Better quality of life and reduced fecal incontinence in rectal cancer patients with the watch-and-wait follow-up strategy.

INTRODUCTION: The watch-and-wait (WW) strategy is an alternative to anterior resection in patients with rectal cancer (RC) that have had a complete clinical response to neoadjuvant treatment. Few reports describe the quality of life and functional anorectal disorders (FADs) in that population. AIM: To analyze and compare the FADs and quality of life in patients with locally advanced adenocarcinoma of the rectum treated with neoadjuvant therapy, divided into two different strategy groups: group 1 (G1), WW; and group 2 (G2), anterior resection. MATERIALS AND METHODS: Thirty patients (G1: n = 20 and G2: n = 10) that had finished neoadjuvant therapy at least 12 months prior were included. Mean patient age was 59.5 years (range: 41-79) and 15 of the patients were men. The FADs were evaluated through: a) clinical history, b) 21-day bowel diary, c) Jorge and Wexner fecal incontinence scale, d) anorectal manometry (ARM), and fecal incontinence quality of life scale (FIQL). RESULTS: Bowel diary: fecal incontinence (40%) and urge to defecate (45%) in G1 vs. fecal incontinence (60%) and urge to defecate (30%) in G2, with no significant differences (p = NS). Fecal incontinence scale: fecal incontinence in G1 was significantly less severe than that in G2 (median 6.5 points vs. 13 points [p = 0.0142]). ARM: no differences between the two groups. Quality of life: significantly different between the two groups (FIQL/G1: 3.7 vs. FIQL/G2: 2.8; p < 0.03). CONCLUSIONS: The WW follow-up strategy in patients with locally advanced rectal cancer was associated with better quality of life and reduced fecal incontinence.

Effect of Bifidobacterium infantis NLS super strain in symptomatic coeliac disease patients on long-term gluten-free diet - an exploratory study.

Bifidobacterium infantis NLS super strain (B. infantis NLS-SS) was previously shown to alleviate gastrointestinal symptoms in newly diagnosed coeliac disease (CD) patients consuming gluten. A high proportion of patients following a gluten-free diet experiences symptoms despite dietary compliance. The role of B. infantis in persistently symptomatic CD patients has not been explored. The aim of the study was to evaluate the effect of B. infantis NLS-SS on persistent gastrointestinal symptoms in patients with CD following a long-term GFD. We conducted a randomised, cross-over, double-blind, placebo-controlled trial in symptomatic adult CD patients on a GFD for at least two years. After one-week run-in, patients were randomised to B. infantis NLS-SS or placebo for 3 weeks with cross-over after a 2-week wash-out period. We estimated changes (Δ) in celiac symptom index (CSI) before and after treatment. Stool samples were collected for faecal microbiota analysis (16S rRNA sequencing). Gluten immunogenic peptide (GIP) excretion in stool and urine samples was measured at each study period. Eighteen patients were enrolled; six patients were excluded due violations in protocol. For patients with the highest clinical burden, CD symptoms were lower in probiotic than in placebo treatment (P=0.046). B. infantis and placebo treated groups had different microbiota profiles as assessed by beta diversity clustering. In probiotic treated groups, we observed an increase in abundance of B. infantis. Treatment with B. infantis was associated with decreased abundance of Ruminococcus sp. and Bifidobacterium adolescentis. GIP excretion in stools and urine was similar at each treatment period. There were no differences in adverse effects between the two groups. B. infantis NLS-SS improves specific CD symptoms in a subset of highly symptomatic treated patients (GFD). This is associated with a shift in stool microbiota profile. Larger studies are needed to confirm these findings. ClinicalTrials.gov: NCT03271138.

Better quality of life and reduced fecal incontinence in rectal cancer patients with the watch-and-wait follow-up strategy. / Mejor calidad de vida y menor incontinencia fecal en pacientes con cáncer de recto con la estrategia de seguimiento watch and wait.

INTRODUCTION: The watch-and-wait (WW) strategy is an alternative to anterior resection in patients with rectal cancer (RC) that have had a complete clinical response to neoadjuvant treatment. Few reports describe the quality of life and functional anorectal disorders (FADs) in that population. AIM: To analyze and compare the FADs and quality of life in patients with locally advanced adenocarcinoma of the rectum treated with neoadjuvant therapy, divided into two different strategy groups: group 1 (G1), WW; and group 2 (G2), anterior resection. MATERIALS AND METHODS: Thirty patients (G1: n = 20 and G2: n = 10) that had finished neoadjuvant therapy at least 12 months prior were included. Mean patient age was 59.5 years (range: 41-79) and 15 of the patients were men. The FADs were evaluated through: a) clinical history, b) 21-day bowel diary, c) Jorge and Wexner fecal incontinence scale, d) anorectal manometry (ARM), and fecal incontinence quality of life scale (FIQL). RESULTS: Bowel diary: fecal incontinence (40%) and urge to defecate (45%) in G1 vs. fecal incontinence (60%) and urge to defecate (30%) in G2, with no significant differences (p = NS). Fecal incontinence scale: fecal incontinence in G1 was significantly less severe than that in G2 (median 6.5 points vs. 13 points [p = 0.0142]). ARM: no differences between the two groups. Quality of life: significantly different between the two groups (FIQL/G1: 3.7 vs. FIQL/G2: 2.8; p < 0.03). CONCLUSIONS: The WW follow-up strategy in patients with locally advanced rectal cancer was associated with better quality of life and reduced fecal incontinence.

Isospora belli infection after isolated intestinal transplant.

Isospora belli is a protozoan that only affects humans, after ingestion of Isospora's oocysts. Immunocompetent patients usually do not develop the infection. Immunocompromised hosts may have profuse diarrhea with other gastrointestinal symptoms. Treatment is based on trimethoprim-sulfamethoxazole. In 2006 we performed an isolated intestinal transplantation in a patient with ultra-short bowel syndrome. Neither rejection nor clinical problems occurred after transplant, but signs of intestinal inflammation were seen in every protocol biopsy starting at the first month post transplant. Almost 3 months after the procedure, the patient was re-admitted with diarrhea. I. belli infection was diagnosed by detection of the oocysts in stool samples. Antibiotic treatment with trimethoprim-sulfamethoxazole was initiated with excellent outcome and without relapses. To the best of our knowledge, this is the first case of isosporosis in a small bowel recipient.

Quality of life in celiac disease patients: prospective analysis on the importance of clinical severity at diagnosis and the impact of treatment.

BACKGROUND/AIMS: Celiac disease (CD) patients are affected in their quality of life (QoL). Our objectives were to assess differences in quality of life of patients according to the clinical presentation at diagnosis, and to determine the time-course impact of a gluten-free diet. PATIENTS/METHODS: We prospectively evaluated 132 newly diagnosed adult CD patients and 70 healthy controls using self-administered questionnaires: the Short Form-36 health survey, the Gastrointestinal Symptoms Rating Scale; the Beck Depression Inventory both, at diagnosis and at 3-, 6- and 12-months on treatment. RESULTS: At diagnosis, patients with classical symptoms (n=97) exhibited a significantly more pronounced alteration of all items of the three questionnaires than atypical/silent cases (n=35) (p<0.01 to <0.00001). Silent CD patients had even better baseline scores (p<0.05 to <0.00001). Treatment produced a substantial and rapid (3-month) improvement of most outcome measures in classical and atypical patients but not in asymptomatic cases. Both subgroups attained comparable final scores with no differences comparing strictly adherents with partially compliant. CONCLUSIONS: Atypical/silent celiac disease patients have a significantly better baseline quality of life than those with classical symptoms. Treatment induces a rapid and significant improvement in symptomatic cases but not in silent patients with all subgroups having similar 1-year scores comparable to healthy controls.

Systematic review and meta-analysis of observational studies on the prevalence of fractures in coeliac disease.

BACKGROUND/AIMS: Evidence of an increased bone fracture risk in coeliac disease is on debate. Our aim was to review systematically the current published information on fractures in coeliac disease and to perform a meta-analysis. METHODS: Case-control and cohort designs were identified by searching MEDLINE (1966-April 2007) and LILACS (1982-April 2007). Participants were adult coeliac disease patients of any sex and the outcome measure was the presence of any fracture. Studies were screened for inclusion by two authors who independently extracted the data. Methodological quality was assessed using the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology Statement) recommendations. Data were analysed using the RevMan Analyses statistical package in Review Manager (version 4.2.8) and reported as pooled odds ratio using a random effect model. Heterogeneity was investigated (standard chi(2) test) and sensitivity analysis was performed based on the reported quality and design type. RESULTS: While 60 of 405 studies met the initial screening criteria, only 8 met inclusion criteria after detailed review. These studies evaluated a total of 20,955 coeliac disease patients having 1819 (8.7%) fractures and 96,777 controls with 5955 (6.1%) fractures (pooled odds ratio=1.43; 95% confidence interval 1.15-1.78) with considerable heterogeneity among studies (p<0.00001). CONCLUSIONS: Our meta-analysis confirms a significant association between bone fractures and coeliac disease. However, qualitative and quantitative differences among studies were evident. Further research is necessary to investigate the relevance of this heterogeneity.

Clinical utility of counting intraepithelial lymphocytes in celiac disease intestinal mucosa / Utilidad clínica del recuento de linfocitos intraepiteliales en la mucosa intestinal para el diagnóstico de enfermedad celíaca

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.

Introducción: El recuento elevado de linfocitos intraepiteliales (LIEs) es un rasgo destacado aunque inespecífico de la enteropatía de la enfermedad celíaca (EC). Un recuento mayor a 40 LIEs/100 células epiteliales ha sido considerado por mucho tiempo esencial para el diagnóstico. Sin embargo, estudios recientes con escaso número de muestras han cuestionado este valor de corte. Objetivos: Determinar el rango normal de LIEs en biopsias intestinales y establecer su capacidad diagnóstica de EC en dos poblaciones con diferente prevalencia. Métodos: Realizamos prospectivamente biopsias de duodeno distal y serología para EC en 349 pacientesconsecutivos a quienes se les realizó una videoendoscopia digestiva alta. El grupo A consistió en 116 pacientes derivados a biopsia intestinal por síntomas sugestivos de malabsorción (considerados de alta prevalencia de EC) y el grupo B consistió en 233 pacientes randomizados entre quienes fueron derivados a endoscopía alta por síntomas gastrointestinales no sugestivos de EC (baja prevalencia de EC). El diagnóstico de EC se basó en criterios histológicos clásicos y serología positiva. Resultados: Cincuenta y ocho pacientes tuvieron EC (52 en el grupo de alto riesgo y 6 en el de baja prevalencia) y 291 individuos no tuvieron criterios de la enfermedad. Los pacientes tuvieron una densidad de LIEs significativamente mayor que los controles (p<0.00001). Basado en las curvas ROC, el conteo de 22.8 LIEs/100 células epiteliales tuvo la mejor sensibilidad y especificidad para el diagnóstico de EC en la población general y entre los sujetos con alta probabilidad y 22.5% fue el mejor valor de corte para la población de bajo riesgo (áreas bajo las curvas: 0.979, 0.979 y 0.993, respectivamente). Todos aquellos pacientes celíacos con recuento de LIEs por debajo de 22% (n=4), tuvieron serología positiva para EC. El clásico valor de 40% tuvo una sensibilidad del 55%. Conclusiones: Nuestro estudio confirma que una...

Clinical utility of counting intraepithelial lymphocytes in celiac disease intestinal mucosa / Utilidad clínica del recuento de linfocitos intraepiteliales en la mucosa intestinal para el diagnóstico de enfermedad celíaca

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.(AU)

Introducción: El recuento elevado de linfocitos intraepiteliales (LIEs) es un rasgo destacado aunque inespecífico de la enteropatía de la enfermedad celíaca (EC). Un recuento mayor a 40 LIEs/100 células epiteliales ha sido considerado por mucho tiempo esencial para el diagnóstico. Sin embargo, estudios recientes con escaso número de muestras han cuestionado este valor de corte. Objetivos: Determinar el rango normal de LIEs en biopsias intestinales y establecer su capacidad diagnóstica de EC en dos poblaciones con diferente prevalencia. Métodos: Realizamos prospectivamente biopsias de duodeno distal y serología para EC en 349 pacientesconsecutivos a quienes se les realizó una videoendoscopia digestiva alta. El grupo A consistió en 116 pacientes derivados a biopsia intestinal por síntomas sugestivos de malabsorción (considerados de alta prevalencia de EC) y el grupo B consistió en 233 pacientes randomizados entre quienes fueron derivados a endoscopía alta por síntomas gastrointestinales no sugestivos de EC (baja prevalencia de EC). El diagnóstico de EC se basó en criterios histológicos clásicos y serología positiva. Resultados: Cincuenta y ocho pacientes tuvieron EC (52 en el grupo de alto riesgo y 6 en el de baja prevalencia) y 291 individuos no tuvieron criterios de la enfermedad. Los pacientes tuvieron una densidad de LIEs significativamente mayor que los controles (p<0.00001). Basado en las curvas ROC, el conteo de 22.8 LIEs/100 células epiteliales tuvo la mejor sensibilidad y especificidad para el diagnóstico de EC en la población general y entre los sujetos con alta probabilidad y 22.5% fue el mejor valor de corte para la población de bajo riesgo (áreas bajo las curvas: 0.979, 0.979 y 0.993, respectivamente). Todos aquellos pacientes celíacos con recuento de LIEs por debajo de 22% (n=4), tuvieron serología positiva para EC. El clásico valor de 40% tuvo una sensibilidad del 55%. Conclusiones: Nuestro estudio confirma que una...(AU)

Decision analysis: an aid to the diagnosis of Whipple's disease.

BACKGROUND: Diagnosis of Whipple's disease, a rare systemic infection affecting predominantly the small bowel, is based on the identification of the bacterium Tropheryma whipplei. AIMS: To make explicit diagnostic uncertainties in Whipple's disease through a decision analysis, considering two different clinical scenarios at presentation. METHODS: Using appropriate software, a decision tree estimated the consequences after testing different strategies for diagnosis of Whipple's disease. Probabilities and outcomes to determine the optimum expected value were based on MEDLINE search. RESULTS: In patients with clinically-predominant intestinal involvement, diagnostic strategies considering intestinal biopsy for histology (including appropriate staining) and the polymerase chain reaction testing for bacterial DNA were similarly effective. In case of failure of one procedure, the best sequential choice was a polymerase chain reaction analysis after a negative histology. Of the five strategies tested for cases with predominant focal neurological involvement, the stereotaxis cerebral biopsy evidenced the highest expected value. However, using quality-adjusted life-years considering the morbidity of methods, intestinal biopsy for PCR determination was the best choice. CONCLUSIONS: In patients with Whipple's disease having predominant digestive involvement, intestinal biopsies for histology should be indicated first and, if negative, a bacterial polymerase chain reaction determination should be the next option. Although the molecular polymerase chain reaction assessment of cerebral biopsies has the highest diagnostic yield in neurological Whipple's disease, its associated morbidity means that analyses of intestinal samples are more appropriate.

The IL-1 gene family and bone involvement in celiac disease.

Celiac disease (CD) is associated with decreased bone mineral mass. Its pathogenesis is multifactorial since both systemic and local mechanisms may play a role. Our objective was to determine whether single-nucleotide polymorphisms in genes encoding members of the interleukin-1 family are associated with bone damage measured by densitometry in a series of 71 adult CD patients assessed at diagnosis. When compared with non-carrier CD patients, carriers of allele T of the interleukin-1beta gene (IL1B-511T) had a significantly lower bone mass at the total skeleton level (p = 0.0484) and a greater prevalence of osteopenia/osteoporosis (p = 0.0102). To our knowledge, this is the first evidence on the association between a genetic predisposition and low bone mass in CD patients. This finding supports the postulated inflammation-associated bone loss pathogenesis as one of the causes of bone weakness in CD.

Significance of smooth muscle/anti-actin autoantibodies in celiac disease / Significado de los anticuerpos anti-músculo liso/anti-actina en la enfermedad celíaca

BACKGROUND/AIM: Smooth muscle antibody (SMA) specific for the protein actin, a major component of the cytoskeleton of epithelial cells, is one of the most prevalent non-organ specific autoantibodies in the serum of celiac disease (CD) patients. Our aim was to explore the clinical relevance of the presence of IgA type anti-actin antibody (AAA) and SMA in a series of patients with CD. METHODS: We evaluated frozen serum samples collected at diagnosis from 92 adult patients with CD and 52 control individuals in whom CD was excluded. Patients were re-evaluated a median time of 5 yr after treatment. IgA type AAA was detected using a modified commercial ELISA assay and IgA SMA was detected using indirect immunofluorescence on primate esophagus substrate. RESULTS: At diagnosis, samples from CD patients had significantly higher AAA values than controls (p<0.00001). While all active CD patients had serum AAA values over the cut-off for healthy controls, we observed a very significant reduction of these antibodies after treatment (p>0.0001). AAA had a highly significant correlation with both, tissue, transglutaminase (r=0.62) and antigliadin (r=0.60, p<0.00001) antibodies as well as the severity of the intestinal injury (p<0.05). SMA was detected in sera of 35 consecutive CD patients. At diagnosis, SMA positive patients had significantly higher values of AAA (p<0.0002), increased number of autoimmune disorders (p<0.04), delayed menarche (p<0.04), lower hemoglobin levels (p<0.01), increased fecal a-I antitrypsin clearance (p<0.01) and more severe diarrhea (p<0.06). We also detected a trend to more severe complications at follow-up (p=0.059). CONCLUSIONS: Based on our findings we suggest that the presence of increased IgA AAA serum levels is a highly sensitive marker of the disturbed architecture of intestinal epithelial cells of CD patients with a potential relevance to diagnosis and follow-up. The presence of SMA seems to define a distinct subset of CD patients with ...

Introduccion/objetivo: El anticuerpo anti-musculo liso (SMA) dirigido contra la proteína actina, un componente mayor del citoesqueleto de las células epiteliales, es el anticuerpo no-órgano específico más prevalente en enfermedad celíaca (EC). Nuestro objetivo fue explorar la importancia clínica de los anticuerpos anti-actina (AAA) y SMA en una serie de pacientes con EC. Métodos: Evaluamos 92 muestras serológicas de pacientes celíacos adultos recolectadas al momento del diagnóstico y la de 52 individuos controles no celíacos. Los pacientes fueron re-evaluados luego de un tiempo medio de 5 años en tratamiento. Evaluamos AAA tipoIgA mediante ELISA empleando un equipo commercial modificado y SMA IgA por inmunofluorescencia indirecta sobre sustrato de esófago de mono. Resultados: Al momento del diagnóstico, los pacientes celíacos tuvieron valores de AAA significativamente más elevados que los controles (p<0.00001). Todos los pacientes con EC activa presentaron niveles de AAA por encima del valor de corte determinado para el grupo control sano y se evidenció una reducción significativa de los nivelesluego del tratamiento (p>0.0001). Los AAA presentaron una correlación significativa con los anticuerpos anti-transglutaminasa tisular (r=0.62) y anti-gliadina (r=0.60) (p<0.00001), de igual modo que con la severidad del daño intestinal (p<0.05). Al momento del diagnóstico, se detectó SMA en el suero de 35 pacientes no controles. Los pacientes SMA positivos tuvieron valores significativamente mayores de AAA (p<0.002), un incremento del número de enfermedades autoinmunes asociadas (p<0.04), menarca tardía (p<0.04), niveles bajos de hemoglobina (p<0.01), incremento del clearance de a-1 antitripsina fecal (p<0.01) y mayor severidad de la diarrea (p<0.06).En ellos se evidenció una tendencia al desarrollo de complicaciones más severas durante el seguimiento (p=0.059). Conclusiones: Sugerimos que la presencia de un valor sérico aumentado de AAA tipo IgA...

Significance of smooth muscle/anti-actin autoantibodies in celiac disease

BACKGROUND/AIM: Smooth muscle antibody (SMA) specific for the protein actin, a major component of the cytoskeleton of epithelial cells, is one of the most prevalent non-organ specific autoantibodies in the serum of celiac disease (CD) patients. Our aim was to explore the clinical relevance of the presence of IgA type anti-actin antibody (AAA) and SMA in a series of patients with CD. METHODS: We evaluated frozen serum samples collected at diagnosis from 92 adult patients with CD and 52 control individuals in whom CD was excluded. Patients were re-evaluated a median time of 5 yr after treatment. IgA type AAA was detected using a modified commercial ELISA assay and IgA SMA was detected using indirect immunofluorescence on primate esophagus substrate. RESULTS: At diagnosis, samples from CD patients had significantly higher AAA values than controls (p<0.00001). While all active CD patients had serum AAA values over the cut-off for healthy controls, we observed a very significant reduction of these antibodies after treatment (p>0.0001). AAA had a highly significant correlation with both, tissue, transglutaminase (r=0.62) and antigliadin (r=0.60, p<0.00001) antibodies as well as the severity of the intestinal injury (p<0.05). SMA was detected in sera of 35 consecutive CD patients. At diagnosis, SMA positive patients had significantly higher values of AAA (p<0.0002), increased number of autoimmune disorders (p<0.04), delayed menarche (p<0.04), lower hemoglobin levels (p<0.01), increased fecal a-I antitrypsin clearance (p<0.01) and more severe diarrhea (p<0.06). We also detected a trend to more severe complications at follow-up (p=0.059). CONCLUSIONS: Based on our findings we suggest that the presence of increased IgA AAA serum levels is a highly sensitive marker of the disturbed architecture of intestinal epithelial cells of CD patients with a potential relevance to diagnosis and follow-up. The presence of SMA seems to define a distinct subset of CD patients with ...(AU)

Introduccion/objetivo: El anticuerpo anti-musculo liso (SMA) dirigido contra la proteína actina, un componente mayor del citoesqueleto de las células epiteliales, es el anticuerpo no-órgano específico más prevalente en enfermedad celíaca (EC). Nuestro objetivo fue explorar la importancia clínica de los anticuerpos anti-actina (AAA) y SMA en una serie de pacientes con EC. Métodos: Evaluamos 92 muestras serológicas de pacientes celíacos adultos recolectadas al momento del diagnóstico y la de 52 individuos controles no celíacos. Los pacientes fueron re-evaluados luego de un tiempo medio de 5 años en tratamiento. Evaluamos AAA tipoIgA mediante ELISA empleando un equipo commercial modificado y SMA IgA por inmunofluorescencia indirecta sobre sustrato de esófago de mono. Resultados: Al momento del diagnóstico, los pacientes celíacos tuvieron valores de AAA significativamente más elevados que los controles (p<0.00001). Todos los pacientes con EC activa presentaron niveles de AAA por encima del valor de corte determinado para el grupo control sano y se evidenció una reducción significativa de los nivelesluego del tratamiento (p>0.0001). Los AAA presentaron una correlación significativa con los anticuerpos anti-transglutaminasa tisular (r=0.62) y anti-gliadina (r=0.60) (p<0.00001), de igual modo que con la severidad del daño intestinal (p<0.05). Al momento del diagnóstico, se detectó SMA en el suero de 35 pacientes no controles. Los pacientes SMA positivos tuvieron valores significativamente mayores de AAA (p<0.002), un incremento del número de enfermedades autoinmunes asociadas (p<0.04), menarca tardía (p<0.04), niveles bajos de hemoglobina (p<0.01), incremento del clearance de a-1 antitripsina fecal (p<0.01) y mayor severidad de la diarrea (p<0.06).En ellos se evidenció una tendencia al desarrollo de complicaciones más severas durante el seguimiento (p=0.059). Conclusiones: Sugerimos que la presencia de un valor sérico aumentado de AAA tipo IgA...(AU)

Antibodies to human recombinant tissue transglutaminase may detect coeliac disease patients undiagnosed by endomysial antibodies.

BACKGROUND: The screening and diagnosis of coeliac disease have been simplified by the advent of new serological tools. AIM: To assess the clinical utility of a newly developed kit for antibodies to human recombinant tissue transglutaminase (hu-anti-tTG) in a large population of patients undergoing intestinal biopsy for suspected intestinal disorders. METHODS: We evaluated 426 serum samples from consecutive adult patients (250 from untreated coeliac disease patients and 176 from individuals in whom a diagnosis of coeliac disease had been excluded), obtained at the time of intestinal biopsy. Samples were tested for immunoglobulin A (IgA) hu-anti-tTG by enzyme-linked immunoabsorbent assay, IgA endomysial antibodies (EmA) by indirect immunofluorescence and IgA and IgG antigliadin antibodies by enzyme-linked immunoabsorbent assay. A sub-group of samples was also assessed for a guinea-pig-based anti-tissue transglutaminase. RESULTS: According to the cut-off for hu-anti-tTG, the sensitivity, specificity and positive and negative predictive values were 91%, 96%, 97% and 87%, respectively. Simultaneous determination of EmA showed values of 86%, 100%, 100% and 83% for the same parameters. Although 19 coeliac disease patients (7.6%) were negative for EmA and hu-anti-tTG, both tests rendered superior statistical values to antigliadin antibody tests. At diagnosis, IgA deficiency was detected in 11 patients, but both assays were able to detect samples with mild to moderate deficiency. The comparison of hu-anti-tTG with EmA showed excellent concordance between the tests (kappa statistic, 0.85). Discordance was observed in 20 samples from coeliac disease patients (8%) and in nine samples from controls (5%). Fifteen samples had an EmA-negative but hu-anti-tTG-positive serology, and five showed the converse pattern. Comparison of human recombinant and guinea-pig tests showed concordant results in 96% of cases. CONCLUSIONS: The quantitative determination of hu-anti-tTG type IgA using a commercial enzyme-linked immunoabsorbent assay kit was highly sensitive and specific for the detection of coeliac disease. Our results in a large population of patients with a clinical condition suggestive of the disorder demonstrated that the test can be used to detect a substantial number of patients otherwise unrecognized by IgA EmA.

Is it necessary to screen for celiac disease in postmenopausal osteoporotic women?

Decreased bone mass is a frequent finding in celiac patients, and subclinical celiac disease (CD) appears to be unusually overrepresented among patients with idiopathic osteoporosis. Since silent CD may be more common than previously believed, it has been suggested that all osteoporotic patients should be checked for occult CD. The aim of this study was to explore the prevalence of CD in a well-defined population of postmenopausal osteoporotic women. We evaluated 127 consecutive postmenopausal patients (mean age: 68 years; range: 50-82 years) with verified osteoporosis. The observed prevalence of CD in this group was compared to that observed in a group of 747 women recruited for a population-based study. The screening algorithm used to diagnose CD was based on a 3-level screening using type IgA and IgG antigliadin antibodies (AGA) in all the patients (1st level) followed by antiendomysial antibodies (EmA) and total IgA (2nd level) of samples testing positive, and intestinal biopsy of positive cases (3rd level). At the end of the serological screening, only 1 of 127 osteoporotic women was eligible for jejunal biopsy showing a characteristic celiac flat mucosa (prevalence 7.9 x 1,000; 95% CI 0.2-43.1). In addition, CD was diagnosed in 6 of 747 women of the population-based study (prevalence: 8.0 x 1,000; 95% CI 3.3-18.3). There was no significant difference between the two groups. Therefore, our study showed that the prevalence of CD in postmenopausal osteoporotic women was lower than that reported in previous studies and similar to that of the general population. In conclusion, although the relatively small size of the group tested does not allow us to be conclusive, the results suggest that a case finding policy in postmenopausal osteoporosis would have a high cost/benefit ratio except for patients not responding to conventional therapies, or presenting borderline laboratory results.

Acute gastrointestinal permeability responses to different non-steroidal anti-inflammatory drugs.

BACKGROUND AND AIMS: Non-steroidal anti-inflammatory drugs (NSAIDs) cause gastrointestinal damage both in the upper and lower gastrointestinal tract. New anti-inflammatory drugs have been developed in an attempt to improve their gastrointestinal side effect profile. Our objective was to compare the effect on gastrointestinal permeability of acute equieffective doses of four different NSAIDs; three were designed to reduce gastrointestinal mucosal injury. MATERIALS: Healthy volunteers underwent sugar tests in a randomised fashion, 15 days apart, at: (1) baseline; (2) after two days of 75 mg slow release (microspheres) indomethacin; (3) after two days of 7.5 mg oral meloxicam which preferentially inhibits cyclooxygenase 2; and (4) after two days of 750 mg naproxen. A subgroup of subjects was tested after two days of 200 mg celecoxib. In each test, subjects ingested a solution containing sucrose, lactulose, and mannitol and sucralose, to evaluate gastroduodenal, intestinal, and colonic permeability, respectively. RESULTS: Gastric permeability was significantly affected by naproxen (p<0.05) but not by slow release indomethacin, meloxicam, or celecoxib. Intestinal permeability was significantly increased by the first three NSAIDs (p<0.05) but not by celecoxib. Abnormal lactulose/mannitol ratios were observed in 42% of meloxicam treatments, in 62% during indomethacin, and in 75% of subjects treated with naproxen. Finally, colonic permeability, as measured by sucralose, was not significantly increased by any of the four drugs. CONCLUSION: Our study provides evidence that the newly developed NSAIDs reduce gastric mucosal permeability significantly. However, most produced significant alteration of small intestinal permeability. In contrast, our results suggest that celecoxib seems to exhibit the most desirable gastrointestinal side effect profile.

Prevalence of celiac disease in Argentina: screening of an adult population in the La Plata area.

OBJECTIVES: Up to now, the epidemiological characteristic of celiac disease among adults in South America remains unknown. The present prospective screening was designed to determine the prevalence of celiac disease in adults from the general population in an urban area of Argentina. METHODS: Between January. 1998, and May, 2000, all couples attending a centralized laboratory for an obligatory prenuptial examination in the La Plata area were offered participation in a screening program for celiac disease. The study included 2000 subjects (996 women; median age 29 yr, range 16-79 yr). All individuals completed a clinical questionnaire at the time that serum samples were obtained. A three-step screening protocol was used, as follows: 1) all samples were tested for antigliadin antibodies (AGAs) (type IgA and IgG); 2) samples that were IgA AGA positive were tested for antiendomysial antibody (EmA type IgA); samples that were positive for AGA-G but negative for IgA AGAs were tested for total IgA serum levels and EmA type IgG; and 3) subjects who were EmA-positive were referred for intestinal biopsy. RESULTS: At the end of the screening we detected 10 subjects who were EmA-A positive and two others who were IgA-deficient (both were EmA-G positive). Up to now, 11 of the 12 subjects (including nine EmA-positive and two IgA-deficient subjects) had endoscopic intestinal biopsies showing the characteristic celiac histology. The remaining EmA-positive individual was considered to be affected by celiac disease. The overall prevalence assessed was 1:167 (6.0 x 1000 subjects; 95% CI = 3.1-10.5). Eight of the 12 (67%) subjects were female (1:124; 8.0 x 1000; 95% CI = 3.5-15.8) and four (33%) were male (1:251; 4.0 x 1000; 95% Cl = 1.1-10.2). Although eight new patients were considered to be asymptomatic, three presented with a subclinical course and one was classically symptomatic. Only one patient had been previously diagnosed with celiac disease. CONCLUSIONS: Our screening protocol showed a very high prevalence of celiac disease for an urban area of Argentina that is ethnically similar to 90% of the general population of the country. The prevalence among women was double that for men, and the heterogeneous clinical picture of new patients showed predominance of asymptomatic cases.

Relation between cigarette smoking and celiac disease: evidence from a case-control study.

OBJECTIVES: It has been suggested that environmental factors other than gliadin might play a role in pathogenesis of celiac disease. Cigarette smoking was reported to exert a protective effect against the development of symptomatic celiac disease; however, this relationship was not confirmed. The aim of this study was to determine the effect of cigarette smoking on celiac disease. METHODS: A cohort of 87 consecutive celiac disease patients attending the clinic of Malabsorption and 174 age- and sex-matched individuals diagnosed with functional GI disorder were included in the study. Clinical information was obtained both at the time of diagnosis and at follow-up by reviewing the clinical history. Smoking information was obtained through an in-person interview using a questionnaire. RESULTS: Although 33% of controls were current smokers at the time of the study, only 16% of celiac patients were smokers at diagnosis (odds ratio, 0.39; 95% confidence interval 0.19-0.79; p < 0.006). The proportion of nonsmokers among patients (84%) was significantly greater than that among controls (67%; odds ratio, 2.54; 95% confidence interval 1.27-5.16; p < 0.007). Current smoker patients had a lower baseline BMI (p < 0.05) and body weight (p < 0.05) compared to former smokers. Compared with nonsmokers, control individuals who were active smokers at entry in the study were younger (p < 0.02) and had lower body weight (p < 0.03) and BMI (p < 0.03). Interestingly, positive lineal correlation was observed between age at diagnosis and daily cigarette consumption (r = 0.72; p < 0.004) in active smokers. We did not detect any relationship either between causes for cessation of smoking and clinical symptoms or between differences in the proportions of smoking habits when patients were stratified according to their clinical status at diagnosis (symptomatic vs subclinical/asymptomatic cases). CONCLUSIONS: This study provides evidence that, compared with control subjects, a significantly lower proportion of patients with celiac disease were current smokers at the time of diagnosis, and that cigarette smoking delayed diagnosis of celiac disease. Our study suggests that the nutritional compromise of patients with celiac disease who smoked resulted from the summation of the effect of celiac disease per se and that produced by the smoking habit. Further studies are necessary to identify whether the relationship between smoking and celiac disease is causal or incidental.

Tissue transglutaminase antibodies in celiac disease: assessment of a commercial kit.

OBJECTIVE: Tissue transglutaminase was identified as the autoantigen eliciting endomysial antibody. A homemade enzyme-linked immunosorbent assay (ELISA)-based test was recently developed to determine quantitative titers of IgA antitissue transglutaminase antibody. Our objective in this study was to assess the suitability of a newly developed commercial kit for quantitative determination of antibody in patients with untreated celiac disease. MATERIALS: We tested serum samples from 79 untreated celiac patients, 42 healthy blood donors, and 18 patients with nonceliac intestinal disorders evaluated in two different centers. Samples were tested for antitissue transglutaminase, and antiendomysial and antigliadin antibodies in the center where diagnosis was performed. To assess interlaboratory variability of methods, 24 samples randomly selected were blindly tested in both centers. Antitissue transglutaminase antibodies were determined using a commercial kit (INOVA Diagnostics, Inc., San Diego, CA). RESULTS: Untreated celiac patients had significantly higher titers of antitissue transglutaminase than healthy and disease controls (p < 0.00001). According to the cut-off provided by the manufacturers (20 AU/mL), overall sensitivity was 92% (85% for one center and 100% for the other) and specificity was 98% (100% and 95%, respectively). Antiendomysial antibody was 86% sensitive and 100% specific. Discordance between antitissue transglutaminase and antiendomysial antibodies was detected in 13% of patients. Although two antitissue transglutaminase-negative cases had a positive antiendomysial antibody, the inverse situation was found in eight cases. A blind determination of antitissue transglutaminase on the same samples evidenced a good agreement (kappa statistic: 0.66) between both centers when assessment was qualitative (based on the decision of positive or negative). Although correlation of titers for both determinations was highly significant (r: 0.902, p < 0.00001), a very wide interlaboratory variability (median: 50%) was detected when absolute values were considered. CONCLUSIONS: The quantitative determination of antitissue transglutaminase using a commercial kit was highly sensitive and specific for detection of celiac disease. We observed an incomplete overlapping with antiendomysial antibody. The very high variability of values between laboratories still remains to be solved so as to propose the commercial ELISA assay for the screening of celiac disease.

The natural history of gluten sensitivity: report of two new celiac disease patients resulting from a long-term follow-up of nonatrophic, first-degree relatives.

OBJECTIVE: Early studies revealed that up to 50% of non-atrophic, first-degree relatives of celiac disease patients exhibit features of gluten sensitivity. However, whether these features progress to a fully expressed celiac disease remain partially known. Our aim was to report two new patients resulting from a prospective, long-term surveillance of relatives who were nonatrophic at initial assessment. METHODS: After a median time of 86 months (range: 42-102 months) from the baseline assessment, we re-evaluated 44 first-degree relatives of propositi who had taken part in family studies and in whom baseline small intestinal biopsies were normal. At the baseline screening, 21 relatives had positive serum antigliadin antibodies and/or increased intraepithelial lymphocyte infiltration, and 23 did not. In addition, 11 of 18 had a celiac-like response to rectal gluten challenge and 16 of 34 possessed the characteristic HLA DQ2 haplotype (DQA1 0501 DQB1 0201). Re-evaluation was based on celiac-related serology antigliadin (AGA) and endomysial (EmA) antibodies. EmA-positive subjects underwent intestinal biopsy. RESULTS: At the end of the study, EmA was positive in only two subjects. Histological examination revealed flat small bowel mucosa in both. At baseline, both cases were EmA-negative and no minor histological changes were observed. One was a woman with positive baseline IgA and IgG AGA and a rectal gluten challenge with a celiac-like response; the other patient has presented only with a positive IgG AGA. In both cases, progression was detected in a clinically silent context. Both new patients had the characteristic HLA DQ2 haplotype. CONCLUSIONS: Our data suggest the need to re-evaluate relatives who have been negative on initial screening for celiac disease. Up to now, the progression to severe enteropathy was only observed in relatives who had presented some evidence of gluten sensitivity and the characteristic HLA DQ2 haplotype. Longer longitudinal studies are necessary to obtain definitive conclusions.