Comparing a New Flow Immune-Chromatography Fast Assay with a Random Access Semi-Automatic Chemiluminescent Immunoassay to Measure Fecal Calprotectin.

OBJECTIVE: The biomarker fecal calprotectin is an efficacious tool for evaluating the level of disease activity in Crohn's and Ulcerative colitis, as well as for discriminating between inflammatory bowel disease and irritable bowel syndrome. The aim of this investigation was to appraise the analytical proficiency of a novel flow immune-chromatography assay through comparison with the established gold standard system in our laboratory. METHODS: A cohort comprising of 125 stool samples, submitted for the purpose of routine calprotectin levels analysis, underwent assessment using two distinct approaches: the Liaison XL system and the SmarTest assay, while adhering to identical cut-off criteria. The present study assessed the performance of the SmarTest assay by calculating its sensitivity, specificity, and accuracy measures. RESULTS: The sensitivity, specificity, and accuracy of the SmarTest assay were found to be 97.75%, 80.56%, and 92.80%, respectively, upon comparison with the gold standard. Moreover, the Pearson correlation coefficient analysis ascertained that the linear correlation pertaining to the calprotectin levels, as identified between both assays, was statistically significant (R=0.8158, P values <0.0001). CONCLUSIONS: Upon comparison with the Liaison XL system, it was found that the SmarTest assay demonstrated satisfactory results in both qualitative and quantitative aspects. This novel and expedient diagnostic assay is commended for evaluating fecal calprotectin in situations where access to laboratory services may be insufficient or nonexistent, rendering it an ideal option for point-of-care or at-home testing purposes.

Serologic Response and Safety after a Third Dose of the COVID-19 BNT162b2 Vaccine in Patients with Inflammatory Bowel Diseases.

Vaccines are pivotal for control of the coronavirus disease (COVID-19) pandemic. Patients with inflammatory bowel diseases (IBDs) treated with antitumor necrosis factor (TNF)-α have lower serologic response after two COVID-19 vaccine doses. Data regarding a third vaccine dose are scarce. An Israeli multicenter prospective observational study recruited 319 subjects: 220 with IBD (79 treated with anti-TNFα) and 99 healthy control (HC) participants. All patients received two mRNA-BNT162b2 vaccines (Pfizer/BioNTech), 80% of whom received a third vaccine dose. Evaluation included disease activity, anti-spike (S) and nucleocapsid (N) antibody levels, anti-TNFα drug levels, and adverse events (AEs). All participants showed significant serologic response one month after receiving a third dose. However, three months later, the anti-S levels decreased significantly in patients treated with anti-TNFα compared with the non-anti-TNFα and HC groups. A correlation between serologic response to the third vaccine dose and anti-TNF drug levels was not found. No significant AE or IBD exacerbation was observed. Importantly, lower serologic response after the third vaccine dose predicted infection. A third dose of BNT162b2 is effective and safe in patients with IBD. Lower serologic response predicted infection, even in seropositive subjects. Lower serologic responses and their rapid decline suggest a fourth vaccine dose in this patient population.

Gluten Immunogenic Peptides Are Not Correlated With Reported Adherence to Gluten-Free Diet in Children With Celiac Disease.

OBJECTIVE: There is no gold standard to assess adherence to gluten-free diet (GFD) among patients with celiac disease (CeD). Gluten immunogenic peptides (GIPs) in urine and stool were suggested as novel markers for evaluating adherence to GFD. Our aim was to assess the presence of GIP in pediatric patients with CeD, and to compare the results with alternative methods for evaluating GFD adherence. METHODS: Pediatric patients diagnosed with CeD, who were on GFD for at least 1 year, were enrolled and followed prospectively between November 2018 and January 2021. Study visits included clinical assessment, a dietitian interview, Biagi score, food questionnaires, anthropometric and laboratory measurements, and urine and stool samples obtained for laboratory GIP analysis. RESULTS: The study included 74 patients (63.5% females), with median (interquartile range, IQR) age of 9.9 (7.8-11.7) years, and median (IQR) duration on GFD of 2.5 (2-5.5) years. Good GFD adherence, assessed by Biagi score, was reported in 93.1% of cases. GIP was evaluated during 134 visits, with GIP detected in 27 of 134 (20.1%) of the visits (16.3% of stool samples and 5.3% of urine samples). Positive GIP results were significantly more common in males compared to females (30.6% vs 14.1%, respectively, P < 0.05). Detection of positive GIP was not associated with dietary assessment of GFD adherence, celiac serology results, or reported symptoms. CONCLUSIONS: Stool and urine GIP can be detected in children with CeD, even when dietary assessment indicate good adherence to GFD. The role of GIP testing in clinical practice should be further explored.

Repeated out-of-Africa expansions of Helicobacter pylori driven by replacement of deleterious mutations.

Helicobacter pylori lives in the human stomach and has a population structure resembling that of its host. However, H. pylori from Europe and the Middle East trace substantially more ancestry from modern African populations than the humans that carry them. Here, we use a collection of Afro-Eurasian H. pylori genomes to show that this African ancestry is due to at least three distinct admixture events. H. pylori from East Asia, which have undergone little admixture, have accumulated many more non-synonymous mutations than African strains. European and Middle Eastern bacteria have elevated African ancestry at the sites of these mutations, implying selection to remove them during admixture. Simulations show that population fitness can be restored after bottlenecks by migration and subsequent admixture of small numbers of bacteria from non-bottlenecked populations. We conclude that recent spread of African DNA has been driven by deleterious mutations accumulated during the original out-of-Africa bottleneck.

A Novel Fecal Elastase Assay for the Detection of Pancreatic Exocrine Insufficiency.

BACKGROUND: Fecal pancreatic elastase 1 (FPE1) is an established screening test for pancreatic exocrine insufficiency (PEI), a condition that is underdiagnosed and if not treated may cause significant morbidity. The aim of this study was to compare a new FPE1 machine based CLIA kit to an ELISA assay which is considered the de facto gold standard in our laboratory for FPE1 measurement. METHODS: Levels of FPE1 from the 227 stool samples were analyzed by the ScheBo ELISA kit and the CLIA Liaison XL system simultaneously with the same cutoff values for both assays. Performance of the Liaison XL system was assessed by calculating sensitivity, specificity, and accuracy. RESULTS: The comparison between the Liaison XL system performance and the ScheBo ELISA kit as reference revealed a sensitivity, specificity, and accuracy of 86.8%, 94.3%, and 92.1%, respectively, using a cutoff of 100 µg FPE1/g stool. When the cutoff is 200 µg FPE1/g stool the sensitivity, specificity, and accuracy were 86.6%, 97.1%, and 90.7%, respectively. Furthermore, linear correlation of FPE1 levels between the two assays were found to be significant by Pearson's correlation coefficient test (R = 0.85, p-values < 0.0001). CONCLUSIONS: The Liaison XL system showed good laboratory performance with our pre-determined cutoff values when compared to our previous assay. An important advantage of this system is its semi-automated mechanism that enables large scale analysis of FPE1. In addition to that, the Liaison XL system is ideal for both qualitative and quantitative analysis of FPE1 allowing for its application to the clinical setting.

Lasting Effects of Helicobacter pylori Infection on the Microbial Communities of Patients with and without Small Intestinal Bacterial Overgrowth.

Gastrointestinal (GI) microbial populations are important in maintaining normal functioning of the GI by preventing disorders. Dysbiotic microbiota may increase the likelihood of small intestinal bacterial overgrowth (SIBO), a syndrome associated with significant morbidity. We aimed to inves- tigate the microbiota populations of patients with SIBO. Patients with symptoms of SIBO were consecutively enrolled; they underwent a SIBO hydrogen breath test and stool was collected for microbiome analysis by sequencing of the 16S rRNA. Of the 55 patients recruited, 42 (76.4%) were positive for SIBO. When visualizing the bacterial ß-di- versity, a sub-cluster of patients was identified. Further examination of these patients' records re- vealed previous treatment for Helicobacter pylori (HP). Microbiome analysis of these patients demonstrated a significant decrease in ß-diversity (p-value<0.001) compared to patients without previous HP therapy. Furthermore, ß-diversity was significantly different in this subgroup, and sev- eral bacterial taxa were differentially expressed, including one from the genus Methanobrevibacter, which was reduced in patients that previously underwent HP treatment. Our findings suggest that while symptoms associated with SIBO may cause dysbiosis, there was no differentiation in fecal microbiome composition based on SIBO diagnosis. Furthermore, our results support previous observations regarding antibiotic-altered microbiota with effects extending two and three years post-treatment.

Risk of consecutive immunogenic failure in switchers of anti-tumor necrosis factor alpha among patients with inflammatory bowel diseases.

BACKGROUND: Evidence regarding the risk of immunogenicity in patients with inflammatory bowel disease (IBD) who switched anti-tumor necrosis factor alpha (anti-TNFα) therapies to a subsequent anti-TNFα (either infliximab or adalimumab) is conflicting. We aimed to assess the risk of consecutive immunogenicity to anti-TNFα in a large cohort of patients. METHODS: This was a multicenter retrospective study. Medical records of adult and pediatric IBD switchers who had pharmacokinetic data for both agents between 2014 and 2020 were retrieved. Data including age, sex, disease type, duration of therapies, and concomitant use of immunomodulators (IMMs) were recorded. RESULTS: Overall, 164 patients were included [52% female; 88% Crohn's disease; mean age = 24.4 ± 14.6 years; 108 (66%) switched from infliximab to adalimumab and 56 (34%) vice versa]; 120 (73.1%) patients switched due to an immunogenic failure. Among patients switching therapy from infliximab to adalimumab due to an immunogenic failure immunogenicity to infliximab was significantly associated with consecutive immunogenicity to adalimumab (p = 0.026). Forthy four out of 120 patients (36.6%) with an immunogenic failure to the first anti-TNFα started an IMM with the second anti-TNFα. This combination with IMM was not associated with reduction of consecutive immunogenicity (p = 0.31), but it was associated with longer drug retention (p = 0.007). Multivariate analysis demonstrated that older age at second anti-TNFα, adjusted to the chronology of therapy and sex, was associated with increased immunogenicity to the second anti-TNFα. CONCLUSION: Patients with IBD who switch from infliximab to adalimumab following an immunogenic failure are at increased risk for consecutive immunogenicity to adalimumab. IMM use after a switch prolongs drug retention.

Lower Serologic Response to COVID-19 mRNA Vaccine in Patients With Inflammatory Bowel Diseases Treated With Anti-TNFα.

BACKGROUND & AIM: Patients with inflammatory bowel diseases (IBD), specifically those treated with anti-tumor necrosis factor (TNF)α biologics, are at high risk for vaccine-preventable infections. Their ability to mount adequate vaccine responses is unclear. The aim of the study was to assess serologic responses to messenger RNA-Coronavirus Disease 2019 vaccine, and safety profile, in patients with IBD stratified according to therapy, compared with healthy controls (HCs). METHODS: Prospective, controlled, multicenter Israeli study. Subjects enrolled received 2 BNT162b2 (Pfizer/BioNTech) doses. Anti-spike antibody levels and functional activity, anti-TNFα levels and adverse events (AEs) were detected longitudinally. RESULTS: Overall, 258 subjects: 185 IBD (67 treated with anti-TNFα, 118 non-anti-TNFα), and 73 HCs. After the first vaccine dose, all HCs were seropositive, whereas ∼7% of patients with IBD, regardless of treatment, remained seronegative. After the second dose, all subjects were seropositive, however anti-spike levels were significantly lower in anti-TNFα treated compared with non-anti-TNFα treated patients, and HCs (both P < .001). Neutralizing and inhibitory functions were both lower in anti-TNFα treated compared with non-anti-TNFα treated patients, and HCs (P < .03; P < .0001, respectively). Anti-TNFα drug levels and vaccine responses did not affect anti-spike levels. Infection rate (∼2%) and AEs were comparable in all groups. IBD activity was unaffected by BNT162b2. CONCLUSIONS: In this prospective study in patients with IBD stratified according to treatment, all patients mounted serologic response to 2 doses of BNT162b2; however, its magnitude was significantly lower in patients treated with anti-TNFα, regardless of administration timing and drug levels. Vaccine was safe. As vaccine serologic response longevity in this group may be limited, vaccine booster dose should be considered.

Effect of the transcutaneous electrical stimulation system on esophageal-acid exposure in patients non-responsive to once-daily proton-pump inhibitor: proof-of-concept study.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a common disorder. Overall, ≤35% of GERD patients fail the standard dose of proton-pump-inhibitor (PPI) treatment. Due to the high prevalence and low satisfaction rate with treatment failure, there is an unmet need for new treatment. Our aim was to evaluate whether the use of the transcutaneous electrical stimulation system (TESS) can reduce esophageal-acid exposure in GERD patients unresponsive to standard-dose PPI. METHODS: We enrolled 10 patients suffering from heartburn and regurgitation with an abnormal esophageal-acid exposure (off PPIs) who failed standard-dose PPI. After the placement of a wireless esophageal pH capsule, all patients were treated with TESS. The primary end point was the reduction in the baseline (pretreatment) 24-hour percent total time pH <4 and/or DeMeester score by 50%. RESULTS: Seven GERD patients (five females and two males, aged 49.3 ± 10.1 years) completed the study. At baseline, the mean percent total time pH <4 was 12.0 ± 4.9. Following TESS, the mean percent total time pH <4 dropped to 5.5 ± 3.4, 4.5 ± 2.6, 3.7 ± 2.9, and 4.4 ± 2.5 on Days 1, 2, 3, and 4, respectively. At baseline, the mean DeMeester score was 39.0 ± 18.5. After TESS, the mean DeMeester score dropped to 15.8 ± 9.2, 13.2 ± 6.8, 11.2 ± 9.4, and 12.0 ± 6.8 on Days 1, 2, 3, and 4, respectively. CONCLUSION: TESS is a safe and potentially effective modality in reducing esophageal-acid exposure in GERD patients unresponsive to standard-dose PPI. A larger and prospective controlled study is needed to verify these preliminary results.

Clinical Accuracy of a New Rapid Assay for Fecal Calprotectin Measurement.

BACKGROUND: Fecal calprotectin is an excellent biomarker for distinguishing inflammatory bowel disease from irritable bowel syndrome and for evaluation of disease activity in Crohn's disease and ulcerative colitis. The aim of this work was to evaluate the analytical performance of a new flow immune chromatography assay by comparing it to our standardized laboratory gold standard system. METHODS: A total of 100 stool samples sent for routine calprotectin level measurements were analyzed by the Liaison XL system and the QuantOn Cal assay simultaneously using the same cutoff values for both assays. Performance of the QuantOn Cal assay was assessed by calculating sensitivity, specificity, and accuracy. RESULTS: Compared with the gold standard, the sensitivity, specificity, and accuracy of the QuantOn Cal assay were 98.7%, 76.2%, and 94.0%, respectively. Furthermore, linear correlation of calprotectin levels between the two assays were found to be significant by Pearson's correlation coefficient test (r = 0.82, p-values < 0.0001). CONCLUSIONS: The QuantOn Cal assay demonstrated good performance, both qualitative and quantitative when compared to the Liaison XL system. This novel and rapid assay is well suited for measuring fecal calprotectin as a point of care or home-based assay when laboratory services are limited or not available.

Comparative Effect of Proton-Pump Inhibitors on the Success of Triple and Quadruple Therapy for Helicobacter pylori Infection.

INTRODUCTION: Suppression of gastric acid secretion with proton-pump inhibitors (PPI) is an integral part of the treatment of Helicobacter pylori infection. Esomeprazole has been shown to be superior to other PPIs when used in the context of triple therapy; however, comparative data for PPI efficacy in quadruple therapy are lacking. Current guidelines recommend H. pylori eradication with quadruple therapy in areas with high clarithromycin resistance. OBJECTIVE: To determine whether esomeprazole is more effective than other PPIs in the context of quadruple therapy for H. pylori eradication. METHODS: We retrospectively identified 25- to 60-year-old subjects with a positive 13C-urea breath test and no prior laboratory or endoscopic test for H. pylori infection. Pharmacy dispensation data were retrieved. RESULTS: A total of 7,896 subjects including 2,856 (36.2%) males, aged 40.4 ± 10.6 years, were identified. Of those, 78.1% received omeprazole, 20.1% received lansoprazole, 1.5% received esomeprazole, and 0.34% received pantoprazole together with antibiotics for H. pylori eradication. Esomeprazole was associated with a greater proportion of successful eradication (85.0 vs. 77.5%, esomeprazole vs. omeprazole, OR 1.64; 95% CI 0.99-2.72; p = 0.05). A nonsignificant trend favored esomeprazole over omeprazole among subjects receiving quadruple therapy (90.0 vs. 82.0%, respectively, OR 1.98; 95% CI 0.68-5.72; p = 0.16). Independent predictors of treatment success included older age and quadruple therapy. CONCLUSION: Esomeprazole is more beneficial than other PPIs for H. pylori eradication. Studies with larger subgroups are necessary to confirm our findings among subjects receiving quadruple therapy.

Use of a Novel Probiotic Formulation to Alleviate Lactose Intolerance Symptoms-a Pilot Study.

Lactose intolerance is a common condition caused by lactase deficiency and may result in symptoms of lactose malabsorption (bloating, flatulence, abdominal discomfort, and change in bowel habits). As current data is limited, the aim of our study was to assess the efficacy of probiotics with a ß-galactosidase activity on symptoms of lactose malabsorption and on the lactose hydrogen breath test (LHBT). The study group comprised eight symptomatic female patients with a positive LHBT. Patients were treated for 6 months with a probiotic formula with ß-galactosidase activity (Bio-25, Ambrosia-SupHerb, Israel). All patients completed a demographic questionnaire as well as a diary for the assessment of symptom severity and frequency at entry, every 8 weeks, and at the end of the treatment period. Measurements of hydrogen (H2) levels (parts per million, ppm) at each of these time points were also performed. End points were a decrease of 50% in symptom severity or frequency, and the normalization (decrease below cutoff point of 20 ppm) of the breath test. Mean age and mean body mass index (BMI) were 36.4 ± 18.6 years and 23.2 kg/m2, respectively. Compared to baseline scores, the frequency of most symptoms, and the severity of bloating and flatulence, improved after treatment. Normalization of LHBT was obtained in only two patients (25%). In this pilot study, Bio-25, a unique formulation of probiotics with ß-galactosidase activity, demonstrated symptom resolution in most patients with lactose malabsorption. A larger randomized trial is warranted to confirm these preliminary findings.

Novel high resolution melt curve assay for the analysis of predominance of Helicobacter pylori clarithromycin resistance.

Clarithromycin resistance is the most common cause of Helicobacter pylori treatment failure and it is attributed to three point mutations, A2142G, A2142C and A2143G, within the 23S rRNA gene. We aimed to determine the prevalence of H. pylori clarithromycin resistance using a novel high resolution melt assay. A total of 151 stool samples were collected from treatment-naïve patients with general gastric discomfort who also performed 13CO2 breath tests. Stool antigen tests were also performed on 126 of the 151 stool samples collected. Bacterial DNA was extracted from the stool and analyzed by comparing it with four reference plasmids incorporating the three mutations and the wild type (WT) sequences. The melt assay detected 106 H. pylori positive samples, of which 54 had a WT sequence, and 52 had a point mutation associated with clarithromycin resistance, including A2142G in 10, A2142C in 13, A2143G in 18 and heterozygosity (multiple peaks) in 11. Compared with the gold standards (13CO2 breath and stool antigen tests), the melt assay had a sensitivity of 100% and 99% and a specificity of 82% and 78%, respectively. Therefore, our stool-based molecular assay is able to identify H. pylori infection and clarithromycin resistance. It could be used for screening prior to administration of clarithromycin eradication therapy.

Rising prevalence of celiac disease is not universal and repeated testing is needed for population screening.

Background: Recent studies suggest that the prevalence of celiac disease is rising. We previously established the prevalence of celiac disease in healthy blood donors in 2002. Objective: The purpose of this study was to examine whether the prevalence of celiac disease and celiac disease autoimmunity has changed over time by performing a similar prospective study. Methods: Healthy blood donors (n = 1908) were tested for tissue transglutaminase antibodies and for anti-endomysial antibodies when positive. Further evaluation followed accepted criteria for diagnosis. Results: Overall, 32 donors had abnormal tissue transglutaminase antibodies (1.68%). Eight donors had tissue transglutaminase antibodies >3 × upper limit of normal (0.42%), two of them with tissue transglutaminase antibodies >10 × upper limit of normal, while 24 donors had tissue transglutaminase antibodies <3 × upper limit of normal (1.26%). Most of the donors with positive tissue transglutaminase antibodies <3 × upper limit of normal had negative tissue transglutaminase antibodies levels on repeated testing (18/19). Celiac disease was diagnosed in four donors with positive tissue transglutaminase antibodies, establishing a prevalence of 1.68% (95% confidence interval 1.15-2.3) for celiac disease autoimmunity and 0.21% for celiac disease (95% confidence interval 0.07-0.5%). Conclusion: The prevalence of celiac disease in blood donors in Israel did not rise in the last 15 years, suggesting that the increased prevalence of diagnosed celiac disease is mainly due to increased awareness. As most of the donors with elevated tissue transglutaminase antibodies <3 × upper limit of normal were endomysial antibody negative and had a negative tissue transglutaminase antibodies result upon re-testing, repeated tissue transglutaminase antibodies testing is required when screening asymptomatic populations for celiac disease.

Optimization of 13 C-urea breath test threshold levels for the detection of Helicobacter pylori infection in a national referral laboratory.

BACKGROUND: Threshold values for 13 C-urea breath test (13C-UBT) positivity may be affected by various sociodemographic, host, bacterial, and laboratory factors. Manufacturer recommended cutoffs for 13C-UBT assays may not be applicable in all settings. Optimizing 13C-UBT cutoffs may have profound public health ramifications. We aimed to determine the optimal threshold for 13C-UBT positivity in our population. METHODS: Consecutive test samples collected at our central laboratory from patients undergoing a first-time 13C-UBT between 1 January 2010 and 31 December 2015 were included. The difference between values at 30 minutes and at baseline (T30-T0) was expressed as delta over baseline (DOB). Cluster analysis was performed on the 13C-UBT test results to determine the optimal cutoff point with minimal interclass variance. RESULTS: Two lakhs thirty four thousand eight hundred thirty one patients (87 291 (37.2%) male, age 39.9 ± 19.9) underwent a first-time 13C-UBT, including 124 701 (53.1%) negative and 110 130 (46.9%) positive tests, using the manufacturer-recommended cutoff of 3.5 DOB. Cluster analysis determined an optimized cutoff of 2.74 DOB, representing an additional 2180 (0.93%) positive subjects who had been previously categorized as negative according to the manufacturer-specified cutoff of 3.5 DOB. Mean positive and negative DOB values were 19.54 ± 14.95 and 0.66 ± 0.51, respectively. The cutoffs for male and female subjects were 2.23 and 3.05 DOB, respectively. Threshold values for <45-year-olds, 45-60-year-olds and >60-year-olds were 2.67, 2.55, and 2.93 DOB, respectively. Of the 2180 (0.93%) patients with DOB 2.73-3.49, 289 (13.3%) performed a subsequent 13C-UBT and 140 (48.4%) remained positive when tested at 20.3 ± 14.4 months. CONCLUSIONS: Major referral laboratories should optimize threshold values for 13C-UBT positivity for their geographical location. Different cutoff values should be applied for male and female subjects.

Correlation between Quantitative 13C-Urea Breath Test and Helicobacter pylori Treatment Success in a Population-Based Cohort.

BACKGROUND: There are continual efforts to identify factors which influence the success of first-line therapy for Helicobacter pylori (H. pylori) infection. The 13C-urea breath test result (C13-UBT) utilizes H. pylori urease activity and is a highly accurate diagnostic assay. We aimed to determine whether the magnitude of C13-UBT result is related to treatment success. METHODS: Adult patients who underwent a first-time 13C-urea breath test between January 2010 and January 2016 were included. In order to isolate a naïve test-and-treat population who were unlikely to have undergone an initial endoscopy-based H. pylori test, we excluded patients > 45 years and those with a previous C13-UBT. Data were extracted from the Clalit Health Services laboratory database. RESULTS: A total of 94,590 subjects (36.1% male, age 28.5 ± 6.0 years) who underwent a first-time C13-UBT during the study period were included. C13-UBT was positive in 48,509 (51.3%) subjects. A confirmatory posttreatment C13-UBT was performed in 18,375 (37.8%), and eradication was successful in 12,018 (65.4%). The mean C13-UBT recording was 20.6 ± 16.2 DOB in subjects with successful eradication and 19.5 ± 13.1 DOB in subjects with treatment failure (OR, 1.01; 95% CI 1.00-1.01, p < 0.01). Among patients in the upper quintile of C13-UBT measurement, eradication was achieved in 67.6%, compared to 62.6% in the lower quintile (OR, 1.22; 95% CI 1.11-1.35, p < 0.01). Subjects in the top 1 percentile (C13-UBT ≥ 70 DOB) achieved eradication in 75.0%, compared to 65.3% among subjects with C13-UBT < 70 DOB (OR, 1.59; 95% CI 1.05-2.41, p < 0.01). CONCLUSIONS: The superiority in H. pylori eradication observed in subjects with a higher C13-UBT DOB is small but significant. Further studies should examine the physiological and microbiological basis for this finding.

Temporal Trends in Helicobacter pylori Eradication Success in a Test-and-Treat Population.

BACKGROUND/AIMS: Although the efficacy of first-line treatment for Helicobacter pylori infection should aim to be > 90%, it is unclear whether this target has been achieved in Israel. We aimed to determine the success rate of treatment for H. pylori and to describe temporal changes in our region. Methods: Adult patients who underwent a first-time -C13-urea breath test (C13-UBT) at Clalit Health Services between January 1, 2010 and December 31, 2015 were included. In order to isolate a naïve "test-and-treat" population who were unlikely to have undergone an initial endoscopy-based H. pylori test, we excluded patients ≥45 years and those with any previous C13-UBT. RESULTS: A total of 94,590 subjects (36.1% male, age 28.5 ± 6.0) who underwent at least one C13-UBT during the study period were included. C13-UBT was positive in 48,509 (51.3%) subjects. A confirmatory post-treatment C13-UBT was performed in 37.8, 44.1, 46.6, and 45.9% following 1st, 2nd, 3rd, and 4th-line treatment respectively. Eradication was successful in 65.4% following first-line treatment, and eradication success improved during the study period (59.2, 63.3, 65.7, 66.0, 69.0, and 73.1% in 2010, 2011, 2012, 2013, 2014, and 2015 respectively; OR 1.11; 95% CI 1.09-1.13; p < 0.0001). Eradication was successful in 44.7% following second-line treatment, although eradication success did not significantly improve during the study period (OR 1.05; 95% CI 0.99-1.10; p = 0.09). CONCLUSIONS: Despite the increasing success of first-line treatment for H. pylori infection over the study period, eradication rates remain suboptimal. Initiatives to implement the Toronto and Maastricht Consensus Reports should be advanced.

Small Intestinal Bacterial Overgrowth May Increase the Likelihood of Lactose and Sorbitol but not Fructose Intolerance False Positive Diagnosis.

BACKGROUND: Small intestinal bacterial overgrowth (SIBO) is defined as a bacterial count of more than 105 colony-forming units per milliliter in duodenal aspirate. It shares many symptoms with carbohydrate intolerance, which makes the clinical distinction of the disorders difficult. The aim of the study was to examine the relationship between a positive carbohydrate breath test and the presence of SIBO suggested by a positive lactulose hydrogen breath test. METHODS: The electronic database of the gastroenterology laboratory of a tertiary medical center was searched for all patients clinically tested for SIBO in 2012-2013 for whom previous results for lactose, fructose, and/or sorbitol breath test were available. The correlation between positive findings for carbohydrate intolerance and for SIBO was statistically analyzed. RESULTS: The study group included 349 patients, 231 female and 118 male, of mean age 53±19 years. All had symptoms of abdominal bloating and gas. There was a statistically significant difference in rates of a positive breath test for lactose and sorbitol at ≤90 minutes between patients who were positive and negative for SIBO [χ2(1)=12.8, p<0.01 and χ2(1)=9.5, p<0.01 respectively]. Findings for fructose were not significant. There was no effect of age or gender. CONCLUSIONS: SIBO may represent an important reversible cause of carbohydrate intolerance. It may be especially prudent to exclude SIBO patients with an early peak (≤90 minutes) in H2 excretion.

Circulating Bone Marrow-Derived CD45-/CD34+/CD133+/VEGF+ Endothelial Progenitor Cells in Adults with Crohn's Disease.

BACKGROUND: Circulating endothelial progenitor cells (EPCs) are bone marrow-derived stem cells able to migrate to sites of damaged endothelium and differentiate into endothelial cells. Altered EPC level and function have been described in various inflammatory diseases and have been shown to augment vasculogenesis in murine models. Previous studies of EPC in the context of Crohn's disease (CD) have yielded conflicting results. AIM: To determine whether the circulating levels of EPCs are changed in the context of CD. METHODS: CD patients and healthy controls were recruited. Disease activity was assessed by CDAI. Peripheral blood mononuclear cells were isolated and EPC numbers evaluated by FACS analysis using anti-CD34, anti-VEGF receptor-2, anti-CD133, and anti-CD45 markers. RESULTS: Eighty-three subjects, including 32 CD patients and 51 controls were recruited, including 19 (59.4 %) and 23 (45 %) males (p = 0.26), aged 34.8 ± 14.9 and 43.3 ± 18.5 years (p = 0.64), in cases and controls, respectively. Mean CDAI was 147 ± 97, disease duration was 12.7 ± 11.1 years, and 28 (87.5 %) were receiving biologics for a mean duration of 21.7 ± 16.8 months. The mean level of peripheral EPCs in CD patients was 0.050 ± 0.086 percent and 0.007 ± 0.013 % in controls (p < 0.01). There was no significant correlation between EPC levels and age (r = -0.13, p = 0.47), CDAI (r = -0.26, p = 0.15), disease duration (r = -0.04, p = 0.84), or duration of treatment with biologics (r = 0.004, p = 0.99). CONCLUSION: EPCs are elevated in patients with CD. Further studies are needed to examine the function of EPCs and their possible role as a marker of disease severity or therapeutic response.