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Temporal and Geographic Trends in Celiac Disease Research: A Bibliometric Analysis
Su1260
assay algorithm was highly sensitive and predictive for diagnosing CD. We recommend screening for CD to patients with CC.
AGA Abstracts
A Phase II, Single Blind, Cross-Over Study of Acute Administration of Trititicum Monococcum (Cultivar Monlis) in Patients With Coeliac Disease (CD) Barbara Zanini, Beatrice Petroboni, Tarcisio Not, Norberto Pogna, Alberto Lanzini
Su1262 Temporal and Geographic Trends in Celiac Disease Research: A Bibliometric Analysis Benjamin Lebwohl, David Narotsky, Peter H. Green
Atoxic, widely available, unexpensive cereals retaining dough properties for production of palatable baked goods for gluten free diet (GFD) of CD patients are actively researched. Triticum monococcum ssp monococcum (Tm) is an ancient wheat with virtually absent toxicity In Vitro1 and ex vivo2. The aim of our stuy was to investigate the “In Vivo” effect of a single dose of gluten of Tm (cultivar Monlis), in patients with CD in GFD. We performed a Phase II, single blind, cross-over study in CD patients adherent to GFD for at least 12 months. Each patient was randomly assigned to receive at time 0, 14 and 28 days a single 2.5 grams dose of one of the following flours: rice flour, Tm flour and Triticum aestivum (Ta) flour mixed with gluten-free pudding. The primary end-point of the study was the change in intestinal permeability (IP) as assessed by changes of urinary lactulose/rhamnose ratio (L/R ratio) measured by HPLC. We also assessed the occurrence of gastrointestinal adverse events graded for intensity and duration (WHO scale). Variables are expressed as mean ± SEM; paired t-test and chi2 test were used as appropriate. Twelve CD patients were enrolled in the study. The urinary L/R ratio was 0.058 ± 0.03 with rice flour, 0.048 ± 0.02 with Tm and 0.063 ± 0.015 with Ta. Differences did not reach statistical level of significance. Gastrointestinal adverse events were 11, 8 and 31 with rice, Tm and Ta, respectively. Eight gastrointestinal events occurred during Tm administration, a value similar to that observed with rice (n = 11). In all cases events were graded as “mild” or “moderate”. By contrast 31 adverse events were reported during Ta administration, a value significantly higher than that observed with Tm (p<0.0001) and with rice (p<0.0001, table). In 4 cases events during Ta administration were graded “severe” or “disabling”. Among extraintestinal adverse events, headache was reported in 13 cases and not specific malaise in 3 cases, equally distributed among the 3 flours. We conclude that administration of a single 2.5 g dose of Tm to CD patients does not cause changes in urinary L/R ratio relative to that observed following administration of rice, the non toxic reference flour. Administration of Ta did not cause a significant increase of L/R ratio that remained similar to that observed with rice and Tm. Tm was well tolerated by all patients thus providing the rationale for further investigation on the safety of this cereal for CD patients. By contrast Ta caused a significant number of gastrointestinal side effects that in 4 cases were severe, but did not alter significantly urinary L/R ratio indicating that this method is not sensitive enough for acute toxicity studies.
Background: Despite the increasing prevalence of celiac disease (CD), research has historically lagged behind that of other gastrointestinal diseases. Anecdotal evidence points to increasing interest in CD, but the rate of research output has not been formally quantified. Methods: We employed an iterative search process to identify all articles in the peer-reviewed medical literature (using Pubmed) from 1980-2009, and compared the quantity of publications featuring CD to that of Crohn's disease and H. pylori. For the most recent 15-year period (1995-2009), we analyzed CD output with regard to its degree of diffusion among journals and authors. We also quantified the CD research output per nation and assessed for an association between economic parameters and CD research output. Results: The number of publications in the field of CD increased steadily since 1980, with an acceleration in the rate of increase beginning in 1995; this trend was also observed in the quantity of publications in Crohn's disease, while rates for H Pylori has begun to decline (Figure). CD publications comprised 0.07% of all publications in 1995-1999 and 0.09% in 2005-2009. The ten journals with the largest number of Crohn's disease publications were responsible for 29% of all Crohn's research output in 1995-1999, and 30% in 2005-2009. In contrast, the top ten CD journals were responsible for 34% of CD output in 1995-1999 but only 25% in 2005-2009 (p for trend <0.0001). The ten most prolific authors in CD participated in 12% of all CD publications, whereas the ten most prolific authors in Crohn's disease participated in 8% of all Crohn's disease publications. In the years 2000-2009, the United States was the largest source (35%) of CD publications. Publication output was weakly associated with population (r=0.12, p=0.34) and with government spending on research and development (r=0.095) but moderately with per-capita GDP (r=0.28, p=0.03). Conclusions: The number of publications in CD is increasing, out of proportion to the overall growth of the peerreviewed medical literature. Compared to Crohn's disease, CD publications are spread throughout a larger number of journals, but are more dominated by high-volume authors. Economic factors are associated with national contributions to the world literature in CD.
Su1263 Effect of Gluten Free Diet (GFD) on Cardiovascular Risk Factors: Results in a Cohort of 765 Celiac Disease (CD) Patients Barbara Zanini, Elisa Mazzoncini, Francesca Caselani, Alberto Magni, Chiara Ricci, Alberto Lanzini
*p<0.0001 Su1261
Introduction/Aim: There is conflicting evidence as to whether CD patients have increased baseline cardiovascular risk, and whether this risk is affected by GFD. The aim of our study was to asses the prevalence of cardiovascular risk factors in a large number of CD patients at diagnosis, and the effect of GFD. Methods: We extracted information from a prospectively maintained data-base on characteristics of CD patients diagnosed in our CD Clinic. Information included total cholesterol (TC), triglycerides, HDL cholesterol, LDL cholesterol (Friedewal formula), homocysteinemia, GGT level and BMI measured in patients studied twice, before and after at least 12 months GFD. Patients with associated diseases affecting lipid profile at baseline were excluded. Results are expressed as mean ± SD; paired and unpaired t-test have been used as appropriate for statistical analysis. Results: A cohort of 765 CD patients was identified: 551 female (72%), 690 (90%) with Marsh III histopathology, and 634 (83%) symptomatic at baseline. At baseline, BMI was ≥ 25 in 124/612 (20%), homocysteinemia was >15 μmol/L in 24/68 (35%), and TC was below 200 mg/dL in 525/650 (81%). Results obtained in patients studied twice,before and during GFD,are summarized in the table. More detailed information was also available for a subgroup of 37 patients. HDL increased from 47 ± 2 mg/dL at baseline to 53 ± 1 mg/dL (p=0.002) during GFD. LDL remained unchanged and LDL/HDL ratio decreased from 2.5 ± 1.0 at baseline to 2.3 ± 0.9 (p=0.05) during GFD. Homocysteinemia remained unchanged during GFD at 15.2 ± 9.8 μmol/L vs. 17.4 ± 8.9 at baseline (NS). Conclusion: Our study indicates that risk and protective factors for cardiovascular diseases coexist in CD both at baseline and during GFD. Hyperhomocysteinemia accompanied by increased GGT level and by increased proportion of overweight patients predicts a pro-atherogenic effect of GFD, but reduced tryglicerides and increased HDL point to the opposite effect. Although these results are in keeping with the uncertainty on prevalence of vascular outcomes in CD, they suggest that in order to be healthy GFD has to go beyond gluten exclusion to include control of body weight and of quality of nutrients.
Increased Prevalence of Celiac Disease and Positive Markers of Gluten Sensitivity in Patients With Chronic Constipation Hui Jer Hwang, Lucila Facio, Guido Iantorno, Emilia Sugai, María Laura Moreno, Horacio Vázquez, Edgardo Smecuol, Maria Ines Pinto Sanchez, Roberto M. Mazure, Eduardo Mauriño, Julio Bai Background: Although celiac disease (CD) diagnosis is commonly associated with the presence of chronic diarrhea, up to 10% of newly diagnosed cases may present chronic constipation (CC). However, no studies have explored the prevalence of CD or markers of gluten sensitivity among patients consulting by CC. Aims: To prospectively determine the prevalence of positive markers of gluten sensitivity and CD in a series of patients with CC. Methods: Serum samples from 105 adult consecutive patients (99 females; age range: 18-65 years) attending the Motility and Functional Disorders Unit at a tertiary referral center with a diagnosis of chronic functional constipation (69.5%) or irritable bowel syndrome with constipation (Rome III criteria) were analyzed with a single ELISA assay to detect IgA and IgG antibodies to deamidated gliadin peptides and tissue transglutaminase (DGP/tTG Screen) (cut-off values: >20 U/mL). Seropositive cases were subsequently tested for IgA tissue transglutaminase (IgA tTG), and all DGP/tTG Screen positive patients underwent endoscopic biopsies from the second duodenal portion. The prevalence of CD was compared with that among 518 control subjects referred for routine upper GI endoscopy due to symptoms not primarily related to CD who were tested using the same algorithm. Diagnosis of CD was based on the presence of a type IIIa Marsh's enteropathy or greater in seropositive cases. Results: Ten patients (9.5%) with CC had a positive DGP/tTG Screen test, compared with 45 subjects (8.7%) of the control population. Intestinal biopsy confirmed CD enteropathy in 3 seropositive patients with CC and 13 of the control population. The estimated prevalence was 2.8% for patients with CC and 2.5% for controls. The IgA tTG test was also positive in 5 of the 10 patients with CC, including the 3 cases finally diagnosed with CD, and in 12 control subjects (100% and 92% sensitivity, respectively). Based on positive serology without enteropathy, 7 patients with CC were considered as gluten sensitive. The effect of the gluten-free diet on CC syndrome in CD patients and gluten sensitive patients is still being evaluated. Conclusions: This study is the first to discover a high prevalence of CD and gluten sensitivity in patients complaining of CC. This prevalence is almost 4 times greater than that estimated for the Argentinean general population (0.7%) and comparable to that of subjects attending an endoscopic unit. The study shows that the proposed serological
AGA Abstracts
S-444
assay algorithm was highly sensitive and predictive for diagnosing CD. We recommend screening for CD to patients with CC.
AGA Abstracts
A Phase II, Single Blind, Cross-Over Study of Acute Administration of Trititicum Monococcum (Cultivar Monlis) in Patients With Coeliac Disease (CD) Barbara Zanini, Beatrice Petroboni, Tarcisio Not, Norberto Pogna, Alberto Lanzini
Su1262 Temporal and Geographic Trends in Celiac Disease Research: A Bibliometric Analysis Benjamin Lebwohl, David Narotsky, Peter H. Green
Atoxic, widely available, unexpensive cereals retaining dough properties for production of palatable baked goods for gluten free diet (GFD) of CD patients are actively researched. Triticum monococcum ssp monococcum (Tm) is an ancient wheat with virtually absent toxicity In Vitro1 and ex vivo2. The aim of our stuy was to investigate the “In Vivo” effect of a single dose of gluten of Tm (cultivar Monlis), in patients with CD in GFD. We performed a Phase II, single blind, cross-over study in CD patients adherent to GFD for at least 12 months. Each patient was randomly assigned to receive at time 0, 14 and 28 days a single 2.5 grams dose of one of the following flours: rice flour, Tm flour and Triticum aestivum (Ta) flour mixed with gluten-free pudding. The primary end-point of the study was the change in intestinal permeability (IP) as assessed by changes of urinary lactulose/rhamnose ratio (L/R ratio) measured by HPLC. We also assessed the occurrence of gastrointestinal adverse events graded for intensity and duration (WHO scale). Variables are expressed as mean ± SEM; paired t-test and chi2 test were used as appropriate. Twelve CD patients were enrolled in the study. The urinary L/R ratio was 0.058 ± 0.03 with rice flour, 0.048 ± 0.02 with Tm and 0.063 ± 0.015 with Ta. Differences did not reach statistical level of significance. Gastrointestinal adverse events were 11, 8 and 31 with rice, Tm and Ta, respectively. Eight gastrointestinal events occurred during Tm administration, a value similar to that observed with rice (n = 11). In all cases events were graded as “mild” or “moderate”. By contrast 31 adverse events were reported during Ta administration, a value significantly higher than that observed with Tm (p<0.0001) and with rice (p<0.0001, table). In 4 cases events during Ta administration were graded “severe” or “disabling”. Among extraintestinal adverse events, headache was reported in 13 cases and not specific malaise in 3 cases, equally distributed among the 3 flours. We conclude that administration of a single 2.5 g dose of Tm to CD patients does not cause changes in urinary L/R ratio relative to that observed following administration of rice, the non toxic reference flour. Administration of Ta did not cause a significant increase of L/R ratio that remained similar to that observed with rice and Tm. Tm was well tolerated by all patients thus providing the rationale for further investigation on the safety of this cereal for CD patients. By contrast Ta caused a significant number of gastrointestinal side effects that in 4 cases were severe, but did not alter significantly urinary L/R ratio indicating that this method is not sensitive enough for acute toxicity studies.
Background: Despite the increasing prevalence of celiac disease (CD), research has historically lagged behind that of other gastrointestinal diseases. Anecdotal evidence points to increasing interest in CD, but the rate of research output has not been formally quantified. Methods: We employed an iterative search process to identify all articles in the peer-reviewed medical literature (using Pubmed) from 1980-2009, and compared the quantity of publications featuring CD to that of Crohn's disease and H. pylori. For the most recent 15-year period (1995-2009), we analyzed CD output with regard to its degree of diffusion among journals and authors. We also quantified the CD research output per nation and assessed for an association between economic parameters and CD research output. Results: The number of publications in the field of CD increased steadily since 1980, with an acceleration in the rate of increase beginning in 1995; this trend was also observed in the quantity of publications in Crohn's disease, while rates for H Pylori has begun to decline (Figure). CD publications comprised 0.07% of all publications in 1995-1999 and 0.09% in 2005-2009. The ten journals with the largest number of Crohn's disease publications were responsible for 29% of all Crohn's research output in 1995-1999, and 30% in 2005-2009. In contrast, the top ten CD journals were responsible for 34% of CD output in 1995-1999 but only 25% in 2005-2009 (p for trend <0.0001). The ten most prolific authors in CD participated in 12% of all CD publications, whereas the ten most prolific authors in Crohn's disease participated in 8% of all Crohn's disease publications. In the years 2000-2009, the United States was the largest source (35%) of CD publications. Publication output was weakly associated with population (r=0.12, p=0.34) and with government spending on research and development (r=0.095) but moderately with per-capita GDP (r=0.28, p=0.03). Conclusions: The number of publications in CD is increasing, out of proportion to the overall growth of the peerreviewed medical literature. Compared to Crohn's disease, CD publications are spread throughout a larger number of journals, but are more dominated by high-volume authors. Economic factors are associated with national contributions to the world literature in CD.
Su1263 Effect of Gluten Free Diet (GFD) on Cardiovascular Risk Factors: Results in a Cohort of 765 Celiac Disease (CD) Patients Barbara Zanini, Elisa Mazzoncini, Francesca Caselani, Alberto Magni, Chiara Ricci, Alberto Lanzini
*p<0.0001 Su1261
Introduction/Aim: There is conflicting evidence as to whether CD patients have increased baseline cardiovascular risk, and whether this risk is affected by GFD. The aim of our study was to asses the prevalence of cardiovascular risk factors in a large number of CD patients at diagnosis, and the effect of GFD. Methods: We extracted information from a prospectively maintained data-base on characteristics of CD patients diagnosed in our CD Clinic. Information included total cholesterol (TC), triglycerides, HDL cholesterol, LDL cholesterol (Friedewal formula), homocysteinemia, GGT level and BMI measured in patients studied twice, before and after at least 12 months GFD. Patients with associated diseases affecting lipid profile at baseline were excluded. Results are expressed as mean ± SD; paired and unpaired t-test have been used as appropriate for statistical analysis. Results: A cohort of 765 CD patients was identified: 551 female (72%), 690 (90%) with Marsh III histopathology, and 634 (83%) symptomatic at baseline. At baseline, BMI was ≥ 25 in 124/612 (20%), homocysteinemia was >15 μmol/L in 24/68 (35%), and TC was below 200 mg/dL in 525/650 (81%). Results obtained in patients studied twice,before and during GFD,are summarized in the table. More detailed information was also available for a subgroup of 37 patients. HDL increased from 47 ± 2 mg/dL at baseline to 53 ± 1 mg/dL (p=0.002) during GFD. LDL remained unchanged and LDL/HDL ratio decreased from 2.5 ± 1.0 at baseline to 2.3 ± 0.9 (p=0.05) during GFD. Homocysteinemia remained unchanged during GFD at 15.2 ± 9.8 μmol/L vs. 17.4 ± 8.9 at baseline (NS). Conclusion: Our study indicates that risk and protective factors for cardiovascular diseases coexist in CD both at baseline and during GFD. Hyperhomocysteinemia accompanied by increased GGT level and by increased proportion of overweight patients predicts a pro-atherogenic effect of GFD, but reduced tryglicerides and increased HDL point to the opposite effect. Although these results are in keeping with the uncertainty on prevalence of vascular outcomes in CD, they suggest that in order to be healthy GFD has to go beyond gluten exclusion to include control of body weight and of quality of nutrients.
Increased Prevalence of Celiac Disease and Positive Markers of Gluten Sensitivity in Patients With Chronic Constipation Hui Jer Hwang, Lucila Facio, Guido Iantorno, Emilia Sugai, María Laura Moreno, Horacio Vázquez, Edgardo Smecuol, Maria Ines Pinto Sanchez, Roberto M. Mazure, Eduardo Mauriño, Julio Bai Background: Although celiac disease (CD) diagnosis is commonly associated with the presence of chronic diarrhea, up to 10% of newly diagnosed cases may present chronic constipation (CC). However, no studies have explored the prevalence of CD or markers of gluten sensitivity among patients consulting by CC. Aims: To prospectively determine the prevalence of positive markers of gluten sensitivity and CD in a series of patients with CC. Methods: Serum samples from 105 adult consecutive patients (99 females; age range: 18-65 years) attending the Motility and Functional Disorders Unit at a tertiary referral center with a diagnosis of chronic functional constipation (69.5%) or irritable bowel syndrome with constipation (Rome III criteria) were analyzed with a single ELISA assay to detect IgA and IgG antibodies to deamidated gliadin peptides and tissue transglutaminase (DGP/tTG Screen) (cut-off values: >20 U/mL). Seropositive cases were subsequently tested for IgA tissue transglutaminase (IgA tTG), and all DGP/tTG Screen positive patients underwent endoscopic biopsies from the second duodenal portion. The prevalence of CD was compared with that among 518 control subjects referred for routine upper GI endoscopy due to symptoms not primarily related to CD who were tested using the same algorithm. Diagnosis of CD was based on the presence of a type IIIa Marsh's enteropathy or greater in seropositive cases. Results: Ten patients (9.5%) with CC had a positive DGP/tTG Screen test, compared with 45 subjects (8.7%) of the control population. Intestinal biopsy confirmed CD enteropathy in 3 seropositive patients with CC and 13 of the control population. The estimated prevalence was 2.8% for patients with CC and 2.5% for controls. The IgA tTG test was also positive in 5 of the 10 patients with CC, including the 3 cases finally diagnosed with CD, and in 12 control subjects (100% and 92% sensitivity, respectively). Based on positive serology without enteropathy, 7 patients with CC were considered as gluten sensitive. The effect of the gluten-free diet on CC syndrome in CD patients and gluten sensitive patients is still being evaluated. Conclusions: This study is the first to discover a high prevalence of CD and gluten sensitivity in patients complaining of CC. This prevalence is almost 4 times greater than that estimated for the Argentinean general population (0.7%) and comparable to that of subjects attending an endoscopic unit. The study shows that the proposed serological
AGA Abstracts
S-444