Urine Extracellular Vesicle GATA2 mRNA Discriminates Biopsy Result in Men with Suspicion of Prostate Cancer.

PURPOSE: Prostate specific antigen has limited performance in detecting prostate cancer. The transcription factor GATA2 is expressed in aggressive prostate cancer. We analyzed the predictive value of urine extracellular vesicle GATA2 mRNA alone and in combination with a multigene panel to improve detection of prostate cancer and high risk disease. MATERIALS AND METHODS: GATA2 mRNA was analyzed in matched extracellular vesicles isolated from urines before and after prostatectomy (16) and paired urine and tissue prostatectomy samples (19). Extracellular vesicle GATA2 mRNA performance to distinguish prostate cancer and high grade disease was tested in training (52) and validation (165) cohorts. The predictive value of a multigene score including GATA2, PCA3 and TMPRSS2-ERG (GAPT-E) was tested in both cohorts. RESULTS: Confirming its prostate origin, urine extracellular vesicle GATA2 mRNA levels decreased significantly after prostatectomy and correlated with prostate cancer tissue GATA2 mRNA levels. In the training and validation cohort GATA2 discriminated prostate cancer (AUC 0.74 and 0.66) and high grade disease (AUC 0.78 and 0.65), respectively. Notably, the GAPT-E score improved discrimination of prostate cancer (AUC 0.84 and 0.72) and high grade cancer (AUC 0.85 and 0.71) in both cohorts when compared with each biomarker alone and PT-E (PCA3 and TMPRSS2-ERG). A GAPT-E score for high grade prostate cancer would avoid 92.1% of unnecessary prostate biopsies, compared to 61.9% when a PT-E score is used. CONCLUSIONS: Urine extracellular vesicle GATA2 mRNA analysis improves the detection of high risk prostate cancer and may reduce the number of unnecessary biopsies.

Using Contingent Reinforcement to Augment Muscle Activation After Perinatal Brachial Plexus Injury: A Pilot Study.

AIM: Examine the feasibility of increasing muscle activation with electromyographically (EMG)-triggered musical-video as reinforcement for children with perinatal brachial plexus injury (PBPI). METHODS: Six children with PBPI (9.3 ± 6.3 months; 5 female, 1 male) and 13 typically developing (TD) controls (7.8 ± 3.5 months; 4 female, 9 males) participated. The left arm was affected in 5/6 children with PBPI. We recorded the integral (Vs) of biceps activation with surface EMG during two conditions per arm in one session: (1) 100 second (s) baseline without reinforcement and (2) 300 s reinforcement (musical-video triggered to play with biceps activation above threshold [V]). We examined the relation between the mean integral with reinforcement and hand preference. RESULTS: Mean biceps activation significantly increased from baseline in the affected arm of the group with PBPI by the 2nd (p < .008) and 3rd (p < .0004) 100 s intervals of reinforcement. Six of 6 children with PBPI and 12/13 TD controls increased activation in at least one arm. A lower integral was linked with hand preference for the unaffected right side in the PBPI group. CONCLUSION: This study supports contingent reinforcement as a feasible method to increase muscle activation. Future work will examine training dose and intensity to increase arm function.

Validation of the National Institute of Neurological Disorders and Stroke Spinal Cord Injury MRI Common Data Elements Instrument.

BACKGROUND AND PURPOSE: The National Institute of Neurological Disorders and Stroke common data elements initiative was created to provide a consistent method for recording and reporting observations related to neurologic diseases in clinical trials. The purpose of this study is to validate the subset of common data elements related to MR imaging evaluation of acute spinal cord injury. MATERIALS AND METHODS: Thirty-five cervical and thoracic MR imaging studies of patients with acute spinal cord injury were evaluated independently in 2 rounds by 5 expert reviewers. Intra- and interrater agreement were calculated for 17 distinct MR imaging observations related to spinal cord injury. These included ordinal, categoric, and continuous measures related to the length and location of spinal cord hemorrhage and edema as well as spinal canal and cord measurements. Level of agreement was calculated using the interclass correlation coefficient and kappa. RESULTS: The ordinal common data elements spinal cord injury elements for lesion center and rostral or caudal extent of edema or hemorrhage demonstrated agreement ranging from interclass correlation coefficient 0.68 to 0.99. Reproducibility ranged from 0.95 to 1.00. Moderate agreement was observed for absolute length of hemorrhage and edema (0.54 to 0.60) with good reproducibility (0.78 to 0.83). Agreement for the Brain and Spinal Injury Center score showed the lowest interrater agreement with an overall kappa of 0.27 (0.20, 0.34). For 7 of the 8 variables related to spinal cord injury, agreement improved between the first and second evaluation. Continuous diameter measures of the spinal cord and spinal canal using interclass correlation coefficient varied substantially (0.23 to 0.83). CONCLUSIONS: Agreement was more consistent for the ordinal measures of spinal cord injury than continuous measures. Good to excellent agreement on length and location of spinal cord hemorrhage and edema can be achieved with ordinal measures alone.

Association of hypertension and sleep-disordered breathing.

BACKGROUND: To our knowledge, the association between sleep-disordered breathing (SDB) and hypertension has not been evaluated in subjects from the general population with a wide age range while adjusting for the possible confounding factors of age, body mass index, sex, menopause and use of hormone replacement therapy, race, alcohol use, and smoking. METHODS: In the first phase of this study, we interviewed 4364 men and 12,219 women, aged 20 to 100 years. In the second phase of this study, 741 men and 1000 women, previously interviewed, were selected based on the presence of risk factors for SDB (snoring, daytime sleepiness, obesity, hypertension, and, for women, menopause). Each subject selected for the second phase of the study provided a comprehensive history, underwent a physical examination, and was evaluated for 1 night in the sleep laboratory. In terms of severity of SDB, 4 groups were identified: moderate or severe (obstructive apnea/hypopnea index > or =15.0), mild (snoring and an obstructive apnea/hypopnea index of 0.1-14.9), snoring, and no SDB, the control group. RESULTS: Sleep-disordered breathing was independently associated with hypertension when potential confounders were controlled for in the logistic regression analysis. The strength of this association decreased with age and was proportional to the severity of SDB. In the best-fitted model, neither sex nor menopause changed the relationship between hypertension and SDB. CONCLUSIONS: In the results of this study, SDB, even snoring, was independently associated with hypertension in both men and women. This relationship was strongest in young subjects, especially those of normal weight, a finding that is consistent with previous findings that SDB is more severe in young individuals.