Lymphocytopenia and neutrophil-lymphocyte count ratio predict bacteremia better than conventional infection markers in an emergency care unit.

INTRODUCTION: Absolute lymphocytopenia has been reported as a predictor of bacteremia in medical emergencies. Likewise, the neutrophil-lymphocyte count ratio (NLCR) has been shown a simple promising method to evaluate systemic inflammation in critically ill patients. METHODS: We retrospectively evaluated the ability of conventional infection markers, lymphocyte count and NLCR to predict bacteremia in adult patients admitted to the Emergency Department with suspected community-acquired bacteremia. The C-reactive protein (CRP) level, white blood cell (WBC) count, neutrophil count, lymphocyte count and NLCR were compared between patients with positive blood cultures (n = 92) and age-matched and gender-matched patients with negative blood cultures (n = 92) obtained upon Emergency Department admission. RESULTS: Significant differences between patients with positive and negative blood cultures were detected with respect to the CRP level (mean ± standard deviation 176 ± 138 mg/l vs. 116 ± 103 mg/l; P = 0.042), lymphocyte count (0.8 ± 0.5 × 109/l vs. 1.2 ± 0.7 × 109/l; P < 0.0001) and NLCR (20.9 ± 13.3 vs. 13.2 ± 14.1; P < 0.0001) but not regarding WBC count and neutrophil count. Sensitivity, specificity, positive and negative predictive values were highest for the NLCR (77.2%, 63.0%, 67.6% and 73.4%, respectively). The area under the receiver operating characteristic curve was highest for the lymphocyte count (0.73; confidence interval: 0.66 to 0.80) and the NLCR (0.73; 0.66 to 0.81). CONCLUSIONS: In an emergency care setting, both lymphocytopenia and NLCR are better predictors of bacteremia than routine parameters like CRP level, WBC count and neutrophil count. Attention to these markers is easy to integrate in daily practice and without extra costs.

MIB-1 (KI-67) proliferation index and cyclin-dependent kinase inhibitor p27(Kip1) protein expression in nephroblastoma.

PURPOSE: A number of studies have indicated that the tumor proliferation marker MIB-1 and cell cycle inhibitor p27(Kip1) expression are of prognostic importance in a variety of cancers. The present study was performed to evaluate the prognostic value of these molecules in Wilms' tumors. EXPERIMENTAL DESIGN: MIB-1 and p27(Kip1) expressions were investigated by the means of immunohistochemical analysis of 62 Wilms' tumor. Patients were preoperatively treated by chemotherapeutic agents and had a mean follow-up of 5.7 years. RESULTS: MIB-1 and p27(Kip1) were expressed in normal kidney tissues and in the three main components of Wilms' tumor, i.e., the blastemal, epithelial, and stromal cells. In Wilms' tumors, the percentage of MIB-1-positive cells in the blastema ranged between 0 and 42% (mean, 9.4%) and in the epithelial component between 0 and 53% (mean, 19.9%), with a significant difference (P < 0.01). The percentage of blastemal p27(Kip1)-positive cells ranged between 3 and 85% (mean, 55.1%) and for the epithelial component between 1 and 87% (mean, 59%). There was a significant inverse relationship between blastemal MIB-1 and p27(Kip1) expression in Wilms' tumor. Univariate analysis showed that blastemal MIB-1 and p27(Kip1) expression were indicative for clinical progression and tumor-specific survival. In a multivariate analysis, blastemal MIB-1 and p27(Kip1) protein expression proved to be an independent prognostic for clinical progression besides stage. CONCLUSIONS: It was concluded that both MIB-1-based proliferative activity and p27(Kip1) protein expression in the blastema have prognostic impact in Wilms' tumor.

Pathological and therapeutic significance of cellular invasion by Proteus mirabilis in an enterocystoplasty infection stone model.

Proteus mirabilis infection often leads to stone formation. We evaluated how bacterium-mucin adhesion, invasion, and intracellular crystal formation are related to antibiotic sensitivity and may cause frequent stone formation in enterocystoplasties. Five intestinal (Caco-2, HT29, HT29-18N2, HT29-FU, and HT29-MTX) and one ureter cell line (SV-HUC-1) were incubated in artificial urine with five Proteus mirabilis strains. Fluorescence-activated cell sorting (FACS), laser scanning microscopy, and electron microscopy evaluated cellular adhesion and/or invasion, pathologic changes to mitochondria, and P. mirabilis-mucin colocalization (MUC2 and MUC5AC). An MTT (thiazolyl blue tetrazolium bromide) assay and FACS analysis of caspase-3 evaluated the cellular response. Infected cells were incubated with antibiotics at dosages representing the expected urinary concentrations in a 10-year-old, 30-kg child to evaluate bacterial invasion and survival. All cell lines showed colocalization of P. mirabilis with human colonic mucin (i.e., MUC2) and human gastric mucin (i.e., MUC5AC). The correlation between membrane mucin expression and invasion was significant and opposite for SV-HUC-1 and HT29-MTX. Microscopically, invasion by P. mirabilis with intracellular crystal formation and mitochondrial damage was found. Double membranes surrounded bacteria in intestinal cells. Relative resistance to cotrimoxazole and augmentin was found in the presence of epithelial cells. Ciprofloxacin and gentamicin remained effective. Membrane mucin expression was correlated with relative antibiotic resistance. Cell invasion by P. mirabilis and mucin- and cell type-related distribution and response differences indicate bacterial tropism that affects crystal formation and mucosal presence. Bacterial invasion seems to have cell type-dependent mechanisms and prolong bacterial survival in antibiotic therapy, giving a new target for therapeutic optimalization of antibiotic treatment.