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Noémi Zádori,1,2 Dávid Németh,1 Levente Frim,1 Nóra Vörhendi,1,2 Lajos Szakó,1,2 Szilárd Váncsa,1– 3 Péter Hegyi,1– 3 József Czimmer1,4 1Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary; 2János Szentágothai Research Centre, University of Pécs, Pécs, Hungary; 3Centre for Translational Medicine, Semmelweis University, Budapest, Hungary; 4Division of Gastroenterology, First Department of Medicine, Medical School, University of Pécs, Pécs, HungaryCorrespondence: József Czimmer, First Department of Medicine, University of Pécs Medical School, Ifjúság street 13, Pécs, H-7624, Hungary, Email czimmer.jozsef@pte.huIntroduction: Dyspeptic symptoms are frequent in the general population, with a high socioeconomic burden. Helicobacter pylori (H. pylori) might be a possible etiological factor; however, it is also common in H. pylori negative gastritis. Clarification of the underlying aetiology might be beneficial to set up the optimal treatment strategy for dyspepsia and chronic gastritis (CG) itself. We aimed to assess the prevalence of dyspeptic symptoms in patients with H. pylori negative CG and explore autoimmunity’s possible role.Methods: This retrospective study included data from patients with H. pylori negative CG. Exclusion criteria were (1) acute gastritis; (2) reactive gastropathy; (3) subjects without any serology testing results; (4) H. pylori positivity; (5) presence of atrophy, intestinal metaplasia (IM), gastroesophageal reflux disease (GERD), ulcer, or cancer. The following endpoints were assessed (1) the rate of dyspepsia-like symptoms; (2) association between dyspepsia and autoimmune disease-related seromarker positivity (AISP); (3) frequency of other symptoms in CG and its association with AISP; (4) location of the inflammation and its association with AISP.Results: From a total of 285 patients, 175 were included in this study. Among these patients, 95 experienced dyspeptic symptoms (54.29%) and were associated more with AISP (p = 0.012), especially with celiac seropositivity (p = 0.045), anti-neutrophil cytoplasmic antibody (ANCA) and anti-Saccharomyces cerevisiae antibodies (ASCA) positivity (p = 0.043). A significant association was not found with other tested autoimmune (AI)-related antibody positivity.Conclusion: Positivity of seromarkers of autoimmune diseases in chronic gastritis may predispose to have dyspeptic symptoms and may be the causative factor behind some cases of uninvestigated dyspepsia. These data suggest that further prospective studies are needed to clarify whether screening for autoantibodies in patients with dyspepsia is cost-effective and helps the earlier diagnosis of autoimmune diseases.Keywords: chronic gastritis, autoimmunity, auto-antibody, dyspepsia

Intravenous (iv) injection of secretin activates neurons in brain areas controlling autonomic function and emotion. Peripheral administration of secretin inhibits gastric functions through a central mechanism that is mediated by vagal dependant pathways. We investigated whether the vagus nerve is involved in intraperitoneal (ip) injection of secretin-induced brain neuronal activation in conscious rats as monitored by Fos immunohistochemistry. Secretin (40 or 100 microgram/kg, ip, -90 min) induced a linear dose-related increase in the number of Fos positive neurons in the central nucleus of the amygdala (CeA), and a plateau Fos response in the area postrema (AP), nucleus tractus solitarii (NTS), locus coeruleus (LC), Barrington's nucleus (Bar), external lateral subnucleus of parabrachial nucleus (PBel) and arcuate nucleus (Arc), and at the highest dose, in the dorsal motor nucleus of the vagus (DMV) compared with ip injection of vehicle. Double immunohistochemistry in the NTS showed that a substantial number of neurons activated by secretin (40 microgram/kg, ip) are tyrosine hydroxylase positive. Subdiaphragmatic vagotomy (-7 days) abolished Fos expression-induced by ip secretin (40 microgram/kg) in the NTS, DMV, LC, Bar, PBel and CeA, while a significant rise in the AP was maintained. In contrast, capsaicin (-10 days) did not influence the Fos induction in the above nuclei. Quantitative real-time polymerase chain reaction (PCR) and reverse transcription PCR showed that secretin receptor mRNA is expressed in the nodose ganglia and levels were higher in the right compared to the left ganglion. These results indicate that peripheral secretin activates catecholaminergic NTS neurons as well as neurons in pontine and limbic nuclei regulating autonomic functions and emotion through vagal dependent capsaicin resistant pathways. Secretin injected ip may signal to the brain by interacting with secretin receptors on vagal afferent as well as on AP neurons outside the blood brain barrier.

Abstract Background Infliximab (IFX) has proven to be an effective addition to the therapeutic arsenal for refractory, fistulizing, and steroid dependent Crohn's disease (CD), with efficacy in the induction and maintenance of clinical remission of CD. Our objective in this study is to report the nationwide, multicenter experience with IFX induction therapy for CD in Hungary. Methods During a 6-year-period, beginning in 2000, a total of 363 CD patients were treated with IFX as induction therapy (5 mg/kg IFX infusions given at week 0, 2 and 6) at eleven centers in Hungary in this observational study. Data analysis included patient demographics, important disease parameters and the outcome of IFX induction therapy. Results Three hundred and sixty three patients (183 women and 180 men) were treated with IFX since 2000. Mean age was 33.5 ± 11.2 years and the mean duration of disease was 6.7 ± 6.1 years. The population included 114 patients (31.4%) with therapy-refractory CD, 195 patients (53.7%) with fistulas, 16 patients (4.4%) with both therapy-refractory CD and fistulas, and 26 patients (7.2%) with steroid dependent CD. Overall response rate was 86.2% (313/363). A higher response rate was observed in patients with shorter disease duration (p = 0.05, OR:0.54, 95%CI:0.29-0.99) and concomitant immunosuppressant therapy (p = 0.05, OR: 2.03, 95%CI:0.165-0.596). Concomitant steroid treatment did not enhance the efficacy of IFX induction therapy. Adverse events included 34 allergic reactions (9.4%), 17 delayed type hypersensitivity (4.7%), 16 infections (4.4%), and 3 malignancies (0.8%). Conclusion IFX was safe and effective treatment in this cohort of Hungarian CD patients. Based on our experience co-administration of immunosuppressant therapy is suggested in patients receiving IFX induction therapy. However, concomitant steroid treatment did not enhanced the efficacy of IFX induction therapy.

There are several overlapping clinical practice guidelines in acute pancreatitis (AP), however, none of them contains suggestions on patient discharge. The Hungarian Pancreatic Study Group (HPSG) has recently developed a laboratory data and symptom-based discharge protocol which needs to be validated. (1) A survey was conducted involving all members of the International Association of Pancreatology (IAP) to understand the characteristics of international discharge protocols. (2) We investigated the safety and effectiveness of the HPSG-discharge protocol. According to our international survey, 87.5% (49/56) of the centres had no discharge protocol. Patients discharged based on protocols have a significantly shorter median length of hospitalization (LOH) (7 (5;10) days vs. 8 (5;12) days) p < 0.001), and a lower rate of readmission due to recurrent AP episodes (p = 0.005). There was no difference in median discharge CRP level among the international cohorts (p = 0.586). HPSG-protocol resulted in the shortest LOH (6 (5;9) days) and highest median CRP (35.40 (13.78; 68.40) mg/l). Safety was confirmed by the low rate of readmittance (n = 35; 5%). Discharge protocol is necessary in AP. The discharge protocol used in this study is the first clinically proven protocol. Developing and testifying further protocols are needed to better standardize patients' care., (© 2023. The Author(s).)

Introduction: The outcomes of surgical interventions for achalasia treatment improved with the advent of minimally invasive surgery. Robotic-assisted Heller-Dor's (RAHD) procedure established over the last years, provides important advantages to surgeons, such as binocular three-dimensional vision and improvement of fine motor control., Method: Between October and December of 2022, first in Hungary, 3 patients (37-year-old man, 55- and 72-year-old women) underwent RAHD procedure for achalasia at the Clinical Centre of the University of Pécs using the da Vinci Xi system., Results: RAHD procedure was feasible without any particular problems and the postoperative course of all three patients was uneventful. The operation times were 198, 204 and 238 minutes, including 23, 19 and 14 minutes for the setup time of the robot. By the last patient, due to an accompanying hiatal hernia, an additional hiatal reconstruction was also performed. In the first 2 cases, the patients were discharged on the 4th postoperative day, while in the last case, with the additional hiatal reconstruction, the patient was emitted on the 6th postoperative day., Discussion: There are several published studies about RAHD cardiomyotomy. The general conclusion is that, in experienced hands, RAHD procedure is easy to perform, ensures a meticulous esophageal and gastric myotomy, allowing to visualize and divide each muscle fiber with a significantly lower rate of mucosal perforations. However, by RAHD procedure, the overall costs are higher, including a longer operation time during the learning curve. At the same time, the avoidance of mucosal lacerations and their possible consequences has to be weighed against the higher overall costs., Conclusion: Laparoscopic cardiomyotomy is the first standard upper-gastrointestinal operation where a clear advantage of the use of a surgical robot has been proven. Thus, wherever this equipment is available, it should be preferred for this procedure. Orv Hetil. 2023; 164(14): 542-547.

Background and Aims: The underlying aetiology of chronic gastritis (CG) often remains unknown due to its underrated significance in clinical practice. However, the role of chronic inflammation of the stomach in the development of atrophy, intestinal metaplasia (IM) and eventually of gastric cancer is well documented. We aimed to explore the possible aetiological factors of CG, determine the prevalence of systemic autoimmune disorders in patients with CG of unknown aetiology, and clarify the role of autoantibodies in the development of precancerous lesions in the stomach., Methods: This is a retrospective, cross-sectional study, conducted from January 2016 to January 2020, including data from 175 patients with CG. Exclusion criteria were: (1) acute gastritis; (2) reactive gastropathy; (3) gastric cancer; (4) subjects without any serology testing results; and (5) Helicobacter pylori positivity. The primary endpoint was a composite endpoint involving gastric atrophy and IM., Results: Fifty-five per cent of patients with CG had autoantibodies. Systemic lupus erythematosus (SLE)-related antibodies were positive in most of the cases, including antinuclear antibody (ANA) positivity, which was found in 19.13% of the patients. Autoimmune positivity was shown to be associated with precancerous lesions in the stomach (p<0.001): IM, atrophy and IM with atrophy. Anti-parietal cell antibody positivity seems to be a significant risk factor for IM and IM with atrophy. Autoimmune thyroiditis-related antibodies and ANA positivity by itself were only associated with atrophy; SLE-related antibodies and inflammatory bowel diseases related antibodies (ASCA and ANCA) correlated either with IM or with atrophy. No significant relation was found between any other investigated autoimmune disease-related antibodies and precancerous lesions., Conclusions: Autoimmune positivity often underlies gastritis of unknown aetiology and predisposes to precancerous lesions in the stomach. These antibodies can serve as non-invasive markers for the of optimal timing of an endoscopic follow-up strategy. Furthermore, CG can be an early symptom of a systemic autoimmune disorder.

Background: Acute pancreatitis (AP) is a potentially severe or even fatal inflammation of the pancreas. Early identification of patients at high risk for developing a severe course of the disease is crucial for preventing organ failure and death. Most of the former predictive scores require many parameters or at least 24 h to predict the severity; therefore, the early therapeutic window is often missed., Methods: The early achievable severity index (EASY) is a multicentre, multinational, prospective and observational study (ISRCTN10525246). The predictions were made using machine learning models. We used the scikit-learn, xgboost and catboost Python packages for modelling. We evaluated our models using fourfold cross-validation, and the receiver operating characteristic (ROC) curve, the area under the ROC curve (AUC), and accuracy metrics were calculated on the union of the test sets of the cross-validation. The most critical factors and their contribution to the prediction were identified using a modern tool of explainable artificial intelligence called SHapley Additive exPlanations (SHAP)., Results: The prediction model was based on an international cohort of 1184 patients and a validation cohort of 3543 patients. The best performing model was an XGBoost classifier with an average AUC score of 0.81 ± 0.033 and an accuracy of 89.1%, and the model improved with experience. The six most influential features were the respiratory rate, body temperature, abdominal muscular reflex, gender, age and glucose level. Using the XGBoost machine learning algorithm for prediction, the SHAP values for the explanation and the bootstrapping method to estimate confidence, we developed a free and easy-to-use web application in the Streamlit Python-based framework (http://easy-app.org/)., Conclusions: The EASY prediction score is a practical tool for identifying patients at high risk for severe AP within hours of hospital admission. The web application is available for clinicians and contributes to the improvement of the model., (© 2022 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Background: Gastric cancer is one of the most common cancers worldwide, with a high mortality rate. The potential etiological role of autoimmune (AI) disorders has been described in gastric cancer; however, the literature is controversial. This study aims to provide a comprehensive summary of the association between autoimmune disorders and the incidence of gastric cancer., Methods: This study was registered on PROSPERO under registration number CRD42021262875. The systematic literature search was conducted in four scientific databases up to May 17, 2021. Studies that reported standardized incidence rate (SIR) of gastric cancer in autoimmune disorders were eligible. We calculated pooled SIRs with 95% confidence intervals (CIs) in this meta-analysis., Results: We included 43 articles describing 36 AI disorders with data of 499,427 patients from four continents in our systematic review and meta-analysis. Significantly increased incidence of gastric cancer was observed in dermatomyositis (SIR = 3.71; CI: 2.04, 6.75), pernicious anemia (SIR = 3.28; CI: 2.71, 3.96), inflammatory myopathies (SIR = 2.68; CI:1.40; 5.12), systemic lupus erythematosus (SIR = 1.48; CI: 1.09, 2.01), diabetes mellitus type I (SIR = 1.29; CI:1.14, 1,47), and Graves' disease (SIR = 1.28; CI: 1.16, 1.41). No significant associations could be found regarding other AI disorders., Conclusions: Pernicious anemia, Graves' disease, dermatomyositis, diabetes mellitus type I, inflammatory myopathies, and systemic lupus erythematosus are associated with higher incidence rates of gastric cancer. Therefore, close gastroenterological follow-up or routinely performed gastroscopy and application of other diagnostic measures may be cost-effective and clinically helpful for patients diagnosed with these autoimmune diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zádori, Szakó, Váncsa, Vörhendi, Oštarijaš, Kiss, Frim, Hegyi and Czimmer.)

Background: Metabolic risk factors, such as obesity, hypertension, and hyperlipidemia are independent risk factors for the development of various complications in acute pancreatitis (AP). Hypertriglyceridemia dose-dependently elicits pancreatotoxicity and worsens the outcomes of AP. The role of hyperglycemia, as a toxic metabolic factor in the clinical course of AP, has not been examined yet., Methods: We analyzed a prospective, international cohort of 2250 AP patients, examining associations between (1) glycosylated hemoglobin (HbA1c), (2) on-admission glucose, (3) peak in-hospital glucose and clinically important outcomes (mortality, severity, complications, length of hospitalization (LOH), maximal C-reactive protein (CRP)). We conducted a binary logistic regression accounting for age, gender, etiology, diabetes, and our examined variables. Receiver Operating Characteristic Curve (ROC) was applied to detect the diagnostic accuracy of the three variables., Results: Both on-admission and peak serum glucose are independently associated with AP severity and mortality, accounting for age, gender, known diabetes and AP etiology. They show a dose-dependent association with severity (p < 0.001 in both), mortality (p < 0.001), LOH (p < 0.001), maximal CRP (p < 0.001), systemic (p < 0.001) and local complications (p < 0.001). Patients with peak glucose >7 mmol/l had a 15 times higher odds for severe AP and a five times higher odds for mortality. We found a trend of increasing HbA1c with increasing LOH (p < 0.001), severity and local complications., Conclusions: On-admission and peak in-hospital glucose are independently and dose-dependently associated with increasing AP severity and mortality. In-hospital laboratory control of glucose and adequate treatment of hyperglycemia are crucial in the management of AP., Competing Interests: Declaration of competing interest Authors declare no conflict of interest., (Copyright © 2021. Published by Elsevier B.V.)

The main causes of acute pancreatitis (AP) are biliary disease, alcohol consumption, hypertriglyceridaemia (HTG) and endoscopic retrograde cholangiopancreatography (ERCP). The aim of this meta-analysis was to evaluate the effects of these aetiological factors on the severity and outcome of AP. Pubmed and Embase were searched between 01/01/2012 and 31/05/2020. Included articles involved adult alcoholic, biliary, HTG- or post-ERCP AP (PAP) patients. Primary outcome was severity, secondary outcomes were organ failures, intensive care unit admission, recurrence rate, pancreatic necrosis, mortality, length of hospital stay, pseudocyst, fluid collection and systematic inflammatory response syndrome. Data were analysed from 127 eligible studies. The risk for non-mild (moderately severe and severe) condition was the highest in HTG-induced AP (HTG-AP) followed by alcoholic AP (AAP), biliary AP (BAP) and PAP. Recurrence rate was significantly lower among BAP vs. HTG-AP or AAP patients (OR = 2.69 and 2.98, 95% CI 1.55-4.65 and 2.22-4.01, respectively). Mortality rate was significantly greater in HTG-AP vs. AAP or BAP (OR = 1.72 and 1.50, 95% CI 1.04-2.84 and 0.96-2.35, respectively), pancreatic necrosis occurred more frequently in AAP than BAP patients (OR = 1.58, 95% CI 1.08-2.30). Overall, there is a potential association between aetiology and the development and course of AP. HTG-AP is associated with the highest number of complications. Furthermore, AAP is likely to be more severe than BAP or PAP. Greater emphasis should be placed on determining aetiology on admission.

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Background: Lactose intolerance is a frequent gastrointestinal disease affecting 47% of the Eastern European population. Small intestinal bacterial overgrowth (SIBO) leads to carbohydrate malabsorption and therefore to false results during lactose breath and tolerance tests., Objectives: We aimed to assess the prevalence of lactose maldigestion and intolerance in Hungary and to investigate the role of combined diagnostic method and testing for SIBO in reducing false results., Methods: We retrospectively analyzed data from 264 adult symptomatic patients who underwent 50g lactose breath and tolerance tests in parallel over a one-year period at our center. A ≥20 ppm elevation of H2 or less than 1.1 mmol/l rise of blood glucose was diagnostic for lactose maldigestion. Patients with maldigestion who had symptoms during the test were defined as lactose intolerant. Patients with an early (≤90 min) significant (≥20 ppm) rise of H2 during lactose and/or lactulose breath tests were determined to have SIBO. Patients with slow/rapid oro-cecal transit and inappropriate preparation before the test were excluded., Results: 49.6% of the 264 patients had lactose maldigestion, and 29.5% had lactose intolerance. The most frequent symptom was bloating (22.7%), while 34.8% of the study population and 60% of the symptomatic patients had SIBO. In 9.1% and 9.8% of the patients, the lactose breath and tolerance test alone gave false positive result compared with the combined method. SIBO was present in 75% of the false positives diagnosed with breath test only., Conclusions: The prevalence of lactose intolerance is lower in Hungary compared to the Eastern European value (29.5% vs 47%), so it is worth performing a population-based prospective analysis in this area. A combination of lactose breath and tolerance tests and the careful monitoring of results (with early H2 rise, lactulose breath test, etc.) can decrease the false cases caused by e.g. SIBO., Competing Interests: The authors have declared that no competing interests exist.

Background: Effective and selective oral rinses are required in the daily medical and dental practice. Currently mouthwashes used have substantial side effects., Objectives: Our aim was to evaluate the efficacy of chlorine dioxide-containing mouthwashes in comparison with other previously established mouth rinses in healthy adults using oral hygiene indices., Methods: This work was registered in PROSPERO (CRD42018099059) and carried out using multiple databases and reported according to the PRISMA statement. The search terms used were "chlorine dioxide" AND "oral", and only randomised controlled trials (RCTs) were included. The primary outcome was the alteration of the plaque index (PI), while the secondary outcomes were the gingival index (GI) and bacterial counts. For the risk of bias assessment, the Cochrane Risk of Bias Tool was used. Statistical analysis for data heterogeneity was performed by Q-value and I2-tests., Results: 364 articles were found in the databases. After the selection process, only five RCTs were eligible for meta-analysis. Data heterogeneity was low. There were no statistical differences in effectiveness between chlorine dioxide and other effective mouth rinses in PI (0.720±0.119 vs 0.745±0.131; 95%; confidence intervals (CIs): 0.487-0.952 vs 0.489-1.001, respectively) and GI (0.712±0.130 vs 0.745±0.131; 95% CIs: 0.457-0.967 vs 0.489- 1.001, respectively) and also in bacterial counts., Conclusion: Chlorine dioxide reduces both plaque and gingival indices and bacterial counts in the oral cavity similar to other routinely used oral rinses, however, the evidence supporting this outcome is very limited. Therefore, further large scale RCTs are needed to decrease the risk of bias., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: C-reactive protein level (CRP) and white blood cell count (WBC) have been variably used in clinical trials on acute pancreatitis (AP). We assessed their potential role., Methods: First, we investigated studies which have used CRP or WBC, to describe their current role in trials on AP. Second, we extracted the data of 1435 episodes of AP from our registry. CRP and WBC on admission, within 24 h from the onset of pain and their highest values were analyzed. Descriptive statistical tools as Kruskal-Wallis, Mann-Whitney U , Levene's F tests, Receiver Operating Characteristic (ROC) curve analysis and AUC (Area Under the Curve) with 95% confidence interval (CI) were performed., Results: Our literature review showed extreme variability of CRP used as an inclusion criterion or as a primary outcome or both in past and current trials on AP. In our cohort, CRP levels on admission poorly predicted mortality and severe cases of AP; AUC: 0.669 (CI:0.569-0.770); AUC:0.681 (CI: 0.601-0.761), respectively. CRP levels measured within 24 h from the onset of pain failed to predict mortality or severity; AUC: 0.741 (CI:0.627-0.854); AUC:0.690 (CI:0.586-0.793), respectively. The highest CRP during hospitalization had equally poor predictive accuracy for mortality and severity AUC:0.656 (CI:0.544-0.768); AUC:0.705 (CI:0.640-0.769) respectively. CRP within 24 h from the onset of pain used as an inclusion criterion markedly increased the combined event rate of mortality and severe AP (13% for CRP > 25 mg/l and 28% for CRP > 200 mg/l)., Conclusion: CRP within 24 h from the onset of pain as an inclusion criterion elevates event rates and reduces the number of patients required in trials on AP.

In cases of difficult biliary cannulation, transpancreatic sphincterotomy (TPS) can be an alternative approach of biliary access. However, its success and safety profile have not been studied in detail. A systematic review and meta-analysis were performed to study the overall cannulation success and adverse events of TPS. These outcomes were also compared to other advanced cannulation methods. A systematic literature search was conducted to find all relevant articles containing data on TPS. Successful biliary cannulation and complications rates [post-ERCP pancreatitis (PEP), bleeding, and perforation rates] were compared in the pooled analyses of prospective comparative studies. The overall outcomes were calculated involving all studies on TPS. TPS was superior compared to needle-knife precut papillotomy (NKPP) and the double-guidewire method (DGW) regarding cannulation success (odds ratio [OR] 2.32; 95% confidence interval [CI] 1.37-3.93; and OR 2.72; 95% CI 1.30-5.69, respectively). The rate of PEP did not differ between TPS and NKPP or DGW; however, TPS (only retrospective studies were available for comparison) proved to be worse than needle-knife fistulotomy in this regard (OR 4.62; 95% CI 1.36-15.72). Bleeding and perforation rates were similar among these advanced techniques. There were no data about long-term consequences of TPS. The biliary cannulation rate of TPS is higher than that of the other advanced cannulation techniques, while the safety profile is similar to those. However, no long-term follow-up studies are available on the later consequences of TPS; therefore, such studies are strongly needed for its full evaluation.

Background: Unwarranted administration of antibiotics in acute pancreatitis presents a global challenge. The clinical reasoning behind the misuse is poorly understood. Our aim was to investigate current clinical practices and develop recommendations that guide clinicians in prescribing antibiotic treatment in acute pancreatitis., Methods: Four methods were used. 1) Systematic data collection was performed to summarize current evidence; 2) a retrospective questionnaire was developed to understand the current global clinical practice; 3) five years of prospectively collected data were analysed to identify the clinical parameters used by medical teams in the decision making process, and finally; 4) the UpToDate Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system was applied to provide evidence based recommendations for healthcare professionals., Results: The systematic literature search revealed no consensus on the start of AB therapy in patients with no bacterial culture test. Retrospective data collection on 9728 patients from 22 countries indicated a wide range (31-82%) of antibiotic use frequency in AP. Analysis of 56 variables from 962 patients showed that clinicians initiate antibiotic therapy based on increased WBC and/or elevated CRP, lipase and amylase levels. The above mentioned four laboratory parameters showed no association with infection in the early phase of acute pancreatitis. Instead, procalcitonin levels proved to be a better biomarker of early infection. Patients with suspected infection because of fever had no benefit from antibiotic therapy., Conclusions: The authors formulated four consensus statements to urge reduction of unjustified antibiotic treatment in acute pancreatitis and to use procalcitonin rather than WBC or CRP as biomarkers to guide decision-making., (Copyright © 2019 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Irritable bowel syndrome (IBS) affects 10%-20% of the adult population and is characterized by abdominal symptoms without relevant organic disease. There are numerous clinical trials available investigating the relationship between IBS, lactose maldigestion (LM), and lactose intolerance (LI), but there have been no meta-analyses on this topic yet. We aimed to assess the prevalence of LM, objective and subjective (self-reported) LI in IBS patients compared to healthy controls (HC) without IBS., Methods: A systematic literature search was conducted up to 24 April 2018 in PubMed, Embase, and Cochrane Library. Adult IBS patients had to be diagnosed according to the Rome criteria or other well-defined criteria system. We enrolled controlled studies including healthy adult participants without IBS, as control group. Odds ratios with 95% confidence intervals were calculated., Key Results: Altogether 14 articles were suitable for statistical analyses. IBS patients reported themselves significantly more frequently lactose intolerant than HCs (odds ratio [OR] = 3.499; 95% confidence interval [CI] = 1.622-7.551). Generally, there was no significant difference in the prevalence of LM based on ingested lactose dose (OR = 1.122; 95% CI = 0.929-1.356) and test type (OR = 1.156; 95% CI = 0.985-1.356). However, significantly more IBS patients had objective LI (OR = 2.521; 95% CI = 1.280-4.965)., Conclusions and Inferences: Lactose intolerance, but not LM is more frequent among patients with IBS compared to HCs. According to our results, IBS among other functional bowel disorders is a possible contributing factor of LI in people with LM., (© 2018 The Authors. Neurogastroenterology & Motility Published by John Wiley & Sons Ltd.)

Background and Aims: Experimental data suggest that the HLA-DQ2 gene dose has a strong quantitative effect on clinical outcomes and severity of celiac disease (CD). We aimed to conduct a meta-analysis with systematic review to investigate the association between HLA-DQB1*02 gene doses and the characteristics of CD., Methods: We searched seven medical databases for studies discussing HLA-DQB1 gene dose in CD and various disease characteristics, such as clinical presentation, histology, age at diagnosis, and comorbidities. Odds ratios (OR, for categorical variables) and weighted mean differences (for age) were calculated to compare patients with a double dose of HLA-DQB1*02 versus those with single and zero doses. Heterogeneity was tested with I2-statistics and explored by study subgroups (children and adults)., Results: Twenty-four publications were eligible for meta-analysis. Classical CD was more frequent with a double versus single dose of the HLA-DQB1*02 allele (OR = 1.758, 95%CI: 1.148-2.692, I2 = 0.0%). In pediatric studies, gene dose effect was more prominent (OR = 2.082, 95%CI: 1.189-3.646, I2 = 0.0% and OR = 3.139, 95%CI: 1.142-8.630, I2 = 0.0% for the comparisons of double versus single and double versus zero dose, respectively). Atrophic histology was more prevalent with a double versus zero dose (OR = 2.626, CI: 1.060-6.505, I2 = 21.3%). We observed no gene dose effect regarding diarrhea, age at diagnosis, the severity of villous atrophy, and the association with type 1 diabetes mellitus., Conclusion: A double dose of HLA-DQB1*02 gene seems to predispose patients to developing classical CD and villous atrophy. Risk stratification by HLA-DQB1*02 gene dose requires further clarification due to the limited available evidence., Competing Interests: The authors have declared that no competing interests exist.

Aims: Our aim was to summarize the available literature on the effect of short- versus long-course antibiotic therapy on acute cholangitis., Methods: A systematic review was performed according to the PRISMA Statement. We searched three databases for papers discussing the length of ABT in acute cholangitis. Long and short therapy groups were defined based on the most recent guideline available at the time of publication of the articles. Primary outcomes were the rate of recurrent cholangitis and mortality; secondary outcomes included length of hospitalization and the duration of fever after ERCP. Data were extracted on these outcomes and on general characteristics. A narrative synthesis was then provided based on collected data., Results: Out of 692 articles produced by our search, four met our inclusion and exclusion criteria. These contained 205 acute cholangitis patients, with 137 and 68 patients receiving short and long antibiotic therapy, respectively. No significant difference was observed in any of the studies on the outcomes of mortality and duration of fever after ERCP between the two groups. One out of four studies found the rate of recurrent cholangitis to be significantly lower in the short antibiotic therapy group (0.0% vs. 13.3%, p = 0.036). Length of hospitalization was only compared in the same retrospective article, where it was found to be significantly shorter in the short-term antibiotic therapy group (with a median of 14 vs. 17.5 days, p < 0.001)., Conclusions: Our review suggests short-course antibiotic therapy is non-inferior to long-course treatment; however, several limitations underline the need for well-designed randomized trials.

Objective: Preeclampsia (PE) is the leading cause of maternal and perinatal mortality around the world. The impaired function of fetal-placental vasculature is a key factor in PE. Several studies have investigated the connection between PE and endothelial dysfunction. Also, many authors have examined the changes in asymmetric dimethylarginine (ADMA) as a prominent marker of endothelial dysfunction. Our study aim is to review and analyse the connections between PE and ADMA levels., Methods: To obtain data we performed a comprehensive literature search in Pubmed, Embase and Web of Science. Standardized mean differences were used to estimate the differences in ADMA levels., Results: The quantitative analysis included 10 studies reporting a total number of 631 PE and 498 healthy pregnant individuals. We found significantly higher ADMA levels in PE patients compared to controls, when comparing the ADMA levels of the patients to the ADMA levels of the controls (z = 5.93, p < 0.001). This difference was present regardless of the measurement method. Regarding the onset of PE, we found significantly higher ADMA levels in patients suffering from early-onset PE when comparing the ADMA levels of the early-onset PE patients to that of the controls (z = 2.82, p = 0.005). However, we did not find such difference when we compared late-onset PE patients' ADMA levels to controls., Conclusion: ADMA is significantly higher in PE patients than in the controls. Elevated ADMA levels can play a major role in the development of PE, but more research is needed to clarify the connection between the two., (Copyright © 2018 Elsevier Ltd. All rights reserved.)