Room for Improvement in the Treatment of Helicobacter pylori Infection: Lessons from the European Registry on H. pylori Management (Hp-EuReg).

BACKGROUND: Managing Helicobacter pylori infection requires constant decision making, and each decision is open to possible errors. AIM: The aim was to evaluate common mistakes in the eradication of H. pylori, based on the "European Registry on Helicobacter pylori management". METHODS: European Registry on Helicobacter pylori management is an international multicentre prospective noninterventional registry evaluating the decisions and outcomes of H. pylori management by European gastroenterologists in routine clinical practice. RESULTS: Countries recruiting more than 1000 patients were included (26,340 patients). The most common mistakes (percentages) were: (1) To use the standard triple therapy where it is ineffective (46%). (2) To prescribe eradication therapy for only 7 to 10 days (69%). (3) To use a low dose of proton pump inhibitors (48%). (4) In patients allergic to penicillin, to prescribe always a triple therapy with clarithromycin and metronidazole (38%). (5) To repeat certain antibiotics after eradication failure (>15%). (6) Failing to consider the importance of compliance with treatment (2%). (7) Not to check the eradication success (6%). Time-trend analyses showed progressive greater compliance with current clinical guidelines. CONCLUSION: The management of H. pylori infection by some European gastroenterologists is heterogeneous, frequently suboptimal and discrepant with current recommendations. Clinical practice is constantly adapting to updated recommendations, although this shift is delayed and slow.

Helicobacter pylori first-line and rescue treatments in patients allergic to penicillin: Experience from the European Registry on H pylori management (Hp-EuReg).

BACKGROUND: Experience in Helicobacter pylori eradication treatment of patients allergic to penicillin is very scarce. A triple combination with a PPI, clarithromycin (C), and metronidazole (M) is often prescribed as the first option, although more recently the use of a quadruple therapy with PPI, bismuth (B), tetracycline (T), and M has been recommended. AIM: To evaluate the efficacy and safety of first-line and rescue treatments in patients allergic to penicillin in the "European Registry of H pylori management" (Hp-EuReg). METHODS: A systematic prospective registry of the clinical practice of European gastroenterologists (27 countries, 300 investigators) on the management of H pylori infection. An e-CRF was created on AEG-REDCap. Patients with penicillin allergy were analyzed until June 2019. RESULTS: One-thousand eighty-four patients allergic to penicillin were analyzed. The most frequently prescribed first-line treatments were as follows: PPI + C + M (n = 285) and PPI + B + T + M (classic or Pylera® ; n = 250). In first line, the efficacy of PPI + C + M was 69%, while PPI + B + T + M reached 91% (P < .001). In second line, after the failure of PPI + C + M, two rescue options showed similar efficacy: PPI + B + T + M (78%) and PPI + C + levofloxacin (L) (71%) (P > .05). In third line, after the failure of PPI + C + M and PPI + C + L, PPI + B + T + M was successful in 75% of cases. CONCLUSION: In patients allergic to penicillin, a triple combination with PPI + C + M should not be generally recommended as a first-line treatment, while a quadruple regimen with PPI + B + T + M seems to be a better option. As a rescue treatment, this quadruple regimen (if not previously prescribed) or a triple regimen with PPI + C + L could be used but achieved suboptimal (<80%) results.

Situación actual del manejo de la hemorragia digestiva alta no varicosa en España / Current management of nonvariceal upper gastrointestinal bleeding in Spain

Introducción La mortalidad en la hemorragia digestiva alta no varicosa (HDA-NV) no ha variado. Se necesita conocer más información para mejorar las estrategias de tratamiento. Los objetivos de este estudio fueron: a) describir el perfil de presentación de los episodios de HDA-NV; b) el manejo clínico según práctica clínica habitual, y c) establecer cuáles son los resultados clínicos asociados a los tratamientos endoscópicos y médicos en España. Métodos ENERGIB fue un estudio retrospectivo de cohortes que recogió información del manejo y forma de presentación de HDA-NV en Europa. Presentamos los datos relativos a España. Los pacientes se trataron según la práctica clínica habitual. Para las variables cuantitativas se calculó la media y la desviación estándar y para las categóricas se calcularon frecuencias absolutas y relativas. Resultados Los pacientes (n = 403) fueron hombres (71%), con edad media 65 años, asociaron comorbilidad (62,5%). Los equipos encargados de su manejo fueron gastroenterólogos (57,1%) o médicos internistas (25,1%). Los inhibidores de la bomba de protones se usaron de forma empírica preendoscopia en un 80% de los casos. El 6,4% presentó persistencia y el 6,7% resangrado después de la endoscopia. La tasa de mortalidad en los 30 días posteriores fue del 3,5%.ConclusionesEste estudio permite conocer el perfil de presentación de los episodios de HDA-NV en España y el manejo en práctica clínica habitual. Este se ajusta a los estándares propuestos por las recientes guías de práctica clínica. Entre otros datos destaca que los pacientes con hemorragia son cada vez de edad más avanzada y presentan un mayor número de enfermedades asociadas, lo que podría explicar que la mortalidad se haya mantenido estable a pesar de los evidentes avances en el manejo de esta entidad (AU)

Background Mortality related to nonvariceal upper gastrointestinal bleeding (NVUGIB) has not changed. More information is needed to improve the management of this entity. The aims of this study were: a) to determine the characteristics of bleeding episodes, b) to describe the clinical approaches routinely used in NVUGIB, and c) to identify adverse outcomes related to endoscopic or medical treatments in Spain. Methods The European survey of nonvariceal upper GI bleeding (ENERGiB) was an observational, retrospective cohort study on NVUGIB with endoscopic evaluation carried out across Europe. The present study focused on Spanish patients in the ENERGiB study. The patients were managed according to routine care. The mean and standard deviation were calculated for quantitative variables and absolute and relative frequencies were calculated for categorical variables. Results Patients (n=403) were mostly men (71%), with a mean age of 65 years, and co-morbidities (62.5%). Most of the patients were managed by gastroenterologists (57.1%) or internal medicine teams (25.1%). A proton pump inhibitor was used empirically in 80% before endoscopy. Bleeding persistence occurred in 6.4% and recurrence in 6.7%. The mortality rate at 30 days was 3.5%.ConclusionsThis study contributes to the characterization of Spanish patients and NVUGIB episodes in a real clinical setting and identifies the routine management of this entity, which is in line with the standards proposed by recent clinical practice guidelines. A notable finding was that age and the number of comorbidities in NVUGIB patients were increasing. These factors could explain the persistent mortality rate, despite the evident advances in the management of this entity (AU)

[Current management of nonvariceal upper gastrointestinal bleeding in Spain]. / Situación actual del manejo de la hemorragia digestiva alta no varicosa en España.

BACKGROUND: Mortality related to nonvariceal upper gastrointestinal bleeding (NVUGIB) has not changed. More information is needed to improve the management of this entity. The aims of this study were: a) to determine the characteristics of bleeding episodes, b) to describe the clinical approaches routinely used in NVUGIB, and c) to identify adverse outcomes related to endoscopic or medical treatments in Spain. METHODS: The European survey of nonvariceal upper GI bleeding (ENERGiB) was an observational, retrospective cohort study on NVUGIB with endoscopic evaluation carried out across Europe. The present study focused on Spanish patients in the ENERGiB study. The patients were managed according to routine care. The mean and standard deviation were calculated for quantitative variables and absolute and relative frequencies were calculated for categorical variables. RESULTS: Patients (n=403) were mostly men (71%), with a mean age of 65 years, and co-morbidities (62.5%). Most of the patients were managed by gastroenterologists (57.1%) or internal medicine teams (25.1%). A proton pump inhibitor was used empirically in 80% before endoscopy. Bleeding persistence occurred in 6.4% and recurrence in 6.7%. The mortality rate at 30 days was 3.5%. CONCLUSIONS: This study contributes to the characterization of Spanish patients and NVUGIB episodes in a real clinical setting and identifies the routine management of this entity, which is in line with the standards proposed by recent clinical practice guidelines. A notable finding was that age and the number of comorbidities in NVUGIB patients were increasing. These factors could explain the persistent mortality rate, despite the evident advances in the management of this entity.

Duodenal expression of Toll-like receptors and interleukins are increased in both children and adult celiac patients.

BACKGROUND: Toll-like receptors (TLRs) have achieved an extraordinary amount of interest in inflammatory diseases due to their role in the inflammatory activation. By activating the production of several biological factors, TLRs induce type I interferons and other cytokines, which drive the inflammatory response and activate the adaptive immune system. AIMS: The aim of this study was to investigate and compare the expression and clinical relevance of TLRs and interleukins in pediatric and adult celiac disease (CD), defined as intolerance to dietary proteins found in wheat, barley, and rye. METHODS: The expression levels of TLR3, TLR4, and TLR7, interleukins, and different transcription factors were analyzed on duodenal biopsies from ten children and 31 adults with CD, and 21 duodenal controls biopsies without CD (ten children and 11 adults). The analyses were performed by immunohistochemistry and real-time PCR. RESULTS: There were no significant differences in the studied parameters between adults and children. TLR4 expression level was increased twofold in CD specimens compared to controls. CD patients with high levels of TLR4 also showed high levels of interleukins (IL1, IL6, IL8, and IL17) as well as transcription factors (IRAK4, MyD88, and NF-κB). CONCLUSIONS: TLR4 expression is associated with CD independently of age at diagnosis. Pediatric patients and adult patients have a similar inflammatory profile, making it possible to treat both with the same immunological therapy in the future.

Anemia ferropénica refractaria e intolerancia al gluten: respuesta a la dieta sin gluten / Refractory iron-deficiency anemia and gluten intolerance - Response to gluten-free diet

Introducción: la anemia ferropénica refractaria presenta un origen multifactorial, relacionado con diversas enfermedades digestivas, siendo las más frecuentes la enfermedad celiaca con malabsorción y la EII junto con la intolerancia al gluten aislada. Objetivos: determinar la prevalencia de marcadores serológicos, genéticos e histológicos de intolerancia al gluten y analizar la respuesta a la retirada del gluten de la dieta en estos pacientes. Métodos: se incluyeron de forma prospectiva y consecutiva una serie de pacientes con anemia refractaria. Se les aplicó un protocolo consistente en determinación marcadores serológicos (TGt-2), genéticos (HLA-DQ2/DQ8) e histológicos de enfermedad celíaca. Todos siguieron una dieta sin gluten durante una mediana de 3,6 años. Se interpretó como respuesta positiva la desaparición mantenida de la anemia durante el seguimiento. Resultados: se estudiaron 98 pacientes (84% mujeres) con una edad media de 54 años. Los ac. anti-TGt2 fueron positivos en el 5% de los casos. Un total de 67 casos (68%) presentaban el haplotipo HLA-DQ2 o DQ8 (+). Encontramos atrofia vellositaria (Marsh III) en el 13% de los casos y patrón inflamatorio (Marsh I o II) en el 13%. Los 72 casos restantes (74%) no presentaban alteraciones histológicas duodenales. Se compararon la edad, el tiempo de evolución de la anemia, número de transfusiones, número de dosis de hierro parenteral y tiempo en dieta sin gluten, en función de la presencia o no de atrofia vellositaria y de la positividad para el HLA-DQ2/8, sin encontrar diferencias significativas en ninguna de las variables analizadas. La respuesta fue positiva en el 92% de los casos. Conclusiones: la enfermedad celiaca con atrofia vellositaria es causa poco frecuente de anemia refractaria. Las formas de intolerancia al gluten sin lesión histológica asociada, representan cerca del 75% de los casos y desempeñan, por lo tanto, un papel importante en su aparición(AU)

Introduction: refractory iron-deficiency anemia has a multifactorial origin related to various gastrointestinal conditions, with celiac disease plus malabsorption and IBD together with isolated gluten intolerance being most common. Objectives: to determine the prevalence of serum, genetic, and histological markers for gluten intolerance, and to analyze the response to gluten withdrawal from the diet in these patients. Methods: a number of patients with refractory anemia were prospectively and consecutively enrolled. A protocol to measure serum (TGt-2), genetic (HLA-DQ2/DQ8), and histological markers for celiac disease was applied. All followed a gluten-free diet for a median 3.6 years. Sustained remission of anemia during follow-up was interpreted as positive response. Results: ninety-eight patients (84% females) with a mean age of 54 years were studied. Anti-TGt2 antibodies were positive in 5% of cases. A total of 67 cases (68%) were haplotype HLA-DQ2 or -DQ8 (+). We found villous atrophy (Marsh III) in 13% of patients, and an inflammatory pattern (Marsh I or II) in 13%. All remaining 72 patients (74%) had no histological duodenal changes. Age, anemia duration, number of transfusions, number of parenteral iron doses, and time on a gluten-free diet were all compared according to the presence or absence of villous atrophy and HLADQ2/ 8 positivity, and no significant differences were found for any of the analyzed variables. Response was positive in 92% of subjects. Conclusions: celiac disease with villous atrophy is rarely a cause of refractory anemia. Gluten intolerance with no histological lesions is seen in almost 75% of patients, and therefore plays a relevant role in its development(AU)

Differences between pediatric and adult celiac disease.

INTRODUCTION: Celiac disease (CD) is a common autoimmune condition (involves 1-2% of the general population) that develops at any age in life but manifests differently in children and adults. OBJECTIVES: To analyze clinical differences in disease expression between both groups, as well as findings at the time of diagnosis. METHODS: A retrospective study of a series of patients diagnosed with CD during childhood (< 14 years) versus a series of adult patients (> 14 years). RESULTS: a total of 187 patients were included, of which 43 were children and 144 were adults. Among clinical manifestations in children classic presentation forms predominated -34 patients(79%) versus 20 adult patients (14%) (p < 0.001) (OR = 23.4;95% CI: 9.8-56.1). In contrast, atypical forms were predominant in the latter, and anemia was the most common finding in 61 patients (42%) versus 8 pediatric patients (19%) (p < 0.01). Adults had a greater diagnostic delay with a mean 10 ± 9 years versus 1 ± 2 years in children (p < 0.001). In adults, we found a higher frequency of associated autoimmune diseases (24.3 versus 9.3% in children) (p < 0.05). Regarding serum markers, TGt-2 was more commonly positive among children (88%) as compared to adults (31%) (p < 0.001); (OR = 21.4: 95% CI: 7.2-63.6). We found similar results with regard to the presence of villous atrophy, which was more common in children (95%) than in adults (33%) (p < 0.001) (OR = 41.0;95% CI: 9.5-76.7). As regards genetic markers, DQ2 was somewhat more common in children (97.7%) than in adults (90.3%) whereas DQ8 wasless common in children (2.3%) than in adults (9.7%), with no significant differences between groups. Patients negative for both markers were not included. CONCLUSIONS: Pediatric CD has clear differences when compared to adult CD, with classic forms predominating in the former, who also display a higher occurrence of positive serology and villous atrophy, and less diagnostic delay. In contrast, atypical forms predominate in the adult, with a lower occurrence of positive serology and milder histological forms. In these patients associated autoimmune conditions are more common and diagnostic delay is longer.

Diferencias entre la enfermedad celiaca infantil y del adulto / Diferences between pediatric and adult celiac disease

Introducción: la enfermedad celiaca (EC) es un proceso frecuente (afecta al 1-2% en población general), de naturaleza autoimmune, que aparece a cualquier edad de la vida, pero que se presenta de forma diferente en el niño que en el adulto. Objetivos: analizar las diferencias clínicas en las formas de expresión de la enfermedad entre ambos grupos, así como los hallazgos al momento del diagnóstico. Métodos: estudio retrospectivo de una serie de pacientes diagnosticados, en la infancia (< 14 años), frente a una serie de adultos (> 14 años). Resultados: se incluyeron un total de 187 pacientes, de los cuales 43 eran niños y 144 adultos. En las manifestaciones clínicas de los niños, predominaron las formas de presentación clá - sicas, 34 casos (79%) frente a los adultos 20 casos (14%) (p < 0,001) (OR = 23,4; IC-95%: 9,8-56,1). Por el contrario, en estos predominaron las formas atípicas, siendo la anemia el hallazgo más frecuente en 61 casos (42%) frente a 8 casos (19%) en los niños (p < 0,01). En los adultos existía un mayor retraso diagnóstico con una media de 10 ± 9 años, frente a los niños, que es de 1 ± 2 años (p < 0,001). Encontramos en los adultos una mayor frecuencia de enfermedades autoinmunes asociadas (24,3%), frente al 9,3% en niños (p < 0,05). Respecto a los marcadores serológicos, la TGt-2 fue más frecuentemente positiva en los niños (88%), que en los adultos (31%) (p < 0,001); (OR = 21,4: IC-95%: 7,2-63,6). Resultados similares encontramos en relación con la presencia de atrofia vellositaria, que estuvo presente más frecuentemente en los niños (95%) que en los adultos (33%) (p < 0,001) (OR = 41,0; IC-95%: 9,5-76,7). Respecto a los marcadores genéticos, el DQ2 fue algo más frecuente en niños (97,7%) que en adultos 90,3%, y el DQ8 ocurrió al contrario, siendo menos frecuente en niños (2,3%) que en adultos (9,7%), no encontrando diferencias entre ambos grupos. No se incluyeron pacientes negativos para ambos marcadores(AU)

Introduction: celiac disease (CD) is a common autoimmune condition (involves 1-2% of the general population) that develops at any age in life but manifests differently in children and adults. Objectives: to analyze clinical differences in disease expression between both groups, as well as findings at the time of diagnosis. Methods: a retrospective study of a series of patients diagnosed with CD during childhood (< 14 years) versus a series of adult patients (> 14 years). Results: a total of 187 patients were included, of which 43 were children and 144 were adults. Among clinical manifestations in children classic presentation forms predominated –34 patients (79%) versus 20 adult patients (14%) (p < 0.001) (OR = 23.4; 95% CI: 9.8-56.1). In contrast, atypical forms were predominant in the latter, and anemia was the most common finding in 61 patients (42%) versus 8 pediatric patients (19%) (p < 0.01). Adults had a greater diagnostic delay with a mean 10 ± 9 years versus 1 ± 2 years in children (p < 0.001). In adults, we found a higher frequency of associated autoimmune diseases (24.3 versus 9.3% in children) (p < 0.05). Regarding serum markers, TGt-2 was more commonly positive among children (88%) as compared to adults (31%) (p < 0.001); (OR = 21.4: 95% CI: 7.2-63.6). We found similar results with regard to the presence of villous atrophy, which was more common in children (95%) than in adults (33%) (p < 0.001) (OR = 41.0; 95% CI: 9.5-76.7). As regards genetic markers, DQ2 was somewhat more common in children (97.7%) than in adults (90.3%) whereas DQ8 was less common in children (2.3%) than in adults (9.7%), with no significant differences between groups. Patients negative for both markers were not included(AU)

[Celiac disease: an unique autoinmune model]. / Enfermedad celíaca: un modelo único de proceso autoinmune.

Celiac disease is a unique autoimmune disorder, because the environmental precipitant factor is known. It is gluten, the major storage protein of wheat and similar grains. Originally was considered a rare malabsorption syndrome of childhood, but nowadays is recognized a common condition, that affects to 1% of the general population, all over the world', involves to all different races, may be diagnosed at any age, and affects to many organ systems. Therapy for the disease is a gluten-free-diet that must be strict and long-term. This diet cause a total recovery clinical and analytical, with excellent quality of life of patients.