MiR-200b categorizes patients into pancreas cystic lesion subgroups with different malignant potential.

Extracellular vesicles (EV) carry their cargo in a membrane protected form, however, their value in early diagnostics is not well known. Although pancreatic cysts are heterogeneous, they can be clustered into the larger groups of pseudocysts (PC), and serous and mucinous pancreatic cystic neoplasms (S-PCN and M-PCN, respectively). In contrast to PCs and S-PCNs, M-PCNs may progress to malignant pancreatic cancers. Since current diagnostic tools do not meet the criteria of high sensitivity and specificity, novel methods are urgently needed to differentiate M-PCNs from other cysts. We show that cyst fluid is a rich source of EVs that are positive and negative for the EV markers CD63 and CD81, respectively. Whereas we found no difference in the EV number when comparing M-PCN with other pancreatic cysts, our EV-based biomarker identification showed that EVs from M-PCNs had a higher level of miR-200b. We also prove that not only EV-derived, but also total cyst fluid miR-200b discriminates patients with M-PCN from other pancreatic cysts with a higher sensitivity and specificity compared to other diagnostic methods, providing the possibility for clinical applications. Our results show that measuring miR-200b in cyst fluid-derived EVs or from cyst fluid may be clinically important in categorizing patients.

[Cholangitis and cholecystitis: diagnostic criteria and management]. / Epeút- és epehólyag-gyulladás: diagnosztikus kritériumok és terápia.

In developed countries, diseases of the gallbladder and the biliary tract count as some of the most frequent gastrointestinal disorders. The inflammation of the gallbladder/biliary tree is a potentially severe, even lethal condition that requires rapid diagnosis and early multidisciplinary approach to be treated. Although the frequency of these diseases is high, the treatment is not unified in Hungary yet. The aim of the evidence-based recommendation is to clarify the diagnostic criteria and severity grading of these diseases and to highlight the indications and rules of proper application of the numerous available therapeutic interventions. The recent guideline is based on the consensus of the Board members of the Endoscopic Section of the Hungarian Gastroenterology Society in contribution with renown experts of surgery, infectology as well as interventional radiology and it counts as a clear and easy applicable guide during the all-day healthcare practice. Our guidelines are based on Tokyo guidelines established on the basis of the consensus reached in the International Consensus Meeting held in Tokyo which were revised in 2013 (TG13) and in 2018 (TG18). Orv Hetil. 2023; 164(20): 770-787.

Quantitative Software Analysis of Endoscopic Ultrasound Images of Pancreatic Cystic Lesions.

Endoscopic ultrasonography (EUS) is the most accurate imaging modality for the evaluation of different types of pancreatic cystic lesions. Our aim was to analyze EUS images of pancreatic cystic lesions using an image processing software. We specified the echogenicity of the lesions by measuring the gray value of pixels inside the selected areas. The images were divided into groups (serous cystic neoplasm /SCN/, intraductal papillary mucinous neoplasms and mucinous cystic neoplasms /Non-SCN/ and Pseudocyst) according to the pathology results of the lesions. Overall, 170 images were processed by the software: 81 in Non-SCN, 30 in SCN and 59 in Pseudocyst group. The mean gray value of the entire lesion in the Non-SCN group was significantly higher than in the SCN group (27.8 vs. 18.8; p < 0.0005). The area ratio in the SCN, Non-SCN and Pseudocyst groups was 57%, 39% and 61%, respectively; significantly lower in the Non-SCN group than in the SCN or Pseudocyst groups (p < 0.0005 and p < 0.0005, respectively). The lesion density was also significantly higher in the Non-SCN group compared to the SCN or Pseudocyst groups (4186.6/mm2 vs. 2833.8/mm2 vs. 2981.6/mm2; p < 0.0005 and p < 0.0005, respectively). The EUS image analysis process may have the potential to be a diagnostic tool for the evaluation and differentiation of pancreatic cystic lesions.

Preoperative Serum Carbohydrate Antigen 19-9 Levels Cannot Predict the Surgical Resectability of Pancreatic Cancer: A Meta-Analysis.

Background and Aims: Pancreatic ductal adenocarcinoma has one of the worst prognosis of all malignancies. This investigated the relationship between the preoperative serum carbohydrate antigen 19-9 and surgical resectability. Methods: A systematic search was performed in three databases (MEDLINE, EMBASE, and Web of Science) to compare the surgical resectability of pancreatic ductal adenocarcinoma in patients with high and low preoperative serum carbohydrate antigen 19-9 values. The receiving operating characteristic curves were constructed and the weighted mean differences for preoperative serum carbohydrate antigen 19-9 levels of resectable and unresectable groups of patients were calculated. The PROSPERO registration number is CRD42019132522. Results: Results showed that there was a significant difference in resectability between the low and high carbohydrate antigen 19-9 groups. Six out of the eight studies utilised receiver operating characteristic curves in order to find the cut-off preoperative carbohydrate antigen 19-9 levels marking unresectability. The overall result from the pooled area under curve values from the receiver operating characteristic curves was 0.794 (CI: 0.694-0.893), showing that the preoperative carbohydrate antigen 19-9 level is a "fair" marker of resectability. The result of the pooled weighted mean differences was 964 U/ml (p < 0.001) showing that there is a significant carbohydrate antigen 19-9 difference between the resectable and unresectable groups. Based on the results of the I-squared test, the result was 87.4%, accounting for "considerable" heterogeneity within the population. Conclusion: Carbohydrate antigen 19-9 is not a reliable marker of unresectability, it should not be used on its own in surgical decision-making.

Percutaneous transhepatic drainage is safe and effective in biliary obstruction-A single-center experience of 599 patients.

BACKGROUND: Historically, surgical bilioenteric bypass was the only treatment option for extrahepatic bile duct obstruction, but with technological advancements, percutaneous transhepatic drainage (PTD) and endoscopic solutions were introduced as a less invasive alternative. Endoscopic methods may lead to a decreasing indication of PTD in the future, but today it is still the standard treatment method, especially in hilar obstructions. METHODS: In our retrospective data analysis, we assessed technical success rate, reintervention rate, morbidity, mortality, and the learning curve of patients treated with PTD over 12 years in a tertiary referral center. RESULTS: 599 patients were treated with 615 percutaneous interventions. 94.5% (566/599) technical success rate; 2.7% (16/599) reintervention rate were achieved. 111 minor and 22 major complications occurred including 1 case of death. In perihilar obstruction, cholangitis were significantly more frequent in cases where endoscopic retrograde cholangiopancreatography had also been performed prior to PTD compared to PTD alone, with 39 (18.2%) and 15 (10.5%) occurrences, respectively. DISCUSSION: The results and especially the excellent success rates demonstrate that PTD is safe and effective, and it is appropriate for first choice in the treatment algorithm of perihilar stenosis. Ultimately, we concluded that PTD should be performed in experienced centers to achieve low mortality, morbidity, and high success rates.

Shared extracellular vesicle miRNA profiles of matched ductal pancreatic adenocarcinoma organoids and blood plasma samples show the power of organoid technology.

Extracellular vesicles (EV) are considered as a promising diagnostic tool for pancreatic ductal adenocarcinoma (PDAC), a disease with a poor 5-year survival that has not improved in the past years. PDAC patient-derived 3D organoids maintain the intratumoral cellular heterogeneity, characteristic for the tumor in vivo.Thus, they represent an ideal in vitro model system to study human cancers. Here we show that the miRNA cargo of EVs from PDAC organoids largely differs among patients. However, we detected a common set of EV miRNAs that were present in matched organoids and blood plasma samples of individual patients. Importantly, the levels of EV miR-21 and miR-195 were higher in PDAC blood EV preparations than in healthy controls, albeit we found no difference compared to chronic pancreatitis (CP) samples. In addition, here we report that the accumulation of collagen I, a characteristic change in the extracellular matrix (ECM) in both CP and PDAC, largely increases EV release from pancreatic ductal organoids. This provides a possible explanation why both CP and PDAC patient-derived plasma samples have an elevated amount of CD63 + EVs. Collectively, we show that PDAC patient-derived organoids represent a highly relevant model to analyze the cargo of tumor cell-derived EVs. Furthermore, we provide evidence that not only driver mutations, but also changes in the ECM may critically modify EV release from pancreatic ductal cells.

Hydroxyapatite-coated implants provide better fixation in total knee arthroplasty. A meta-analysis of randomized controlled trials.

BACKGROUND: The potential advantages of hydroxyapatite (HA)-coated cementless total knee arthroplasty (TKA) implants are bone stock preservation and biological fixation. Studies comparing the outcomes of HA-coated cementless, non HA-coated cementless (uncemented) and cemented TKA implants reported contradictory data. Our aim was to provide a comparison of the effects of HA coating of tibial stem on the stability and functionality of TKA implants. METHODS: A systematic literature search was performed using MEDLINE, Scopus, EMBASE and the CENTRAL databases up to May 31st, 2019. The primary outcome was Maximum Total Point Motion (MTPM) of the tibial stem. This parameter is determined by radiosterometric analysis and refers to the migration pattern of the prosthesis stems. The clinical outcomes of the implanted joints were evaluated by the Knee Society Knee Score (KSS) and the Knee Society Function Score (KFS). Weighted mean difference (WMD) with 95% confidence interval (CI) were calculated with the random-effects model. RESULTS: Altogether, 11 randomized controlled trials (RCTs) with 902 patients for primary TKA implants were included. There was a statistically significant difference in the MTPM values with the use of HA-coated and uncoated uncemented implants (WMD = +0.28, CI: +0.01 to +0.56, P<0.001). However, HA-coated stems showed significantly higher migration when compared with the cemented prostheses (WMD = -0.29, CI: -0.41 to -0.16, P<0.001). The KSS values of HA-coated implants were significantly higher than those for the uncemented implants; moreover, KSS and KFS outcome scores were statistically not different between the HA-coated and cemented prosthesis cases. CONCLUSION: HA-coating yields better stability than other, uncemented prostheses. More importantly, the HA-coating is not outperformed by cemented prosthesis in providing good functional outcome.

International Consensus Guidelines for Risk Factors in Chronic Pancreatitis. Recommendations from the working group for the international consensus guidelines for chronic pancreatitis in collaboration with the International Association of Pancreatology, the American Pancreatic Association, the Japan Pancreas Society, and European Pancreatic Club.

BACKGROUND: Chronic pancreatitis (CP) is a complex inflammatory disease with remarkably impaired quality of life and permanent damage of the pancreas. This paper is part of the international consensus guidelines on CP and presents the consensus on factors elevating the risk for CP. METHODS: An international working group with 20 experts on CP from the major pancreas societies (IAP, APA, JPS, and EPC) evaluated 14 statements generated from evidence on four questions deemed to be the most clinically relevant in CP. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the level of evidence available per statement. To determine the level of agreement, the working group voted on the 14 statements for strength of agreement, using a nine-point Likert scale in order to calculate Cronbach's alpha reliability coefficient. RESULTS: Strong consensus and agreement were obtained for the following statements: Alcohol, smoking, and certain genetic alterations are risk factors for CP. Past history, family history, onset of symptoms, and life-style factors including alcohol intake and smoking history should be determined. Alcohol consumption dose-dependently elevates the risk of CP up to 4-fold. Ever smokers, even smoking less than a pack of cigarettes per day, have an increased risk for CP, as compared to never smokers. CONCLUSIONS: Both genetic and environmental factors can markedly elevate the risk for CP. Therefore, health-promoting lifestyle education and in certain cases genetic counselling should be employed to reduce the incidence of CP.

Sarcopenia as an independent predictor of the surgical outcomes of patients with inflammatory bowel disease: a meta-analysis.

Patients with inflammatory bowel disease (IBD) are at risk of sarcopenia, which is associated with poor clinical outcomes. We conducted this study to assess whether sarcopenia predicts the need for surgery and postoperative complications in patients with IBD. We performed a systematic search of four electronic databases, last updated in March, 2019. Data from studies comparing rates of surgery and postoperative complications in sarcopenic IBD patients versus non-sarcopenic IBD patients were pooled with the random-effects models. We calculated the odds ratios (OR) with a 95% confidence interval (CI). Ten studies with a collective total of 885 IBD patients were included in our meta-analysis. Although the analysis of raw data did not reveal significant differences between the two groups with respect to the rate of surgery and postoperative complications (OR = 1.826; 95% CI 0.913-3.654; p = 0.089 and OR = 3.265; 95% CI 0.575-18.557; p = 0.182, respectively), the analysis of adjusted data identified sarcopenia as an independent predictor for both of the undesirable outcomes (OR = 2.655; 95% CI 1.121-6.336; p = 0.027 and OR = 6.097; 95% CI 1.756-21.175; p = 0.004, respectively). Thus, early detection of sarcopenia in patients with IBD is important to prevent undesirable outcomes.

A novel percutaneous transhepatic treatment of a benign bile duct stricture - a pilot study.

AIM: To assess the effectiveness and outcome of repeated percutaneous transhepatic balloon dilatation combined with targeted intramucosal corticosteroid injection in patients with benign biliary stricture. METHODS: This single-center pilot study, conducted between February 2014 and June 2016, involved five patients with benign biliary stricture (4 men and 1 woman, mean age 58.2 years). The study included only patients in whom previous surgical or/and non-surgical treatments failed or could not be performed due to patients' medical history and local status. RESULTS: We successfully developed an alternative treatment for patients with benign biliary stricture and performed it without side effects. There were no major complications, and the only one minor complication was cholangitis. In the median follow-up period of 30.24 months (range 14.5 to 44.6 months), no re-occlusion was detected. The disease-free survival, calculated after excluding the first patient (who died of heart attack), was 34.175 months. CONCLUSION: Percutaneous transhepatic corticosteroid injection combined with balloon dilatation could provide an alternative method for the treatment of benign biliary strictures that is effective in the long term and results in positive outcomes.

Baveno Criteria Safely Identify Patients With Compensated Advanced Chronic Liver Disease Who Can Avoid Variceal Screening Endoscopy: A Diagnostic Test Accuracy Meta-Analysis.

Background: The Baveno VI Consensus Workshop defined criteria (liver stiffness measured by transient elastography <20 kPa and platelet count >150 × 109 cells/L) to identify those patients with compensated advanced chronic liver diseases (cACLD) who are unlikely to have varices needing treatment (VNTs) and can safely avoid variceal screening endoscopy. This meta-analysis aimed to quantify the safety and efficacy of these criteria in suspected cACLD with liver stiffness >10 kPa and in compensated chronic liver diseases (cCLD) irrespective of liver stiffness. Methods: A systematic search was conducted in nine databases for studies discussed cACLD or cCLD and tested Baveno criteria against variceal screening endoscopy. The main safety and efficacy endpoints were missed VNT rate and spared endoscopy rate (SER), respectively; calculated with the random effect model. Pooled sensitivity, specificity, and area under the curve (AUC) were calculated with the hierarchical summary receiver operating characteristic model. For all outcome measures, 95% confidence intervals were computed. Heterogeneity was tested with I 2-statistics. Results: The search yielded 13 studies including 4,464 patients which reported on suspected cACLD. Pooled missed VNT rate was 0.3% (0.1-0.6%; I 2 = 45.5%), pooled SER was 32.8% (24.8-41.4%; I 2 = 97.0%). Sensitivity, specificity, and AUC of Baveno criteria were 97% (95-98%), 41% (27-57%), and 96% (94-97%), respectively. In the subgroups of cACLD from hepatitis C and B viruses, non-alcoholic fatty liver disease/steatohepatitis, or alcohol, missed VNT rates were 0.0% (0.0-0.3%), 1.2% (0.4-2.2%), 0.0% (0.0-1.3%), or 0.0% (0.0-0.4%), while SERs were 24.2% (20.5-28.1%), 24.9% (21.7-28.4%), 38.6% (10.9-70.8%), or 27.0% (16.9-38.4%), respectively. If we expanded the study population to cCLD, 27 studies included 7,534 patients. Missed VNT rate was 0.2% (0.1-0.5%; I 2 = 39.8%) with a SER of 30.5% (25.2-36.2%; I 2 = 96.1%) while Se, Sp, and AUC were 97% (93-99%), 35% (27-44%), and 80% (77-84%), respectively. Conclusions: The application of Baveno criteria significantly reduces the number of unnecessary variceal screening endoscopies while being safe: cACLD patients with liver stiffness <20 kPa and platelet count > 150 × 109 cells/L carry a very low chance (i.e., 0.3%) of having VNTs. The criteria preserve low missed VNT rate with lower diagnostic performance among cCLD patients.

Antibiotic therapy in acute pancreatitis: From global overuse to evidence based recommendations.

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.

Classical celiac disease is more frequent with a double dose of HLA-DQB1*02: A systematic review with meta-analysis.

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.

From eosinophilic esophagitis to esophagus perforation: clinical management strategies.

INTRODUCTION: Eosinophilic esophagitis is a chronic, antigen-mediated inflammation of the esophagus. The disease is most common at young ages, with a male to female ratio of 3:1. Eosinophilic granulocyte infiltration induced by oral/aeroantigens in the esophagus, mucosal hyperplasia, and fibrosis of the subepithelial layers can lead to constriction, dysphagia, blockage and esophageal perforation. CASE REPORT: A 36-year-old male patient presented in June 2016 with dysphagia as the main complaint. Workup with plain chest radiography with a water soluble contrast swallow did not reveal any pathological lesions. The patient's swallowing difficulties persisted and one year later he was treated by esophageal food bolus impaction (EFBI) in another institution. A new plain chest radiography with a water soluble contrast swallow confirmed a 9 cm long stricture in the middle third with an EFBI. During gastroscopy, a clinical picture of eosinophilic esophagitis was noted, with partially destroyed foreign body at 25cm and iatrogenic perforation at the upper half of the esophagus. After preoperative intensive care unit valuation and preparation, transhiatal esophagectomy without thoracotomy and cervical esophagostomy was performed with pyloromyotomy and feeding jejunostomy. The postoperative period was uneventful. Histological examination confirmed the presence of strictures and perforation on the background of eosinophilic esophagitis. Elective esophageal reconstruction with cervical esophagogastric anastomosis was performed on January 2018. Control blood tests revealed persistent eosinophilia, while the plain chest radiography with a water soluble contrast swallow showed no contrast leakage. Per os nutrition was resumed and the patient was discharged in good general condition. CONCLUSIONS: Eosinophilic esophagitis is a rare and difficult to diagnose entity due to its non-specific clinical presentation. In order to avoid complications and undesired delay in diagnosis, one should take into consideration this entity in every clinical situation of a young male patient with swallowing complaints.

The common truncation variant in pancreatic lipase related protein 2 (PNLIPRP2) is expressed poorly and does not alter risk for chronic pancreatitis.

A nonsense variant (p.W358X) of human pancreatic lipase related protein 2 (PNLIPRP2) is present in different ethnic populations with a high allele frequency. In cell culture experiments, the truncated protein mainly accumulates inside the cells and causes endoplasmic reticulum stress. Here, we tested the hypothesis that variant p.W358X might increase risk for chronic pancreatitis through acinar cell stress. We sequenced exon 11 of PNLIPRP2 in a cohort of 256 subjects with chronic pancreatitis (152 alcoholic and 104 non-alcoholic) and 200 controls of Hungarian origin. We observed no significant difference in the distribution of the truncation variant between patients and controls. We analyzed mRNA expression in human pancreatic cDNA samples and found the variant allele markedly reduced. We conclude that the p.W358X truncation variant of PNLIPRP2 is expressed poorly and has no significant effect on the risk of chronic pancreatitis.

Detection and proteomic characterization of extracellular vesicles in human pancreatic juice.

AIMS: The prognosis of patients with pancreatic cancer has remained virtually unchanged with a high mortality rate compared to other types of cancers. An earlier detection would provide a time window of opportunity for treatment and prevention of deaths. In the present study we investigated extracellular vesicle (EV)-associated potential biomarkers for pancreatic cancer by directly assessing EV size-based subpopulations in pancreatic juice samples of patients with chronic pancreatitis or pancreatic cancer. In addition, we also studied blood plasma and pancreatic cancer cell line-derived EVs. METHODS: Comparative proteomic analysis was performed of 102 EV preparations from human pancreatic juices, blood, and pancreatic cancer cell lines Capan-1 and MIA PaCa-2. EV preparations were also characterized by electron microscopy, tunable resistive pulse sensing, and flow cytometry. RESULTS: Here we describe the presence of EVs in human pancreatic juice samples. Pancreatic juice EV-associated proteins that we identified as possible candidate markers for pancreatic cancer included mucins, such as MUC1, MUC4, MUC5AC, MUC6 and MUC16, CFTR, and MDR1 proteins. These candidate biomarkers could also be detected by flow cytometry in EVs found in pancreatic juice and those secreted by pancreatic cancer cell lines. CONCLUSIONS: Together our data show that detection and characterization of EVs directly in pancreatic juice is feasible and may prove to be a valuable source of potential biomarkers of pancreatic cancer.

PPIs Prevent Aspirin-Induced Gastrointestinal Bleeding Better than H2RAs. A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: Aspirin is one of the most widely used medication for its analgesic and anti-platelet properties and thus a major cause for gastrointestinal (GI) bleeding. This study compared the preventive effect of histamine-2 receptor antagonists (H2RAs) and proton-pump inhibitors (PPIs) against chronic low-dose aspirin (LDA)-related GI bleeding and ulcer formation. METHODS: Electronic databases of Pubmed, Embase and Cochrane Central Register of Controlled Trials were searched for human observations (randomised controlled trials and observational studies) comparing the long term effects of PPIs and H2RAs treatment in the prevention of GI bleeding or ulcer formation in patients on chronic LDA treatment listed up till September 30, 2016. Two independent authors searched databases using PICO questions (aspirin, H2RA, PPI, GI bleeding or ulcer), and reviewed abstracts and articles for comprehensive studies keeping adequate study quality. Data of weighted odds ratios were statistically evaluated using Comprehensive Metaanalysis (Biostat, Inc., Engelwood, MJ, USA), potential bias was checked. RESULTS: Nine studies for GI bleeding and eight studies for ulcer formation were found meeting inclusion criteria, altogether 1,879 patients were included into review. The H2RAs prevented less effectively LDA-related GI bleeding (OR= 2.102, 95% CI: 1.008-4.385, p<0.048) and ulcer formation (OR= 2.257, 95% CI: 1.277-3.989, p<0.005) than PPIs. CONCLUSION: The meta-analysis showed that H2RAs were less effective in the prevention of LDA-related GI bleeding and ulcer formation suggesting the preferable usage of PPIs in case of tolerance.

In middle-aged and old obese patients, training intervention reduces leptin level: A meta-analysis.

BACKGROUND: Leptin is one of the major adipokines in obesity that indicates the severity of fat accumulation. It is also an important etiological factor of consequent cardiometabolic and autoimmune disorders. Aging has been demonstrated to aggravate obesity and to induce leptin resistance and hyperleptinemia. Hyperleptinemia, on the other hand, may promote the development of age-related abnormalities. While major weight loss has been demonstrated to ameliorate hyperleptinemia, obese people show a poor tendency to achieve lasting success in this field. The question arises whether training intervention per se is able to reduce the level of this adipokine. OBJECTIVES: We aimed to review the literature on the effects of training intervention on peripheral leptin level in obesity during aging, in order to evaluate the independent efficacy of this method. In the studies that were included in our analysis, changes of adiponectin levels (when present) were also evaluated. DATA SOURCES: 3481 records were identified through searching of PubMed, Embase and Cochrane Library Database. Altogether 19 articles were suitable for analyses. STUDY ELIGIBILITY CRITERIA: Empirical research papers were eligible provided that they reported data of middle-aged or older (above 45 years of age) overweight or obese (body mass index above 25) individuals and included physical training intervention or at least fitness status of groups together with corresponding blood leptin values. STATISTICAL METHODS: We used random effect models in each of the meta-analyses calculating with the DerSimonian and Laird weighting methods. I-squared indicator and Q test were performed to assess heterogeneity. To assess publication bias Egger's test was applied. In case of significant publication bias, the Duval and Tweedie's trim and fill algorithm was used. RESULTS: Training intervention leads to a decrease in leptin level of middle-aged or older, overweight or obese male and female groups, even without major weight loss, indicated by unchanged serum adiponectin levels. Resistance training appears to be more efficient in reducing blood leptin level than aerobic training alone. CONCLUSIONS: Physical training, especially resistance training successfully reduces hyperleptinemia even without diet or major weight loss.