Anemia From Inflammation After Intracerebral Hemorrhage and Relationships With Outcome.

BACKGROUND: Baseline anemia is associated with poor intracerebral hemorrhage (ICH) outcomes. However, underlying drivers for anemia and whether anemia development after ICH impacts clinical outcomes are unknown. We hypothesized that inflammation drives anemia development after ICH and assessed their relationship to outcomes. METHODS AND RESULTS: Patients with serial hemoglobin and iron biomarker concentrations from the HIDEF (High-Dose Deferoxamine in Intracerebral Hemorrhage) trial were analyzed. Adjusted linear mixed models assessed laboratory changes over time. Of 42 patients, significant decrements in hemoglobin occurred with anemia increasing from 19% to 45% by day 5. Anemia of inflammation iron biomarker criteria was met in 88%. A separate cohort of 521 patients with ICH with more granular serial hemoglobin and long-term neurological outcome data was also investigated. Separate regression models assessed whether (1) systemic inflammatory response syndrome (SIRS) scores related to hemoglobin changes over time and (2) hemoglobin changes related to poor 90-day outcome. In this cohort, anemia prevalence increased from 30% to 71% within 2 days of admission yet persisted beyond this time. Elevated systemic inflammatory response syndrome was associated with greater hemoglobin decrements over time (adjusted parameter estimate: -0.27 [95% CI, -0.37 to -0.17]) and greater hemoglobin decrements were associated with poor outcomes (adjusted odds ratio per 1 g/dL increase, 0.76 [95% CI, 0.62-0.93]) independent to inflammation and ICH severity. CONCLUSIONS: We identified novel findings that acute anemia development after ICH is common, rapid, and related to inflammation. Because anemia development is associated with poor outcomes, further work is required to clarify if anemia, or its underlying drivers, are modifiable treatment targets that can improve ICH outcomes. REGISTRATION: https://www.clinicaltrials.gov Unique identifier: NCT01662895.

Concordance Between Active Partial Thromboplastin Time and Anti-Factor Xa Assays in Neurocritically Ill Patients Receiving Subcutaneous Heparin Prophylaxis.

Background: Laboratory monitoring is not recommended when subcutaneous unfractionated heparin (SQ-UFH) is administered at prophylactic doses. However, aPTT prolongation and associated hemorrhage has been reported in the neurocritically ill. At our institution, Neuroscience Intensive Care Unit (Neuro-ICU) patients with prolonged aPTT are further evaluated with a follow up aPTT and anti-factor Xa. Purpose: The purpose of this study was to describe concordance between aPTT and anti-factor Xa in neurocritically ill patients receiving prophylactic SQ-UFH with evidence of aPTT prolongation. Methods: A retrospective chart review of adult patients admitted to the Neuro-ICU from June 2017 to June 2019 was performed. Patients were included if they received SQ-UFH with aPTT levels and at least one anti-factor Xa level drawn within one hour of each other. Concordance between paired aPTT and anti-factor Xa was evaluated using Cohen's weighted kappa. Results: Forty two patients with 56 paired aPTT and anti-factor Xa levels were included. The most prescribed SQ-UFH regimen was 5000 units every 8 hours (60.7%) and anti-factor Xa levels were drawn a median (IQR) of 5.7 (3.1-10.7) hours after the SQ-UFH dose. Only 16 (28.6%) pairs were in concordance. The analysis showed a weighted kappa of .09; 95% CI [-.05 to .22] indicating poor agreement. Conclusions: In neurocritically ill patients receiving prophylactic SQ-UFH with aPTT prolongation, there was poor concordance between aPTT and anti-factor Xa. This suggests that aPTT prolongation may not be solely driven by heparin activity and further evaluation of mechanistic drivers for coagulopathy in this population is necessary.

Systematic Review of Resource Use and Costs in the Hospital Management of Intracerebral Hemorrhage.

BACKGROUND: While clinical guidelines provide a framework for hospital management of spontaneous intracerebral hemorrhage (ICH), variation in the resource use and costs of these services exists. We sought to perform a systematic literature review to assess the evidence on hospital resource use and costs associated with management of adult patients with ICH, as well as identify factors that impact variation in such hospital resource use and costs, regarding clinical characteristics and delivery of services. METHODS: A systematic literature review was performed using PubMed, Cochrane Central Register of Controlled Trials, and Ovid MEDLINE(R) 1946 to present. Articles were assessed against inclusion and exclusion criteria. Study design, ICH sample size, population, setting, objective, hospital characteristics, hospital resource use and cost data, and main study findings were abstracted. RESULTS: In total, 43 studies met the inclusion criteria. Pertinent clinical characteristics that increased hospital resource use included presence of comorbidities and baseline ICH severity. Aspects of service delivery that greatly impacted hospital resource consumption included intensive care unit length of stay and performance of surgical procedures and intensive care procedures. CONCLUSIONS: Hospital resource use and costs for patients with ICH were high and differed widely across studies. Making concrete conclusions on hospital resources and costs for ICH care was constrained, given methodologic and patient variation in the studies. Future research should evaluate the long-term cost-effectiveness of ICH treatment interventions and use specific economic evaluation guidelines and common data elements to mitigate study variation.

Systematic review of novel technology-based interventions for ischemic stroke.

PURPOSE: To identify novel technologies pertinent to the prevention, diagnosis, treatment, and rehabilitation of ischemic stroke, and recommend the technologies that show the most promise in advancing ischemic stroke care. METHOD: A systematic literature search on PubMed and Medscape was performed. Articles were assessed based on pre-determined criteria. Included journal articles were evaluated for specific characteristics and reviewed according to a structured paradigm. A search on www.clinicaltrials.gov was performed to identify pre-clinical ischemic stroke technological interventions. All clinical trial results were included. An additional search on PubMed was conducted to identify studies on robotic neuroendovascular procedures. RESULTS: Thirty journal articles and five clinical trials were analyzed. Articles were categorized as follows: six studies pertinent to pre-morbidity and prevention of ischemic stroke, three studies relevant to the diagnosis of ischemic stroke, 16 studies about post-ischemic stroke rehabilitation, and five studies on robotic neuroendovascular interventions. CONCLUSIONS: Novel technologies across the spectrum of ischemic stroke care were identified, and the ones that appear to have the most clinical utility are recommended. Future investigation of the feasibility and long-term efficacy of the recommended technologies in clinical settings is warranted.

History of Nonsteroidal Anti-inflammatory Drug Use and Functional Outcomes After Spontaneous Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Preclinical and clinical studies have suggested a potential benefit from COX-2 inhibition on secondary injury activation after spontaneous intracerebral hemorrhage (ICH). The aim of this study was to investigate the effect of pre-admission NSAID use on functional recovery in spontaneous ICH patients. METHODS: Consecutive adult ICH patients enrolled in the Intracerebral Hemorrhage Outcomes Project (2009-2018) with available 90-day follow-up data were included. Patients were categorized as NSAID (daily COX inhibitor use ≤ 7 days prior to ICH) and non-NSAID users (no daily COX inhibitor use ≤ 7 days prior to ICH). Primary outcome was the ordinal 90-day modified Rankin Scale (mRS) score. Outcomes were compared between cohorts using multivariable regression and propensity score-matched analyses. A secondary analysis excluding aspirin users was performed. RESULTS: The NSAID and non-NSAID cohorts comprised 228 and 361 patients, respectively. After 1:1 matching, the matched cohorts each comprised 140 patients. The 90-day mRS were comparable between the NSAID and non-NSAID cohorts in both the unmatched (aOR = 0.914 [0.626-1.336], p = 0.644) and matched (aOR = 0.650 [0.392-1.080], p = 0.097) analyses. The likelihood of recurrent ICH at 90 days was also comparable between the NSAID and non-NSAID cohorts in both the unmatched (aOR = 0.845 [0.359-1.992], p = 0.701) and matched analyses (aOR = 0.732 [0.241-2.220], p = 0.581). In the secondary analysis, the non-aspirin NSAID and non-NSAID cohorts comprised 38 and 361 patients, respectively. After 1:1 matching, the matched cohorts each comprised 38 patients. The 90-day mRS were comparable between the non-aspirin NSAID and non-NSAID cohorts in both the unmatched (aOR = 0.615 [0.343-1.101], p = 0.102) and matched (aOR = 0.525 [0.219-1.254], p = 0.147) analyses. The likelihood of recurrent ICH at 90 days was also comparable between the non-aspirin NSAID and non-NSAID cohorts in both the unmatched (aOR = 2.644 [0.258-27.091], p = 0.413) and matched (aOR = 2.586 [0.228-29.309], p = 0.443) analyses. After the exclusion of patients with DNR or withdrawal of care status, NSAID use was associated with lower mRS at 90 days (aOR = 0.379 [0.212-0.679], p = 0.001), lower mRS at hospital discharge (aOR = 0.505 [0.278-0.919], p = 0.025) and lower 90-day mortality rates (aOR = 0.309 [0.108-0.877], p = 0.027). CONCLUSIONS: History of nonselective COX inhibition may affect functional outcomes in ICH patients. Pre-admission NSAID use did not appear to worsen the severity of presenting ICH or increase the risk of recurrent ICH. Additional clinical studies may be warranted to investigate the effects of pre-admission NSAID use on ICH outcomes.

Fully Automated Segmentation Algorithm for Perihematomal Edema Volumetry After Spontaneous Intracerebral Hemorrhage.

Background and Purpose- Perihematomal edema (PHE) is a promising surrogate marker of secondary brain injury in patients with spontaneous intracerebral hemorrhage, but it can be challenging to accurately and rapidly quantify. The aims of this study are to derive and internally validate a fully automated segmentation algorithm for volumetric analysis of PHE. Methods- Inpatient computed tomography scans of 400 consecutive adults with spontaneous, supratentorial intracerebral hemorrhage enrolled in the Intracerebral Hemorrhage Outcomes Project (2009-2018) were separated into training (n=360) and test (n=40) datasets. A fully automated segmentation algorithm was derived from manual segmentations in the training dataset using convolutional neural networks, and its performance was compared with that of manual and semiautomated segmentation methods in the test dataset. Results- The mean volumetric dice similarity coefficients for the fully automated segmentation algorithm were 0.838±0.294 and 0.843±0.293 with manual and semiautomated segmentation methods as reference standards, respectively. PHE volumes derived from the fully automated versus manual (r=0.959; P<0.0001), fully automated versus semiautomated (r=0.960; P<0.0001), and semiautomated versus manual (r=0.961; P<0.0001) segmentation methods had strong between-group correlations. The fully automated segmentation algorithm (mean 18.0±1.8 seconds/scan) quantified PHE volumes at a significantly faster rate than both of the manual (mean 316.4±168.8 seconds/scan; P<0.0001) and semiautomated (mean 480.5±295.3 seconds/scan; P<0.0001) segmentation methods. Conclusions- The fully automated segmentation algorithm accurately quantified PHE volumes from computed tomography scans of supratentorial intracerebral hemorrhage patients with high fidelity and greater efficiency compared with manual and semiautomated segmentation methods. External validation of fully automated segmentation for assessment of PHE is warranted.

Location-specific differences in hematoma volume predict outcomes in patients with spontaneous intracerebral hemorrhage.

BACKGROUND AND OBJECTIVE: Functional outcome after spontaneous intracerebral hemorrhage (ICH) may vary depending on hematoma volume and location. We assessed the interaction between hematoma volume and location, and modified the original ICH score to include such an interaction. METHODS: Consecutive ICH patients were enrolled in the Intracerebral Hemorrhage Outcomes Project from 2009 to 2017. Inclusion criteria were age≥18 years, baseline modified Rankin Scale (mRS) score 0-2, neuroimaging, and follow-up. Functional dependence and mortality were defined as 90-day mRS>2 and death, respectively. A location ICH score was developed using multivariable regression and area under the receiver operator characteristic curve (AUROC) analyses. RESULTS: The study cohort comprised 311 patients, and the derivation and validation cohorts comprised 209 and 102 patients, respectively. Interactions between hematoma volume and location predicted functional dependence (p = 0.008) and mortality (p = 0.025). The location ICH score comprised age≥80 years (1 point), Glasgow Coma Scale score (3-9 = 2 points; 10-13 = 1 point), volume-location (lobar:≥24 mL=2 points, 21-24 mL=1 point; deep:≥8 mL=2 points, 7-8 mL=1 point; brainstem:≥6 mL=2 points, 3-6 mL=1 point; cerebellum:≥24 mL=2 points, 12-24 mL=1 point), and intraventricular hemorrhage (1 point). AUROC of the location ICH score was higher in functional dependence (0.883 vs. 0.770, p = 0.002) but not mortality (0.838 vs. 0.841, p = 0.918) discrimination compared to the original ICH score. CONCLUSIONS: The interaction between hematoma volume and location exerted an independent effect on outcomes. Excellent discrimination of functional dependence and mortality was observed with incorporation of location-specific volume thresholds into a prediction model. Therefore, the volume-location relationship plays an important role in ICH outcome prediction.

Fully Automated Segmentation Algorithm for Hematoma Volumetric Analysis in Spontaneous Intracerebral Hemorrhage.

Background and Purpose- Hematoma volume measurements influence prognosis and treatment decisions in patients with spontaneous intracerebral hemorrhage (ICH). The aims of this study are to derive and validate a fully automated segmentation algorithm for ICH volumetric analysis using deep learning methods. Methods- In-patient computed tomography scans of 300 consecutive adults (age ≥18 years) with spontaneous, supratentorial ICH who were enrolled in the ICHOP (Intracerebral Hemorrhage Outcomes Project; 2009-2018) were separated into training (n=260) and test (n=40) datasets. A fully automated segmentation algorithm was derived using convolutional neural networks, and it was trained on manual segmentations from the training dataset. The algorithm's performance was assessed against manual and semiautomated segmentation methods in the test dataset. Results- The mean volumetric Dice similarity coefficients for the fully automated segmentation algorithm when tested against manual and semiautomated segmentation methods were 0.894±0.264 and 0.905±0.254, respectively. ICH volumes derived from fully automated versus manual (R2=0.981; P<0.0001), fully automated versus semiautomated (R2=0.978; P<0.0001), and semiautomated versus manual (R2=0.990; P<0001) segmentation methods had strong between-group correlations. The fully automated segmentation algorithm (mean 12.0±2.7 s/scan) was significantly faster than both of the manual (mean 201.5±92.2 s/scan; P<0.001) and semiautomated (mean 288.58±160.3 s/scan; P<0.001) segmentation methods. Conclusions- The fully automated segmentation algorithm quantified hematoma volumes from computed tomography scans of supratentorial ICH patients with similar accuracy and substantially greater efficiency compared with manual and semiautomated segmentation methods. External validation of the fully automated segmentation algorithm is warranted.

A phase II randomized controlled trial of tiopronin for aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Delayed cerebral ischemia (DCI) is a significant contributor to poor outcomes after aneurysmal subarachnoid hemorrhage (aSAH). The neurotoxin 3-aminopropanal (3-AP) is upregulated in cerebral ischemia. This phase II clinical trial evaluated the efficacy of tiopronin in reducing CSF 3-AP levels in patients with aSAH. METHODS: In this prospective, randomized, double-blind, placebo-controlled, multicenter clinical trial, 60 patients were assigned to receive tiopronin or placebo in a 1:1 ratio. Treatment was commenced within 96 hours after aSAH onset, administered at a dose of 3 g daily, and continued until 14 days after aSAH or hospital discharge, whichever occurred earlier. The primary efficacy outcome was the CSF 3-AP level at 7 ± 1 days after aSAH. RESULTS: Of the 60 enrolled patients, 29 (97%) and 27 (93%) in the tiopronin and placebo arms, respectively, received more than one dose of the study drug or placebo. At post-aSAH day 7 ± 1, CSF samples were available in 41% (n = 12/29) and 48% (n = 13/27) of patients in the tiopronin and placebo arms, respectively. No difference in CSF 3-AP levels at post-aSAH day 7 ± 1 was observed between the study arms (11 ± 12 nmol/mL vs 13 ± 18 nmol/mL; p = 0.766). Prespecified adverse events led to early treatment cessation for 4 patients in the tiopronin arm and 2 in the placebo arm. CONCLUSIONS: The power of this study was affected by missing data. Therefore, the authors could not establish or refute an effect of tiopronin on CSF 3-AP levels. Additional observational studies investigating the role of 3-AP as a biomarker for DCI may be warranted prior to its use as a molecular target in future clinical trials.Clinical trial registration no.: NCT01095731 (ClinicalTrials.gov).

Effect of Cigarette Smoking on Functional Outcomes in Patients with Spontaneous Intracerebral Hemorrhage.

BACKGROUND: Nicotine may have neuroprotective effects on the injured brain through modulation of the cholinergic anti-inflammatory pathway. AIMS: This study aimed to evaluate the relationship between cigarette smoking and outcomes in patients with spontaneous intracerebral hemorrhage (ICH). METHODS: This was a retrospective review of consecutive ICH patients enrolled in the ICH Outcomes Project from 2009 to 2017. Patients with age ≥18 years and baseline modified Rankin Scale (mRS) score 0-2 were included. Smoking patterns were categorized as recent smoker (≤30 days prior to ICH) and not recent smoker (>30 days prior to ICH). Not recent smokers were further categorized into former smokers and nonsmokers. The primary outcome was good outcome (90-day mRS ≤ 2). Secondary outcomes were excellent outcome (90-day mRS 0-1), 90-day Barthel Index, and in-hospital and 90-day mortality. RESULTS: The study cohort comprised 545 patients, including 60 recent smokers and 485 not recent smokers. Recent smokers had higher rates of good (35% versus 23%; odds ratio [OR] = 1.787, P = .047) and excellent (25% versus 13%; OR = 2.220, P = .015) outcomes compared to not recent smokers. These differences were not significant after baseline adjustments. Recent smokers had higher rates of good (36% versus 24%; OR = 1.732, P = .063) and excellent (25% versus 13%; OR = 2.203, P = .018) outcomes compared to nonsmokers. These differences were not significant after baseline adjustments. A 90-day Barthel Index, in-hospital, and 90-day mortality were comparable between recent and not recent smokers, recent and nonsmokers, and former and nonsmokers. CONCLUSIONS: Despite potential neuroprotective effects of nicotine found in cigarettes, these may be outweighed by the detrimental effects of cigarette smoking on health outcomes.

Easily Screenable Characteristics Associated with Cognitive Improvement and Dysfunction After Carotid Endarterectomy.

BACKGROUND: Carotid endarterectomy (CEA) is an effective treatment for the prevention of stroke in patients with carotid artery stenosis. We aimed to clarify the incidence and risk factors for early cognitive dysfunction (eCD) and early cognitive improvement (eCI), defined as change in cognitive performance ≤24 hours after surgery, using a battery of neuropsychometric tests. METHODS: In total, 585 patients undergoing CEA were tested with neuropsychometric tests before and after surgery; 155 patients undergoing "simple" spine surgery were the reference group. Patient performance for each test was evaluated by z scores. Cognitive change was defined as eCD (or eCI) if: 1) patients had a z score ≤-2 (or ≥2) in ≥2 cognitive domains or 2) patients had mean z scores across all domains ≤-1.5 (or ≥1.5). Associations between the categorical cognitive outcomes and variables of interest were modeled using the proportional odds model. RESULTS: Of the 585 subjects, 24% had eCD, 6% had eCI, and 70% had "no change." Patients who had eCD were more likely to be statin naïve (odds ratio [OR] 1.23 [1.03-1.48], P = 0.02) or women (OR 1.27 [1.06-1.53], P = 0.02). Those with eCI were less likely to have less formal education (OR 0.95 [0.90-1.00], P = 0.04) and less likely to have diabetes mellitus (OR 0.8 [0.65-0.99], P = 0.04). CONCLUSIONS: Patients having CEA may develop eCD or eCI postoperatively. Medications likely to be associated with less eCD are statins and aspirin, which correlate most strongly in asymptomatic patients. In addition to confirming previous findings, we found that women were more likely than men to develop eCD. More sex-specific studies and analysis are needed to better explore these findings.

ABO Blood Type and Hematoma Expansion After Intracerebral Hemorrhage: An Exploratory Analysis.

BACKGROUND/PURPOSE: Blood type has become an increasingly recognized risk factor for coagulopathy. We explored the association between blood type and hematoma expansion (HE) after intracerebral hemorrhage (ICH). METHODS: Spontaneous ICH patients prospectively enrolled in an ongoing ICH cohort study at Columbia University Irving Medical Center from 2009 to 2016 were evaluated. Primary ICH patients with admission blood type testing were evaluated for HE differences, defined as > 33% relative HE. The association of blood type with radiographic HE outcomes was assessed using multivariable logistic regression models. The association of blood type and poor clinical outcomes using modified Rankin Scale (mRS 4-6) was additionally explored. RESULTS: Of 272 ICH patients with blood type data and neuroimaging available to determine HE, there were 146 (54%) type-O, 82 (30%) type-A, 34 (13%) type-B, and 10 (3%) type-AB patients. No significant baseline demographic, clinical, or radiographic differences were noted between blood types. Type-B blood was associated with more HE compared to other blood types (OR 2.82; 95% CI 1.23-6.45) after adjusting for known covariates of HE (anticoagulant use, time to admission computed tomography scan, and baseline hematoma volume). No associations with blood type and poor 3 month mRS were identified, but these analyses were limited secondary to our smaller cohort. CONCLUSIONS: There may be differences in HE after ICH in patients with different blood types. Further work is required to replicate these findings and identify the pathophysiologic mechanisms behind coagulopathy between blood types after ICH.

Systematic review and meta-analysis of perioperative and long-term outcomes in patients receiving statin therapy before carotid endarterectomy.

BACKGROUND: Carotid endarterectomy (CEA) is associated with perioperative stroke and mortality in a minority of cases. The aim of this systematic review and meta-analysis was to investigate the effect of pre-operative statins on perioperative outcomes in patients undergoing CEA for internal carotid artery (ICA) stenosis. METHODS: A systematic review of PubMed, Medline, and the Cochrane Database of Systematic Reviews was performed. Studies were included which reported perioperative stroke and/or survival outcomes following CEA for ICA stenosis and compared patients who were and were not taking pre-operative statins. Relevant data were extracted and pooled using meta-analysis. RESULTS: Seven studies met the inclusion criteria, comprising 21,387 patients. A total of 68.9% (14,976) were administered statins and 31.1% (6657) were statin-free. Pre-operative statin use was higher in patients with a history of cardiac disease (12.2 vs. 23.6% in the statin-free group), diabetes (31.6 vs. 25.1% in the statin-free group), and hypertension (83.5 vs. 72.2% in the statin-free group), while a greater proportion of statin-free patients had symptomatic disease (44.9 vs. 55.5% in the statin-free group). Statins were associated with reduced perioperative stroke in all patients (OR 0.57; 95% CI 0.34-0.95; p = 0.03) and in symptomatic patients (OR 0.57; 95% CI 0.35-0.93; p = 0.03). A trend towards lower perioperative mortality (OR 0.54; 95% CI 0.29, 1.03; p = 0.06) and significantly improved overall survival was observed in the statin group (HR 0.69; 95% CI 0.59-0.81; p < 0.001) at a mean follow-up of 62 months (range 27-76 months). CONCLUSIONS: Administration of statins before CEA is associated with lower rates of perioperative stroke and improved overall survival. Compliance with optimal medical treatment associated with the use of pre-operative statins may limit the clinical significance of these findings. Future investigation to characterize the potential benefit of statin therapy in patients undergoing CEA for ICA stenosis is warranted.

Incorporating High-Frequency Physiologic Data Using Computational Dictionary Learning Improves Prediction of Delayed Cerebral Ischemia Compared to Existing Methods.

PURPOSE: Accurate prediction of delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) can be critical for planning interventions to prevent poor neurological outcome. This paper presents a model using convolution dictionary learning to extract features from physiological data available from bedside monitors. We develop and validate a prediction model for DCI after SAH, demonstrating improved precision over standard methods alone. METHODS: 488 consecutive SAH admissions from 2006 to 2014 to a tertiary care hospital were included. Models were trained on 80%, while 20% were set aside for validation testing. Modified Fisher Scale was considered the standard grading scale in clinical use; baseline features also analyzed included age, sex, Hunt-Hess, and Glasgow Coma Scales. An unsupervised approach using convolution dictionary learning was used to extract features from physiological time series (systolic blood pressure and diastolic blood pressure, heart rate, respiratory rate, and oxygen saturation). Classifiers (partial least squares and linear and kernel support vector machines) were trained on feature subsets of the derivation dataset. Models were applied to the validation dataset. RESULTS: The performances of the best classifiers on the validation dataset are reported by feature subset. Standard grading scale (mFS): AUC 0.54. Combined demographics and grading scales (baseline features): AUC 0.63. Kernel derived physiologic features: AUC 0.66. Combined baseline and physiologic features with redundant feature reduction: AUC 0.71 on derivation dataset and 0.78 on validation dataset. CONCLUSION: Current DCI prediction tools rely on admission imaging and are advantageously simple to employ. However, using an agnostic and computationally inexpensive learning approach for high-frequency physiologic time series data, we demonstrated that we could incorporate individual physiologic data to achieve higher classification accuracy.

Causes and Timing of Unplanned Early Readmission After Neurosurgery.

BACKGROUND: Reducing the rate of 30-day hospital readmission has become a priority in healthcare quality improvement policy, with a focus on better characterizing the reasons for unplanned readmission. In neurosurgery, however, peer-reviewed analyses describing the patterns of readmission have been limited in their number and generalizability. OBJECTIVE: To determine the incidence, timing, and causes of 30-day readmission after neurosurgical procedures. METHODS: We conducted a retrospective longitudinal study from 2009 to 2012 using the Statewide Planning And Research Cooperative System, which collects patient-level details for all admissions and discharges within New York. We identified patients readmitted within 30 days of initial discharge. The rate of, reasons for, and time to readmission were determined overall and within 4 subgroups: craniotomies, cranial surgery without craniotomy, spine, and neuroendovascular procedures. RESULTS: There were 163 743 index admissions, of whom 14 791 (9.03%) were readmitted. The most common reasons for unplanned readmission were infection (29.52%) and medical complications (19.22%). Median time to readmission was 11 days, with hemorrhagic strokes and seizures occurring earlier, and medical complications and infections occurring later. Readmission rates were highest among patients undergoing cerebrospinal fluid shunt revision and malignant tumor resection (15.57%-22.60%). Spinal decompressions, however, accounted for the largest volume of readmissions (33.13%). CONCLUSION: Many readmissions may be preventable and occur at predictable time intervals. The causes and timing of readmission vary significantly across neurosurgical subgroups. Future studies should focus on detecting specific complications in select cohorts at predefined time points, which may allow for interventions to lower costs and reduce patient morbidity. ABBREVIATIONS: CSF, cerebrospinal fluidIQR, interquartile rangeSPARCS, Statewide Planning And Research Cooperative System.

Genome-wide association study of intracranial aneurysm identifies a new association on chromosome 7.

BACKGROUND AND PURPOSE: Common variants have been identified using genome-wide association studies which contribute to intracranial aneurysms (IA) susceptibility. However, it is clear that the variants identified to date do not account for the estimated genetic contribution to disease risk. METHODS: Initial analysis was performed in a discovery sample of 2617 IA cases and 2548 controls of white ancestry. Novel chromosomal regions meeting genome-wide significance were further tested for association in 2 independent replication samples: Dutch (717 cases; 3004 controls) and Finnish (799 cases; 2317 controls). A meta-analysis was performed to combine the results from the 3 studies for key chromosomal regions of interest. RESULTS: Genome-wide evidence of association was detected in the discovery sample on chromosome 9 (CDKN2BAS; rs10733376: P<1.0×10(-11)), in a gene previously associated with IA. A novel region on chromosome 7, near HDAC9, was associated with IA (rs10230207; P=4.14×10(-8)). This association replicated in the Dutch sample (P=0.01) but failed to show association in the Finnish sample (P=0.25). Meta-analysis results of the 3 cohorts reached statistical significant (P=9.91×10(-10)). CONCLUSIONS: We detected a novel region associated with IA susceptibility that was replicated in an independent Dutch sample. This region on chromosome 7 has been previously associated with ischemic stroke and the large vessel stroke occlusive subtype (including HDAC9), suggesting a possible genetic link between this stroke subtype and IA.