Bacterial endocarditis with AACEK (HACEK) organisms.

INTRODUCTION: Gram-negative organisms of the AACEK group, formerly known as HACEK, rarely cause endocarditis. CASE SERIES: We present three cases of bacterial endocarditis, involving native and prosthetic valves, caused by AACEK organisms. In two patients, Cardiobacterium hominis was the responsible organism, and in a third, Aggregatibacter aphrophilus was implicated. A dental source of infection was identified in two patients, and in all three patients, the presentation of endocarditis was subacute. DISCUSSION: This case series highlights the indolent nature of infection with the AACEK organisms. It also demonstrates the crucial role of multimodality imaging, especially transesophageal echocardiography, in the diagnosis of AACEk endocarditis of both native and prosthetic valves, and in delineating the extent of abscess in those with prosthetic valve infection.

Association of Chronic Kidney Disease With Risk of Intracerebral Hemorrhage.

Importance: The evidence linking chronic kidney disease (CKD) to spontaneous intracerebral hemorrhage (ICH) is inconclusive owing to possible confounding by comorbidities that frequently coexist in patients with these 2 diseases. Objective: To determine whether there is an association between CKD and ICH risk. Design, Setting, and Participants: A 3-stage study that combined observational and genetic analyses was conducted. First, the association between CKD and ICH risk was tested in the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study, a multicenter case-control study in the US. All participants with available data on CKD from ERICH were included. Second, this analysis was replicated in the UK Biobank (UKB), an ongoing population study in the UK. All participants in the UKB were included in this study. Third, mendelian randomization analyses were implemented in the UKB using 27 CKD-related genetic variants to test for genetic associations. ERICH was conducted from August 1, 2010, to August 1, 2017, and observed participants for 1 year. The UKB enrolled participants between 2006 and 2010 and will continue to observe them for 30 years. Data analysis was performed from November 11, 2019, to May 10, 2022. Exposures: CKD stages 1 to 5. Main Outcomes and Measures: The outcome of interest was ICH, ascertained in ERICH via expert review of neuroimages and in the UKB via a combination of self-reported data and International Statistical Classification of Diseases, Tenth Revision, codes. Results: In the ERICH study, a total of 2914 participants with ICH and 2954 controls who had available data on CKD were evaluated (mean [SD] age, 61.6 [14.0] years; 2433 female participants [41.5%]; 3435 male participants [58.5%]); CKD was found to be independently associated with higher risk of ICH (odds ratio [OR], 1.95; 95% CI, 1.35-2.89; P < .001). This association was not modified by race and ethnicity. Replication in the UKB with 1341 participants with ICH and 501 195 controls (mean [SD] age, 56.5 [8.1] years; 273 402 female participants [54.4%]; 229 134 male participants [45.6%]) confirmed this association (OR, 1.28; 95% CI, 1.01-1.62; P = .04). Mendelian randomization analyses indicated that genetically determined CKD was associated with ICH risk (OR, 1.56; 95% CI, 1.13-2.16; P = .007). Conclusions and Relevance: In this 3-stage study that combined observational and genetic analyses among study participants enrolled in 2 large observational studies with different characteristics and study designs, CKD was consistently associated with higher risk of ICH. Mendelian randomization analyses suggest that this association was causal. Further studies are needed to identify the specific biological pathways that mediate this association.

Development and Validation of a Model to Identify Critical Brain Injuries Using Natural Language Processing of Text Computed Tomography Reports.

Importance: Clinical text reports from head computed tomography (CT) represent rich, incompletely utilized information regarding acute brain injuries and neurologic outcomes. CT reports are unstructured; thus, extracting information at scale requires automated natural language processing (NLP). However, designing new NLP algorithms for each individual injury category is an unwieldy proposition. An NLP tool that summarizes all injuries in head CT reports would facilitate exploration of large data sets for clinical significance of neuroradiological findings. Objective: To automatically extract acute brain pathological data and their features from head CT reports. Design, Setting, and Participants: This diagnostic study developed a 2-part named entity recognition (NER) NLP model to extract and summarize data on acute brain injuries from head CT reports. The model, termed BrainNERD, extracts and summarizes detailed brain injury information for research applications. Model development included building and comparing 2 NER models using a custom dictionary of terms, including lesion type, location, size, and age, then designing a rule-based decoder using NER outputs to evaluate for the presence or absence of injury subtypes. BrainNERD was evaluated against independent test data sets of manually classified reports, including 2 external validation sets. The model was trained on head CT reports from 1152 patients generated by neuroradiologists at the Yale Acute Brain Injury Biorepository. External validation was conducted using reports from 2 outside institutions. Analyses were conducted from May 2020 to December 2021. Main Outcomes and Measures: Performance of the BrainNERD model was evaluated using precision, recall, and F1 scores based on manually labeled independent test data sets. Results: A total of 1152 patients (mean [SD] age, 67.6 [16.1] years; 586 [52%] men), were included in the training set. NER training using transformer architecture and bidirectional encoder representations from transformers was significantly faster than spaCy. For all metrics, the 10-fold cross-validation performance was 93% to 99%. The final test performance metrics for the NER test data set were 98.82% (95% CI, 98.37%-98.93%) for precision, 98.81% (95% CI, 98.46%-99.06%) for recall, and 98.81% (95% CI, 98.40%-98.94%) for the F score. The expert review comparison metrics were 99.06% (95% CI, 97.89%-99.13%) for precision, 98.10% (95% CI, 97.93%-98.77%) for recall, and 98.57% (95% CI, 97.78%-99.10%) for the F score. The decoder test set metrics were 96.06% (95% CI, 95.01%-97.16%) for precision, 96.42% (95% CI, 94.50%-97.87%) for recall, and 96.18% (95% CI, 95.151%-97.16%) for the F score. Performance in external institution report validation including 1053 head CR reports was greater than 96%. Conclusions and Relevance: These findings suggest that the BrainNERD model accurately extracted acute brain injury terms and their properties from head CT text reports. This freely available new tool could advance clinical research by integrating information in easily gathered head CT reports to expand knowledge of acute brain injury radiographic phenotypes.

Early Deterioration, Hematoma Expansion, and Outcomes in Deep Versus Lobar Intracerebral Hemorrhage: The FAST Trial.

BACKGROUND: In patients with intracerebral hemorrhage (ICH), it is unclear whether early neurological deterioration, hematoma expansion (HE), and outcome vary by supratentorial ICH location (deep versus lobar). Herein, we assessed these relationships in a clinical trial cohort that underwent brain imaging early after symptom onset. We hypothesized that HE would occur more frequently, and outcome would be worse in patients with deep ICH. METHODS: We performed a post hoc analysis of the FAST (Factor-VII-for-Acute-Hemorrhagic-Stroke-Treatment) trial including all patients with supratentorial hemorrhage. Enrolled patients underwent brain imaging within 3 hours of symptom onset and 24 hours after randomization. Multivariable regression was used to test the association between ICH location and 3 outcomes: HE (increase of ≥33% or 6mL), early neurological deterioration (decrease in Glasgow Coma Scale score ≥2 points or increase in National Institutes of Health Stroke Scale ≥4 points within 24 hours of admission), and 90-day outcome (modified Rankin Scale). RESULTS: Of 841 FAST trial patients, we included 728 (mean age 64 years, 38% women) with supratentorial hemorrhages (deep n=623, lobar n=105). HE (44 versus 27%, P=0.001) and early neurological deterioration (31 versus 17%, P=0.001) were more common in lobar hemorrhages. Deep hemorrhages were smaller than lobar hemorrhages at baseline (12 versus 35mL, P<0.001) and 24 hours (14 versus 38mL, P<0.001). Unadjusted 90-day outcome was worse in lobar compared with deep ICH (median modified Rankin Scale score 5 versus 4, P=0.03). However, when adjusting for variables included in the ICH score including ICH volume, deep location was associated with worse and lobar location with better outcome (odds ratio lobar location, 0.58 [95% CI, 0.38-0.89]; P=0.01). CONCLUSIONS: In this secondary analysis of randomized trial patients, lobar ICH location was associated with larger ICH volume, more HE and early neurological deterioration, and worse outcome than deep ICH. After adjustment for prognostic variables, however, deep ICH was associated with worse outcome, likely due to their proximity to eloquent brain structures.

Hospital Revisits for Post-Ischemic Stroke Epilepsy after Acute Stroke Interventions.

OBJECTIVES: Improvements in acute stroke care have led to an increase in ischemic stroke survivors, who are at risk for development of post-ischemic stroke epilepsy (PISE). The impact of therapies such as thrombectomy and thrombolysis on risk of hospital revisits for PISE is unclear. We utilized administrative data to investigate the association between stroke treatment and PISE-related visits. MATERIALS AND METHODS: Using claims data from California, New York, and Florida, we performed a retrospective analysis of adult survivors of acute ischemic strokes. Patients with history of epilepsy, trauma, infections, or tumors were excluded. Included patients were followed for a primary outcome of revisits for seizures or epilepsy. Cox proportional hazards regression was used to identify covariates associated with PISE. RESULTS: In 595,545 included patients (median age 74 [IQR 21], 52% female), the 6-year cumulative rate of PISE-related revisit was 2.20% (95% CI 2.16-2.24). In multivariable models adjusting for demographics, comorbidities, and indicators of stroke severity, IV-tPA (HR 1.42, 95% CI 1.31-1.54, p<0.001) but not MT (HR 1.62, 95% CI 0.90-1.50, p=0.2) was associated with PISE-related revisit. Patients who underwent decompressive craniectomy experienced a 2-fold increase in odds for returning with PISE (HR 2.35, 95% CI 1.69-3.26, p<0.001). In-hospital seizures (HR 4.06, 95% CI 3.76-4.39, p<0.001) also elevated risk for PISE. SIGNIFICANCE: We demonstrate that ischemic stroke survivors who received IV-tPA, underwent decompressive craniectomy, or experienced acute seizures were at increased risk PISE-related revisit. Close attention should be paid to these patients with increased potential for long-term development of and re-hospitalization for PISE.

Association of Serum IL-6 (Interleukin 6) With Functional Outcome After Intracerebral Hemorrhage.

BACKGROUND AND OBJECTIVES: IL-6 (interleukin 6) is a proinflammatory cytokine and an established biomarker in acute brain injury. We sought to determine whether admission IL-6 levels are associated with severity and functional outcome after spontaneous intracerebral hemorrhage (ICH). METHODS: We performed an exploratory analysis of the recombinant activated FAST trial (Factor VII for Acute ICH). Patients with admission serum IL-6 levels were included. Regression analyses were used to assess the associations between IL-6 and 90-day modified Rankin Scale. In secondary analyses, we used linear regression to evaluate the association between IL-6 and baseline ICH and perihematomal edema volumes. RESULTS: Of 841 enrolled patients, we included 552 (66%) with available admission IL-6 levels (mean age 64 [SD 13], female sex 203 [37%]). IL-6 was associated with poor outcome (modified Rankin Scale, 4-6; per additional 1 ng/L, odds ratio, 1.30 [95% CI, 1.04-1.63]; P=0.02) after adjustment for known predictors of outcome after ICH and treatment group. IL-6 was associated with ICH volume after adjustment for age, sex, and ICH location, and this association was modified by location (multivariable interaction, P=0.002), with a stronger association seen in lobar (ß, 12.51 [95% CI, 6.47-18.55], P<0.001) versus nonlobar (ß 5.32 [95% CI, 3.36-7.28], P<0.001) location. IL-6 was associated with perihematomal edema volume after adjustment for age, sex, ICH volume, and ICH location (ß 1.22 [95% CI, 0.15-2.29], P=0.03). Treatment group was not associated with IL-6 levels or outcome. CONCLUSIONS: In the FAST trial population, higher admission IL-6 levels were associated with worse 90-day functional outcome and larger ICH and perihematomal edema volumes.

Admission Hemoglobin Levels Are Associated With Functional Outcome in Spontaneous Intracerebral Hemorrhage.

OBJECTIVES: To test the hypothesis that admission hemoglobin levels are associated with outcome in primary, nontraumatic intracerebral hemorrhage. DESIGN: Individual patient data meta-analysis of three studies of intracerebral hemorrhage. SETTING: Two randomized clinical trials and one multiethnic observational study. PATIENTS: Patients with spontaneous, nontraumatic intracerebral hemorrhage. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Our exposure of interest was admission hemoglobin levels and the primary outcome was 3-month postintracerebral hemorrhage-dichotomized modified Rankin Scale (0-3 vs 4-6). Intermediate outcomes were admission hematoma volume and hematoma expansion defined as 6 mL or 33% increase in hemorrhage size on repeat CT. A total of 4,172 intracerebral hemorrhage patients were included in the study (mean age 63 [sd = 14]; female sex 1,668 [40%]). Each additional g/dL of admission hemoglobin was associated with 14% (odds ratio, 0.86; 95% CI, 0.82-0.91) and 7% (odds ratio, 0.93; 95% CI, 0.88-0.98) reductions in the risk of poor outcome in unadjusted and adjusted analyses, respectively. Dose-response analyses indicated a linear relationship between admission hemoglobin levels and poor outcome across the entire evaluated range (test-for-trend p < 0.001). No consistent associations were found between the admission hemoglobin levels and hematoma volume or hematoma expansion. CONCLUSIONS: Higher hemoglobin levels are associated with better outcome in intracerebral hemorrhage. Further research is needed to evaluate admission hemoglobin levels as both a therapeutic target and predictor of outcome.

Excess Cerebrovascular Mortality in the United States During the COVID-19 Pandemic.

BACKGROUND AND PURPOSE: The magnitude and drivers of excess cerebrovascular-specific mortality during the coronavirus disease 2019 (COVID-19) pandemic are unknown. We aim to quantify excess stroke-related deaths and characterize its association with social distancing behavior and COVID-19-related vascular pathology. METHODS: United States and state-level excess cerebrovascular deaths from January to May 2020 were quantified using National Center for Health Statistic data and Poisson regression models. Excess cerebrovascular deaths were analyzed as a function of time-varying stroke-related emergency medical service (EMS) calls and cumulative COVID-19 deaths using linear regression. A state-level regression analysis was performed to determine the association between excess cerebrovascular deaths and time spent in residences, measured by Google Community Mobility Reports, during the height of the pandemic after the first COVID-19 death (February 29). RESULTS: Forty states and New York City were included. Excess cerebrovascular mortality occurred nationally from the weeks ending March 28 to May 2, 2020, up to a 7.8% increase above expected levels during the week of April 18. Decreased stroke-related EMS calls were associated with excess stroke deaths one (70 deaths per 1000 fewer EMS calls [95% CI, 20-118]) and 2 weeks (85 deaths per 1000 fewer EMS calls [95% CI, 37-133]) later. Twenty-three states and New York City experienced excess cerebrovascular mortality during the pandemic height. A 10% increase in time spent at home was associated with a 4.3% increase in stroke deaths (incidence rate ratio, 1.043 [95% CI, 1.001-1.085]) after adjusting for COVID-19 deaths. CONCLUSIONS: Excess US cerebrovascular deaths during the COVID-19 pandemic were observed and associated with decreases in stroke-related EMS calls nationally and mobility at the state level. Public health measures are needed to identify and counter the reticence to seeking medical care for acute stroke during the COVID-19 pandemic.

Cause of death in spontaneous intracerebral hemorrhage survivors: Multistate longitudinal study.

OBJECTIVE: To determine the leading causes of death in intracerebral hemorrhage (ICH) survivors, we used administrative data from 3 large US states to identify adult survivors of a first-time spontaneous ICH and track all hospital readmissions resulting in death. METHODS: We performed a longitudinal analysis of prospectively collected claims data from hospitalizations in California (2005-2011), New York (2005-2014), and Florida (2005-2014). Adult residents admitted with a nontraumatic ICH who survived to discharge were included. Patients were followed for a primary outcome of any readmission resulting in death. The cause of death was defined as the primary diagnosis assigned at discharge. Multivariable Cox proportional hazards and multinomial logistic regression were used to determine factors associated with the risk for and cause of death. RESULTS: Of 72,432 ICH survivors (mean age 68 years [SD 16], 48% female), 12,753 (18%) died during a median follow-up period of 4.0 years (interquartile range 2.3-6.3). The leading causes of death were infection (34%), recurrent intracranial hemorrhage (14%), cardiac disease (8%), respiratory failure (8%), and ischemic stroke (5%). Death in patients with atrial fibrillation (AF) was more likely to be caused by ischemic stroke (odds ratio [OR] 2.4, 95% confidence interval [CI] 1.9-2.9, p < 0.001) and less likely to be caused by recurrent intracranial hemorrhage (OR 0.7, 95% CI 0.6-0.8, p < 0.001) compared to patients without AF. CONCLUSIONS: Infection is the leading cause of death in all ICH survivors. Survivors with AF were at increased risk for death from ischemic stroke. These findings will help prioritize interventions aimed to improve long-term survival and recovery in ICH survivors.