External validation of a multiplex urinary protein panel for the detection of bladder cancer in a multicenter cohort.

BACKGROUND: Because of the faltering sensitivity and/or specificity, urine-based assays currently have a limited role in the management of patients with bladder cancer. The aim of this study was to externally validate our previously reported protein biomarker panel from multiple sites in the United States and Europe. METHODS: This multicenter external validation study included a total of 320 subjects (bladder cancer = 183). The 10 biomarkers (IL8, MMP9, MMP10, SERPINA1, VEGFA, ANG, CA9, APOE, SDC1, and SERPINE1) were measured using commercial ELISA assays in an external laboratory. The diagnostic performance of the biomarker panel was assessed using receiver operator curves (ROC) and descriptive statistical values. RESULTS: Utilizing the combination of all 10 biomarkers, the area under the ROC for the diagnostic panel was noted to be 0.847 (95% confidence interval, 0.796-0.899), outperforming any single biomarker. The multiplex assay at optimal cutoff value achieved an overall sensitivity of 0.79, specificity of 0.79, positive prediction value of 0.73, and negative prediction value of 0.84 for bladder cancer classification. Sensitivity values of the diagnostic panel for high-grade bladder cancer, low-grade bladder cancer, muscle invasive bladder cancer, and non-muscle invasive bladder cancer were 0.81, 0.90, 0.95, and 0.77, respectively. CONCLUSIONS: Urinary levels of the biomarker panel enabled discrimination of patients with bladder cancer and controls, and the levels of biomarker subsets were associated with advancing tumor grade and stage. IMPACT: If proven to be reliable, urinary diagnostic biomarker assays can detect bladder cancer in a timely manner such that the patient can expect improvements in overall survival and quality of life.

Fetal outcome for infants in breech by method of delivery: experiences with a stand-by service system of senior obstetricians and women's choices of mode of delivery.

OBJECTIVE: To show that the fetal outcome in vaginal deliveries (VD) of breech presentation in a setting of a senior obstetrician stand-by system is as good as in planned cesarean sections. PATIENTS AND METHODS: This observational prospective intent-to-treat study (n=211 singleton breech presentation pregnancies of ≥35 weeks of gestation) compared two groups of breech deliveries: planned cesarean sections (PCS, n=126) and intended VD (IVD, n=85) resulting in vaginal deliveries (VD, n=46) as well as secondary cesarean sections (SCS, n=39). Women's informed choice as well as strict pre-selection criteria for vaginally intended breech presentation deliveries was followed. RESULTS: Fetal outcome of vaginal breech deliveries and of primary as well as SCS (45.9% of IVD) was comparable in terms of cord blood pH, base excess, Apgar score, fetal trauma, and transfer to neonatal intensive care unit. CONCLUSIONS: Vaginal breech delivery is a safe option in a stand-by system of senior obstetricians with controlled decision-making before labor.