RESUMEN
Surgery in Crohn's disease may be the cause of short bowel syndrome that may lead to kidney dysfunction. Dual biologic therapy is rarely needed to control activity. We present a case of a 61-year-old steroid dependent (A2L1B3p) female who had undergone surgery on three occasions: ileocecal resection (resection of 15 cm of terminal ileum); resection of right and left colon up to sigmoid; proctectomy with intersphincteric resection along with ileostomy due to a rectovaginal fistula. She had been previously treated with prednisone, azathioprine, methotrexate, infliximab and adalimumab but the treatment was discontinued owing to adverse effects. Vedolizumab was started, showing good control of the luminal activity but the rectovaginal fistula recurred. Treatment changed to ustekinumab, the fistula activity was controlled but the mucosa activity recurred. 11 months after commencing with ustekinumab, vedolizumab was added to the treatment and complete remission was achieved for three years. Simultaneously, the patient developed renal dysfunction derived from the short bowel syndrome that led to chronic kidney failure. In the face of potential renal replacement therapy, a new therapy with 2.5 mg/sc/d teduglutide was started achieving stable figures of creatinine and normalization of the glomerular filtration rate.
Asunto(s)
Enfermedad de Crohn , Síndrome del Intestino Corto , Femenino , Humanos , Persona de Mediana Edad , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/inducido químicamente , Ustekinumab/efectos adversos , Síndrome del Intestino Corto/tratamiento farmacológico , Fístula Rectovaginal , Terapia Biológica , Resultado del TratamientoRESUMEN
PURPOSE OF REVIEW: Although Glucagon-like peptide (GLP)-1 receptor agonists have been used for almost two decades in the treatment of diabetes mellitus type 2 and, lately, in obesity, recent years have seen an increasing interest in the pharmacological agonism of other proglucagon-derived peptides, including GLP-2. Herein, we aimed to review the available evidence on the effects of GLP-2 agonism from animal and clinical studies. Furthermore, we summarize the current clinical applications of GLP-2 agonists among patients with intestinal failure associated with short bowel syndrome (SBS-IF) as well as potential future expansion of their indications to other intestinal disorders. RECENT FINDINGS: Evidence from preclinical studies has highlighted the cellular trophic and functional beneficial actions of GLP-2 on small intestinal and colonic mucosa. Subsequently, pharmacologic agonism of GLP-2 has gathered interest for the treatment of patients with conditions pertaining to the loss of intestinal anatomical and/or functional integrity to a degree requiring parenteral support, collectively referred to as intestinal failure. GLP-2 analogs positively influence nutrient absorption in animal models and humans, although continued therapy is likely needed for sustained effects. The degradation-resistant GLP-2-analog teduglutide has received approval for the treatment of SBS-IF, in which it may decisively reduce patient dependency on parenteral support and improve quality of life. Another two longer-acting analogs, glepaglutide and apraglutide, are currently undergoing phase III clinical trials. The use of GLP-2 analogs is effective in the management of SBS-IF and may show promise in the treatment of other severe gastrointestinal disorders associated with loss of effective intestinal resorptive surface area.
Asunto(s)
Enfermedades Gastrointestinales , Insuficiencia Intestinal , Síndrome del Intestino Corto , Animales , Humanos , Calidad de Vida , Péptido 2 Similar al Glucagón/uso terapéutico , Síndrome del Intestino Corto/tratamiento farmacológico , Enfermedades Gastrointestinales/tratamiento farmacológicoRESUMEN
PURPOSE OF REVIEW: Intestinal failure (IF) evolved from being the last recognized organ failure, to become one of the most progressive fields in terms of therapeutic alternatives and results. Short bowel syndrome (SBS) is the main cause of IF in adults and children. The use of surgery allowed patients with unfavorable anatomy type and length to be wean off parenteral nutrition. We aim to evaluate its current impact on intestinal rehabilitation. RECENT FINDINGS: Autologous gastro-intestinal reconstructive surgery (AGIRS), including bowel lengthening contributes by converting patient's anatomy to a more favorable one, improving quality of life, and modifying the natural history of the disease, allowing to recover intestinal autonomy in approximately 70% of the adults and 50% of the children's with SBS-IF. The current use of postsurgical medical rehabilitation strategies including the use of enterohormones complement the path to sufficiency, increasing the chances of success in both age group of patients. SUMMARY: The development of AGIRS has changed the outcome of SBS-IF patients, becoming the main surgical procedure prescribed in multidisciplinary units, allowing to enhance the number of patients achieving intestinal autonomy throughout rehabilitation, leaving transplantation as the last surgical alternative.
Asunto(s)
Procedimientos Quirúrgicos del Sistema Digestivo , Síndrome del Intestino Corto , Adulto , Niño , Procedimientos Quirúrgicos del Sistema Digestivo/efectos adversos , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Humanos , Intestinos , Nutrición Parenteral/métodos , Calidad de Vida , Síndrome del Intestino Corto/tratamiento farmacológico , Síndrome del Intestino Corto/cirugía , Resultado del TratamientoRESUMEN
Panitumumab, a fully human anti-epidermal growth factor receptor (EGFR) monoclonal antibody, has been shown to be useful in treating either advanced or recurrent KRAS/NRAS/BRAF wild-type colorectal cancer. We herein report the case of a 60-year-old man with short bowel syndrome who developed hematochezia due to panitumumab-induced colitis with vitamin K deficiency during third-line chemotherapy. The cause of vitamin K deficiency was the lack of intravenous vitamin K supplementation following a change from central venous nutrition to peripheral venous nutrition. We advise clinicians to carefully check for colitis and manage the infusions of chemotherapy patients with short bowel syndrome.
Asunto(s)
Antineoplásicos , Colitis , Neoplasias Colorrectales , Síndrome del Intestino Corto , Deficiencia de Vitamina K , Anticuerpos Monoclonales/efectos adversos , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Colitis/tratamiento farmacológico , Neoplasias Colorrectales/tratamiento farmacológico , Hemorragia Gastrointestinal/etiología , Humanos , Masculino , Persona de Mediana Edad , Mutación , Recurrencia Local de Neoplasia/tratamiento farmacológico , Panitumumab/efectos adversos , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Síndrome del Intestino Corto/tratamiento farmacológico , Deficiencia de Vitamina K/inducido químicamente , Deficiencia de Vitamina K/tratamiento farmacológicoRESUMEN
OBJECTIVES: Supplementing diet with citrulline has proved an efficient means of preserving nitrogen balance and improving nutritional status after massive intestinal resection. The aim of this study was to model the action of citrulline in gut-resected rats using a dose-ranging study focused on skeletal muscle nitrogen homeostasis. METHODS: Forty-six rats were randomly assigned to one of the following groups: citrulline 0.5 g·kg·d-1 (n = 9), citrulline 1 g·kg·d-1 (n = 7), citrulline 2.5 g·kg·d-1 (n = 8), citrulline 5 g·kg·d-1 (n = 8), control (n = 6), and sham (n = 8). The sham group underwent transection and the other groups underwent resection of 80% of the small intestine. All rats were then fed enteral nutrition (EN; all diets were isocaloric and isonitrogenous). After 10 d, the rats were sacrificed to measure and analyze animal weight; duodenum, jejunum, and ileum weight; and muscle trophicity. Protein fractional synthesis rate (FSR) and mammalian target of rapamycin complex (mTORC)1 activation were measured in the tibialis muscle. RESULTS: There was a significant dose-dependent association between rat weight and citrulline dose up to 2.5 g·kg·d-1 (P = 0.004). There was a significant improvement in tibialis weight correlated to plasma citrulline. Net protein FSR in the tibialis tended to be greater after resection and tended to return to baseline after citrulline supplementation. Citrulline supplementation significantly decreased the activated phosphorylated forms of S6 K1 (P = 0.003) and S6 RP (P = 0.003), with a significant positive association between myofibrillar FSR and activation of S6 K1 (r = 0.614; P = 0.02) and S6 RP (r = 0.601; P = 0.023). Jejunum weight was significantly positively correlated with plasma citrulline (r = 0.319; P = 0.0345). CONCLUSION: Citrulline promotes body weight gain, preserves muscle trophicity, and enhances intestinal adaptation in a dose-dependent manner in a model of resected rats.
Asunto(s)
Síndrome del Intestino Corto , Animales , Citrulina , Suplementos Dietéticos , Íleon , Mucosa Intestinal , Intestino Delgado , Ratas , Síndrome del Intestino Corto/tratamiento farmacológicoRESUMEN
Short bowel syndrome in neonates is a severe and life-threatening disease after a major loss of small bowel with or without large bowel. Intestinal adaptation, by which the organism tries to restore digestive and absorptive capacities, is entirely dependent on stimulation of the active enterocytes by enteral nutrition. This review summarizes recent knowledge about the pathophysiologic consequences after the loss of different intestinal parts and outlines the options for enteral nutrition and pharmacological therapies to support the adaptation process.
Asunto(s)
Nutrición Enteral/métodos , Fármacos Gastrointestinales/uso terapéutico , Síndrome del Intestino Corto/terapia , Humanos , Lactante , Recién Nacido , Intestino Delgado/fisiopatología , Síndrome del Intestino Corto/tratamiento farmacológico , Síndrome del Intestino Corto/fisiopatologíaRESUMEN
BACKGROUND: Intestinal failure-associated liver disease (IFALD) is a serious complication of parenteral nutrition (PN). We report 2 cases of IFALD, which occurred in adult patients while on a regimen of multi-oil intravenous lipid emulsion containing fish oil. METHODS: Patients initially received PN containing 1-g/kg/d SMOFlipid 20% (SMOFlipid). When IFALD developed, lipid composition in PN was altered to include higher proportions of fish oil. RESULTS: Case 1 was a 23-year-old man with short-bowel syndrome. He had been fully dependent on PN for approximately 11 months with a direct bilirubin level of 15.1 mg/dL. Doses of 0.15-g/kg/d pure fish oil and 0.3-0.6-g/kg/d SMOFlipid were administered for 56 days, and IFALD was resolved 59 days after adding fish oil. Case 2 was an 85-year-old man who received extensive small-bowel resection because of internal herniation and small-bowel necrosis. He had elevated direct bilirubin levels and was diagnosed with IFALD. Fish-oil treatment was initiated after 50 days of receiving PN. The average daily amount of fish oil given was 0.14 g/kg/d. IFALD was resolved 44 days after adding Omegaven (Fresenius Kabi Austria Gmbh, Austria). CONCLUSION: Two patients with advanced IFALD showed reversal of cholestasis by altering the lipid content of their PN to include more fish oil.
Asunto(s)
Enfermedades Intestinales , Hepatopatías , Síndrome del Intestino Corto , Adulto , Anciano de 80 o más Años , Emulsiones Grasas Intravenosas , Aceites de Pescado , Humanos , Enfermedades Intestinales/complicaciones , Enfermedades Intestinales/tratamiento farmacológico , Masculino , Aceite de Oliva , Síndrome del Intestino Corto/complicaciones , Síndrome del Intestino Corto/tratamiento farmacológico , Aceite de Soja , Triglicéridos , Adulto JovenRESUMEN
We report the case of a 62-y-old woman with short bowel syndrome (SBS) and chronic renal failure, successfully treated with teduglutide, who underwent comprehensive systematic nutritional assessment including bioelectrical impedance vectorial analysis (BIVA). The patient did not tolerate the attempt of gradual suspension of parenteral nutrition (PN), bumping into the worsening of nutritional status and renal function. She was declared eligible for teduglutide, a glucagonlike peptide 2 analog that stimulates structural and functional intestinal adaptation and increases nutrient and fluid absorption. To date, there is no standardized nutritional management protocol for PN-dependent SBS patients treated with teduglutide. We here report our first 1-y follow-up data. The patient underwent comprehensive systematic nutritional assessment initially every 2 wk, then monthly. It included handgrip strength (HGS), blood tests (particularly serum creatinine, estimated glomerular filtration rate, urea, electrolytes, micronutrients, serum albumin), fluid intake, urine output, quality-of-life (QoL) evaluation, and BIVA, which estimates fat-free mass (FFM) and measures phase angle (PhA) and hydration status. At treatment initiation, the patient was on PN 3 d/wk. After 3 mo, she was weaned off PN. At 1 y, weight and serum albumin were reduced (-7.5 kg and -0.6 g/dL, respectively); FFM, PhA, and HGS slightly decreased; hydration status and renal function were preserved; and QoL subtly improved. No relevant clinical complications or metabolic imbalances occurred. The inclusion of BIVA in the comprehensive systematic nutritional assessment of SBS patients treated with teduglutide could be proposed for appropriate and safe management, particularly in the presence of renal impairment.
Asunto(s)
Fallo Renal Crónico , Síndrome del Intestino Corto , Femenino , Fármacos Gastrointestinales/uso terapéutico , Fuerza de la Mano , Humanos , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Evaluación Nutricional , Péptidos/uso terapéutico , Calidad de Vida , Síndrome del Intestino Corto/complicaciones , Síndrome del Intestino Corto/tratamiento farmacológicoAsunto(s)
Terapia Biológica , Enfermedad de Crohn/tratamiento farmacológico , Fármacos Gastrointestinales/uso terapéutico , Péptidos/uso terapéutico , Síndrome del Intestino Corto/tratamiento farmacológico , Adulto , Enfermedad de Crohn/patología , Combinación de Medicamentos , Humanos , Masculino , Pronóstico , Síndrome del Intestino Corto/patologíaRESUMEN
It is not known whether Teduglutide can allow patients with Short bowel syndrome, previously dependent on continuous or periodic intravenous (IV) magnesium, to attain oral autonomy with or without supplementation. Here, we report on two patients previously dependent on continuous or intermittently administered IV magnesium to achieve autonomy from IV, one with and one without oral supplementation that was previously ineffective in both patients.
Asunto(s)
Fármacos Gastrointestinales/uso terapéutico , Deficiencia de Magnesio/tratamiento farmacológico , Magnesio/administración & dosificación , Péptidos/uso terapéutico , Síndrome del Intestino Corto/tratamiento farmacológico , Anciano , Suplementos Dietéticos , Femenino , Humanos , Absorción Intestinal , Deficiencia de Magnesio/etiología , Deficiencia de Magnesio/fisiopatología , Persona de Mediana Edad , Estado Nutricional , Síndrome del Intestino Corto/complicaciones , Síndrome del Intestino Corto/fisiopatología , Resultado del TratamientoRESUMEN
Intestinal failure-associated liver disease (IFALD) is a fatal complication of short bowel syndrome managed with parenteral nutrition. A clinical cohort study reported the usefulness of parenteral administration of fish-derived omega-3 fatty acids in improving IFALD; however, no biomarker has been developed as yet. The authors report the case of a preterm infant with IFALD complicated by extensive short bowel syndrome. Intravenous administration of omega-3 fatty acids were introduced using Omegaven®at the age of 4 mo for IFALD. The IFALD improved with an increase in Eicosapentaenoic acid (EPA)/ Arachidonic acid (AA) ratio (from 0.08 to 1.99) 7 d after the intravenous treatment. It is important to administer omega-3 fatty acids intravenously at an early stage for IFALD associated with extensive short bowel syndrome. A low EPA/AA ratio may be a serum marker of disease activity in IFALD.
Asunto(s)
Ácido Araquidónico/sangre , Ácido Eicosapentaenoico/sangre , Ácidos Grasos Omega-3/uso terapéutico , Enfermedades Intestinales/etiología , Hepatopatías/etiología , Síndrome del Intestino Corto/complicaciones , Administración Oral , Biomarcadores/sangre , Ácidos Grasos Omega-3/administración & dosificación , Femenino , Humanos , Recién Nacido , Infusiones Intravenosas , Enfermedades Intestinales/sangre , Enfermedades Intestinales/tratamiento farmacológico , Hepatopatías/sangre , Hepatopatías/tratamiento farmacológico , Síndrome del Intestino Corto/tratamiento farmacológicoRESUMEN
BACKGROUND: Patients with intestinal failure associated with short bowel syndrome (SBS-IF) require parenteral support (PS) to maintain fluid balance or nutrition. Teduglutide (TED) reduced PS requirements in patients with SBS-IF in the randomized, placebo (PBO)-controlled STEPS study (NCT00798967) and its 2-year, open-label extension, STEPS-2 (NCT00930644). METHODS: STEPS-3 (NCT01560403), a 1-year, open-label extension study in patients with SBS-IF who completed STEPS-2, further monitored the safety and efficacy of TED (0.05 mg/kg/day). Baseline was the start of TED treatment, in either STEPS or STEPS-2. At the end of STEPS-3, patients treated with TED in both STEPS and STEPS-2 (TED-TED) received TED for ≤42 months, and patients treated with TED only in STEPS-2 (no TED treatment [NT]/PBO-TED) received TED for ≤36 months. RESULTS: Fourteen patients enrolled (TED-TED, n = 5; NT/PBO-TED, n = 9) and 13 completed STEPS-3. At the last dosing visit, mean (SD) PS was reduced from baseline by 9.8 (14.4 [50%]) and 3.9 (2.8 [48%]) L/week in TED-TED and NT/PBO-TED, respectively. Mean (SD) PS infusions decreased by 3.0 (4.6) and 2.1 (2.2) days per week from baseline in TED-TED and NT/PBO-TED, respectively. Two patients achieved PS independence; 2 additional patients who achieved independence in STEPS-2 maintained enteral autonomy throughout STEPS-3. All patients reported ≥1 treatment-emergent adverse event (TEAE); 3 patients had TEAEs that were reported as treatment related. No patient had a treatment-related treatment-emergent serious AE. CONCLUSIONS: Long-term TED treatment yielded a safety profile consistent with previous studies, sustained efficacy, and a further decline in PS requirements.
Asunto(s)
Fluidoterapia , Fármacos Gastrointestinales/uso terapéutico , Intestinos , Nutrición Parenteral , Péptidos/uso terapéutico , Síndrome del Intestino Corto/tratamiento farmacológico , Adulto , Anciano , Femenino , Humanos , Enfermedades Intestinales , Masculino , Persona de Mediana Edad , Síndrome del Intestino Corto/terapia , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Teduglutide is a glucagon-like peptide 2 (GLP-2) analog that has been approved for the treatment of adult short bowel syndrome (SBS)-associated intestinal failure (IF; SBS-IF). Teduglutide increases villus height and crypt depth in the small bowel mucosa, promoting nutrition absorption and enteral independence from parenteral nutrition (PN). We aim to report our single-center experience with teduglutide in adult patients with SBS to provide real-world context to its use. METHOD: We conducted a retrospective analysis on patients managed within our tertiary-level intestinal rehabilitation program to identify patients with SBS-IF treated with teduglutide from 2009-2015. The current report includes all patients at our center who had any exposure to teduglutide, including those who received commercial drug after approval by the Food and Drug Administration (FDA) and outside the scope of clinical trials. RESULTS: A total of 18 patients were treated with teduglutide. Eleven patients (61%) achieved complete enteral independence from PN and/or intravenous fluids (IV) at a median time of 10 months (range: 3-36 months). PN/IV volume requirement was reduced in all patients except two. Ten of the 11 patients (91%) who achieved enteral autonomy had colon. All patients off PN/IV required additional oral vitamins and electrolyte supplementations. CONCLUSION: Our preliminary experience is consistent with prior reports of successful partial or complete weaning from PN/IV with teduglutide treatment in adult patients with SBS. The presence of colon appears to be favorable in obtaining enteral independence from PN/IV, regardless of residual small bowel length. Patients on teduglutide may remain at high risk of micronutrient deficiencies.
Asunto(s)
Fármacos Gastrointestinales/uso terapéutico , Péptidos/uso terapéutico , Síndrome del Intestino Corto/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND AND AIMS: Patients on parenteral nutrition for short bowel syndrome (SBS) have a high risk of thrombotic complications and are often treated with parenteral anticoagulation. Direct oral anticoagulants are absorbed proximally in the digestive tract and may represent alternative regimens in selected SBS patients. In our pilot study, we provided pharmacokinetics parameters of dabigatran etexilate and rivaroxaban in this setting and compared peak (Cmax), trough (Ctrough) concentrations, and areas-under-the-concentration-time-curve (AUC0-t) to reference values retrieved from phase I-III studies. METHODS: We enrolled 6 adults with a remaining small bowel length≤200cm, normal renal/hepatic function, and intact stomach. In our crossover study, patients were exposed to twice-daily dabigatran etexilate 150mg and once-daily rivaroxaban 20mg. RESULTS: After 5days of dabigatran dosing, Ctrough and Cmax geometric means were 39µg/L (90% CI: 23-66) and 88µg/L (90% CI: 56-137), respectively; AUC0-12h was 958µg∗h/L (90% CI: 635-1445). After 5days of rivaroxaban dosing, Ctrough and Cmax geometric means were 9µg/L (90% CI: 1-71) and 167µg/L (90% CI: 102-276), respectively; AUC0-24h was 1720µg∗h/L (90% CI: 899-3300). Absorption was negligible in one patient with ultra-short (~15cm) bowel. For dabigatran, Cmax ratio was 0.57 (SD 0.33) and Ctrough ratio was 0.35 (SD 0.44). For rivaroxaban, the mean observed-to-reference ratios AUC0-24h and Cmax ratios were 0.73 (SD 0.32) and 0.76 (SD 0.34), respectively. CONCLUSIONS: While in SBS patients there is some absorption of the oral anticoagulants dabigatran etexilate and rivaroxaban, it appears to be lower than reference values. Plasma drug levels showed significant inter-individual variability.
Asunto(s)
Antitrombinas/uso terapéutico , Dabigatrán/uso terapéutico , Nutrición Parenteral/métodos , Rivaroxabán/uso terapéutico , Síndrome del Intestino Corto/tratamiento farmacológico , Adulto , Anciano , Antitrombinas/farmacocinética , Dabigatrán/farmacocinética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Rivaroxabán/farmacocinética , Síndrome del Intestino Corto/patologíaRESUMEN
BACKGROUND: Short bowel syndrome (SBS) is a common indication for home parenteral nutrition (HPN). Oral rehydration solutions (ORSs) have the ability to supplement or reduce HPN dependence. However, ORSs have suffered from poor taste profiles, making long-term consumption and compliance unlikely. The goal of the current study was to assess the taste and compliance of 2 ORSs among patients with SBS requiring HPN. METHODS: All participants with SBS receiving HPN with anticipated duration >3 months were offered enrollment: 31 participants met inclusion criteria; 3 declined enrollment; and 28 were randomized to receive a modified World Health Organization ORS (group A) or a commercially available ORS (DripDrop; group B). RESULTS: Six participants dropped out shortly after randomization (3 in each group) due to poor taste or intolerance. An additional 3 (1 in group A and 2 in group B) discontinued the ORS before the end of the study at 6 months. At the end of the study, 19 remained. The mean taste rating given by the participants was, on a scale of 1-10, 7.3 ± 1.9 for group A and 7.6 ± 1.6 for group B ( P = .61). The mean number of days that ORSs were consumed each week was 6.0 ± 1.3 for group A and 6.6 ± 1 days for group B ( P = .06). CONCLUSION: Taste rating was not different for both ORSs; however, a significant number of participants did not complete the study.
Asunto(s)
Nutrición Parenteral en el Domicilio , Soluciones para Rehidratación/farmacología , Síndrome del Intestino Corto/tratamiento farmacológico , Administración Oral , Adulto , Anciano , Bicarbonatos , Método Doble Ciego , Femenino , Glucosa , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Cloruro de Potasio , Estudios Prospectivos , Calidad de Vida , Cloruro de Sodio , GustoRESUMEN
INTRODUCTION: Glucagon-like peptide-2 (GLP-2) is a known intestinal growth factor that enhances mucosal mass and function in residual small intestine after massive small bowel resection (MSBR). Luminal omega-3 (OM-3) has been shown to have some growth factor properties. It is possible that their mechanisms of action differ. Thus, we hypothesized that administering these two substances together may have a synergistic effect. METHODS: A total of 60 adult female Sprague-Dawley rats underwent 80% MSBR and divided as follows (n = 15/group): Saline (Control) + regular feeds; GLP-2 + regular feeds; Saline + OM-3 enriched feeds; and GLP-2 + OM-3 enriched feeds. Five animals per group were sacrificed at 7, 14, and 28 days. Small intestine mucosa was harvested. DNA and protein content were measured (mucosal mass markers) at all three time points. Galactose and Glycine absorption were measured (functional capacity markers) at 28 days. Statistical analysis was done by ANOVA with post hoc Tukey's HSD test. RESULTS: At all three time points, DNA was increased in all treatment groups compared to control (P < 0.05), but GLP-2 + OM-3 group did not have increased DNA content when compared to either treatments alone. At 7 and 14 d, all three treatment groups had increased protein content compared to control (P < 0.05). At 28 d, GLP-2 + OM-3 did not have increased protein content compared to control or individual treatments (P < 1.0). All three treatment groups had increased absorption of galactose and glycine compared to control (P < 0.05) but not each other. CONCLUSIONS: Individually, GLP-2 and OM-3 are very effective in enhancing the adaptive process by increasing mucosal mass and function, at all three time points. More importantly, clinically, GLP-2 and OM-3 increase substrate absorption in a rat model of intestinal failure. However, the combination is not synergistic.
Asunto(s)
Ácidos Grasos Omega-3/uso terapéutico , Fármacos Gastrointestinales/uso terapéutico , Péptido 2 Similar al Glucagón/uso terapéutico , Síndrome del Intestino Corto/tratamiento farmacológico , Animales , Biomarcadores/metabolismo , ADN/metabolismo , Sinergismo Farmacológico , Quimioterapia Combinada , Ácidos Grasos Omega-3/farmacología , Femenino , Fármacos Gastrointestinales/farmacología , Péptido 2 Similar al Glucagón/farmacología , Absorción Intestinal/efectos de los fármacos , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Intestino Delgado/efectos de los fármacos , Intestino Delgado/metabolismo , Ratas , Ratas Sprague-Dawley , Síndrome del Intestino Corto/metabolismo , Resultado del TratamientoRESUMEN
Vitamin D deficiency is common in patients with intestinal failure and short bowel syndrome who have been weaned of parenteral nutrition. Dietary supplementation with vitamin D is necessary to correct this deficiency. In certain cases, routine supplementation strategy may be ineffective. We report 3 cases of vitamin D deficiency in patients with intestinal failure who showed improvement in serum 25-hydroxyvitamin D levels after supplementation with a loading dose of 20,000-40,000 IU vitamin D provided weekly.
Asunto(s)
Síndrome del Intestino Corto/tratamiento farmacológico , Deficiencia de Vitamina D/tratamiento farmacológico , Vitamina D/administración & dosificación , Niño , Preescolar , Suplementos Dietéticos , Relación Dosis-Respuesta a Droga , Humanos , Masculino , Síndrome del Intestino Corto/complicaciones , Vitamina D/sangre , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/etiologíaRESUMEN
Introduction: Short bowel syndrome (SBS) refers to the malabsorptive state that occurs following extensive intestinal resection and is associated with several complications. Methods: The research for this review was conducted in the Pubmed database. Relevant scientific articles dated between 1991 and 2015 and written in Portuguese, Spanish or English were selected. Results: Several therapies, including nutritional support, pharmacological options and surgical procedures have been used in these patients. Conclusions: Over the last decades new surgical and pharmacological approaches emerged, increasing survival and quality of life (QoL) in patients with SBS. All SBS patients ought to have an individualized and multidisciplinary care that promotes intestinal rehabilitation.
Introdução: A Síndrome do Intestino Curto (SIC) resulta da perda da capacidade de absorção do intestino após resseção intestinal extensa e está associada a diversas complicações. Métodos: Esta revisão foi realizada com base em artigos científicos originais pesquisados na base de dados MEDLINE via Pubmed, na língua portuguesa, inglesa e espanhola, com o limite temporal de 1991 a 2015. Resultados: O tratamento instituído pode ser a nível nutricional, farmacológico ou cirúrgico. Conclusões: Ao longo das últimas décadas surgiram novas abordagens terapêuticas cirúrgicas e não-cirúrgicas que melhoraram a sobrevivência e a qualidade de vida (QoL) destes pacientes. Deve-se estabelecer uma abordagem multidisciplinar e individualizada para garantir a melhor reabilitação.
Asunto(s)
Humanos , Masculino , Femenino , Síndrome del Intestino Corto/cirugía , Síndrome del Intestino Corto/tratamiento farmacológico , Síndrome del Intestino Corto/terapia , Suplementos Dietéticos , Síndrome del Intestino Corto , Síndrome del Intestino Corto/rehabilitación , Síndrome del Intestino Corto/epidemiología , Nutrición Enteral , Nutrición Parenteral en el Domicilio , Colectomía , Adaptación a DesastresRESUMEN
Introducción: la nutrición parenteral (NP) a largo plazo puede asociarse a complicaciones graves, con un deterioro importante de la calidad de vida de los pacientes con síndrome de intestino corto (SIC). La teduglutida, un análogo del péptido-2 similar al glucagón, pertenece a una nueva familia terapéutica y representa el primer abordaje no sintomático del SIC. Objetivos: revisar los datos preclínicos y clínicos en cuanto a eficacia y seguridad de la teduglutida. Resultados: la aprobación de la teduglutida se basó en los resultados de un estudio en fase III de 24 semanas, doble ciego, controlado con placebo (STEPS). Pacientes con fallo intestinal por SIC dependientes de NP ≥ 3 veces/semana durante ≥ 12 meses recibieron 0,05 mg/kg de teduglutida (n = 43) o placebo (n = 43) 1 vez/día. En la semana 24 hubo significativamente más respondedores en el grupo de la teduglutida que en el de placebo (63 s. 30%; p = 0,002). La reducción absoluta media del volumen de NP frente al valor basal en la semana 24 fue significativamente mayor con la teduglutida (4,4 vs. 2,3 l/semana; p < 0,001). La necesidad de NP se redujo ≥ 1 día en la semana 24 en el 54% de pacientes tratados con teduglutida vs. 23% con placebo. Del total de pacientes que recibieron teduglutida en los ensayos en fase III (n = 134), el 12% consiguió una autonomía completa de la NP. Por lo general, la administración subcutánea de teduglutida se toleró bien. Conclusiones: se ha demostrado que teduglutida recupera la absorción intestinal y reduce significativamente la dependencia de la NP, consiguiendo incluso la independencia en algunos pacientes (AU)
Introduction: Long-term Parenteral Support (PS) can be associated with serious complications, with a significant deterioration in the quality of life of patients with short bowel syndrome (SBS). Teduglutide is a recombinant analogue of glucagon-like peptide-2; it belongs to a novel therapeutic family and represents the first non-symptomatic approach against SBS. Objectives: To review the non-clinical and clinical data on efficacy and safety of teduglutide. Results: Teduglutide approval was based on results from a pivotal Phase III, 24-week, double-blind, placebo-controlled study (STEPS). SBS patients dependent on PS ≥ 3 times/week for ≥ 12 months received 0.05 mg/kg teduglutide (n = 43) or placebo (n = 43) 1 time/day. At week 24 there were signifi cantly more responders in the teduglutide group vs. placebo (63 vs. 30%; p = 0.002). The overall mean reduction vs. PS baseline volume at week 24 was significantly higher with teduglutide vs. placebo (4.4 vs. 2.3 l/ week, p < 0.001). At week 24 the need for PS was reduced in at least 1 day in 54% of patients treated with teduglutide vs. 23% with placebo. Of the total of patients who received teduglutide in phase III trials (n = 134), 12% achieved complete autonomy from PS. Subcutaneous teduglutide was generally well tolerated. Conclusions: Teduglutide has been shown to enhance intestinal absorptive capacity and signifi cantly reduce PS dependency, even achieving independency in some patients (AU)