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BACKGROUND & AIMS: There is a need to develop safe and effective pharmacologic options for the treatment of celiac disease (CeD); however, consensus on the appropriate design and configuration of randomized controlled trials (RCTs) in this population is lacking. METHODS: A 2-round modified Research and Development/University of California Los Angeles Appropriateness Method study was conducted. Eighteen gastroenterologists (adult and pediatric) and gastrointestinal pathologists voted on statements pertaining to the configuration of CeD RCTs, inclusion and exclusion criteria, gluten challenge, and trial outcomes. Two RCT designs were considered, representing the following distinct clinical scenarios for which pharmacotherapy may be used: trials incorporating a gluten challenge to simulate exposure; and trials evaluating reversal of histologic changes, despite attempted adherence to a gluten-free diet. Each statement was rated as appropriate, uncertain, or inappropriate, using a 9-point Likert scale. RESULTS: For trials evaluating prevention of relapse after gluten challenge, participants adherent to a gluten-free diet for 12 months or more with normal or near-normal-sized villi should be enrolled. Gluten challenge should be FODMAPS (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) free, and efficacy evaluated using histology with a secondary patient-reported outcome measure. For trials evaluating reversal of villus atrophy, the panel voted it appropriate to enroll participants with a baseline villus height to crypt depth ratio ≤2 and measure efficacy using a primary histologic end point. Guidance for measuring histologic, endoscopic, and patient-reported outcomes in adult and pediatric patients with CeD are provided, along with recommendations regarding the merits and limitations of different end points. CONCLUSIONS: We developed standardized recommendations for clinical trial design, eligibility criteria, outcome measures, gluten challenge, and disease evaluations for RCTs in patients with CeD.
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Enfermedad Celíaca , Adulto , Humanos , Niño , Enfermedad Celíaca/patología , Recurrencia Local de Neoplasia , Ensayos Clínicos Controlados Aleatorios como Asunto , Glútenes/efectos adversos , Dieta Sin GlutenRESUMEN
BACKGROUND: Gastroduodenal endoscopy and biopsy following positive specific serology is considered the gold standard to diagnose celiac disease (CeD) in adults. Whether upper endoscopy helps detect comorbid conditions is unknown. AIM: To investigate the prevalence of non-celiac endoscopic findings in patients in whom endoscopy was performed to confirm CeD diagnosis. METHODS: This is an observational, descriptive, multicenter, retrospective study that reports endoscopic findings obtained in adult patients enrolled in local registries from four tertiary centers. We collected data reported on first endoscopy, indicated for investigation of CeD. Diagnosis of CeD was performed by histology (≥ Marsh 2 type mucosal damage) and specific serology. Two European and one North American center included biopsy-confirmed CeD following positive serology. A fourth center (South America) included symptomatic patients undergoing endoscopy, irrespective of CeD serology. The latter cohort included a non-CeD control group. RESULTS: A total of 1328 patients (80% female; 35 years median age) were enrolled, of whom 95.6% had positive specific serology. In 135 patients, endoscopy revealed 163 abnormalities unrelated to CeD (prevalence: 10.1%). Erosive reflux esophagitis (6.4%), gastric erosions (2.0%), and suspicion of esophageal metaplasia (1.2%) were the most common findings. Biopsy-confirmed Barrett's esophagus was infrequent (0.2%). No endoscopic cancer was detected. Older patients (≥ 51 years of age) had a higher prevalence of endoscopic findings than those ≤ 50 (P < 0.01). Within the South American cohort, CeD was associated with a lower rate (8.2%) of comorbid endoscopic findings compared with controls (29.1%; P < 0.001). In the adjusted multivariate analysis of this cohort, having CeD was associated with a 72% reduction in the risk of any endoscopic abnormality (P < 0.0001), and having alarm symptoms was associated with a 37% reduction in the risk of finding at least one endoscopic lesion (P < 0.02). CONCLUSION: In this large multicenter study, young adults with positive CeD serology had few comorbid endoscopic findings. Although patients over 51 years had a high prevalence of non-CeD gastroduodenal mucosal damage, no malignancy or premalignant lesions were found.
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Enfermedad Celíaca , Humanos , Femenino , Masculino , Enfermedad Celíaca/diagnóstico , Enfermedad Celíaca/epidemiología , Estudios Retrospectivos , América del SurRESUMEN
Background & Aims. Postoperative weight loss is common following hepato-pancreato-biliary (HPB) surgical resections; however, the extent of weight loss and the association with poor outcomes have not been well described. We assessed the average percentage of weight loss and risk factors associated with sustained postoperative weight loss. Materials and Methods. We enrolled patients undergoing major HPB surgical resections from 2011-2016 at a single institution. We evaluated percent change in weight postoperatively, incidence of complications, and nutritional clinical markers at 1, 3, and 6 months postoperatively compared to preoperative baseline. We used multiple logistic regression to evaluate factors associated with significant weight loss (>10% from baseline) at 3 months from surgery. Results. Among 262 patients undergoing HPB surgery, liver surgery patients lost 2.5% of baseline weight at 3 months postoperatively but regained baseline weight by 6 months. Pancreatic surgery patients lost 7.7% at 3 months and were unable to recover their baseline weights at 6 months. Forty-three (16%) patients had major postoperative complications including abdominal abscess (5.3%) and anastomotic leak (3.8%). Patients who experienced major postoperative complications had a greater percentage weight loss at 3 months compared to those without major complications: median 11% (interquartile range (IQR): 7%-15%) vs 4% (IQR: 0%-8%), P < .001. In the multivariable analysis, major postoperative complications were associated with significant weight loss at 3 months (OR 3.39, 95% CI 1.38-8.33). Conclusions. Due to the association of weight loss and major postoperative complications, patients who experience significant weight loss (>10% from baseline) may benefit from nutritional assessment for dietary intervention.
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Procedimientos Quirúrgicos del Sistema Biliar , Procedimientos Quirúrgicos del Sistema Digestivo , Procedimientos Quirúrgicos del Sistema Biliar/efectos adversos , Procedimientos Quirúrgicos del Sistema Digestivo/efectos adversos , Humanos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Pérdida de PesoRESUMEN
Gluten free diet is the only available treatment for celiac disease (CeD). Patients with CeD who do not adhere to a strict gluten-free diet (GFD) have been found to have complications involving nutritional deficiencies, increased risk of bone fractures, increased risk of mortality, and certain types of cancers. Complete removal of gluten from the diet in a patient with CeD often results in symptomatic, serologic, and histologic remission. However, strict compliance with the diet is challenging. Long-term follow-up care is needed to assure treatment compliance and positive health outcomes. Monitoring celiac specific serology, nutrient deficiencies, bone mineral density, and assessment of GFD compliance have been recommended in clinical practice. However, there is no consensus on which specific tests and how often they should be performed during the follow up. Here, we have performed a review of the literature on current strategies to follow up patients with CeD. There are new tools for monitoring adherence to the GFD which could change some paradigms in following up treated patients.
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In the last 30 years, non-celiac gluten sensitivity (NCGS) has emerged as an intriguing and controversial topic in gastroenterology. The diagnosis of NCGS/NCWS requires a symptomatic reaction to gluten, or wheat-containing food, and remission of symptoms with gluten or wheat challenge, in patients in whom celiac disease and wheat allergy have been excluded. There have been several randomized clinical trials (RCT) addressing this issue which have produced controversial results. In this issue of Neurogastroenterology and Motility, a double-blind placebo-controlled randomized trial in patients with suspected NCGS on GFD, did not reproduce symptoms after gluten intake compared to placebo. This mini-review addresses outstanding issues related to the diagnosis of NCGS/NCWS as well as areas of interest for future studies that could explain, in part, the controversy in this area.
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Enfermedad Celíaca/diagnóstico , Hipersensibilidad al Trigo/diagnóstico , Glútenes , Humanos , TriticumRESUMEN
BACKGROUND: We have previously shown a reduction of gastrointestinal symptoms after the oral administration of Bifidobacterium infantis Natren Life Start super strain (NLS-SS) in untreated celiac disease (CD) patients. The symptomatic improvement was not associated with changes in intestinal permeability or serum levels of cytokines, chemokines, or growth factors. Therefore, we hypothesized that the beneficial symptomatic effect observed previously in patients with CD treated with B. infantis may be related to the modulation of innate immunity. GOALS: To investigate the potential mechanisms of a probiotic B. infantis Natren Life Start super strain on the mucosal expression of innate immune markers in adult patients with active untreated CD compared with those treated with B. infantis×6 weeks and after 1 year of gluten-free diet (GFD). METHODS: Numbers of macrophages and Paneth cells and α-defensin-5 expression were assessed by immunohistochemistry in duodenal biopsies. RESULTS: We showed that GFD decreases duodenal macrophage counts in CD patients more effectively than B. infantis. In contrast, B. infantis decreases Paneth cell counts and expression of α-defensin-5 in CD (P<0.001). CONCLUSIONS: The results identify differential innate immune effects of treatment with B. infantis compared with 1 year of GFD. Further studies are needed to investigate synergistic effects of GFD and B. infantis supplementation in CD.
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Bifidobacterium longum subspecies infantis/crecimiento & desarrollo , Enfermedad Celíaca/terapia , Dieta Sin Gluten , Duodeno/metabolismo , Inmunidad Innata , Inmunidad Mucosa , Mucosa Intestinal/metabolismo , Probióticos/uso terapéutico , alfa-Defensinas/metabolismo , Adulto , Biomarcadores/metabolismo , Biopsia , Enfermedad Celíaca/inmunología , Enfermedad Celíaca/metabolismo , Enfermedad Celíaca/microbiología , Regulación hacia Abajo , Duodeno/inmunología , Duodeno/microbiología , Femenino , Microbioma Gastrointestinal , Humanos , Inmunohistoquímica , Mucosa Intestinal/inmunología , Mucosa Intestinal/microbiología , Macrófagos/inmunología , Macrófagos/metabolismo , Macrófagos/microbiología , Masculino , Persona de Mediana Edad , Células de Paneth/inmunología , Células de Paneth/metabolismo , Células de Paneth/microbiología , Probióticos/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenAsunto(s)
Enfermedad Celíaca/diagnóstico , Proteínas de Unión al GTP/inmunología , Gliadina/inmunología , Inmunoglobulina A/inmunología , Inmunoglobulina G/inmunología , Guías de Práctica Clínica como Asunto , Transglutaminasas/inmunología , Adulto , Enfermedad Celíaca/genética , Enfermedad Celíaca/inmunología , Estudios de Cohortes , Antígenos HLA-DQ/genética , Humanos , Estudios Prospectivos , Proteína Glutamina Gamma Glutamiltransferasa 2 , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Alterations in the intestinal microbiota, characterized by depletion of anti-inflammatory bacteria, such as Firmicutes, in patients with ulcerative colitis (UC) have prompted interest in microbiota-modulating strategies for this condition. The aim of this study was to evaluate the role of fecal and synthetic human microbial ecosystems, low or enriched in Firmicutes, on colitis susceptibility and host immune responses. METHODS: The microbiota of selected healthy and UC human donors was characterized by culture method and 16S rRNA-based sequencing. Germ-free mice were colonized with fecal or a synthetic ecosystem enriched (healthy donors) or low (UC donors) in Firmicutes. Experimental colitis was induced using dextran sodium sulfate. Colon transcriptome and colon lamina propria cells were evaluated in mice postcolonization by RNA-seq and flow cytometry, respectively, and T helper (TH) 17 differentiation was assessed in vitro. RESULTS: Mice colonized with microbiota from patients with UC low in Firmicutes had increased sensitivity to colitis compared with mice colonized with fecal or synthetic ecosystems rich in Firmicutes. Microbiota low in Firmicutes increased expression of TH17-related genes and expansion of interleukin-17A-expressing CD4 cells in vivo. Supplementation with bacterial isolates belonging to the Firmicutes phylum abrogated the heightened TH17 responses in vitro. CONCLUSIONS: A microbiota rich in Firmicutes derived from fecal samples of a healthy human donor, or assembled synthetically, downregulated colonic inflammation and TH17 pathways in mice. The results support the use of ecobiotherapy strategies, enriched in Firmicutes, for the prevention or treatment of UC.
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Colitis/inmunología , Colitis/prevención & control , Modelos Animales de Enfermedad , Heces/microbiología , Firmicutes/fisiología , Vida Libre de Gérmenes , Animales , Diferenciación Celular , Colitis/microbiología , Susceptibilidad a Enfermedades , Femenino , Citometría de Flujo , Humanos , Mucosa Intestinal/microbiología , Masculino , Ratones , Ratones Endogámicos C57BL , MicrobiotaRESUMEN
INTRODUCCION: Aunque la enfermedad celíaca (EC) se asocia comúnmente a diarrea crónica, 10% de los casos pueden presentarse con constipación crónica (CC). No hay estudios que exploren la prevalencia de EC o marcadores potenciales de la sensibilidad al gluten (SG) en pacientes que consultan por CC.OBJETIVO: Determinar la prevalencia de marcadores potenciales de SG y EC en pacientes con CC que consultan a un centro terciario de referencia.METODOS: Estudio exploratorio prospectivo. Se evaluó a 121 pacientes adultos consecutivos con diagnóstico de CC funcional (67,8%) o SII-C (criterios de Roma III) con anticuerpos contra péptidos deamidados de gliadina IgA e IgG y anti-transglutaminasa tisular (DGP/tTGscreen valor corte=20). Los casos seropositivos fueron analizados con IgA tTG y todos los DGP/tTG Screen casos positivos se sometieron a biopsias endoscópicas de duodeno. La prevalencia se comparó con la de 518 sujetos (endoscopía digestiva alta por síntomas no relacionados primariamente con EC) y con la estimada para la población urbana del Gran La Plata. Se consideró diagnóstico de EC a la presencia de una enteropatía Marsh Illa o mayor en los casos seropositivos. Se consideró SG a los casos seropositivos sin enteropatía ni autoanticuerpos (IgA tTG).RESULTADOS: 10 pacientes (8,3%) y 46 sujetos del grupo control (8,9%) con CC tuvieron resultados positivos DGP/tTG Screen. 3 pacientes seropositivos con CC y 14 controles presentaron biopsia compatible con EC. Se estimó una prevalencia de 2,5% para los pacientes con CC y 2,7% para los controles. La prueba de IgA tTG fue positiva en 5 de los 10 pacientes con CC (incluidos los 2 casos diagnosticados con EC) y en 13 controles (100% y 92% de sensibilidad, respectivamente), 5 pacientes con CC fueron considerados como SG.CONCLUSIONES: Este estudio fue el primero en determinar la prevalencia en EC y SG en pacientes con CC, la cual resultó casi cuatro veces mayor que la estimada para la población general de Argentina (1/133).
INTRODUCTION: Celiac disease (CD) diagnosis is strongly associated with the presence of chronic diarrhea, but up to 10% of newly diagnosed cases may complain of chronic constipation (CC). No studies have explored the prevalence of CD or potential markers of gluten sensitivity among patients consulting for CC.OBJECTIVE: TO determine the prevalence of potential markers of gluten sensitivity and CD in a series of consecutive patients with chronic constipation attending a tertiary referral center.METHODS: An exploratory study was conducted at Gastroenterology Hospital of Buenos Aires. 121 adult consecutive patients with diagnosis of chronic constipation (67.8%) or IBS-C (Rome III criteria) were assessed for antibodies to deamidatedgliadin peptides IgA and IgG and tissue transglutaminase (DGP/tTG Screen cut-off: 20 U/mL). Seropositive cases were tested (IgA tTG) and all DGP/tTG Screen positive cases underwent duodenal biopsies. Prevalece was compared with that obtained from a control population of 518 subjects (upper endoscopy due to symptoms not primarily related to CD). Type Illa Marshs enteropathy or greater in seropositive cases was considered as CD diagnosis.RESULTS: 10 patients (8.3%) and 46 controls (8.9%) with CC had a positive DGP/tTGScreen test. 3 seropositive patients with CC and 14 controls had a CD compatible biopsy. The IgA tTG test was positive in 5 of the 10 patients with CC (including those 3 cases finally diagnosed with CD) and in 13 from control population (100% and 92% sensitivity, respectively). 5 patients with CC were considered as gluten sensitive (serology positive, but no enteropathy).CONCLUSIONS: This study was the first to determine a higher prevalence of CD and gluten sensitivity in patients complaining of CC. This prevalence was almost four times greater than that estimated for the general Argentinean population (1/133).
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Enfermedad Celíaca , Estreñimiento , Glútenes/efectos adversos , Salud Pública , ArgentinaRESUMEN
INTRODUCCION: Aunque la enfermedad celíaca (EC) se asocia comúnmente a diarrea crónica, 10% de los casos pueden presentarse con constipación crónica (CC). No hay estudios que exploren la prevalencia de EC o marcadores potenciales de la sensibilidad al gluten (SG) en pacientes que consultan por CC.OBJETIVO: Determinar la prevalencia de marcadores potenciales de SG y EC en pacientes con CC que consultan a un centro terciario de referencia.METODOS: Estudio exploratorio prospectivo. Se evaluó a 121 pacientes adultos consecutivos con diagnóstico de CC funcional (67,8%) o SII-C (criterios de Roma III) con anticuerpos contra péptidos deamidados de gliadina IgA e IgG y anti-transglutaminasa tisular (DGP/tTGscreen valor corte=20). Los casos seropositivos fueron analizados con IgA tTG y todos los DGP/tTG Screen casos positivos se sometieron a biopsias endoscópicas de duodeno. La prevalencia se comparó con la de 518 sujetos (endoscopía digestiva alta por síntomas no relacionados primariamente con EC) y con la estimada para la población urbana del Gran La Plata. Se consideró diagnóstico de EC a la presencia de una enteropatía Marsh Illa o mayor en los casos seropositivos. Se consideró SG a los casos seropositivos sin enteropatía ni autoanticuerpos (IgA tTG).RESULTADOS: 10 pacientes (8,3%) y 46 sujetos del grupo control (8,9%) con CC tuvieron resultados positivos DGP/tTG Screen. 3 pacientes seropositivos con CC y 14 controles presentaron biopsia compatible con EC. Se estimó una prevalencia de 2,5% para los pacientes con CC y 2,7% para los controles. La prueba de IgA tTG fue positiva en 5 de los 10 pacientes con CC (incluidos los 2 casos diagnosticados con EC) y en 13 controles (100% y 92% de sensibilidad, respectivamente), 5 pacientes con CC fueron considerados como SG.CONCLUSIONES: Este estudio fue el primero en determinar la prevalencia en EC y SG en pacientes con CC, la cual resultó casi cuatro veces mayor que la estimada para la población general de Argentina (1/133).
INTRODUCTION: Celiac disease (CD) diagnosis is strongly associated with the presence of chronic diarrhea, but up to 10% of newly diagnosed cases may complain of chronic constipation (CC). No studies have explored the prevalence of CD or potential markers of gluten sensitivity among patients consulting for CC.OBJECTIVE: TO determine the prevalence of potential markers of gluten sensitivity and CD in a series of consecutive patients with chronic constipation attending a tertiary referral center.METHODS: An exploratory study was conducted at Gastroenterology Hospital of Buenos Aires. 121 adult consecutive patients with diagnosis of chronic constipation (67.8%) or IBS-C (Rome III criteria) were assessed for antibodies to deamidatedgliadin peptides IgA and IgG and tissue transglutaminase (DGP/tTG Screen cut-off: 20 U/mL). Seropositive cases were tested (IgA tTG) and all DGP/tTG Screen positive cases underwent duodenal biopsies. Prevalece was compared with that obtained from a control population of 518 subjects (upper endoscopy due to symptoms not primarily related to CD). Type Illa Marshs enteropathy or greater in seropositive cases was considered as CD diagnosis.RESULTS: 10 patients (8.3%) and 46 controls (8.9%) with CC had a positive DGP/tTGScreen test. 3 seropositive patients with CC and 14 controls had a CD compatible biopsy. The IgA tTG test was positive in 5 of the 10 patients with CC (including those 3 cases finally diagnosed with CD) and in 13 from control population (100% and 92% sensitivity, respectively). 5 patients with CC were considered as gluten sensitive (serology positive, but no enteropathy).CONCLUSIONS: This study was the first to determine a higher prevalence of CD and gluten sensitivity in patients complaining of CC. This prevalence was almost four times greater than that estimated for the general Argentinean population (1/133).