Psychological, Psychiatric, and Organic Brain Manifestations of Celiac Disease.

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. Here, attention is paid 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. 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. 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.

A computer-aided polyp detection system in screening and surveillance colonoscopy: an international, multicentre, randomised, tandem trial.

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.

Serological Investigation of Persistent Villous Atrophy in Celiac Disease.

INTRODUCTION: Persistent villous atrophy (VA) is not uncommon in celiac disease (CeD) while patients take a gluten-free diet (GFD). METHODS: We conducted a retrospective study with 122 serum samples collected from controls and patients with CeD either at the initial diagnosis or at the follow-up during endoscopy. These samples were assigned to 3 groups: nonceliac control, non-VA CeD (Marsh score 0-2), and VA CeD (Marsh score 3a-3c). We established an in-house multiplex assay to identify potential serological biomarkers for VA. We assessed autoantibodies reported to affect the small intestine, including IgA and IgG antibodies against tissue transglutaminase (tTG), interferons, villin, actin, autoimmune enteropathy-related 75 kDa antigen (AIE-75), and tryptophan hydroxylase (TPH)-1, as well as 27 cytokines. The apolipoproteins quantified included apo A1, apo B-100, and apo A4, which were produced predominantly by the intestinal epithelium or expressed specifically in villi. RESULTS: Autoantibody levels were high only for tTG antibodies, which performed well in initial CeD diagnosis, but suboptimally for VA prediction during follow-up, because 14.6% of the follow-up patients with VA had low tTG-IgA. Increasing dilution improved tTG-IgA quantification, particularly when the antibody levels were extremely high but did not significantly improve VA detection. Among those with low tTG-IgA and persistent VA, high proinflammatory cytokines were observed in 2 patients. Median low-density lipoprotein cholesterol levels were significantly lower in the VA CeD group ( P = 0.03). Apolipoprotein levels were similar in patients with and without VA but diverged between those on a GFD or not. DISCUSSION: tTG-IgA as a biomarker is suboptimal for VA prediction while on a GFD. Persistent VA is associated with low low-density lipoprotein cholesterol levels and partially related to persistent high proinflammatory cytokines.

Automated analysis of small intestinal lamina propria to distinguish normal, Celiac Disease, and Non-Celiac Duodenitis biopsy images.

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.

Automated interpretation of biopsy images for the detection of celiac disease using a machine learning approach.

BACKGROUND AND OBJECTIVES: Celiac disease is an autoimmune disease occurring in about 1 in 100 people worldwide. Early diagnosis and efficient treatment are crucial in mitigating the complications that are associated with untreated celiac disease, such as intestinal lymphoma and malignancy, and the subsequent high morbidity. The current diagnostic methods using small intestinal biopsy histopathology, endoscopy, and video capsule endoscopy (VCE) involve manual interpretation of photomicrographs or images, which can be time-consuming and difficult, with inter-observer variability. In this paper, a machine learning technique was developed for the automation of biopsy image analysis to detect and classify villous atrophy based on modified Marsh scores. This is one of the first studies to employ conventional machine learning to automate the use of biopsy images for celiac disease detection and classification. METHODS: The Steerable Pyramid Transform (SPT) method was used to obtain sub bands from which various types of entropy and nonlinear features were computed. All extracted features were automatically classified into two-class and multi-class, using six classifiers. RESULTS: An accuracy of 88.89%, was achieved for the classification of two-class villous abnormalities based on analysis of Hematoxylin and Eosin (H&E) stained biopsy images. Similarly, an accuracy of 82.92% was achieved for the two-class classification of red-green-blue (RGB) biopsy images. Also, an accuracy of 72% was achieved in the classification of multi-class biopsy images. CONCLUSION: The results obtained are promising, and demonstrate the possibility of automating biopsy image interpretation using machine learning. This can assist pathologists in accelerating the diagnostic process without bias, resulting in greater accuracy, and ultimately, earlier access to treatment.

Immunophenotypic Spectrum and Genomic Landscape of Refractory Celiac Disease Type II.

Refractory celiac disease type II (RCD II), also referred to as "cryptic" enteropathy-associated T-cell lymphoma (EATL) or "intraepithelial T-cell lymphoma," is a rare clonal lymphoproliferative disorder that arises from innate intraepithelial lymphocytes. RCD II has a poor prognosis and frequently evolves to EATL. The pathogenesis of RCD II is not well understood and data regarding the immunophenotypic spectrum of this disease and underlying genetic alterations are limited. To gain further biological insights, we performed comprehensive immunophenotypic, targeted next-generation sequencing, and chromosome microarray analyses of 11 RCD II cases: CD4-/CD8- (n=6), CD8+ (n=4), and CD4+ (n=1), and 2 of 3 ensuing EATLs. Genetic alterations were identified in 9/11 (82%) of the RCD II cases. All 9 displayed mutations in members of the JAK-STAT signaling pathway, including frequent, recurrent STAT3 (7/9, 78%) and JAK1 (4/9, 44%) mutations, and 9/10 evaluable cases expressed phospho-STAT3. The mutated cases also harbored recurrent alterations in epigenetic regulators (TET2, n=5 and KMT2D, n=5), nuclear factor-κB (TNFAIP3, n=4), DNA damage repair (POT1, n=3), and immune evasion (CD58, n=2) pathway genes. The CD4-/CD8- and other immunophenotypic subtypes of RCD II exhibited similar molecular features. Longitudinal genetic analyses of 4 RCD II cases revealed stable mutation profiles, however, additional mutations were detected in the EATLs, which occurred at extraintestinal sites and were clonally related to antecedent RCD II. Chromosome microarray analysis demonstrated copy number changes in 3/6 RCD II cases, and 1 transformed EATL with sufficient neoplastic burden for informative analysis. Our findings provide novel information about the immunophenotypic and genomic characteristics of RCD II, elucidate early genetic events in EATL pathogenesis, and reveal potential therapeutic targets.

Evaluating Responses to Gluten Challenge: A Randomized, Double-Blind, 2-Dose Gluten Challenge Trial.

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.

Genetic and phenotypic characterization of indolent T-cell lymphoproliferative disorders of the gastrointestinal tract.

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.

Measurement of Forearm Bone Density by Dual Energy X-Ray Absorptiometry Increases the Prevalence of Osteoporosis in Men With Celiac Disease.

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.

Celiac disease diagnosis from videocapsule endoscopy images with residual learning and deep feature extraction.

BACKGROUND AND OBJECTIVE: Videocapsule endoscopy (VCE) is a relatively new technique for evaluating the presence of villous atrophy in celiac disease patients. The diagnostic analysis of video frames is currently time-consuming and tedious. Recently, computer-aided diagnosis (CAD) systems have become an attractive research area for diagnosing celiac disease. However, the images captured from VCE are susceptible to alterations in light illumination, rotation direction, and intestinal secretions. Moreover, textural features of the mucosal villi obtained by VCE are difficult to characterize and extract. This work aims to find a novel deep learning feature learning module to assist in the diagnosis of celiac disease. METHODS: In this manuscript, we propose a novel deep learning recalibration module which shows significant gain in diagnosing celiac disease. In this recalibration module, the block-wise recalibration component is newly employed to capture the most salient feature in the local channel feature map. This learning module was embedded into ResNet50, Inception-v3 to diagnose celiac disease using a 10-time 10-fold cross-validation based upon analysis of VCE images. In addition, we employed model weights to extract feature points from training and test samples before the last fully connected layer, and then input to a support vector machine (SVM), k-nearest neighbor (KNN), and linear discriminant analysis (LDA) for differentiating celiac disease images from heathy controls. RESULTS: Overall, the accuracy, sensitivity and specificity of the 10-time 10-fold cross-validation were 95.94%, 97.20% and 95.63%, respectively. CONCLUSIONS: A novel deep learning recalibration module, with global response and local salient factors is proposed, and it has a high potential for utilizing deep learning networks to diagnose celiac disease using VCE images.

Automated diagnosis of celiac disease by video capsule endoscopy using DAISY Descriptors.

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.

Capsule Endoscopy and Enteroscopy in Celiac Disease.

Celiac disease predominantly involves the proximal small bowel, but villus atrophy can be patchy, spare the duodenum, and be present more distally. Video capsule endoscopy is more sensitive than standard endoscopy to detect villus atrophy, and can define extent of disease, though it cannot obtain biopsies. Duodenal biopsy is the gold standard for diagnosis. Video capsule endoscopy assists in special circumstances when biopsy is not possible, and in equivocal diagnosis. Video capsule endoscopy and enteroscopy are recommended for evaluating complicated celiac disease, especially refractory celiac disease type II. Future developments include computer-assisted capsule programs and advanced capsule and enteroscope design.

Color masking improves classification of celiac disease in videocapsule endoscopy images.

BACKGROUND: Videocapsule endoscopy images are useful to detect pathologic alterations, including villous atrophy, in the small intestinal mucosa, which is helpful for diagnosing celiac disease. In prior work, quantitative videocapsule analysis was found useful to classify celiac versus control images. However, the effect of dark/extraneous substances on classification efficacy requires remediation. METHOD: For quantitative analysis, data from the Medtronic SB2 and SB3 systems were pooled. Videocapsule images of the distal duodenum/proximal jejunum were acquired from 13 celiac and 13 control patients. Dark regions, extraneous fluids, and air bubbles were mostly removed by utilizing color masking. Two different red-green-blue (RGB) color masks were constructed from 20 to 30 reference pixels obtained from mucosal and from extraneous regions. Each image pixel was accepted or rejected for subsequent analysis based on whether its distance was closest to a mucosal or to an extraneous reference in RGB space. Four images were then randomly selected from each videoclip for processing (52 images from each group). After masking, celiac versus control images were plotted in a three-space consisting of mean and standard deviation in pixel brightness, and surface area remaining after masking. A linear discriminant function was used for classification. The paradigm was repeated with a second random data set for validation. RESULTS: Masking improved classification of celiac versus control images to nearly 80% accuracy as compared to 70-77% without masking. Celiac disease patients tended to have lesser mean pixel brightness and greater variability in brightness, in accord with prior work, and more masking was needed to remove extraneous features. CONCLUSIONS: Color masking is useful to remove dim/extraneous features from videocapsule images and it results in improved classification/assessment to distinguish celiac with villous atrophy from control videocapsule image. This can be helpful to detect and map regions of pathology, to screen for celiac disease, and to determine the efficacy of a gluten free diet.

Clonal T cell receptor gene rearrangements in coeliac disease: implications for diagnosing refractory coeliac disease.

AIMS: Refractory coeliac disease type II (RCDII), a rare complication of coeliac disease (CD) associated with high morbidity, requires identification of a clonal population of phenotypically aberrant intraepithelial lymphocytes (IELs) for diagnosis. However, data regarding the frequency and significance of clonal T cell receptor (TCR) gene rearrangements (TCR-GRs) in small bowel (SB) biopsies of patients without RCDII are limited. METHODS: We analysed results of TCR-GR analyses performed on SB biopsies at our institution over a 3-year period, which were obtained from eight active CD, 172 CD on gluten-free diet (GFD), 33 RCDI, and three RCDII patients and 14 patients without CD. TCR-GR patterns were divided into clonal, polyclonal and prominent clonal peaks (PCPs) and these patterns were correlated with clinical and pathological features. RESULTS: Clonal TCR-GR products were detected in biopsies from 67% of patients with RCDII, 17% of patients with RCDI and 6% of patients with GFD. PCPs were observed in all disease phases (range 12%-33%). There was no significant difference in the TCR-GR patterns between the non-RCDII disease categories (p=0.39). A higher frequency of surface CD3(-) IELs was noted in cases with clonal TCR-GR, but the PCP pattern did not show associations with any clinical or pathological feature. Persistence of clonal or PCP pattern on repeat biopsy was seen for up to 2 years without evidence of RCDII. CONCLUSIONS: Clonal TCR-GRs are not infrequent in cases lacking features of RCDII, while PCPs are frequent in all disease phases. TCR-GR results should be assessed in conjunction with immunophenotypic, histological and clinical findings for appropriate diagnosis and classification of RCD.

Stool PCR for Gastrointestinal Pathogens in Patients With and Without Immune-Mediated Intestinal Diseases.

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.

Determinants of Follow-up Care for Patients With Celiac Disease.

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.

Outcome of breath tests in adult patients with suspected small intestinal bacterial overgrowth.

AIM: The aim was to investigate breath test outcomes in patients with suspected SIBO and indicative symptoms of SIBO, diagnosed by breath testing. BACKGROUND: Breath testing is used to detect small intestinal bacterial overgrowth (SIBO) by measuring hydrogen and methane produced by intestinal bacteria. METHODS: This retrospective cross sectional study included 311 patients with gastrointestinal symptoms who underwent the breath test for evaluation of SIBO at Celiac Disease Center at Columbia University, New York, in 2014-2015. The patients were divided into two groups based on the physician's choice: lactulose breath test group (72%) and glucose breath test group (28%). Among them, 38% had a history of celiac disease or non-celiac gluten sensitivity. RESULTS: In total, 46% had a positive breath test: 18% were positive for methane, 24 % positive for hydrogen and 4% positive for both gases (p=0.014). Also, 50% had a positive lactulose breath result and 37% had a positive glucose breath result (p=0.036). The most common symptom for performing the breath test was bloating and the only clinical symptom that significantly showed a positive glucose breath test was increased gas (p=0.028). CONCLUSION: Lactulose breath test was more often positive than glucose breath test. Positivity for hydrogen was more common than methane. Bloating was the most frequently perceived symptom of the patients undergoing the breath test but the only statistically significant clinical symptom for a positive glucose breath test was increased gas. Furthermore, the results showed that there was no significant association between positive breath test result and gender, age, non-celiac gluten sensitivity or celiac disease.

Cardiovascular involvement in celiac disease.

Celiac disease (CD) is an autoimmune response to ingestion of gluten protein, which is found in wheat, rye, and barley grains, and results in both small intestinal manifestations, including villous atrophy, as well as systemic manifestations. The main treatment for the disease is a gluten-free diet (GFD), which typically results in the restoration of the small intestinal villi, and restoration of other affected organ systems, to their normal functioning. In an increasing number of recently published studies, there has been great interest in the occurrence of alterations in the cardiovascular system in untreated CD. Herein, published studies in which CD and cardiovascular terms appear in the title of the study were reviewed. The publications were categorized into one of several types: (1) articles (including cohort and case-control studies); (2) reviews and meta-analyses; (3) case studies (one to three patient reports); (4) letters; (5) editorials; and (6) abstracts (used when no full-length work had been published). The studies were subdivided as either heart or vascular studies, and were further characterized by the particular condition that was evident in conjunction with CD. Publication information was determined using the Google Scholar search tool. For each publication, its type and year of publication were tabulated. Salient information from each article was then compiled. It was determined that there has been a sharp increase in the number of CD - cardiovascular studies since 2000. Most of the publications are either of the type "article" or "case study". The largest number of documents published concerned CD in conjunction with cardiomyopathy (33 studies), and there have also been substantial numbers of studies published on CD and thrombosis (27), cardiovascular risk (17), atherosclerosis (13), stroke (12), arterial function (11), and ischemic heart disease (11). Based on the published research, it can be concluded that many types of cardiovascular issues can occur in untreated CD patients, but that most tend to resolve on a GFD, often in conjunction with the healing of small intestinal villous atrophy. However, in some cases the alterations are irreversible, underscoring the need for CD screening and treatment when cardiovascular issues arise of unknown etiology.

Use of shape-from-shading to characterize mucosal topography in celiac disease videocapsule images.

AIM: To use a computerized shape-from-shading technique to characterize the topography of the small intestinal mucosa. METHODS: Videoclips comprised of 100-200 images each were obtained from the distal duodenum in 8 celiac and 8 control patients. Images with high texture were selected from each videoclip and projected from two to three dimensions by using grayscale pixel brightness as the Z-axis spatial variable. The resulting images for celiac patients were then ordered using the Marsh score to estimate the degree of villous atrophy, and compared with control data. RESULTS: Topographic changes in celiac patient three-dimensional constructs were often more variable as compared to controls. The mean absolute derivative in elevation was 2.34 ± 0.35 brightness units for celiacs vs 1.95 ± 0.28 for controls (P = 0.014). The standard deviation of the derivative in elevation was 4.87 ± 0.35 brightness units for celiacs vs 4.47 ± 0.36 for controls (P = 0.023). Celiac patients with Marsh IIIC villous atrophy tended to have the largest topographic changes. Plotted in two dimensions, celiac data could be separated from controls with 80% sensitivity and specificity. CONCLUSION: Use of shape-from-shading to construct three-dimensional projections approximating the actual spatial geometry of the small intestinal substrate is useful to observe features not readily apparent in two-dimensional videocapsule images. This method represents a potentially helpful adjunct to detect areas of pathology during videocapsule analysis.