Early electroencephalography for outcome prediction of postanoxic coma:A prospective cohort study

OBJECTIVE: To provide evidence that early electroencephalography (EEG) allows for reliable prediction of poor or good outcome after cardiac arrest.METHODS: In a 5-center prospective cohort study, we included consecutive, comatose survivors of cardiac arrest. Continuous EEG recordings were started as soon as possible and continued up to 5 days. Five-minute EEG epochs were assessed by 2 reviewers, independently, at 8 predefined time points from 6 hours to 5 days after cardiac arrest, blinded for patients' actual condition, treatment, and outcome. EEG patterns were categorized as generalized suppression (&lt;10 μV), synchronous patterns with ≥50% suppression, continuous, or other. Outcome at 6 months was categorized as good (Cerebral Performance Category [CPC] = 1-2) or poor (CPC = 3-5).RESULTS: We included 850 patients, of whom 46% had a good outcome. Generalized suppression and synchronous patterns with ≥50% suppression predicted poor outcome without false positives at ≥6 hours after cardiac arrest. Their summed sensitivity was 0.47 (95% confidence interval [CI] = 0.42-0.51) at 12 hours and 0.30 (95% CI = 0.26-0.33) at 24 hours after cardiac arrest, with specificity of 1.00 (95% CI = 0.99-1.00) at both time points. At 36 hours or later, sensitivity for poor outcome was ≤0.22. Continuous EEG patterns at 12 hours predicted good outcome, with sensitivity of 0.50 (95% CI = 0.46-0.55) and specificity of 0.91 (95% CI = 0.88-0.93); at 24 hours or later, specificity for the prediction of good outcome was &lt;0.90.INTERPRETATION: EEG allows for reliable prediction of poor outcome after cardiac arrest, with maximum sensitivity in the first 24 hours. Continuous EEG patterns at 12 hours after cardiac arrest are associated with good recovery. ANN NEUROL 2019.</p

Cognition, emotional state, and quality of life of survivors after cardiac arrest with rhythmic and periodic EEG patterns

Aim: Rhythmic and periodic patterns (RPPs) on the electroencephalogram (EEG) in comatose patients after cardiac arrest have been associated with high case fatality rates. A good neurological outcome according to the Cerebral Performance Categories (CPC) has been reported in up to 10% of cases. Data on cognitive, emotional, and quality of life outcomes are lacking. We aimed to provide insight into these outcomes at one-year follow-up. Methods: We assessed outcome of surviving comatose patients after cardiac arrest with RPPs included in the ‘treatment of electroencephalographic status epilepticus after cardiopulmonary resuscitation’ (TELSTAR) trial at one-year follow-up, including the CPC for functional neurological outcome, a cognitive assessment, the hospital anxiety and depression scale (HADS) for emotional outcomes, and the 36-item short-form health survey (SF-36) for quality of life. Cognitive impairment was defined as a score of more than 1.5 SD below the mean on = 2 (sub)tests within a cognitive domain. Results: Fourteen patients were included (median age 58 years, 21% female), of whom 13 had a cognitive impairment. Eleven of 14 were impaired in memory, 9/14 in executive functioning, and 7/14 in attention. The median scores on the HADS and SF-36 were all worse than expected. Based on the CPC alone, 8/14 had a good outcome (CPC 1–2). Conclusion: Nearly all cardiac arrest survivors with RPPs during the comatose state have cognitive impairments at one-year follow-up. The incidence of anxiety and depression symptoms seem relatively high and quality of life relatively poor, despite ‘good’ outcomes according to the CPC

Delineation of prognostic biomarkers in prostate cancer

Prostate cancer is the most frequently diagnosed cancer in American men(1,2). Screening for prostate-specific antigen (PSA) has led to earlier detection of prostate cancer(3), but elevated serum PSA levels may be present in non-malignant conditions such as benign prostatic hyperlasia (BPH). Characterization of gene-expression profiles that molecularly distinguish prostatic neoplasms may identify genes involved in prostate carcinogenesis, elucidate clinical biomarkers, and lead to an improved classification of prostate cancer(4-6). Using microarrays of complementary DNA, we examined gene-expression profiles of more than 50 normal and neoplastic prostate specimens and three common prostate-cancer cell lines. Signature expression profiles of normal adjacent prostate (NAP), BPH, localized prostate cancer, and metastatic, hormone-refractory prostate cancer were determined. Here we establish many associations between genes and prostate cancer. We assessed two of these genes-hepsin, a transmembrane serine protease, and pim-1, a serine/threonine kinase-at the protein level using tissue microarrays consisting of over 700 clinically stratified prostate-cancer specimens. Expression of hepsin and pim-1 proteins was significantly correlated with measures of clinical outcome. Thus, the integration of cDNA microarray, high-density tissue microarray, and linked clinical and pathology data is a powerful approach to molecular profiling of human cancer.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62849/1/412822a0.pd

Outcome Prediction of Postanoxic Coma:A Comparison of Automated Electroencephalography Analysis Methods

BACKGROUND: To compare three computer-assisted quantitative electroencephalography (EEG) prediction models for the outcome prediction of comatose patients after cardiac arrest regarding predictive performance and robustness to artifacts. METHODS: A total of 871 continuous EEGs recorded up to 3 days after cardiac arrest in intensive care units of five teaching hospitals in the Netherlands were retrospectively analyzed. Outcome at 6 months was dichotomized as "good" (Cerebral Performance Category 1-2) or "poor" (Cerebral Performance Category 3-5). Three prediction models were implemented: a logistic regression model using two quantitative features, a random forest model with nine features, and a deep learning model based on a convolutional neural network. Data from two centers were used for training and fivefold cross-validation (n = 663), and data from three other centers were used for external validation (n = 208). Model output was the probability of good outcome. Predictive performances were evaluated by using receiver operating characteristic analysis and the calculation of predictive values. Robustness to artifacts was evaluated by using an artifact rejection algorithm, manually added noise, and randomly flattened channels in the EEG. RESULTS: The deep learning network showed the best overall predictive performance. On the external test set, poor outcome could be predicted by the deep learning network at 24 h with a sensitivity of 54% (95% confidence interval [CI] 44-64%) at a false positive rate (FPR) of 0% (95% CI 0-2%), significantly higher than the logistic regression (sensitivity 33%, FPR 0%) and random forest models (sensitivity 13%, FPR, 0%) (p < 0.05). Good outcome at 12 h could be predicted by the deep learning network with a sensitivity of 78% (95% CI 52-100%) at a FPR of 12% (95% CI 0-24%) and by the logistic regression model with a sensitivity of 83% (95% CI 83-83%) at a FPR of 3% (95% CI 3-3%), both significantly higher than the random forest model (sensitivity 1%, FPR 0%) (p < 0.05). The results of the deep learning network were the least affected by the presence of artifacts, added white noise, and flat EEG channels. CONCLUSIONS: A deep learning model outperformed logistic regression and random forest models for reliable, robust, EEG-based outcome prediction of comatose patients after cardiac arrest

Testing mutual exclusivity of ETS rearranged prostate cancer

Prostate cancer is a clinically heterogeneous and multifocal disease. More than 80% of patients with prostate cancer harbor multiple geographically discrete cancer foci at the time of diagnosis. Emerging data suggest that these foci are molecularly distinct consistent with the hypothesis that they arise as independent clones. One of the strongest arguments is the heterogeneity observed in the status of E26 transformation specific (ETS) rearrangements between discrete tumor foci. The clonal evolution of individual prostate cancer foci based on recent studies demonstrates intertumoral heterogeneity with intratumoral homogeneity. The issue of multifocality and interfocal heterogeneity is important and has not been fully elucidated due to lack of the systematic evaluation of ETS rearrangements in multiple tumor sites. The current study investigates the frequency of multiple gene rearrangements within the same focus and between different cancer foci. Fluorescence in situ hybridization (FISH) assays were designed to detect the four most common recurrent ETS gene rearrangements. In a cohort of 88 men with localized prostate cancer, we found ERG, ETV1, and ETV5 rearrangements in 51% (44/86), 6% (5/85), and 1% (1/86), respectively. None of the cases demonstrated ETV4 rearrangements. Mutual exclusiveness of ETS rearrangements was observed in the majority of cases; however, in six cases, we discovered multiple ETS or 5′ fusion partner rearrangements within the same tumor focus. In conclusion, we provide further evidence for prostate cancer tumor heterogeneity with the identification of multiple concurrent gene rearrangements

Propofol does not affect the reliability of early EEG for outcome prediction of comatose patients after cardiac arrest

Objective: To quantify the effects of propofol on the EEG after cardiac arrest and to assess their influence on predictions of outcome. Methods: In a prospective multicenter cohort study, we analyzed EEG recordings within the first 72 h after cardiac arrest. At six time points, EEGs were classified as favorable (continuous background), unfavorable (generalized suppression or synchronous patterns with ≥50% suppression), or intermediate. Quantitative EEG included measures for amplitude, background continuity, dominant frequency, and burst-suppression amplitude ratio (BSAR). The effect of propofol on each measure was estimated using mixed effects regression. Results: We included 496 patients. The EEG after propofol cessation had no additional value over EEG-based outcome predictions during propofol administration at 12 h after cardiac arrest. Propofol was associated with decreased EEG amplitude, background continuity and dominant frequency, and increased BSAR. However, propofol did neither increase the chance of unfavorable EEG patterns (adjusted odds ratio (aOR)0.95 per increase of 2 mg/kg/h, 95%-CI: 0.81–1.11)nor decrease the chance of favorable EEG patterns (aOR 0.98, 95%-CI: 0.89–1.09). Conclusions: Propofol induces changes of the postanoxic EEG, but does not affect its value for the prediction of outcome. Significance: We confirm the reliability of EEG-based outcome predictions in propofol-sedated patients after cardiac arrest