High level of D-dimer predicts ischemic stroke in patients with infective endocarditis.

BACKGROUND: Ischemic stroke is one of the most prominent and serious neurological complications of infective endocarditis (IE). Our study was designed to evaluate the predictive value of higher level of plasma D-dimer on admission for the development of ischemic stroke in patients with IE. METHODS: In this prospective study, a total of 173 consecutive patients with IE were recruited from January 2016 to December 2018. Plasma D-dimer and other clinical indexes of IE patients were measured after admission. The number of patients who developed ischemic stroke during 6-month follow-up was recorded, as well as the occurrence time of ischemic stroke. RESULTS: Ischemic stroke was observed in 38 (22%) patients during 6-month follow-up since definite diagnosis of IE. Patients with ischemic stroke had significantly higher levels of plasma D-dimer than those of patients without stroke (4982 vs 2205 µg/L, P < .001). In addition, Staphylococcus aureus infection (HR: 1.96, 95% CI: 1.51-2.42), mitral valve vegetation (HR: 1.52, 95% CI: 1.32-1.75), and higher levels of on-admission plasma D-dimer (HR: 1.35, 95% CI: 1.27-1.43) were significantly associated with ischemic stroke. Moreover, D-dimer levels ≥3393 µg/L served as a strong predictor for ischemic stroke in patients with IE, and the sensitivity and specificity were 78% and 83%, respectively. CONCLUSION: Our study suggested that higher level of D-dimer on admission was an independent predictor for ischemic stroke in patients with IE. These patients may require special attention, in particular within the first trimester after IE diagnosis.

Autoinducer-2 regulates Pseudomonas aeruginosa PAO1 biofilm formation and virulence production in a dose-dependent manner.

BACKGROUND: Pseudomonas aeruginosa is an opportunistic pathogen that is the leading cause of iatrogenic infections in critically ill patients, especially those undergoing mechanical ventilation. In this study, we investigated the effects of the universal signaling molecule autoinducer-2 (AI-2) in biofilm formation of P. aeruginosa PAO1. RESULTS: The addition of 0.1 nM, 1 nM, and 10 nM exogenous AI-2 to P. aeruginosa PAO1 increased biofilm formation, bacterial viability, and the production of virulence factors. However, compared to the 10 nM AI-2 group, higher concentrations of AI-2 (100 nM and 1 µM) reduced biofilm formation, bacterial viability, and the production of virulence factors. Consistent with the changes in morphology, gene expression analysis revealed that AI-2 up-regulated the expression of quorum sensing-associated genes and genes encoding virulence factors at lower concentrations and down-regulated these genes at higher concentrations. CONCLUSIONS: Our study demonstrated that exogenous AI-2 acted in a dose-dependent manner to regulate P. aeruginosa biofilm formation and virulence factors secretion via modulating the expression of quorum sensing-associated genes and may be targeted to treat P. aeruginosa biofilm infections.

Synergy of ambroxol with vancomycin in elimination of catheter-related Staphylococcus epidermidis biofilm in vitro and in vivo.

Central venous catheters are widely used in neonatal intensive care units (NICUs) nowadays. The commonest cause of catheter-related bloodstream infections (CRBSIs) is coagulase-negative staphylococci (CoNS). Ambroxol, an active metabolite of bromhexine, exhibits antimicrobial activity against strains producing biofilm and enhances the bactericidal effect of some antibiotic by breaking the structure of biofilm. In this study, we aimed to determine the effect of ambroxol with vancomycin on the biofilm of Staphylococcus epidermidis (S. epidermidis) in vitro and in vivo. In the in vitro study, the biofilm of S. epidermidis was assessed by XTT reduction assay and analysed by confocal laser scanning microscopy (CLSM). In the in vivo study, a rabbit model of CRBSIs was created by intravenous intubation with a tube covered with S. epidermidis biofilm. The rabbits received one of the following four treatments by means of antibiotic lock therapy: normal heparin, ambroxol, vancomycin, or vancomycin plus ambroxol each for 3 days. The microstructure of the biofilm was assessed by scanning electron microscopy (SEM). The number of bacterial colonies in the organs (liver, heart, and kidney) and on the intravenous tubes was measured on agar plates. Pathological changes in the organs (liver, heart, and kidney) were observed with Hematoxylin-Eosin staining. The ambroxol exhibits significant efficacy to potentiate the bactericidal effect of vancomycin on S. epidermidis biofilm both in vitro and in vivo. The antibiotic lock therapy using a combination of ambroxol and vancomycin reveals a high ability to eradicate S. epidermidis biofilms in vivo. These results provide the basis of a useful anti-infection strategy for the treatment of CRBSIs.

[The impact of non-alcoholic fatty liver disease on islet function in type 2 diabetes].

OBJECTIVE: To analyze the influence of hepatosteatosis on pancreatic P-cell function in type 2 diabetes mellitus (22DM). METHODS: A total of 213 subjects with T2DM from Metabolic Disease Hospital, Tianjin Medical University from January 2013 to December 2013 were included in the study. Non-alcoholic fatty liver disease (NAFLD) was diagnosed with abdominal ultrasonography. Patients were divided into two groups: 22DM with NAFLD and 22DM without NAFLD. ALT, AST, gamma-glutamyltransferase, serum lipid, glycosylated hemoglobin A1c ( HbA1c), fructosamine, fasting glucose, insulin and 2 hours plasma glucose, insulin after 75g glucoseload were detected. The insulin resistance and P-cell function were assessed by HOMA-IR and HOMA-P. RESULTS: Among the 213 22DM subjects, 51% (108 cases) were with NAFLD. The HOMA-IR [4.76(2.83,7.21) vs. 2.79 (1.76, 4.37),P <0.05] and HOMA-P [49.18 (37.78, 85.09) vs. 29.50 (18.09, 45.54), P < 0.05] were significantly higher in 22DM with NAFLD than those in 22DM alone. Within subjects with 22DM and NAFLD,the HOMA-IR [6.28 (2.87, 8.17) vs. 2.95 (2.07, 3.66)P <0. 05] and HOMA-P [59.18 (37.78, 85.09) vs. 30.59 (28.56, 34.49), P < 0.05] levels were higher in subjects with normal liver function than those with abnormal liver function. CONCLUSIONS: T2DM patients with NAFLD have severer insulin resistance than those without NAFLD. The P-cell function of those patients was compensatory increased, which was decreased in subjects with abnormal liver function.

Association of Helicobacter pylori infection with diabetic complications: a meta-analysis.

UNLABELLED: BACKGROUND. Helicobacter pylori (HP) infects more than half of the world's population. The aim of the study was to quantify the association between HP and the risk of diabetic complications. METHODS: A literature search was performed to identify studies published between 1998 and 2012 for relevant risk estimates. Fixed and random effect meta-analytical techniques were conducted for ischemic heart disease, retinopathy, neuropathy and nephropathy. RESULTS: Eight studies were included. HP was associated with an increase risk of nephropathy and neuropathy (relative risk [RR]: 1.35, 95% CI: 1.06-1.73, p = 0.45 and RR: 1.20, 95% CI: 1.03-1.40, p = 0.29). We also discovered significant associations between bacterial infection and nephropathy risk in Oriental people (RR: 1.73, 95% CI: 1.19-2.50, p = 0.82) and in type 2 diabetic patients (RR: 1.50, 95% CI: 1.11-2.02, p = 0.29). CONCLUSIONS: Our meta-analyses suggest a possible relationship between HP and the risk of nephropathy and neuropathy. Our results also suggest that the effect of HP on the risk of nephropathy is stronger in Oriental people and in type 2 DM patients.

Does Streptococcus mitis, a neonatal oropharyngeal bacterium, influence the pathogenicity of Pseudomonas aeruginosa?

Microorganisms in a biofilm might promote or suppress each other. We previously found that Pseudomonas aeruginosa (P. aeruginosa) and the normal colonized bacteria in the oropharynx, Streptococcus mitis (S. mitis), were the most common bacteria in the biofilm found on newborns' endotracheal tubes. Here, we found that S. mitis enhanced the adhesion and biofilm formation of P. aeruginosa. Furthermore, it alleviated the immune response induced by P. aeruginosa. These findings remind us that we should not ignore the role of traditionally viewed non-pathogenic bacteria in biofilms and provide new insights into exploring bacterial interaction mechanisms in biofilm related infections.