Association Between EEG Patterns and Serum Neurofilament Light After Cardiac Arrest: A Post Hoc Analysis of the TTM Trial.

BACKGROUND AND OBJECTIVES: EEG is widely used for prediction of neurologic outcome after cardiac arrest. To better understand the relationship between EEG and neuronal injury, we explored the association between EEG and neurofilament light (NfL) as a marker of neuroaxonal injury, evaluated whether highly malignant EEG patterns are reflected by high NfL levels, and explored the association of EEG backgrounds and EEG discharges with NfL. METHODS: We performed a post hoc analysis of the Target Temperature Management After Out-of-Hospital Cardiac Arrest trial. Routine EEGs were prospectively performed after the temperature intervention ≥36 hours postarrest. Patients who awoke or died prior to 36 hours postarrest were excluded. EEG experts blinded to clinical information classified EEG background, amount of discharges, and highly malignant EEG patterns according to the standardized American Clinical Neurophysiology Society terminology. Prospectively collected serum samples were analyzed for NfL after trial completion. The highest available concentration at 48 or 72 hours postarrest was used. RESULTS: A total of 262/939 patients with EEG and NfL data were included. Patients with highly malignant EEG patterns had 2.9 times higher NfL levels than patients with malignant patterns and NfL levels were 13 times higher in patients with malignant patterns than those with benign patterns (95% CI 1.4-6.1 and 6.5-26.2, respectively; effect size 0.47; p < 0.001). Both background and the amount of discharges were independently strongly associated with NfL levels (p < 0.001). The EEG background had a stronger association with NfL levels than EEG discharges (R2 = 0.30 and R2 = 0.10, respectively). NfL levels in patients with a continuous background were lower than for any other background (95% CI for discontinuous, burst-suppression, and suppression, respectively: 2.26-18.06, 3.91-41.71, and 5.74-41.74; effect size 0.30; p < 0.001 for all). NfL levels did not differ between suppression and burst suppression. Superimposed discharges were only associated with higher NfL levels if the EEG background was continuous. DISCUSSION: Benign, malignant, and highly malignant EEG patterns reflect the extent of brain injury as measured by NfL in serum. The extent of brain injury is more strongly related to the EEG background than superimposed discharges. Combining EEG and NfL may be useful to better identify patients misclassified by single methods. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov NCT01020916.

Changes in breast density over serial mammograms: A case-control study.

PURPOSE: In addition to a breast density category, temporal changes in breast density have gained attention as a dynamic breast cancer risk marker. This case-control study aimed to investigate a potential change in breast density preceding tumor development and the relationship of this potential change to prognostic pathological tumor variables. METHOD: A total of 51 consecutive, eligible-for-analyses, biopsy-proven breast cancers were diagnosed between 1 st of August and 31 st of December 2014 at Skåne University Hospital, Sweden. Mammogram data and patient- and tumor characteristics were retrieved retrospectively from medical charts. Breast density was quantitatively estimated using LIBRA (a free open source software package). The cases were matched for year of birth, number of screening rounds, and date for first and last mammograms with controls from the Malmö Breast Tomosynthesis Screening Trial in a 1:2 ratio, resulting in median time between mammograms of 4.5 (1.3-11.9) years for cases and 4.7 (1.4-11.1) years for controls, averaging approximately three screening rounds (1-6 rounds). RESULTS: We detected a statistically significant difference in breast density change over time, with cases showing an increase in breast density (1.7 %) as compared to controls (-0.3 %) (p = 0.045). We found that in women with breast cancer, older women (≥ 55 years) experienced a higher breast density increase compared to younger women (5.1 % vs. 0.3 %, p = 0.002). CONCLUSIONS: There was a statistically significant difference in density change, where women with breast cancer showed an increased density over time, which was particularly evident in women > 55 years of age.

Recombinant factor VIIa use in acute type A aortic dissection repair: A multicenter propensity-score-matched report from the Nordic Consortium for Acute Type A Aortic Dissection.

BACKGROUND: Surgery for acute type A aortic dissection (ATAAD) is often complicated by excessive bleeding. Recombinant factor VIIa (rFVIIa) effectively treats refractory bleeding associated with ATAAD surgery; however, adverse effects of rFVIIa in these patients have not been fully assessed. Here we evaluated rFVIIa treatment in ATAAD surgery using the Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD) database. METHODS: This was a multicenter, propensity score-matched, retrospective study. Information about rFVIIa use was available for 761 patients, of whom 171 were treated with rFVIIa. We successfully matched 120 patients treated with rFVIIa with 120 controls. Primary endpoints were in-hospital mortality, postoperative stroke, and renal replacement therapy (RRT). Survival data were presented using Kaplan-Meier estimates. RESULTS: Compared with controls, patients treated with rFVIIa received more transfusions of packed red blood cells (median, 9.0 U [4.0-17.0 U] vs 5.0 U [2.0-11.0 U]; P = .008), platelets (4.0 U [2.0-8.0 U] vs 2.0 U [1.0-4.4 U]; P <.001), and fresh frozen plasma (8.0 U [4.0-18.0 U] vs 5.5 U [2.0-10.3 U]; P = .01) underwent reexploration for bleeding more often (31.0% vs 16.8%; P = .014); and had greater 24-hour chest tube output (1500 L [835-2500 mL] vs 990 mL [520-1720 mL]). Treatment with rFVIIa was not associated with significantly increased rates of in-hospital mortality (odds ratio [OR], 0.74; 95% confidence interval [CI], 0.34-1.55; P = .487), postoperative stroke (OR, 1.75; 95% CI, 0.82-3.91; P = .163), or RRT (OR, 1.18; 95% CI, 0.48-2.92; P = .839). CONCLUSIONS: In this propensity-matched cohort study of patients undergoing ATAAD surgery, treatment with rFVIIa for major bleeding was not associated with a significantly increased risk of stroke, RRT, or mortality.

Standardized EEG interpretation accurately predicts prognosis after cardiac arrest.

OBJECTIVE: To identify reliable predictors of outcome in comatose patients after cardiac arrest using a single routine EEG and standardized interpretation according to the terminology proposed by the American Clinical Neurophysiology Society. METHODS: In this cohort study, 4 EEG specialists, blinded to outcome, evaluated prospectively recorded EEGs in the Target Temperature Management trial (TTM trial) that randomized patients to 33°C vs 36°C. Routine EEG was performed in patients still comatose after rewarming. EEGs were classified into highly malignant (suppression, suppression with periodic discharges, burst-suppression), malignant (periodic or rhythmic patterns, pathological or nonreactive background), and benign EEG (absence of malignant features). Poor outcome was defined as best Cerebral Performance Category score 3-5 until 180 days. RESULTS: Eight TTM sites randomized 202 patients. EEGs were recorded in 103 patients at a median 77 hours after cardiac arrest; 37% had a highly malignant EEG and all had a poor outcome (specificity 100%, sensitivity 50%). Any malignant EEG feature had a low specificity to predict poor prognosis (48%) but if 2 malignant EEG features were present specificity increased to 96% (p < 0.001). Specificity and sensitivity were not significantly affected by targeted temperature or sedation. A benign EEG was found in 1% of the patients with a poor outcome. CONCLUSIONS: Highly malignant EEG after rewarming reliably predicted poor outcome in half of patients without false predictions. An isolated finding of a single malignant feature did not predict poor outcome whereas a benign EEG was highly predictive of a good outcome.

Interrater variability of EEG interpretation in comatose cardiac arrest patients.

OBJECTIVE: EEG is widely used to predict outcome in comatose cardiac arrest patients, but its value has been limited by lack of a uniform classification. We used the EEG terminology proposed by the American Clinical Neurophysiology Society (ACNS) to assess interrater variability in a cohort of cardiac arrest patients included in the Target Temperature Management trial. The main objective was to evaluate if malignant EEG-patterns could reliably be identified. METHODS: Full-length EEGs from 103 comatose cardiac arrest patients were interpreted by four EEG-specialists with different nationalities who were blinded for patient outcome. Percent agreement and kappa (κ) for the categories in the ACNS EEG terminology and for prespecified malignant EEG-patterns were calculated. RESULTS: There was substantial interrater agreement (κ 0.71) for highly malignant patterns and moderate agreement (κ 0.42) for malignant patterns. Substantial agreement was found for malignant periodic or rhythmic patterns (κ 0.72) while agreement for identifying an unreactive EEG was fair (κ 0.26). CONCLUSIONS: The ACNS EEG terminology can be used to identify highly malignant EEG-patterns in post cardiac arrest patients in an international context with high reliability. SIGNIFICANCE: The establishment of strict criteria with high transferability between interpreters will increase the usefulness of routine EEG to assess neurological prognosis after cardiac arrest.