Adjunctive S100A8/A9 Immunomodulation Hinders Ciprofloxacin Resistance in Pseudomonas aeruginosa in a Murine Biofilm Wound Model.

Objective: Pseudomonas aeruginosa is known to contribute to the pathogenesis of chronic wounds by biofilm-establishment with increased tolerance to host response and antibiotics. The neutrophil-factor S100A8/A9 has a promising adjuvant effect when combined with ciprofloxacin, measured by quantitative bacteriology, and increased anti- and lowered pro-inflammatory proteins. We speculated whether a S100A8/A9 supplement could prevent ciprofloxacin resistance in infected wounds. Method: Full-thickness 2.9cm2-necrosis was inflicted on 32 mice. On day 4, P.aeruginosa in seaweed alginate was injected sub-eschar to mimic a mono-pathogenic biofilm. Mice were randomized to receive ciprofloxacin and S100A8/A9 (n=14), ciprofloxacin (n=12) or saline (n=6). Half of the mice in each group were euthanized day 6 and the remaining day 10 post-infection. Mice were treated until sacrifice. Primary endpoint was the appearance of ciprofloxacin resistant P.aeruginosa. The study was further evaluated by genetic characterization of resistance, means of quantitative bacteriology, wound-size and cytokine-production. Results: Three mice receiving ciprofloxacin monotherapy developed resistance after 14 days. None of the mice receiving combination therapy changed resistance pattern. Sequencing of fluoroquinolone-resistance determining regions in the ciprofloxacin resistant isolates identified two high-resistant strains mutated in gyrA C248T (MIC>32µg/ml) and a gyr B mutation was found in the sample with low level resistance (MIC=3µg/ml). Bacterial densities in wounds were lower in the dual treated group compared to the placebo group on both termination days. Conclusion: This study supports the ciprofloxacin augmenting effect and indicates a protective effect in terms of hindered ciprofloxacin resistance of adjuvant S100A8/A9 in P.aeruginosa biofilm infected chronic wounds.

Improved apnea-hypopnea index and lowest oxygen saturation after maxillomandibular advancement with or without counterclockwise rotation in patients with obstructive sleep apnea: a meta-analysis.

PURPOSE: This study investigated whether patients with obstructive sleep apnea (OSA) who undergo maxillomandibular advancement (MMA) with counterclockwise (CCW) rotation compared with those who undergo MMA without CCW rotation have better outcomes. MATERIALS AND METHODS: This was a systematic review with meta-analysis. The Medline and Cochrane databases were searched for randomized controlled trials using Medical Subject Headings. The predictor variable was operative technique, namely MMA with or without CCW rotation of the maxillofacial complex. The key outcome variables were changes in pre- and postsurgical values of pharyngeal volume measured on computed tomogram or cone-beam computed tomogram and changes in Apnea-Hypopnea Index (AHI) and lowest oxygen saturation (LSAT) values after surgery. Data were subjected to a meta-analysis based on odds ratios (OR) with 95% confidence intervals (CIs) and P values lower than .05 by χ(2) test were considered significant. RESULTS: Twenty-one randomized controlled trials were identified and 4 were assessed for the variables of interest. Postoperative AHI and LSAT measurements showed vast improvement. The sample was not large enough to make a correlation between pharyngeal volume changes and surgical method used. Postoperative parameters included an AHI lower than 5 (OR = 14.9; 95% CI, 2.7-83.5; P = .002), an AHI lower than 20 (OR = 114.8; 95% CI, 23.5-561.1; P <.00001), pooled results of a 50% decrease in the AHI (OR = 6.1; 95% CI, 2.2-17.0; P = .0006), and an increase greater than 90% in LSAT measurements during sleep (OR = 6.0; 95% CI, 1.8-19.9; P = .003). The funnel plot showed no evidence of publication bias. CONCLUSION: CCW-MMA or MMA in patients with OSA results in a statistically meaningful decrease in postoperative AHI and a statistically meaningful increase in postoperative LSAT.

Meta-analysis of routine blood tests as predictors of mortality in COPD.

OBJECTIVE: The purpose of this study was to examine whether routine blood tests can be useful in predicting mortality in COPD patients. METHODS: Eligible studies were found through a search conducted in the PubMed and Embase databases, the Cochrane Library, and the Web of Knowledge. Twelve studies were included for the meta-analysis of five biochemical markers. Pooled odds ratios (ORs), matching 95% confidence intervals (CIs), and p-values for each of the biochemical markers were calculated using the random effect model. RESULTS: The following four examined biochemical markers were shown to be associated with mortality in patients suffering from COPD: anemia (OR=2.62, 95% CI: 1.60; 4.29, p=0.01), hypoalbuminemia (OR=2.90, 95% CI: 1.56; 5.40, p=0.0008), elevated NT-proBNP (OR=7.54, 95% CI: 4.04; 14.10, p<0.00001), and elevated cardiac troponin T (OR=3.10, 95% CI: 1.11; 8.25, p=0.03). hs-CRP was not found to be associated with increased mortality. CONCLUSION: In this study, we found that anemia, hypoalbuminemia, elevated NT-proBNP, and elevated cardiac troponin T were associated with increased mortality in patients suffering from COPD.

Routine blood tests as predictors of mortality in hip fracture patients.

OBJECTIVE: The aim of this study was to assess the evidence for the association between different biochemical markers at admission and mortality through a meta-analysis. DATA SOURCES: PubMed-, Embase-, Cochran Library and the Web of Knowledge were searched for cohort studies. STUDY SELECTION: Eligible studies were observational studies with a study population larger than 150 subjects, a mean age above 60 years and a study duration below 730 days. DATA EXTRACTION: Characteristics of studies and outcomes of all-cause mortality were extracted from the retrieved articles. Data were pooled across studies for the individual biomarker using random- or fixed-effect analysis. DATA SYNTHESIS: 15 eligible studies of 5 different markers on mortality were studied. The following markers were found to be of prognostic value on mortality in hip fracture patients: low haemoglobin (odds ratio, 2.78; 95% confidence interval, 2.17-3.55; P<0.00001, 3148 subjects included), low total lymphocyte count, TLC (odds ratio, 2.60; 95% confidence interval, 1.61-4.20; P<0.00001, 1689 subjects included), low albumin (odds ratio, 1.83; 95% confidence interval, 1.31-2.56; P=0.0004, 1680 subjects included), low albumin/low TLC (odds ratio, 3.00; 95% confidence interval, 1.81-4.99; P<0.0001, 704 subjects included), low albumin/high TLC (odds ratio, 3.39; 95% confidence interval, 1.83-6.29; P=0.0001, 704 subjects included), high creatinine (odds ratio, 1.58; 95% confidence interval, 1.25-1.99; P=0.0001, 3761 subjects included), and high PTH (odds ratio, 15.43; 95% confidence interval, 3.60-66.14; P=0.0002, 525 subjects included). CONCLUSION: Biochemical markers at admission are valid predictors of mortality in hip fracture patients.