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

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.

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.

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.

Altered Esophageal Mucosal Structure in Patients with Celiac Disease.

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.

The prevalence of laryngeal pathologies in an academic population.

OBJECTIVE: The main purposes of the present study were to determine the prevalence of laryngeal pathology and voice disorders and to identify their associated risk factors among the workers, teachers, and nonteachers, from a Portuguese university. STUDY DESIGN: Cross-sectional study. METHODOLOGY: A total of 101 participants have volunteered to participate in a voice survey. Data were collected using a questionnaire followed by the diagnosis of laryngeal pathology based on the videolaryngoscopic examination conducted by experienced otolaryngologists. RESULTS: The mean age of the participants was 43 years. Nearly half of the sample had a diagnosis of pathology, with functional disorders being the most frequent laryngeal pathology. None of the demographic, behavioral, and occupational factors analyzed were statistically associated with laryngeal pathology. Although university teachers do not have an increased risk of laryngeal pathology, self-perceived voice disorders were more prevalent in teachers than in nonteachers. Vocal effort and the number of years teaching have a significant effect on voice disorders prevalence among teachers. CONCLUSIONS: Voice disorders have a higher rate of occurrence among university teachers. Demands of teaching, like vocal effort and years of teaching, and not other demographic and/or behavioral factors, are the risk factors that increase the rate of occurrence of voice disorders among the university teachers. Risk factors that predispose to laryngeal pathology were not detected in the present study. However, the high prevalence of functional laryngeal pathologies underlines the importance of further investigation toward this type of laryngeal pathology in this academic population.

Use of cepstral analyses for differentiating normal from dysphonic voices: a comparative study of connected speech versus sustained vowel in European Portuguese female speakers.

OBJECTIVE: The aim of this study was to investigate the use of cepstral peak prominence (CPP) and CPP-smoothed (CPPs) to differentiate dysphonic from nondysphonic voices, using two speech tasks: sustained vowel /a/ and connected speech. STUDY DESIGN: A retrospective study was based on data selected from an archival database of recorded voices. METHODS: Sixty age- and occupation-matched individuals (30 participants with dysphonia and 30 controls) were recorded producing the sustained vowel /a/ and reading the European Portuguese version of "The Story of Arthur the Rat." Recorded voices were analyzed acoustically by measuring CPP and CPPs and auditory-perceptual ratings were related to the acoustic measurements. RESULTS: For the sustained vowel, both CPP and CPPs measures were significantly different between dysphonic and control groups. For connected speech, only CPP values revealed significant differences between the two groups, both in direct and narrative speech. Acoustic measurements correlated with the auditory-perceptual classifications in both sustained vowel and connected speech, although the strongest correlation (0.6 < r < 0.7) was obtained between CPP and the perception of breathiness. CONCLUSIONS: The results of this study suggest that analysis of CPP and CPPs is a promising tool in clinical practice with European Portuguese speakers.

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

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-1ß 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.

Individualised vs fixed dose of oral 17ß-oestradiol for induction of puberty in girls with Turner syndrome: an open-randomised parallel trial.

CONTEXT: Oestrogen induction of pubertal changes in Turner girls may reinforce their psychological well-being and may also optimise final height; however, oestrogen type, dose, and route are not well established. OBJECTIVE: To induce normal pubertal development in Turner girls and ovarian insufficiency with oral 17ß-oestradiol (E(2)), either as individualised dose (ID) or as fixed dose (FD), and to determine whether growth is affected. DESIGN: Open-label randomised, parallel groups, multicentre clinical trial in 48 GH-treated Turner girls. Oral E(2) was given in tablets, either as an ID of 5-15 µg/kg per day during 2 years or as a FD of 0.2 mg daily during the first year followed by 0.5 mg daily during the second year. Main outcome measures were the event of attaining a Tanner breast staging ≥4 (primary), FSH, and auxological variables (secondary). RESULTS: Shorter median time to Tanner staging ≥ B4 in the FD group (733 days) compared with the ID group (818 days) (P=0.046). Higher proportion of girls with Tanner staging ≥ B4 (65%) in the FD group compared with the ID group (42%) (P=0.068). Bone age did not show inadequate acceleration and adult height prediction was maintained in both groups. No oestrogen-related adverse events were reported. CONCLUSIONS: Two-year treatment with oral E(2) can progressively induce normal pubertal development in Turner syndrome. Low-dose oral E(2) given as a FD produces a satisfactory pubertal development not inferior to ID. Treatment was well tolerated and did not interfere with the growth-promoting effect of GH.

Estudio epidemiológico prospectivo para el análisis de la prevalencia de enfermedad celíaca en pacientes con constipación crónica / Prospective epidemiological study for the analysis of prevalence of celiac disease in patients with chronic constipation

INTRODUCCION: Aunque la enfermedad celíaca (EC) se asocia comúnmente a diarrea crónica, 10% de los casos pueden presentarse con constipación crónica (CC). No hay estudios que exploren la prevalencia de EC o marcadores potenciales de la sensibilidad al gluten (SG) en pacientes que consultan por CC.OBJETIVO: Determinar la prevalencia de marcadores potenciales de SG y EC en pacientes con CC que consultan a un centro terciario de referencia.METODOS: Estudio exploratorio prospectivo. Se evaluó a 121 pacientes adultos consecutivos con diagnóstico de CC funcional (67,8%) o SII-C (criterios de Roma III) con anticuerpos contra péptidos deamidados de gliadina IgA e IgG y anti-transglutaminasa tisular (DGP/tTGscreen valor corte=20). Los casos seropositivos fueron analizados con IgA tTG y todos los DGP/tTG Screen casos positivos se sometieron a biopsias endoscópicas de duodeno. La prevalencia se comparó con la de 518 sujetos (endoscopía digestiva alta por síntomas no relacionados primariamente con EC) y con la estimada para la población urbana del Gran La Plata. Se consideró diagnóstico de EC a la presencia de una enteropatía Marsh Illa o mayor en los casos seropositivos. Se consideró SG a los casos seropositivos sin enteropatía ni autoanticuerpos (IgA tTG).RESULTADOS: 10 pacientes (8,3%) y 46 sujetos del grupo control (8,9%) con CC tuvieron resultados positivos DGP/tTG Screen. 3 pacientes seropositivos con CC y 14 controles presentaron biopsia compatible con EC. Se estimó una prevalencia de 2,5% para los pacientes con CC y 2,7% para los controles. La prueba de IgA tTG fue positiva en 5 de los 10 pacientes con CC (incluidos los 2 casos diagnosticados con EC) y en 13 controles (100% y 92% de sensibilidad, respectivamente), 5 pacientes con CC fueron considerados como SG.CONCLUSIONES: Este estudio fue el primero en determinar la prevalencia en EC y SG en pacientes con CC, la cual resultó casi cuatro veces mayor que la estimada para la población general de Argentina (1/133).

INTRODUCTION: Celiac disease (CD) diagnosis is strongly associated with the presence of chronic diarrhea, but up to 10% of newly diagnosed cases may complain of chronic constipation (CC). No studies have explored the prevalence of CD or potential markers of gluten sensitivity among patients consulting for CC.OBJECTIVE: TO determine the prevalence of potential markers of gluten sensitivity and CD in a series of consecutive patients with chronic constipation attending a tertiary referral center.METHODS: An exploratory study was conducted at Gastroenterology Hospital of Buenos Aires. 121 adult consecutive patients with diagnosis of chronic constipation (67.8%) or IBS-C (Rome III criteria) were assessed for antibodies to deamidatedgliadin peptides IgA and IgG and tissue transglutaminase (DGP/tTG Screen cut-off: 20 U/mL). Seropositive cases were tested (IgA tTG) and all DGP/tTG Screen positive cases underwent duodenal biopsies. Prevalece was compared with that obtained from a control population of 518 subjects (upper endoscopy due to symptoms not primarily related to CD). Type Illa Marsh’s enteropathy or greater in seropositive cases was considered as CD diagnosis.RESULTS: 10 patients (8.3%) and 46 controls (8.9%) with CC had a positive DGP/tTGScreen test. 3 seropositive patients with CC and 14 controls had a CD compatible biopsy. The IgA tTG test was positive in 5 of the 10 patients with CC (including those 3 cases finally diagnosed with CD) and in 13 from control population (100% and 92% sensitivity, respectively). 5 patients with CC were considered as gluten sensitive (serology positive, but no enteropathy).CONCLUSIONS: This study was the first to determine a higher prevalence of CD and gluten sensitivity in patients complaining of CC. This prevalence was almost four times greater than that estimated for the general Argentinean population (1/133).

Estudio epidemiológico prospectivo para el análisis de la prevalencia de enfermedad celíaca en pacientes con constipación crónica / Prospective epidemiological study for the analysis of prevalence of celiac disease in patients with chronic constipation

INTRODUCCION: Aunque la enfermedad celíaca (EC) se asocia comúnmente a diarrea crónica, 10% de los casos pueden presentarse con constipación crónica (CC). No hay estudios que exploren la prevalencia de EC o marcadores potenciales de la sensibilidad al gluten (SG) en pacientes que consultan por CC.OBJETIVO: Determinar la prevalencia de marcadores potenciales de SG y EC en pacientes con CC que consultan a un centro terciario de referencia.METODOS: Estudio exploratorio prospectivo. Se evaluó a 121 pacientes adultos consecutivos con diagnóstico de CC funcional (67,8%) o SII-C (criterios de Roma III) con anticuerpos contra péptidos deamidados de gliadina IgA e IgG y anti-transglutaminasa tisular (DGP/tTGscreen valor corte=20). Los casos seropositivos fueron analizados con IgA tTG y todos los DGP/tTG Screen casos positivos se sometieron a biopsias endoscópicas de duodeno. La prevalencia se comparó con la de 518 sujetos (endoscopía digestiva alta por síntomas no relacionados primariamente con EC) y con la estimada para la población urbana del Gran La Plata. Se consideró diagnóstico de EC a la presencia de una enteropatía Marsh Illa o mayor en los casos seropositivos. Se consideró SG a los casos seropositivos sin enteropatía ni autoanticuerpos (IgA tTG).RESULTADOS: 10 pacientes (8,3%) y 46 sujetos del grupo control (8,9%) con CC tuvieron resultados positivos DGP/tTG Screen. 3 pacientes seropositivos con CC y 14 controles presentaron biopsia compatible con EC. Se estimó una prevalencia de 2,5% para los pacientes con CC y 2,7% para los controles. La prueba de IgA tTG fue positiva en 5 de los 10 pacientes con CC (incluidos los 2 casos diagnosticados con EC) y en 13 controles (100% y 92% de sensibilidad, respectivamente), 5 pacientes con CC fueron considerados como SG.CONCLUSIONES: Este estudio fue el primero en determinar la prevalencia en EC y SG en pacientes con CC, la cual resultó casi cuatro veces mayor que la estimada para la población general de Argentina (1/133).

INTRODUCTION: Celiac disease (CD) diagnosis is strongly associated with the presence of chronic diarrhea, but up to 10% of newly diagnosed cases may complain of chronic constipation (CC). No studies have explored the prevalence of CD or potential markers of gluten sensitivity among patients consulting for CC.OBJECTIVE: TO determine the prevalence of potential markers of gluten sensitivity and CD in a series of consecutive patients with chronic constipation attending a tertiary referral center.METHODS: An exploratory study was conducted at Gastroenterology Hospital of Buenos Aires. 121 adult consecutive patients with diagnosis of chronic constipation (67.8%) or IBS-C (Rome III criteria) were assessed for antibodies to deamidatedgliadin peptides IgA and IgG and tissue transglutaminase (DGP/tTG Screen cut-off: 20 U/mL). Seropositive cases were tested (IgA tTG) and all DGP/tTG Screen positive cases underwent duodenal biopsies. Prevalece was compared with that obtained from a control population of 518 subjects (upper endoscopy due to symptoms not primarily related to CD). Type Illa Marshs enteropathy or greater in seropositive cases was considered as CD diagnosis.RESULTS: 10 patients (8.3%) and 46 controls (8.9%) with CC had a positive DGP/tTGScreen test. 3 seropositive patients with CC and 14 controls had a CD compatible biopsy. The IgA tTG test was positive in 5 of the 10 patients with CC (including those 3 cases finally diagnosed with CD) and in 13 from control population (100% and 92% sensitivity, respectively). 5 patients with CC were considered as gluten sensitive (serology positive, but no enteropathy).CONCLUSIONS: This study was the first to determine a higher prevalence of CD and gluten sensitivity in patients complaining of CC. This prevalence was almost four times greater than that estimated for the general Argentinean population (1/133).

Serological tests for celiac disease as indicators of long-term compliance with the gluten-free diet.

OBJECTIVES: The efficacy of celiac disease (CD)-related antibodies in monitoring clinical outcome of patients remains unclear. Our aims were to determine dynamics of antibodies after diagnosis and to assess their performances in monitoring patients' long-term compliance with the gluten-free diet (GFD). METHODS: We prospectively estimated the performance of seven celiac disease-related antibody tests at diagnosis and at 1 year and more than 4 years after treatment initiation in 53 adults. The ability of antibodies to identify patients partially compliant to treatment was explored by the receiver operating characteristic curve analysis. The derived cut-off values ('compliance' cutoffs) were compared with cut-off values used for diagnosis ('diagnostic' cutoffs). The degree of compliance with the GFD was assessed using a standardized, multidisciplinary approach. RESULTS: Concentrations of all antibodies decreased significantly at 1 year after diagnosis. The decline continued for more than 4 years in strictly compliant patients (P<0.05-0.001). The gap between 'compliance' and 'diagnostic' cut-offs values was wider at 1 year than at more than 4 years. The predictability of partial compliance determined by the area under receiver operating characteristic curves was relevant for most tests examined at 1 year (areas ranging: 0.64-0.72) and more than 4 years (0.58-0.78). Immunoglobulin A antibodies to deamidated gliadin peptides and tissue transglutaminase had the best performance for monitoring long-term compliance. CONCLUSION: Decreased concentrations of antibodies were significantly associated with the degree of compliance with the GFD. Immunoglobulin A antibodies to deamidated gliadin peptides and tissue transglutaminase had the best and more consistent performances. The serial measurement of antibody levels seems to be more reliable in monitoring compliance than the positive/negative expression of results.

Celiac disease serology in patients with different pretest probabilities: is biopsy avoidable?

AIM: To establish the diagnostic performance of several serological tests, individually and in combination, for diagnosing celiac disease (CD) in patients with different pretest probabilities, and to explore potential serological algorithms to reduce the necessity for biopsy. METHODS: We prospectively performed duodenal biopsy and serology in 679 adults who had either high risk (n = 161) or low risk (n = 518) for CD. Blood samples were tested using six assays (enzyme-linked immunosorbent assay) that detected antibodies to tissue transglutaminase (tTG) and deamidated gliadin peptide (DGP). RESULTS: CD prevalence was 39.1% in the high-risk population and 3.3% in the low-risk group. In high-risk patients, all individual assays had a high diagnostic efficacy [area under receiving operator characteristic curves (AU ROC): 0.968 to 0.999]. In contrast, assays had a lower diagnostic efficacy (AU ROC: 0.835 to 0.972) in the low-risk group. Using assay combinations, it would be possible to reach or rule out diagnosis of CD without biopsy in 92% of cases in both pretest populations. We observed that the new DGP/tTG Screen assay resulted in a surplus compared to more conventional assays in any clinical situation. CONCLUSION: The DGP/tTG Screen assay could be considered as the best initial test for CD. Combinations of two tests, including a DGP/tTG Screen, might be able to diagnose CD accurately in different clinical scenarios making biopsy avoidable in a high proportion of subjects.

A prospective evaluation of endoscopic markers for identifying celiac disease in patients with high and low probability of having the disease.

BACKGROUND/OBJECTIVES: the usefulness of duodenoscopic markers for predicting celiac disease (CD) has been questioned. We assessed the diagnostic efficacy of endoscopic markers of mucosal atrophy in individuals with different pretest probability of CD. METHODS: we prospectively performed endoscopic intestinal biopsies and CD-related serology tests in 661 individuals, including 143 consecutive patients attending a malabsorption clinic (high pretest probability) and 518 subjects randomly selected fom those undergoing routine endoscopy because of upper GI symptoms (low pretest probability). Duodenoscopic markers reported were: mosaic pattern, scalloped folds, and reduction in number or loss of Kerkring's folds. RESULTS: sixty-three (44.1%) and 18 (3.5%) patients were diagnosed with CD in the high and low risk groups, respectively Among high pretest subjects, the presence of any marker had very high sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for the identification of CD (92.1%, 93.8%, 92.1%, 93.8% and 93.0%, respectively). The performance of these parameters for the presence of any marker in the low pretest population were 61.1%, 96.8%, 40.7%, 98.6% and 95.6%, respectively. Sensitivity (p < 0.004) and positive predictive value (p < 0.0001) of markers were significantly higher for the high risk patients. The identification of a reduction in number or loss of Kerkring'sfolds was not a reliable finding unless other signs were also present. CONCLUSIONS: we confirm that endoscopic markers are useful in predicting CD in different clinical scenarios. The high negative predictive value in the low probability group suggests that intestinal biopsy is not required if endoscopic markers are absent.

Antibodies against synthetic deamidated gliadin peptides as predictors of celiac disease: prospective assessment in an adult population with a high pretest probability of disease.

BACKGROUND: Noninvasive serologic tests have shown high diagnostic accuracy for celiac disease (CD) in selected populations. Our aim was to determine prospectively the performance of CD-related serology in individuals undergoing intestinal biopsy because of clinical suspicion of small-bowel disorders. METHODS: We enrolled 141 unselected consecutive adult patients attending a small-bowel disease clinic. Patients underwent endoscopy and biopsy; serum samples were obtained at that time for measurements of anti-tissue transglutaminase (a-tTG), IgA and IgG anti-deamidated gliadin-related peptide (a-DGP), and IgA antiactin antibodies (AAAs). Characterization of patients was based on histological criteria (Marsh type II lesion or greater). RESULTS: The prevalence of CD was 42.5%. Sensitivity, specificity, and positive and negative predictive values were >90% for most assays. Diagnostic accuracy based on ROC curve analysis was similar for all assays [area under the curve (95% CI): 0.996 (0.967-0.998) for a-tTG, 0.995 (0.964-0.998) for IgA a-DGP, 0.989 (0.954-0.999) for IgG a-DGP, 0.996 (0.966-0.998) for blended conjugated of IgA + IgG a-DGP in a single assay, and 0.967 (0.922-0.990) for AAA]. The combinations of 2 tests, IgG a-DGP plus IgA a-tTG or the single blended conjugate detecting IgA + IgG a-DGP plus IgA a-tTG had 100% positive and negative predictive values if concentrations of both tests in either combination were above or below the cutoff. CONCLUSIONS: In a population with high pretest probability, the newly developed a-DGP tests have diagnostic accuracy that is at least equivalent to that of established assays.

Clinical utility of counting intraepithelial lymphocytes in celiac disease intestinal mucosa.

BACKGROUND/AIMS: Our aims were to establish the clinical utility of assessing the intraepithelial lymphocyte (IEL) density in intestinal biopsies from a large series of individuals and to determine the best threshold discriminating celiac disease (CD) patients and controls in two populations with different pre-test prevalence. METHODS: We prospectively performed intestinal biopsy and CD-related serology in 349 subjects undergoing upper GI endoscopy. While 116 had symptoms suggestive of a small bowel disorder (high prevalence), 233 individuals were randomly selected from patients referred to endoscopy because upper GIsymptoms (low prevalence). Diagnosis of CD was based on the concordance of classical histological features and a positive CD serology. RESULTS: While 58 patients had a newly diagnosed CD (52 in the high and 6 in the low prevalence groups), 291 subjects did not meet diagnostic criteria of the disorder. Patients had a highly significant greater IEL density than controls (p < 0.00001). Based on the ROC curve, a count of 22.8 IEL/100 epithelial cells had the highest performance for diagnosing CD in the overall population and for subjects in the high pre-test probability subgroup and 22.5% was ,he best cut-off for those diagnosed in the low risk population (area under the curves: 0.979, 0.979 and 0.993, respectively). An abnormal CD serology confirmed the diagnosis of CD in all the four patients with counts below 22.8%. CONCLUSIONS: Our study confirms that an IEL density of 22.8% is an adequate threshold to discriminate CD patients and controls in individuals irrespective of the prevalence of the disorder.

Clinical characteristics and long-term outcome of patients with refractory sprue diagnosed at a single institution.

BACKGROUND: Refractory sprue (RS) is a rare and severe celiac-like enteropathy not responding to a strict gluten-free diet. Although prognosis is generally poor, little is known about the long-term outcome of patients. AIM: to report baseline characteristics and long-term outcome of a series of patients diagnosed and treated in a single institution. MATERIALS: We report a retrospective cohort of 25 consecutive patients (15 females; mean age 46 yr; range 28-71) diagnosed with RS based on the presence of a non-responsive celiac-like enteropathy. All patients were intensively treated with a gluten-free diet, steroids, nutritional support and immunosupression. RESULTS: Clinical and biological characteristics of patients suggest that, at least, 24 patients had clear evidences of celiac disease. HLA DQ2/DQ8 genes were present in all the 24 patients typed and autoimmune enteropathy was excluded in all. According to the genotyping, 12 patients had a polyclonal lymphocyte population (RS type I) and 13 exhibited monoclonal TCR-gamma gene rearrangements (RS type II). Sixteen patients had evidence of ulcerative jejunitis (UJ) (7 in RS type I and 9 in type II). Overall median follow-up time after diagnosis of RS was 29 mo/patient (range 7 to 204) (45 mo for type I and 24 mo for type II). Overall mortality was 48% (12 patients), 6 in each type. Eight patients with UJ (50%), 3 with lymphoma (two T-cell and one B-cell type) and 4 (44%) without ulcers died during follow-up. The causes of death were sepsis in the context of a progressive deterioration but without overt malignancies (n=5), vascular causes (n=3) and severe malnutrition (n=1). Three- and 5-yr survival rate after diagnosis of RS for the overall population was 60% and 56%. There was no differences between type I (67%, 58%) and type II RS patients (54% for both periods). Patients with UJ had lower but non-significant 3- and 5-yr survival rates (56% and 50%, respectively) compared with patients without ulcers (78% and 66%). Survivors had a favorable outcome. While 11 patients persists asymptomatic, two other cases still have mild diarrhea and one low body weight. CONCLUSIONS: We confirm that RS is a severe celiac disease-related disorder with very high mortality. Diagnosis of overt lymphoma (12%) in our long-term follow-up was not as frequent as was reported by other groups. A proportion of patients persist in good health for a long time irrespective of the nature of the IEL infiltration or the presence of UJ.

Clinical characteristics and long-term outcome of patients with refractory sprue diagnosed at a single institution / Características clínicas y evolución a largo plazo de una serie de pacientes con sprue refractario diagnosticados en una sola institución

BACKGROUND: Refractory sprue (RS) is a rare and severe celiac-like enteropathy not responding to a strict gluten-free diet. Although prognosis is generally poor, little is known about the long-term outcome of patients. AIM: to report baseline characteristics and long-term outcome of a series of patients diagnosed and treated in a single institution. MATERIALS: We report a retrospective cohort of 25 consecutive patients (15 females; mean age 46 yr; range 28-71) diagnosed with RS based on the presence of a non-responsive celiac-like enteropathy. All patients were intensively treated with a gluten-free diet, steroids, nutritional support and immunosupression. RESULTS: Clinical and biological characteristics of patients suggest that, at least, 24 patients had clear evidences of celiac disease. HLA DQ2/DQ8 genes were present in all the 24 patients typed and autoimmune enteropathy was excluded in all. According to the genotyping, 12 patients had a polyclonal lymphocyte population (RS type I) and 13 exhibited monoclonal TCR-gamma gene rearrangements (RS type II). Sixteen patients had evidence of ulcerative jejunitis (UJ) (7 in RS type I and 9 in type II). Overall median follow-up time after diagnosis of RS was 29 mo/patient (range 7 to 204) (45 mo for type I and 24 mo for type II). Overall mortality was 48% (12 patients), 6 in each type. Eight patients with UJ (50%), 3 with lymphoma (two T-cell and one B-cell type) and 4 (44%) without ulcers died during follow-up. The causes of death were sepsis in the context of a progressive deterioration but without overt malignancies (n=5), vascular causes (n=3) and severe malnutrition (n=1). Three- and 5-yr survival rate after diagnosis of RS for the overall population was 60% and 56%. There was no differences between type I (67%, 58%) and type II RS patients (54% for both periods). Patients with UJ had lower but non-significant 3- and 5-yr survival rates (56% and 50%, respectively) compared with patients without ulcers...

Introducción: El sprue refractario (SR) es una rara y severa entidad consistente en una enteropatía tipo celíaca que no responde a una estricta dieta libre degluten. Aún cuando el pronóstico es generalmente pobre, poco es conocido acerca de la evolución de lospacientes a largo plazo. Objetivo: reportar las característicasclínicas y la evolución a largo plazo de una serie de pacientes diagnosticados y tratados en una solainstitución. Materiales: Reportamos una cohorteretrospectiva de 25 pacientes consecutivos (15 mujeres; edad media 46 años; rango 28-71) diagnosticadoscomo SR sobre la base de una enteropatía tipo celíaca que no respondió a la dieta libre de gluten. Todos los pacientes recibieron un tratamiento intensivo consistenteen dieta libre de gluten, alimentación enteral o parenteral, corticosteroides e inmunosupresión. Resultados: Los elementos clínicos y biológicos sugierenque 24 pacientes exhibían claras evidencias de enfermedadcelíaca. Los genes HLA DQ2/DQ8 estuvieron presentes en los 24 pacientes estudiados y se excluyó laenteropatía autoinmune en todos los casos. De acuerdo al genotipo, 12 pacientes presentaron una poblaciónlinfocitaria intraepitelial policlonal (SR tipo I) y 13 exhibieron un rearreglo genético monoclonal del TCR-γ (SR tipo II). Dieciséis pacientes presentaron evidencias de yeyunitis ulcerativa (YU) (7 en SR tipo I y 9 enel tipo II). El tiempo promedio de seguimiento luego del diagnóstico de SR fue 29 meses/paciente (rango 7 -204) (45 y 24 meses para tipo I y tipo II, respectivamente). La mortalidad global fue del 48% (12 pacientes),6 en cada tipo de SR. Ocho pacientes con YU (50%) murieron durante el seguimiento, 3 con linfoma(dos de células T y uno de células B) y cuatro(44%) individuos sin úlceras también fallecieron. Lascausas de muerte fueron vasculares (n=3), sepsis en elmarco de deterioro progresivo sin desarrollo de malignidad(n=5) y desnutrición progresiva (n=1)...

Clinical characteristics and long-term outcome of patients with refractory sprue diagnosed at a single institution

BACKGROUND: Refractory sprue (RS) is a rare and severe celiac-like enteropathy not responding to a strict gluten-free diet. Although prognosis is generally poor, little is known about the long-term outcome of patients. AIM: to report baseline characteristics and long-term outcome of a series of patients diagnosed and treated in a single institution. MATERIALS: We report a retrospective cohort of 25 consecutive patients (15 females; mean age 46 yr; range 28-71) diagnosed with RS based on the presence of a non-responsive celiac-like enteropathy. All patients were intensively treated with a gluten-free diet, steroids, nutritional support and immunosupression. RESULTS: Clinical and biological characteristics of patients suggest that, at least, 24 patients had clear evidences of celiac disease. HLA DQ2/DQ8 genes were present in all the 24 patients typed and autoimmune enteropathy was excluded in all. According to the genotyping, 12 patients had a polyclonal lymphocyte population (RS type I) and 13 exhibited monoclonal TCR-gamma gene rearrangements (RS type II). Sixteen patients had evidence of ulcerative jejunitis (UJ) (7 in RS type I and 9 in type II). Overall median follow-up time after diagnosis of RS was 29 mo/patient (range 7 to 204) (45 mo for type I and 24 mo for type II). Overall mortality was 48% (12 patients), 6 in each type. Eight patients with UJ (50%), 3 with lymphoma (two T-cell and one B-cell type) and 4 (44%) without ulcers died during follow-up. The causes of death were sepsis in the context of a progressive deterioration but without overt malignancies (n=5), vascular causes (n=3) and severe malnutrition (n=1). Three- and 5-yr survival rate after diagnosis of RS for the overall population was 60% and 56%. There was no differences between type I (67%, 58%) and type II RS patients (54% for both periods). Patients with UJ had lower but non-significant 3- and 5-yr survival rates (56% and 50%, respectively) compared with patients without ulcers... (AU)

Introducción: El sprue refractario (SR) es una rara y severa entidad consistente en una enteropatía tipo celíaca que no responde a una estricta dieta libre degluten. Aún cuando el pronóstico es generalmente pobre, poco es conocido acerca de la evolución de lospacientes a largo plazo. Objetivo: reportar las característicasclínicas y la evolución a largo plazo de una serie de pacientes diagnosticados y tratados en una solainstitución. Materiales: Reportamos una cohorteretrospectiva de 25 pacientes consecutivos (15 mujeres; edad media 46 años; rango 28-71) diagnosticadoscomo SR sobre la base de una enteropatía tipo celíaca que no respondió a la dieta libre de gluten. Todos los pacientes recibieron un tratamiento intensivo consistenteen dieta libre de gluten, alimentación enteral o parenteral, corticosteroides e inmunosupresión. Resultados: Los elementos clínicos y biológicos sugierenque 24 pacientes exhibían claras evidencias de enfermedadcelíaca. Los genes HLA DQ2/DQ8 estuvieron presentes en los 24 pacientes estudiados y se excluyó laenteropatía autoinmune en todos los casos. De acuerdo al genotipo, 12 pacientes presentaron una poblaciónlinfocitaria intraepitelial policlonal (SR tipo I) y 13 exhibieron un rearreglo genético monoclonal del TCR-γ (SR tipo II). Dieciséis pacientes presentaron evidencias de yeyunitis ulcerativa (YU) (7 en SR tipo I y 9 enel tipo II). El tiempo promedio de seguimiento luego del diagnóstico de SR fue 29 meses/paciente (rango 7 -204) (45 y 24 meses para tipo I y tipo II, respectivamente). La mortalidad global fue del 48% (12 pacientes),6 en cada tipo de SR. Ocho pacientes con YU (50%) murieron durante el seguimiento, 3 con linfoma(dos de células T y uno de células B) y cuatro(44%) individuos sin úlceras también fallecieron. Lascausas de muerte fueron vasculares (n=3), sepsis en elmarco de deterioro progresivo sin desarrollo de malignidad(n=5) y desnutrición progresiva (n=1)...(AU)

Clinical characteristics and long-term outcome of patients with refractory sprue diagnosed at a single institution

BACKGROUND: Refractory sprue (RS) is a rare and severe celiac-like enteropathy not responding to a strict gluten-free diet. Although prognosis is generally poor, little is known about the long-term outcome of patients. AIM: to report baseline characteristics and long-term outcome of a series of patients diagnosed and treated in a single institution. MATERIALS: We report a retrospective cohort of 25 consecutive patients (15 females; mean age 46 yr; range 28-71) diagnosed with RS based on the presence of a non-responsive celiac-like enteropathy. All patients were intensively treated with a gluten-free diet, steroids, nutritional support and immunosupression. RESULTS: Clinical and biological characteristics of patients suggest that, at least, 24 patients had clear evidences of celiac disease. HLA DQ2/DQ8 genes were present in all the 24 patients typed and autoimmune enteropathy was excluded in all. According to the genotyping, 12 patients had a polyclonal lymphocyte population (RS type I) and 13 exhibited monoclonal TCR-gamma gene rearrangements (RS type II). Sixteen patients had evidence of ulcerative jejunitis (UJ) (7 in RS type I and 9 in type II). Overall median follow-up time after diagnosis of RS was 29 mo/patient (range 7 to 204) (45 mo for type I and 24 mo for type II). Overall mortality was 48% (12 patients), 6 in each type. Eight patients with UJ (50%), 3 with lymphoma (two T-cell and one B-cell type) and 4 (44%) without ulcers died during follow-up. The causes of death were sepsis in the context of a progressive deterioration but without overt malignancies (n=5), vascular causes (n=3) and severe malnutrition (n=1). Three- and 5-yr survival rate after diagnosis of RS for the overall population was 60% and 56%. There was no differences between type I (67%, 58%) and type II RS patients (54% for both periods). Patients with UJ had lower but non-significant 3- and 5-yr survival rates (56% and 50%, respectively) compared with patients without ulcers... (AU)

Introducción: El sprue refractario (SR) es una rara y severa entidad consistente en una enteropatía tipo celíaca que no responde a una estricta dieta libre degluten. Aún cuando el pronóstico es generalmente pobre, poco es conocido acerca de la evolución de lospacientes a largo plazo. Objetivo: reportar las característicasclínicas y la evolución a largo plazo de una serie de pacientes diagnosticados y tratados en una solainstitución. Materiales: Reportamos una cohorteretrospectiva de 25 pacientes consecutivos (15 mujeres; edad media 46 años; rango 28-71) diagnosticadoscomo SR sobre la base de una enteropatía tipo celíaca que no respondió a la dieta libre de gluten. Todos los pacientes recibieron un tratamiento intensivo consistenteen dieta libre de gluten, alimentación enteral o parenteral, corticosteroides e inmunosupresión. Resultados: Los elementos clínicos y biológicos sugierenque 24 pacientes exhibían claras evidencias de enfermedadcelíaca. Los genes HLA DQ2/DQ8 estuvieron presentes en los 24 pacientes estudiados y se excluyó laenteropatía autoinmune en todos los casos. De acuerdo al genotipo, 12 pacientes presentaron una poblaciónlinfocitaria intraepitelial policlonal (SR tipo I) y 13 exhibieron un rearreglo genético monoclonal del TCR-γ (SR tipo II). Dieciséis pacientes presentaron evidencias de yeyunitis ulcerativa (YU) (7 en SR tipo I y 9 enel tipo II). El tiempo promedio de seguimiento luego del diagnóstico de SR fue 29 meses/paciente (rango 7 -204) (45 y 24 meses para tipo I y tipo II, respectivamente). La mortalidad global fue del 48% (12 pacientes),6 en cada tipo de SR. Ocho pacientes con YU (50%) murieron durante el seguimiento, 3 con linfoma(dos de células T y uno de células B) y cuatro(44%) individuos sin úlceras también fallecieron. Lascausas de muerte fueron vasculares (n=3), sepsis en elmarco de deterioro progresivo sin desarrollo de malignidad(n=5) y desnutrición progresiva (n=1)...(AU)