Laboratory findings on admission and the extreme data during hospitalization in 39 <i>V</i>. <i>vulnificus</i>-infected patients treated between 2007 and 2010.

<p>Data are presented as mean ± SE, unless otherwise indicated.</p><p>^† Wilcoxon rank sum test, unless otherwise indicated.</p><p>* The difference is significant (p < 0.05).</p><p>^a CRP, C-reactive protein.</p><p>^b WBC, white blood cells.</p><p>^c INR, international normalized ratio.</p><p>^d LRINEC, laboratory risk indicator for necrotizing fasciitis.</p><p>^e MELD, model for end-stage liver disease.</p><p>^f MELD-Na, modified model for end-stage liver disease including sodium.</p><p>Laboratory findings on admission and the extreme data during hospitalization in 39 <i>V</i>. <i>vulnificus</i>-infected patients treated between 2007 and 2010.</p

Receiver operating characteristic (ROC) curve for predicting case fatality risk in 39 <i>V</i>. <i>vulnificus</i>-infected patients.

<p>The areas under the ROC curve (AOC) of the MELD and ΔMELD are 0.929 (95% CI = 0.818–1.000; <i>p</i> = 0.002) and 0.897 (95% CI = 0.772–1.000; <i>p</i> = 0.005), respectively. The diagonal reference line indicates no discrimination.</p

Odds ratio of the index variables in relation to the case fatality.

<p>* P value < 0.05 is significant and all analysis was done by logistic regression model in SPSS 17.0.</p><p>^a LRINEC, laboratory risk indicator for necrotizing fasciitis.</p><p>^b MELD, model for end-stage liver disease.</p><p>^c MELD-Na, modified model for end-stage liver disease including sodium.</p><p>^d Δ, difference between the admission and the extreme scores.</p><p>^e OR, odds ratio;</p><p>^f CI, confidence interval.</p><p>Odds ratio of the index variables in relation to the case fatality.</p

Area under the receiver operating characteristic (ROC) curve for predicting mortality risk in 39 <i>V</i>. <i>vulnificus</i>-infected patients treated between 2007 and 2010.

<p>* P value < 0.05 is significant and all analysis was done by logistic regression model in SPSS 17.0.</p><p>^a LRINEC, laboratory risk indicator for necrotizing fasciitis.</p><p>^b MELD, model for end-stage liver disease.</p><p>^c MELD-Na, modified model for end-stage liver disease including sodium.</p><p>^d Δ, difference between the admission and the extreme scores.</p><p>^e AUC, area under the receiver operating characteristic curve.</p><p>^f CI, confidence interval.</p><p>Area under the receiver operating characteristic (ROC) curve for predicting mortality risk in 39 <i>V</i>. <i>vulnificus</i>-infected patients treated between 2007 and 2010.</p

Group comparison of laboratory findings on admission and the extreme data during hospitalization.

<p>Data are presented as mean ± SE, unless otherwise indicated.</p><p>^† Wilcoxon rank sum test, unless otherwise indicated.</p><p>* The difference is significant (p < 0.05).</p><p>^a CRP, C-reactive protein.</p><p>^b WBC, white blood cells.</p><p>^c INR, international normalized ratio.</p><p>Group comparison of laboratory findings on admission and the extreme data during hospitalization.</p

<i>Staphylococcus aureus</i> biofilm elicits the expansion, activation and polarization of myeloid-derived suppressor cells <i>in vivo</i> and <i>in vitro</i>

<div><p><i>Staphylococcus aureus</i> (<i>S</i>. <i>aureus</i>) is one of the most common causes of biofilm infections in periprosthetic joint infections (PJIs). Accumulating evidence has shown that the immunosuppressive environment established by <i>S</i>. <i>aureus</i> biofilm infection in PJIs involves the presence of myeloid-derived suppressor cells (MDSCs) and M2-macrophages. Due to the diversity of MDSCs, little is known about whether <i>S</i>. <i>aureus</i> biofilm preferentially expands specific MDSC subsets or whether MDSCs can further differentiate into M2-macrophages during <i>S</i>. <i>aureus</i> biofilm infection. Here, we show that in agreement with the results from an established rat PJI model, <i>S</i>. <i>aureus</i> biofilm cocultured with freshly isolated bone marrow cells (BMCs) <i>in vitro</i> significantly increases the proportions of MDSCs, total macrophages and M2-macrophages. Interestingly, we find that treatment of the BMCs <i>in vitro</i> with <i>S</i>. <i>aureus</i> biofilm preferentially promotes the expansion of monocytic MDSCs but not granulocytic MDSCs. Biofilm treatment also substantially enhances the overall MDSC immunosuppressive activity in addition to the MDSC expansion <i>in vitro</i>. Importantly, we provide evidence that <i>S</i>. <i>aureus</i> biofilm is capable of further stimulating the conversion of monocytic MDSCs into M2-macrophages <i>in vitro</i> and <i>in vivo</i>. Collectively, our studies reveal a direct link between MDSCs and M2-macrophages occurring in <i>S</i>. <i>aureus</i>-associated PJIs.</p></div

Single Nucleotide Polymorphisms Other than Factor V Leiden Are Associated with Coagulopathy and Osteonecrosis of the Femoral Head in Chinese Patients

<div><p>Single nucleotide polymorphisms (SNPs) of factor V Leiden have been associated with osteonecrosis of the femoral head (ONFH) in Caucasians but remains controversial in Asians. We used an SNP microarray to screen 55 loci of factor V gene in patients with ONFH of Chinese. Significantly different candidate SNPs at 14 loci were analyzed in 146 patients and 116 healthy controls using MALDI-TOF (matrix-assisted laser desorption/ionization time-of-flight) mass spectrometry and gene sequencing. The factor V Leiden (rs6025) was not found in all participants. Six SNP loci (rs9332595, rs6020, rs9332647, rs3766110, rs10919186, and rs12040141) were confirmed with significant differences in patients but not in controls. The rs6020 G-to-A polymorphism was found in 88.9% of the patients. In addition, a high percentage (87.6%) of the patients had an abnormal coagulation profile that included hyperfibrinogen, elevated fibrinogen degradation products, elevated D-dimer, abnormal protein S, abnormal protein C, or a decrease in anti-thrombin III. Patients with the rs6020 G-to-A polymorphism (mutation) had a higher risk (odds ratio: 4.62; 95% confidence interval: 1.44–14.8) of having coagulation abnormalities than did those without the mutation (wild-type) (χ²<i>p</i>  =  0.006). Our findings suggested that the rs6020 polymorphism might be the genetic trait that accounts for the higher prevalence of ONFH in the Chinese population than in Westerners. Exposure to risk factors such as alcohol and steroids in patients with the rs6020 polymorphism causes coagulation abnormalities and, subsequently, thromboembolisms in the femoral head.</p></div

Recruitment and polarization of exogenous EGFP-expressing, CD11b-positive cells during <i>S</i>. <i>aureus</i> biofilm infection in mice.

<p>(a and b) Representative confocal microscopic images showing the recruitment and polarization of the EGFP-expressing cells in tissues near the <i>S</i>. <i>aureus</i> infection sites. Tissues near the <i>S</i>. <i>aureus</i> infected site were taken, frozen in -80°C, cryosectioned and stained with F4/80-PE (a and b, iii) and CD206-PerCP antibody (a and b, iv). White boxes indicate the EGFP⁺F4/80⁺CD206⁺ cells, and dashed boxes indicate the EGFP⁺F4/80^-CD206^- cells (probably MDSCs). Notably, only a very small proportion (<15%) of EGFP-positive cells were detected as the EGFP⁺F4/80^-CD206^- or EGFP⁺F4/80⁺CD206^- phenotype in the infected sites. Moreover, cells double positive for F4/80 and CD206 (arrows; endogenous M2-macrophages) were commonly detected in the infected sites. (c) A model for the development and polarization of MDSCs during <i>S</i>. <i>aureus</i> biofilm stimulation.</p

<i>S</i>. <i>aureus</i> biofilm is capable of stimulating the conversion of the CD11b-positive MDSCs into macrophages or M2-macrophgates <i>in vitro</i>.

<p>The isolated CD11b-positive MDSCs were cocultured with elevated amounts (0.2, 0.6 and 2.0 mg/ml) of <i>S</i>. <i>aureus</i> biofilm for 48 hr. The proportions of total macrophages (F4/80⁺) (a) and M2-macrophages (F4/80⁺CD206⁺) (b) in the CD11b-positive cell population were measured by flow cytometry. **p < 0.001.</p

<i>S</i>. <i>aureus</i> biofilm is able to promote expansion of CD4⁺CD25⁺Foxp3⁺ Tregs from CD4⁺ lymphocytes through modulation of MDSC function <i>in vitro</i>.

<p>(a and b) The CD11b-positive MDSC fractions were individually isolated from BMCs that were untreated or treated with different amounts (0.2, 0.6 and 2.0 mg/ml) of biofilm. The isolated CD11b-positive MDSCs were subsequently cocultured with spleen T cells (activated by anti-CD3/CD28 beads) at a 1:1 ratio. After 24- or 48-hr coculture, the frequency of CD4⁺CD25⁺Foxp3⁺ T cells was analyzed by flow cytometry using a Treg Flow kit. (c and d) Bars indicate the percentages of CD4⁺CD25⁺Foxp3⁺ T cells out of CD4⁺ lymphocytes in coculture experiments as described above (N = 2).</p