Significant infections in liver transplant recipients undergoing endoscopic retrograde cholangiography are few and unaffected by prophylactic antibiotics

IntroductionCurrent practice guidelines recommend prophylactic antibiotics prior to endoscopic retrograde cholangiopancreatography (ERCP) in liver transplant recipients (LTR). This study evaluated the risk of clinically significant infections after ERCP in LTR who received antibiotic prophylaxis compared to those who did not.MethodsThis retrospective case-cohort study evaluated all LTR who underwent elective, outpatient ERCP from 2008 to 2015. Hospitalized patients, pediatric allograft recipients and patients with cholangitis or incomplete biliary drainage were excluded. The primary outcome was unanticipated hospitalization from procedure-related clinically significant infection occurring within 3 days of ERCP.ResultsSixty-nine patients (48 males; mean age 60.5 ± 7.4 years) underwent 191 ERCPs after liver transplantation. Prophylactic antibiotics were administered during 82 ERCPs and not administered for 109 ERCPs. Unscheduled admissions for fever within 3 days occurred in 4 patients. Only 2 patients had documented bacteremia, of which only 1 patient received prophylactic antibiotics and also met primary outcome. Interventions during ERCP, patient demographics, and time from transplantation were not associated with increased risk of hospitalization from infections or bacteremia.ConclusionsThe risk of infectious complications after ERCP in LTR is low and not affected by administration of prophylactic antibiotics. A tailored approach to antibiotic prophylaxis may be more appropriate than universal prophylaxis in selected LTR at low risk of infections.     

Prasugrel Versus Ticagrelor in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: a Systematic Review and Meta-analysis of Randomized Trials

Purpose

Dual antiplatelet therapy (DAPT) with aspirin and ticagrelor or prasugrel is the mainstay of treatment for patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). We aimed to systematically perform a head-to-head comparison of ticagrelor vs prasugrel in terms of efficacy and safety.

Methods

We searched PubMed/Medline, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) for relevant published randomized controlled trials (RCTs). The primary outcome was adverse cardiovascular events and secondary outcome was bleeding events. A random-effects meta-analysis was used to obtain the pooled estimate of each outcome.

Results

Nine RCTs with a total number of 6990 patients (3550 treated with prasugrel and 3481 treated with ticagrelor) were included. No significant difference between prasugrel and ticagrelor was observed in terms of mortality (OR 0.86, 95% CI 0.66 to 1.13, P?=?0.28), major adverse cardiovascular events (MACEs) (OR 0.85, 95% CI 0.70 to 1.03, P?=?0.10), non-fatal myocardial infarction (OR 0.78, 95% CI 0.57 to 1.06, P?=?0.11), stroke (OR 1.02, 95% CI 0.60 to 1.72, P?=?0.95), stent thrombosis (OR 0.76, 95% CI 0.47 to 1.21, P?=?0.25), thrombolysis in myocardial infarction (TIMI) defined major (OR 0.94, 95% CI 0.19 to 4.67, P?=?0.94), minor (OR 0.35, 95% CI 0.08 to 1.62, P?=?0.18) and minimal (OR 0.48, 95% CI 0.19 to 1.18, P?=?0.11) bleeding and Bleeding Academic Research Consortium (BARC) defined bleeding (OR 1.06, 95% CI 0.82 to 1.36, P?=?0.68).

Conclusion

In patients with ACS undergoing PCI, both prasugrel and ticagrelor were associated with similar cardiovascular outcomes and adverse bleeding events.

     

Preoperative ERCP has no impact on islet yield following total pancreatectomy and islet autotransplantation (TPIAT): Results from the Prospective Observational Study of TPIAT (POST) cohort

Background and aimsMany patients undergoing total pancreatectomy with islet autotransplant (TPIAT) for severe, refractory chronic pancreatitis or recurrent acute pancreatitis have a history of endoscopic retrograde cholangiopancreatography (ERCP). Using data from the multicenter POST (Prospective Observational Study of TPIAT) cohort, we aimed to determine clinical characteristics associated with ERCP and the effect of ERCP on islet yield.MethodsUsing data from 230 participants (11 centers), demographics, pancreatitis history, and imaging features were tested for association with ERCP procedures. Logistic and linear regression were used to assess association of islet yield measures with having any pre-operative ERCPs and with the number of ERCPs, adjusting for confounders.Results175 (76%) underwent ERCPs [median number of ERCPs (IQR) 2 (1-4). ERCP was more common in those with obstructed pancreatic duct (p = 0.0009), pancreas divisum (p = 0.0009), prior pancreatic surgery (p = 0.005), and longer disease duration (p = 0.004). A greater number of ERCPs was associated with disease duration (p < 0.0001), obstructed pancreatic duct (p = 0.006), and prior pancreatic surgery (p = 0.006) and increased risk for positive islet culture (p < 0.0001). Mean total IEQ/kg with vs. without prior ERCP were 4145 (95% CI 3621-4669) vs. 3476 (95% CI 2521-4431) respectively (p = 0.23). Adjusting for confounders, islet yield was not significantly associated with prior ERCP, number of ERCPs, biliary or pancreatic sphincterotomy or stent placement.ConclusionsERCP did not appear to adversely impact islet yield. When indicated, ERCP need not be withheld to optimize islet yield but the risk-benefit ratio of ERCP should be considered given its potential harms, including risk for excessive delay in TPIAT.     

What Would Be the Appropriate Number of Clinical ERCP Cases for Trainees to Acquire Basic Competence? A Systematic Review and Meta-Analysis

Endoscopic retrograde cholangiopancreatography (ERCP) is technically demanding and carries significant risks. It is performed by gastrointestinal and surgical endoscopists. There is no consensus on the minimum number of ERCPs required during training. This study was conducted to analyze the minimum number of clinical ERCPs that a trainee needs to perform to achieve competency. PubMed, Ovid-Embase, and the Cochrane library were searched systematically for prospective and retrospective studies reporting on trainees’ ERCP performance. Mete-analysis was conducted to analyze the success rate of cannulation, other basic techniques, and adverse event rate, using the random-effect model with Review Manager 5.3. Thirteen studies met the inclusion criteria, with 149 trainees performing a total of 18 794 ERCP procedures. The pooled cannulation success rate was 85.7% (95% CI: 78.1%-91.0%) at completion of training. The cannulation success rate was 76.5% (95% CI: 69.2%-82.5%) when the trainees had completed 180 ERCPs, which increased to 81.8% (95% CI: 69.8%-90.6%) after 200 ERCP procedures. Adverse events and post-ERCP pancreatitis rates were 4.7% (95% CI: 2.9%-9.1%) and 2.0% (0.9%-3.9%), respectively. Achieving a cannulation success rate of >90% was considered a quality indicator for ERCP training by most societal guidelines. However, our retrospective analysis indicated that trainees only attained a pooled cannulation success rate of only 81.8% after 200 procedures. Therefore, the minimum number of ERCPs required to achieve competency during training may need to be redefined to meet the basic requirement.     

Drug-Eluting Versus Bare-Metal Stents in Older Patients: A Meta-Analysis of Randomized Controlled Trials

BackgroundDespite the high prevalence of ischemic heart disease in older patients, there is a substantial lack of evidence to guide clinical decision-making in this population. Hence, we performed a meta-analysis to determine the safety and efficacy of percutaneous coronary intervention (PCI) with drug-eluting stents (DES) versus bare-metal stents (BMS).MethodsElectronic databases were searched for randomized trials comparing DES with BMS in patients ≥70 years-old. The primary outcome was major adverse cardiovascular events (MACE). Secondary outcomes included different ischemic and bleeding events. Subgroup analyses for dual-antiplatelet therapy (DAPT) duration were conducted.ResultsWe included 7 trials with a total of 5449 patients. The use of DES compared with BMS was associated with a significant reduction in MACE (odds ratio [OR]:0.76; 95% confidence interval [CI]:0.62–0.93; P = 0.007) with no increased risk of bleeding events (OR: 1.07; 95% CI: 0.89–1.27; P = 0.48). However, longer duration of DAPT (>6 months) for the DES group increased bleeding events (OR: 1.52; 95% CI: 1.05–2.20; P = 0.03). In contrast, shorter DAPT showed persistent efficacy in reducing MACE in DES-treated patients with no increased bleeding events (OR: 0.72; 95% CI: 0.60–0.87; P < 0.01 and OR: 1.01; 95% CI: 0.84–1.22; P = 0.89, respectively).ConclusionsIn older patients who had undergone PCI, DES showed superior efficacy in reducing MACE with no increased risk of bleeding compared with BMS. Persistent MACE reduction was evident with shorter DAPT durations in DES-treated patients.SummaryThis meta-analysis of randomized clinical trials demonstrated that drug-eluting stents were associated with a significant reduction in major adverse cardiovascular events with no increased risk of bleeding compared with bare-metal stents. The risk of bleeding was high with longer dual antiplatelet therapy duration for patients who underwent DES placement. However, short duration of dual antiplatelet therapy substantially reduced major adverse cardiovascular events with no increased bleeding risk.     

Sirolimus may be associated with early recurrence of biliary obstruction in liver transplant patients undergoing endoscopic stenting of biliary strictures

Introduction. Recurrent biliary obstruction necessitating premature repeat endoscopic retrograde pancreatography (ERCP) remains a costly and morbid problem in patients undergoing treatment of post-or-thotopic liver transplantation (OLT) biliary strictures. We evaluated the relationship between prednisone or sirolimus use and early recurrence of biliary obstruction given their negative effects on collagen production and cholangiocyte regeneration.Methods. Medical records of adult patients who underwent OLT from 1998-2008 and developed anastomotic (ABS) and/or nonanastomotic (NABS) biliary strictures requiring endoscopic plastic stent therapy were reviewed. Outcome was early recurrence of biliary obstruction requiring repeat ERCP. Univariate and multivariable logistic regression analysis, adjusting for age, sex, and time from OLT to ERCP, were performed.Results. 35 patients with ABS and 9 patients with NABS underwent a total of 157 ERCPs. Median patient age was 56 years, 68% were male, and hepatitis C was the most common OLT indication (52%). Early recurrence of biliary obstruction ocurred following 17.1% of ERCPs. In univariate analysis, neither prednisone nor sirolimus was associated with early recurrence of biliary obstruction. In multivariate analysis, however, sirolimus use was associated with increased incidence of early recurrent biliary obstruction (OR = 2.53; 95% CI: 0.77-8.32; p = 0.12); this was more pronounced at doses > 3 (OR = 4.27; 95% CI: 0.62-29.3; p = 0.14) than at ≤ 3 mg/day (OR = 2.24; 95% CI: 0.62-8.13; p = 0.22) and statistically significant in patients with ABS only (OR = 1.44 per mg increase in sirolimus dose; 95% CI 1.02-2.03; p = 0.037).Conclusions. Sirolimus use, particularly at higher doses and patients with ABS, may be associated with an increased risk of early recurrence of biliary obstruction requiring repeat ERCP for post-OLT biliary strictures. Additional studies are needed to further investigate these findings and elucidate other risk factors.     

Aggressive hydration with lactated ringer solution in prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: A systematic review and meta-analysis

Background:Acute pancreatitis is the most common complication of Endoscopic Retrograde Cholangiopancreatography (ERCP). There was no conclusion on the prevention of Post-ERCP Pancreatitis (PEP) by Lactated Ringer Solution.Aim:The purpose of this meta analyses is to determine whether aggressive hydration with Lactated Ringer Solution reduced the incidence of PEP.Methods:We retrieved randomized clinical trials comparing the preventive effects of aggressive hydration with Lactated Ringer Solution and standard hydration on PEP from PubMed, the Cochrane Library, Embase, the Web of Science, Clinical Trial.gov, Scopus database, CNKI, CQVIP and WanFang Data. Primary outcome was incidence of PEP. Secondary outcomes included incidence of hyperamylasemia, abdominal pain and adverse events.Results:Ten randomized controlled trials with 2200 patients were included in this meta-analysis. Meta-analysis showed that compared with standard hydration, aggressive hydration reduced the incidence of PEP (odds ratio [OR], 0.40; 95% confidence intervals [CI], 0.26–0.63; P < .0001). Compared with standard hydration, aggressive hydration also reduced the incidence of hyperamylasemia after ERCP (OR, 0.48; 95% CI, 0.38–0.60; P < .0001). There was significant difference between aggressive hydration and standard hydration in the incidence of abdominal pain (OR, 0.29; 95% CI, 0.11–0.73; P = .008). There was no difference in adverse events between aggressive hydration and standard hydration (OR, 0.93; 95% CI, 0.21–4.13; P = .93). Sensitivity analyses showed that neither alternative effect measures nor statistical models regarding heterogeneity affected the conclusions of this meta-analysis.Conclusion:Aggressive hydration with Lactated Ringer Solution during perioperative period of ERCP can prevent PEP.     

Hospital ownership and preventable adverse events

OBJECTIVE: To determine if type of hospital ownership is associated with preventable adverse events. DESIGN: Medical record review of a random sample of 15,000 nonpsychiatric, non-Veterans Administration hospital discharges in Utah and Colorado in 1992. MEASUREMENTS AND MAIN RESULTS: A two-stage record review process using nurse and physician reviewers was used to detect adverse events. Preventability was then judged by 2 study investigators who were blinded to hospital characteristics. The association among preventable adverse events and hospital ownership was evaluated using logistic regression with nonprofit hospitals as the reference group while controlling for other patient and hospital characteristics. We analyzed 4 hospital ownership categories: nonprofit, for-profit, major teaching government (e.g., county or state ownership), and minor or nonteaching government. RESULTS: When compared with patients in nonprofit hospitals, multivariate analyses adjusting for other patient and hospital characteristics found that patients in minor or nonteaching government hospitals were more likely to suffer a preventable adverse event of any type (odds ratio [OR] 2.46; 95% confidence interval [CI], 1.45 to 4.20); preventable operative adverse events (OR, 4.85; 95% CI, 2.44 to 9.62); and preventable adverse events due to delayed diagnoses and therapies (OR, 4.27; 95% CI, 1.48 to 12.31). Patients in forprofit hospitals were also more likely to suffer preventable adverse events of any type (OR, 1.57; 95% CI, 1.03 to 2.38); preventable operative adverse events (OR, 2.63; 95% CI, 1.42 to 4.87); and preventable adverse events due to delayed diagnoses and therapies (OR, 4.15; 95% CI, 1.84 to 9.34). Patients in major teaching government hospitals were less likely to suffer preventable adverse drug events (OR, 0.38; 95% CI, 0.16 to 0.89). CONCLUSIONS: Patients in for-profit and minor teaching or nonteaching government-owned hospitals were more likely to suffer several types of preventable adverse events. Further research is needed to determine how these events could be prevented. Presented in part at The Enhancing Patient Safety and Reducing Errors in Health Care Conference, Rancho Mirage, Calif, November 8–10, 1998. Funding for this work was provided by the Robert Wood Johnson Foundation.     

Efficacy and Safety of an Aclidinium Bromide Treatment for 12 Weeks or Longer in Patients with Moderate-To-Severe COPD: A Meta-Analysis

Background: Bronchodilators are commonly used to manage patients with stable chronic obstructive pulmonary disease (COPD). This meta-analysis assessed the efficacy of aclidinium bromide with respect to clinical events, health-related quality of life and symptom scales, pulmonary function, and safety among patients with stable COPD. Methods: A comprehensive search of MEDLINE, EMBASE, CINAHL and the Cochrane Library databases was undertaken to identify randomized controlled trials (RCTs) that compared aclidinium with placebo, treatment over at least 12 weeks. Trials were measured using either odds ratios (OR) or mean differences (MD) with 95% confidence intervals (CI). Results: Seven studies, containing 7001 patients, were included in this meta-analysis. Compared with placebo, aclidinium bromide reduced the incidence of exacerbation-related hospitalizations (OR 0.64; 95% CI 0.47 to 0.89) and improved quality of life as measured by a lower total George's Respiratory Questionnaire [SGRQ] score (MD ?2.34; 95% CI ?3.18 to ?1.51) and attenuated dyspnea symptom as assessed by changes in the Transitional Dyspnea Index [TDI] (MD 0.76; 95% CI 0.43 to 1.10). Similar changes were observed with regard to trough FEV₁ and FVC and peak FEV₁ and FVC. No significant differences were observed with regard to all-cause mortality, COPD exacerbations, non-fatal serious adverse events or cardiac adverse events. Conclusions: Aclidinium reduced the incidence of exacerbation-related hospitalizations and improved quality of life, COPD symptoms and pulmonary function. In addition, aclidinium did not increase the incidence of non-fatal serious adverse events, cardiac adverse events, or COPD exacerbations and was not associated with increased mortality.     

Sufficient versus deficient rims during percutaneous closure of ostium secundum type atrial septal defect: A systematic review and meta-analysis

BackgroundThe aim of this meta-analysis was to compare the efficacy and adverse events of percutaneous occlusion among patients with sufficient and deficient rims.MethodsA systematic review of all articles published in the Pubmed, MEDLINE and Google Scholar databases was performed. Odds ratio (OR) and 95% CI were used as a measure of effect of the combination of studies. I² with 95% CI was estimated to assess study heterogeneity. For the meta-analysis, a random effects model was used.ResultsThe systematic search identified ten studies which included 4355 patients; 2661 of those had sufficient rim and the remaining 1694 patients showed some rim deficiency. Implant failure rate was 4.13% CI 95% 3.53–4.72%. Compared to frequency of failures in the group with a deficient rim (5.43% CI 95% 4.35–6.50%), implant failure in patients with a sufficient rim was significantly lower (3.30% CI 95% 2.62–3.97%), OR 2.27 CI 1.34–3.83 (p 0.002).The combined adverse events were 5.19% CI 95% 4.22–6.35% vs 2.7% CI 95% 2.08–3.31% in the deficient vs sufficient rim groups respectively (OR 2.21 CI 0.93–5.29; p 0.07). Implant failures and adverse events were more frequent in patients with posterior inferior rim deficiency.ConclusionPatients presenting a posteroinferior rim deficiency are associated to both, an increased incidence of closure failure and a combined adverse events occurrence. More studies on posterior rim deficiency are necessary to ensure the feasibility and safety of the percutaneous approach.     

A dynamic risk factor assessment for myocardial infarction and cardiac arrest in patients undergoing pancreatectomy

BackgroundTo identify pancreatectomy specific risk factors for myocardial infarction and cardiac arrest (MICA) and to assess whether addition of new information obtained during the hospitalization changes these risk factors.MethodsAnalysis was performed on elective pancreatectomy data from the ACS-NSQIP database (2014–2019). Risk factors were grouped into pre-operative, intra-operative, and postoperative phases. Factors were selected using a bootstrap resampling procedure to determine MICA association. Independent significance was assessed by logistic regression.ResultsIn the first 30 days post-op, 650 of 39779 patients (1.88%) developed MICA. Some of the surgery specific, intra- and post-operative factors that were identified are: delayed gastric emptying (OR: 2.61; 95% CI: 2.12–3.21), total pancreatectomy (OR: 2.16; 95% CI: 1.29–3.42), pancreatic fistula (OR: 1.54; 95% CI: 1.25–1.90), post-operative transfusion (OR: 1.28; 95% CI: 1.03–1.58), and open approach (OR: 1.36; 95% CI: 1.05–1.77). Adding new variables improved statistical model performance and the c-statistic improved from 0.69 to 0.76 in the final analysis.ConclusionSurgery specific, intra-, and post-operative factors were associated with MICA. Addition of new information during the hospital course changed risk factors and the statistical prediction of MICA risk improved.     

Prophylactic antibiotic treatment in acute necrotizing pancreatitis: Results from a meta-analysis

Objective. The effect of prophylactic antibiotic treatment on infection and survival of acute necrotizing pancreatitis (ANP) remains uncertain. The aim of this study was to assess the long-term efficacy of prophylactic antibiotic treatment for ANP. Material and methods. Searches were carried out of electronic databases including Medline, EMBASE, the Cochrane Controlled Trials Register, the Science Citation Index, and PubMed (updated to December 2007), and manual bibliographical searches were also conducted. A meta-analysis of all randomized controlled trials (RCTs) comparing prophylactic antibiotic treatment with placebo or no treatment was performed. Results. Eight RCTs including 540 patients were assessed. The outcomes included infected necrosis, death, non-pancreatic infection, surgical intervention, and length of hospital stay. Prophylactic antibiotic use leads to a significant reduction of infected necrosis (relative risk (RR) 0.69, 95% CI, 0.50–0.95; p=0.02), non-pancreatic infections (RR 0.66 95% CI, 0.48–0.91; p=0.01), and length of hospital stay (p=0.004) but was not associated with a statistically significant reduction in mortality (RR 0.76 95% CI, 0.50–1.18; p=0.22) and surgical intervention (RR 0.90 95% CI, 0.66–1.23; p=0.52). In a subgroup analysis, carbapenem was associated with a significant reduction in infected necrosis (p=0.009) and non-pancreatic infections (p=0.006), whereas other antibiotics were not. Conclusions. Prophylactic antibiotic treatment is associated with a significant reduction of pancreatic or peripancreatic infection, non-pancreatic infection, and length of hospital stay, but cannot prevent death and surgical intervention in acute necrotizing pancreatitis.     

Antithrombotic Regimens for Patients Taking Oral Anticoagulation After Coronary Intervention: A Meta‐analysis of 16 Clinical Trials and 9185 Patients

The optimal antithrombotic regimen remains controversial in patients taking oral anticoagulation (OAC) undergoing coronary stenting. This study sought to compare efficacy and safety outcomes of triple therapy (OAC, aspirin, and clopidogrel) vs dual therapy (clopidogrel with aspirin or OAC) in these patients. We hypothesize OAC plus clopidogrel could be the optimal regimen for patients with indications for OAC receiving stent implantation. Medline, the Cochrane Library, and other Internet sources were searched for clinical trials comparing the efficacy and safety of triple vs dual therapy for patients taking OAC after coronary stenting. Sixteen eligible trials including 9185 patients were identified. The risks of major adverse cardiac events (odds ratio [OR]: 1.06, 95% confidence interval [CI]: 0.82‐1.39, P = 0.65), all‐cause mortality (OR: 0.98, 95% CI: 0.76‐1.27, P = 0.89), myocardial infarction (OR: 1.01, 95% CI: 0.77‐1.31, P = 0.97), and stent thrombosis (OR: 0.91, 95% CI: 0.49‐1.69, P = 0.75) were similar between triple and dual therapy. Compared with dual therapy, triple therapy was associated with a reduced risk of ischemic stroke (OR: 0.57, 95% CI: 0.35‐0.94, P = 0.03) but with higher major bleeding (OR: 1.52, 95% CI: 1.11‐2.10, P = 0.01) and minor bleeding (OR: 1.59, 95% CI: 1.05‐2.42, P = 0.03). Subgroup analysis indicated there were similar ischemic stroke and major bleeding outcomes between triple therapy and therapy with OAC plus clopidogrel. Treatment with OAC and clopidogrel was associated with similar efficacy and safety outcomes compared with triple therapy. Triple therapy could be replaced by OAC plus clopidogrel without any concern about additional risk of thrombotic events.     

The angiographic and clinical outcomes after coronary stenting in patients with metabolic syndrome

BackgroundMetabolic syndrome (MetS) is regarded as a risk factor for coronary artery disease (CAD). But the influence of MetS on morbidity and mortality after stent implantation in CAD patients remains unknown.MethodsThis article presents a meta-analysis of available data on the association between the MetS and the risk of angiographic and clinical outcomes following stent implantation.ResultsMetS was associated with a significant increased risk of post-stent all-cause mortality (odd ratio (OR), 2.17, 95% CI, 1.56–3.01), in-lesion restenosis (OR, 1.35, 95% CI, 1.00–1.84) and major adverse cardiac events (MACE) (OR 1.35, 95% CI 1.13–1.61) in CAD patients. Even with drug-eluting stent (DES) implantation, significant increased risk in all-cause mortality (OR, 2.25, 95% CI, 1.61–3.15) and MACE (OR 1.42, 95% CI 1.14–1.76) were remain in patients with MetS. However, the OR of cardiovascular (CV) mortality (1.25, 95% CI 0.71–2.22), MI (1.27, 95% CI 0.87–1.85) and TLR (OR 1.21, 95% CI 0.96–1.53) was not statistically different between the patients with and without metabolic syndrome.ConclusionsMetabolic syndrome is an important risk factor in patients with CAD following stent implantation. Although DES implantation decreased the incidence of angiographic events, further progress in adequate treatment of MetS is still required to improve the clinical outcome.     

Risk factors for knee osteoarthritis in Japanese men: a case-control study

Abstract

Risk of knee osteoarthritis (OA) was assessed in a population-based case-control study of Japanese men. The study covered three health districts in Wakayama and Osaka prefectures, Japan. Subjects were male individuals ≥45 years old diagnosed radiographically with knee OA, and who did not display any established causes of secondary OA. Controls selected randomly from the general population were individually matched to cases for age, sex, and residential district. Subjects were interviewed using structured questionnaires to determine medical history, physical activity, socio-economic factors, and occupation. Interviews were obtained from 37 cases and 37 controls. In univariate analysis, heaviest weight in the past and physical work such as factory, construction, agricultural, or fishery work as the principal occupation significantly raised the risk of male knee OA (P < 0.05). Odds ratios (OR) were determined using conditional logistic regression analysis mutually adjusted for potential risk factors using the results of univariate analysis. Heaviest weight in the past (OR 6.01, 95% confidence interval (CI) 1.18–30.5, P < 0.05), past knee injury (OR 6.25, 95% CI 1.13–34.5, P < 0.05), and physical work as the principal occupation (OR 6.20, 95% CI 1.40–27.5, P < 0.05) represented independent factors associated with knee OA after controlling for other risk factors. Physical work is associated with knee OA, demonstrating the influence of working activity on the development of OA. The present study suggests that risk factors for knee OA in men resemble those in women.     

Metabolic biomarkers and gallstone disease – a population-based study

Objectives: The objectives for this study were to examine the associations between metabolic biomarkers of obesity including insulin resistance, vascular dysfunction, systemic inflammation, genetic susceptibility and ultrasound proven gallstone disease or cholecystectomy in a population-based cross-sectional study.

Material and methods: A total of 2650 participants were included, of whom 422 had gallstone disease. Associations between selected metabolic biomarkers and gallstone disease were estimated by multivariable logistic regression models and expressed as odds ratio (OR) and 95% confidence interval (CI).

Results: Gallstone disease was associated with fasting glucose (OR 1.14, 95% CI [1.05;1.24]), fasting insulin (OR 1.03, 95% CI [1.01;1.05]), homeostasis model assessment insulin resistance (OR 1.18, 95% CI [1.02;1.36]), the metabolic syndrome (OR 1.51, 95% CI [1.16;1.96]), white blood cell count (OR 1.07, 95% CI [1.00;1.15]) and C-reactive protein (OR 1.03, 95% CI [1.01;1.05]). A tendency towards an association for soluble urokinase plasminogen activator receptor was also found (OR 1.08, 95% CI [0.99;1.18]). The MC4R(rs17782313) (OR 1.27, 95% CI [1.02;1.58]), MAP2K5(rs2241423) (OR 1.80, 95% CI [1.04;3.41]), NRXN3(rs10146997) (OR 1.26, 95% CI [1.01;1.57]), HHEX(rs1111875) (OR 1.29, 95% CI [1.03;1.62]), FAIM2(rs7138803) (OR 0.66, 95% CI [0.48;0.91]), and apolipoprotein E4 allele (OR 0.76, 95% CI [0.59;0.98]) were associated with gallstone disease. Urinary albumin was not associated with gallstone disease. The association between BMI and gallstone disease was explained by insulin resistance.

Conclusions: Biomarkers of insulin resistance, systemic inflammation and genetic obesity or type 2 diabetes risk alleles seem to be associated with gallstone disease. Future studies should explore temporal associations and genetic associations in other populations in order to clarify targets for prevention or intervention.     

Indomethacin down-regulating HMGB1 and TNF-α to prevent pancreatitis after endoscopic retrograde cholangiopancreatography

Abstract

Background and aims: Several articles demonstrated that non-steroidal anti-inflammation drugs (NSAIDs) were effective in reducing the incidence of pancreatitis after endoscopic retrograde cholangiopancreatography (PEP). However, studies revealed inconsistent results. The mechanism of NSAIDs in preventing PEP is still little known. Therefore, the aim of our study was to evaluate the efficacy of NSAIDs for PEP prophylaxis and further to explore the mechanism of NSAIDs for prevention of PEP.

Methods: Patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) were randomly assigned to receive 100?mg rectal indomethacin or glycerin suppository 15–20?min before ERCP. The primary outcome was the rate of PEP. And the levels of serum HMGB1 and TNF-α were also measured before ERCP and 3 and 24?h after ERCP. Univariate analysis and multivariate analysis were carried out to estimate the independent risk factors for PEP.

Results: Totally, 100 patients were enrolled, 50 received indomethacin and 50 with placebo (glycerin suppository). PEP developed in six patients in indomethacin group and 16 in the control group, the difference was significant (p?=?.016). The levels of HMGB1 and TNF-α were significantly decreased in indomethacin group at 3 (p?p?p?=?.008) and usage of NSAIDs (OR, 0.278; 95% CI, 0.090–0.861; p?=?.026) were independent predictors of PEP.

Conclusions: Rectal indomethacin could significantly reduce the risk of PEP by down-regulating the levels of HMGB1 and TNF-α.     

Phosphodiesterase-5 Inhibitors and Outcomes During Left Ventricular Assist Device Support: A Systematic Review and Meta-Analysis

BackgroundPhosphodiesterase-5 inhibitors (PDE5i) have been used to treat pulmonary hypertension and right ventricular failure in patients with left ventricular assist devices (LVAD). The effects of PDE5i on post-LVAD outcomes including hemocompatibility-related adverse events are not well-established. This systematic review and meta-analysis aims to evaluate the effects of PDE5i on post-LVAD outcomes.Methods and ResultsA comprehensive literature search was conducted using Pubmed and Embase databases from inception through November 25, 2020, to compare post-LVAD outcomes in patients with or without PDE5i use. Pooled odds ratio (OR) with 95% confidence intervals (CI) and I² statistic were calculated. Thirteen observational studies were included in this analysis. The use of PDE5i was not significantly associated with lower postoperative right ventricular failure (OR 0.38, 95% CI 0.02–5.96, P = .41). There was no significant association between PDE5i and gastrointestinal bleeding (OR 1.23, 95% CI 0.76–1.98, P = .2), overall stroke (OR 0.60, 95% CI 0.21–1.68, P = .17), ischemic stroke (OR 0.61, 95% CI 0.09–4.07, P = .38), or pump thrombosis (OR 0.71, 95% CI 0.14–3.54, P = .46).ConclusionsOur meta-analysis showed no significant association between PDE5i and post-LVAD right ventricular failure. Despite the antiplatelet effects of PDE5i, there was no significant association between PDE5i and gastrointestinal bleeding, overall stroke, ischemic stroke, or pump thrombosis. Randomized controlled studies are warranted to evaluate the net benefits or harms of PDE5i in the LVAD population.     

Outcomes of optical coherence tomography guided percutaneous coronary intervention against angiography guided in patients with coronary artery disease: A systematic reviews and meta-analyses

BackgroundPrevious studies compared optical coherence tomography (OCT) guided percutaneous coronary intervention (PCI) and angiography-guided was still limited. Therefore, we performed comprehensive meta-analyses to investigate the clinical outcomes of OCT-guided compared with angiography-guided PCI to provide a higher level of evidence.MethodsA systematic search from electronic databases such as Pubmed, EMBASE, SpringerLink, and Cochrane Library was conducted to obtain original articles comparing OCT and angiography. Major adverse cardiac events (MACE), cardiovascular death, myocardial infarction (MI), stent thrombosis, target vessel revascularization, stenosis area, PCI procedure time, contrast volume, and procedural side effects were the measured outcomes. The primary end-points were MACE and cardiovascular death.ResultsTotal 11 studies included 5814 patients were analyzed, with 3431 using OCT-guided and 2383 using angiography-guided. Pooled estimates of outcomes, presented as odds ratios (OR) [95% confidence intervals], were generated with random-effect models. Regarding clinical outcomes, OCT-guided PCI showed significantly lower rate of MACE (odds ratio [OR] 0.52, 95% confidence interval [CI] 0.38 to 0.72, p < 0.001), cardiovascular death (OR 0.47, 95% CI 0.33 to 0.67, p < 0.001), and higher contrast volume (OR 1.6, 95% CI 0.81 to 2.39, p < 0.001). OCT-guided has longer PCI procedure time (OR 2.42, 95% CI 1.33 to 4.42, p = 0.004). OCT-guided has no significant difference in lower risk of periprocedural MI (OR 0.59, 95% CI 0.35 to 1.00, p = 0.05), stent thrombosis (OR 0.69, 95% CI 0.2 to 2.43, p = 0.56), target vessel repeat revascularization (OR 0.74, 95% CI 0.47 to 1.14, p = 0.17), stenosis area (OR -0.63, 95% CI -1.5 to 0.25, p = 0.56), and adverse events related to procedures (OR 1.33, 95% CI 0.8 to 2.19, p = 0.27).ConclusionOur meta-analysis demonstrated that OCT-guided PCI is significantly associated with lower MACE, cardiovascular death, and higher contrast volume. It is also associated with a longer duration of PCI. However, it is not associated with MI, stent thrombosis, target vessel revascularization, stenosis area, and adverse events related to procedures.     

The net clinical benefits of febuxostat versus allopurinol in patients with gout or asymptomatic hyperuricemia – A systematic review and meta-analysis

Background and aimsSystemic reviews and meta-analyses suggest hyperuricemia is a cardiovascular risk factor. The effects of xanthine oxidase inhibitors on cardiac outcomes remain unclear. We assessed the effects of febuxostat and allopurinol on mortality and adverse reactions in adult patients with hyperuricemia.Methods and resultsPubMed and EMBASE were searched to retrieve randomized controlled trials of febuxostat and allopurinol from January 2005 to July 2018. The meta-analysis consisted of 13 randomized controlled trials with a combined sample size of 13,539 patients. Febuxostat vs. allopurinol was not associated with an increased risk of cardiac-related mortality in the overall population (OR: 0.72, 95% CI: 0.24–2.13, P = 0.55). Regarding adverse skin reactions, the patients receiving febuxostat had significantly fewer adverse skin reactions than those receiving allopurinol treatment (OR: 0.50, 95% CI: 0.30–085, P = 0.01). Compared with allopurinol, febuxostat was associated with an improved safety outcome of cardiac-related mortality and adverse skin reactions (OR: 0.72, 95% CI: 0.55–0.96, P = 0.02). The net clinical outcome, composite of incident gout and the safety outcome, was not different significantly in the patients receiving febuxostat or allopurinol (OR: 1.04, 95% CI: 0.76–0.1.42, P = 0.79). In sensitivity analyses, a borderline significance was found in the patients randomized to febuxostat vs. allopurinol regarding cardiac-related mortality (OR: 1.29, 95% CI: 1.00–1.67, P = 0.05) after the CARES study was included.ConclusionFebuxostat vs. allopurinol was associated with the improved safety outcome and have comparable mortality and net clinical outcome in patients with hyperuricemia.Registration numberPROSPERO(CRD42018091657).