PPIs Are Not Responsible for Elevating Cardiovascular Risk in Patients on Clopidogrel—A Systematic Review and Meta-Analysis

Background: Clopidogrel and proton pump inhibitors (PPIs) are metabolized by cytochrome P450 enzymes. Contradictory results have been reported on possible complications of simultaneous PPI and clopidogrel use. Our aim was to investigate the clinical relevance of this debate with a systematic review and meta-analysis.Methods: The PubMed, Embase, and Cochrane Central Register of Controlled Trials electronic databases were searched for human studies [randomized controlled trials (RCTs) and observational studies] using the PICO format (P: patients on clopidogrel; I: patients treated with PPI; C: patients without PPI treatment; O: cardiovascular risk). We screened eligible studies from 2009 to 2016. After study exclusions, we extracted data from 27 articles for three outcomes: major adverse cardiac event (MACE), myocardial infarction (MI) and cardiovascular (CV) death. The meta-analysis was registered on PROSPERO (CRD42017054316).Results: Data were extracted on 156,823 patients from the 27 trials included (MACE: 23, CV death: 10, MI: 14). The risks of MACE (RR = 1.22, 95% CI = 1.06–1.396, p = 0.004) and MI (RR = 1.43, 95% CI = 1.24–1.66, p < 0.001) were significantly higher in the PPI plus clopidogrel group. However, subgroup analysis demonstrated that this significance disappeared in RCTs (RR = 0.99, 95% CI = 0.76–1.28, p = 0.93) in the MACE outcome group. There was no effect of combined PPI and clopidogrel therapy on CV death outcome (RR = 1.21, 95% CI = 0.97–1.50, p = 0.09).Conclusion: Concomitant use of PPIs and clopidogrel has been proved not to be associated with elevated cardiovascular risks according to RCTs. Based on our results, no restrictions should be applied whenever PPIs and clopidogrel are administered simultaneously

Fatty Pancreas Is a Risk Factor for Pancreatic Cancer: A Systematic Review and Meta-Analysis of 2956 Patients

Pancreatic cancer (PC) is one of the most lethal cancers worldwide. Recently, fatty pancreas (FP) has been studied thoroughly, and although its relationship to PC is not fully understood, FP is suspected to contribute to the development of PC. We aimed to assess the association between PC and FP by conducting a systematic review and meta-analysis. We systematically searched three databases, MEDLINE, Embase, and CENTRAL, on 21 October 2022. Case-control and cross-sectional studies reporting on patients where the intra-pancreatic fat deposition was determined by modern radiology or histology were included. As main outcome parameters, FP in patients with and without PC and PC in patients with and without FP were measured. Proportion and odds ratio (OR) with a 95% confidence interval (CI) were used for effect size measure. PC among patients with FP was 32% (OR 1.32; 95% CI 0.42-4.16). However, the probability of having FP among patients with PC was more than six times higher (OR 6.13; 95% CI 2.61-14.42) than in patients without PC, whereas the proportion of FP among patients with PC was 0.62 (95% CI 0.42-0.79). Patients identified with FP are at risk of developing PC. Proper screening and follow-up of patients with FP may be recommended

Exosomes as prognostic biomarkers in pancreatic ductal adenocarcinoma—a systematic review and meta-analysis

Extensive research is focused on the role of liquid biopsy in pancreatic cancer since reliable diagnostic and follow-up biomarkers represent an unmet need for this highly lethal malignancy. We performed a systematic review and meta-analysis on the prognostic value of exosomal biomarkers in pancreatic ductal adenocarcinoma (PDAC). MEDLINE, Embase, Scopus, Web of Science, and CENTRAL were systematically searched on the 18th of January, 2021 for studies reporting on the differences in overall (OS) and progression-free survival (PFS) in PDAC patients with positive versus negative exosomal biomarkers isolated from blood. The random-effects model estimated pooled multivariate-adjusted (AHR) and univariate hazard ratios (UHRs) with 95% confidence intervals (CIs). Eleven studies comprising 634 patients were eligible for meta-analysis. Detection of positive exosomal biomarkers indicated increased risk of mortality (UHR=2.81, CI:1.31-6,00, I2=88.7%, p<0.001), and progression (UHR=3.33, CI: 2.33-4.77, I2=0, p=0.879) across various disease stages. Positive exosomal biomarkers identified preoperatively revealed a higher risk of mortality in resectable stages (UHR=5.55, CI: 3.24-9.49, I2=0, p=0.898). The risk of mortality in unresectable stages was not significantly increased with positive exosomal biomarkers (UHR=2.51, CI: 0.55-11.43, I2=90.3%, p<0.001). Detectable exosomal micro ribonucleic acids were associated with a decreased OS (UHR=4.08, CI: 2.16-7.69, I2=46.9%, p=0.152) across various stages. Our results reflect the potential of exosomal biomarkers for prognosis evaluation in PDAC. The associated heterogeneity reflects the variability of study methods and need for their uniformization before transition to clinical use

Antimicrobial Efficacy of Chlorhexidine and Sodium Hypochlorite in Root Canal Disinfection: A Systematic Review and Meta-analysis of Randomized Controlled Trials

We aimed to compare the antimicrobial efficacy of chlorhexidine (CHX) and sodium hypochlorite (NaOCl), two irrigants routinely used in root canal therapy of permanent teeth.Electronic databases, including PubMed, EMBASE, Web of Science, and Cochrane Library, were searched for randomized controlled trials published until March 2020. The meta-analysis of relative risk (RR) and standardized mean difference (SMD) was performed using a random-effect model with a 95% confidence interval (CI). Subgroup analysis was performed for culture and molecular methods of bacterial detection.The literature search yielded 2,110 records without duplicates. Eight studies were eligible for a systematic review. No significant differences in the incidence of samples with positive bacterial growth after irrigation (RR=1.003, 95% CI: 0.729-1.380, p=0.987) and mean bacterial number changes (SMD=0.311, 95% CI: -0.368-0.991, p=0.369) were observed between CHX and NaOCl in the culture and molecular subgroups. Heterogeneity in RR (I2=0%, p=0.673) was low among studies, while considerable heterogeneity was observed in the analysis of SMD (I2=76.336%, p=0.005).Our findings suggest that both CHX and NaOCl can reduce bacterial infections after irrigation, without any significant difference in antimicrobial efficacy between them. Although CHX and NaOCl showed similar efficacy, their molecular mechanisms were different. Therefore, they can be used as the main antibacterial root canal irrigants. However, our results were limited by inconsistencies among retrieved articles and a lack of clinically relevant outcomes. Further well-designed clinical studies are warranted to supplement our results

Restoration of energy level in the early phase of acute pediatric pancreatitis

Acute pancreatitis (AP) is a serious inflammatory disease with rising incidence both in the adult and pediatric populations. It has been shown that mitochondrial injury and energy depletion are the earliest intracellular events in the early phase of AP. Moreover, it has been revealed that restoration of intracellular ATP level restores cellular functions and defends the cells from death. We have recently shown in a systematic review and meta-analysis that early enteral feeding is beneficial in adults; however, no reviews are available concerning the effect of early enteral feeding in pediatric AP. In this minireview, our aim was to systematically analyse the literature on the treatment of acute pediatric pancreatitis. The preferred reporting items for systematic review (PRISMA-P) were followed, and the question was drafted based on participants, intervention, comparison and outcomes: P: patients under the age of twenty-one suffering from acute pancreatitis; I: early enteral nutrition (per os and nasogastric- or nasojejunal tube started within 48 h); C: nil per os therapy; O: length of hospitalization, need for treatment at an intensive care unit, development of severe AP, lung injury (including lung oedema and pleural effusion), white blood cell count and pain score on admission. Altogether, 632 articles (PubMed: 131; EMBASE: 501) were found. After detailed screening of eligible papers, five of them met inclusion criteria. Only retrospective clinical trials were available. Due to insufficient information from the authors, it was only possible to address length of hospitalization as an outcome of the study. Our mini-meta-analysis showed that early enteral nutrition significantly (SD = 0.806, P = 0.034) decreases length of hospitalization compared with nil per os diet in acute pediatric pancreatitis. In this minireview, we clearly show that early enteral nutrition, started within 24-48 h, is beneficial in acute pediatric pancreatitis. Prospective studies and better presentation of research are crucially needed to achieve a higher level of evidence

The quadrivalent HPV vaccine is protective against genital warts: a meta-analysis

The quadrivalent human papillomavirus (HPV) vaccine has been assumed to give protection against genital warts (GW) as well as cervical cancer. Our main question was whether HPV vaccine has any effects on the prevention of GW reported in randomised controlled clinical trials (RCTs) and time-trend analyses.This meta-analysis was performed according to the PRISMA guidelines using the PICO format. We searched in three electronic databases (PubMed, Embase, Cochrane Trials), and assessed heterogeneity using the Q-test and I-squared statistics, meta-regression was also performed. Odds ratios (OR) and their confidence intervals (CI) were calculated. The sensitivity was tested by leave-one-out method. We evaluated the presence of publication bias using the funnel plot graph and the Copas selection model. The strength of evidence was assessed using the GRADE approach.Eight RCTs (per-protocol populations) and eight time-trend ecological studies were included in this meta-analysis. A significant reduction (pooled OR = 0.03, 95% CI: 0.01-0.09; I-squared = 53.6%) of GW in young women was recorded in RCTs, and in time-trend analyses both in young women (pooled OR = 0.36, CI 95% = 0.26-0.51; I-squared = 98.2%), and in young men (pooled OR = 0.69, 95% CI = 0.61-0.78; I-squared = 92.7%). In subgroup analysis, a significant reduction of the number of GW events was observed especially in women under 21 years (pooled OR = 0.33, 95% CI = 0.17-0.63). Leave-one-out analysis showed that similar results could be obtained after excluding one study, meta-regression did not show significant difference.Prophylactic, quadrivalent HPV vaccination can prevent GW in healthy women and men, therefore, it should be included in routine immunization programme

Suprapapillary Biliary Stents Have Longer Patency Times than Transpapillary Stents - A Systematic Review and Meta-Analysis

Endoscopic biliary stent placement is a minimally invasive intervention for patients with biliary strictures. Stent patency and function time are crucial factors. Suprapapillary versus transpapillary stent positioning may contribute to stent function time, so a meta-analysis was performed in this comparison.A comprehensive literature search was conducted in the CENTRAL, Embase, and MEDLINE databases to find data on suprapapillary stent placement compared to the transpapillary method via endoscopic retrograde cholangiopancreatography in cases of biliary stenosis of any etiology and any stent type until December 2020. We carried out a meta-analysis focusing on the following outcomes: stent patency, stent migration, rate of cholangitis and pancreatitis, and other reported complications.Three prospective and ten retrospective studies involving 1028 patients were included. Suprapapillary stent placement appeared to be superior to transpapillary stent positioning in patency (weighted mean difference = 50.23 days, 95% CI: 8.56, 91.98; p = 0.0.018). In a subgroup analysis of malignant indications, suprapapillary positioning showed a lower rate of cholangitis (OR: 0.34, 95% CI: 0.13, 0.93; p = 0.036). Another subgroup analysis investigating metal stents in a suprapapillary position resulted in a lower rate of pancreatitis (OR: 0.16, 95% CI: 0.03, 0.95; p = 0.043) compared to transpapillary stent placement. There was no difference in stent migration rates between the two groups (OR: 0.67, 95% CI: 0.17, 2.72; p = 0.577).Based on our results, suprapapillary biliary stenting has longer stent patency. Moreover, the stent migration rate did not differ between the suprapapillary and transpapillary groups