Interrater Variability in Identifying Ventilator Associated Pneumonia Using Six Different Definitions

Objective There is no widely accepted standard definition for Ventilator Associated Pneumonia (VAP). The reliability of the current definitions in use remains controversial. Our objective was to assess the reliability of six commonly used VAP definitions: The Loose, The Rigorous, The Modified Clinical Pulmonary Infection Score (CPIS), The Canadian Critical Care Trials Group (CCCTG), The International Sepsis Forum Consensus (ISFC) and The Center for Disease Control and Prevention (CDC). Design We examined the electronic health records of all the consecutively admitted adult patients at our institution who received invasive mechanical ventilation (IMV) for ≥ 48 hours, from January 2006 through December 2006.Patients were excluded if they developed pneumonia within the first 48 hours or if they had a tracheostomy before IMV. Two expert intensivists independently reviewed the following data for each patient: indications and duration of IMV, vital signs, oxygen requirements, frequency of respiratory suctioning, amount, color and consistency of secretion, ventilator settings, leukocyte count, microbiologic and radiographic data. Interreviewer reliability in diagnosing VAP independently were compared using Cohen’s-Kappa statistics. Results A total of 115 patients met the initial inclusion criteria of which 47 patients were excluded (40 had pneumonia on presentation, 6 developed pneumonia within 48 hours and 1 had a tracheostomy on admission). The inter-reviewer agreement Kappa for the Loose, the Rigorous, CPIS, CCCTG, ISFC and CDC definitions for VAP were 0.22, 0.49, 0.33, 0.41, 0.38 and 0.68 respectively. Conclusion The CDC definition of VAP proved to be statistically more reliable than other tested definitions of VAP, as demonstrated by the lowest interrater variability between two independent reviewers

Norepinephrine stimulates mobilization of endothelial progenitor cells after limb ischemia.

OBJECTIVE: During several pathological processes such as cancer progression, thermal injury, wound healing and hindlimb ischemia, the mobilization of endothelial progenitor cells (EPCs) mobilization was enhanced with an increase of sympathetic nerve activity and norepinephrine (NE) secretion, yet the cellular and molecular mechanisms involved in the effects of NE on EPCs has less been investigated. METHODS AND RESULTS: EPCs from BMs, peripheral circulation and spleens, the VEGF concentration in BM, skeletal muscle, peripheral circulation and spleen and angiogenesis in ischemic gastrocnemius were quantified in mice with hindlimbs ischemia. Systemic treatment of NE significantly increased EPCs number in BM, peripheral circulation and spleen, VEGF concentration in BM and skeletal muscle and angiogenesis in ischemic gastrocnemius in mice with hind limb ischemia, but did not affair VEGF concentration in peripheral circulation and spleen. EPCs isolated from healthy adults were cultured with NE in vitro to evaluate proliferation potential, migration capacity and phosphorylations of Akt and eNOS signal moleculars. Treatment of NE induced a significant increase in number of EPCs in the S-phase in a dose-dependent manner, as well as migrative activity of EPCs in vitro (p<0.05). The co-treatment of Phentolamine, I127, LY294002 and L-NAME with NE blocked the effects of NE on EPCs proliferation and migration. Treatment with NE significantly increased phosphorylation of Akt and eNOS of EPCs. Addition of phentolamine and I127 attenuated the activation of Akt/eNOS pathway, but metoprolol could not. Pretreatment of mice with either Phentolamine or I127 significantly attenuated the effects of NE on EPCs in vivo, VEGF concentration in BM, skeletal muscle and angiogenesis in ischemic gastrocnemius, but Metoprolol did not. CONCLUSION: These results unravel that sympathetic nervous system regulate EPCs mobilization and their pro-angiogenic capacity via α adrenoceptor, β 2 adrenoceptor and meanwhile Akt/eNOS signaling pathway

Association of Interleukin-6 Genetic Polymorphisms and Environment Factors Interactions with Coronary Artery Disease in a Chinese Han Population

Objectives: To investigate the influence of IL-6 single nucleotide polymorphisms (SNPs), additional gene-gene and gene-environment interactions on coronary artery disease (CAD) risk. Methods: A total of 751 participants (429 CAD patients and 322 controls) were recruited in this study. Logistic regression analysis was conducted to evaluate the association of IL-6 SNPs with CAD risk and generalized multifactor dimensionality reduction (GMDR) was performed to investigate the best interaction combinations for gene-gene and gene-environment interactions. Results: CAD risk is significantly higher in carriers of C allele of the rs1800795 polymorphism than those with GG genotype (CC + CG versus GG, adjusted OR (95%CI) = 2.07 (1.56–2.86), p < 0.001). GMDR analysis revealed rs1800795 was significantly interacted with tobacco smoking and alcohol drinking in two-locus model (p < 0.0010). Current smokers with CC or CG of rs1800795 genotype have the highest CAD risk, OR (95%CI) = 3.22 (2.45–3.94) and current drinkers with CC or CG of rs1800795 genotype have the highest CAD risk, OR (95%CI) = 3.17 (2.20–4.24). Conclusion: The C allele of rs1800795 within IL-6 gene promoter, rs1800795-tobacco smoking and rs1800795-alcohol drinking interaction were all associated with increased CAD risk

Relationship between the deep features of the full-scan pathological map of mucinous gastric carcinoma and related genes based on deep learning

Background: Long-term differential expression of disease-associated genes is a crucial driver of pathological changes in mucinous gastric carcinoma. Therefore, there should be a correlation between depth features extracted from pathology-based full-scan images using deep learning and disease-associated gene expression. This study tried to provides preliminary evidence that long-term differentially expressed (disease-associated) genes lead to subtle changes in disease pathology by exploring their correlation, and offer a new ideas for precise analysis of pathomics and combined analysis of pathomics and genomics. Methods: Full pathological scans, gene sequencing data, and clinical data of patients with mucinous gastric carcinoma were downloaded from TCGA data. The VGG-16 network architecture was used to construct a binary classification model to explore the potential of VGG-16 applications and extract the deep features of the pathology-based full-scan map. Differential gene expression analysis was performed and a protein-protein interaction network was constructed to screen disease-related core genes. Differential, Lasso regression, and extensive correlation analyses were used to screen for valuable deep features. Finally, a correlation analysis was used to determine whether there was a correlation between valuable deep features and disease-related core genes. Result: The accuracy of the binary classification model was 0.775 ± 0.129. A total of 24 disease-related core genes were screened, including ASPM, AURKA, AURKB, BUB1, BUB1B, CCNA2, CCNB1, CCNB2, CDCA8, CDK1, CENPF, DLGAP5, KIF11, KIF20A, KIF2C, KIF4A, MELK, PBK, RRM2, TOP2A, TPX2, TTK, UBE2C, and ZWINT. In addition, differential, Lasso regression, and extensive correlation analyses were used to screen eight valuable deep features, including features 51, 106, 109, 118, 257, 282, 326, and 487. Finally, the results of the correlation analysis suggested that valuable deep features were either positively or negatively correlated with core gene expression. Conclusion: The preliminary results of this study support our hypotheses. Deep learning may be an important bridge for the joint analysis of pathomics and genomics and provides preliminary evidence for long-term abnormal expression of genes leading to subtle changes in pathology

Association of rs662799 in APOA5 with CAD in Chinese Han population

Abstract Background CAD (Coronary Artery Disease) is a complex disease that influenced by various environmental and genetic factors. Previous studies have found many single nucleotide polymorphisms (SNPs) associated with the risk of CAD occurrence. However, the results are inconsistent. In this study, we aim to investigate genetic etiology in Chinese Han population by analysis of 7 SNPs in lipid metabolism pathway that previously has been reported to be associated with CAD. Methods A total of 631 samples were used in this study, including 435 CAD cases and 196 normal healthy controls. SNP genotyping were conducted via multiplex PCR amplifying followed by NGS (next-generation sequencing). Results Rs662799 in APOA5 (Apolipoprotein A5) gene was associated with CAD in Chinese Han population (Odds-ratio = 1.374, P-value = 0.03). No significant association was observed between the rest of SNPs and CAD. Stratified association analysis revealed rs5882 was associated with CAD in non-hypertension group (Odds-ratio = 1.593, P-value = 0.023). Rs1800588 was associated with CAD in smoking group (Odds-ratio = 1.603, P-value = 0.035). Conclusion The minor allele of rs662799 was the risk factor of CAD occurrences in Chinese Han population

NE increased EPCs in spleen in mice bearing limb ischemia.

<p>Cells from splenic tissue homogenates were lysed and analyzed with flow cytometry. EPCs in spleen were defined as CD34+/KDR+ cells (B). Proportion of EPCs in spleen was increased from 1.94±0.39% to 4.89±0.36% after intraperitoneal injection of NE in mice with limb ischemia (A, * P<0.05 compared with model group). Representative flow cytometric analysis of EPCs (CD34+/Flk-1+cells) were showed in part B.</p

Characterization of EPCs derived from human peripheral circulation.

<p>EPCs exhibitedspindle-shaped or cobblestone-like morphology and were stained by DAPI and double labeled by Dil-Ac-LDL and FITC-UEA-I.</p

NE increased EPCs in BM in mice with limb ischemia.

<p>Cells from peripheral blood were lysed and analyzed with flow cytometry. BM derived EPCs were defined as CD34+/KDR+ cells (B). Proportion of EPCs in BM was increased from 1.47±0.29% to 4.23±1.01% after intraperitoneal injection of NE in mice with limb ischemia (A, * P<0.05 compared with model group). Representative flow cytometric analysis of EPCs (CD34+/Flk-1+cells) were showed in part B.</p

Migrative activity of EPCs was increased by NE and blocked by Phentolamine and 127 in vitro.

<p>The migrative activity of EPCs was detected using transwell chamber assay. EPCs stayed on the membrane in the upper chamber were wiped off with a cotton swab. EPCs stayed on the lower membrane of transwell filter were stained with 1% crystal violet solution and counted in six random high-power (100×) microscope fields. NE increased migration of EPCs in a dose dependent manner (* P<0.05 compared with control group). This effect could be blocked by either pretreatment of phentolamine or I127, but not Metoprolol. Representative figure of EPCs passed through the holes into the lower chamber of each group are showed here.</p