Infectious complications after cardiac implantable electronic device (CIED) implantation are increasing over time and are associated with substantial mortality and healthcare costs. The aim of this ...study was to systematically summarize the literature on risk factors for infection after pacemaker, implantable cardioverter-defibrillator, and cardiac resynchronization therapy device implantation. Electronic searches (up to January 2014) were performed in PubMed, Scopus, and Web of Science databases. Sixty studies (21 prospective, 9 case-control, and 30 retrospective cohort studies) met the inclusion criteria. The average device infection rate was 1-1.3%. In the meta-analysis, significant host-related risk factors for infection included diabetes mellitus (odds ratio (OR) 95% confidence interval = 2.08 1.62-2.67), end-stage renal disease (OR = 8.73 3.42-22.31), chronic obstructive pulmonary disease (OR = 2.95 1.78-4.90), corticosteroid use (OR = 3.44 1.62-7.32), history of the previous device infection (OR = 7.84 1.94-31.60), renal insufficiency (OR = 3.02 1.38-6.64), malignancy (OR = 2.23 1.26-3.95), heart failure (OR = 1.65 1.14-2.39), pre-procedural fever (OR = 4.27 1.13-16.12), anticoagulant drug use (OR = 1.59 1.01-2.48), and skin disorders (OR = 2.46 1.04-5.80). Regarding procedure-related factors, post-operative haematoma (OR = 8.46 4.01-17.86), reintervention for lead dislodgement (OR = 6.37 2.93-13.82), device replacement/revision (OR = 1.98 1.46-2.70), lack of antibiotic prophylaxis (OR = 0.32 0.18-0.55), temporary pacing (OR = 2.31 1.36-3.92), inexperienced operator (OR = 2.85 1.23-6.58), and procedure duration (weighted mean difference = 9.89 0.52-19.25) were all predictors of CIED infection. Among device-related characteristics, abdominal pocket (OR = 4.01 2.48-6.49), epicardial leads (OR = 8.09 3.46-18.92), positioning of two or more leads (OR = 2.02 1.11-3.69), and dual-chamber systems (OR = 1.45 1.02-2.05) predisposed to device infection. This systematic review on risk factors for CIED infection may contribute to developing better infection control strategies for high-risk patients and can also help risk assessment in the management of device revisions.
The epidemiology and antibiotic resistance of Staphylococcus aureus have evolved, underscoring the need for novel antibiotics, particularly against methicillin-resistant S. aureus (MRSA). Telavancin ...is a bactericidal lipoglycopeptide with potent activity against Gram-positive pathogens.
To systematically review and synthesize the available evidence from randomized controlled trials (RCTs) evaluating telavancin in the treatment of patients with infections due to Gram-positive organisms with the methodology of meta-analysis.
Six RCTs comparing telavancin with vancomycin were included; 4 (2229 patients) referred to complicated skin and soft tissue infections (cSSTIs) and 2 (1503 patients) to hospital-acquired pneumonia (HAP). Regarding cSSTIs, telavancin and vancomycin showed comparable efficacy in clinically evaluable patients (odds ratio OR =1.10 95% confidence intervals: 0.82-1.48). Among patients with MRSA infection, telavancin showed higher eradication rates (OR=1.71 1.08-2.70) and a trend towards better clinical response (OR=1.55 0.93-2.58). Regarding HAP, telavancin was non-inferior to vancomycin in terms of clinical response in two Phase III RCTs; mortality rates for the pooled trials were comparable with telavancin (20%) and vancomycin (18.6%). Pooled data from cSSTIs and HAP studies on telavancin 10 mg/kg indicated higher rates of serum creatinine increases (OR=2.22 1.38-3.57), serious adverse events (OR=1.53 1.05-2.24), and adverse event-related withdrawals (OR=1.49 1.14-1.95) among telavancin recipients.
Telavancin might be an alternative to vancomycin in cases of difficult-to-treat MRSA infections. The potent antistaphylococcal activity of telavancin should be weighted against the potential for nephrotoxicity.
The objective of this review was to evaluate the frequency of treatment failure and recurrence of Clostridium difficile infection (CDI) following treatment with vancomycin or metronidazole in ...recently performed studies (last 10 years). Searches in PubMed and Scopus were performed by two reviewers independently. Data regarding treatment failure and recurrence following metronidazole and vancomycin treatment were extracted and analysed. In total, 39 articles (7005 patients) were selected for inclusion in the systematic review. The reported treatment failure was 22.4% with metronidazole (16 studies) and 14.2% with vancomycin (8 studies). Recurrence of CDI occurred in 27.1% of patients following metronidazole treatment (18 studies) and 24.0% of patients following vancomycin treatment (8 studies). Mean treatment failure and recurrence in the selected studies was 22.3% (24 studies) and 22.1% (37 studies). The reported outcomes depended on the study design (higher in prospective and retrospective cohort studies than in randomised controlled trials), geographic location of the study (higher in North America than in Europe and Asia), funding (higher in studies funded by non-profit organisations than pharmaceutical companies), mean age of the studied population (higher in older patients) and duration of follow-up (higher in studies with follow-up >1 month). In conclusion, infection with C. difficile is associated with 22.4% and 14.2% treatment failure and 27.1% and 24.0% recurrence after treatment with metronidazole and vancomycin, respectively. The variation in the reported outcomes amongst studies depends on the study design, location, funding, age and follow-up period.
Abstract Hypoadiponectinemia might represent a risk factor for nonalcoholic fatty liver disease (NAFLD). We performed a systematic review and meta-analysis to evaluate the serum total adiponectin ...levels in patients with simple nonalcoholic fatty liver (NAFL), those with nonalcoholic steatohepatitis (NASH), and controls. Data were extracted from PubMed, EMBASE, and Cochrane Central Register of Controlled Trials electronic databases (up to December 2009). The main outcome was the weighted mean differences (WMDs) in adiponectin between comparison groups. Twenty-eight studies were included in the systematic review. A meta-analysis of 27 studies that reported data on 2243 subjects (698 controls and 1545 patients with NAFLD) was performed. Controls had higher serum adiponectin compared with NAFL patients (12 studies, random-effects WMD 95% confidence interval {CI} = 3.00 1.57-4.43, I2 = 80.4%) or NASH patients (19 studies, random-effects WMD 95% CI = 4.75 3.71-5.78, I2 = 84.1%). The NASH patients demonstrated lower adiponectin compared with NAFL patients (19 studies, random-effects WMD 95% CI = 1.81 1.09-2.53, I2 = 71.7%). By performing a meta-regression analysis, body mass index, age, sex, and type 2 diabetes mellitus failed to account for heterogeneity. However, the performance of liver biopsy on controls had significant effect on the outcome and accounted for 76.7%, 85.5%, and 22.8% of the between-study variance for comparisons between controls vs NAFLD, NAFL, and NASH patients, respectively. Based on liver histology, serum adiponectin levels are similar in NAFL patients and controls, but hypoadiponectinemia may play an important pathophysiological role in the progression from NAFL to NASH.
Numerous studies have examined the effect of psychological variables on surgical recovery, but no definite conclusion has been reached yet. We sought to examine whether psychological factors ...influence early surgical recovery.
We performed a systematic search in PubMed, Scopus and PsycINFO databases to identify studies examining the association of preoperative psychological variables or interventions with objectively measured, early surgical outcomes.
We identified 16 eligible studies, 15 of which reported a significant association between at least one psychological variable or intervention and an early postoperative outcome. However, most studies also reported psychological factors not influencing surgical recovery and there was significant heterogeneity across the studies. Overall, trait and state anxiety, state anger, active coping, subclinical depression, and intramarital hostility appeared to complicate recovery, while dispositional optimism, religiousness, anger control, low pain expectations, and external locus of control seemed to promote healing. Psychological interventions (guided relaxation, couple support visit, and psychiatric interview) also appeared to favor recovery. Psychological factors unrelated to surgical outcomes included loneliness, perceived social support, anger expression, and trait anger.
Although the heterogeneity of the available evidence precludes any safe conclusions, psychological variables appear to be associated with early surgical recovery; this association could bear important implications for clinical practice. Large clinical trials and further analyses are needed to precisely evaluate the contribution of psychology in surgical recovery.
OBJECT The aim of this study was to evaluate the effectiveness of antimicrobial-impregnated and -coated shunt catheters (antimicrobial catheters) in reducing the risk of infection in patients ...undergoing CSF shunting or ventricular drainage. METHODS The PubMed and Scopus databases were searched. Catheter implantation was classified as either shunting (mainly ventriculoperitoneal shunting) or ventricular drainage (mainly external EVD). Studies evaluating antibioticimpregnated catheters (AICs), silver-coated catheters (SCCs), and hydrogel-coated catheters (HCCs) were included. A random effects model meta-analysis was performed. RESULTS Thirty-six studies (7 randomized and 29 nonrandomized, 16,796 procedures) were included. The majority of data derive from studies on the effectiveness of AICs, followed by studies on the effectiveness of SCCs. Statistical heterogeneity was observed in several analyses. Antimicrobial shunt catheters (AICs, SCCs) were associated with lower risk for CSF catheter-associated infections than conventional catheters (CCs) (RR 0.44, 95% CI 0.35-0.56). Fewer infections developed in the patients treated with antimicrobial catheters regardless of randomization, number of participating centers, funding, shunting or ventricular drainage, definition of infections, de novo implantation, and rate of infections in the study. There was no difference regarding gram-positive bacteria, all staphylococci, coagulase-negative streptococci, and Staphylococcus aureus, when analyzed separately. On the contrary, the risk for methicillin-resistant S. aureus (MRSA, RR 2.64, 95% CI 1.26-5.51), nonstaphylococcal (RR 1.75, 95% CI 1.22-2.52), and gram-negative bacterial (RR 2.13, 95% CI 1.33-3.43) infections increased with antimicrobial shunt catheters. CONCLUSIONS Based on data mainly from nonrandomized studies, AICs and SCCs reduce the risk for infection in patients undergoing CSF shunting. Future studies should evaluate the higher risk for MRSA and gram-negative infections. Additional trials are needed to investigate the comparative effectiveness of the different types of antimicrobial catheters.
Atherosclerosis is a chronic inflammatory disease that is initiated by the retention and accumulation of low-density lipoprotein in the artery, leading to maladaptive response of cells from the ...immune system and vessel wall. Strong evidence implicates indoleamine 2,3-dioxygenase (IDO), the first and rate-limiting enzyme of the kynurenine pathway of tryptophan (Trp) degradation, with immune regulation and anti-inflammatory mechanisms in different diseases. However, the role of IDO and the endogenous degradation of Trp have never been directly examined in atherosclerosis development. We used the IDO inhibitor 1-methyl-Trp (1-MT) to determine the role of IDO-mediated Trp metabolism in vascular inflammation and atherosclerosis.
Apoe(-/-) mice were treated with 1-MT in drinking water for 8 weeks. Systemic IDO inhibition led to a significant increase in atherosclerotic lesions that were ∼58 and 54% larger in the aortic arch and root, respectively. 1-MT treatment enhanced vascular inflammation, up-regulated VCAM-1 and CCL2, and increased CD68 macrophage accumulation into the plaque. Notably, the rise in VCAM-1 expression was not limited to the plaque but also found in smooth muscle cells (SMCs) of the tunica media. Furthermore, we found that IDO-dependent Trp metabolism by SMCs regulates VCAM-1 expression, and that 1-MT-induced acceleration of atherosclerosis and vascular inflammation can be reversed by exogenous administration of the Trp metabolite 3-hydroxyanthranilic acid (3-HAA).
IDO-mediated Trp metabolism regulates vascular inflammation and plaque formation in hypercholesterolaemic Apoe(-/-) mice. Our data establish that this pathway plays a major role in the pathological process of atherogenesis.
To systematically summarize the literature on maternal influenza vaccination and the risk for congenital malformations using the methodology of meta-analysis.
PubMed, Scopus, and Embase databases (up ...to December 2014) as well as ClinicalTrials.gov (May 2015) and references of relevant articles were searched. The search strategy included combinations of the terms "influenza," "vaccin*," "pregnan*," "safe*," "adverse," "congenital," "malformation," "defect," and "anomal*."
Eligible studies examined the association between antepartum or preconceptional maternal immunization with inactivated influenza vaccines (seasonal trivalent or monovalent H1N1) and the risk for congenital malformations. Studies with no or inappropriate control group (comparison with population background rates or other vaccine types) were excluded.
The risk for congenital anomalies after influenza vaccination was examined in 15 studies: 14 cohorts (events per vaccinated compared with unvaccinated: 859/32,774 2.6% compared with 7,644/245,314 3.1%) and one case-control study (vaccinated per cases compared with controls: 1,351/3,618 37.3% compared with 511/1,225 41.7%). Eight studies reported on first-trimester immunization (events per vaccinated compared with unvaccinated: 258/4,733 5.4% compared with 6,470/196,054 3.3%). No association was found between congenital defects and influenza vaccination at any trimester of pregnancy (odds ratio OR 0.96, 95% confidence interval 0.86-1.07; 15 studies; I2=36) or at the first trimester (OR 1.03, 0.91-1.18; eight studies; I2=0). When assessing only major malformations, no increased risk was detected after immunization at any trimester (OR 0.99, 0.88-1.11; 12 studies; I2=31.5) or at the first trimester (OR 0.98, 0.83-1.16; seven studies; I2=0). Neither adjuvanted (OR 1.06, 0.95-1.20; five studies; I2=18.8) nor unadjuvanted vaccines (OR 0.89, 0.75-1.04; seven studies; I2=22.6) were associated with an increased risk for congenital defects.
This systematic review did not indicate an increased risk for congenital anomalies after maternal influenza immunization adding to the evidence base on the safety of influenza vaccination in pregnancy.
Abstract
Aims
Atherosclerosis is a chronic inflammatory disease involving immunological and metabolic processes. Metabolism of tryptophan (Trp) via the kynurenine pathway has shown immunomodulatory ...properties and the ability to modulate atherosclerosis. We identified 3-hydroxyanthranilic acid (3-HAA) as a key metabolite of Trp modulating vascular inflammation and lipid metabolism. The molecular mechanisms driven by 3-HAA in atherosclerosis have not been completely elucidated. In this study, we investigated whether two major signalling pathways, activation of SREBPs and inflammasome, are associated with the 3-HAA-dependent regulation of lipoprotein synthesis and inflammation in the atherogenesis process. Moreover, we examined whether inhibition of endogenous 3-HAA degradation affects hyperlipidaemia and plaque formation.
Methods and results
In vitro, we showed that 3-HAA reduces SREBP-2 expression and nuclear translocation and apolipoprotein B secretion in HepG2 cell cultures, and inhibits inflammasome activation and IL-1β production by macrophages. Using Ldlr−/− mice, we showed that inhibition of 3-HAA 3,4-dioxygenase (HAAO), which increases the endogenous levels of 3-HAA, decreases plasma lipids and atherosclerosis. Notably, HAAO inhibition led to decreased hepatic SREBP-2 mRNA levels and lipid accumulation, and improved liver pathology scores.
Conclusions
We show that the activity of SREBP-2 and the inflammasome can be regulated by 3-HAA metabolism. Moreover, our study highlights that targeting HAAO is a promising strategy to prevent and treat hypercholesterolaemia and atherosclerosis.
Hypercholesterolemia promotes the inflammation against lipoproteins in atherosclerosis. Development of atherosclerosis is affected by the balance between pro-inflammatory effector T cells and ...anti-inflammatory regulatory T (Treg) cells. However, phenotype and function of T cell subpopulations in hypercholesterolemia remain to be investigated. Here, we found that cholesterol-containing diet increased the expression of the Treg cell lineage-defining transcription factor FoxP3 among thymocytes and splenocytes. Hypercholesterolemia elevated the FoxP3 expression level and population size of peripheral Treg cells, but did not prevent enhanced proliferation of stimulated T cells. Moreover, cholesterol supplementation in diet as well as in cell culture medium promoted T cell antigen receptor (TCR) signaling in CD4+ T cells. Our results demonstrate that hypercholesterolemia enhances TCR stimulation, Treg cell development as well as T cell proliferation. Thus, our findings may help to understand why hypercholesterolemia correlates with altered CD4+ T cell responses.
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