Decrease In Positive Predictive Value Research Articles

CXCL12 and CXCR4 as Potential Early Biomarkers for Luminal A and Luminal B Subtypes of Breast Cancer.

Breast cancer is the most common type of malignancy in women. Factors that increase the risk of occurrence include chronic inflammation, with chemokines as its mediators. Therefore, the purpose of the present study was to determine the diagnostic utility of CXCL12 and CXCR4 as modern tumor markers in patients with early-stage luminal A and luminal B subtype of breast cancer and also to compare the results with the routinely used marker - CA 15-3. The study included 100 patients with early breast cancer of luminal A and B subtypes, 50 women with benign breast lesion and 50 healthy women. The levels of CXCL12 and CXCR4 concentrations were determined by enzyme-linked immunosorbent assay (ELISA), comparative marker CA 15-3 - by electrochemiluminescence method (ECLIA). Concentrations of CXCL12 were significantly lower, while CXCR4 and CA 15-3 - significantly higher among patients with early-stage breast cancer than healthy women. CXCL12 also showed lower concentrations among fibroadenoma patients in comparison to healthy women, while CXCR4 - lower concentrations among fibroadenoma patients than cancer group. CXCL12 showed significantly higher values of sensitivity (79%), specificity (82%), positive predictive value (89.72%), negative predictive value (80%), diagnostic accuracy (80%) and diagnostic power (AUC = 0.8196) in the whole breast cancer group compared to the CA 15-3 marker (58%; 72%; 80.56%; 46.15%, 62.67%, 0.6434, resp.). Analysis of combined parameters resulted in increased sensitivity, negative predictive value and power of the test with a slight decrease in positive predictive value and a more significant decrease in specificity, reaching the best values for the three-parameter test CXCL12+CXCR4+CA15-3 (96%; 85.71%; AUC = 0.8812; 78.69%; 48%, resp.). The results indicate the preliminary usefulness of CXCL12 and CXCR4 as early biomarkers in the diagnosis of breast cancer, especially in the combined panel with CA 15-3.

Utility of prior cultures in predicting antibiotic resistance of bloodstream infections due to Gram-negative pathogens: a multicentre observational cohort study

ObjectivesAppropriate empiric antibiotic therapy in patients with bloodstream infections due to Gram-negative pathogens can improve outcomes. We evaluated the utility of prior microbiologic results for guiding empiric treatment in Gram-negative bloodstream infections. MethodsWe conducted a multicentre observational cohort study in two large health systems in Canada and the United States, including 1832 hospitalized patients with Gram-negative bloodstream infection (community, hospital and intensive care unit acquired) from April 2010 to March 2015. ResultsAmong 1832 patients with Gram-negative bloodstream infection, 28% (n = 504) of patients had a documented prior Gram-negative organism from a nonscreening culture within the previous 12 months. A most recent prior Gram-negative organism resistant to a given antibiotic was strongly predictive of the current organism's resistance to the same antibiotic. The overall specificity was 0.92 (95% confidence interval (CI) 0.91–0.93), and positive predictive value was 0.66 (95% CI 0.61–0.70) for predicting antibiotic resistance. Specificities and positive predictive values ranged from 0.77 to 0.98 and 0.43 to 0.78, respectively, across different antibiotics, organisms and patient subgroups. Increasing time between cultures was associated with a decrease in positive predictive value but not specificity. An heuristic based on a prior resistant Gram-negative pathogen could have been applied to one in four patients and in these patients would have changed therapy in one in five. ConclusionsIn patients with a bloodstream infection with a Gram-negative organism, identification of a most recent prior Gram-negative organism resistant to a drug of interest (within the last 12 months) is highly specific for resistance and should preclude use of that antibiotic.

DNA methylation analysis for the diagnosis of thyroid nodules - a pilot study with reference to BRAF(V) (600E) mutation and cytopathology results.

Promoter hypermethylation and the BRAF(V) (600E) mutation are both involved in thyroid tumorigenesis. We conducted a pilot study on the diagnosis of thyroid nodules by analysis of promoter hypermethylation status with reference to BRAF(V) (600E) mutation and cytopathology results using formalin-fixed, paraffin-embedded (FFPE) tissues and liquid-based preparation (LBP) thyroid fine needle aspiration (FNA) samples to predict more reliably the possibility of papillary carcinoma. We initially performed MethyLight analysis for 30 genes that are known to be hypermethylated in malignancies using 164 papillary carcinomas and 77 benign tissue samples. Five genes selected from the tissue analysis were subsequently analysed in 75 surgically proven benign and 66 surgically proven papillary carcinoma LBP FNA samples. Samples that showed two or more positive results among the five genes were classified as methylation positive. We also analysed the BRAF(V) (600E) mutation status of the FNA samples. We identified five genes that were significantly hypermethylated in malignant tissues: PTGS2, HOXA1, TMEFF2, p16 and PTEN. With respect to diagnostic potential, results obtained using the BRAF(V) (600E) mutation test combined with cytological examination were not significantly different from those obtained with cytological examination only. Combining methylation analyses with cytological examination or performing all three tests for diagnoses did not improve significantly the negative predictive values and sensitivity, but a significant decrease in positive predictive value and specificity was observed. Further studies are needed on larger samples to assess the potential value of methylation analysis of thyroid FNA.

The predictive value of cholesterol in young men for anelevated cholesterol ten to twelve years later

We reviewed the charts of 322 randomly selected male Airforce personnel with no known illnesses, who were first seen between 1970–1974 when aged 20–24 years. The results of all annual determinations of fasting serum total cholesterol (TC) during the following 10–12 years ending 1980–1984 were compiled. The cut-off point separating ‘normal’ from ‘elevated’ TC was arbitrarily set at the upper decile. The predictive value of the TC at entry for an elevated TC on follow-up was calculated. Subjects aged 20–24 years with a single elevated serum TC on entry had a 25% probability of having a similarly elevated TC 10–12 years later. Most of the decrease in positive predictive value could be accounted for by intra-individual variation. Subjects with elevated TC on 2 of 3 annual examinations after entry had a 50% probability of having a similarly elevated TC on 2 of 3 annual examinations 7–10 years later. We conclude that tracking of individuals with elevated TC is improved by multiple sampling.