Publications by authors named "Julio C Bai"

55 Publications

Gluten Induces Subtle Histological Changes in Duodenal Mucosa of Patients with Non-Coeliac Gluten Sensitivity: A Multicentre Study.

Nutrients 2022 Jun 15;14(12). Epub 2022 Jun 15.

Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, MN 55907, USA.

Histological changes induced by gluten in the duodenal mucosa of patients with non-coeliac gluten sensitivity (NCGS) are poorly defined. To evaluate the structural and inflammatory features of NCGS compared to controls and coeliac disease (CeD) with milder enteropathy (Marsh I-II). Well-oriented biopsies of 262 control cases with normal gastroscopy and histologic findings, 261 CeD, and 175 NCGS biopsies from 9 contributing countries were examined. Villus height (VH, in μm), crypt depth (CrD, in μm), villus-to-crypt ratios (VCR), IELs (intraepithelial lymphocytes/100 enterocytes), and other relevant histological, serologic, and demographic parameters were quantified. The median VH in NCGS was significantly shorter (600, IQR: 400-705) than controls (900, IQR: 667-1112) ( < 0.001). NCGS patients with Marsh I-II had similar VH and VCR to CeD [465 µm (IQR: 390-620) vs. 427 µm (IQR: 348-569, = 0·176)]. The VCR in NCGS with Marsh 0 was lower than controls ( < 0.001). The median IEL in NCGS with Marsh 0 was higher than controls (23.0 vs. 13.7, < 0.001). To distinguish Marsh 0 NCGS from controls, an IEL cut-off of 14 showed 79% sensitivity and 55% specificity. IEL densities in Marsh I-II NCGS and CeD groups were similar. : NCGS duodenal mucosa exhibits distinctive changes consistent with an intestinal response to luminal antigens, even at the Marsh 0 stage of villus architecture.
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http://dx.doi.org/10.3390/nu14122487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9230100PMC
June 2022

The global burden of coeliac disease: opportunities and challenges.

Nat Rev Gastroenterol Hepatol 2022 05 3;19(5):313-327. Epub 2022 Jan 3.

Universidad del Salvador, Buenos Aires, Argentina.

Coeliac disease is a systemic disorder characterized by immune-mediated enteropathy, which is caused by gluten ingestion in genetically susceptible individuals. The clinical presentation of coeliac disease is highly variable and ranges from malabsorption through solely extra-intestinal manifestations to asymptomatic. As a result, the majority of patients with coeliac disease remain undiagnosed, misdiagnosed or experience a substantial delay in diagnosis. Coeliac disease is diagnosed by a combination of serological findings of disease-related antibodies and histological evidence of villous abnormalities in duodenal biopsy samples. However, variability in histological grading and in the diagnostic performance of some commercially available serological tests remains unacceptably high and confirmatory assays are not readily available in many parts of the world. Currently, the only effective treatment for coeliac disease is a lifelong, strict, gluten-free diet. However, many barriers impede patients' adherence to this diet, including lack of widespread availability, high cost, cross-contamination and its overall restrictive nature. Routine follow-up is necessary to ensure adherence to a gluten-free diet but considerable variation is evident in follow-up protocols and the optimal disease management strategy is not clear. However, these challenges in the diagnosis and management of coeliac disease suggest opportunities for future research.
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http://dx.doi.org/10.1038/s41575-021-00552-zDOI Listing
May 2022

Accuracy of a no-biopsy approach for the diagnosis of coeliac disease across different adult cohorts.

Gut 2021 05 2;70(5):876-883. Epub 2020 Nov 2.

Academic Unit of Gastroenterology, Royal Hallamshire Hospital, Sheffield, UK

Objective: We aimed to determine the predictive capacity and diagnostic yield of a 10-fold increase in serum IgA antitissue transglutaminase (tTG) antibody levels for detecting small intestinal injury diagnostic of coeliac disease (CD) in adult patients.

Design: The study comprised three adult cohorts. Cohort 1: 740 patients assessed in the specialist CD clinic at a UK centre; cohort 2: 532 patients with low suspicion for CD referred for upper GI endoscopy at a UK centre; cohort 3: 145 patients with raised tTG titres from multiple international sites. Marsh 3 histology was used as a reference standard against which we determined the performance characteristics of an IgA tTG titre of ≥10×ULN for a diagnosis of CD.

Results: Cohort 1: the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 54.0%, 90.0%, 98.7% and 12.5%, respectively. Cohort 2: the sensitivity, specificity, PPV and NPV for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 50.0%, 100.0%, 100.0% and 98.3%, respectively. Cohort 3: the sensitivity, specificity, PPV and NPV for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 30.0%, 83.0%, 95.2% and 9.5%, respectively.

Conclusion: Our results show that IgA tTG titres of ≥10×ULN have a strong predictive value at identifying adults with intestinal changes diagnostic of CD. This study supports the use of a no-biopsy approach for the diagnosis of adult CD.
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http://dx.doi.org/10.1136/gutjnl-2020-320913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040155PMC
May 2021

Gluten-Free Diet Reduces Symptoms, Particularly Diarrhea, in Patients With Irritable Bowel Syndrome and Antigliadin IgG.

Clin Gastroenterol Hepatol 2021 11 19;19(11):2343-2352.e8. Epub 2020 Aug 19.

Department of Medicine, Farncombe Institute, McMaster University, Hamilton, Ontario, Canada. Electronic address:

Background & Aims: Many patients with irritable bowel syndrome (IBS) perceive that their symptoms are triggered by wheat-containing foods. We assessed symptoms and gastrointestinal transit before and after a gluten-free diet (GFD) in unselected patients with IBS and investigated biomarkers associated with symptoms.

Methods: We performed a prospective study of 50 patients with IBS (ROME III, all subtypes), with and without serologic reactivity to gluten (antigliadin IgG and IgA), and 25 healthy subjects (controls) at a university hospital in Hamilton, Ontario, Canada, between 2012 and 2016. Gastrointestinal transit, gut symptoms, anxiety, depression, somatization, dietary habits, and microbiota composition were studied before and after 4 weeks of a GFD. HLA-DQ2/DQ8 status was determined. GFD compliance was assessed by a dietitian and by measuring gluten peptides in stool.

Results: There was no difference in symptoms among patients at baseline, but after the GFD, patients with antigliadin IgG and IgA reported less diarrhea than patients without these antibodies (P = .03). Compared with baseline, IBS symptoms improved in 18 of 24 patients (75%) with antigliadin IgG and IgA and in 8 of 21 patients (38%) without the antibodies. Although constipation, diarrhea, and abdominal pain were reduced in patients with antigliadin IgG and IgA, only pain decreased in patients without these antibodies. Gastrointestinal transit normalized in a higher proportion of patients with antigliadin IgG and IgA. Anxiety, depression, somatization, and well-being increased in both groups. The presence of antigliadin IgG was associated with overall reductions in symptoms (adjusted odds ratio compared with patients without this antibody, 128.9; 95% CI, 1.16-1427.8; P = .04). Symptoms were reduced even in patients with antigliadin IgG and IgA who reduced gluten intake but were not strictly compliant with the GFD. In controls, a GFD had no effect on gastrointestinal symptoms or gut function.

Conclusions: Antigliadin IgG can be used as a biomarker to identify patients with IBS who might have reductions in symptoms, particularly diarrhea, on a GFD. Larger studies are needed to validate these findings. ClinicalTrials.gov: NCT03492333.
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http://dx.doi.org/10.1016/j.cgh.2020.08.040DOI Listing
November 2021

Toward New Paradigms in the Follow Up of Adult Patients With Celiac Disease on a Gluten-Free Diet.

Front Nutr 2019 1;6:153. Epub 2019 Oct 1.

Research Institute, Universidad del Salvador, Buenos Aires, Argentina.

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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http://dx.doi.org/10.3389/fnut.2019.00153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781794PMC
October 2019

Evolving Paradigms in the Diagnosis of Adult Patients With Celiac Disease.

Am J Gastroenterol 2019 06;114(6):854-857

Farncombe Family Digestive Health Research Institute, McMaster University Health Sciences Centre, Hamilton, Ontario, Canada.

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http://dx.doi.org/10.14309/ajg.0000000000000279DOI Listing
June 2019

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

Clin Gastroenterol Hepatol 2020 01 10;18(1):99-106. Epub 2019 Apr 10.

Division of Gastroenterology, Celiac Disease Center, Department of Medicine, Columbia University Medical Center, New York, New York.

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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http://dx.doi.org/10.1016/j.cgh.2019.03.049DOI Listing
January 2020

Follow-up of Celiac Disease.

Gastroenterol Clin North Am 2019 03 14;48(1):127-136. Epub 2018 Dec 14.

Hospital de Gastroenterología Dr. C. Bonorino Udaondo, Av. Caseros 2061, Buenos Aires 1236, Argentina.

Currently, the only effective treatment for celiac disease is complete removal of gluten from the diet. However, patients need to follow a strict gluten-free diet that results in symptomatic, serologic, and histologic remission in most patients. Histologic remission is usually complete in children, but recovery is slower and more frequently incomplete in adults. When remission has been achieved, yearly follow-up is recommended for adults, children, and adolescents. This article deals with conventional strategies used in order to follow-up patients on treatment and aiming to obtain the best clinical outcome.
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http://dx.doi.org/10.1016/j.gtc.2018.09.009DOI Listing
March 2019

Galectins in Intestinal Inflammation: Galectin-1 Expression Delineates Response to Treatment in Celiac Disease Patients.

Front Immunol 2018 1;9:379. Epub 2018 Mar 1.

Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.

Galectins, a family of animal lectins characterized by their affinity for N-acetyllactosamine-enriched glycoconjugates, modulate several immune cell processes shaping the course of innate and adaptive immune responses. Through interaction with a wide range of glycosylated receptors bearing complex branched N-glycans and core 2-O-glycans, these endogenous lectins trigger distinct signaling programs thereby controling immune cell activation, differentiation, recruitment and survival. Given the unique features of mucosal inflammation and the differential expression of galectins throughout the gastrointestinal tract, we discuss here key findings on the role of galectins in intestinal inflammation, particularly Crohn's disease, ulcerative colitis, and celiac disease (CeD) patients, as well as in murine models resembling these inflammatory conditions. In addition, we present new data highlighting the regulated expression of galectin-1 (Gal-1), a proto-type member of the galectin family, during intestinal inflammation in untreated and treated CeD patients. Our results unveil a substantial upregulation of Gal-1 accompanying the anti-inflammatory and tolerogenic response associated with gluten-free diet in CeD patients, suggesting a major role of this lectin in favoring resolution of inflammation and restoration of mucosal homeostasis. Thus, a coordinated network of galectins and their glycosylated ligands, exerting either anti-inflammatory or proinflammatory responses, may influence the interplay between intestinal epithelial cells and the highly specialized gut immune system in physiologic and pathologic settings.
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http://dx.doi.org/10.3389/fimmu.2018.00379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5837985PMC
May 2019

A Prospective Study on Cognitive Impairment in Middle-aged Adults With Newly Diagnosed Celiac Disease.

J Clin Gastroenterol 2019 04;53(4):290-294

Small Bowel Section, Department of Medicine, Dr. C. Bonorino Udaondo Gastroenterology Hospital.

Aims: Our objectives were to: (1) determine whether celiac disease (CD) patients have cognitive impairment at diagnosis; and (2) compare their cognitive performance with nonceliac subjects who have similar chronic symptoms and healthy controls.

Materials And Methods: Fifty adults (age range: 18 to 50 y) with symptoms and signs compatible with CD were enrolled in a prospective cohort irrespective of the final diagnosis. At baseline, all individuals underwent cognitive functional and psychological evaluation. CD patients were compared with subjects in whom CD was ruled out and with healthy controls matched by sex, age, and years of schooling.

Results: Thirty-three subjects (66%) were diagnosed with CD. Compared with the healthy controls (n=26), CD cases and disease controls (n=17; mostly irritable bowel syndrome) had impaired cognitive performance (P=0.02 and P=0.04, respectively), functional impairment (P<0.01), and higher depression (P<0.01). CD patients had similar cognitive performance and anxiety, but nonsignificant lower depression scores compared with disease controls.

Conclusions: Abnormal cognitive functions detected in newly diagnosed CD adult patients seem not to be disease specific. Our results suggest that cognitive dysfunction could be related to the presence of prolonged symptoms due to a chronic disease.
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http://dx.doi.org/10.1097/MCG.0000000000001018DOI Listing
April 2019

Improved Bone Microarchitecture in Patients With Celiac Disease After 3 Years on a Gluten-Free Diet.

Clin Gastroenterol Hepatol 2018 05 6;16(5):774-775. Epub 2017 Oct 6.

Research Institute, Universidad del Salvador, Buenos Aires, Argentina; Department of Medicine, Dr C. Bonorino Udaondo Gastroenterology Hospital, Buenos Aires, Argentina. Electronic address:

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http://dx.doi.org/10.1016/j.cgh.2017.09.054DOI Listing
May 2018

World Gastroenterology Organisation Global Guidelines: Celiac Disease February 2017.

J Clin Gastroenterol 2017 10;51(9):755-768

*Hospital de Gastroenterología Dr. C. Bonorino Udaondo †Universidad del Salvador, Buenos Aires, Argentina ‡Department of Medicine and Surgery, Scuola Medica Salernitana, University of Salerno, Salerno, Italy.

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http://dx.doi.org/10.1097/MCG.0000000000000919DOI Listing
October 2017

The CD That Pays Dividends: More Than 15 Years of Deamidated Gliadin Peptide Antibodies.

Dig Dis Sci 2017 05;62(5):1110-1112

Farncombe Family Digestive Health Research Institute, McMaster University Health Sciences Centre, Hamilton, ON, Canada.

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http://dx.doi.org/10.1007/s10620-017-4528-8DOI Listing
May 2017

Bifidobacterium infantis NLS Super Strain Reduces the Expression of α-Defensin-5, a Marker of Innate Immunity, in the Mucosa of Active Celiac Disease Patients.

J Clin Gastroenterol 2017 Oct;51(9):814-817

*Medicine Department, Farcombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada †Small Intestinal Section, Department of Medicine ‡Department of Alimentation, Dr. C. Bonorino Udaondo, Gastroenterology Hospital §Research Institute, Universidad del Salvador, Buenos Aires, Argentina.

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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http://dx.doi.org/10.1097/MCG.0000000000000687DOI Listing
October 2017

Altered Esophageal Mucosal Structure in Patients with Celiac Disease.

Can J Gastroenterol Hepatol 2016 29;2016:1980686. Epub 2016 Feb 29.

Department of Medicine, "Dr. Carlos Bonorino Udaondo" Gastroenterology Hospital, 1264 Buenos Aires, Argentina; Consejo de Investigación en Salud, MSAL, Gobierno de la Ciudad Autónoma de Buenos Aires, 1425 Buenos Aires, Argentina; Gastroenterology Chair, Universidad del Salvador, 1056 Buenos Aires, Argentina.

Background/Aim. Reflux symptoms (RS) are common in patients with celiac disease (CD), a chronic enteropathy that affects primarily the small intestine. We evaluated mucosal integrity and motility of the lower esophagus as mechanisms contributing to RS generation in patients with CD. Methods. We enrolled newly diagnosed CD patients with and without RS, nonceliac patients with classical reflux disease (GERD), and controls (without RS). Endoscopic biopsies from the distal esophagus were assessed for dilated intercellular space (DIS) by light microscopy and electron microscopy. Tight junction (TJ) mRNA proteins expression for zonula occludens-1 (ZO-1) and claudin-2 and claudin-3 (CLDN-2; CLDN-3) was determined using qRT-PCR. Results. DIS scores were higher in patients with active CD than in controls, but similar to GERD patients. The altered DIS was found even in CD patients without RS and normalized after one year of a gluten-free diet. CD patients with and without RS had lower expression of ZO-1 than controls. The expression of CLDN-2 and CLDN-3 was similar in CD and GERD patients. Conclusions. Our study shows that patients with active CD have altered esophageal mucosal integrity, independently of the presence of RS. The altered expression of ZO-1 may underlie loss of TJ integrity in the esophageal mucosa and may contribute to RS generation.
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http://dx.doi.org/10.1155/2016/1980686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4904646PMC
March 2017

Extraintestinal manifestations of celiac disease.

Dig Dis 2015 22;33(2):147-154. Epub 2015 Apr 22.

Case finding for celiac disease (CD) is becoming increasingly common practice and is conducted in a wide range of clinical situations ranging from the presence of gastrointestinal symptoms to failure to thrive in children, prolonged fatigue, unexpected weight loss and anemia. Case finding is also performed in associated conditions, such as autoimmune thyroid disease, dermatitis herpetiformis and type 1 diabetes, as well as in patients with irritable bowel syndrome, unexplained neuropsychiatric disorders and first-degree relatives of patients with diagnosed CD. This aggressive active case finding has dramatically changed the clinical characteristics of newly diagnosed patients. For instance, higher numbers of patients who present with extraintestinal symptoms are now being diagnosed with CD. Current recommendations state that due to a high risk for complications if the disease remains undiagnosed, patients with extraintestinal symptoms due to CD require appropriate diagnosis and treatment. Despite criticism regarding the cost-effectiveness of case finding in CD, such an aggressive approach has been considered cost-effective for high-risk patients. The diagnosis of CD among patients with extraintestinal symptoms requires a high degree of awareness of the clinical conditions that carry a high risk for underlying CD. Also, understanding the correct use of specific serology and duodenal histology is key for an appropriate diagnostic approach. Both procedures combined are able to confirm diagnosis in the vast majority of cases. However, in certain circumstances, serology and even duodenal histology cannot confirm or rule out CD. A common cause of negative IgA serology is IgA deficiency. For such eventuality, IgG-based serological tests can help confirm the diagnosis. Importantly, some histologically diagnosed cases still remain seronegative despite exclusion of IgA deficiency. On the other hand, duodenal histology may be normal despite the presence of CD-specific antibodies and active CD. This has been clearly demonstrated in some cases of untreated dermatitis herpetiformis, but may also be due to the patchy condition of CD or lesions that are not adequately recognized by nonexpert endoscopists and/or pathologists. The effectiveness of agluten-free diet depends on the clinical end point addressed. A good example is the outcome of bone loss. While risk for fracture normalizes after the first year of dietary treatment, bone parameters measured by densitometry may not be normalized in the long-term follow-up. Moreover, it is still unclear how far an early gluten-free diet will positively affect associated autoimmune diseases like type 1 diabetes and autoimmune thyroiditis.
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http://dx.doi.org/10.1159/000369541DOI Listing
January 2016

Psychological morbidity of celiac disease: A review of the literature.

United European Gastroenterol J 2015 Apr;3(2):136-45

Department of Medicine, "C. Bonorino Udaondo" Gastroenterology Hospital, Universidad del Salvador, Buenos Aires, Argentina.

Background: Celiac disease has been linked to decreased quality of life and certain mood disorders. The effect of the gluten free diet on these psychological aspects of the disease is still unclear.

Objectives: The objective of this article is to review the literature on psychological morbidity of celiac disease.

Methods: We performed a PubMed search for the time period from 1900 until June 1, 2014, to identify papers on psychological aspects of celiac disease looking specifically at quality of life, anxiety, depression and fatigue.

Results: Anxiety, depression and fatigue are common complaints in patients with untreated celiac disease and contribute to lower quality of life. While aspects of these conditions may improve within a few months after starting a gluten-free diet, some patients continue to suffer from significant psychological morbidity. Psychological symptoms may affect the quality of life and the dietary adherence.

Conclusion: Health care professionals need to be aware of the ongoing psychological burden of celiac disease in order to support patients with this disease.
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http://dx.doi.org/10.1177/2050640614560786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4406898PMC
April 2015

Understanding the role of probiotics in coeliac disease.

Br J Nutr 2015 May 14;113(10):1664-5. Epub 2015 Apr 14.

Small Bowel Section, Department of Medicine, Hospital de Gastroenterología Dr Carlos Bonorino Udaondo, Gastroenterology Chair, Univeridad del Salvador,Buenos

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http://dx.doi.org/10.1017/S0007114515000847DOI Listing
May 2015

Tax-deductible provisions for gluten-free diet in Canada compared with systems for gluten-free diet coverage available in various countries.

Can J Gastroenterol Hepatol 2015 Mar;29(2):104-10

Celiac disease affects 1% of the North American population, with an estimated 350,000 Canadians diagnosed with this condition. The disease is triggered by the ingestion of gluten, and a lifelong, strict gluten-free diet (GFD) is the only currently available treatment. Compliance with a strict GFD is essential not only for intestinal mucosal recovery and alleviation of symptoms, but also for the prevention of complications such as anemia, osteoporotic fractures and small bowel lymphoma. However, a GFD is difficult to follow, socially inconvenient and expensive. Different approaches, such as tax reduction, cash transfer, food provision, prescription and subsidy, have been used to reduce the additional costs of the GFD to patients with celiac disease. The current review showed that the systems in place exhibit particular advantages and disadvantages in relation to promoting uptake and compliance with GFD. The tax offset system used in Canada for GFD coverage takes the form of a reimbursement of a cost previously incurred. Hence, the program does not help celiac patients meet the incremental cost of the GFD - it simply provides some future refund of that cost. An ideal balanced approach would involve subsidizing gluten-free products through controlled vouchers or direct food provision to those who most need it, independently of 'ability or willingness to pay'. Moreover, if the cost of such a program is inhibitive, the value of the benefits could be made taxable to ensure that any patient contribution, in terms of additional taxation, is directly related to ability to pay. The limited coverage of GFD in Canada is concerning. There is an unmet need for GFD among celiac patients in Canada. More efforts are required by the Canadian medical community and the Canadian Celiac Association to act as agents in identifying ways of improving resource allocation in celiac disease.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4373559PMC
http://dx.doi.org/10.1155/2015/508156DOI Listing
March 2015

Advances in diagnosis and management of celiac disease.

Gastroenterology 2015 May 3;148(6):1175-86. Epub 2015 Feb 3.

Celiac Program, Harvard Medical School and Department of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.

Celiac disease is an autoimmune disorder that is induced by dietary gluten in genetically predisposed individuals. It has a prevalence of approximately 1% in many populations worldwide. New diagnoses have increased substantially, owing to increased awareness, better diagnostic tools, and probable real increases in incidence. The breadth of recognized clinical presentations continues to expand, making the disorder highly relevant to all physicians. Newer diagnostic tools, including serologic tests for antibodies against tissue transglutaminase and deamidated gliadin peptide, greatly facilitate diagnosis. Tests for celiac-permissive HLA-DQ2 and HLA-DQ8 molecules are useful in defined clinical situations. Celiac disease is diagnosed by histopathologic examination of duodenal biopsy specimens. However, according to recent controversial guidelines, a diagnosis can be made without a biopsy in certain circumstances, especially in children. Symptoms, mortality, and risk for malignancy each can be reduced by adherence to a gluten-free diet. This treatment is a challenge, however, because the diet is expensive, socially isolating, and not always effective in controlling symptoms or intestinal damage. Hence, there is increasing interest in developing nondietary therapies.
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http://dx.doi.org/10.1053/j.gastro.2015.01.044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4409570PMC
May 2015

Diagnosis and management of adult coeliac disease: guidelines from the British Society of Gastroenterology.

Gut 2014 Aug 10;63(8):1210-28. Epub 2014 Jun 10.

Gastroenterology and Liver Unit, Royal Hallamshire Hospital & University of Sheffield, Sheffield, UK.

A multidisciplinary panel of 18 physicians and 3 non-physicians from eight countries (Sweden, UK, Argentina, Australia, Italy, Finland, Norway and the USA) reviewed the literature on diagnosis and management of adult coeliac disease (CD). This paper presents the recommendations of the British Society of Gastroenterology. Areas of controversies were explored through phone meetings and web surveys. Nine working groups examined the following areas of CD diagnosis and management: classification of CD; genetics and immunology; diagnostics; serology and endoscopy; follow-up; gluten-free diet; refractory CD and malignancies; quality of life; novel treatments; patient support; and screening for CD.
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http://dx.doi.org/10.1136/gutjnl-2013-306578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4112432PMC
August 2014

Issues associated with the emergence of coeliac disease in the Asia–Pacific region: a working party report of the World Gastroenterology Organization and the Asian Pacific Association of Gastroenterology.

J Gastroenterol Hepatol 2014 Apr;29(4):666-77

Background And Aim: Once thought to be uncommon in Asia, coeliac disease (CD) is now being increasingly recognized in Asia–Pacific region. In many Asian nations, CD is still considered to be either nonexistent or very rare. In recognition of such heterogeneity of knowledge and awareness, the World Gastroenterology Organization and the Asian Pacific Association of Gastroenterology commissioned a working party to address the key issues in emergence of CD in Asia.

Methods: A working group consisting of members from Asia–Pacific region, Europe, North America, and South America reviewed relevant existing literature with focus on those issues specific to Asia–Pacific region both in terms of what exists and what needs to be done.

Results: The working group identified the gaps in epidemiology, diagnosis, and management of CD in Asian–Pacific region and recommended the following: to establish prevalence of CD across region, increase in awareness about CD among physicians and patients, and recognition of atypical manifestations of CD. The challenges such as variability in performance of serological tests, lack of population-specific cut-offs values for a positive test, need for expert dietitians for proper counseling and supervision of patients, need for gluten-free infrastructure in food supply and creation of patient advocacy organizations were also emphasized.

Conclusions: Although absolute number of patients with CD at present is not very large, this number is expected to increase over the next few years or decades. It is thus appropriate that medical community across the Asia–Pacific region define extent of problem and get prepared to handle impending epidemic of CD.
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http://dx.doi.org/10.1111/jgh.12514DOI Listing
April 2014

Novel role of the serine protease inhibitor elafin in gluten-related disorders.

Am J Gastroenterol 2014 May 8;109(5):748-56. Epub 2014 Apr 8.

Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Canada.

Objectives: Elafin, an endogenous serine protease inhibitor, modulates colonic inflammation. We investigated the role of elafin in celiac disease (CD) using human small intestinal tissues and in vitro assays of gliadin deamidation. We also investigated the potential beneficial effects of elafin in a mouse model of gluten sensitivity.

Methods: Epithelial elafin expression in the small intestine of patients with active CD, treated CD, and controls without CD was determined by immunofluorescence. Interaction of elafin with human tissue transglutaminase-2 (TG-2) was investigated in vitro. The 33-mer peptide, a highly immunogenic gliadin peptide, was incubated with TG-2 and elafin at different concentrations. The degree of deamidation of the 33-mer peptide was analyzed by liquid chromatography-mass spectrometry. Elafin was delivered to the intestine of gluten-sensitive mice using a recombinant Lactococcus lactis vector. Small intestinal barrier function, inflammation, proteolytic activity, and zonula occludens-1 (ZO-1) expression were assessed.

Results: Elafin expression in the small intestinal epithelium was lower in patients with active CD compared with control patients. In vitro, elafin significantly slowed the kinetics of the deamidation of the 33-mer peptide to its more immunogenic form. Treatment of gluten-sensitive mice with elafin delivered by the L. lactis vector normalized inflammation, improved permeability, and maintained ZO-1 expression.

Conclusions: The decreased elafin expression in the small intestine of patients with active CD, the reduction of 33-mer peptide deamidation by elafin, coupled to the barrier enhancing and anti-inflammatory effects observed in gluten-sensitive mice, suggest that this molecule may have pathophysiological and therapeutic importance in gluten-related disorders.
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http://dx.doi.org/10.1038/ajg.2014.48DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4219532PMC
May 2014

Non-Celiac Gluten sensitivity: the new frontier of gluten related disorders.

Nutrients 2013 Sep 26;5(10):3839-53. Epub 2013 Sep 26.

Department of Pediatrics, Università Politecnica delle Marche, Ancona 60121, Italy.

Non Celiac Gluten sensitivity (NCGS) was originally described in the 1980s and recently a "re-discovered" disorder characterized by intestinal and extra-intestinal symptoms related to the ingestion of gluten-containing food, in subjects that are not affected with either celiac disease (CD) or wheat allergy (WA). Although NCGS frequency is still unclear, epidemiological data have been generated that can help establishing the magnitude of the problem. Clinical studies further defined the identity of NCGS and its implications in human disease. An overlap between the irritable bowel syndrome (IBS) and NCGS has been detected, requiring even more stringent diagnostic criteria. Several studies suggested a relationship between NCGS and neuropsychiatric disorders, particularly autism and schizophrenia. The first case reports of NCGS in children have been described. Lack of biomarkers is still a major limitation of clinical studies, making it difficult to differentiate NCGS from other gluten related disorders. Recent studies raised the possibility that, beside gluten, wheat amylase-trypsin inhibitors and low-fermentable, poorly-absorbed, short-chain carbohydrates can contribute to symptoms (at least those related to IBS) experienced by NCGS patients. In this paper we report the major advances and current trends on NCGS.
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http://dx.doi.org/10.3390/nu5103839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3820047PMC
September 2013

Diagnosis of celiac disease during pre-operative work-up for bariatric surgery.

Acta Gastroenterol Latinoam 2012 Dec;42(4):321-4

Department of Surgery, Dr C Bonorino Udaondo Gastroenterology Hospital, Buenos Aires, Argentina.

Background And Aim: Morbid obesity is a highly prevalent condition. In selected cases, bariatric surgery is indicated. Although for decades celiac disease (CD) has been associated with chronic diarrhea and weight loss, now it becomes clear that the clinical spectrum is extremely wide.

Methods: We report 5 morbidly obese patients that were diagnosed of CD during preoperative work-up for bariatric surgery. Diagnosis was suspected during routine upper endoscopy, and confirmed by histology and positive CD-specific serology.

Result: Four of the 5 cases were asymptomatic. One complained of chronic diarrhea and anemia. All cases initiated a gluten-free diet. Due to CD, patients were offered a purely restrictive bariatric procedure. Three patients underwent a sleeve gastrectomy while the other two are still undergoing pre-operative evaluations.

Conclusion: This report enlarges the clinical spectrum of untreated CD. Although prevalence of CD in obese patients seems to be similar to that in the general population, morbid obese patients should be tested for CD in order to establish the best surgical strategy and outcome.
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December 2012

Exploratory, randomized, double-blind, placebo-controlled study on the effects of Bifidobacterium infantis natren life start strain super strain in active celiac disease.

J Clin Gastroenterol 2013 Feb;47(2):139-47

Small Intestinal Section, Department of Medicine, Hospital de Clínicas José de San Martín, Universidad de Buenos Aires, Argentina.

Background/aims: The aim of this exploratory trial was to establish if the probiotic Bifidobacterium natren life start (NLS) strain strain may affect the clinical course and pathophysiological features of patients with untreated celiac disease (CD). Positive findings would be helpful in directing future studies.

Methods: Twenty-two adult patients having 2 positives CD-specific tests were enrolled. Patients were randomized to receive 2 capsules before meals for 3 weeks of either Bifidobacterium infantis natren life start strain super strain (Lifestart 2) (2×10(9) colony-forming units per capsule) (n = 12) or placebo (n = 10), whereas they also consumed at least 12 g of gluten/day. A biopsy at the end of the trial confirmed CD in all cases. The primary outcome was intestinal permeability changes. Secondary endpoints were changes in symptoms and the Gastrointestinal Symptom Rating Scale, and in immunologic indicators of inflammation.

Results: The abnormal baseline intestinal permeability was not significantly affected by either treatment. In contrast to patients on placebo, those randomized to B. infantis experienced a significant improvement in Gastrointestinal Symptom Rating Scale (P = 0.0035 for indigestion; P = 0.0483 for constipation; P = 0.0586 for reflux). Final/baseline IgA tTG and IgA DGP antibody concentration ratios were lower in the B. infantis arm (P = 0.055 for IgA tTG and P = 0.181 for IgA DGP). Final serum macrophage inflammatory protein-1β increased significantly (P < 0.04) only in patients receiving B. infantis. The administration of B. infantis was safe.

Conclusions: The study suggests that B. infantis may alleviate symptoms in untreated CD. The probiotic produced some immunologic changes but did not modify abnormal intestinal permeability. Further studies are necessary to confirm and/or expand these observations.
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http://dx.doi.org/10.1097/MCG.0b013e31827759acDOI Listing
February 2013

The Oslo definitions for coeliac disease and related terms.

Gut 2013 Jan 16;62(1):43-52. Epub 2012 Feb 16.

Division of Gastroenterology, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215, USA.

Objective: The literature suggests a lack of consensus on the use of terms related to coeliac disease (CD) and gluten.

Design: A multidisciplinary task force of 16 physicians from seven countries used the electronic database PubMed to review the literature for CD-related terms up to January 2011. Teams of physicians then suggested a definition for each term, followed by feedback of these definitions through a web survey on definitions, discussions during a meeting in Oslo and phone conferences. In addition to 'CD', the following descriptors of CD were evaluated (in alphabetical order): asymptomatic, atypical, classical, latent, non-classical, overt, paediatric classical, potential, refractory, silent, subclinical, symptomatic, typical, CD serology, CD autoimmunity, genetically at risk of CD, dermatitis herpetiformis, gluten, gluten ataxia, gluten intolerance, gluten sensitivity and gliadin-specific antibodies.

Results: CD was defined as 'a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals'. Classical CD was defined as 'CD presenting with signs and symptoms of malabsorption. Diarrhoea, steatorrhoea, weight loss or growth failure is required.' 'Gluten-related disorders' is the suggested umbrella term for all diseases triggered by gluten and the term gluten intolerance should not to be used. Other definitions are presented in the paper.

Conclusion: This paper presents the Oslo definitions for CD-related terms.
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http://dx.doi.org/10.1136/gutjnl-2011-301346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3440559PMC
January 2013
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