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INTRODUCTION: Celiac disease is an autoimmune condition that affects approximately 1% of the population worldwide. Although its main impact often concerns the small intestine, resulting in villous atrophy and nutrient malabsorption, it can also cause systemic manifestations, particularly when undiagnosed or left untreated. METHOD: Attention is directed to the possible psychological, psychiatric, and organic brain manifestations of celiac disease. Specific topics related to the influence and risk of such manifestations with respect to celiac disease are defined and discussed. Overall, eighteen main topics are considered, sifted from over 500 references. RESULTS: The most often studied topics were found to be the effect on quality of life, organic brain dysfunction and ataxia, epilepsy, Down syndrome, generalized psychological disorders, eating dysfunction, depression, and schizophrenia. For most every topic, although many studies report a connection to celiac disease, there are often one or more contrary studies and opinions. A bibliographic analysis of the cited articles was also done. There has been a sharp increase in interest in this research since 1990. Recently published articles tend to receive more referencing, up to as many as 15 citations per year, suggesting an increasing impact of the topics. The number of manuscript pages per article has also tended to increase, up to as many as 12 pages. The impact factor of the publishing journal has remained level over the years. CONCLUSION: This compendium may be useful in developing a consensus regarding psychological, psychiatric, and organic brain manifestations that can occur in celiac disease and for determining the best direction for ongoing research focus.
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BACKGROUND & AIMS: Gluten challenge is used to diagnose celiac disease (CeD) and for clinical research. Sustained gluten exposure reliably induces histologic changes but is burdensome. We investigated the relative abilities of multiple biomarkers to assess disease activity induced by 2 gluten doses, and aimed to identify biomarkers to supplement or replace histology. METHODS: In this randomized, double-blind, 2-dose gluten-challenge trial conducted in 2 US centers (Boston, MA), 14 adults with biopsy-proven CeD were randomized to 3 g or 10 g gluten/d for 14 days. The study was powered to detect changes in villous height to crypt depth, and stopped at planned interim analysis on reaching this end point. Additional end points included gluten-specific cluster of differentiation (CD)4 T-cell analysis with HLA-DQ2-gluten tetramers and enzyme-linked immune absorbent spot, gut-homing CD8 T cells, interleukin-2, symptoms, video capsule endoscopy, intraepithelial leukocytes, and tissue multiplex immunofluorescence. RESULTS: All assessments showed changes with gluten challenge. However, time to maximal change, change magnitude, and gluten dose-response relationship varied. Villous height to crypt depth, video capsule endoscopy enteropathy score, enzyme-linked immune absorbent spot, gut-homing CD8 T cells, intraepithelial leukocyte counts, and HLA-DQ2-restricted gluten-specific CD4 T cells showed significant changes from baseline at 10 g gluten only; symptoms were significant at 3 g. Symptoms and plasma interleukin-2 levels increased significantly or near significantly at both doses. Interleukin-2 appeared to be the earliest, most sensitive marker of acute gluten exposure. CONCLUSIONS: Modern biomarkers are sensitive and responsive to gluten exposure, potentially allowing less invasive, lower-dose, shorter-duration gluten ingestion. This work provides a preliminary framework for rational design of gluten challenge for CeD research. ClinicalTrials.gov number, NCT03409796.
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Enfermedad Celíaca/diagnóstico , Glútenes/administración & dosificación , Pruebas Inmunológicas/métodos , Adulto , Biomarcadores/sangre , Linfocitos T CD4-Positivos/inmunología , Enfermedad Celíaca/sangre , Enfermedad Celíaca/inmunología , Método Doble Ciego , Ensayo de Inmunoadsorción Enzimática , Femenino , Glútenes/inmunología , Antígenos HLA-DQ/sangre , Antígenos HLA-DQ/inmunología , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND & AIMS: Guidelines advise measurement of bone mineral density (BMD) in patients with a diagnosis of celiac disease. The lumbar spine (LS) and hip sites are usually measured. Although skeletal sites rich in trabecular bone are believed to be vulnerable to osteoporosis in patients with celiac disease, most studies have not measured the cortical distal 1/3-radius. METHODS: We collected data from 721 patients (mean age, 43.6 years; 68.4% female) with celiac disease who underwent 3-site dual energy x-ray absorptiometry (DXA, at a median 1.22 years after diagnosis). We assessed skeletal site- and sex-specific osteoporosis prevalence and the incremental utility of 1/3-radius measurement by DXA. RESULTS: Mean T- and Z-scores were normal in patients, but 43.3% had osteopenia and 19.6% had osteoporosis. Osteoporosis was found in 12.1% of patients at the LS, 5.3% of patients at the total hip, 7.6% of patients at the femoral neck, and 11.5% of patients at the 1/3-radius. A greater degree of villous atrophy at diagnosis was associated with male sex and lower T-scores at the 1/3-radius (P = .03), but not other skeletal sites. Isolated forearm osteoporosis was detected in 4.9% of patients. A higher proportion of patients with isolated forearm osteoporosis were male and had a greater weight and body mass index (all P < .01, compared to patients with osteoporosis only at other sites). Z-scores were lower at the LS and 1/3-radius and osteoporosis was more common in men than women. In men, the 1/3-radius was the most frequent site for osteoporosis. Among patients 50 years or older, isolated forearm osteoporosis was present in 10.7%. CONCLUSIONS: Based on DXA analysis of patients with celiac disease, the prevalence of osteoporosis appears to be underestimated-particularly in men when BMD at the 1/3-radius is not measured. Degree of villous atrophy is associated with BMD at the 1/3-radius and nearly 5% of patients have osteoporosis limited to that site. Recommendations for osteoporosis screening in patients with celiac disease should include measurement of the distal 1/3-radius in addition to the hip and LS.
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Absorciometría de Fotón , Densidad Ósea , Enfermedad Celíaca/complicaciones , Osteoporosis/diagnóstico , Radio (Anatomía)/diagnóstico por imagen , Adulto , Femenino , Antebrazo , Humanos , Masculino , Persona de Mediana Edad , Osteoporosis/diagnóstico por imagen , Osteoporosis/epidemiología , Osteoporosis/etiología , PrevalenciaRESUMEN
Indolent T-cell lymphoproliferative disorders of the gastrointestinal tract are rare clonal T-cell diseases that more commonly occur in the intestines and have a protracted clinical course. Different immunophenotypic subsets have been described, but the molecular pathogenesis and cell of origin of these lymphocytic proliferations is poorly understood. Hence, we performed targeted next-generation sequencing and comprehensive immunophenotypic analysis of ten indolent T-cell lymphoproliferative disorders of the gastrointestinal tract, which comprised CD4+ (n=4), CD8+ (n=4), CD4+/CD8+ (n=1) and CD4-/CD8- (n=1) cases. Genetic alterations, including recurrent mutations and novel rearrangements, were identified in 8/10 (80%) of these lymphoproliferative disorders. The CD4+, CD4+/CD8+, and CD4-/CD8- cases harbored frequent alterations of JAK-STAT pathway genes (5/6, 82%); STAT3 mutations (n=3), SOCS1 deletion (n=1) and STAT3-JAK2 rearrangement (n=1), and 4/6 (67%) had concomitant mutations in epigenetic modifier genes (TET2, DNMT3A, KMT2D). Conversely, 2/4 (50%) of the CD8+ cases exhibited structural alterations involving the 3' untranslated region of the IL2 gene. Longitudinal genetic analysis revealed stable mutational profiles in 4/5 (80%) cases and acquisition of mutations in one case was a harbinger of disease transformation. The CD4+ and CD4+/CD8+ lymphoproliferative disorders displayed heterogeneous Th1 (T-bet+), Th2 (GATA3+) or hybrid Th1/Th2 (T-bet+/GATA3+) profiles, while the majority of CD8+ disorders and the CD4-/CD8- disease showed a type-2 polarized (GATA3+) effector T-cell (Tc2) phenotype. Additionally, CD103 expression was noted in 2/4 CD8+ cases. Our findings provide insights into the pathogenetic bases of indolent T-cell lymphoproliferative disorders of the gastrointestinal tract and confirm the heterogeneous nature of these diseases. Detection of shared and distinct genetic alterations of the JAK-STAT pathway in certain immunophenotypic subsets warrants further mechanistic studies to determine whether therapeutic targeting of this signaling cascade is efficacious for a proportion of patients with these recalcitrant diseases.
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Trastornos Linfoproliferativos , Linfocitos T , Tracto Gastrointestinal , Humanos , Inmunofenotipificación , Trastornos Linfoproliferativos/diagnóstico , Trastornos Linfoproliferativos/genética , FenotipoRESUMEN
Celiac disease is a genetically determined disorder of the small intestine, occurring due to an immune response to ingested gluten-containing food. The resulting damage to the small intestinal mucosa hampers nutrient absorption, and is characterized by diarrhea, abdominal pain, and a variety of extra-intestinal manifestations. Invasive and costly methods such as endoscopic biopsy are currently used to diagnose celiac disease. Detection of the disease by histopathologic analysis of biopsies can be challenging due to suboptimal sampling. Video capsule images were obtained from celiac patients and controls for comparison and classification. This study exploits the use of DAISY descriptors to project two-dimensional images onto one-dimensional vectors. Shannon entropy is then used to extract features, after which a particle swarm optimization algorithm coupled with normalization is employed to select the 30 best features for classification. Statistical measures of this paradigm were tabulated. The accuracy, positive predictive value, sensitivity and specificity obtained in distinguishing celiac versus control video capsule images were 89.82%, 89.17%, 94.35% and 83.20% respectively, using the 10-fold cross-validation technique. When employing manual methods rather than the automated means described in this study, technical limitations and inconclusive results may hamper diagnosis. Our findings suggest that the computer-aided detection system presented herein can render diagnostic information, and thus may provide clinicians with an important tool to validate a diagnosis of celiac disease.
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Endoscopía Capsular/métodos , Enfermedad Celíaca/diagnóstico , Procesamiento de Imagen Asistido por Computador/métodos , Algoritmos , Endoscopía Capsular/normas , Enfermedad Celíaca/diagnóstico por imagen , Enfermedad Celíaca/patología , Humanos , Mucosa Intestinal/patología , Sensibilidad y EspecificidadRESUMEN
GOALS: This study aimed to investigate follow-up patterns among celiac disease (CD) patients. BACKGROUND: Gender factors are important in CD with women diagnosed more frequently than men despite equal seropositivity in screening studies. To determine if gender influences postdiagnosis care, we performed a retrospective cohort study investigating the impact of gender and mode of presentation on follow-up patterns after diagnosis. STUDY: The study included adults with biopsy-proven CD presenting to a single tertiary care center between 2005 and 2014. The primary exposure was at least 1 visit with a CD specialist. The primary outcome was ≥2 follow-up visits, including office visits and endoscopic procedures. Data extracted included whether patients had tissue transglutaminase antibodies performed by our laboratory. RESULTS: We analyzed 708 patients of which 70.5% were female. Follow-up was good with a majority of patients (69%) having at least 1 follow-up visit. On bivariate analysis, patients least likely to follow-up were ages 18 to 29 (P=0.03) and women with atypical presentations (P=0.003). After adjusting for potential confounders, individuals over age 65 were significantly more likely to attend at least 2 follow-up visits (odds ratio, 2.07; 95% confidence interval, 1.21-3.55; P=0.0079). Individuals with an abnormal baseline tissue transglutaminase antibody value in our laboratory were significantly more likely to follow-up (odds ratio, 1.99; 95% confidence interval, 1.39-2.85; P=0.0002). CONCLUSIONS: Gender had no impact on follow-up patterns despite prior studies demonstrating an impact on diagnosis rates. Future attention should focus on retaining young patients and those with atypical modes of presentation.
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Cuidados Posteriores/estadística & datos numéricos , Enfermedad Celíaca/terapia , Proteínas de Unión al GTP/inmunología , Visita a Consultorio Médico/estadística & datos numéricos , Transglutaminasas/inmunología , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Biopsia , Enfermedad Celíaca/diagnóstico , Estudios de Cohortes , Endoscopía/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteína Glutamina Gamma Glutamiltransferasa 2 , Estudios Retrospectivos , Factores Sexuales , Centros de Atención Terciaria , Adulto JovenRESUMEN
BACKGROUND: Patients with celiac disease and inflammatory bowel disease, two immune-mediated luminal conditions, have higher rates of certain infections than healthy counterparts. The prevalence of many gastrointestinal infections in these patients, however, is unknown. AIMS: Using a novel clinical stool pathogen PCR test, we investigated the hypothesis that patients with celiac disease/inflammatory bowel disease had different distributions of diarrheal pathogens than other patients. METHODS: We performed a retrospective cohort study of outpatients who underwent stool pathogen testing with the FilmArray Gastrointestinal PCR Panel (BioFire Diagnostics, Salt Lake City, UT) at our institution from January 1 to December 31, 2015. Rates of pathogens were measured in patients with or without celiac disease/inflammatory bowel disease. RESULTS: Of 955 patients, 337 had positive test for any pathogen, with 465 bacterial, parasitic, or viral pathogens identified. One hundred and twenty-seven patients (13.3%) had celiac disease or inflammatory bowel disease, of which 29/127 (22.8%) had a positive test, compared to 308/828 other patients (37.2%) (p = 0.002). Patients with celiac disease/inflammatory bowel disease had significantly fewer viruses (1.6 vs. 8.1% of patients; p = 0.008) and parasites (0 vs. 3.3%; p = 0.039), with nonsignificant trend toward fewer bacteria (21.3 vs. 29.2%; p = 0.063). Escherichia coli species were most common in both populations. CONCLUSIONS: Stool PCR identified numerous pathogens in patients with or without celiac disease/inflammatory bowel disease. Patients with celiac disease/inflammatory bowel disease were significantly less likely to have any pathogen identified, and had significantly fewer viruses and parasites. In this population, knowledge of common pathogens can guide diagnostic evaluation and offer opportunities for treatment.
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Enfermedad Celíaca/epidemiología , Enfermedad Celíaca/microbiología , Diarrea/microbiología , Heces/microbiología , Enfermedades Inflamatorias del Intestino/epidemiología , Enfermedades Inflamatorias del Intestino/microbiología , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Enfermedad Celíaca/diagnóstico , Femenino , Humanos , Enfermedades Inflamatorias del Intestino/diagnóstico , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Adulto JovenRESUMEN
PURPOSE: Truncating mutations in the maternally imprinted, paternally expressed gene MAGEL2, which is located in the Prader-Willi critical region 15q11-13, have recently been reported to cause Schaaf-Yang syndrome, a Prader-Willi-like disease that manifests as developmental delay/intellectual disability, hypotonia, feeding difficulties, and autism spectrum disorder. The causality of the reported variants in the context of the patients' phenotypes was questioned, as MAGEL2 whole-gene deletions seem to cause little or no clinical phenotype. METHODS: Here we report a total of 18 newly identified individuals with Schaaf-Yang syndrome from 14 families, including 1 family with 3 individuals found to be affected with a truncating variant of MAGEL2, 11 individuals who are clinically affected but were not tested molecularly, and a presymptomatic fetal sibling carrying the pathogenic MAGEL2 variant. RESULTS: All cases harbor truncating mutations of MAGEL2, and nucleotides c.1990-1996 arise as a mutational hotspot, with 10 individuals and 1 fetus harboring a c.1996dupC (p.Q666fs) mutation and 2 fetuses harboring a c.1996delC (p.Q666fs) mutation. The phenotypic spectrum of Schaaf-Yang syndrome ranges from fetal akinesia to neurobehavioral disease and contractures of the small finger joints. CONCLUSION: This study provides strong evidence for the pathogenicity of truncating mutations of the paternal allele of MAGEL2, refines the associated clinical phenotypes, and highlights implications for genetic counseling for affected families.Genet Med 19 1, 45-52.
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Trastorno del Espectro Autista/genética , Discapacidades del Desarrollo/genética , Discapacidad Intelectual/genética , Síndrome de Prader-Willi/genética , Proteínas/genética , Adolescente , Adulto , Trastorno del Espectro Autista/fisiopatología , Niño , Preescolar , Cromosomas Humanos Par 15 , Discapacidades del Desarrollo/fisiopatología , Femenino , Expresión Génica , Impresión Genómica , Humanos , Lactante , Recién Nacido , Discapacidad Intelectual/fisiopatología , Masculino , Mutación , Fenotipo , Síndrome de Prader-Willi/fisiopatologíaRESUMEN
Primary gastrointestinal (GI) T- and NK-cell lymphomas are usually aggressive neoplasms associated with high morbidity and mortality. Over the past two decades, however, cases of primary GI lymphoproliferative disorders (LPDs) or lymphomas of T- or NK-cell derivation with indolent behavior have been reported. These LPDs are rare and they can be challenging to diagnose as they share clinical and pathological features with both, inflammatory disorders and aggressive T- and NK-cell lymphomas. Primary, indolent clonal T-cell proliferations of the GI tract, which can be CD4+, CD8+ or CD4- CD8-, have been included as a provisional entity in the newly revised World Health Organization (WHO) classification of lymphoid neoplasms and designated 'indolent T-cell LPD of the GI tract'. It is currently unclear whether the indolent NK-cell LPDs represent reactive or neoplastic proliferations. In this review, we describe the clinical, morphologic, immunophenotypic and genetic features of indolent GI T- and NK-cell LPDs and provide guidance in differentiating them from other inflammatory and neoplastic diseases. We believe that greater awareness of these LPDs amongst physicians and the research community will lead to timely and accurate diagnoses, stimulate investigations into the pathogenetic mechanisms underlying different entities thereby enhancing our understanding of disease biology and enable the development of effective therapeutic regimens. Copyright © 2016 John Wiley & Sons, Ltd.
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Enfermedades Gastrointestinales/diagnóstico , Tracto Gastrointestinal/fisiopatología , Linfoma de Células T/diagnóstico , Linfoma/diagnóstico , Trastornos Linfoproliferativos/diagnóstico , Linfocitos T CD4-Positivos/citología , Linfocitos T CD8-positivos/citología , Diferenciación Celular , Proliferación Celular , Endoscopía , Enfermedades Gastrointestinales/terapia , Humanos , Inmunofenotipificación , Inflamación , Células Asesinas Naturales/citología , Linfoma/terapia , Linfoma de Células T/terapia , Trastornos Linfoproliferativos/terapiaRESUMEN
BACKGROUND: Serologic testing for celiac disease includes tissue transglutaminase and endomysial antibodies. In addition to these tools, assays for deamidated gliadin peptide antibodies have been shown to have sensitivity and specificity that are comparable to tissue transglutaminase testing, and are increasingly being used for celiac disease testing. AIMS: The goal of this study is to evaluate the utility of deamidated gliadin peptide (DGP) testing in the setting of a negative tissue transglutaminase (TTG) IgA test. METHODS: We reviewed the records of all patients seen at two U.S. celiac disease referral centers and identified those who had an elevated DGP IgA and/or IgG in the setting of a negative TTG IgA. Of these patients, those who underwent duodenal biopsy while on a gluten-containing diet were included. Patients with prior biopsy-proven celiac disease or prior TTG IgA positivity were excluded. The results of the biopsy were used as the gold standard for celiac disease diagnosis, and patients with villous atrophy (Marsh class 3) on duodenal biopsy were considered to have celiac disease. RESULTS: Between the two institutions, 84 patients were identified with negative TTG IgA and positive DGP IgA or IgG who also had duodenal biopsies performed while maintaining a gluten-containing diet. Of these patients, 13 patients (15.5%; 95% CI 8.5-25.0%) were found to have celiac disease on duodenal biopsy. CONCLUSIONS: DGP antibody testing can identify cases of celiac disease in TTG-negative individuals, although the low positive predictive value suggests that the yield may be low.
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Anticuerpos/sangre , Enfermedad Celíaca/sangre , Enfermedad Celíaca/diagnóstico , Gliadina/inmunología , Femenino , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Sensibilidad y Especificidad , Pruebas SerológicasRESUMEN
BACKGROUND AND AIMS: Celiac disease (CD) is increasingly diagnosed through screening of at-risk groups (relatives of individuals and associated autoimmune disorders). The impact of diagnosis and treatment on screen-detected CD patients is poorly studied, particularly in the United States. We therefore compared the quality of life (QOL) between screen-detected and symptom-detected CD patients. METHODS: Patients with a known diagnosis of CD were invited to complete 3 validated survey instruments: the CD Quality of Life (CDQOL), the CD Adherence Test for dietary adherence and the general Psychological General Well-Being index. In addition, demographic details, mode of presentation, and compliance with gluten-free diet (GFD) were assessed. RESULTS: The overall response rate was high at 69%. Of 226 responses received, 211 were eligible for inclusion; the median age was 47, and the median duration of GFD was 4 years. One third of the sample (71, 34%) was screen detected. Of these, 57 (80%) had a relative diagnosed with CD, whereas 14 (20%) had an associated condition. Despite being screen detected, 49 (69%) reported symptoms before diagnosis. GFD adherence was excellent and did not differ between groups. Overall, there were no significant differences between screen-detected and symptom-detected patients with regard to CDQOL, CD Adherence Test, and Psychological General Well-Being scores. CONCLUSIONS: Screen-detected and symptom-detected CD patients do not differ with regard to QOL or disease adherence as measured by validated disease-specific instruments. A high proportion of screen-detected patients reported symptoms before diagnosis, which often improve with GFD.
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Enfermedad Celíaca/psicología , Dieta Sin Gluten , Tamizaje Masivo/métodos , Calidad de Vida , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad Celíaca/diagnóstico , Enfermedad Celíaca/dietoterapia , Estudios Transversales , Humanos , Masculino , Persona de Mediana Edad , Cooperación del Paciente/estadística & datos numéricos , Encuestas y Cuestionarios , Estados Unidos , Adulto JovenRESUMEN
BACKGROUND: The diagnosis of celiac disease is dependent on the quality of biopsy specimens obtained at EGD. Endoscopists may obtain a single- or double-biopsy specimen with each pass of the forceps. OBJECTIVE: To compare the quality of biopsy specimens obtained with the single-biopsy and double-biopsy techniques. DESIGN: Prospective cohort study. SETTING: U.S. tertiary-care university hospital. PATIENTS: Patients undergoing upper endoscopy with confirmed, suspected, or unknown celiac disease status. INTERVENTIONS: Four biopsy specimens from the second portion of the duodenum: 2 by using the single-biopsy technique (1 bite per pass of the forceps) and an additional 2 by using the double-biopsy technique (2 bites per pass of the forceps). Specimens were blindly reviewed to determine orientation, consecutive crypt-to-villous units, and Marsh score. MAIN OUTCOME MEASUREMENTS: Proportion of well-oriented biopsy specimens. RESULTS: Patients (N = 86) were enrolled, 47% with known celiac disease, 36% with suspected celiac disease, and 17% with an unknown celiac disease status. Well-oriented biopsy specimens were noted in 66% of patients with the single-biopsy technique and 42% of patients with the double-biopsy technique (P < .01). Analysis of matched pairs showed improved orientation with the single-biopsy technique (odds ratio 3.1; 95% confidence interval, 1.5-7.1; P < .01). This persisted in subgroup analysis of patients with known celiac disease (P = .02), villous atrophy (P = .02), and a final diagnosis of celiac disease (P < .01). LIMITATIONS: A single-center trial. CONCLUSION: The single-biopsy technique improves the yield of well-oriented duodenal biopsy specimens. Endoscopists should consider taking only 1 biopsy specimen per pass of the forceps in patients undergoing biopsies of the duodenal mucosa.
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Biopsia/normas , Enfermedad Celíaca/patología , Duodeno/patología , Adulto , Anciano , Biopsia/métodos , Endoscopía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Gastrointestinal symptoms that respond to the removal of wheat and/or gluten are becoming more common. Patients who avoid wheat and/or gluten (PWAWG) are a heterogeneous group and predominantly self-diagnosed prior to presenting for clinical evaluation. SPECIFIC AIM: We characterized PWAWGs seen at a tertiary care referral center and compared them to patients with celiac disease (CD) and subjects in the National Health and Nutrition examination survey (NHANES). METHODS: This was a cross-sectional study evaluating patients seen by four gastroenterologists at a CD referral center. Baseline characteristics, laboratory values, and medical comorbidities were compared to CD patients who presented at the same center and subjects enrolled in NHANES. RESULTS: Eighty-four PWAWGs were identified and compared to 585 CD patients and 2,686 NHANES patients. Thirty-two alternative diagnoses were made in 25 (30%) PWAWGs, including small intestinal bacterial overgrowth and fructose/lactose intolerance. When compared to patients with CD, PWAWGs had similar body mass index (BMI, 23.1 vs. 23.5, p = 0.54) and mean hemoglobin value (13.4 vs. 13.3, p = 0.6). When compared to male and female patients in NHANES, BMI, folate, and mean hemoglobin values were lower in PWAWGs. Both male and female PWAWGs had a lower prevalence of hypertension. CONCLUSION: While there are similarities between CD and PWAWGs that could possibly be due to shared HLA haplotypes or an effect of the gluten-free diet, alternative diagnoses are common in these patients. PWAWGs have a similar cardiovascular profile as CD patients in terms of lower BMI and lower prevalence of hypertension.
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Enfermedad Celíaca/genética , Dieta Sin Gluten/estadística & datos numéricos , Glútenes/efectos adversos , Triticum , Adulto , Estudios de Casos y Controles , Enfermedad Celíaca/diagnóstico , Enfermedad Celíaca/patología , Proteínas en la Dieta/efectos adversos , Femenino , Análisis de los Alimentos , Hipersensibilidad a los Alimentos , Humanos , Masculino , Cooperación del Paciente , AutoinformeRESUMEN
BACKGROUND: The female predominance in celiac disease is difficult to explain because population-based screening studies reveal similar rates for celiac disease-specific autoantibodies in males and females. AIM: The aim of this study was to explore the role of age and gender in the presentation of celiac disease. METHODS: The frequency of presentation according to age, gender and mode of presentation was determined by analysis of a prospectively maintained database of children and adults seen at a tertiary medical center. RESULTS: Of 1,682 patients (68 % female) aged 3 months to 86 years who were diagnosed with celiac disease, age at diagnosis in females peaked at 40-45 years, whereas the age at diagnosis for males had two peaks: 10-15 and 35-40 years. A significantly lower percentage of males in early adulthood were diagnosed compared with males in all other age groups (P < 0.0001). The young and elderly had a more even gender distribution. CONCLUSIONS: Based on our analysis, males are diagnosed with celiac disease less frequently than females, especially in early adulthood. There should be more emphasis on the diagnosis of celiac disease among young adult males.
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Enfermedad Celíaca/diagnóstico , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Bases de Datos Factuales , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Ciudad de Nueva York , Distribución por Sexo , Adulto JovenRESUMEN
BACKGROUND: Studies on the effect of computer-aided detection (CAD) in a daily clinical screening and surveillance colonoscopy population practice are scarce. The aim of this study was to evaluate a novel CAD system in a screening and surveillance colonoscopy population. METHODS: This multicentre, randomised, controlled trial was done in ten hospitals in Europe, the USA, and Israel by 31 endoscopists. Patients referred for non-immunochemical faecal occult blood test (iFOBT) screening or surveillance colonoscopy were included. Patients were randomomly assigned to CAD-assisted colonoscopy or conventional colonoscopy; a subset was further randomly assigned to undergo tandem colonoscopy: CAD followed by conventional colonoscopy or conventional colonoscopy followed by CAD. Primary objectives included adenoma per colonoscopy (APC) and adenoma per extraction (APE). Secondary objectives included adenoma miss rate (AMR) in the tandem colonoscopies. The study was registered at ClinicalTrials.gov, NCT04640792. FINDINGS: A total of 916 patients were included in the modified intention-to-treat analysis: 449 in the CAD group and 467 in the conventional colonoscopy group. APC was higher with CAD compared with conventional colonoscopy (0·70 vs 0·51, p=0·015; 314 adenomas per 449 colonoscopies vs 238 adenomas per 467 colonoscopies; poisson effect ratio 1·372 [95% CI 1·068-1·769]), while showing non-inferiority of APE compared with conventional colonoscopy (0·59 vs 0·66; p<0·001 for non-inferiority; 314 of 536 extractions vs 238 of 360 extractions). AMR in the 127 (61 with CAD first, 66 with conventional colonoscopy first) patients completing tandem colonoscopy was 19% (11 of 59 detected during the second pass) in the CAD first group and 36% (16 of 45 detected during the second pass) in the conventional colonoscopy first group (p=0·024). INTERPRETATION: CAD increased adenoma detection in non-iFOBT screening and surveillance colonoscopies and reduced adenoma miss rates compared with conventional colonoscopy, without an increase in the resection of non-adenomatous lesions. FUNDING: Magentiq Eye.
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Adenoma , Hominidae , Humanos , Animales , Colonoscopía , Adenoma/diagnóstico por imagen , Computadores , Europa (Continente)RESUMEN
BACKGROUND & AIMS: Anemia is considered to be an atypical or silent presentation of celiac disease, compared with the classic presentation with diarrhea. However, little information is available about how these groups compare in terms of disease severity. We compared the severity of celiac disease between patients who present with anemia vs those who present with diarrhea. METHODS: The study cohort was selected from a database of patients with celiac disease who were evaluated at a tertiary referral center between 1990 and 2011. Severity of celiac disease was assessed by the degree of villous atrophy and clinical and serologic parameters. Patients were compared according to mode of presentation and sex. Multivariable analyses, adjusting for age and sex, were conducted to assess the association between the mode of celiac disease presentation and cholesterol level, bone density, severity of villous atrophy, erythrocyte sedimentation rate, and level of anti-tissue transglutaminase. RESULTS: Of 727 patients, 77% presented with diarrhea and 23% with anemia (92% iron deficient). On multiple regression analysis, presentation with anemia was associated with lower levels of total cholesterol (P = .02) and high-density lipoprotein (P = .002) and a higher erythrocyte sedimentation rate (P = .001) and level of anti-tissue transglutaminase (P = .01). Presentation with anemia was associated with lower level of cholesterol only in women. Anemic patients were more than 2-fold more likely to have severe villous atrophy and a low bone mass density at the time they were diagnosed with celiac disease than patients who presented with diarrhea. CONCLUSIONS: Celiac disease patients who present with anemia have more severe disease than those who present with diarrhea. There also appear to be sex-specific differences with regard to the association between anemia and the different features of celiac disease.
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Anemia/etiología , Anemia/patología , Enfermedad Celíaca/complicaciones , Enfermedad Celíaca/patología , Diarrea/etiología , Diarrea/patología , Adulto , Anciano , Autoanticuerpos/sangre , Sedimentación Sanguínea , Densidad Ósea , Colesterol/sangre , Estudios de Cohortes , Femenino , Proteínas de Unión al GTP/inmunología , Humanos , Mucosa Intestinal/patología , Masculino , Persona de Mediana Edad , Proteína Glutamina Gamma Glutamiltransferasa 2 , Índice de Severidad de la Enfermedad , Factores Sexuales , Transglutaminasas/inmunologíaRESUMEN
OBJECTIVES: Patients with villous atrophy (VA) and negative celiac disease (CD) serologies pose a diagnostic and therapeutic dilemma. When a definitive etiology for VA is not determined, patients are characterized as having unclassified sprue (US), the optimal management of which is unknown. METHODS: We studied adult patients with VA on biopsy and negative celiac serologies, evaluated at our tertiary referral center over a 10-year period. Testing for HLA DQ2/8 alleles, antienterocyte antibodies, giardia stool antigen, bacterial overgrowth, total serum immunoglobulins, and HIV was noted. Treatment, response, and repeat-biopsy findings were recorded. RESULTS: The most common diagnoses of the 72 patients were seronegative CD, medication-related villous atrophy, and US. Of those with US, the majority reported symptomatic improvement with immunosuppressive therapy. Some patients initially labeled as unclassified were found to have VA associated with olmesartan use. CONCLUSIONS: The role of medications in the development of VA and the optimal dose and length of immunosuppression for patients with US should be investigated further.
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Enfermedad Celíaca/diagnóstico , Duodeno/patología , Inmunosupresores/uso terapéutico , Mucosa Intestinal/patología , Adulto , Anciano , Anciano de 80 o más Años , Bloqueadores del Receptor Tipo 1 de Angiotensina II/administración & dosificación , Bloqueadores del Receptor Tipo 1 de Angiotensina II/efectos adversos , Atrofia/etiología , Autoanticuerpos/sangre , Biopsia , Enfermedad Celíaca/tratamiento farmacológico , Enfermedad Celíaca/inmunología , Bases de Datos Factuales , Duodeno/efectos de los fármacos , Duodeno/inmunología , Femenino , Antígenos HLA-DQ/sangre , Humanos , Imidazoles/administración & dosificación , Imidazoles/efectos adversos , Inmunoglobulinas/sangre , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/inmunología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tetrazoles/administración & dosificación , Tetrazoles/efectos adversosRESUMEN
OBJECTIVE: To assess the prevalence of headache in clinic and support group patients with celiac disease and inflammatory bowel disease (IBD) compared with a sample of healthy controls. BACKGROUND: European studies have demonstrated increased prevalence of headache of patients with celiac disease compared with controls. METHODS: Subjects took a self-administered survey containing clinical, demographic, and dietary data, as well as questions about headache type and frequency. The ID-Migraine screening tool and the Headache Impact Test (HIT-6) were also used. RESULTS: Five hundred and two subjects who met exclusion criteria were analyzed - 188 with celiac disease, 111 with IBD, 25 with gluten sensitivity (GS), and 178 controls (C). Chronic headaches were reported by 30% of celiac disease, 56% of GS, 23% of IBD, and 14% of control subjects (P<.0001). On multivariate logistic regression, celiac disease (odds ratio [OR] 3.79, 95% confidence interval [CI] 1.78-8.10), GS (OR 9.53, 95%CI 3.24-28.09), and IBD (OR 2.66, 95%CI 1.08-6.54) subjects all had significantly higher prevalence of migraine headaches compared with controls. Female sex (P=.01), depression, and anxiety (P=.0059) were independent predictors of migraine headaches, whereas age >65 was protective (P=.0345). Seventy-two percent of celiac disease subjects graded their migraine as severe in impact, compared with 30% of IBD, 60% of GS, and 50% of C subjects (P=.0919). There was no correlation between years on gluten-free diet and migraine severity. CONCLUSIONS: Migraine was more prevalent in celiac disease and IBD subjects than in controls. Future studies should include screening migraine patients for celiac disease and assessing the effects of gluten-free diet on migraines in celiac disease.
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Enfermedad Celíaca/epidemiología , Enfermedades Inflamatorias del Intestino/epidemiología , Trastornos Migrañosos/epidemiología , Adolescente , Adulto , Anciano , Estudios Transversales , Femenino , Encuestas Epidemiológicas , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Autoinforme , Estados Unidos , Adulto JovenRESUMEN
BACKGROUND: Celiac disease (CD) is under-diagnosed in the United States, and factors related to the performance of endoscopy may be contributory. AIM: To identify newly diagnosed patients with CD who had undergone a prior esophagogastroduodenoscopy (EGD) and examine factors contributing to the missed diagnosis. METHODS: We identified all patients age ≥ 18 years whose diagnosis of CD was made by endoscopy with biopsy at our institution (n = 316), and searched the medical record for a prior EGD. We compared those patients with a prior EGD to those with without a prior EGD with regard to age at diagnosis and gender, and enumerated the indications for EGD. RESULTS: Of the 316 patients diagnosed by EGD with biopsy at our center, 17 (5 %) had previously undergone EGD. During the prior non-diagnostic EGD, a duodenal biopsy was not performed in 59 % of the patients, and ≥ 4 specimens (the recommended number) were submitted in only 29 % of the patients. On the diagnostic EGD, ≥ 4 specimens were submitted in 94 %. The mean age of diagnosis of those with missed/incident CD was 53.1 years, slightly older than those diagnosed with CD on their first EGD (46.8 years, p = 0.11). Both groups were predominantly female (missed/incident CD: 65 vs. 66 %, p = 0.94). CONCLUSIONS: Among 17 CD patients who had previously undergone a non-diagnostic EGD, non-performance of duodenal biopsy during the prior EGD was the dominant feature. Routine performance of duodenal biopsy during EGD for the indications of dyspepsia and reflux may improve CD diagnosis rates.
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Enfermedad Celíaca/diagnóstico , Endoscopía Gastrointestinal/estadística & datos numéricos , Estudios Transversales , Diagnóstico Tardío , Duodeno/patología , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND AND OBJECTIVE: Celiac Disease (CD) is characterized by gluten intolerance in genetically predisposed individuals. High disease prevalence, absence of a cure, and low diagnosis rates make this disease a public health problem. The diagnosis of CD predominantly relies on recognizing characteristic mucosal alterations of the small intestine, such as villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis. However, these changes are not entirely specific to CD and overlap with Non-Celiac Duodenitis (NCD) due to various etiologies. We investigated whether Artificial Intelligence (AI) models could assist in distinguishing normal, CD, and NCD (and unaffected individuals) based on the characteristics of small intestinal lamina propria (LP). METHODS: Our method was developed using a dataset comprising high magnification biopsy images of the duodenal LP compartment of CD patients with different clinical stages of CD, those with NCD, and individuals lacking an intestinal inflammatory disorder (controls). A pre-processing step was used to standardize and enhance the acquired images. RESULTS: For the normal controls versus CD use case, a Support Vector Machine (SVM) achieved an Accuracy (ACC) of 98.53%. For a second use case, we investigated the ability of the classification algorithm to differentiate between normal controls and NCD. In this use case, the SVM algorithm with linear kernel outperformed all the tested classifiers by achieving 98.55% ACC. CONCLUSIONS: To the best of our knowledge, this is the first study that documents automated differentiation between normal, NCD, and CD biopsy images. These findings are a stepping stone toward automated biopsy image analysis that can significantly benefit patients and healthcare providers.