Evaluation of an automated von Willebrand factor glycoprotein IbM activity assay compared with 3 alternative von Willebrand factor activity assays.

Background: To overcome deficiencies of the traditional von Willebrand factor (VWF) ristocetin cofactor activity assay (VWF:RCo), several automated assays for VWF platelet-binding activity have been developed. Information on the performance of these assays and their diagnostic utility remains limited. Objectives: To validate the VWF:glycoprotein IbM assay INNOVANCE VWF Ac and compare it with an automated VWF:RCo assay as well as with an automated assay and a manual VWF:Ab assay and to generate reference ranges and analyze reproducibility of the VWF:glycoprotein IbM assay. Methods: Clinical sites enrolled healthy subjects and patients representing the intended use population; VWF activity assays were performed, and results were analyzed. The performance of the INNOVANCE VWF Ac assay was also compared between the BCS XP System and the CS-2500 and CS-5100 analyzers. Results: The INNOVANCE VWF Ac assay correlated well with the VWF:RCo assay and the automated HemosIL VWF:Ab assay, with Pearson coefficients of >.9 and a predicted bias of ≤5.0 IU/dL at VWF levels of 30 IU/dL and ≤5.8 IU/dL at the levels of 50 IU/dL, but correlation and bias were not as good when compared with the REAADS manual VWF:Ab assay. Reference ranges observed for healthy subjects correlated well with previously published findings. Reproducibility of the INNOVANCE VWF Ac assay on the BCS XP System and the CS analyzers was excellent, as was correlation among devices. Conclusion: The characteristics of the INNOVANCE VWF Ac assay regarding comparability with other VWF activity assays, reference ranges, and precision support the use of this assay for evaluation of patients with concern for von Willebrand disease.

An Interpretable Deep Learning Model for Speech Activity Detection Using Electrocorticographic Signals.

Numerous state-of-the-art solutions for neural speech decoding and synthesis incorporate deep learning into the processing pipeline. These models are typically opaque and can require significant computational resources for training and execution. A deep learning architecture is presented that learns input bandpass filters that capture task-relevant spectral features directly from data. Incorporating such explainable feature extraction into the model furthers the goal of creating end-to-end architectures that enable automated subject-specific parameter tuning while yielding an interpretable result. The model is implemented using intracranial brain data collected during a speech task. Using raw, unprocessed timesamples, the model detects the presence of speech at every timesample in a causal manner, suitable for online application. Model performance is comparable or superior to existing approaches that require substantial signal preprocessing and the learned frequency bands were found to converge to ranges that are supported by previous studies.

Anti-factor IIa (FIIa) heparin assay for patients on direct factor Xa (FXa) inhibitors.

BACKGROUND: Direct factor Xa (FXa) inhibitors are increasingly prescribed for outpatients, and those transitioning to unfractionated heparin (UFH) for hospital admission are monitored via an anti-FXa assay. Because of assay interference, UFH results would often be critically elevated, confounding dosing. OBJECTIVES: An anti-factor IIa (FIIa) UFH assay was evaluated for clinical use. METHODS: The BIOPHEN ANTI-IIa (Aniara Diagnostica) assay and anti-FXa INNOVANCE Heparin assay (Siemens Healthcare Diagnostics Products GmbH) were compared on the Siemens BCS XP system. Samples included UFH controls and calibrators and specimens from patients transitioning from apixaban or rivaroxaban to UFH. Method comparison, linearity, recovery, precision, and interference by direct FXa inhibitors were evaluated. The effect of the BIOPHEN ANTI-IIa assay on the rate of critically high UFH results was retrospectively reviewed 4 months after implementation. RESULTS: Accuracy studies using 0.24 and 0.50 IU/mL UFH yielded means and standard deviations of 0.26 ± 0.01 and 0.58 ± 0.01 IU/mL, respectively. Within-run and between-run coefficients of variation were 4.6% and 15.5% for the low control, and 1.8% and 10.6% for the high control. The method comparison slope was 0.9965 (r2  = 0.9468). The linear range was 0.1 to 1.3 IU/mL. The assay measured UFH in the presence of 192 ng/mL apixaban or 158 ng/mL rivaroxaban. Introduction of the assay for clinical use reduced the monthly percentage of critically high results from 9.4% to 3.8% for admitted heparinized patients who recently discontinued apixaban or rivaroxaban. CONCLUSIONS: The BIOPHEN ANTI-IIa assay is suitable for patients transitioning off apixaban or rivaroxaban.

Effects of the neurological wake-up test on clinical examination, intracranial pressure, brain metabolism and brain tissue oxygenation in severely brain-injured patients.

INTRODUCTION: Daily interruption of sedation (IS) has been implemented in 30 to 40% of intensive care units worldwide and may improve outcome in medical intensive care patients. Little is known about the benefit of IS in acutely brain-injured patients. METHODS: This prospective observational study was performed in a neuroscience intensive care unit in a tertiary-care academic center. Twenty consecutive severely brain-injured patients with multimodal neuromonitoring were analyzed for levels of brain lactate, pyruvate and glucose, intracranial pressure (ICP), cerebral perfusion pressure (CPP) and brain tissue oxygen tension (PbtO2) during IS trials. RESULTS: Of the 82 trial days, 54 IS-trials were performed as interruption of sedation and analgesics were not considered safe on 28 days (34%). An increase in the FOUR Score (Full Outline of UnResponsiveness score) was observed in 50% of IS-trials by a median of three (two to four) points. Detection of a new neurologic deficit occurred in one trial (2%), and in one-third of IS-trials the trial had to be stopped due to an ICP-crisis (> 20 mmHg), agitation or systemic desaturation. In IS-trials that had to be aborted, a significant increase in ICP and decrease in PbtO2 (P < 0.05), including 67% with critical values of PbtO2 < 20 mmHg, a tendency to brain metabolic distress (P < 0.07) was observed. CONCLUSIONS: Interruption of sedation revealed new relevant clinical information in only one trial and a large number of trials could not be performed or had to be stopped due to safety issues. Weighing pros and cons of IS-trials in patients with acute brain injury seems important as related side effects may overcome the clinical benefit.

Intracerebral monitoring of silent infarcts after subarachnoid hemorrhage.

BACKGROUND: Silent infarction is common in poor-grade subarachnoid hemorrhage (SAH) patients and associated with poor outcome. Invasive neuromonitoring devices may detect changes in cerebral metabolism and oxygenation. METHODS: From a consecutive series of 32 poor-grade SAH patients we identified all CT-scans obtained during multimodal neuromonitoring and analyzed microdialysis parameters and brain tissue oxygen tension (PbtO2) preceding CT-scanning. RESULTS: Eighteen percent of the reviewed head-CTs (12/67) revealed new infarcts. Of the eight infarcts in the vascular territory of the neuromonitoring, seven were clinically silent. Neuromonitoring changes preceding radiological evidence of infarction included lactate-pyruvate-ratio elevation and brain glucose decreases when compared to those with distant or no ischemia (P ≤ 0.03, respectively). PbtO2 was lower, but this did not reach statistical significance. CONCLUSIONS: These data suggest that there may be distinct changes in brain metabolism and oxygenation associated with the development of silent infarction within the monitored vascular territory in poor-grade SAH patients. Larger prospective studies are needed to determine whether treatment triggered by neuromonitoring data has an impact on outcome.

Spontaneous hyperventilation and brain tissue hypoxia in patients with severe brain injury.

BACKGROUND: Hyperventilation has been shown to be associated with cerebral vasoconstriction and increased risk of infarction. Our aim was to determine whether spontaneous reduction in end-tidal CO(2) (EtCO(2)) was associated with an increased in brain tissue hypoxia (BTH). METHOD: We studied 21 consecutive patients (mean age 50+/-16 years; 15 women) undergoing continuous monitoring for brain tissue oxygenation (PbtO(2)), intracranial pressure (ICP), cerebral perfusion pressure (CPP) and EtCO(2); mean values were recorded hourly BTH was defined as brain tissue oxygen tension (PbtO(2)) <15 mm Hg. RESULTS: Diagnoses included subarachnoid haemorrhage (67%), intracranial haemorrhage (24%) and traumatic brain injury (10%). Overall, BTH occurred during 22.5% of the study period (490/2179 hourly data). The frequency of BTH increased progressively from 15.7% in patients with normal EtCO(2) (35-44 mm Hg) to 33.9% in patients with EtCO(2)<25 mm Hg (p<0.001). The mean tidal volume and minute ventilation were 7+/-2 ml/kg and 9+/-2 1/min, respectively. Hypocapnia was associated with higher measured-than-set respiratory rates and maximal minute ventilation values, suggestive of spontaneous hyperventilation. Using a generalised estimated equation (GEE) and after adjustment for GCS, ICP and core temperature, the variables independently associated with BTH events were EtCO(2) (OR: 0.94; 95% CI 0.90 to 0.97; p<0.001) and CPP (OR: 0.98; 95% CI 0.97 to 0.99; p=0.004). CONCLUSION: The risk of brain tissue hypoxia in critically brain-injured patients increases when EtCO(2) values are reduced. Unintentional spontaneous hyperventilation may be a common and under-recognised cause of brain tissue hypoxia after severe brain injury.