Transpancreatic sphincterotomy has a higher cannulation success rate than needle-knife precut papillotomy - a meta-analysis.

Background and aim While many studies have discussed the different cannulation techniques used in patients with difficult biliary access, no previous meta-analyses have compared transpancreatic sphincterotomy (TPS) to other advanced techniques. Therefore, we aimed to identify all studies comparing the efficacy and adverse event rates of TPS with needle-knife precut papillotomy (NKPP), the most commonly used technique, and to perform a meta-analysis. Methods The Embase, PubMed, and Cochrane databases were searched for trials comparing the outcomes of TPS with NKPP up till December 2016. A meta-analysis focusing on outcome (cannulation success, post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP), post-procedural bleeding, and total adverse events) was performed. The population, intervention, comparison, outcome (PICO) format was used to compare these cannulation approaches. Five prospective and eight retrospective studies were included in our meta-analysis. Results NKPP has a significantly lower success rate (odds ratio [OR] 0.50, P = 0.046; relative risk [RR] 0.92, P = 0.03) and a higher rate of bleeding complications (OR 2.24, P = 0.02; RR 2.18, P = 0.02) than TPS. However, no significant differences were found in PEP (OR 0.79, P = 0.24; RR 0.80, P = 0.19), perforation (risk difference [RD] 0.01, P = 0.23), or total complication rates (OR 1.22, P = 0.44; RR 1.17, P = 0.47). Conclusion While TPS has a higher success rate in difficult biliary access and causes less bleeding than NKPP, there are no differences in PEP, perforation, or total complication rates between the two approaches. We conclude that TPS, in the hands of expert endoscopists, is a safe procedure, which should be used more widely in patients with difficult biliary access.

Meta-Analysis of Early Nutrition: The Benefits of Enteral Feeding Compared to a Nil Per Os Diet Not Only in Severe, but Also in Mild and Moderate Acute Pancreatitis.

The recently published guidelines for acute pancreatitis (AP) suggest that enteral nutrition (EN) should be the primary therapy in patients suffering from severe acute pancreatitis (SAP); however, none of the guidelines have recommendations on mild and moderate AP (MAP). A meta-analysis was performed using the preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P). The following PICO (problem, intervention, comparison, outcome) was applied: P: nutrition in AP; I: enteral nutrition (EN); C: nil per os diet (NPO); and O: outcome. There were 717 articles found in Embase, 831 in PubMed, and 10 in the Cochrane database. Altogether, seven SAP and six MAP articles were suitable for analyses. In SAP, forest plots were used to illustrate three primary endpoints (mortality, multiorgan failure, and intervention). In MAP, 14 additional secondary endpoints were analyzed (such as CRP (C-reactive protein), WCC (white cell count), complications, etc.). After pooling the data, the Mann-Whitney U test was used to detect significant differences. Funnel plots were created for testing heterogeneity. All of the primary endpoints investigated showed that EN is beneficial vs. NPO in SAP. In MAP, all of the six articles found merit in EN. Analyses of the primary endpoints did not show significant differences between the groups; however, analyzing the 17 endpoints together showed a significant difference in favor of EN vs. NPO. EN is beneficial compared to a nil per os diet not only in severe, but also in mild and moderate AP.

Co-Administration of Proton Pump Inhibitors May Negatively Affect the Outcome in Inflammatory Bowel Disease Treated with Vedolizumab.

Concomitant medications may alter the effect of biological therapy in inflammatory bowel disease. The aim was to investigate the effect of proton pump inhibitors on remission rates in patients with inflammatory bowel disease treated with the gut-selective vedolizumab. Patients from the Hungarian nationwide, multicenter vedolizumab cohort were selected for post hoc analysis. Primary outcomes were the assessment of clinical response and endoscopic and clinical remission at weeks 14 and 54. Secondary outcomes were the evaluation of the combined effect of concomitant steroid therapy and other factors, such as smoking, on remission. A total of 108 patients were identified with proton pump inhibitor data from 240 patients in the original cohort. Patients on steroids without proton pump inhibitors were more likely to have a clinical response at week 14 than patients on concomitant PPI (95% vs. 67%, p = 0.005). Non-smokers with IBD treated with VDZ were more likely to develop a clinical response at week 14 than smokers, particularly those not receiving PPI compared with patients on co-administered PPI therapy (81% vs. 53%, p = 0.041, and 92% vs. 74%, p = 0.029, respectively). We found that the use of PPIs in patients treated with VDZ may impair the achievement of response in certain subgroups. Unnecessary PPI prescriptions should be avoided.

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.

Shared responsibility in the diagnosis and treatment of inflammatory bowel disease: When to refer a patient with inflammatory bowel disease to a biological therapy center? / Közös felelosség a gyulladásos bélbetegség diagnosztikájában és kezelésében: Mikor utaljuk a gyulladásos bélbetegséggel kezelt beteget biológiai terápiás centrumba?

Összefoglaló. Az idült betegségek, köztük a gyulladásos bélbetegség kezelése összetett feladat, amely a megfelelo technikai feltételek mellett naprakész szaktudással és tapasztalattal rendelkezo egészségügyi személyzet együttmuködését igényli. Célunk a gyulladásos bélbetegség ellátásának célirányos összegzése volt. Kiemelten foglalkoztunk a korai diagnosztika és szakorvoshoz utalás kérdésével, a korszeru ellátáshoz szükséges, személyre szabott terápia és a célértékre történo kezelés, valamint a biológiai terápiás centrumba utalás szükségességével. Részleteztük továbbá a kompetens és felelosségteljes gondozás ellátószintjeit, és bemutattuk az ellátásban együttmuködo multidiszciplináris csoport felépítését is. Az összefoglaló közleményhez a nemzetközi irodalmat és a hazai terápiás protokollokat tekintettük át. A krónikus betegségek gondozásában elengedhetetlen a társszakmák együttmuködése. A betegség kezelésében fontos a folyamatosan változó ajánlások, protokollok ismerete és a kompetenciaszintek elfogadása a beteg megfelelo életminoségének elérése és a szövodmények csökkentése céljából. Orv Hetil. 2021; 162(33): 1311-1317. Summary. The treatment of chronic diseases, including inflammatory bowel disease, is a complex task that requires the collaboration of health professionals with up-to-date expertise and experience under the appropriate technical conditions. Our aim was to systematically review the management of inflammatory bowel disease. We focused on the issue of early diagnosis and referral to a specialist, the need for personalized therapy and "treat-to-target" concept, and the appropriate timing of referral to a biological therapy center. The levels of competent and responsible care and the structure of a multidisciplinary team were also discussed. For the article, international and Hungarian therapeutic protocols and literature were reviewed. The collaboration of disciplines is essential in the management of chronic diseases. For disease management, it is critical to be up-to-date with changing recommendations, protocols, and to adopt competency levels to achieve a patient's adequate quality of life and reduce disease complications. Orv Hetil. 2021; 162(33): 1311-1317.

Comparable Long-Term Outcomes of Cyclosporine and Infliximab in Patients With Steroid-Refractory Acute Severe Ulcerative Colitis: A Meta-Analysis.

Background: In steroid-refractory acute severe ulcerative colitis (ASUC), cyclosporine (CYS) or infliximab (IFX) may be considered as a second-line alternative to avoid colectomy. There are short-term data reported, but until now, there is no meta-analysis regarding long-term outcomes of CYS and IFX in patients with ASUC. Aim: To compare long-term efficacy and safety of CYS and IFX in a meta-analysis. Methods: Three electronic databases (PubMed, Embase, Cochrane Central Register of Controlled Trials) were searched for studies which compared CYS vs. IFX in adults with ASUC. Long-term colectomy-free rate from 1 to 10 years during CYS or IFX therapy was collected, last updated up to 22nd May 2019. Primary outcome was long-term colectomy-free rate, secondary outcomes were adverse events (AE), serious adverse events (SAE), and mortality. Long-term colectomy-free survival and safety measures were pooled with the random-effect model. Odds ratios (OR) with 95% confidence intervals (CI) were calculated. Results: Data from 1,607 patients in 15 trials were extracted. In the first 3 years, pooled OR for colectomy-free survival was higher with IFX than with CYS (OR = 1.59, 95% CI: 1.11-2.29, p = 0.012; OR = 1.57, 95% CI: 1.14-2.18, p = 0.006; and OR = 1.75, 95% CI: 1.08-2.84, p = 0.024; at 1, 2, and 3 years, respectively). However, the significant difference remained undetected from the fourth year of follow-up and in subgroup of RCTs (OR = 1.35, 95% CI: 0.90-2.01, p = 0.143; OR = 1.41, 95% CI: 0.94-2.12, p = 0.096; and OR = 1.34, 95% CI: 0.89-2.00, p = 0.157; at 1, 2, and 3 years, respectively). No significant difference was detected regarding adverse events, serious adverse events and mortality between the groups. The neutral associations proved to be underpowered with trial sequential analysis. Conclusion: However observational studies show IFX as a better choice, according to the RCTs, choosing either CYS or IFX as rescue therapy for ASUC, the long-term outcomes are not different, although further large RCTs are warranted.

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.

Steroid but not Biological Therapy Elevates the risk of Venous Thromboembolic Events in Inflammatory Bowel Disease: A Meta-Analysis.

BACKGROUND AND AIMS: Inflammatory bowel disease [IBD] is associated with a 1.5- to 3-fold increased risk of venous thromboembolism [VTE] events. The aim of this study was to determine the risk of VTE in IBD as a complication of systemic corticosteroids and anti-tumour necrosis factor alpha [TNFα] therapies. METHODS: A systematic review and meta-analysis was conducted, which conforms to the Preferred Reporting Items for Systematic Reviews and Meta-analyses [PRISMA] statement. PubMed, EMBASE, Cochrane Library and Web of Science were searched for English-language studies published from inception inclusive of 15 April 2017. The population-intervention-comparison-outcome [PICO] format and statistically the random-effects and fixed-effect models were used to compare VTE risk during steroid and anti-TNFα treatment. Quality of the included studies was assessed using the Newcastle-Ottawa scale. The PROSPERO registration number is 42017070084. RESULTS: We identified 817 records, of which eight observational studies, involving 58518 IBD patients, were eligible for quantitative synthesis. In total, 3260 thromboembolic events occurred. Systemic corticosteroids were associated with a significantly higher rate of VTE complication in IBD patients as compared to IBD patients without steroid medication (odds ratio [OR]: 2.202; 95% confidence interval [CI]: 1.698-2.856, p < 0.001). In contrast, treatment with anti-TNFα agents resulted in a 5-fold decreased risk of VTE compared to steroid medication [OR: 0.267; 95% CI: 0.106-0.674, p = 0.005]. CONCLUSION: VTE risk should be carefully assessed and considered when deciding between anti-TNFα and steroids in the management of severe flare-ups. Thromboprophylaxis guidelines should be followed, no matter the therapy choice.

Association between AIRE gene polymorphism and rheumatoid arthritis: a systematic review and meta-analysis of case-control studies.

Autoimmune regulator (AIRE) is a transcription factor that functions as a novel player in immunological investigations. In the thymus, it has a pivotal role in the negative selection of naive T-cells during central tolerance. Experimental studies have shown that single nucleotide polymorphism (SNP) alters transcription of the AIRE gene. SNPs thereby provide a less efficient negative selection, propagate higher survival of autoimmune T-cells, and elevate susceptibility to autoimmune diseases. To date, only rheumatoid arthritis (RA) has been analysed by epidemiological investigations in relation to SNPs in AIRE. In our meta-analysis, we sought to encompass case-control studies and confirm that the association between SNP occurrence and RA. After robust searches of Embase, PubMed, Cochrane Library, and Web of Science databases, we found 19 articles that included five independent studies. Out of 11 polymorphisms, two (rs2075876, rs760426) were common in the five case-control studies. Thus, we performed a meta-analysis for rs2075876 (7145 cases and 8579 controls) and rs760426 (6696 cases and 8164 controls). Our results prove that rs2075876 and rs760426 are significantly associated with an increased risk of RA in allelic, dominant, recessive, codominant heterozygous, and codominant homozygous genetic models. These findings are primarily based on data from Asian populations.

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.

Is Heller myotomy better than balloon dilation? A meta-analysis.

BACKGROUND AND AIM: Endoscopic balloon dilation (EBD) and laparoscopic Heller myotomy (LHM) are the most commonly performed treatment options for achalasia. Decision between these treatment options is difficult. The aim of this meta-analysis was to evaluate the efficacy of EBD compared to LHM. METHODS: The electronic databases PubMed, Embase and Cochrane Controlled Trials Registry were systematically searched for the period between January 1, 1976 and December 31, 2015. Meta-analysis was performed using the PICOS (problem, intervention, comparison, outcome, study design) format. Efficacy and safety of EBD were compared to LHM. Forest plot analyses were used to illustrate the success rate, perforation rate and post-procedural gastroesophageal reflux. RESULTS: Using the search strategy, eight studies met the selection criteria and were included in the meta-analysis. The total number of patients included was 749 (360 in the EBD group and 389 in the LHM group). The success rate was lower in the EBD group than in the LHM group (OR=0.486; CI: 0.304-0.779; p=0.003). The rate of perforation did not differ significantly between the EBD and LHM group (RR= 0.635, CI: 0.340-1.186, p=0.154). The incidence of post-procedural symptomatic gastroesophageal reflux did not differ between the two treatment groups (RR=0.663, CI: 0.328-1.343, p=0.254). CONCLUSION: Our data suggest that the efficacy of LHM is superior to that of EBD, while there is no difference in safety between the two treatment groups.

High versus low energy administration in the early phase of acute pancreatitis (GOULASH trial): protocol of a multicentre randomised double-blind clinical trial.

INTRODUCTION: Acute pancreatitis (AP) is an inflammatory disease with no specific treatment. Mitochondrial injury followed by ATP depletion in both acinar and ductal cells is a recently discovered early event in its pathogenesis. Importantly, preclinical research has shown that intracellular ATP delivery restores the physiological function of the cells and protects from cell injury, suggesting that restoration of energy levels in the pancreas is therapeutically beneficial. Despite several high quality experimental observations in this area, no randomised trials have been conducted to date to address the requirements for energy intake in the early phase of AP. METHODS/DESIGN: This is a randomised controlled two-arm double-blind multicentre trial. Patients with AP will be randomly assigned to groups A (30 kcal/kg/day energy administration starting within 24 hours of hospital admission) or B (low energy administration during the first 72 hours of hospital admission). Energy will be delivered by nasoenteric tube feeding with additional intravenous glucose supplementation or total parenteral nutrition if necessary. A combination of multiorgan failure for more than 48 hours and mortality is defined as the primary endpoint, whereas several secondary endpoints such as length of hospitalisation or pain will be determined to elucidate more detailed differences between the groups. The general feasibility, safety and quality checks required for high quality evidence will be adhered to. ETHICS AND DISSEMINATION: The study has been approved by the relevant organisation, the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (55961-2/2016/EKU). This study will provide evidence as to whether early high energy nutritional support is beneficial in the clinical management of AP. The results of this trial will be published in an open access way and disseminated among medical doctors. TRIAL REGISTRATION: The trial has been registered at the ISRCTN (ISRTCN 63827758).