The use of artificial intelligence (AI) has grown dramatically in the past few years in the United States and worldwide, with more than 300 AI-enabled devices approved by the U.S. Food and Drug ...Administration (FDA). Most of these AI-enabled applications focus on helping radiologists with detection, triage, and prioritization of tasks by using data from a single point, but clinical practice often encompasses a dynamic scenario wherein physicians make decisions on the basis of longitudinal information. Unfortunately, benchmark data sets incorporating clinical and radiologic data from several points are scarce, and, therefore, the machine learning community has not focused on developing methods and architectures suitable for these tasks. Current AI algorithms are not suited to tackle key image interpretation tasks that require comparisons to previous examinations. Focusing on the curation of data sets and algorithm development that allow for comparisons at different points will be required to advance the range of relevant tasks covered by future AI-enabled FDA-cleared devices.
Background/Objective
There are limited data on the risks and benefits of using andexanet alfa (AA) in comparison with four-factor prothrombin complex concentrate (4F-PCC) to reverse factor Xa ...inhibitors (FXi) associated intracranial hemorrhage (ICH). We sought to describe our experience with AA or 4F-PCC in patients with oral FXi-related traumatic and spontaneous ICH.
Methods
We conducted a retrospective review of consecutive adult patients with FXi-related ICH who received AA or 4F-PCC. FXi-related ICH cases included traumatic and spontaneous intracranial hemorrhages. Our primary analysis evaluated ICH stability on head computed tomography scan (CT), defined as a similar amount of blood from the initial scan at the onset of ICH to subsequent scans, at 6-h and 24-h post-administration of AA or 4F-PCC. For the subset of spontaneous intraparenchymal hemorrhages, volume was measured at 6-h and 24-h post-reversal. In secondary analyses, we evaluated good functional outcome at discharge, defined as a Modified Rankin Score of less than 3, and the incidence of thrombotic events after AA or 4F-PCC adminstration, during hospitalization.
Results
A total of 44 patients (16 traumatic and 28 spontaneous ICH) with median age of 79 years 72–86, 36% females, with a FXi-related ICH, were included in this study. The majority of spontaneous ICHs were intraparenchymal 19 (68%). Twenty-eight patients (64%) received AA and 16 patients (36%) received 4F-PCC. There was no difference between AA and 4F-PCC in terms of CT stability at 6 h (21 78% vs 10 71%,
p
= 0.71) and 24 h (15 88% vs 6 60%,
p
= 0.15). In a subgroup of patients with spontaneous intraparenchymal hemorrhage, there was no difference in the degree of achieved hemostasis based on hematoma volume between AA and 4F-PCC at 6 h (9.3 mL 6.9–26.4 vs 10 mL 9.4–22.1, adjusted
p
= 0. 997) and 24-h (9.2 mL 6.1–18.8 vs 9.9 9.4–21.1, adjusted
p
= 1). The number of patients with good outcome based on mRS on discharge were 10 (36%) and 6 (38%) in the AA and 4F-PCC groups, respectively (adjusted
p
= 0.81). The incidence of thromboembolic events was similar in the AA and 4F-PCC groups (2 7% vs 0,
p
= 0.53).
Conclusion
In this limited sample of patients, we found no difference in neuroimaging stability, functional outcome and thrombotic events when comparing AA and 4F-PCC in patients with FXi-related ICH. Since our analysis is likely underpowered, a multi-center collaborative network devoted to this question is warranted.
Ischemic stroke (IS) is a highly heritable trait, and genome-wide association studies have identified several commonly occurring susceptibility risk loci for this condition. However, there are ...limited data on the contribution of rare genetic variation to IS.
We conducted an exome-wide study using whole-exome sequencing data from 152 058 UK Biobank participants, including 1777 IS cases. We performed single-variant analyses for rare variants and gene-based analyses for loss-of-function and deleterious missense rare variants. We validated these results through (1) gene-based testing using summary statistics from MEGASTROKE-a genome-wide association study of IS that included 67 162 IS cases and 454 450 controls, (2) gene-based testing using individual-level data from 1706 IS survivors, including 142 recurrent IS cases, enrolled in the VISP trial (Vitamin Intervention for Stroke Prevention); and (3) gene-based testing against neuroimaging phenotypes related to cerebrovascular disease using summary-level data from 42 310 UK Biobank participants with available magnetic resonance imaging data.
In single-variant association analyses, none of the evaluated variants were associated with IS at genome-wide significance levels (
<5×10
). In the gene-based analysis focused on loss-of-function and deleterious missense variants, rare genetic variation at
was significantly associated with IS risk (
=2.6×10
), exceeding the Bonferroni-corrected threshold for 16 074 tests (
<3.1×10
). Validations analyses indicated that
was associated with IS risk in MEGASTROKE (gene-based test,
=0.003), with IS recurrence in the VISP trial (gene-based test,
=0.001) and with neuroimaging traits (white matter hyperintensity, mean diffusivity, and fractional anisotropy) in the UK Biobank neuroimaging study (all gene-based tests,
<0.05).
Because
plays an important role in vitamin D metabolism and existing observational evidence suggests an association between vitamin D levels and cerebrovascular disease, our results support a role of this pathway in the occurrence of IS.
To test the hypothesis that admission hemoglobin levels are associated with outcome in primary, nontraumatic intracerebral hemorrhage.
Individual patient data meta-analysis of three studies of ...intracerebral hemorrhage.
Two randomized clinical trials and one multiethnic observational study.
Patients with spontaneous, nontraumatic intracerebral hemorrhage.
None.
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.
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.
As the number of stroke survivors continues to increase, identification of therapeutic targets for stroke recovery has become a priority in stroke genomics research. The introduction of ...high-throughput genotyping technologies and novel analytical tools has significantly advanced our understanding of the genetic underpinnings of stroke recovery.
Frailty is a prevalent state associated with several aging-related traits and conditions. The relationship between frailty and stroke remains understudied. Here we aim to investigate whether the ...hospital frailty risk score (HFRS) is associated with the risk of stroke and determine whether a significant association between genetically determined frailty and stroke exists.
Observational study using data from
research program and Mendelian Randomization analyses.
Participants from
with available electronic health records were selected for analysis.
began national enrollment in 2018 and is expected to continue for at least 10 years.
is recruiting members of groups that have traditionally been underrepresented in research. All participants provided informed consent at the time of enrollment, and the date of consent was recorded for each participant. Incident stroke was defined as stroke event happening on or after the date of consent to the
study HFRS was measured with a 3-year look-back period before the date of consent for stroke risk. The HFRS was stratified into 4 categories: no-frailty (HFRS=0), low (HFRS ≥1 and <5), intermediate (≥5 and <15), and high (HFRS ≥15). Last, we implemented Mendelian Randomization analyses to evaluate whether genetically determined frailty is associated with stroke risk.
Two hundred fifty-three thousand two hundred twenty-six participants were at risk of stroke. In multivariable analyses, frailty status was significantly associated with risk of any (ischemic or hemorrhagic) stroke following a dose-response way: not-frail versus low HFRS (HR, 4.9 CI, 3.5-6.8;
<0.001), not-frail versus intermediate HFRS (HR, 11.4 CI, 8.3-15.7;
<0.001) and not-frail versus high HFRS (HR, 42.8 CI, 31.2-58.6;
<0.001). We found similar associations when evaluating ischemic and hemorrhagic stroke separately (
value for all comparisons <0.05). Mendelian Randomization confirmed this association by indicating that genetically determined frailty was independently associated with risk of any stroke (OR, 1.45 95% CI, 1.15-1.84;
=0.002).
Frailty, based on the HFRS was associated with higher risk of any stroke. Mendelian Randomization analyses confirmed this association providing evidence to support a causal relationship.
Blood pressure (BP) is often not at goal in stroke survivors, leaving individuals vulnerable to additional vascular events. Given that BP is a highly heritable trait, we hypothesize that a higher ...polygenic susceptibility to hypertension (PSH) leads to worse BP control in stroke survivors.
We conducted a study within the UK Biobank evaluating persons of European ancestry who survived an ischemic or hemorrhagic stroke. To model the PSH, we created polygenic risk scores (PRSs) for systolic and diastolic BP using 732 genetic variants. We divided the PRSs into quintiles and used linear/logistic regression to test whether higher PSH led to higher observed BP, uncontrolled BP (systolic BP > 140 mm Hg or diastolic BP > 90 mm Hg), and resistant BP (uncontrolled BP despite being on ≥3 antihypertensive drugs). We conducted an independent replication using data from the Vitamin Intervention for Stroke Prevention (VISP) trial.
We analyzed 5,940 stroke survivors. When comparing stroke survivors with very low vs very high PSH, the mean systolic BP was 137 (SD 18) vs 143 (SD 20,
< 0.001), the mean diastolic BP was 81 (SD 10) vs 84 (SD 11,
< 0.001), the prevalence of uncontrolled BP was 42.8% vs 57.2% (
< 0.001), and the prevalence of resistant hypertension was 3.9% vs 11% (
< 0.001). Results remained significant using multivariable models (
< 0.001) and were replicated in the VISP study (all tests with
< 0.05).
A higher PSH is associated with worse BP control in stroke survivors. These findings point to genetic predisposition as an important determinant of poorly controlled BP in this population.
Background All of Us is a novel research program that aims to accelerate research in populations traditionally underrepresented in biomedical research. Our objective was to evaluate the burden of ...cardiovascular disease (CVD) in broadly defined underrepresented groups. Methods and Results We evaluated the latest data release of All of Us. We conducted a cross-sectional analysis combining survey and electronic health record data to estimate the prevalence of CVD upon enrollment in underrepresented groups defined by race, ethnicity, age (>75 years), disability (not able to carry out everyday physical activities), sexual orientation and gender identity lesbian, gay, bisexual, transgender, queer, intersex, and asexual (LGBTQIA+), income (annual household income <$35 000 US dollars) and education (less than a high school degree). We used multivariate logistic regression to estimate the adjusted odds ratio (OR) and product terms to test for interaction. The latest All of Us data release includes 315 297 participants. Of these, 230 577 (73%) had information on CVD and 17 958 had CVD (overall prevalence, 7.8%; 95% CI, 7.7-7.9). Multivariate analyses adjusted by hypertension, hyperlipidemia, type 2 diabetes mellitus, body mass index, and smoking indicated that, compared with White participants, Black participants had a higher adjusted odds of CVD (OR, 1.21; 95% CI, 1.16-1.27). Higher adjusted odds of CVD were also observed in underrepresented groups defined by other factors, including age >75 years (OR, 1.90; 95% CI, 1.81-1.99), disability (OR, 1.60; 95% CI, 1.53-1.68), and income <$35 000 US dollars (OR, 1.22; 95% CI, 1.17-1.27). Sex significantly modified the odds of CVD in several of the evaluated groups. Conclusions Among participants enrolled in All of Us, underrepresented groups defined based on race, ethnicity and other factors have a disproportionately high burden of CVD. The All of Us research program constitutes a powerful platform to accelerate research focused on individuals in underrepresented groups.
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