262-268. [PMID: 39863259 DOI: 10.1016/j.clnesp.2025.01.040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Revised: 12/04/2024] [Accepted: 01/14/2025] [Indexed: 01/27/2025]
Abstract
BACKGROUND AND AIMS Measurement of the urine sodium concentration (USC) is a simple procedure that in many patients adequately indicates their hydration status. This is of particular importance in patients suffering from short bowel syndrome (SBS), who may very rapidly dehydrate and are at risk for permanently compromising their kidney function. A point of care testing (POCT) that allows reliable measurement of USC would enable these patients to effectively evaluate their sodium- and water balance in the at home setting, thereby avoiding hospital visits and delayed test results. In this study, a POCT device to assess USC was first analytically validated after which it was applied for the at home evaluation of the hydration status in patients with SBS. METHODS First, we validated the imprecision, bias and limit of quantification of USC as measured with the Fisic Medimate POCT device in comparison to an automated routine chemistry system. Next, the device was used for monitoring USC at home in 21 patients with SBS, including an evaluation of user friendliness System Usability Scale (SUS) and accuracy for detecting low sodium levels as compared to the routine chemistry system. RESULTS The imprecision of the POCT device at low USC was 6.1 %. In samples at the clinical decision threshold to identify patients at the verge of dehydration of 20 mmol/l as measured by routine chemistry USC, the POCT device demonstrated a mean estimation of USC of 20.6 mmol/l (95 % CI 18.8-22.4). Dehydration was detected with a sensitivity of 95 % when the medical decision limit for urinary sodium on the POCT device was set at a safe concentration of 30 mmol/l. Using the device was straightforward and easy to learn for patients with an overall System Usability Scale (SUS) score of 86. CONCLUSION USC measurements using this POCT device can be safely integrated into daily practice for early detection of dehydration in patients with SBS. Clear patient instructions to ensure accurate drop dispensing and a higher clinical decision threshold of USC of 30 mmol/l will allow a high sensitivity for detecting dehydration in patients with short bowel syndrome.
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Affiliation(s)
- Miranda Van Berkel
- Department of Laboratory Medicine, Radboud University Medical Center, Geert Grooteplein 10, 6500 HB, Nijmegen, the Netherlands.
| | - Judith Beurskens-Meijerink
- Department of Gastroenterology and Hepatology, Intestinal Failure Unit, Radboud University Medical Centre Nijmegen, Geert Grooteplein 10, 6500 HB, Nijmegen, the Netherlands.
| | - Nicole Buters-Ambrosius
- Department of Laboratory Medicine, Radboud University Medical Center, Geert Grooteplein 10, 6500 HB, Nijmegen, the Netherlands.
| | - Eline Van Der Hagen
- Department of Laboratory Medicine, Radboud University Medical Center, Geert Grooteplein 10, 6500 HB, Nijmegen, the Netherlands.
| | - Getty Huisman-De Waal
- Scientific Institute for Quality of Healthcare, IQ Health, Kapittelweg 54, 6525 EP, Nijmegen, the Netherlands.
| | - Geert Wanten
- Department of Gastroenterology and Hepatology, Intestinal Failure Unit, Radboud University Medical Centre Nijmegen, Geert Grooteplein 10, 6500 HB, Nijmegen, the Netherlands.
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Tsang JTW, Fung ACH, Lau SCL, Wong KKY. Outcomes of Children With Short Bowel Syndrome: Experiences in a Multidisciplinary Intestinal Rehabilitation Unit Over Two Decades. J Pediatr Surg 2025; 60:161646. [PMID: 39147684 DOI: 10.1016/j.jpedsurg.2024.07.031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Revised: 07/01/2024] [Accepted: 07/22/2024] [Indexed: 08/17/2024]
Abstract
BACKGROUND Short bowel syndrome (SBS) is a rare but serious form of organ failure, and patients with SBS depend on total parenteral nutrition (PN) to maintain growth and development. The present study aimed to evaluate the experiences and outcomes of children with SBS managed by a multidisciplinary intestinal rehabilitation programme in a tertiary paediatric centre. METHODS A retrospective single-centre analysis of all paediatric patients with a clinical diagnosis of SBS between 2001 and 2022 was performed. Clinical outcomes and their predictors were extracted and analysed. RESULTS Of the 64 children included in the study, 43 (67%) had extensive necrotising enterocolitis. The median bowel length was 45 cm (interquartile range (IQR) = 18-65) and 18.9% (IQR = 10-28.5) of the expected length based on age. Over a mean follow-up period of 8.9 years, 57 patients (89%) survived, and 50 (78%) weaned off PN. The presence of intestinal failure-associated liver disease (IFALD) (OR = 6.375, p = 0.02) and patients managed before the introduction of fish oil-based PN in 2007 (OR = 5.895, p = 0.001) were significant predictors of mortality. There was an overall improvement in survival over time (p = 0.003). Ultrashort bowel length was not associated with significantly higher mortality (OR = 1.1, p = 0.65) but was a poor prognostic factor for weaning off PN (OR = 3.57, p = 0.004). Among all patients who weaned off PN, two had bowel lengthening procedures and one received a glucagon-like peptide 2 (GLP-2) analogue. CONCLUSIONS A multidisciplinary intestinal rehabilitation programme offers a comprehensive approach for patients with SBS and has been shown to be effective with favourable outcomes. Improvements in the choice of PN and the development of new treatment strategies potentially improved the survival and enteral autonomy of SBS patients. LEVEL OF EVIDENCE III.
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Affiliation(s)
- Jaime Tsz-Wing Tsang
- Department of Surgery, School of Clinical Medicine, University of Hong Kong, Hong Kong
| | - Adrian Chi-Heng Fung
- Department of Surgery, School of Clinical Medicine, University of Hong Kong, Hong Kong
| | | | - Kenneth Kak-Yuen Wong
- Department of Surgery, School of Clinical Medicine, University of Hong Kong, Hong Kong.
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Moran‐Lev H, Kocoshis SA, Córdova Amador I, Mukasa M, Oliveira SB, Helmrath M, Cole CR. Factors associated with accelerated parenteral weaning in children with intestinal failure: A descriptive cohort study. JPEN J Parenter Enteral Nutr 2025; 49:207-213. [PMID: 39690722 PMCID: PMC11794671 DOI: 10.1002/jpen.2711] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Revised: 11/20/2024] [Accepted: 11/20/2024] [Indexed: 12/19/2024]
Abstract
BACKGROUND The goal of intestinal rehabilitation in children is to wean from parenteral nutrition (PN). The aim of this study was to identify factors associated with accelerated weaning and to evaluate long-term outcomes of children receiving long-term PN. METHODS This was a retrospective study of children managed by the Intestinal Rehabilitation Center at Cincinnati Children's Hospital. Medical history data were retrieved. The outcomes of children receiving long-term chronic PN (>2 years) were compared with those of children receiving short-term chronic PN regimen (<2 years). RESULTS The cohort consisted of 112 children (58% boys, median [IQR] age of 6.0 [3.7-9.5] years). The group treated with a long-term PN regimen had significantly shorter residual small bowel and large bowel compared with the group treated with a short-term PN regimen (20% vs 60% and 75% vs 100%, respectively; P < 0.05). The lapse of time between PN and enteral feed initiation was longer in the group undergoing long-term PN regimen than in the short-term group (71 vs 32.5 days; P = 0.012). More episodes of central line-associated bloodstream infection (CLABSI) and a higher percentage of feeding aversion was demonstrated in the long-term PN group (2 [1-3] vs 1 [0-2] episodes and 36% vs 0%, respectively). CONCLUSION Small bowel, colon length, enteral feed initiation, and frequency of CLABSI are factors associated with duration of PN regimen. A long-term chronic PN regimen is associated with a higher risk of food aversion.
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Affiliation(s)
- Hadar Moran‐Lev
- Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical CenterUniversity of Cincinnati School of MedicineCincinnatiOhioUSA
- Division of Gastroenterology, Hepatology and Nutrition, Dana Dwek Children's Hospitalaffiliated to Tel Aviv UniversityTel AvivIsrael
| | - Samuel A. Kocoshis
- Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical CenterUniversity of Cincinnati School of MedicineCincinnatiOhioUSA
| | - Isabel Córdova Amador
- Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical CenterUniversity of Cincinnati School of MedicineCincinnatiOhioUSA
| | - Mariah Mukasa
- Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical CenterUniversity of Cincinnati School of MedicineCincinnatiOhioUSA
| | - Stephanie B. Oliveira
- Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical CenterUniversity of Cincinnati School of MedicineCincinnatiOhioUSA
| | - Michael Helmrath
- Department of Surgery, Division of Pediatric Surgery, Cincinnati Children's Hospital Medical CenterUniversity of Cincinnati College of MedicineCincinnatiOhioUSA
| | - Conrad R. Cole
- Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical CenterUniversity of Cincinnati School of MedicineCincinnatiOhioUSA
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Canbolat AA, Lombardo M, Mondragon ADC, López JMM, Bechelany M, Karav S. Bovine Colostrum in Pediatric Nutrition and Health. Nutrients 2024; 16:4305. [PMID: 39770926 PMCID: PMC11677144 DOI: 10.3390/nu16244305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2024] [Revised: 12/04/2024] [Accepted: 12/10/2024] [Indexed: 01/11/2025] Open
Abstract
Bovine colostrum (BC), the first milk secreted by mammals after birth, is a trending alternative source for supplementing infants and children, offering benefits for gut and immune health. Its rich components, such as proteins, immunoglobulins, lactoferrin, and glycans, are used to fortify diets and support development. Preterm development is crucial, especially in the maturation of essential systems, and from 2010 to 2020, approximately 15% of all premature births occurred at less than 32 weeks of gestation worldwide. This review explores the composition, benefits, and effects of BC on general infants and children, along with preterm infants who require special care, and highlights its role in growth and development. BC is also associated with specific pediatric diseases, including necrotizing enterocolitis (NEC), infectious diarrhea, inflammatory bowel disease (IBD), short-bowel syndrome (SBS), neonatal sepsis, gastrointestinal and respiratory infections, and some minor conditions. This review also discusses the clinical trials regarding these specific conditions which are occasionally encountered in preterm infants. The anti-inflammatory, antimicrobial, immunomodulatory, and antiviral properties of BC are discussed, emphasizing its mechanisms of action. Clinical trials, particularly in humans, provide evidence supporting the inclusion of BC in formulas and diets, although precise standards for age, feeding time, and amounts are needed to ensure safety and efficacy. However, potential adverse effects, such as allergic reactions to caseins and immunoglobulin E, must be considered. More comprehensive clinical trials are necessary to expand the evidence on BC in infant feeding, and glycans, important components of BC, should be further studied for their synergistic effects on pediatric diseases. Ultimately, BC shows promise for pediatric health and should be incorporated into nutritional supplements with caution.
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Affiliation(s)
- Ahmet Alperen Canbolat
- Department of Molecular Biology and Genetics, Çanakkale Onsekiz Mart University, Çanakkale 17000, Türkiye;
| | - Mauro Lombardo
- Department for the Promotion of Human Science and Quality of Life, San Raffaele Open University, Via di 11 Val Cannuta 247, 00166 Rome, Italy;
| | - Alicia del Carmen Mondragon
- Laboratorio de Higiene Inspección y Control de Alimentos, Departamento de Química Analítica, Nutrición Bromatología, Universidade de Santiago de Compostela, Campus Terra, 27002 Lugo, Spain; (A.d.C.M.); (J.M.M.L.)
| | - Jose Manuel Miranda López
- Laboratorio de Higiene Inspección y Control de Alimentos, Departamento de Química Analítica, Nutrición Bromatología, Universidade de Santiago de Compostela, Campus Terra, 27002 Lugo, Spain; (A.d.C.M.); (J.M.M.L.)
| | - Mikhael Bechelany
- Institut Européen des Membranes (IEM), UMR 5635, University Montpellier, ENSCM, CNRS, F-34095 Montpellier, France;
- Functional Materials Group, Gulf University for Science and Technology (GUST), Masjid Al Aqsa Street, Mubarak Al-Abdullah 32093, Kuwait
| | - Sercan Karav
- Department of Molecular Biology and Genetics, Çanakkale Onsekiz Mart University, Çanakkale 17000, Türkiye;
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Vara-Luiz F, Glória L, Mendes I, Carlos S, Guerra P, Nunes G, Oliveira CS, Ferreira A, Santos AP, Fonseca J. Chronic Intestinal Failure and Short Bowel Syndrome in Adults: The State of the Art. GE PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2024; 31:388-400. [PMID: 39633906 PMCID: PMC11614447 DOI: 10.1159/000538938] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Accepted: 04/13/2024] [Indexed: 12/07/2024]
Abstract
Background Short bowel syndrome (SBS) is a devastating malabsorptive condition and the most common cause of chronic intestinal failure (CIF). During the intestinal rehabilitation process, patients may need parenteral support for months or years, parenteral nutrition (PN), or hydration/electrolyte supplementation, as a bridge for the desired enteral autonomy. Summary Several classification criteria have been highlighted to reflect different perspectives in CIF. The management of CIF-SBS in adults is a multidisciplinary process that aims to reduce gastrointestinal secretions, slow transit, correct/prevent malnutrition, dehydration, and specific nutrient deficiencies, and prevent refeeding syndrome. The nutritional support team should have the expertise to take care of these complex patients: fluid support; oral, enteral, and PN; disease/PN-related complications; pharmacologic treatment; and surgical prevention/treatment. Key Messages CIF-SBS is a complex disease with undesired consequences, if not adequately identified and managed. A comprehensive approach performed by a multidisciplinary team is essential to reduce PN dependence, promote enteral independence, and improve quality of life.
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Affiliation(s)
- Francisco Vara-Luiz
- GENE – Artificial Feeding Team, Gastroenterology Department, Hospital Garcia de Orta, Almada, Portugal
- Aging Lab, Egas Moniz Center for Interdisciplinary Research (CiiEM), Egas Moniz School of Health and Science, Almada, Portugal
| | - Luísa Glória
- Gastroenterology Department, Hospital Beatriz Ângelo, Loures, Portugal
| | - Ivo Mendes
- GENE – Artificial Feeding Team, Gastroenterology Department, Hospital Garcia de Orta, Almada, Portugal
| | - Sandra Carlos
- Surgery Department, Hospital Garcia de Orta, Almada, Portugal
| | - Paula Guerra
- Pediatrics Department, Centro Hospitalar Universitário de São João, Porto, Portugal
| | - Gonçalo Nunes
- GENE – Artificial Feeding Team, Gastroenterology Department, Hospital Garcia de Orta, Almada, Portugal
- Aging Lab, Egas Moniz Center for Interdisciplinary Research (CiiEM), Egas Moniz School of Health and Science, Almada, Portugal
| | - Cátia Sofia Oliveira
- GENE – Artificial Feeding Team, Gastroenterology Department, Hospital Garcia de Orta, Almada, Portugal
| | - Andreia Ferreira
- Nutrition Department, Hospital Lusíadas Lisboa, Lisboa, Portugal
| | | | - Jorge Fonseca
- GENE – Artificial Feeding Team, Gastroenterology Department, Hospital Garcia de Orta, Almada, Portugal
- Aging Lab, Egas Moniz Center for Interdisciplinary Research (CiiEM), Egas Moniz School of Health and Science, Almada, Portugal
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Jones D, Allsopp K, Sowerbutts AM, Lal S, Farrer K, Harrison S, Burden S. Outcomes for Patients Receiving Multi-Chamber Bags for the Delivery of Parenteral Nutrition: A Systematic Review. Nutrients 2024; 16:3964. [PMID: 39599751 PMCID: PMC11597339 DOI: 10.3390/nu16223964] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Revised: 11/12/2024] [Accepted: 11/14/2024] [Indexed: 11/29/2024] Open
Abstract
BACKGROUND Parenteral nutrition (PN) is required by people with intestinal failure and can be delivered as multi-chambered bags (MCBs) or individually compounded (COM) bags. This systematic review aimed to examine the evidence base for clinical outcomes and/or quality of life (QoL) in adults receiving PN as MCBs compared to COMs in hospital and community settings. METHODS A systematic database search was conducted between January 2015 and May 2024. Studies assessing adults in receipt of MCBs were included. Quality was assessed using Joanna Briggs appraisal tools. A narrative synthesis was performed due to study heterogeneity. PROSPERO CRD42022352806. RESULTS Ten studies including 87,727 adults were included, with 20,192 receiving PN from MCBs and 67,535 from COMs. Eight studies reported on PN given in hospital and two in the home. Five hospital-based and one home-based study reported that MCBs were well tolerated and provided adequate nutrition. Three hospital-based studies reported that MCBs had lower post-operative infections and a lower mean risk of catheter-related bloodstream infections (CRBSIs). Two home-based studies reported no difference in CRBSI. Five hospital-based studies reported no difference between groups in length of hospital stay. Three hospital-based studies reported the cost to be lower for MCBs than COMs, and no studies reported QoL. CONCLUSIONS The studies included show that MCBs provided in hospital are safe and non-inferior to COMs and may be more cost-effective. There were few high-quality studies and no data on QoL; therefore, further work is required to improve the certainty of the evidence and to establish the level of QoL when using MCBs.
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Affiliation(s)
- Debra Jones
- School of Health Sciences, University of Manchester, Oxford Road, Manchester M13 9PL, UK; (K.A.); (A.M.S.); (S.B.)
| | - Karen Allsopp
- School of Health Sciences, University of Manchester, Oxford Road, Manchester M13 9PL, UK; (K.A.); (A.M.S.); (S.B.)
- Salford Care Organisation, Northern Care Alliance NHS Trust, Stott Lane, Salford M6 8HD, UK; (S.L.); (K.F.); (S.H.)
| | - Anne Marie Sowerbutts
- School of Health Sciences, University of Manchester, Oxford Road, Manchester M13 9PL, UK; (K.A.); (A.M.S.); (S.B.)
| | - Simon Lal
- Salford Care Organisation, Northern Care Alliance NHS Trust, Stott Lane, Salford M6 8HD, UK; (S.L.); (K.F.); (S.H.)
| | - Kirstine Farrer
- Salford Care Organisation, Northern Care Alliance NHS Trust, Stott Lane, Salford M6 8HD, UK; (S.L.); (K.F.); (S.H.)
| | - Simon Harrison
- Salford Care Organisation, Northern Care Alliance NHS Trust, Stott Lane, Salford M6 8HD, UK; (S.L.); (K.F.); (S.H.)
| | - Sorrel Burden
- School of Health Sciences, University of Manchester, Oxford Road, Manchester M13 9PL, UK; (K.A.); (A.M.S.); (S.B.)
- Salford Care Organisation, Northern Care Alliance NHS Trust, Stott Lane, Salford M6 8HD, UK; (S.L.); (K.F.); (S.H.)
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10
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Rumbo C, Solar H, Ortega M, Busoni V, de Barrio S, Martinuzzi A, Martínez MI, Plata C, Donnadio L, Aurora SZ, Saure C, Perez C, Tanzi MN, Consuelo A, Becerra A, Manzur A, Moya DA, Rudi L, Moreira E, Buncuga M, Hodgson MI, Clariá RS, Fernandez A, Gondolesi G. Short bowel syndrome related intestinal failure outcomes in Latin America: Insights from the RESTORE Registry. JPEN J Parenter Enteral Nutr 2024; 48:956-964. [PMID: 39367870 DOI: 10.1002/jpen.2693] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Revised: 09/16/2024] [Accepted: 09/17/2024] [Indexed: 10/07/2024]
Abstract
BACKGROUND Short bowel syndrome is considered a low prevalence disease. The scant information available about intestinal failure in Latin America was the driving force to expand this registry. METHODS A prospective, multicenter observational registry was created for patients with chronic intestinal failure short bowel at specialized centers in Latin America. Demographics, clinical characteristics, nutrition assessment, parenteral nutrition management, intestinal rehabilitation, related complications, clinical outcome, and survival were analyzed. RESULTS From May 2020 to July 2023, 167 patients (115 adults, 52 children) from 20 centers were enrolled. For the adults, the mean age was 37.2 ± 18 years, 48% were female, and the mean follow-up was 22.6 ± 18.3 months. The main etiology was surgical resections (postsurgical complications: 37%; ischemia: 25%); the mean intestinal length was 73 ± 55 cm. The complications were as follows: infections: 0.4/1000 catheter-days; thrombosis: 0.24/1000 catheter-days; liver disease: 2.6%. The outcomes were as follows: 28% were rehabilitated, 15% died, 9.6% were lost to follow-up, 0.9% underwent transplant, and 45.6% continued follow-up. For the children, the mean age 48 ± 52 months, 48% were female, 52% were premature. The mean follow-up was 17.2 ± 5.6 months; the mean remaining intestinal length was 38 ± 45 cm. The leading etiologies were atresia (25%), NEC (23%), and gastroschisis (21%). The complication were as follows: infections: 2/1000 catheter-days; thrombosis: 2.22/1000 catheter-day; 25% developed liver disease. The outcomes were as follows: 7.7% died, 3.8% were rehabilitated, and 88.5% continued follow-up. CONCLUSION The RESTORE amendment served as a registry and educational tool for the participating teams. The aspiration is to objectively show current aspects of intestinal failure in the region and carry them to international standards. Including all Latin American countries and etiologies of chronic intestinal failure besides short gut would serve to complete this registry.
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Affiliation(s)
- Carolina Rumbo
- Hospital Universitario Fundación Favaloro, Buenos Aires, Argentina
| | - Hector Solar
- Hospital Universitario Fundación Favaloro, Buenos Aires, Argentina
| | - Mariana Ortega
- Hospital Universitario Fundación Favaloro, Buenos Aires, Argentina
| | | | | | | | | | - Clara Plata
- Hospital Universitario San Ignacio, Bogotá, Colombia
| | | | - Serralde-Zuñiga Aurora
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Carola Saure
- Hospital Prof. Dr Juan P. Garrahan, Buenos Aires, Argentina
| | - Claudia Perez
- Hospital Nacional Profesor Alejandro Posadas, El Palomar, Argentina
| | | | | | - Andrés Becerra
- Hospital Universitario de San Vicente Fundación, Medellin, Colombia
| | | | | | - Lorena Rudi
- Hospital Nacional Profesor Alejandro Posadas, El Palomar, Argentina
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11
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Korn LL, Kutyavin VI, Bachtel ND, Medzhitov R. Adverse Food Reactions: Physiological and Ecological Perspectives. Annu Rev Nutr 2024; 44:155-178. [PMID: 38724028 DOI: 10.1146/annurev-nutr-061021-022909] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/15/2024]
Abstract
While food is essential for survival, it can also cause a variety of harmful effects, ranging from intolerance to specific nutrients to celiac disease and food allergies. In addition to nutrients, foods contain myriads of substances that can have either beneficial or detrimental effects on the animals consuming them. Consequently, all animals evolved defense mechanisms that protect them from harmful food components. These "antitoxin" defenses have some parallels with antimicrobial defenses and operate at a cost to the animal's fitness. These costs outweigh benefits when defense responses are exaggerated or mistargeted, resulting in adverse reactions to foods. Additionally, pathological effects of foods can stem from insufficient defenses, due to unabated toxicity of harmful food components. We discuss the structure of antitoxin defenses and how their failures can lead to a variety of adverse food reactions.
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Affiliation(s)
- Lisa L Korn
- Department of Medicine, Section of Rheumatology, Allergy, and Clinical Immunology, Yale University School of Medicine, New Haven, Connecticut, USA
- Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA;
| | - Vassily I Kutyavin
- Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA;
| | - Nathaniel D Bachtel
- Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA;
| | - Ruslan Medzhitov
- Tananbaum Center for Theoretical and Analytical Human Biology, Yale University School of Medicine, New Haven, Connecticut, USA
- Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut, USA
- Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA;
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12
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Hirsch TI, Fligor SC, Tsikis ST, Mitchell PD, DeVietro A, Carbeau S, Wang SZ, McClelland J, Carey AN, Gura KM, Puder M. Administration of 4% tetrasodium EDTA lock solution and central venous catheter complications in high-risk pediatric patients with intestinal failure: A retrospective cohort study. JPEN J Parenter Enteral Nutr 2024; 48:624-632. [PMID: 38837803 PMCID: PMC11216891 DOI: 10.1002/jpen.2644] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Revised: 05/06/2024] [Accepted: 05/07/2024] [Indexed: 06/07/2024]
Abstract
BACKGROUND Selection of central venous catheter (CVC) lock solution impacts catheter mechanical complications and central line-associated bloodstream infections (CLABSIs) in pediatric patients with intestinal failure. Disadvantages of the current clinical standards, heparin and ethanol lock therapy (ELT), led to the discovery of new lock solutions. High-risk pediatric patients with intestinal failure who lost access to ELT during a recent shortage were offered enrollment in a compassionate use trial with 4% tetrasodium EDTA (T-EDTA), a lock solution with antimicrobial, antibiofilm, and antithrombotic properties. METHODS We performed a descriptive cohort study including 14 high-risk pediatric patients with intestinal failure receiving 4% T-EDTA as a daily catheter lock solution. CVC complications were documented (repairs, occlusions, replacements, and CLABSIs). Complication rates on 4% T-EDTA were compared with baseline rates, during which patients were receiving either heparin or ELT (designated as heparin/ELT). RESULTS Patients initiated 4% T-EDTA at the time they were enrolled in the compassionate use protocol. Use of 4% T-EDTA resulted in a 50% reduction in CVC complications, compared with baseline rates on heparin/ELT (incidence rate ratio: 0.50; 95% CI, 0.25-1.004; P = 0.051). CONCLUSION In a compassionate use protocol for high-risk pediatric patients with intestinal failure, the use of 4% T-EDTA reduced composite catheter complications, including those leading to emergency department visits, hospital admissions, additional procedures, and mortality. This outcome suggests 4% T-EDTA has benefits over currently available lock solutions.
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Affiliation(s)
- Thomas I Hirsch
- Vascular Biology Program, Department of Surgery, Boston Children’s Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Scott C Fligor
- Vascular Biology Program, Department of Surgery, Boston Children’s Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Savas T Tsikis
- Vascular Biology Program, Department of Surgery, Boston Children’s Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Paul D Mitchell
- Biostatistics and Research Design Center, Boston Children’s Hospital, Boston, MA, USA
| | - Angela DeVietro
- Vascular Biology Program, Department of Surgery, Boston Children’s Hospital, Boston, MA, USA
| | - Sarah Carbeau
- Vascular Biology Program, Department of Surgery, Boston Children’s Hospital, Boston, MA, USA
| | - Sarah Z Wang
- Vascular Biology Program, Department of Surgery, Boston Children’s Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Jennifer McClelland
- Division of Gastroenterology, Hepatology, and Nutrition, Boston Children’s Hospital, Boston, MA, USA
| | - Alexandra N Carey
- Harvard Medical School, Boston, MA, USA
- Division of Gastroenterology, Hepatology, and Nutrition, Boston Children’s Hospital, Boston, MA, USA
| | - Kathleen M Gura
- Harvard Medical School, Boston, MA, USA
- Division of Gastroenterology, Hepatology, and Nutrition, Boston Children’s Hospital, Boston, MA, USA
- Department of Pharmacy, Boston Children’s Hospital, Boston, MA, USA
| | - Mark Puder
- Vascular Biology Program, Department of Surgery, Boston Children’s Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
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13
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Micic D, Robinson I, Kidd T, Terreri B, Raphael BP. Teduglutide improves liver chemistries in short bowel syndrome-associated intestinal failure: Post hoc analysis. Nutr Clin Pract 2024; 39:634-640. [PMID: 38491966 DOI: 10.1002/ncp.11139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Revised: 02/01/2024] [Accepted: 02/02/2024] [Indexed: 03/18/2024] Open
Abstract
BACKGROUND Chronic hepatic complications are common in patients with short bowel syndrome-associated intestinal failure (SBS-IF). Teduglutide, a glucagon-like peptide-2 analogue, demonstrated efficacy in reducing parenteral nutrition and/or intravenous fluid dependence among patients with SBS-IF in phase 3 clinical studies. METHODS This was a post hoc analysis of pooled data from two separate randomized, double-blind, placebo-controlled, multinational phase 3 clinical studies. Adult patients with SBS-IF with parenteral nutrition and/or intravenous fluid dependence without liver disease at baseline were randomized to treatment with the glucagon-like peptide-2 analogue teduglutide (0.05 or 0.10 mg/kg/day) or placebo subcutaneously once daily for 24 weeks. Mixed-effects models assessed the baseline predictors of change in liver chemistries. RESULTS Between baseline and week 24, teduglutide treatment (n = 109) was associated with least squares mean reductions in aspartate aminotransferase (-7.51 IU/L; P = 0.014), alanine aminotransferase (-12.15 IU/L; P = 0.002), and bilirubin (-5.03 µmol/L [-0.057 mg/dl]; P < 0.001) compared with that of the placebo (n = 59). These values were independent of reductions in parenteral nutrition and/or intravenous fluid dependence. CONCLUSION Teduglutide treatment was associated with reductions in liver chemistries by week 24, which is beneficial for patients with SBS-IF beyond improvements in parenteral nutrition and/or intravenous fluid dependence. Future studies should examine how long-term teduglutide might mitigate the risk of liver disease in patients with SBS-IF.
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Affiliation(s)
- Dejan Micic
- Department of Internal Medicine, Section of Gastroenterology, Hepatology and Nutrition, University of Chicago Medicine, Chicago, Illinois, USA
| | - Ian Robinson
- Takeda Pharmaceuticals, USA, Inc, Lexington, Massachusetts, USA
| | - Tanya Kidd
- Takeda Pharmaceuticals, USA, Inc, Lexington, Massachusetts, USA
| | - Brian Terreri
- Takeda Pharmaceuticals, USA, Inc, Lexington, Massachusetts, USA
| | - Bram P Raphael
- Takeda Pharmaceuticals, USA, Inc, Lexington, Massachusetts, USA
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14
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Hou L, Wang H, Yan M, Cai Y, Zheng R, Ma Y, Tang W, Jiang W. Obeticholic acid attenuates the intestinal barrier disruption in a rat model of short bowel syndrome. Biochim Biophys Acta Mol Basis Dis 2024; 1870:167221. [PMID: 38718845 DOI: 10.1016/j.bbadis.2024.167221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Revised: 05/02/2024] [Accepted: 05/03/2024] [Indexed: 05/12/2024]
Abstract
BACKGROUND Short bowel syndrome (SBS) features nutrients malabsorption and impaired intestinal barrier. Patients with SBS are prone to sepsis, intestinal flora dysbiosis and intestinal failure associated liver disease. Protecting intestinal barrier and preventing complications are potential strategies for SBS treatment. This study aims to investigate the effects of farnesoid X receptor (FXR) agonist, obeticholic acid (OCA), have on intestinal barrier and ecological environment in SBS. METHODS AND RESULTS Through testing the small intestine and serum samples of patients with SBS, impaired intestinal barrier was verified, as evidenced by reduced expressions of intestinal tight junction proteins (TJPs), increased levels of apoptosis and epithelial cell damage. The intestinal expressions of FXR and related downstream molecules were decreased in SBS patients. Then, global FXR activator OCA was used to further dissect the potential role of the FXR in a rat model of SBS. Low expressions of FXR-related molecules were observed on the small intestine of SBS rats, along with increased proinflammatory factors and damaged barrier function. Furthermore, SBS rats possessed significantly decreased body weight and elevated death rate. Supplementation with OCA mitigated the damaged intestinal barrier and increased proinflammatory factors in SBS rats, accompanied by activated FXR-related molecules. Using 16S rDNA sequencing, the regulatory role of OCA on gut microbiota in SBS rats was witnessed. LPS stimulation to Caco-2 cells induced apoptosis and overexpression of proinflammatory factors in vitro. OCA incubation of LPS-pretreated Caco-2 cells activated FXR-related molecules, increased the expressions of TJPs, ameliorated apoptosis and inhibited overexpression of proinflammatory factors. CONCLUSIONS OCA supplementation could effectively ameliorate the intestinal barrier disruption and inhibit overexpression of proinflammatory factors in a rat model of SBS and LPS-pretreated Caco-2 cells. As a selective activator of FXR, OCA might realize its protective function through FXR activation.
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Affiliation(s)
- Li Hou
- Department of Pediatric Surgery, Children's Hospital of Nanjing Medical University, Nanjing, China; Department of Surgical Oncology, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Hanfei Wang
- Department of Pediatric Surgery, Children's Hospital of Nanjing Medical University, Nanjing, China
| | - Meng Yan
- Department of Pediatrics, Huai'an Maternal and Child Health Care Center, Huai'an, China
| | - Yaoyao Cai
- Department of Pediatric Surgery, Children's Hospital of Nanjing Medical University, Nanjing, China
| | - Ruifei Zheng
- Department of Pediatric Surgery, Children's Hospital of Nanjing Medical University, Nanjing, China
| | - Yujun Ma
- Department of Pediatric Surgery, Children's Hospital of Nanjing Medical University, Nanjing, China
| | - Weibing Tang
- Department of Pediatric Surgery, Children's Hospital of Nanjing Medical University, Nanjing, China.
| | - Weiwei Jiang
- Department of Pediatric Surgery, Children's Hospital of Nanjing Medical University, Nanjing, China.
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15
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Greig G, Youssef NN, Bolognani F. Pharmacokinetics and Tolerability of a Single Dose of Apraglutide, a Novel, Long-Acting, Synthetic glucagon-like peptide-2 Analog With a Unique Pharmacologic Profile, in Individuals With Impaired Renal Function. J Clin Pharmacol 2024; 64:744-754. [PMID: 38465515 DOI: 10.1002/jcph.2423] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Accepted: 01/18/2024] [Indexed: 03/12/2024]
Abstract
Renal impairment is a common complication in patients with short bowel syndrome with intestinal failure (SBS-IF). Glucagon-like peptide-2 analogs, such as apraglutide, have been developed as a treatment option for SBS-IF. This study assessed the potential for apraglutide overexposure in individuals with severely impaired renal function versus healthy volunteers with normal renal function. In this phase 1, open-label, multicenter, nonrandomized, parallel-group study, a single dose of apraglutide 5 mg was administered subcutaneously to individuals with severely impaired renal function (<30 mL/min/1.73 m2) and healthy volunteers with normal renal function (≥90 mL/min/1.73 m2). Primary pharmacokinetic endpoints were maximum observed concentration (Cmax) and exposure to apraglutide (area under the curve [AUC] from time 0 to infinity [AUCinf], and AUC from time 0 to the last quantifiable concentration [AUClast]). Each group comprised 8 individuals. Results show that patients with severe renal impairment do not have increased apraglutide exposure. Apraglutide achieved a lower Cmax and AUCinf in individuals with severe renal impairment versus those with normal renal function (Cmax = 36.9 vs 59.5 ng/L; AUCinf = 3100 vs 4470 h · ng/mL, respectively). The respective geometric mean ratios were 0.620 and 0.693 for Cmax and AUCinf, and the upper bound of their 90% confidence intervals were <2, indicating patients with severe renal impairment were not overexposed to apraglutide versus those with normal renal function. Adverse events were mild or moderate in severity. Apraglutide does not require dose reduction for any degree of renal impairment and could be used in a broader patient population of renally impaired patients without dose adjustment.
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16
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Kania A, Branchi V, Braun L, Verrel F, Kalff JC, Vilz TO. [Indications and surgical strategy for bowel resection in mesenteric ischemia : Resection margins considering current guidelines and literature as well as the influence of new technical possibilities]. CHIRURGIE (HEIDELBERG, GERMANY) 2024; 95:367-374. [PMID: 38378936 DOI: 10.1007/s00104-024-02041-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 01/16/2024] [Indexed: 02/22/2024]
Abstract
Acute mesenteric ischemia (AMI) is still a time-critical and life-threatening clinical picture. If exploration of the abdominal cavity is necessary during treatment, an intraoperative assessment of which segments of the intestines have a sufficient potential for recovery must be made. These decisions are mostly based on purely clinical parameters, which are subject to high level of uncertainty. This review article provides an overview of how this decision-making process and the determination of resection margins can be improved using technical aids, such as laser Doppler flowmetry (LDF), indocyanine green (ICG) fluorescence angiography or hyperspectral imaging (HSI). Furthermore, this article compiles guideline recommendations on the role of laparoscopy and the value of a planned second-look laparotomy. In addition, an overview of strategies for preventing short bowel syndrome is given and other aspects, such as the timing and technical aspects of placement of a preternatural anus and an anastomosis are highlighted.
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Affiliation(s)
- Alexander Kania
- Klinik und Poliklinik für Allgemein‑, Viszeral‑, Thorax- und Gefäßchirurgie, Universitätsklinikum Bonn, Venusberg Campus 1, 53127, Bonn, Deutschland.
| | - Vittorio Branchi
- Klinik und Poliklinik für Allgemein‑, Viszeral‑, Thorax- und Gefäßchirurgie, Universitätsklinikum Bonn, Venusberg Campus 1, 53127, Bonn, Deutschland
| | - Lara Braun
- Klinik und Poliklinik für Allgemein‑, Viszeral‑, Thorax- und Gefäßchirurgie, Universitätsklinikum Bonn, Venusberg Campus 1, 53127, Bonn, Deutschland
| | - Frauke Verrel
- Klinik und Poliklinik für Allgemein‑, Viszeral‑, Thorax- und Gefäßchirurgie, Universitätsklinikum Bonn, Venusberg Campus 1, 53127, Bonn, Deutschland
| | - Jörg C Kalff
- Klinik und Poliklinik für Allgemein‑, Viszeral‑, Thorax- und Gefäßchirurgie, Universitätsklinikum Bonn, Venusberg Campus 1, 53127, Bonn, Deutschland
| | - Tim O Vilz
- Klinik und Poliklinik für Allgemein‑, Viszeral‑, Thorax- und Gefäßchirurgie, Universitätsklinikum Bonn, Venusberg Campus 1, 53127, Bonn, Deutschland
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17
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Gombošová L, Suchanský M, Krivuš J, Hornová J, Havlíčeková Z, Fojtová A, Norek B, Valachová I, Šprláková J, Gazda J, Ondrušová M. Evaluation of the Effectiveness of Teduglutide Treatment in Patients with Short Bowel Syndrome in Slovakia-Multicenter Real-World Study. J Clin Med 2024; 13:1238. [PMID: 38592065 PMCID: PMC10931580 DOI: 10.3390/jcm13051238] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2024] [Revised: 02/16/2024] [Accepted: 02/20/2024] [Indexed: 04/10/2024] Open
Abstract
(1) Background: We present the first real-world-data study on teduglutide-treated SBS patients in the Slovak Republic and the first study to enable the comparison of the effects of teduglutide treatment between the adult and pediatric populations. (2) Methods: This was a non-interventional retrospective cohort study of adult and pediatric SBS patients treated with teduglutide. Primary and secondary endpoints were the results of teduglutide use at 12 weeks and 6 months after the initiation of treatment, compared to baseline. (3) Results: Teduglutide treatment led to a statistically significant reduction in the volume of intravenous hydration, HPN caloric intake, HPN and intravenous hydration applications per week and to increased urine output in adult patients. The results in the pediatric population were similar, but not statistically significant. A complete weaning off HPN was achieved in 57.14% of all patients (50.00% of children; 62.50% of adults) after a median of 0.99 years of teduglutide treatment (1.07 and 0.98 years for children and adults, respectively). (4) Conclusions: Teduglutide treatment in SBS patients leads to considerable reduction in or even weaning off PN in both pediatric and adult patients.
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Affiliation(s)
- Laura Gombošová
- 2nd Internal Clinic, University Hospital of L. Pasteur and Faculty of Medicine University of Pavol Jozef Šafárik Košice, Tr. SNP 1, 04011 Košice, Slovakia;
| | | | - Juraj Krivuš
- 1st Internal Clinic, University Hospital and Jessenius Faculty of Medicine Comenius University, Kollárova 2, 03659 Martin, Slovakia;
| | - Jarmila Hornová
- Department of Pediatrics, Faculty of Medicine Comenius University and National Institute of Children’s Diseases, Limbová 1, 83340 Bratislava, Slovakia;
| | - Zuzana Havlíčeková
- Department of Paediatrics, University Hospital Martin and Jessenius Faculty of Medicine Comenius University, Kollárova 2, 03601 Martin, Slovakia;
| | - Andrea Fojtová
- Gastroenterology Clinic, Slovak Medical University and Bratislava University Hospital, Antolská 11, 85107 Bratislava, Slovakia; (A.F.); (B.N.)
| | - Barbora Norek
- Gastroenterology Clinic, Slovak Medical University and Bratislava University Hospital, Antolská 11, 85107 Bratislava, Slovakia; (A.F.); (B.N.)
| | - Iveta Valachová
- 2nd Children Clinic, Slovak Medical University and Children's Faculty Hospital, Nám L. Svobodu 4, 97409 Banská Bystrica, Slovakia;
| | - Jana Šprláková
- Gastroenterology and Hepatology Department, Children’s Faculty Hospital, Tr. SNP 1, 04011 Košice, Slovakia;
| | - Jakub Gazda
- 2nd Internal Clinic, University Hospital of L. Pasteur and Faculty of Medicine University of Pavol Jozef Šafárik Košice, Tr. SNP 1, 04011 Košice, Slovakia;
| | - Martina Ondrušová
- PharmIn Ltd., Karadžičova 16, 82108 Bratislava, Slovakia;
- Faculty of Public Health, Slovak Medical University, 83303 Bratislava, Slovakia
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18
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Dowhan L, Moccia L, Fujiki M. Nutrition care for the adult post-intestinal transplant patient. Nutr Clin Pract 2024; 39:60-74. [PMID: 38069605 DOI: 10.1002/ncp.11100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Revised: 11/04/2023] [Accepted: 11/06/2023] [Indexed: 01/13/2024] Open
Abstract
Intestinal transplantation has emerged as an accepted treatment choice for individuals experiencing irreversible intestinal failure. This treatment is particularly relevant for those who are not candidates or have poor response to autologous gut reconstruction or trophic hormone therapy, and who can no longer be sustained on parenteral nutrition. One of the main goals of transplant is to eliminate the need for parenteral support and its associated complications, while safely restoring complete nutrition autonomy. An intestinal transplant is a complex process that goes beyond merely replacing the intestines to provide nourishment and ceasing parenteral support. It requires an integrated management approach in the pretransplant and posttransplant setting, and high-quality nutrition treatment is one of the cornerstones leading to favorable outcomes and long-term management. Since the outset of intestinal transplant in the early 2000s, there is observed improvement of achieving nutrition autonomy sooner in the initial posttransplant phase; however, the development of nutrition complications in the chronic posttransplant period remains a long-term risk. This review delineates the decision-making process and clinical protocols used to nutritionally manage and monitor pre- and post-intestine transplant patients.
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Affiliation(s)
- Lindsay Dowhan
- Center for Gut Rehabilitation and Transplantation, Cleveland Clinic, Cleveland, Ohio, USA
| | - Lisa Moccia
- Center for Gut Rehabilitation and Transplantation, Cleveland Clinic, Cleveland, Ohio, USA
| | - Masato Fujiki
- Center for Gut Rehabilitation and Transplantation, Cleveland Clinic, Cleveland, Ohio, USA
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19
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Sznurkowska K, Borkowska A, Zagierska A, Malanowska M, Zieliński M, Zagierski M, Trzonkowski P, Łosin M, Szlagatys-Sidorkiewicz A. Does Massive Bowel Resection in Newborns Affect Further Immunity in Children? CHILDREN (BASEL, SWITZERLAND) 2024; 11:114. [PMID: 38255427 PMCID: PMC10814972 DOI: 10.3390/children11010114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Revised: 12/19/2023] [Accepted: 01/05/2024] [Indexed: 01/24/2024]
Abstract
BACKGROUND The massive resection of the small intestine leading to short bowel syndrome (SBS) deprives an organism of many immunocompetent cells concentrated in gut-associated lymphoid tissue, the largest immune organ in humans. We have aimed to access the influence of bowel resection on adaptive immunity in children, based on peripheral lymphocyte subsets and serum immunoglobulins. METHODS 15 children who underwent bowel resection in the first months of their life and required further home parenteral nutrition were enrolled into the study. Based on flow cytometry, the following subsets of lymphocytes were evaluated: T, B, NK, CD4+, C8+, and activated T cells. RESULTS Statistically significant differences were found for the rates of lymphocytes B, T, CD8+, and NK cells. The absolute count of NK cells was lower in the SBS group than in the control group. Absolute counts of lymphocytes, lymphocytes B, T, CD4+, and percentages of lymphocytes CD4+, and activated T cells inversely correlated with age in SBS group. CONCLUSIONS Children with SBS do not present with clinical signs of immunodeficiency as well as deficits in peripheral lymphocyte subsets and serum immunoglobulins. The tendency of the lymphocyte subpopulations to decrease over time points out the necessity for longer follow- up.
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Affiliation(s)
- Katarzyna Sznurkowska
- Department of Paediatrics, Pediatric Gastroenterology, Allergology and Nutrition, Medical University of Gdańsk, Nowe Ogrody 1-6, 80-803 Gdańsk, Poland; (A.B.); (A.Z.); (M.Z.); (A.S.-S.)
| | - Anna Borkowska
- Department of Paediatrics, Pediatric Gastroenterology, Allergology and Nutrition, Medical University of Gdańsk, Nowe Ogrody 1-6, 80-803 Gdańsk, Poland; (A.B.); (A.Z.); (M.Z.); (A.S.-S.)
| | - Agnieszka Zagierska
- Department of Paediatrics, Pediatric Gastroenterology, Allergology and Nutrition, Medical University of Gdańsk, Nowe Ogrody 1-6, 80-803 Gdańsk, Poland; (A.B.); (A.Z.); (M.Z.); (A.S.-S.)
| | - Magdalena Malanowska
- Department of Paediatrics, Hematology and Oncology, Medical University of Gdańsk, Dębinki 7, 80-211 Gdańsk, Poland;
| | - Maciej Zieliński
- Department of Medical Immunology, Medical University of Gdańsk, Dębinki 7, 80-211 Gdańsk, Poland; (M.Z.); (P.T.)
| | - Maciej Zagierski
- Department of Paediatrics, Pediatric Gastroenterology, Allergology and Nutrition, Medical University of Gdańsk, Nowe Ogrody 1-6, 80-803 Gdańsk, Poland; (A.B.); (A.Z.); (M.Z.); (A.S.-S.)
| | - Piotr Trzonkowski
- Department of Medical Immunology, Medical University of Gdańsk, Dębinki 7, 80-211 Gdańsk, Poland; (M.Z.); (P.T.)
| | - Marcin Łosin
- Department of Surgery and Urology for Children and Adolescents, Medical University of Gdansk, Dębinki 7, 80-211 Gdańsk, Poland;
| | - Agnieszka Szlagatys-Sidorkiewicz
- Department of Paediatrics, Pediatric Gastroenterology, Allergology and Nutrition, Medical University of Gdańsk, Nowe Ogrody 1-6, 80-803 Gdańsk, Poland; (A.B.); (A.Z.); (M.Z.); (A.S.-S.)
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20
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Utrilla Fornals A, Costas-Batlle C, Medlin S, Menjón-Lajusticia E, Cisneros-González J, Saura-Carmona P, Montoro-Huguet MA. Metabolic and Nutritional Issues after Lower Digestive Tract Surgery: The Important Role of the Dietitian in a Multidisciplinary Setting. Nutrients 2024; 16:246. [PMID: 38257141 PMCID: PMC10820062 DOI: 10.3390/nu16020246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Revised: 12/31/2023] [Accepted: 01/08/2024] [Indexed: 01/24/2024] Open
Abstract
Many patients undergo small bowel and colon surgery for reasons related to malignancy, inflammatory bowel disease (IBD), mesenteric ischemia, and other benign conditions, including post-operative adhesions, hernias, trauma, volvulus, or diverticula. Some patients arrive in the operating theatre severely malnourished due to an underlying disease, while others develop complications (e.g., anastomotic leaks, abscesses, or strictures) that induce a systemic inflammatory response that can increase their energy and protein requirements. Finally, anatomical and functional changes resulting from surgery can affect either nutritional status due to malabsorption or nutritional support (NS) pathways. The dietitian providing NS to these patients needs to understand the pathophysiology underlying these sequelae and collaborate with other professionals, including surgeons, internists, nurses, and pharmacists. The aim of this review is to provide an overview of the nutritional and metabolic consequences of different types of lower gastrointestinal surgery and the role of the dietitian in providing comprehensive patient care. This article reviews the effects of small bowel resection on macronutrient and micronutrient absorption, the effects of colectomies (e.g., ileocolectomy, low anterior resection, abdominoperineal resection, and proctocolectomy) that require special dietary considerations, nutritional considerations specific to ostomized patients, and clinical practice guidelines for caregivers of patients who have undergone a surgery for local and systemic complications of IBD. Finally, we highlight the valuable contribution of the dietitian in the challenging management of short bowel syndrome and intestinal failure.
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Affiliation(s)
| | - Cristian Costas-Batlle
- Department of Nutrition and Dietetics, Bradford Teaching Hospitals NHS Foundation Trust, Bradford BD9 6RJ, UK;
| | | | - Elisa Menjón-Lajusticia
- Gastroenterology, Hepatology and Nutrition Unit, University Hospital San Jorge, 22004 Huesca, Spain;
| | - Julia Cisneros-González
- Faculty of Health and Sport Sciences, University of Zaragoza, 22002 Huesca, Spain; (J.C.-G.); (P.S.-C.)
| | - Patricia Saura-Carmona
- Faculty of Health and Sport Sciences, University of Zaragoza, 22002 Huesca, Spain; (J.C.-G.); (P.S.-C.)
| | - Miguel A. Montoro-Huguet
- Gastroenterology, Hepatology and Nutrition Unit, University Hospital San Jorge, 22004 Huesca, Spain;
- Faculty of Health and Sport Sciences, University of Zaragoza, 22002 Huesca, Spain; (J.C.-G.); (P.S.-C.)
- Department of Medicine, Faculty of Health and Sport Sciences, University of Zaragoza, 22002 Huesca, Spain
- Aragon Health Research Institute (IIS Aragon), University of Zaragoza, 22002 Huesca, Spain
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21
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Endo R, Sugimoto S, Shirosaki K, Kato H, Wada M, Kanai T, Sato T. Clinical challenges of short bowel syndrome and the path forward for organoid-based regenerative medicine. Regen Ther 2023; 24:64-73. [PMID: 37868721 PMCID: PMC10584670 DOI: 10.1016/j.reth.2023.06.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Revised: 05/25/2023] [Accepted: 06/01/2023] [Indexed: 10/24/2023] Open
Abstract
Short bowel syndrome (SBS) is a rare condition, the main symptom of which is malabsorption following extensive resection of the small intestine. Treatment for SBS is mainly supportive, consisting of supplementation, prevention and treatment of complications, and promotion of intestinal adaptation. While development of parenteral nutrition and drugs promoting intestinal adaptation has improved clinical outcomes, the prognosis of patients with SBS remains poor. Intestinal transplantation is the only curative therapy but its outcome is unsatisfactory. In the absence of definitive therapy, novel treatment is urgently needed. With the advent of intestinal organoids, research on the intestine has developed remarkably in recent years. Concepts such as the "tissue-engineered small intestine" and "small intestinalized colon," which create a functional small intestine by combining organoids with other technologies, are potentially novel regenerative therapeutic approaches for SBS. Although they are still under development and there are substantial issues to be resolved, the problems that have prevented establishment of the complex function and structure of the small intestine are gradually being overcome. This review discusses the current treatments for SBS, the fundamentals of the intestine and organoids, the current status of these new technologies, and future perspectives.
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Affiliation(s)
- Ryoma Endo
- Department of Organoid Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
- Department of Pediatric Surgery, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan
| | - Shinya Sugimoto
- Department of Organoid Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Koji Shirosaki
- Department of Organoid Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
- Department of Pediatric Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Hirochika Kato
- Department of Organoid Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
- Department of Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Motoshi Wada
- Department of Pediatric Surgery, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan
| | - Takanori Kanai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Toshiro Sato
- Department of Organoid Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
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22
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Salazar JA, Goldsmith JD, Jimenez L, Fox VL, Duggan CP, Carey AN. Gastric Foveolar Hyperplastic Polyps in 2 Children With Short Bowel Syndrome on Long-Term Teduglutide. JPGN REPORTS 2023; 4:e389. [PMID: 38034466 PMCID: PMC10684249 DOI: 10.1097/pg9.0000000000000389] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Accepted: 08/23/2023] [Indexed: 12/02/2023]
Abstract
The natural history of short bowel syndrome involves intestinal adaptation wherein the remnant small intestine undergoes histologic and anatomic changes aimed at increasing absorption. Teduglutide-a glucagon-like peptide 2 analog approved for pediatric use in 2019-stimulates this process by causing proliferation of intestinal epithelial cells resulting in increased villous height and crypt depth. Food and Drug Administration approval for pediatric patients followed safety and efficacy studies in children that were limited to 24-week duration. Pediatric-specific postmarketing studies evaluating long-term safety and efficacy are underway. Formation of colorectal polyps has been repeatedly observed in studies of adult patients on long-term teduglutide, including in individuals without endoscopic evidence of polyps before treatment initiation. Recent studies, however, suggest increased risk of small bowel hyperplastic and dysplastic polyp formation with long-term glucagon-like peptide 2 analog use. We report 2 cases of small bowel foveolar hyperplastic polyps found during surveillance endoscopies after 1 year of treatment with teduglutide.
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Affiliation(s)
- Jonathan A. Salazar
- From the Division of Gastroenterology, Hepatology and Nutrition, Boston Children’s Hospital, Harvard Medical School, Boston, MA
| | - Jeffrey D. Goldsmith
- Department of Pathology, Boston Children’s Hospital, Harvard Medical School, Boston, MA
| | - Lissette Jimenez
- From the Division of Gastroenterology, Hepatology and Nutrition, Boston Children’s Hospital, Harvard Medical School, Boston, MA
| | - Victor L. Fox
- From the Division of Gastroenterology, Hepatology and Nutrition, Boston Children’s Hospital, Harvard Medical School, Boston, MA
| | - Christopher P. Duggan
- From the Division of Gastroenterology, Hepatology and Nutrition, Boston Children’s Hospital, Harvard Medical School, Boston, MA
| | - Alexandra N. Carey
- From the Division of Gastroenterology, Hepatology and Nutrition, Boston Children’s Hospital, Harvard Medical School, Boston, MA
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23
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Tsikis ST, Fligor SC, Hirsch TI, Mitchell PD, Pan A, Moskowitzova K, Whitlock AE, Loring G, First E, Nedder A, Gura KM, Puder M. A Digestive Cartridge Reduces Parenteral Nutrition Dependence and Increases Bowel Growth in a Piglet Short Bowel Model. Ann Surg 2023; 278:e876-e884. [PMID: 36924229 PMCID: PMC10481911 DOI: 10.1097/sla.0000000000005839] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/18/2023]
Abstract
OBJECTIVE To determine whether the use of an immobilized lipase cartridge (ILC) to hydrolyze fats in enteral nutrition (EN) reduces parenteral nutrition (PN) dependence in a porcine model of short bowel syndrome with intestinal failure (SBS-IF). BACKGROUND SBS-IF occurs after intestinal loss resulting in malabsorption and PN dependence. Limited therapeutic options are available for achieving enteral autonomy. METHODS Eleven Yorkshire piglets underwent 75% jejunoileal resection and were randomized into control (n=6) and treatment (n = 5) groups. PN was initiated postoperatively and reduced as EN advanced if predefined clinical criteria were fulfilled. Animals were studied for 14 days and changes in PN/EN calories were assessed. Intestinal adaptation, absorption, and nutrition were evaluated at the end of the study (day 15). Comparisons between groups were performed using analysis of covariance adjusted for baseline. RESULTS ILC animals demonstrated a 19% greater reduction in PN calories ( P < 0.0001) and higher mean EN advancement (66% vs 47% of total calories, P < 0.0001) during the 14-day experiment. Treatment animals had increased intestinal length (19.5 vs 0.7%, P =0.03) and 1.9-fold higher crypt cell proliferation ( P =0.02) compared with controls. By day 15, ILC treatment resulted in higher plasma concentrations of glucagon-like peptide-2 ( P = 0.02), eicosapentaenoic acid ( P < 0.0001), docosahexaenoic acid ( P = 0.004), vitamin A ( P = 0.02), low-density lipoprotein ( P = 0.02), and high-density lipoprotein ( P = 0.04). There were no differences in liver enzymes or total bilirubin between the two groups. CONCLUSIONS ILC use in conjunction with enteral feeding reduced PN dependence, improved nutrient absorption, and increased bowel growth in a porcine SBS-IF model. These results support a potential role for the ILC in clinical SBS-IF.
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Affiliation(s)
- Savas T. Tsikis
- Vascular Biology Program, Boston Children’s Hospital, Harvard Medical School, Boston, MA
- Department of Surgery, Boston Children’s Hospital, Harvard Medical School, Boston, MA
| | - Scott C. Fligor
- Vascular Biology Program, Boston Children’s Hospital, Harvard Medical School, Boston, MA
- Department of Surgery, Boston Children’s Hospital, Harvard Medical School, Boston, MA
| | - Thomas I. Hirsch
- Vascular Biology Program, Boston Children’s Hospital, Harvard Medical School, Boston, MA
- Department of Surgery, Boston Children’s Hospital, Harvard Medical School, Boston, MA
| | - Paul D. Mitchell
- Institutional Centers for Clinical and Translational Research, Boston Children’s Hospital, Boston, MA
| | - Amy Pan
- Vascular Biology Program, Boston Children’s Hospital, Harvard Medical School, Boston, MA
- Department of Surgery, Boston Children’s Hospital, Harvard Medical School, Boston, MA
| | - Kamila Moskowitzova
- Department of Surgery, Boston Children’s Hospital, Harvard Medical School, Boston, MA
| | - Ashlyn E. Whitlock
- Department of Surgery, Boston Children’s Hospital, Harvard Medical School, Boston, MA
| | | | | | - Arthur Nedder
- Animal Care Resources Children’s Hospital, Boston Children’s Hospital, Boston, MA
| | - Kathleen M. Gura
- Department of Pharmacy and the Division of Gastroenterology and Nutrition, Boston Children’s Hospital, Harvard Medical School, Boston, MA
| | - Mark Puder
- Vascular Biology Program, Boston Children’s Hospital, Harvard Medical School, Boston, MA
- Department of Surgery, Boston Children’s Hospital, Harvard Medical School, Boston, MA
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24
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Moran-Lev H, Kocoshis SA, Oliveira SB, Helmrath M, Cole CR. Chronic Mucosal Inflammation in Pediatric Intestinal Failure Patients-A Unique Phenomenon. J Pediatr Gastroenterol Nutr 2023; 77:e29-e35. [PMID: 37098159 DOI: 10.1097/mpg.0000000000003811] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/27/2023]
Abstract
INTRODUCTION/OBJECTIVES As intestinal failure (IF) management improves and long-term survival rate increases, its physiological complications have become more apparent. The development of chronic intestinal inflammation resembling inflammatory bowel disease (IBD) in this population has been reported, but the literature describing it in detail is sparse. The present study was designed to characterize children with IF who developed chronic intestinal inflammation and identify the potential predisposing clinical factors. METHODS This retrospective study was based on the electronic medical records of pediatric patients seen at the Cincinnati Children's Hospital Medical Center between January 2000 and July 2022. Demographic and medical history data were collected and compared between children with IF that developed chronic intestinal inflammation and children with IF that did not develop chronic intestinal inflammation. RESULTS During the follow-up period, 23 children were diagnosed with chronic intestinal inflammation. Of these, 12 (52%) were males, with a median age of 4.5 (3-7) years at diagnosis. Nearly one-third of the patients had gastroschisis (31%), followed by necrotizing enterocolitis (26%), and malrotation and volvulus (21.7%). More children in the chronic intestinal inflammation group lacked an ileocecal valve (ICV) and adjoining distal ileum as compared to the short bowel syndrome (SBS)-IF control group (15 patients, 65% vs 8 patients, 33%). Moreover, more children in the chronic intestinal inflammation group had undergone a prior lengthening procedure than the SBS-IF control group (5 patients, 21.7% vs. 0, respectively). DISCUSSION SBS patients are at risk of relatively early onset chronic intestinal inflammation. The absence of an ICV (and adjoin ileum) and prior lengthening procedures emerge as factors associated with the risk of IBD in these patients.
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Affiliation(s)
- Hadar Moran-Lev
- From the Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati School of Medicine, Cincinnati, OH
- the Division of Gastroenterology, Hepatology and Nutrition, Dana Dwek Children's Hospital, affiliated to Tel Aviv University, Tel Aviv, Israel
| | - Samuel A Kocoshis
- From the Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati School of Medicine, Cincinnati, OH
| | - Stephanie B Oliveira
- From the Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati School of Medicine, Cincinnati, OH
| | - Michael Helmrath
- the Division of Pediatric Surgery, Department of Surgery, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH
| | - Conrad R Cole
- From the Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati School of Medicine, Cincinnati, OH
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25
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Maklad M, Mazariegos G, Ganoza A. Pediatric intestine and multivisceral transplant. Curr Opin Organ Transplant 2023; 28:316-325. [PMID: 37418582 DOI: 10.1097/mot.0000000000001082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/09/2023]
Abstract
PURPOSE OF REVIEW Intestinal and multivisceral transplantation (ITx, MVTx) is the cornerstone in treatment of irreversible intestinal failure (IF) and complications related to parenteral nutrition. This review aims to highlight the unique aspects of the subject in pediatrics. RECENT FINDINGS Etiology of intestinal failure (IF) in children shares some similarity with adults but several unique considerations when being evaluated for transplantation will be discussed. Owing to significant advancement in IF management and home parenteral nutrition (PN), indication criteria for pediatric transplantation continues to be updated. Outcomes have continued to improve with current long-term patient and graft survival in multicenter registry reports reported at 66.1% and 48.8% at 5 years, respectively. Pediatric specific surgical challenges such abdominal closure, post transplantation outcomes, and quality of life are discussed in this review. SUMMARY ITx and MVTx remain lifesaving treatment for many children with IF. However long-term graft function is still a major challenge.
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Affiliation(s)
- Mohamed Maklad
- Hillman Center for Pediatric Transplantation, Thomas E. Starzl Transplantation Institute, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
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26
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Alizadeh AA, Rasouli S, Jamshidi Kandjani O, Hemmati S, Dastmalchi S. Expression, Purification and Characterization of Functional Teduglutide Using GST Fusion System in Prokaryotic Cells. Adv Pharm Bull 2023; 13:592-600. [PMID: 37646058 PMCID: PMC10460804 DOI: 10.34172/apb.2023.064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2022] [Revised: 11/15/2022] [Accepted: 12/04/2022] [Indexed: 09/01/2023] Open
Abstract
Purpose Teduglutide is the first and only FDA-approved drug for long-term treatment of short bowel syndrome (SBS). The current study aimed to present an approach for production of teduglutide using recombinant DNA technology. Methods The coding gene for teduglutide was cloned into pGEX-2T vector, where coding sequence for factor Xa cleavage site was added between GST and teduglutide coding genes. The GST-teduglutide protein was overexpressed in E. coli BL21 (DE3) strain and affinity purified using glutathione sepharose affinity column. Results On-column proteolytic activity of factor Xa followed by size exclusion chromatography resulted in the pure teduglutide. Circular dichroism (CD) spectropolarimetry showed that the produced teduglutide folds into mainly α-helical structure (>50%), as expected. In mass spectroscopy analysis, the fragments of teduglutide resulted by cyanogen bromide cleavage as well as those expected theoretically due to mass fragmentation were identified. The functionality of the produced peptide was evaluated by measuring its proliferative effect on Caco2 intestinal epithelial cells, and the results indicated that produced teduglutide induces cell proliferation by 19±0.30 and 33±7.82 % at 1.21 and 3.64 µM concentrations, respectively, compared to untreated cells. Conclusion Teduglutide was successfully expressed and purified and its functionality and structural integrity were confirmed by in vitro experiments. We believe that the experimental-scale method presented in the current study can be useful for pilot-scale and also industrial-scale production of teduglutide.
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Affiliation(s)
- Ali Akbar Alizadeh
- Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Saba Rasouli
- Pharmaceutical Analysis Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Salar Hemmati
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Siavoush Dastmalchi
- Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
- Faculty of Pharmacy, Near East University, Po.Box: 99138, Nicosia, North Cyprus, Mersin 10, Turkey
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27
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Douda L, Hyšpler R, Mžik M, Vokurková D, Drahošová M, Řeháček V, Čermáková E, Douda T, Cyrany J, Fejfar T, Jirkovský V, Kopáčová M, Kupková B, Vašátko T, Tachecí I, Bureš J. Serum Citrulline and Ornithine: Potential Markers of Coeliac Disease Activity. ACTA MEDICA (HRADEC KRALOVE) 2023; 65:75-82. [PMID: 36735884 DOI: 10.14712/18059694.2022.22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
INTRODUCTION To date, there is not generally accepted and universal indicator of activity, and functional integrity of the small intestine in patients with coeliac disease. The aim of our study was to investigate whether serum concentrations of the non-essential amino acids citrulline and ornithine might have this function. METHODS We examined serum citrulline and ornithine concentrations in a subgroup of patients with proven coeliac disease and healthy controls (blood donors). RESULTS A total of 94 patients with coeliac disease (29 men, mean age 53 ± 18 years; 65 women, mean age 44 ± 14 years) and 35 healthy controls (blood donors) in whom coeliac disease was serologically excluded (10 men, mean age 51 ± 14 years; 25 women, mean age 46 ± 12 years) were included in the study. Significantly lower concentrations of serum ornithine were found in patients with coeliac disease (mean 65 ± 3 μmol/L; median 63 μmol/L, IQR 34 μmol/L, p < 0.001). No statistically nor clinically significant differences were found in the citrulline concentrations between the study and control group. CONCLUSIONS Serum ornithine (but not citrulline) may be useful for assessing the functional status of the small intestine in uncomplicated coeliac disease. Further studies involving more detailed analysis of dietary and metabolic changes in patients will be needed to reach definitive conclusions.
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Affiliation(s)
- Ladislav Douda
- 2nd Department of Internal Medicine - Gastroenterology, Charles University, Faculty of Medicine in Hradec Králové and University Hospital Hradec Králové, Czech Republic
| | - Radomír Hyšpler
- Institute of Clinical Biochemistry and Diagnostics, Charles University, Faculty of Medicine in Hradec Králové and University Hospital Hradec Králové, Czech Republic
| | - Martin Mžik
- Institute of Clinical Biochemistry and Diagnostics, Charles University, Faculty of Medicine in Hradec Králové and University Hospital Hradec Králové, Czech Republic
| | - Doris Vokurková
- Department of Clinical Immunology and Allergology, Charles University, Faculty of Medicine in Hradec Králové and University Hospital Hradec Králové, Czech Republic
| | - Marcela Drahošová
- Department of Clinical Immunology and Allergology, Charles University, Faculty of Medicine in Hradec Králové and University Hospital Hradec Králové, Czech Republic
| | - Vít Řeháček
- Transfusion Department, University Hospital Hradec Králové, Czech Republic
| | - Eva Čermáková
- Department of Medical Biophysic, Charles University, Faculty of Medicine in Hradec Králové, Czech Republic
| | - Tomáš Douda
- 2nd Department of Internal Medicine - Gastroenterology, Charles University, Faculty of Medicine in Hradec Králové and University Hospital Hradec Králové, Czech Republic
| | - Jiří Cyrany
- 2nd Department of Internal Medicine - Gastroenterology, Charles University, Faculty of Medicine in Hradec Králové and University Hospital Hradec Králové, Czech Republic
| | - Tomáš Fejfar
- 2nd Department of Internal Medicine - Gastroenterology, Charles University, Faculty of Medicine in Hradec Králové and University Hospital Hradec Králové, Czech Republic
| | - Václav Jirkovský
- 2nd Department of Internal Medicine - Gastroenterology, Charles University, Faculty of Medicine in Hradec Králové and University Hospital Hradec Králové, Czech Republic
| | - Marcela Kopáčová
- 2nd Department of Internal Medicine - Gastroenterology, Charles University, Faculty of Medicine in Hradec Králové and University Hospital Hradec Králové, Czech Republic
| | - Blanka Kupková
- 2nd Department of Internal Medicine - Gastroenterology, Charles University, Faculty of Medicine in Hradec Králové and University Hospital Hradec Králové, Czech Republic
| | - Tomáš Vašátko
- 2nd Department of Internal Medicine - Gastroenterology, Charles University, Faculty of Medicine in Hradec Králové and University Hospital Hradec Králové, Czech Republic
| | - Ilja Tachecí
- 2nd Department of Internal Medicine - Gastroenterology, Charles University, Faculty of Medicine in Hradec Králové and University Hospital Hradec Králové, Czech Republic.
| | - Jan Bureš
- Biomedical Research Centre, University Hospital Hradec Králové, Hradec Králové, Czech Republic
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Choi J, Lee J, Park E, Kwon H, Kim D, Bae S, Choi IY, Kim HH. HM15912, a Novel Long-Acting Glucagon-Like Peptide-2 Analog, Improves Intestinal Growth and Absorption Capacity in a Male Rat Model of Short Bowel Syndrome. J Pharmacol Exp Ther 2023; 384:277-286. [PMID: 36410792 DOI: 10.1124/jpet.122.001381] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 11/07/2022] [Accepted: 11/10/2022] [Indexed: 11/22/2022] Open
Abstract
Extensive bowel resection caused by various diseases that affect the intestines, such as Crohn's disease, volvulus, and cancer, leads to short bowel syndrome (SBS). Teduglutide is the only approved glucagon-like peptide-2 (GLP-2) drug for SBS; however, it requires daily administration. A novel GLP-2 analog with a prolonged duration of action to reduce dosing frequency and promote a greater efficacy may provide patients with a better quality of life. In the present study, the sustained exposure of HM15912 was characterized in normal male rats. The efficacy of HM15912 on intestinal growth and absorption capacity was also evaluated in normal male mice, rats, and SBS rats. HM15912 exhibited a remarkably extended half-life (42.3 hours) compared with teduglutide (0.6 hours) in rats. Despite somewhat lower in vitro potency on GLP-2 receptor than human GLP-2 or teduglutide, this longer-lasting mode of action promotes HM15912 to be more effective in terms of small intestinal growth than existing GLP-2 analogs even with a less frequent dosing interval of as little as once a week in rodents, including SBS rats. Furthermore, the small intestinal weight was approximately doubled, and the D-xylose absorption was significantly increased after pre-treatment of existing GLP-2 analogs on the market or under clinical development followed by HM15912 in rodents. These results indicate that HM15912 possesses a significant small bowel trophic effect driven by continuously increased exposure, supporting that HM15912 may be a novel treatment option with greater efficacy and the longest dosing interval among existing GLP-2 analogs for SBS with intestinal failure. SIGNIFICANCE STATEMENT: HM15912, a novel long-acting glucagon-like peptide-2 (GLP-2) analog, has a significant small bowel hypertrophic effect in rodents with a reduced frequency of administration compared to the existing GLP-2 analogs on the market or currently under clinical development. This study supports the possibility that HM15912 could be administered much less frequently than other long-acting GLP-2 analogs for patients with short bowel syndrome.
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Affiliation(s)
- Jaehyuk Choi
- Hanmi Research Center, Hanmi Pharm. Co. Ltd., Gyeonggi-do, Republic of Korea (J.C., J.L., E.P., H.K., D.K., S.B., IY.C.); Biotherapeutics and Glycomics Laboratory, College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea (J.C., HH.K.); and Department of Global Innovative Drugs, Graduate School of Chung-Ang University, Seoul, Republic of Korea (HH.K.)
| | - Jinbong Lee
- Hanmi Research Center, Hanmi Pharm. Co. Ltd., Gyeonggi-do, Republic of Korea (J.C., J.L., E.P., H.K., D.K., S.B., IY.C.); Biotherapeutics and Glycomics Laboratory, College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea (J.C., HH.K.); and Department of Global Innovative Drugs, Graduate School of Chung-Ang University, Seoul, Republic of Korea (HH.K.)
| | - Eunjin Park
- Hanmi Research Center, Hanmi Pharm. Co. Ltd., Gyeonggi-do, Republic of Korea (J.C., J.L., E.P., H.K., D.K., S.B., IY.C.); Biotherapeutics and Glycomics Laboratory, College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea (J.C., HH.K.); and Department of Global Innovative Drugs, Graduate School of Chung-Ang University, Seoul, Republic of Korea (HH.K.)
| | - Hyunjoo Kwon
- Hanmi Research Center, Hanmi Pharm. Co. Ltd., Gyeonggi-do, Republic of Korea (J.C., J.L., E.P., H.K., D.K., S.B., IY.C.); Biotherapeutics and Glycomics Laboratory, College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea (J.C., HH.K.); and Department of Global Innovative Drugs, Graduate School of Chung-Ang University, Seoul, Republic of Korea (HH.K.)
| | - Daejin Kim
- Hanmi Research Center, Hanmi Pharm. Co. Ltd., Gyeonggi-do, Republic of Korea (J.C., J.L., E.P., H.K., D.K., S.B., IY.C.); Biotherapeutics and Glycomics Laboratory, College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea (J.C., HH.K.); and Department of Global Innovative Drugs, Graduate School of Chung-Ang University, Seoul, Republic of Korea (HH.K.)
| | - Sungmin Bae
- Hanmi Research Center, Hanmi Pharm. Co. Ltd., Gyeonggi-do, Republic of Korea (J.C., J.L., E.P., H.K., D.K., S.B., IY.C.); Biotherapeutics and Glycomics Laboratory, College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea (J.C., HH.K.); and Department of Global Innovative Drugs, Graduate School of Chung-Ang University, Seoul, Republic of Korea (HH.K.)
| | - In Young Choi
- Hanmi Research Center, Hanmi Pharm. Co. Ltd., Gyeonggi-do, Republic of Korea (J.C., J.L., E.P., H.K., D.K., S.B., IY.C.); Biotherapeutics and Glycomics Laboratory, College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea (J.C., HH.K.); and Department of Global Innovative Drugs, Graduate School of Chung-Ang University, Seoul, Republic of Korea (HH.K.)
| | - Ha Hyung Kim
- Hanmi Research Center, Hanmi Pharm. Co. Ltd., Gyeonggi-do, Republic of Korea (J.C., J.L., E.P., H.K., D.K., S.B., IY.C.); Biotherapeutics and Glycomics Laboratory, College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea (J.C., HH.K.); and Department of Global Innovative Drugs, Graduate School of Chung-Ang University, Seoul, Republic of Korea (HH.K.)
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Oh TY, Hofmekler T, Freeman AJ. Update in Pediatric Gastroenterology and Nutrition. UPDATE IN PEDIATRICS 2023:369-398. [DOI: 10.1007/978-3-031-41542-5_15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Abstract
Short bowel syndrome (SBS) is a chronic disease whose natural history requires a changing array of management strategies over time. Chief amongst these is the chronic use of parenteral nutrition (PN) to ensure adequate nutritional intake. With time and appropriate management, approximately half of all SBS patients will successfully regain a functional, baseline level of intrinsic bowel function that will allow for them to achieve PN independence. However, the other half of SBS patients will progress into chronic intestinal failure which warrants a change in therapy to include more aggressive medical and potentially surgical measures. This review examines the evolving treatment strategies involved in the management of SBS as well as intestinal failure.
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Zhou Z, Li K, Shi L, Wang Y, He Y, Hu W, Guo J. Self-Assembled Integrative Nutrient Carrier Platform Containing Green Tea Catechin for Short Bowel Syndrome Treatment. Adv Healthc Mater 2023; 12:e2201933. [PMID: 36337003 DOI: 10.1002/adhm.202201933] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Revised: 09/28/2022] [Indexed: 11/09/2022]
Abstract
Extensive resection of the small intestine leads to the development of short bowel syndrome (SBS), which reduces the effective absorptive surface area of the intestine and predisposes patients to emaciation, malnutrition, and other severe symptoms. Herein, green tea catechin (-)-epigallocatechin gallate (EGCG) and ferrous ions (Fe2+ ) are utilized to construct a nutrient carrier platform that self-assembles with nutrients to form phenolic-based nutrient complexes (PNCs). PNCs effectively prolong the residence and absorption time of nutrients in the intestine. Further this platform is applied to integrate full nutrient formula, an enteral nutrition (EN) preparation containing a range of full nutrient components. In an SBS rat model, the prepared phenolic-based integrative nutrient complexes (PINCs) enhance nutritional status, improve anemia and immune function, as well as facilitate the growth of remaining intestinal villi and crypts, and maintain the integrity of the intestinal barrier. In addition, PINCs enable the modulation of gut microbial dysbiosis, enrich the abundance of beneficial bacteria, and have no toxic effects after the long-term ingestion. These results provide a proof of principle for the use of polyphenol-based nanocomplexes as EN preparation, offering a feasible strategy for both nutritional support and therapeutic perspectives for SBS treatment.
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Affiliation(s)
- Zhengming Zhou
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Ke Li
- Department of Clinical Nutrition, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Lei Shi
- Department of Clinical Nutrition, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Yunfeng Wang
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Yunxiang He
- BMI Center for Biomass Materials and Nanointerfaces, College of Biomass Science and Engineering, Sichuan University, Chengdu, Sichuan, 610065, China
| | - Wen Hu
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.,Department of Clinical Nutrition, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Junling Guo
- BMI Center for Biomass Materials and Nanointerfaces, College of Biomass Science and Engineering, Sichuan University, Chengdu, Sichuan, 610065, China.,Bioproducts Institute, Department of Chemical and Biological Engineering, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada.,State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu, Sichuan, 610065, China
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32
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Sueyoshi R, Furuhashi N, Ishii J, Yamaguchi R, Kawakami M, Tanabe K, Segawa O. Decreased liver damage in rat models of short bowel syndrome through DPP4 inhibition. Pediatr Surg Int 2022; 39:21. [PMID: 36449115 DOI: 10.1007/s00383-022-05301-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/14/2022] [Indexed: 12/05/2022]
Abstract
PURPOSE Total parenteral nutrition causes liver damage in patients with short bowel syndrome (SBS), in whom intestinal failure-associated liver disease (IFALD) is the strongest risk factor for mortality. We previously demonstrated the efficacy of dipeptidyl peptidase-4 inhibitors (DPP4-Is) for nutritional absorption and intestinal barrier function enhancement. Herein, we investigated the efficacy of DPP4-Is in preventing liver damage in SBS rat models. METHODS Rats were allocated to one of five groups: normal saline (NS) + sham, DPP4-I + sham, NS + SBS, DPP4-I + SBS, and GLP-2 + SBS. DPP4-I or NS was administered orally once daily. Serum aspartate aminotransferase, alanine aminotransferase (ALT), alkaline phosphatase, and total bile acid levels were measured to assess liver function. Moreover, we evaluated liver damage using the SAF (steatosis activity fibrosis) score, which is also used to assess nonalcoholic steatohepatitis. RESULTS ALT levels and SAF scores were significantly lower in the DPP4-I + SBS group than in the NS + SBS group. Jejunal and ileal villus heights were significantly higher in the DPP4-I + SBS group than in the GLP-2 + SBS group. CONCLUSIONS The downregulation of ALT levels and SAF scores triggered by DPP4-I use may be correlated with DPP4-I-induced adiposis inhibition in SBS and NASH models. Therefore, DPP4-I may be used to reduce IFALD in patients with SBS.
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Affiliation(s)
- Ryo Sueyoshi
- Department of Pediatric Surgery, Tokyo Women's Medical University, 8-1 Kawada-Cho, Shinjuku-Ku, Tokyo, 162-8666, Japan.
| | - Nanami Furuhashi
- Department of Pediatric Surgery, Tokyo Women's Medical University, 8-1 Kawada-Cho, Shinjuku-Ku, Tokyo, 162-8666, Japan
| | - Junya Ishii
- Department of Pediatric Surgery, Tokyo Women's Medical University, 8-1 Kawada-Cho, Shinjuku-Ku, Tokyo, 162-8666, Japan
| | - Ryusuke Yamaguchi
- Department of Pediatric Surgery, Tokyo Women's Medical University, 8-1 Kawada-Cho, Shinjuku-Ku, Tokyo, 162-8666, Japan
| | - Marumi Kawakami
- Institute for Comprehensive Medical Sciences, Tokyo Women's Medical University, Tokyo, Japan
| | - Kenji Tanabe
- Institute for Comprehensive Medical Sciences, Tokyo Women's Medical University, Tokyo, Japan
| | - Osamu Segawa
- Department of Pediatric Surgery, Tokyo Women's Medical University, 8-1 Kawada-Cho, Shinjuku-Ku, Tokyo, 162-8666, Japan
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Lakkasani S, Seth D, Khokhar I, Touza M, Dacosta TJ. Concise review on short bowel syndrome: Etiology, pathophysiology, and management. World J Clin Cases 2022; 10:11273-11282. [PMID: 36387822 PMCID: PMC9649563 DOI: 10.12998/wjcc.v10.i31.11273] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Revised: 08/12/2022] [Accepted: 09/20/2022] [Indexed: 02/05/2023] Open
Abstract
Adults have approximately 20 feet of small intestine, which is the primary site for absorbing essential nutrients and water. Resection of the intestine for any medical reason may result in short bowel syndrome (SBS), leading to loss of major absorptive surface area and resulting in various malabsorption and motility disorders. The mainstay of treatment is personalized close dietary management. Here we present SBS with its pathophysiology and different nutritional management options available. The central perspective of this paper is to provide a concise review of SBS and the treatment options available, along with how proper nutrition can solve major dietary issues in SBS and help patients recover faster.
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Affiliation(s)
- Saraswathi Lakkasani
- Gastroenterology and Hepatology, Saint Michael’s Medical Center in Affiliation with New York Medical College, Newark, NJ 07102, United States
| | - Deeksha Seth
- Gastroenterology, Chandan Institute of Liver and Biliary Sciences, Lucknow 226001, India
| | - Imran Khokhar
- Medicine, Suburban Medical Center, Norristown, PA 19401, United States
| | - Masara Touza
- Medicine, Saint Michael’s Medical Center in Affiliation with New York Medical College, Newark, NJ 07102, United States
| | - Theodore Jr Dacosta
- Gastroenterology and Hepatology, Saint Michael’s Medical Center in Affiliation with New York Medical College, Newark, NJ 07102, United States
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Belcher E, Mercer D, Raphael BP, Salinas GD, Stacy S, Tappenden KA. Management of short-bowel syndrome: A survey of unmet educational needs among healthcare providers. JPEN J Parenter Enteral Nutr 2022; 46:1839-1846. [PMID: 35511707 PMCID: PMC9790246 DOI: 10.1002/jpen.2388] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Revised: 04/12/2022] [Accepted: 04/23/2022] [Indexed: 12/30/2022]
Abstract
BACKGROUND Management of short-bowel syndrome with intestinal failure (SBS-IF) is complex and requires a multidisciplinary approach. Because of the rarity of SBS-IF, healthcare professionals (HCPs) often lack clinical experience with the disease and may benefit from education regarding SBS-IF and its management. This study identified unmet educational needs related to the management of patients with SBS-IF. METHODS This was a prospective, web-based survey (December 2019-January 2020) in which a series of clinical questions were posed to US HCPs after presenting three standardized SBS-IF cases to assess current practice patterns. HCPs were then asked a series of questions to identify potential knowledge gaps and unmet educational needs relating to SBS-IF management. RESULTS Overall, 558 HCPs completed the survey, with 12%-38% having a formal SBS-IF multidisciplinary team currently available to make treatment decisions within their institution. Clinicians involved in care included gastroenterologists (93%), registered dietitians (79%), gastroenterology nurse practitioners and physician assistants (37%), registered nurses (43%), social workers (45%), and psychologists/psychiatrists (27%). There was underuse of published guidelines and limited understanding of the course of intestinal adaptation. Responses to the clinical scenarios highlighted disparities in SBS-IF care delivery, including diagnosis, management goals, medications prescribed, and nutrition practices. CONCLUSIONS Future SBS-IF educational interventions for HCPs should aim to improve awareness and understanding of the disease, facilitate timely diagnosis, and standardize management practices to ensure patients receive optimal interdisciplinary care as widely as possible.
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Affiliation(s)
| | - David Mercer
- Department of Surgery, Division of TransplantationUniversity of Nebraska Medical CenterOmahaNebraskaUSA
| | | | | | | | - Kelly A. Tappenden
- Department of Kinesiology and NutritionUniversity of Illinois ChicagoChicagoIllinoisUSA
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Tuveri M, Paiella S, Boschi F, Luchini C, Perri G, Gasparini C, Aresta A, Scarpa A, Salvia R, Bassi C. Evidence of glucose absorption in a neoformed intestine. Updates Surg 2022; 74:1705-1713. [PMID: 35050488 PMCID: PMC9481485 DOI: 10.1007/s13304-022-01241-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2021] [Accepted: 01/08/2022] [Indexed: 12/04/2022]
Abstract
Recent advances in the field of tissue regeneration are offering promising therapeutic options for the treatment of short bowel syndrome. This study aimed to evaluate the glucose absorptive capacity of a neoformed intestine obtained from a biological scaffold in a rodent model and the steadiness of the engrafted segment area. Twenty-four male Sprague-Dawley rats were used for this study. Under anesthesia, a patch of biological material (2.2 × 1.5 cm) was engrafted in the anti-mesenteric border of the small bowels of 12 rats. Twelve rats were sham-operated. Animals were studied at 4, 8, and 10 months postengraftment. Functional and histological analyses were performed. The functional analysis was performed using an 18F-FDG analog as a probe and the results were acquired with an optical imager. The intensity of the fluorescent signal emitted by the neointestine was comparable with that emitted by the native intestine in all animals and was visible after injection in the preserved mesentery. The mean intestinal volume at time of engraftment and after 10 months was 4.08 cm3 (95% CI [3.58-4.58]) and 3.26 cm3 (CI 95% [3.23-3.29]), respectively, with a mean shrinkage of 17.3% (range 10.6-23.8%), without any evidence of stenosis. Morphological analysis revealed the progression of the biological material toward a neoformed intestine similar to the native intestine, especially at 8 and 10 months. In a rodent model, we demonstrated that a neointestine, obtained from a biological scaffold showed glucose absorption and a durable increase in diameter.
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Affiliation(s)
- Massimiliano Tuveri
- General and Pancreatic Surgery Unit, Pancreas Institute, University of Verona, P.le L.A. Scuro n° 10, 37134 Verona, Italy
| | - Salvatore Paiella
- General and Pancreatic Surgery Unit, Pancreas Institute, University of Verona, P.le L.A. Scuro n° 10, 37134 Verona, Italy
| | - Federico Boschi
- Department of Computer Science, University of Verona, Verona, Italy
| | - Claudio Luchini
- Section of Pathology, Department of Diagnostics and Public Health, Pancreas Institute, University of Verona, Verona, Italy
| | - Giampaolo Perri
- General and Pancreatic Surgery Unit, Pancreas Institute, University of Verona, P.le L.A. Scuro n° 10, 37134 Verona, Italy
| | - Clizia Gasparini
- Radiology Unit, Pancreas Institute, University of Verona, Verona, Italy
| | - Alex Aresta
- Section of Pathology, Department of Diagnostics and Public Health, Pancreas Institute, University of Verona, Verona, Italy
| | - Aldo Scarpa
- Section of Pathology, Department of Diagnostics and Public Health, Pancreas Institute, University of Verona, Verona, Italy
- ARC-Net Research Center, University of Verona, Verona, Italy
| | - Roberto Salvia
- General and Pancreatic Surgery Unit, Pancreas Institute, University of Verona, P.le L.A. Scuro n° 10, 37134 Verona, Italy
| | - Claudio Bassi
- General and Pancreatic Surgery Unit, Pancreas Institute, University of Verona, P.le L.A. Scuro n° 10, 37134 Verona, Italy
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Iyer K, DiBaise JK, Rubio-Tapia A. AGA Clinical Practice Update on Management of Short Bowel Syndrome: Expert Review. Clin Gastroenterol Hepatol 2022; 20:2185-2194.e2. [PMID: 35700884 DOI: 10.1016/j.cgh.2022.05.032] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Revised: 04/22/2022] [Accepted: 05/24/2022] [Indexed: 02/07/2023]
Affiliation(s)
- Kishore Iyer
- Recanati Miller Transplant Institute, Department of Surgery, Mount Sinai Hospital, New York, New York.
| | - John K DiBaise
- Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Arizona.
| | - Alberto Rubio-Tapia
- Division of Gastroenterology, Hepatology, and Nutrition, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio
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Pulvirenti G, Sortino V, Manti S, Parisi GF, Papale M, Giallongo A, Leonardi S. Pathogenesis, diagnosis, dietary management, and prevention of gastrointestinal disorders in the paediatric population. Ital J Pediatr 2022; 48:172. [PMID: 36089576 PMCID: PMC9465927 DOI: 10.1186/s13052-022-01366-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Accepted: 09/04/2022] [Indexed: 11/13/2022] Open
Abstract
Nutrition has a central role in child growth with long-term effects, and nutrition management in gastrointestinal disorders has great importance for child health and disease outcomes. Breast milk is the first choice for infant nutrition. When it is not available, special milk formulas are adopted in specific conditions, as a medical treatment. Moving from the strong guidelines, recommendations and the new possibilities of special diet treatment, this review will analyse the current diet treatment in different gastrointestinal disorders, including food allergy, cystic fibrosis, inflammatory bowel diseases, short-bowel syndrome, gastroesophageal reflux, and eosinophilic esophagitis. The review also aimed at understanding the role of diet and its effects on these diseases. The growth monitoring can prevent malnutrition and improve disease outcomes, particularly in children, and an appropriate dietary management targeted to specific disorders is the best therapeutic choice alone or in combination with pharmacological therapy.
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Affiliation(s)
- Giulio Pulvirenti
- Pediatric Respiratory and Cystic Fibrosis Unit, Department of Clinical and Experimental Medicine, San Marco Hospital, University of Catania, Via Santa Sofia 78, 95123, Catania, Italy
| | - Vincenzo Sortino
- Pediatric Respiratory and Cystic Fibrosis Unit, Department of Clinical and Experimental Medicine, San Marco Hospital, University of Catania, Via Santa Sofia 78, 95123, Catania, Italy
| | - Sara Manti
- Pediatric Respiratory and Cystic Fibrosis Unit, Department of Clinical and Experimental Medicine, San Marco Hospital, University of Catania, Via Santa Sofia 78, 95123, Catania, Italy.
- Pediatric Unit, Department of Human and Pediatric Pathology "Gaetano Barresi", AOUP G. Martino, University of Messina, Via Consolare Valeria, 1, 98124, Messina, Italy.
| | - Giuseppe Fabio Parisi
- Pediatric Respiratory and Cystic Fibrosis Unit, Department of Clinical and Experimental Medicine, San Marco Hospital, University of Catania, Via Santa Sofia 78, 95123, Catania, Italy
| | - Maria Papale
- Pediatric Respiratory and Cystic Fibrosis Unit, Department of Clinical and Experimental Medicine, San Marco Hospital, University of Catania, Via Santa Sofia 78, 95123, Catania, Italy
| | - Alessandro Giallongo
- Pediatric Respiratory and Cystic Fibrosis Unit, Department of Clinical and Experimental Medicine, San Marco Hospital, University of Catania, Via Santa Sofia 78, 95123, Catania, Italy
| | - Salvatore Leonardi
- Pediatric Respiratory and Cystic Fibrosis Unit, Department of Clinical and Experimental Medicine, San Marco Hospital, University of Catania, Via Santa Sofia 78, 95123, Catania, Italy
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Schubert DC, Mößeler A, Ahlfänger B, Langeheine M, Brehm R, Visscher C, Abd El-Wahab A, Kamphues J. Influences of exocrine pancreatic insufficiency on nutrient digestibility, growth parameters as well as anatomical and histological morphology of the intestine in a juvenile pig model. Front Med (Lausanne) 2022; 9:973589. [PMID: 36160141 PMCID: PMC9505903 DOI: 10.3389/fmed.2022.973589] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Accepted: 08/24/2022] [Indexed: 11/20/2022] Open
Abstract
In a pig model, pancreatic duct ligation (PL) leads to a complete loss of exocrine function, causing an exocrine pancreatic insufficiency (EPI) without affecting endocrine function, allowing research of clinical effects and therapy options. This study aimed to investigate effects of experimentally induced EPI in juvenile pigs on digestion and intestinal morphology. Eight female juvenile cross-bred pigs (BW 54.8 kg at the start of the study) were included. Three animals were considered as a control (CON group), and in five animals the ductus pancreaticus accessorius was ligated (PL group). During the 10-week trial period, body weight and body measurements were recorded regularly. At the end of the trial, gastrointestinal tract (GIT) was investigated macroscopically and histologically and weight and digesta samples of individual segments were obtained. The pigs in the CON showed a significantly higher apparent total tract digestibility of crude protein and crude fat (87.8 and 79.9%, respectively) compared to PL (52.4 and 16.6%, respectively). Significant differences were noted in relative weights of duodenum, jejunum and colon (with and without digesta) and also in absolute weights of jejunum and colon. The mean number of nuclei in the transverse section in stratum circulare were significantly higher in all intestinal segments in CON compared to PL. Overall, EPI results in impaired nutrient digestibility with a greater filling of the GIT with digesta. The elongation of the small intestine does not represent "stretching" of the intestine, but rather increased synthesis of intestinal tissue.
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Affiliation(s)
- Dana Carina Schubert
- Institute for Animal Nutrition, University of Veterinary Medicine Hannover, Foundation, Hanover, Germany
| | - Anne Mößeler
- Institute for Animal Nutrition, University of Veterinary Medicine Hannover, Foundation, Hanover, Germany
- Vetsuisse Faculty, Institute of Animal Nutrition and Dietetics, University of Zurich, Zurich, Switzerland
| | - Bianca Ahlfänger
- Institute for Animal Nutrition, University of Veterinary Medicine Hannover, Foundation, Hanover, Germany
| | - Marion Langeheine
- Institute for Anatomy, University of Veterinary Medicine Hannover, Foundation, Hanover, Germany
| | - Ralph Brehm
- Institute for Anatomy, University of Veterinary Medicine Hannover, Foundation, Hanover, Germany
| | - Christian Visscher
- Institute for Animal Nutrition, University of Veterinary Medicine Hannover, Foundation, Hanover, Germany
| | - Amr Abd El-Wahab
- Institute for Animal Nutrition, University of Veterinary Medicine Hannover, Foundation, Hanover, Germany
- Department of Nutrition and Nutritional Deficiency Diseases, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt
| | - Josef Kamphues
- Institute for Animal Nutrition, University of Veterinary Medicine Hannover, Foundation, Hanover, Germany
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Masciopinto P, Bellitti E, Arcuti E, Battisti O, Cazzato G, Perrone T, Longo MC, Laddaga FE, Maiorano E, Musto P, Ingravallo G, Gaudio F. Indolent Lymphoproliferative T-Cell Disorders Associated With Gastrointestional Disease: Diagnostic Challenges and Outcomes. CLINICAL LYMPHOMA, MYELOMA & LEUKEMIA 2022; 22:e745-e750. [PMID: 35501257 DOI: 10.1016/j.clml.2022.04.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Revised: 03/18/2022] [Accepted: 04/03/2022] [Indexed: 02/05/2023]
Abstract
Lymphoproliferative diseases arise when the physiological mechanisms that control the proliferation of T and B lymphocytes are disrupted, resulting in an uncontrolled and autonomous increase in immune cells leading to lymphocytosis and lymphadenopathy, and often to the involvement of extranodal sites. The differential diagnosis of malignant T cell tumors involves other neoplasms and non-clonal T cell proliferations. Immunological markers are essential, as a first step, to distinguish between T-cell and non-T-cell disorders. It must be established based on the configuration of the genes of the TCR chain to rule out that the picture is not reactive to other underlying diseases. This clinical review and accompanying case reports highlight the diagnostic challenges associated with indolent lymphoproliferative T-cell disorders, which in many cases may represent the clinical manifestation of a single disease. Particularly we focus on gastrointestinal manifestations that could be expression either of lymphoproliferative disorder either of autoimmune disease either of both. The correct interpretation of the different clinical situations can help in the diagnostic and therapeutic process.
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Affiliation(s)
| | | | - Elena Arcuti
- Hematology and Stem Cell Transplantation Unit, AOUC Policlinico, Bari, Italy
| | - Olga Battisti
- Hematology and Stem Cell Transplantation Unit, AOUC Policlinico, Bari, Italy
| | | | - Tommasina Perrone
- Hematology and Stem Cell Transplantation Unit, AOUC Policlinico, Bari, Italy
| | - Maria Chiara Longo
- Hematology and Stem Cell Transplantation Unit, AOUC Policlinico, Bari, Italy
| | | | | | - Pellegrino Musto
- Hematology and Stem Cell Transplantation Unit, AOUC Policlinico, Bari, Italy
| | | | - Francesco Gaudio
- Hematology and Stem Cell Transplantation Unit, AOUC Policlinico, Bari, Italy.
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Schmidt LH, Aa JS, Hartmann B, Madsen GI, Qvist N, Ellebæk MB. Segmental reversal of the distal small intestine in a short bowel syndrome model in piglets showed detrimental effect on weight gain. BMC Gastroenterol 2022; 22:349. [PMID: 35858830 PMCID: PMC9297615 DOI: 10.1186/s12876-022-02418-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Accepted: 07/06/2022] [Indexed: 11/15/2022] Open
Abstract
BACKGROUND To investigate the effects of a reversed segment of the distal small intestine to improve weight gain in an experimental short bowel syndrome (SBS) model in piglets. METHODS Twenty-four piglets underwent resection of 70% of the distal small intestine. In half of the animals a conventional anastomosis was performed, and in the other half, the distal 25 cm of the remnant jejunum was reversed before the intestinal continuity was recreated. Weight was measured daily until day 28, where the animals were euthanized. Glucagon-Like Peptide-2 (GLP-2) and Glucose-dependent Insulinotropic Peptide (GIP) was measured pre- and postoperatively at day 28. RESULTS The group with reversal of small intestine had a significant lower weight gain at 5.26 ± 3.39 kg (mean ± SD) compared to the control group with 11.14 ± 3.83 kg (p < 0.05). In the control group greater villus height and crypt depth was found distally, and greater muscular thickness was found proximally in the intervention group. GLP-2 and GIP levels increased significantly in the control group. CONCLUSIONS Treatment of short bowel syndrome with a reversed jejunal segment of 25 cm had a detrimental effect on the weight gain.
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Affiliation(s)
- Lasse Hartmann Schmidt
- Research Unit for Surgery, Odense University Hospital, University of Southern Denmark, J. B. Winsløws Vej 4, 5000 Odense C, Denmark
| | - Jesper Stensig Aa
- Research Unit for Surgery, Odense University Hospital, University of Southern Denmark, J. B. Winsløws Vej 4, 5000 Odense C, Denmark
| | - Bolette Hartmann
- Department of Medical Sciences, NNF Center for Basic Metabolic Research, Faculty of Health Science, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark
| | - Gunvor Iben Madsen
- Research Unit for Pathology, Odense University Hospital, University of Southern Denmark, J. B. Winsløws Vej 4, 5000 Odense C, Denmark
| | - Niels Qvist
- Research Unit for Surgery, Odense University Hospital, University of Southern Denmark, J. B. Winsløws Vej 4, 5000 Odense C, Denmark
| | - Mark Bremholm Ellebæk
- Research Unit for Surgery, Odense University Hospital, University of Southern Denmark, J. B. Winsløws Vej 4, 5000 Odense C, Denmark
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Sakarellos P, Papalois A, Gakiopoulou H, Zacharioudaki I, Katsimpoulas M, Belia M, Moris D, Aggelou K, Vagios I, Davakis S, Vailas M, Liakakos T, Diamantis T, Felekouras E, Kontos M. Growth of Intestinal Neomucosa on Pedicled Gastric Wall Flap, a Novel Technique in an Animal Model. J INVEST SURG 2022; 35:1329-1339. [PMID: 35196939 DOI: 10.1080/08941939.2022.2034196] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Revised: 01/13/2022] [Accepted: 01/21/2022] [Indexed: 10/19/2022]
Abstract
Background: Short bowel syndrome (SBS) remains an unsolved issue in modern medicine. Numerous experimental surgical techniques have been proposed in the attempt to increase the intestinal absorptive capacity.Materials and Methods: Ten female Landrace pigs, divided in two groups of 5 (A and B), were explored through a midline incision. A spindle-shaped vascularized full-thickness gastric wall flap (GWF) consisting of part of the major curvature with the gastroepiploic arch preserved was de-epithelialized and then placed as a "patch" to cover an antimesenteric border defect of either a nonfunctional blind intestinal loop (group A) or a functional intestinal loop of the gastrointestinal tract (group B). A spindle-shaped curved, rigid, low density polyethylene (LDPE) splint was sutured on the external surface of the patch in order to prevent shrinkage of GWF and collapse of the intestinal wall in group A.Results: There was a decrease of both dimensions of the patch. Microscopically a thin layer of columnar epithelial cells covered the center of the patch, evolving in shorter, blunt, poorly developed villi with increasing maturation laterally. The patch surface was covered by nearly 90%. In the three animals that died prematurely the coverage of GWF was negligent or suboptimal directly dependent on the length of survival.Conclusions: The hereby-described patching technique demonstrated the growth of intestinal neomucosa on the GWF. The capability of the stomach to provide large flaps and the advantages of the use of native tissues render this animal model valuable for the future research in the field.
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Affiliation(s)
- Panagiotis Sakarellos
- First Department of Surgery, Laiko General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | | | - Harikleia Gakiopoulou
- First Department of Pathology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Iro Zacharioudaki
- Experimental, Educational and Research Centre, ELPEN, Athens, Greece
| | - Michalis Katsimpoulas
- Experimental Surgery Unit, Center of Clinical, Experimental Surgery and Translational Research, Βιοmedical Research Foundation of the Academy of Athens, Athens, Greece
| | - Marina Belia
- Department of Haematology and Bone Marrow Transplantation, Laiko General Hospital, National and Kapodistrian University of Athens, Athens Greece
| | - Dimitrios Moris
- First Department of Surgery, Laiko General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Kyveli Aggelou
- Department of Obstetrics and Gynecology, Alexandra Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Ilias Vagios
- First Department of Surgery, Laiko General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Spiridon Davakis
- First Department of Surgery, Laiko General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Michail Vailas
- First Department of Surgery, Laiko General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Theodoros Liakakos
- First Department of Surgery, Laiko General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Theodoros Diamantis
- First Department of Surgery, Laiko General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Evangelos Felekouras
- First Department of Surgery, Laiko General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Michael Kontos
- First Department of Surgery, Laiko General Hospital, National and Kapodistrian University of Athens, Athens, Greece
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Abstract
Short bowel syndrome (SBS) is a rare disorder characterized by severe intestinal dysfunction leading to malabsorption of macronutrients and micronutrients that often results in permanent need of parenteral nutrition support. Patients can develop SBS because of massive intestinal resection or loss of intestinal function and consequently experience significant morbidity and increased healthcare utilization. The remaining anatomy and length of bowel after intestinal resection have important prognostic and therapeutic implications. Because patients with SBS constitute a heterogenous group, management is complex and multifaceted, involving nutrition support, fluid and electrolyte management, and pharmacologic therapies in particular to control diarrhea. Surgical interventions including intestinal transplantation may be considered in selected individuals. Successful care of these patients is best accomplished by a multidisciplinary team that is experienced in the management of this syndrome.
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Wang J, Yan W, Lu L, Tao Y, Huang L, Cai W, Wang Y. Intestinal Continuity Alleviates Pediatric Intestinal Failure-Associated Liver Disease. Front Surg 2022; 9:881782. [PMID: 35651678 PMCID: PMC9149254 DOI: 10.3389/fsurg.2022.881782] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Accepted: 04/18/2022] [Indexed: 11/13/2022] Open
Abstract
Background Type I short bowel syndrome (SBS) occurs after a critical reduction in the functional gut mass and resection of intestinal continuity after ileostomy or jejunostomy for necrotizing enterocolitis (NEC), intestinal atresia or other causes. SBS is often accompanied with intestinal failure-associated liver disease (IFALD) who requires long-term parenteral nutrition (PN). Our study aimed to observe the effect of intestinal continuity on the hepatic function of pediatric intestinal failure (IF) patients with type I SBS. Methods The pre-and post-anastomosis medical records of 35 pediatric patients with type I SBS from April 2013 to April 2019 were reviewed retrospectively. The average growth (cm/month) in the proximal and distal small bowel lengths was calculated as the growth in intestinal length (cm)/the duration (month) from enterostomy to anastomosis. The changes in hepatic function from enterostomy to anastomosis were evaluated by assessment of hepatic function before anastomosis for 6 weeks and after anastomosis for 4 weeks. Results The average growth in proximal intestinal length was 9.3 cm/month (±7.2) in neonates and 2.8 cm/month (1.3, 11.9) in infants and children, and in distal intestinal length was 1.5 cm/month (0, 2.7) in neonates and 0.4 cm/month (0, 1.4) in infants and children. The incidence of IFALD was 28.6% 1 month before anastomosis and 20.0% 1 month after anastomosis (p < 0.05). Conclusion In pediatric type I SBS with IFALD, restoration of intestinal continuity may alleviate liver injury. There was an intestinal compensatory effect on the growth in the intestinal length after resection, and better results were seen in neonates in terms of intestinal length growth.
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Affiliation(s)
- Jinling Wang
- Division of Pediatric Gastroenterology and Nutrition; Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Weihui Yan
- Division of Pediatric Gastroenterology and Nutrition; Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China
| | - Lina Lu
- Division of Pediatric Gastroenterology and Nutrition; Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yijing Tao
- Division of Pediatric Gastroenterology and Nutrition; Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Liufang Huang
- Division of Pediatric Gastroenterology and Nutrition; Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Wei Cai
- Division of Pediatric Gastroenterology and Nutrition; Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China
- Department of Pediatric Surgery; Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Shanghai Institute for Pediatric Research, Shanghai, China
| | - Ying Wang
- Division of Pediatric Gastroenterology and Nutrition; Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China
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Kokorina АA, Mikhailova EV, Krylova SA, Kriventsov AV, Kromsky SV, Sakhovsky ES, Shabarov IA, Sidorin VS, Sokolova MO, Sigareva LP, Pak NV, Aleksandrov VN. A Model of Short Bowel Syndrome in Rodents in a Long-Term Experiment. Bull Exp Biol Med 2022; 172:779-784. [PMID: 35501652 DOI: 10.1007/s10517-022-05477-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Indexed: 11/27/2022]
Abstract
Simulation of short bowel syndrome (SBS) in experimental animals is of great interest for studies in translational medicine. The processes of intestinal adaptation are most often studied in rats aged 8-10 weeks with up to 70% resection the small bowel. In this case, the animals are euthanized in 2 weeks after the surgery; further development of the pathological process remains practically unexplored. In our experiment, a number of blood biochemical parameters and morphological signs of intestinal adaptation were assessed within 34 weeks after surgery. It was shown that after resection of 70% of the small bowel in rats (180±15 g), clinical symptoms are observed only during the first 2 weeks, however, the mortality in the group was observed throughout the entire period of the study in the absence of clear clinical signs. Morphological compensatory changes in the walls of the small intestine continued up to 34 weeks after resection, and their morphometry can be used to describe adaptation in the dynamics of the study.
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Affiliation(s)
- А A Kokorina
- S. M. Kirov Military Medical Academy, St. Petersburg, Russia. .,St. Petersburg State Pediatric Medical University, Ministry of Health of the Russian Federation, St. Petersburg, Russia.
| | - E V Mikhailova
- St. Petersburg State Pediatric Medical University, Ministry of Health of the Russian Federation, St. Petersburg, Russia.,Institute of Cytology, Russian Academy of Sciences, St. Petersburg, Russia
| | - S A Krylova
- St. Petersburg State Pediatric Medical University, Ministry of Health of the Russian Federation, St. Petersburg, Russia
| | - A V Kriventsov
- S. M. Kirov Military Medical Academy, St. Petersburg, Russia
| | - S V Kromsky
- St. Petersburg State Pediatric Medical University, Ministry of Health of the Russian Federation, St. Petersburg, Russia
| | - E S Sakhovsky
- St. Petersburg State Pediatric Medical University, Ministry of Health of the Russian Federation, St. Petersburg, Russia
| | - I A Shabarov
- St. Petersburg State Pediatric Medical University, Ministry of Health of the Russian Federation, St. Petersburg, Russia
| | - V S Sidorin
- S. M. Kirov Military Medical Academy, St. Petersburg, Russia
| | - M O Sokolova
- S. M. Kirov Military Medical Academy, St. Petersburg, Russia
| | - L P Sigareva
- St. Petersburg State Pediatric Medical University, Ministry of Health of the Russian Federation, St. Petersburg, Russia
| | - N V Pak
- S. M. Kirov Military Medical Academy, St. Petersburg, Russia
| | - V N Aleksandrov
- S. M. Kirov Military Medical Academy, St. Petersburg, Russia.,St. Petersburg State Pediatric Medical University, Ministry of Health of the Russian Federation, St. Petersburg, Russia
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Improvement in metabolic indices including thyroid hormones via enhanced absorption of nutrients by Teduglutide in short bowel syndrome. Int J Surg Case Rep 2022; 94:107107. [PMID: 35658285 PMCID: PMC9093015 DOI: 10.1016/j.ijscr.2022.107107] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Revised: 04/13/2022] [Accepted: 04/15/2022] [Indexed: 11/23/2022] Open
Abstract
Introduction and importance Short bowel syndrome is characterized by maldigestion and malabsorption resulting in deficiencies of multiple nutrients including vitamins and minerals. Most subjects required parental elimination for survival. GLP-2 RA Teduglutide was recently approved for treatment of short bowel syndrome especially for those requiring parenteral support. Our intent in reporting this subject is to demonstrate the utility of Teduglutide in improving multiple metabolic indices in presence of short bowel syndrome. Case presentation and clinical discussion 66-year-old Caucasian female presented with a history of short bowel syndrome and associated vitamin deficiencies, hypothyroidism requiring large dose (300 μg) of levothyroxine, diarrhea and liver cirrhosis. Upon starting teduglutide the subject saw improvement in her symptoms. Moreover, daily dose of Levothyroxine required a gradual decrease to maintain desirable serum concentrations of Free T4, Free T3 and TSH. Serum levels of several vitamins attained greater than therapeutic concentrations requiring dosage reductions. Also notable was the improvement in her liver function tests, remission from ascites and episodes of hepatic encephalopathy and regeneration of liver nodules. Conclusion Following administration of GLP2 therapy, an adult subject with short bowel syndrome with concurrent hypothyroidism and multiple vitamin deficiencies, demonstrated a marked improvement in her metabolic parameters resulting in reduction in daily medication doses along with improvement in manifestations of liver cirrhosis.
Unique case report of remission of Metabolic abnormalities hepatic cirrhosis and encephalopathy following administration of GLP2 receptor agonist in a patient short bowel syndrome
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Severe Coagulopathy in a Patient With Short Bowel Syndrome. J Emerg Med 2022; 62:e101-e104. [PMID: 35109974 DOI: 10.1016/j.jemermed.2021.12.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2021] [Accepted: 12/23/2021] [Indexed: 11/23/2022]
Abstract
BACKGROUND Short bowel syndrome (SBS) refers to a malabsorptive state caused by extensive resection of the intestinal tract that leads to chronic diarrhea, electrolyte disturbances, and malnutrition. Although relatively uncommon, patients with SBS can present to the emergency department with more serious complications that are potentially life-threatening. Among these complications, coagulopathy secondary to SBS is an underrecognized condition. CASE REPORT We present a case of severe coagulopathy secondary to vitamin K deficiency in SBS. The patient presented with unexplained coagulopathy and spontaneous bleeding in multiple organs. With a review of surgical history and detailed clinical evaluation, SBS complicated with vitamin K deficiency was diagnosed, and the patient was treated successfully. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: When a patient with a history of repeated intestinal surgery presents with diarrhea, malnutrition, or electrolyte abnormalities, emergency physicians should suspect SBS. Among complications of SBS, vitamin K deficiency is a rare but serious cause of unexplained coagulopathy presenting to the emergency department. Understanding the pathophysiology of SBS facilitates early identification of complications and improves patient outcomes.
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Zaczek Z, Jurczak-Kobus P, Panczyk M, Braszczyńska-Sochacka J, Majewska K, Kunecki M, Dąbrowska K, Sobocki J. Changes in Parenteral Nutrition Requirements and BMI in Patients with Parenteral Nutrition-Dependent Short Bowel Syndrome after Stopping Teduglutide-9 Years of Follow-Up. Nutrients 2022; 14:nu14081634. [PMID: 35458196 PMCID: PMC9024979 DOI: 10.3390/nu14081634] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 04/09/2022] [Accepted: 04/12/2022] [Indexed: 12/12/2022] Open
Abstract
Teduglutide (TED) is widely used in patients with short-bowel-syndrome-associated intestinal failure (SBS-IF) to enhance intestinal adaptation and reduce the need for parenteral support (PS). There are limited data on the effects of discontinuing TED. In this study, we describe the changes in parenteral nutrition (PN) requirements and body mass index (BMI) in a 9-year follow-up of patients receiving home parenteral nutrition after discontinuation of the TED treatment. We performed a retrospective analysis of changes in weekly PN orders and BMI in all patients with PN-dependent SBS from two Polish home parenteral nutrition (HPN) centers who received teduglutide between 2009 and 2013 and still required HPN 9 years after discontinuation of the TED treatment. Data included in the analysis were collected prospectively at mandatory visits to the HPN centers at 12, 24, 60, 84, and 108 months after drug discontinuation and compared with values before and after TED treatment. Weekly PN volume values varied significantly between all of the above time points from baseline to 9 years after TED discontinuation (χ2 = 34.860, p < 0.001). After an initial increase within the first year after treatment discontinuation (not statistically significant), the PN volume requirements remained stable for 4 years and increased 5−9 years after treatment discontinuation. The rate of patients requiring an increase in PN volume was 84.62% at 60 and 84 months and 92.30% at 108 months. At 9 years after cessation of the TED treatment, 53.85% of the study group required a 21.21% increase in PN volume compared with values before treatment. The need for PN volume in patients with PN-dependent SBS who discontinued the TED treatment increased within the first year and 4−5 years after treatment cessation, and in some cases might even exceed pretreatment values after 9 years.
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Affiliation(s)
- Zuzanna Zaczek
- Department of Human Nutrition, Faculty of Health Sciences, Medical University of Warsaw, Erazma Ciołka 27, 01-445 Warsaw, Poland
- Department of General Surgery and Clinical Nutrition, Centre of Postgraduate Medical Education, Czerniakowska 231, 00-416 Warsaw, Poland; (P.J.-K.); (K.M.); (K.D.); (J.S.)
- Correspondence: ; Tel.: +48-(22)-584-13-20
| | - Paulina Jurczak-Kobus
- Department of General Surgery and Clinical Nutrition, Centre of Postgraduate Medical Education, Czerniakowska 231, 00-416 Warsaw, Poland; (P.J.-K.); (K.M.); (K.D.); (J.S.)
| | - Mariusz Panczyk
- Department of Education and Research in Health Sciences, Faculty of Health Sciences, Medical University of Warsaw, Litewska 14/16, 00-581 Warsaw, Poland;
| | | | - Krystyna Majewska
- Department of General Surgery and Clinical Nutrition, Centre of Postgraduate Medical Education, Czerniakowska 231, 00-416 Warsaw, Poland; (P.J.-K.); (K.M.); (K.D.); (J.S.)
| | - Marek Kunecki
- Clinical Nutrition Department, M. Pirogov Hospital, Wólczańska 191/195, 90-531 Lodz, Poland; (J.B.-S.); (M.K.)
| | - Karolina Dąbrowska
- Department of General Surgery and Clinical Nutrition, Centre of Postgraduate Medical Education, Czerniakowska 231, 00-416 Warsaw, Poland; (P.J.-K.); (K.M.); (K.D.); (J.S.)
| | - Jacek Sobocki
- Department of General Surgery and Clinical Nutrition, Centre of Postgraduate Medical Education, Czerniakowska 231, 00-416 Warsaw, Poland; (P.J.-K.); (K.M.); (K.D.); (J.S.)
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Maya‐Enero S, Prat‐Ortells J, Martín‐Solé O, De Haro‐Jorge I, Pertierra‐Cortada À, Iriondo‐Sanz M. Distinguishing outcomes of neonatal intestinal volvulus: Review of our experience over the last 20 years. Acta Paediatr 2022; 111:284-290. [PMID: 34704280 DOI: 10.1111/apa.16167] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Revised: 07/29/2021] [Accepted: 10/25/2021] [Indexed: 12/01/2022]
Abstract
AIM There are two types of intestinal volvulus: midgut (MGV) and segmental (SV). Patients with different types of intestinal volvulus are often included in the same case series, which may affect the perception of how severe "intestinal volvuli" are. We aimed to compare both types of intestinal volvulus. METHODS This is a retrospective observational study including all patients with MGV and SV up to 28 days of life admitted to a tertiary hospital in Spain over a 20-year-period (1999-2019). A comparison between groups and a logistic regression model for mortality were done. RESULTS We identified 32 patients: 23 MGV and 9 SV. Malrotation was exclusive of MGV. Prenatal diagnosis, cystic fibrosis, and intestinal resection were significantly more frequent in SV. Surgery was performed at a significantly lower age in SV. The mortality observed in acute MGV with intestinal compromise (41.7%) is four times higher than the mortality of SV (11.1%). The overall mortality of all MGV patients (21.7%) is almost twice that of SV. Mortality was best predicted by the presence of hemodynamic instability (OR 27.5 95% CI 2.50-302.17; p = 0.007). CONCLUSION SV and MGV have a different clinical presentation. Hemodynamic instability is the major risk factor for death.
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Affiliation(s)
- Silvia Maya‐Enero
- Department of Neonatology Service of Pediatrics, Hospital del Mar Universitat Autònoma de Barcelona Barcelona Spain
| | - Jordi Prat‐Ortells
- Service of Pediatric Surgery Hospital Sant Joan de DéuUniversitat de Barcelona Barcelona Spain
| | - Oriol Martín‐Solé
- Service of Pediatric Surgery Hospital Sant Joan de DéuUniversitat de Barcelona Barcelona Spain
| | - Irene De Haro‐Jorge
- Service of Pediatric Surgery Hospital Sant Joan de DéuUniversitat de Barcelona Barcelona Spain
| | | | - Martín Iriondo‐Sanz
- Service of Neonatology Hospital Sant Joan de DéuUniversitat de Barcelona Barcelona Spain
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Peters FB, Bone JN, Van Oerle R, Albersheim S, Casey L, Piper H. The Importance of the ileocecal valve and colon in achieving intestinal independence in infants with short bowel syndrome. J Pediatr Surg 2022; 57:117-121. [PMID: 34696920 DOI: 10.1016/j.jpedsurg.2021.09.028] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Accepted: 09/08/2021] [Indexed: 12/23/2022]
Abstract
PURPOSE Infants with short bowel syndrome (SBS) wean from parenteral nutrition (PN) support at variable rates. Small bowel length is a predictor, but the importance of the ileocecal valve (ICV) and colon are unclear. We aim to determine if the ICV and/or colon predict enteral autonomy. METHODS Infants from a single intestinal rehabilitation program were retrospectively reviewed. Etiology of SBS, intestinal anatomy, and duration of nutritional support were collected for three years. The primary outcome was time to full enteral nutrition. ANCOVA and Cox proportional hazards model were used, with p < 0.05 significant. RESULTS 55 infants with SBS were included. After accounting for the effect of small bowel, PN duration was shorter for infants with the ICV compared to those without (mean 218 vs. 538 days, p = 0.003), and had a more significant effect on infants with ≤50% of small bowel. Increased small bowel length was a positive predictor of weaning. Patients with ≤50% of colon spent less time on PN with the ICV, compared to without (mean 220 vs 715 days, p = 0.009). CONCLUSIONS Preservation of the ICV was associated with shorter duration of PN support, while colon was not. Small bowel length is a positive predictor of enteral autonomy. LEVEL OF EVIDENCE Level III retrospective comparative study TYPE OF STUDY: Retrospective review.
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Affiliation(s)
- Francesca Bell Peters
- Faculty of Medicine, University of British Columbia, 317-2194 Health Sciences Mall, Vancouver, BC V6T1Z3, Canada.
| | - Jeffrey N Bone
- BC Children's Hospital Research Institute, Vancouver, BC, Canada
| | - Rhonda Van Oerle
- Division of Neonatology, University of British Columbia/BC Women's Hospital and Health Center, Vancouver, BC, Canada
| | - Susan Albersheim
- Division of Neonatology, University of British Columbia/BC Women's Hospital and Health Center, Vancouver, BC, Canada
| | - Linda Casey
- Department of Pediatrics, University of British Columbia/BC Children's Hospital, Vancouver, BC, Canada
| | - Hannah Piper
- Division of Pediatric Surgery, University of British Columbia/BC Children's Hospital, Vancouver, BC, Canada.
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The effects of different parenteral nutrition lipid formulations on clinical and laboratory endpoints in patients receiving home parenteral nutrition: A systematic review. Clin Nutr 2021; 41:80-90. [PMID: 34864457 DOI: 10.1016/j.clnu.2021.11.009] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Revised: 10/21/2021] [Accepted: 11/06/2021] [Indexed: 11/24/2022]
Abstract
BACKGROUND Home parenteral nutrition (HPN) is a life-sustaining therapy for individuals with intestinal failure in a community setting. It refers to the intravenous infusion of macronutrients, micronutrients, fluids and electrolytes. Routinely used HPN solutions contain different quantities of these components. Consequently, each HPN solution may have different impacts on metabolism, inflammation and oxidative stress. Long-term use of HPN can lead to a number of adverse health outcomes including the development of metabolic bone disease, intestinal failure associated liver disease and poor quality of life but whether, and how, the composition of HPN solutions contributes to these health sequelae is poorly understood. The aim of this study is to systematically review and evaluate the evidence for the differential effects of HPN solutions and to understand what features are associated with differences in clinical endpoints. METHODS A systematic literature search was conducted between September and December 2020, and updated in July 2021 using the MEDLINE (Ovid), EMBASE, Scopus, and Web of Science databases. Studies were selected according to the following criteria (a) adult participants (>18 years old) dependent on HPN; (b) randomised controlled trials, prospective cohort and cross-sectional study designs; (c) primary research comparing two or more HPN solutions and (d) published in English language. Data were extracted and study quality assessed using Cochrane Collaboration's tools: Risk of Bias for Randomised Controlled Trials (RCTs); Risk of Bias in Non-Randomised Studies of Interventions; and the Newcastle Ottawa Scale for cross-sectional studies. RESULTS Of the 5148 articles identified, seven RCTs, two prospective cohort and one cross-sectional study were included with a total of 295 participants. Studies varied in terms of duration (one to 60 months) and sample size (n = 5 to 88). Ten studies compared lipid emulsions (LE) and one study also compared LE with lipid-free HPN. No studies were found that compared the amino acid, vitamin, trace element or electrolyte components of HPN. In general, LE were well tolerated with no significant adverse effects. LE containing olive +/or fish oil were associated with a lower ω-6:ω-3 fatty acid ratio, positive reductions in markers of liver function, and changes in blood and cell fatty acid profiles. CONCLUSIONS Despite the increasing use of HPN, there is surprisingly little evidence available to guide the provision of macro and micronutrients in the adult population requiring this therapy. Although LE containing olive +/or fish oil show promise with regards to liver function and blood and cell fatty acid profiles, further studies are needed before drawing definitive conclusions on the clinical value of these emulsions. It is likely that one type of HPN solution alone cannot be uniformly applied to patient care, and each patient should be assessed on an individual basis.
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