New entity of adult ultra-short coeliac disease: the first international cohort and case-control study.

BACKGROUND: Ultra-short coeliac disease (USCD) is defined as villous atrophy only present in the duodenal bulb (D1) with concurrent positive coeliac serology. We present the first, multicentre, international study of patients with USCD. METHODS: Patients with USCD were identified from 10 tertiary hospitals (6 from Europe, 2 from Asia, 1 from North America and 1 from Australasia) and compared with age-matched and sex-matched patients with conventional coeliac disease. FINDINGS: Patients with USCD (n=137, median age 27 years, IQR 21-43 years; 73% female) were younger than those with conventional coeliac disease (27 vs 38 years, respectively, p<0.001). Immunoglobulin A-tissue transglutaminase (IgA-tTG) titres at index gastroscopy were lower in patients with USCD versus conventional coeliac disease (1.8×upper limit of normal (ULN) (IQR 1.1-5.9) vs 12.6×ULN (IQR 3.3-18.3), p<0.001).Patients with USCD had the same number of symptoms overall (median 3 (IQR 2-4) vs 3 (IQR 1-4), p=0.875). Patients with USCD experienced less iron deficiency (41.8% vs 22.4%, p=0.006).Both USCD and conventional coeliac disease had the same intraepithelial lymphocytes immunophenotype staining pattern; positive for CD3 and CD8, but not CD4.At follow-up having commenced a gluten-free diet (GFD) (median of 1181 days IQR: 440-2160 days) both USCD and the age-matched and sex-matched controls experienced a similar reduction in IgA-tTG titres (0.5 ULN (IQR 0.2-1.4) vs 0.7 ULN (IQR 0.2-2.6), p=0.312). 95.7% of patients with USCD reported a clinical improvement in their symptoms. INTERPRETATION: Patients with USCD are younger, have a similar symptomatic burden and benefit from a GFD. This study endorses the recommendation of D1 sampling as part of the endoscopic coeliac disease diagnostic workup.

Helicobacter pylori Diagnostic Tests Used in Europe: Results of over 34,000 Patients from the European Registry on Helicobacter pylori Management.

BACKGROUND AND AIMS: Several methods are available to diagnose Helicobacter pylori infection. Our objective was to evaluate the tests used for both the initial diagnosis and the confirmation of eradication after treatment in Europe. METHODS: The European Registry on the management of Helicobacter pylori infection is an international, multicentre, prospective, non-interventional registry aiming to evaluate the management of Helicobacter pylori-infected patients in Europe. Countries with at least 100 cases registered from June 2013 to April 2021, and with a validated diagnostic method were analysed. Data were quality reviewed. RESULTS: A total of 34,920 adult patients from 20 countries were included (mean age 51 years; 61% women). To establish the initial diagnosis, invasive tests were performed in 19,801 (71%) patients, non-invasive in 11,369 (41%), and both in 3437 (12%). The most frequent were histology (n = 11,885; 43%), a rapid urease test (n = 10,636; 38%) and an urea breath test (n = 7577; 27%). According to the age, invasive tests were indicated in 11,179 (77%) ≥50 years, and in 8603 (65%) <50 years. Depending on the country, the use of invasive tests ranged from 29-99% in <50 years to 60-99% in ≥50. Most of the tests used to confirm eradication were non-invasive (n = 32,540; 93%), with the urea breath test being the most frequent (n = 32,540; 78%). In 2983 (9%) post-treatment tests, histology (n = 1887; 5%) or a rapid urease test (n = 1223; 4%) were performed. CONCLUSION: A great heterogeneity was observed for the initial diagnosis and confirmation of the eradication. The reasons for the apparent lack of adherence to the clinical guidelines should be further explored.

New approaches to diet therapy for eosinophilic esophagitis.

PURPOSE OF REVIEW: An empiric step-up (2-4-6) elimination diet remains the most common dietary approach in clinical practice when treating eosinophilic esophagitis (EoE). However, research in this field has fallen behind pharmacological therapy. This review aims to summarize novel approaches to dietary therapy for EoE. RECENT FINDINGS: A first prospective multicenter study in 41 pediatric patients (mean age 9 years) has evaluated the efficacy of a cow's milk elimination diet. This dietary approach led to histological remission in 51% of patients, albeit a caveat is that up to 80% of patients were receiving concomitant therapy with proton pump inhibitors. In a series of 18 adult patients with documented milk-induced EoE, ingestión of 400 ml of sterilized milk (boiled for up to 20 min) daily for 8 weeks did not induce histologic relapse in two-thirds of patients. SUMMARY: Milk elimination diet is effective in one-half of pediatric EoE patients and should likely be the first choice in children with EoE (within a step-up dietary approach). Promising data on tolerance of sterilized milk in adults with milk-induced EoE (66%) merit further replication in children, which may radically improve quality of life for patients and their caregivers.

Ultra-short celiac disease exhibits differential genetic and immunophenotypic features compared to conventional celiac disease / La enfermedad celiaca ultra corta presenta una expresión genética e inmunológica distinta a la de la enfermedad celiaca convencional

Background: Ultra-short coeliac disease (USCD) is a novel celiac disease (CD) subtype limited to the duodenal bulb (D1). HLA haplotypes and flow cytometry have not been assessed yet. Aims: To compare genetic, clinical, serologic, histopathologic and inmmunophenotypic parameters between USCD and conventional celiac disease (CCD) patients. Methods: Prospective single-center study in children and adult patients undergoing duodenal biopsies on a gluten-containing diet. Biopsies for histology and flow cytometry were taken separately from D1 and distal duodenum. Biopsies in seronegative patients with celiac lymphogram were repeated after 2 years on a gluten-free diet. Results: Among 505 included patients, 127 were diagnosed with CD, of whom 7 (5.5%) showed USCD. HLADQ2 was significantly less common in USCD compared to CCD (71% vs. 95%, p 0.003). Likewise, USCD patients showed more frequent non-significant seronegativity (28% vs. 8%, p 0.07) and significantly lower titrations (7–15IU/ml) of tissue transglutaminase antibodies (tTG-IgA) (60% vs. 13%, p<0.001). Biopsies from D1 revealed significant less NK cells down-expression in USCD patients (1.4 vs. 5, p 0.04). Conclusions: Up to 5.5% of CD patients showed USCD. A lower frequency of HLADQ2, along with less serum tTG-IgA titration and duodenal NK cell suppression, were differential features of USCD.(AU)

Antecedentes: La enfermedad celiaca ultracorta (ECUC) es un nuevo fenotipo de la enfermedad celiaca, que afecta exclusivamente al bulbo duodenal (D1), cuyas características genéticas e inmunológicas no han sido descritas. Objetivos: Comparar las características genéticas, clínicas, serológicas, histológicas e inmunológicas entre ECUC y enfermedad celiaca convencional (ECC). Métodos: Estudio prospectivo, unicéntrico, en el que se realizaron biopsias duodenales a pacientes adultos y pediátricos que seguían una dieta con gluten. Se realizó análisis histológico y por citometría de flujo por separado de duodeno distal y D1. En pacientes seronegativos con histología o linfograma concordante con EC, se repitió la biopsia tras 2 años con dieta sin gluten. Resultados: Se incluyeron 505 pacientes, siendo diagnosticados 127 de enfermedad celiaca, de los cuales 7 (5,5%) tenían ECUC. Los pacientes con ECUC expresaron el haplotipo DQ2 con menor frecuencia que en la ECC (71% vs. 95%, p 0,003) y presentaron mayor seronegatividad (28% vs. 8%, p 0,07) y, de manera significativa, titulaciones bajas de anticuerpos antitransglutaminasa (7-15IU/ml) (60% vs. 13%, p < 0,001). Comparado con la ECC, la citometría de flujo en las biopsias bulbares reveló una reducción atenuada significativa de células NK (1,4 vs. 5, p 0,04) en pacientes con ECUC. Conclusiones: Un 5,5% de los pacientes celiacos presentaron ECUC. Comparada con la ECC, las características diferenciales de la ECUC son menor expresión de HLADQ2, títulos más bajos de anticuerpos antitranglutaminasa y menor supresión de células NK a nivel bulbar.(AU)

Ultra-short celiac disease exhibits differential genetic and immunophenotypic features compared to conventional celiac disease.

BACKGROUND: Ultra-short coeliac disease (USCD) is a novel celiac disease (CD) subtype limited to the duodenal bulb (D1). HLA haplotypes and flow cytometry have not been assessed yet. AIMS: To compare genetic, clinical, serologic, histopathologic and inmmunophenotypic parameters between USCD and conventional celiac disease (CCD) patients. METHODS: Prospective single-center study in children and adult patients undergoing duodenal biopsies on a gluten-containing diet. Biopsies for histology and flow cytometry were taken separately from D1 and distal duodenum. Biopsies in seronegative patients with celiac lymphogram were repeated after 2 years on a gluten-free diet. RESULTS: Among 505 included patients, 127 were diagnosed with CD, of whom 7 (5.5%) showed USCD. HLADQ2 was significantly less common in USCD compared to CCD (71% vs. 95%, p 0.003). Likewise, USCD patients showed more frequent non-significant seronegativity (28% vs. 8%, p 0.07) and significantly lower titrations (7-15IU/ml) of tissue transglutaminase antibodies (tTG-IgA) (60% vs. 13%, p<0.001). Biopsies from D1 revealed significant less NK cells down-expression in USCD patients (1.4 vs. 5, p 0.04). CONCLUSIONS: Up to 5.5% of CD patients showed USCD. A lower frequency of HLADQ2, along with less serum tTG-IgA titration and duodenal NK cell suppression, were differential features of USCD.

Endoscopic ultrasound-guided fine-needle biopsy in patients with unexplained diffuse gastrointestinal wall thickening.

Background and study aims Endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) is recommended after non-diagnostic biopsy in gastrointestinal wall thickening, although the performance of currently available FNB needles in this setting is unknown. We aimed to assess the diagnostic accuracy and safety of EUS-FNB and to evaluate the "T" wall staging in malignant pathology. Patients and methods This was a single center retrospective study that included all consecutive patients undergoing EUS-FNB for diffuse gastrointestinal wall thickening with at least one previous negative conventional endoscopic biopsy between January 2016 and November 2019. EUS-FNB was performed using linear-array echoendoscopes with slow-pull/fanning technique. Tissue acquisition was done with 19- or 22-gauge biopsy needles. Samples were included in formalin without rapid on-site evaluation and submitted for histopathological processing. The final diagnosis was based on conclusive histology or absence of evidence of disease progression after follow-up at least 6 months. Results Twenty-nine patients (21 men), with a median age of 68 (IQR: 56-77), were included. EUS-FNB was technically feasible and the sample quality was adequate for full histological assessment in all patients (100 %). Sensitivity, specificity, positive and negative predictive values, and overall accuracy for diagnosis of malignancy were 95.5 %, 100 %, 100 %, 83.3 %, and 96.3 %, respectively. In patients with malignant disease, the samples obtained allowed detection of signs of deep layer infiltration ("histological staging") in 17 of 21 cases (81 %). No adverse events were noted. Conclusions The EUS-FNB technique demonstrated excellent diagnostic performance and safety in the study of unexplained diffuse gastrointestinal wall thickening. Histological staging was obtained in a high percentage of samples.

European Registry on Helicobacter pylori Management: Effectiveness of First and Second-Line Treatment in Spain.

The management of Helicobacter pylori infection has to rely on previous local effectiveness due to the geographical variability of antibiotic resistance. The aim of this study was to evaluate the effectiveness of first and second-line H. pylori treatment in Spain, where the empirical prescription is recommended. A multicentre prospective non-interventional registry of the clinical practice of European gastroenterologists concerning H. pylori infection (Hp-EuReg) was developed, including patients from 2013 until June 2019. Effectiveness was evaluated descriptively and through a multivariate analysis concerning age, gender, presence of ulcer, proton-pump inhibitor (PPI) dose, therapy duration and compliance. Overall, 53 Spanish hospitals were included, and 10,267 patients received a first-line therapy. The best results were obtained with the 10-day bismuth single-capsule therapy (95% cure rate by intention-to-treat) and with both the 14-day bismuth-clarithromycin quadruple (PPI-bismuth-clarithromycin-amoxicillin, 91%) and the 14-day non-bismuth quadruple concomitant (PPI-clarithromycin-amoxicillin-metronidazole, 92%) therapies. Second-line therapies were prescribed to 2448 patients, with most-effective therapies being the triple quinolone (PPI-amoxicillin-levofloxacin/moxifloxacin) and the bismuth-levofloxacin quadruple schemes (PPI-bismuth-levofloxacin-amoxicillin) prescribed for 14 days (92%, 89% and 90% effectiveness, respectively), and the bismuth single-capsule (10 days, 88.5%). Compliance, longer duration and higher acid inhibition were associated with higher effectiveness. "Optimized" H. pylori therapies achieve over 90% success in Spain.

Bismuth quadruple regimen with tetracycline or doxycycline versus three-in-one single capsule as third-line rescue therapy for Helicobacter pylori infection: Spanish data of the European Helicobacter pylori Registry (Hp-EuReg).

BACKGROUND: Different bismuth quadruple therapies containing proton-pump inhibitors, bismuth salts, metronidazole, and a tetracycline have been recommended as third-line Helicobacter pylori eradication treatment after failure with clarithromycin and levofloxacin. AIM: To evaluate the efficacy and safety of third-line treatments with bismuth, metronidazole, and either tetracycline or doxycycline. METHODS: Sub-study with Spanish data of the "European Registry on H pylori Management" (Hp-EuReg), international multicenter prospective non-interventional Registry of the routine clinical practice of gastroenterologists. After previous failure with clarithromycin- and levofloxacin-containing therapies, patients receiving a third-line regimen with 10/14-day bismuth salts, metronidazole, and either tetracycline (BQT-Tet) or doxycycline (BQT-Dox), or single capsule (BQT-three-in-one) were included. Data were registered at AEG-REDCap database. Univariate and multivariate analyses were performed. RESULTS: Four-hundred and fifty-four patients have been treated so far: 85 with BQT-Tet, 94 with BQT-Dox, and 275 with BQT-three-in-one. Average age was 53 years, 68% were women. Overall modified intention-to-treat and per-protocol eradication rates were 81% (BQT-Dox: 65%, BQT-Tet: 76%, BQT-three-in-one: 88%) and 82% (BQT-Dox: 66%, BQT-Tet: 77%, BQT-three-in-one: 88%), respectively. By logistic regression, higher eradication rates were associated with compliance (OR = 2.96; 95% CI = 1.01-8.84) and no prior metronidazole use (OR = 1.96; 95% CI = 1.15-3.33); BQT-three-in-one was superior to BQT-Dox (OR = 4.46; 95% CI = 2.51-8.27), and BQT-Tet was marginally superior to BQT-Dox (OR = 1.67; 95% CI = 0.85-3.29). CONCLUSION: Third-line H pylori eradication with bismuth quadruple treatment (after failure with clarithromycin and levofloxacin) offers acceptable efficacy and safety. Highest efficacy was found in compliant patients and those taking 10-day BQT-three-in-one or 14-day BQT-Tet. Doxycycline seems to be less effective and therefore should not be recommended.

Rising incidence and prevalence of adult eosinophilic esophagitis in midwestern Spain (2007-2016).

OBJECTIVES: Epidemiologic studies on eosinophilic esophagitis (EoE) are scarce and patient responders to proton pump inhibitor (PPI) therapy have usually been excluded. We aimed to evaluate population-based incidence rates, prevalence and trends in adult EoE over the past decade, including responders to PPI therapy. METHODS: We conducted an analysis of a prospectively established case registry in the health area of Cáceres, located in midwestern Spain. From the first EoE case diagnosed in 2007, endoscopy and pathology reports up to December 2016 were manually reviewed. A baseline diagnosis of EoE was confirmed upon symptoms of esophageal dysfunction (dysphagia/food impaction) and esophageal eosinophilia ≥ 15 eos/HPF. All patients were re-evaluated on PPI therapy during follow-up. RESULTS: A total of 137 patients were diagnosed with EoE during the study period, of whom 63 (46%) achieved clinicohistologic remission on PPI therapy. The prevalence of autoimmune disorders was low. Mean incidence rate was 8.09 new cases/100,000 inhabitants/year, increasing to 9.95 during the last lustrum and peaking in 2016 with 13.7. This trend coincided with late declining of esophageal biopsies rate. Overall prevalence in 2016 was 81.73 patients/100,000 inhabitants, with the highest prevalence in males between age 35 and 44 years (273 cases/100,000). No seasonal variation was observed in the diagnosis of EoE (53% during pollen season vs. 47%, p = 0.4). CONCLUSIONS: In midwestern Spain, incidence (13.7 cases/100,000 inhabitants/year) and prevalence (81.73 patients/100,000 inhabitants) in 2016 have grown remarkably in just one decade, coming closer to those figures recently reported for Crohn's disease in Spain.