Exploring the Impact of COVID-19 on Ulcerative Colitis Patients: A Lifestyle Perspective.

Background and Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 is the new coronavirus that caused the coronavirus disease 2019 (COVID-19) outbreak. Studies have increasingly reported the involvement of organs outside the respiratory system, including the gastrointestinal tract. Data on the association between COVID-19 and ulcerative colitis (UC) are lacking. Materials and Methods: In this one-centre cross-sectional study, 49 patients with UC from the Riga East Clinical University Hospital outpatient clinic were included from June 2021 to December 2021. The patients were divided into two groups according to their history of a confirmed positive or negative COVID-19 status. Data on their lifestyle, diet, and medications and the food supplements used by the patients were collected during interviews and analysed using the R 4.2.1 software. Results: Out of 49 patients, 33 (63.3%) were male and 13 (36.7%) were female, with a mean age of 32.33 ± 8.6 years. Fourteen patients (28.6%) had a confirmed COVID-19 infection in the last year. The most common COVID-19-related symptoms were a fever and rhinorrhoea. A third of patients followed the inflammatory bowel disease diet (16; 32.7%); out of these patients, 12 (34.3%) did not contract COVID-19 (OR: 0.78 (0.18; 2.98), p > 0.05). In the COVID-19-positive group, the majority of patients did not use vitamin D (11; 79% vs. 3; 21%, (OR: 0.38 (0.07; 1.51), p = 0.28) or probiotics (11; 78.6% vs. 3; 21.4%, OR: 1.33 (0.23; 6.28), p = 0.7). In the COVID-19-positive group, most patients did not smoke (12; 85.7% vs. 2; 14.3%, p = 0.475) and did not use alcohol (9; 64.3% vs. 5; 35.7%, OR: 0.63 (0.16; 2.57), p = 0.5). Most of the patients who participated in sports activities were COVID-negative (18; 51.4% vs. 6; 42.9%, p = 0.82). Conclusions: There were no statistically significant differences in the use of food supplements, probiotics, or vitamins; the lifestyle habits; or the COVID-19 status in patients with UC.

Evaluation of Antimicrobial Resistancein Clinical Isolates of Enterococcus spp. Obtained from Hospital Patients in Latvia.

Background and Objective: Enterococci are typically found in a healthy human gastrointestinal tract but can cause severe infections in immunocompromised patients. Such infections are treated with antibiotics. This study addresses the rising concern of antimicrobial resistance (AMR) in Enterococci, focusing on the prevalence of vancomycin-resistant enterococcus (VRE) strains. Materials and Methods: The pilot study involved 140 Enterococci isolates collected between 2021 and 2022 from two multidisciplinary hospitals (with and without local therapeutic drug monitoring protocol of vancomycin) in Latvia. Microbiological assays and whole genome sequencing were used. AMR gene prevalence with resistance profiles were determined and the genetic relationship and outbreak evaluation were made by applying core genome multi-locus sequence typing (cgMLST). Results: The acquired genes and mutations were responsible for resistance against 10 antimicrobial classes, including 25.0% of isolates expressing resistance to vancomycin, predominantly of the vanB type. Genetic diversity among E. faecalis and E. faecium isolates was observed and seven potential outbreak clusters were identified, three of them containing sequence types ST6, ST78 and ST80. The prevalence of vancomycin resistance was highest in the hospital without a therapeutic drug-monitoring protocol and in E. faecium. Notably, a case of linezolid resistance due to a mutation was documented. Conclusions: The study illustrates the concerning prevalence of multidrug-resistant Enterococci in Latvian hospitals, showcasing the rather widespread occurrence of vancomycin-resistant strains. This highlights the urgency of implementing efficient infection control mechanisms and the need for continuous VRE surveillance in Latvia to define the scope and pattern of the problem, influencing clinical decision making and planning further preventative measures.

Toll-Like Receptor 1 Locus Re-examined in a Genome-Wide Association Study Update on Anti-Helicobacter pylori IgG Titers.

BACKGROUND & AIMS: A genome-wide significant association between anti-Helicobacter pylori (H pylori) IgG titers and Toll-like receptor (TLR1/6/10) locus on 4p14 was demonstrated for individuals of European ancestry, but not uniformly replicated. We re-investigated this association in an updated genome-wide association study (GWAS) meta-analysis for populations with low gastric cancer incidence, address potential causes of cohort heterogeneity, and explore functional implications of genetic variation at the TLR1/6/10 locus. METHODS: The dichotomous GWAS (25% individuals exhibiting highest anti-H pylori IgG titers vs remaining 75%) included discovery and replication sampls of, respectively, n = 15,685 and n = 9676, all of European ancestry. Longitudinal analysis of serologic data was performed on H pylori-eradicated subjects (n = 132) and patients under surveillance for premalignant gastric lesions (n = 107). TLR1/6/10 surface expression, TLR1 mRNA, and cytokine levels were measured in leukocyte subsets of healthy subjects (n = 26) genotyped for TLR1/6/10 variants. RESULTS: The association of the TLR1/6/10 locus with anti-H pylori IgG titers (rs12233670; ß = -0.267 ± SE 0.034; P = 4.42 × 10-15) presented with high heterogeneity and failed replication. Anti-H pylori IgG titers declined within 2-4 years after eradication treatment (P = 0.004), and decreased over time in patients with premalignant gastric lesions (P < 0.001). Variation at the TLR1/6/10 locus affected TLR1-mediated cytokine production and TLR1 surface expression on monocytes (P = 0.016) and neutrophils (P = 0.030), but not mRNA levels. CONCLUSIONS: The association between anti-H pylori IgG titers and TLR1/6/10 locus was not replicated across cohorts, possibly owing to dependency of anti-H pylori IgG titers on therapy, clearance, and antibody decay. H pylori-mediated immune cell activation is partly mediated via TLR1 signaling, which in turn is affected by genetic variation.

Accuracy of two plasma antibody tests and faecal antigen test for non-invasive detection of H. pylori in middle-aged Caucasian general population sample.

OBJECTIVE: The aim of the study was to assess the accuracy of two plasma Helicobacter pylori (H. pylori) antibody test-systems and a stool antigen test (SAT) system in a general population sample in Latvia. MATERIALS AND METHODS: Blood and faecal samples were analysed in healthy individuals (40-64 years), referred for upper gastrointestinal endoscopy according to pilot study protocol within a population-based study investigating gastric cancer prevention strategies (GISTAR pilot study). Antibodies to H. pylori were assessed in plasma by latex-agglutination test and enzyme-linked immunosorbent assay (ELISA). H. pylori antigen in faecal samples was detected by a monoclonal enzyme immunoassay-based SAT. Histological assessment of H. pylori based on a modified Giemsa staining method was used as the gold standard. Individuals having received H. pylori eradication within one year prior to enrolment were excluded. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and overall accuracy were calculated. Receiver-operating characteristic curves were designed to estimate the optimal diagnostic cut-off value of tests. RESULTS: The analysis included 779 participants for latex-agglutination test, 1002 for ELISA and 672 individual samples for SAT. The sensitivity, specificity, PPV, NPV and overall accuracy were as follows: latex-agglutination test (86;81;87;80;84%), ELISA (97;72;83;94;86%) and SAT (87;81;87;81;85%), respectively. The optimal diagnostic cut-off value for ELISA test was ≥50.26 g/L. CONCLUSIONS: Although the performance of the three tests was comparable to each other, the three test systems showed suboptimal accuracy, with important implications for public health programs based on 'test-and-treat' strategy.

Detection of gastric atrophy by circulating pepsinogens: A comparison of three assays.

BACKGROUND: Circulating levels of pepsinogens have been used in high gastric cancer-risk Asian and European populations to triage endoscopic evaluation for more severe pathology. There are different analytic methods with uncertain correlations. We therefore compared diagnostic performance of three commonly used pepsinogen assays to detect histologically confirmed gastric atrophy. METHODS: We tested plasma samples from adult patients with (n=50) and without (n=755) moderate or severe gastric corpus atrophy, as determined histologically by consensus of three expert pathologists. A single laboratory measured pepsinogens I (PgI) and II (PgII) using commercially available assays: two ELISA assays produced by Biohit (Finland) and Vector Best (Russia), and a latex agglutination assay from Eiken (Japan). Quantitative correlations were assessed by Spearman statistics. Receiver operating characteristic (ROC) curves vs histological diagnosis were calculated using both the manufacturers' and optimized cutoffs. RESULTS: Pepsinogen levels were highly correlated among the assays (pairwise Rhos: PgI≥0.84, PgII≥0.87; all P-values<.01). Based on manufacturers' cutoffs, sensitivities, specificities and areas under the ROC curve for detecting moderate to severe histological corpus atrophy by PgI/PgII were 44%/91%/0.70, 56%/84%/0.76, and 52%/90%/0.77 for Biohit, Vector Best and Eiken, respectively. Cutoffs optimized by ROC or data mining analyses did not substantially improve test performance. CONCLUSIONS: Commercial assays for pepsinogen have good relative agreement but are imperfect tests for clinical diagnosis of gastric atrophy. IMPACT: Pepsinogen testing alone does not provide sufficient information for gastric cancer risk stratification. Future investigations should focus on other potential markers, in combination with pepsinogens.

Prevalence of Helicobacter pylori infection among preschool children in Latvia: no significant decrease in prevalence during a ten year period.

AIMS: Published data show a trend of decreasing prevalence of Helicobacter pylori in Eastern European countries due to socioeconomic changes. The aim of this study was to determine the prevalence of H. pylori infection among children in Latvia and to compare these results with previous studies in the same population. The risk factors associated with infection were also analysed. METHODS: Preschool children in kindergartens and primary health care centres were investigated using a stool antigen test. Their parents were asked to fill out a questionnaire about possible risk factors. Statistical analysis included Pearson's χ(2) test and linear regression analysis. RESULTS: The prevalence of H. pylori infection determined by the monoclonal stool antigen test in children aged 1-6 years (median 5 years) was 15.5% (15/101) (95% confidence interval 8.67-23.48%). In the regression analysis, H. pylori positivity was significantly negatively associated with the consumption of imported fruit at least once per week (p=0.02). CONCLUSIONS THE PREVALENCE OF H PYLORI IN THE STUDIED POPULATION HAS NOT DECREASED SIGNIFICANTLY DURING THE LAST DECADE AND IS STILL ASSOCIATED WITH SOCIOECONOMIC FACTORS THE ROLE OF SOME DIETARY FACTORS EG THE CONSUMPTION OF FRUIT IN THE SPREAD OF INFECTION SHOULD BE STUDIED FURTHER.

Pepsinogen testing for evaluation of the success of Helicobacter pylori eradication at 4 weeks after completion of therapy.

BACKGROUND AND OBJECTIVE: Pepsinogen levels in plasma are increased by inflammation in the gastric mucosa, including inflammation resulting from Helicobacter pylori infection. A decrease in pepsinogen II level has been suggested as a reliable marker to confirm the successful eradication of infection. The aim of our study was to evaluate the potential role of pepsinogens I and II, gastrin-17 and H. pylori antibodies in confirming successful eradication. MATERIAL AND METHODS: Altogether 42 patients (25 women, 17 men), mean age 45 years (range 23-74), were enrolled. Pepsinogens I and II, gastrin-17 and H. pylori IgG antibodies were measured in plasma samples using an ELISA test (Biohit, Oyj., Finland) before the eradication and 4 weeks after completing the treatment. The success of eradication was determined by a urea breath test. RESULTS: Eradication was successful in 31 patients (74%) and unsuccessful in 11 patients (26%). Pepsinogen II decreased significantly in both the successful (P=0.029) and unsuccessful (P=0.042) eradication groups. Pepsinogen I decreased significantly in the successful (P=0.025) but not the unsuccessful (P=0.29) eradication group. The pepsinogen I/II ratio increased in the successful eradication group (P=0.0018) but not in the group in which treatment failed (P=0.12). There were no differences in gastrin-17 or H. pylori antibody values. CONCLUSIONS: A decrease in pepsinogen II levels cannot be used as a reliable marker for the successful eradication of H. pylori 4 weeks after the completion of treatment. The increase in pepsinogen I/II ratio reflects differences in pepsinogen production following the eradication irrespective of improvement in atrophy.

Autoimmune gastritis serological biomarkers in gastric cancer patients.

The role of autoimmunity in the pathogenesis of gastric cancer remains controversial. We studied antiparietal cell antibody (anti-PCA) and anti-intrinsic factor antibody (anti-IFA) levels and their associations with pepsinogen I/pepsinogen II levels in patients with gastric adenocarcinoma compared to a control group with mild or no atrophy of the stomach mucosa. Plasma levels of anti-PCA and anti-IFA were measured by ELISA (Inova Diagnostics Inc, San Diego, California, USA). The cutoff value for anti-PCA and anti-IFA positivity was ≥25 units. Altogether 214 patients (126 men, 88 women, median age 64.46, range: 35-86) with confirmed gastric adenocarcinoma and 214 control cases paired for age and sex were included in the study. Positive anti-PCA was present in 22 (10.3%) gastric cancer patients and controls (P ≥ 0.999); positive anti-IFA in 6 (2.8%) and 4 (1.9.%), P < 0.232, respectively. We did not find significant differences in anti-PCA and anti-IFA positivity between gastric cancer patients and the control group; further investigation is required to better understand the potential involvement of autoimmune gastritis in the development of gastric cancer.

Assessing the utility of pepsinogens and gastrin-17 in gastric cancer detection.

OBJECTIVES: The aim of the study was to determine the proportion of gastric cancer patients with decreased levels of pepsinogen and gastrin-17 in plasma, with the goal of providing indirect evidence of the sensitivity of these biomarkers when applied in a cancer screening setting. METHODS: The levels of pepsinogens I and II, gastrin-17, and Helicobacter pylori immunoglobulin antibodies in plasma samples of gastric cancer patients were evaluated using the GastroPanel test system (Biohit Oyj, Helsinki, Finland). A decreased level of the pepsinogen I/II ratio was defined as less than three, while a decrease in gastrin-17 was defined as less than 1 pmol/L. Univariate analysis using non-parametric tests was used to investigate differences between normal and low concentrations of biomarkers. RESULTS: In total, 481 plasma samples from patients (59.9% male) with a median age of 64 years (ranging from 27 to 88 years) were analyzed. Out of the 400 cases of gastric cancer (83.2% of the total), 182 were categorized as the intestinal type, 141 as the diffuse type, 60 as the mixed type, and 17 as indeterminate according to the Lauren classification system. The H. pylori immunoglobulin test was positive in 74.0% of the patients. Pepsinogen I/II ratio was decreased in 32.4% (36.8% of the intestinal type); gastrin-17 in 12.3% (10.1% of the antral region) of all cases. CONCLUSION: The majority of gastric cancer patients had normal levels of pepsinogen and gastrin-17, suggesting that these biomarkers have limited application as screening tools in the Caucasian population.

Factors Associated with False Negative Results in Serum Pepsinogen Testing for Precancerous Gastric Lesions in a European Population in the GISTAR Study.

The accuracy of plasma pepsinogen (Pg) as a marker for precancerous gastric lesions (PGL) has shown variable results. We aimed to identify factors associated with false negative (FN) cases in Pg testing and to adjust cut-off values for these factors in order to improve Pg yield. Plasma Pg was measured and upper endoscopy with biopsy was performed within the "Multicentric randomized study of Helicobacter pylori eradication and pepsinogen testing for prevention of gastric cancer mortality: the GISTAR study". A multivariable logistic model was built for FN and multiple factors. Values of Pg were compared and sensitivity and specificity were calculated using pre-existing Pg cut-offs for factors showing strong associations with FN. New cut-offs were calculated for factors that showed substantially lower sensitivity. Of 1210 participants, 364 (30.1%) had histologically confirmed PGL, of which 160 (44.0%) were FN. Current smokers, men, and H. pylori positives were more likely FN. Smoking in H. pylori negatives was associated with a higher Pg I/II ratio and substantially lower sensitivity of Pg testing than in other groups. Adjusting Pg cut-offs for current smokers by H. pylori presence improved sensitivity for detecting PGL in this group. Our study suggests that adjusting Pg cut-offs for current smokers by H. pylori status could improve Pg test performance.

Assessment of Serum Pepsinogens with and without Co-Testing with Gastrin-17 in Gastric Cancer Risk Assessment-Results from the GISTAR Pilot Study.

Introduction−−Serum pepsinogen tests for gastric cancer screening have been debated for decades. We assessed the performance of two pepsinogen assays with or without gastrin-17 for the detection of different precancerous lesions alone or as a composite endpoint in a Latvian cohort. Methods−−Within the intervention arm of the GISTAR population-based study, participants with abnormal pepsinogen values by ELISA or latex-agglutination tests, or abnormal gastrin-17 by ELISA and a subset of subjects with all normal biomarker values were referred for upper endoscopy with biopsies. Performance of biomarkers, corrected by verification bias, to detect five composite outcomes based on atrophy, intestinal metaplasia, dysplasia or cancer was explored. Results−−Data from 1045 subjects were analysed, of those 273 with normal biomarker results. Both pepsinogen assays showed high specificity (>93%) but poor sensitivity (range: 18.4−31.1%) that slightly improved when lesions were restricted to corpus location (40.5%) but decreased when dysplasia and prevalent cancer cases were included (23.8%). Adding gastrin-17 detection, sensitivity reached 33−45% while specificity decreased (range: 61.1−62%) and referral rate for upper endoscopy increased to 38.6%. Conclusions−−Low sensitivity of pepsinogen assays is a limiting factor for their use in population-based primary gastric cancer screening, however their high specificity could be useful for triage.

Lifestyle and dietary factors associated with serologically detected gastric atrophy in a Caucasian population in the GISTAR study.

OBJECTIVE: To identify dietary and lifestyle factors associated with decreased pepsinogen levels indicative of gastric atrophy. METHODS: Participants aged 40 to 64 from the "Multicentric randomized study of H. pylori eradication and pepsinogen testing for prevention of gastric cancer mortality (GISTAR study)" in Latvia tested for serum pepsinogen, as well as for Helicobacter pylori infection by 13 C-urea breath test or serology were included. Data on sex, age, education, employment, diet, smoking, alcohol and proton pump inhibitor use were obtained by survey and compared for participants with and without serologically detected gastric atrophy defined as pepsinogen I/pepsinogen II ≤ 2 and pepsinogen I ≤ 30 ng/mL. RESULTS: Of 3001 participants (median age 53, interquartile range, 11.0, 36.9% male) 52.8% had H. pylori and 7.7% had serologically detected gastric atrophy. In multivariate analysis, increasing age, consumption of alcohol, coffee, and onions were positively, while H. pylori , former smoking, pickled product and proton pump inhibitor use were inversely associated with gastric atrophy. Pepsinogen values were higher in smokers and those with H. pylori . Pepsinogen ratio was lower in those with H. pylori . When stratifying by H. pylori presence, significantly higher pepsinogen levels remained for smokers without H. pylori . CONCLUSION: Several dietary factors and smoking were associated with serologically detected gastric atrophy. Pepsinogen levels differed by smoking and H. pylori status, which may affect the serologic detection of gastric atrophy. There seems to be a complicated interaction between multiple factors. A prospective study including atrophy determined by both serology and histology is necessary.

Who Could Be Blamed in the Case of Discrepant Histology and Serology Results for Helicobacter pylori Detection?

BACKGROUND: Discrepancies between histology and serology results for Helicobacter pylori detection could be caused by a variety of factors, including a biopsy sampling error, expertise of the pathologist, natural loss of infection due to advanced atrophy, or a false-positive serology in the case of a previous infection, since antibodies may be present in blood following recovery from the infection. AIMS: To identify true H. pylori-positive individuals in discrepant cases by serology and histology using real time polymerase chain reaction (RT-PCR) as a gold standard. METHODS: Study subjects with discrepant histology and serology results were selected from the GISTAR pilot study data base in Latvia. Subjects having received previous H. pylori eradication therapy or reporting use of proton pump inhibitors, antibacterial medications, or bismuth containing drugs one month prior to upper endoscopy were excluded. We compared the discrepant cases to the corresponding results of RT-PCR performed on gastric biopsies. RESULTS: In total, 97 individuals with discrepant results were identified: 81 subjects were serology-positive/histology-negative, while 16 were serology-negative/histology-positive. Among the serology-positive/histology-negative cases, 64/81 (79.0%) were false-positives by serology and, for the majority, inflammation was absent in all biopsies, while, in the serology-negative/histology-positive group, only 6.2% were proven false-positives by histology. CONCLUSIONS: Among this high H. pylori prevalent, middle-aged population, the majority of discrepant cases between serology and histology were due to false positive-serology, rather than false-negative histology. This confirms the available evidence that the choice of treatment should not be based solely on the serological results, but also after excluding previous, self-reported eradication therapy.

The Diagnostic Value of Anti-Parietal Cell and Intrinsic Factor Antibodies, Pepsinogens, and Gastrin-17 in Corpus-Restricted Atrophic Gastritis.

We aimed to determine the diagnostic value of anti-parietal cell antibodies (anti-PCA), anti-intrinsic factor antibodies (anti-IFA), pepsinogen ratio (PGI/II), and gastrin-17 (G-17) in corpus-restricted atrophic gastritis (CRAG) detected by ELISA (Inova, Biohit). Our study compared 29 CRAG cases against 58 age- and sex-matched controls with mild or no atrophy. Anti-PCA and anti-IFA positive cutoff values were ≥25 units for both. PGI/II value <3 was considered characteristic for atrophy; positive cutoff values for G-17 and anti-H. pylori IgG were >5 pg/L and >30 EIU. Anti-PCA was positive in 65.5% For CRAG cases and 13.8% of the controls (p < 0.0001), anti-IFA was positive in 13.8% and 0% (p = 0.01), respectively. Decreased pepsinogen levels were present in 79.3% of CRAG cases and 10.3% of the controls (p < 0.0001). PGI/II ratio was the best single biomarker, with sensitivity = 79%, specificity = 90%, and AUC 0.90. The combined use of PGI/II and anti-PCA resulted in AUC 0.93 for detecting CRAG. Our study suggests that the best combination of non-invasive biomarkers for detecting CRAG is PGI/II with anti-PCA. The addition of G-17 and anti-IFA is of little utility in clinical application.

Prevalence and Potential Risk Factors of Helicobacter pylori Infection among Asymptomatic Individuals in Kazakhstan.

BACKGROUND: Helicobacter pylori (H. pylori) infection is associated with several risk factors such as demographic, socioeconomic status and personal habits, which vary in different populations. This is the most up-to-date data on H. pylori prevalence and potential risk factors for H. pylori infection among asymptomatic middle-aged individuals in Kazakhstan. METHODS: Apparently healthy individuals aged 40 to 64, who took part in the health control in the outpatient clinic, were invited to participate in the study; answered a questionnaire, donated a blood sample. The antibodies to H. pylori were analysed by latex agglutination method. The baseline characteristics of study subjects with or without H. pylori infection were compared using the Chi-square test. Odds ratio (OR) and 95% confidence intervals (CI) for the association between H. pylori infection and potential risk factors were estimated using multivariable logistic regression models. RESULTS: Altogether 166 subjects (59% male; the median age - 51 years old) were included; 104 (62.7%) were H. pylori positive. There were no statistically significant differences between H. pylori positive and H. pylori negative groups in respect to the gender, anthropometric measurements, socioeconomic factors and personal habits. The multiple variable analysis showed that age (OR, 1.99; 95% CI, 1.03 - 3.86; P=0.04) and increased salt intake (OR, 2.21; 95% CI, 1.12 - 4.35; P=0.02) were associated with H. pylori infection. CONCLUSIONS: More than half of the study subjects were infected with H. pylori in Kazakhstan. The prevalence of H. pylori infection was independently associated with older age and regular high salt consumption.

Prevalence of Atrophic Gastritis in Kazakhstan and the Accuracy of Pepsinogen Tests to Detect Gastric Mucosal Atrophy.

BACKGROUND: Atrophic gastritis is considered precursor condition for gastric cancer. There is so far limited evidence on the performance of pepsinogens for atrophy detection in Central Asia. The aim of our study was to detect the prevalence of atrophic gastritis in the asymptomatic adult population in Kazakhstan as well as address the accuracy of pepsinogen testing in atrophy detection. METHODS: Healthy individuals aged 40-64 were included. Upper endoscopy and pepsinogens (PG) evaluation were performed. PG were analysed in plasma by latex agglutination. Cut off values were used to define decreased PG values (PGR ≤ 3 and PG I ≤ 70 ng/mL); severely decreased PG values (PGR ≤ 2 and PG I ≤ 30 ng/mL). Biopsies were analyzed and obtained according to the updated Sydney System. PG test sensitivity, specificity and overall accuracy were assessed using the histological diagnosis as the "gold standard". RESULTS: Altogether 157 individuals - female 40,1% and male 59,9% were included. Histologically, moderate to severe corpus atrophy, was present only in 1,3% cases. From all study subjects, 26,8% had decreased plasma PG values with cut-off values PGR ≤ 3 and PG I ≤ 70 ng/mL. The sensitivity of the PG test with this cut-off values was 50,0%, specificity 73,5%, overall accuracy 73,2% for detection of moderate to severe atrophy in the corpus. The sensitivity of PG test with cut-off values PGR ≤ 2 and PG I ≤30 ng/mL was 50,0%, specificity 90,9% and overall accuracy 90,4%. CONCLUSIONS: The prevalence of gastric mucosal atrophy was low in the Kazakh population. Serological PG test screening nevertheless can play an important role in the diagnosis of gastric precancerous lesions. However, the diagnostic accuracy of the PG test is mainly dependent on the cut-off values for positive results.

Associations of Epstein-Barr Virus-Positive Gastric Adenocarcinoma with Circulating Mediators of Inflammation and Immune Response.

Epstein-Barr virus (EBV)-positive gastric adenocarcinoma exhibits locally intense inflammation but systemic manifestations are uncertain. Our study examined whether circulating mediators of inflammation and immune response differ by tumor EBV status. From a Latvian series of 302 gastric cancer cases, we measured plasma levels of 92 immune-related proteins in the 28 patients with EBV-positive tumors and 34 patients with EBV-negative tumors. Eight markers were statistically significantly higher with tumor EBV positivity: chemokine C-C motif ligand (CCL) 20 (Odds Ratio (OR) = 3.6; p-trend = 0.001), chemokine C-X-C motif ligand 9 (OR = 3.6; p-trend = 0.003), programmed death-ligand 1 (PD-L1; OR = 3.4; p-trend = 0.004), interleukin (IL)-10 (OR = 2.4; p-trend = 0.019), CCL19 (OR = 2.3; p-trend = 0.019), CCL11 (OR = 2.2; p-trend = 0.026), IL-17A (OR = 2.0; p-trend = 0.038) and CCL8 (OR = 1.9; p-trend = 0.049). Systemic responses to EBV-positive gastric cancer are characterized by alterations in chemokines and PD-L1. Profiling of these molecules may enable non-invasive diagnosis of EBV status when tumor tissue is unavailable. Our findings provide theoretical justification for clinical evaluations of immune checkpoint therapy for EBV-positive gastric cancer.

Gut colonization with extended-spectrum ß-lactamase-producing Enterobacteriaceae may increase disease activity in biologic-naive outpatients with ulcerative colitis: an interim analysis.

BACKGROUND: Certain Enterobacteriaceae strains have been associated with the development of ulcerative colitis (UC). Extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae are the most commonly found multi-drug-resistant (MDR) bacteria colonizing the gut in UC patients and might trigger a more severe disease activity in UC patients. OBJECTIVE: The aim of this study was to evaluate whether disease activity is higher in UC patients with gut colonization with ESBL-producing Enterobacteriaceae. MATERIALS AND METHODS: A cross-sectional, pilot study was carried out in a tertiary medical center in Latvia. Demographic data were collected; UC disease activity and extent were evaluated according to the full Mayo score, Montreal classification, and adapted Truelove and Witt's index. Rectal swabs with fecal biomaterial were collected, ESBL-producing Enterobacteriaceae were isolated, and bacterial plasmid genes responsible for ESBL production, blaCTX-M, blaTEM, and blaSHV, were detected. UC disease activity was compared in patients with and without gut colonization with ESBL-producing Enterobacteriaceae. RESULTS: A total of 65 patients with UC were included in the initial analysis. Gut colonization with ESBL-producing Enterobacteriaceae was found in seven (11%) patients - mostly Escherichia coli [5 (71%)] containing the blaCTX-M bacterial plasmid gene. Patients with gut colonization with ESBL-producing Enterobacteriaceae had more severe disease compared with patients without gut colonization according to the full Mayo score (5.86 vs. 3.40; P=0.015), Montreal classification (moderate disease vs. clinical remission; P=0.031), and adapted Truelove and Witt's index (moderate disease vs. mild disease; P=0.008). CONCLUSION: Gut colonization with ESBL-producing Enterobacteriaceae may increase UC disease activity. Further research is needed to analyze the possible confounding factors that could contribute toward this outcome.

Pepsinogen test for the evaluation of precancerous changes in gastric mucosa: a population-based study.

AIMS: The aim of the study was to evaluate the rationale of blood pepsinogen (PG) testing in population based screening settings. METHODS: Participants from a cross-sectional population-based study of cardiovascular risk factors in Latvia were invited to participate in the current study. Pepsinogen I and II were measured in blood samples taken during the initial study and at follow-up; upper gastrointestinal endoscopy was performed. There were three groups of patients: with moderately decreased (PG I< 70 ng/ml and PG I/PG II ratio < 3), with strongly decreased (PG I< 30 ng/ml and PG I/PG II ratio < 2), and with normal PG level. Biopsy with H. pylori detection was performed (updated Sydney system). RESULTS: Results from 259 patients were analyzed. Pepsinogens were decreased in 133 (51.4%), H. pylori was positive in 177 (66.0%) cases. Mean age was significantly lower in patients with normal compared to strongly decreased PG level group (52.8 vs. 64.1 years, p<0.001). Prevalence of severe corpus atrophy was higher in the strongly decreased compared to the normal PG test group: 7.0% vs. 0%; the same tendency was noted in the distribution of OLGA stages III-IV - 10.5% and 0.0%, OLGIM stages III-IV - 3.5% and 0%, and low-grade dysplasia - 15.8% and 2.4% (p<0.05). Two cases of gastric cancer were found; both presented decreased PG levels. A strong association between H. pylori eradication and PG ratio dynamics was found (p<0.05). CONCLUSIONS: All high-risk lesions were found in the decreased PG test groups; two cancer cases were revealed. However, PG demonstrated low specificity and low value of repeated testing. The value of PG as a sole test for gastric cancer risk is limited.

Multicentric randomised study of Helicobacter pylori eradication and pepsinogen testing for prevention of gastric cancer mortality: the GISTAR study.

INTRODUCTION: Population-based eradication of Helicobacter pylori has been suggested to be cost-effective and is recommended by international guidelines. However, the potential adverse effects of widespread antibiotic use that this would entail have not been sufficiently studied. An alternative way to decrease gastric cancer mortality is by non-invasive search for precancerous lesions, in particular gastric atrophy; pepsinogen tests are the best currently available alternative. The primary objective of GISTAR is to determine whether H pylori eradication combined with pepsinogen testing reduces mortality from gastric cancer among 40-64-year-old individuals. The secondary objectives include evaluation of H pylori eradication effectiveness in gastric cancer prevention in patients with precancerous lesions and evaluation of the potential adverse events, including effects on microbiome. METHODS AND ANALYSIS: Individuals are recruited from general population (50% men) in areas with high gastric cancer risk in Europe and undergo detailed lifestyle and medical history questionnaire before being randomly allocated to intervention or control groups. The intervention group undergoes H pylori testing and is offered eradication therapy if positive; in addition, pepsinogen levels are detected in plasma and those with decreased levels are referred for upper endoscopy. All participants are offered faecal occult blood testing as an incentive for study participation. Effectiveness of eradication and the spectrum of adverse events are evaluated in study subpopulations. A 35% difference in gastric cancer mortality between the groups is expected to be detectable at 90% power after 15 years if 30 000 individuals are recruited. Biological materials are biobanked for the main and ancillary studies. The study procedure and assumptions will be tested during the pilot phase. ETHICS AND DISSEMINATION: The study was approved by the respective ethics committees. An independent Data Safety and Monitoring Board has been established. The findings will be published in peer-reviewed journals and presented at scientific meetings. TRIAL REGISTRATION NUMBER: NCT02047994.