Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection: The STOP-CAD Study.

BACKGROUND: Small, randomized trials of patients with cervical artery dissection showed conflicting results regarding optimal stroke prevention strategies. We aimed to compare outcomes in patients with cervical artery dissection treated with antiplatelets versus anticoagulation. METHODS: This is a multicenter observational retrospective international study (16 countries, 63 sites) that included patients with cervical artery dissection without major trauma. The exposure was antithrombotic treatment type (anticoagulation versus antiplatelets), and outcomes were subsequent ischemic stroke and major hemorrhage (intracranial or extracranial hemorrhage). We used adjusted Cox regression with inverse probability of treatment weighting to determine associations between anticoagulation and study outcomes within 30 and 180 days. The main analysis used an as-treated crossover approach and only included outcomes occurring with the above treatments. RESULTS: The study included 3636 patients (402 [11.1%] received exclusively anticoagulation and 2453 [67.5%] received exclusively antiplatelets). By day 180, there were 162 new ischemic strokes (4.4%) and 28 major hemorrhages (0.8%); 87.0% of ischemic strokes occurred by day 30. In adjusted Cox regression with inverse probability of treatment weighting, compared with antiplatelet therapy, anticoagulation was associated with a nonsignificantly lower risk of subsequent ischemic stroke by day 30 (adjusted hazard ratio [HR], 0.71 [95% CI, 0.45-1.12]; P=0.145) and by day 180 (adjusted HR, 0.80 [95% CI, 0.28-2.24]; P=0.670). Anticoagulation therapy was not associated with a higher risk of major hemorrhage by day 30 (adjusted HR, 1.39 [95% CI, 0.35-5.45]; P=0.637) but was by day 180 (adjusted HR, 5.56 [95% CI, 1.53-20.13]; P=0.009). In interaction analyses, patients with occlusive dissection had significantly lower ischemic stroke risk with anticoagulation (adjusted HR, 0.40 [95% CI, 0.18-0.88]; Pinteraction=0.009). CONCLUSIONS: Our study does not rule out the benefit of anticoagulation in reducing ischemic stroke risk, particularly in patients with occlusive dissection. If anticoagulation is chosen, it seems reasonable to switch to antiplatelet therapy before 180 days to lower the risk of major bleeding. Large prospective studies are needed to validate our findings.

Health Care Encounters Prior to Hospitalization for Cerebral Venous Thrombosis Patients.

BACKGROUND: Unlike other causes of stroke, symptoms in cerebral venous thrombosis (CVT) can be nonspecific at onset with gradual worsening over time. To explore potential opportunities for earlier diagnosis, we analyzed healthcare interactions in the week prior to hospitalization for patients admitted with incident CVT in British Columbia (BC). METHODS: We constructed a population-based cohort (2000-2017) using linked patient-level administrative data to identify patients aged ≥18 diagnosed with CVT in BC. We used descriptive analysis to describe the frequency and types of healthcare encounters within the 7 and 3 days prior to hospitalization. Multivariable logistic regression modeling was performed to examine risk factors associated with prior encounters. RESULTS: The cohort included 554 patients (mean age 50.9 years, 55.4% female). Within the 7 days prior to CVT hospitalization, 57.9% of patients had ≥1 outpatient encounter and 5.6% had ≥1 inpatient encounter. In the 3 days prior to hospitalization, 46.8% of patients had ≥1 outpatient encounter and 2.0% had ≥1 inpatient encounter. Women more frequently had outpatient interactions within 7 days (64.8% women vs. 35.2% men, p < 0.001) and 3 days (51.8% vs. 48.2%, p = 0.01) before admission. Common provider specialties for outpatient encounters were general practice (58.0%), emergency (8.3%) and neurology (5.7%). Females had higher odds (OR = 1.79) of having ≥1 outpatient encounter after adjusting for confounding. CONCLUSIONS: Within our Canadian cohort, over half of patients had a healthcare encounter within 7 days before their hospitalization with incident CVT. Women more commonly had an outpatient encounter preceding hospital admission.

Trends in cerebral venous thrombosis before and during the COVID-19 pandemic: Analysis of the National Inpatient Sample.

OBJECTIVES: We sought to provide updated incidence and trend data for cerebral venous thrombosis (CVT) in the United States from 2016-2020, examine the impact of the COVID-19 pandemic on CVT, and identify predictors of in-hospital mortality. MATERIALS AND METHODS: Validated ICD-10 codes were used to identify discharges with CVT in the National Inpatient Sample (NIS). Sample weights were applied to generate nationally representative estimates, and census data were used to compute incidence rates. The first wave of the COVID-19 pandemic was defined as January-May 2020. Trend analysis was completed using Joinpoint regression. RESULTS: From 2016 to 2020, the incidence of CVT increased from 24.34 per 1,000,000 population per year (MPY) to 33.63 per MPY (Annual Percentage Change (APC) 8.6 %; p < 0.001). All-cause in-hospital mortality was 4.9 % [95 % CI 4.5-5.4]. On multivariable analysis, use of thrombectomy, increased age, atrial fibrillation, stroke diagnosis, infection, presence of prothrombotic hematologic conditions, lowest quartile of income, intracranial hemorrhage, and male sex were associated with in-hospital mortality. CVT incidence was similar comparing the first 5 months of 2020 and 2019 (31.37 vs 32.04; p = 0.322) with no difference in median NIHSS (2 [IQR 1-10] vs. 2 [1-9]; p = 0.959) or mortality (4.2 % vs. 5.6 %; p = 0.176). CONCLUSIONS: CVT incidence increased in the US from 2016 to 2020 while mortality did not change. Increased age, prothrombotic state, stroke diagnosis, infection, atrial fibrillation, male sex, lowest quartile of income, intracranial hemorrhage, and use of thrombectomy were associated with in-hospital mortality following CVT. During the first wave of the COVID-19 pandemic, CVT volumes and mortality were similar to the prior year.

Incidence of Cerebral Venous Thrombosis: A Population-Based Study, Systematic Review, and Meta-Analysis.

BACKGROUND: Studying the baseline incidence of cerebral venous thrombosis (CVT) prior to COVID-19 and the limitations of how this has been previously reported in the literature will help improve understanding of this disease and how risks may have changed in the post-COVID era. METHODS: We examined CVT incidence using linked administrative data in British Columbia, Canada (population 5.2 million). To contextualize our findings, we also examined CVT incidence in the published literature and searched MEDLINE and EMBASE for article titles and abstracts up to Nov 2, 2021 on CVT incidence in adults. We performed abstract screening and full-text review prior to data extraction and explored associations between CVT incidence and year of study, geographic location, and study quality with meta-analyses and meta-regression. A random-effects restricted maximum likelihood model was used. Publication bias was assessed using the Egger tests and using visual inspection of the funnel plot for symmetry. RESULTS: There were 554 unique CVT cases (mean age 50.9 years, 55.4% women) in British Columbia from 2000 to 2017; overall annual incidence was 8.7 (95%CI' 8.0-9.4) per million. Incidence increased over time in men across the entire study period, and from 2011 to 2017 in women. We identified 22 other studies on CVT incidence before 2020 (21/23 total studies included in meta-analysis). Annual incidence overall was 12.1 (95% CI' 9.9-14.3) per million with significant between-study heterogeneity (I2 98.8%, Qp-value<0.001). There were no significant associations on meta-regression between incidence and study year, study quality score, or gross national income per capita of the study country. Visual inspection of the funnel plot and a significant Egger test (z=2.8, P<0.01) suggested possible publication bias. CONCLUSIONS: Incidence of CVT in Canadian data increased over time but remained lower than in other population-based studies. Significant heterogeneity exists in the literature, which may be subject to publication bias.

Effect of COVID-19 on Acute Ischemic Stroke Severity and Mortality in 2020: Results From the 2020 National Inpatient Sample.

BACKGROUND: There is a paucity of nationally representative data regarding the impact of COVID-19 on acute ischemic stroke (AIS) outcome. METHODS: We created a cross-sectional cohort of nationally weighted National Inpatient Sample nonelective hospital discharges aged ≥18 years with a diagnosis of ischemic stroke from 2016 to 2020. The outcome was in-hospital mortality and exposure was COVID-19 status. To understand the effect of COVID-19 on AIS severity, we report National Institutes of Health Stroke Scale by exposure status. In a final analysis, we used a nationally weighted logistic regression and marginal effects to compare April to December 2020 to the same period in 2019 to understand how the pandemic modified the effect of race and ethnicity and median household income on in-hospital AIS mortality. RESULTS: We observed significantly higher AIS mortality in 2020 than prior years (2020 versus 2016-19, 7.3% versus 6.3%, P<0.001) and higher National Institutes of Health Stroke Scale in those with COVID-19 than those without (mean: 9.7±9.1 versus 6.6±7.4, P<0.001), but patients with AIS without COVID in 2020 had only marginally higher mortality (2020 versus 2016-2019, 6.6% versus 6.3%, P=0.001). Comparing April to December 2020 to 2019, the adjusted risk of in-hospital AIS mortality was most notably increased in Hispanics (2020 versus 2019: 9.2% versus 5.8%, P<0.001) and the lowest quartile of income (2020 versus 2019: 8.0% versus 6.0%, P<0.001). CONCLUSIONS: In-hospital stroke mortality increased in 2020 in the United States because of comorbid AIS and COVID-19, which had higher stroke severity. The increase in AIS mortality during April-December 2020 was significantly more pronounced in Hispanics and those in the lowest quartile of household income.

MitoVisualize: a resource for analysis of variants in human mitochondrial RNAs and DNA.

SUMMARY: We present MitoVisualize, a new tool for analysis of the human mitochondrial DNA (mtDNA). MitoVisualize enables visualization of: (i) the position and effect of variants in mitochondrial transfer RNA and ribosomal RNA secondary structures alongside curated variant annotations, (ii) data across RNA structures, such as to show all positions with disease-associated variants or with post-transcriptional modifications and (iii) the position of a base, gene or region in the circular mtDNA map, such as to show the location of a large deletion. All visualizations can be easily downloaded as figures for reuse. MitoVisualize can be useful for anyone interested in exploring mtDNA variation, though is designed to facilitate mtDNA variant interpretation in particular. AVAILABILITY AND IMPLEMENTATION: MitoVisualize can be accessed via https://www.mitovisualize.org/. The source code is available at https://github.com/leklab/mito_visualize/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Quantifying Improved Outcomes, Cost Savings, and Hospital Volume Changes From Optimized Emergency Stroke Transport.

BACKGROUND: A previously published conditional probability model optimizes prehospital emergency transport protocols for patients with suspected large-vessel occlusion by recommending the transport strategy, drip-and-ship or mothership, that results in a higher probability of an excellent outcome. In this study, we create generalized models to quantify the change in annual hospital patient volume, the expected annual increase in the number of patients with an excellent outcome, and the annual cost savings to a single-payer healthcare system resulting from these optimized transport protocols. METHODS: We calculated the expected number of patients with suspected large-vessel occlusion transported by ambulance over a 1-year period in a region of interest, using the annual stroke incidence rate and a large-vessel occlusion screening tool. Assuming transport to the closest hospital is the baseline transport policy across the region (drip-and-ship), we determined the change in annual hospital patient volume from implementing optimized transport protocols. We also calculated the resulting annual increase in the number of patients with an excellent outcome (modified Rankin Score of 0-1 at 90 days) and associated cost savings to a single-payer healthcare system. We then performed a case study applying these generalized models to the stroke system serving the Greater Vancouver and Fraser Valley Area, BC, Canada. RESULTS: In the Greater Vancouver and Fraser Valley Area, there was an annual increase of 36 patients with an excellent outcome, translating to an annual cost savings of CA$2 182 824 to the British Columbia healthcare system. We also studied how these results change depending on our assumptions of treatment times at the regional stroke centers. CONCLUSIONS: Our framework quantifies the impact of optimized emergency stroke transport protocols on hospital volume, outcomes, and cost savings to a single-payer healthcare system. When applied to a specific region of interest, these models can help inform health policies concerning emergency transport of patients with suspected large-vessel occlusion.

Validity of ICD-10 Codes for Cerebral Venous Thrombosis Depends on Clinical Context.

We examined the accuracy of International Classification of Disease 10th iteration (ICD-10) diagnosis codes within Canadian administrative data in identifying cerebral venous thrombosis (CVT). Of 289 confirmed cases of CVT admitted to our comprehensive stroke center between 2008 and 2018, 239/289 were new diagnoses and 204/239 were acute events with only 75/204 representing symptomatic CVTs not provoked by trauma or structural processes. Using ICD-10 codes in any position, sensitivity was 39.1% and positive predictive value was 94.2% for patients with a current or history of CVT and 84.0% and 52.5% for acute and symptomatic CVTs not provoked by trauma or structural processes.

Mule/Huwe1/Arf-BP1 suppresses Ras-driven tumorigenesis by preventing c-Myc/Miz1-mediated down-regulation of p21 and p15.

Tumorigenesis results from dysregulation of oncogenes and tumor suppressors that influence cellular proliferation, differentiation, apoptosis, and/or senescence. Many gene products involved in these processes are substrates of the E3 ubiquitin ligase Mule/Huwe1/Arf-BP1 (Mule), but whether Mule acts as an oncogene or tumor suppressor in vivo remains controversial. We generated K14Cre;Mule(flox/flox(y)) (Mule kKO) mice and subjected them to DMBA/PMA-induced skin carcinogenesis, which depends on oncogenic Ras signaling. Mule deficiency resulted in increased penetrance, number, and severity of skin tumors, which could be reversed by concomitant genetic knockout of c-Myc but not by knockout of p53 or p19Arf. Notably, in the absence of Mule, c-Myc/Miz1 transcriptional complexes accumulated, and levels of p21CDKN1A (p21) and p15INK4B (p15) were down-regulated. In vitro, Mule-deficient primary keratinocytes exhibited increased proliferation that could be reversed by Miz1 knockdown. Transfer of Mule-deficient transformed cells to nude mice resulted in enhanced tumor growth that again could be abrogated by Miz1 knockdown. Our data demonstrate in vivo that Mule suppresses Ras-mediated tumorigenesis by preventing an accumulation of c-Myc/Miz1 complexes that mediates p21 and p15 down-regulation.

Cerebral Small Vessel Disease, Risk Factors, and Cognition in Tenants of Precarious Housing.

BACKGROUND AND PURPOSE: We aim to describe the burden, characteristics, and cognitive associations of cerebral small vessel disease in a Canadian sample living with multimorbidity in precarious housing. METHODS: Participants received T1, T2-fluid-attenuated inversion recovery, and susceptibility-weighted imaging 3T magnetic resonance imaging sequences and comprehensive clinical, laboratory, and cognitive assessments. Cerebral small vessel disease burden was characterized using a modified Small Vessel Disease (mSVD) score. One point each was given for moderate-severe white matter hyperintensities, ≥1 cerebral microbleeds, and ≥1 lacune. Multivariable regression explored associations between mSVD score, risk factors, and cognitive performance. RESULTS: Median age of the 228 participants (77% male) was 44.7 years (range, 23.3-63.2). In n=188 participants with consistent good quality magnetic resonance imaging sequences, mSVD scores were 0 (n=127, 68%), 1 (n=50, 27%), and 2 (n=11, 6%). Overall, one-third had an mSVD ≥1 n=61 (32%); this proportion was unchanged when adding participants with missing sequences n=72/228 (32%). The most prevalent feature was white matter hyperintensities 53/218 (24%) then cerebral microbleed 16/191 (8%) and lacunes 16/228 (7%). Older age (odds ratio, 1.10 [95% CI, 1.05-1.15], P<0.001), higher diastolic blood pressure (odds ratio, 1.05 [95% CI, 1.01-1.09], P=0.008), and a history of injection drug use (odds ratio, 3.13 [95% CI, 1.07-9.16], P=0.037) had significant independent associations with a mSVD score of ≥1 in multivariable analysis. mSVD ≥1 was associated with lower performance on tests of verbal memory, sustained attention, and decision-making, contributing 4% to 5% of the variance in each cognitive domain. CONCLUSIONS: The 32% prevalence of cerebral small vessel disease in this young, socially marginalized cohort was higher than expected for age and was associated with poorer cognitive performance.

TAp73 is required for spermatogenesis and the maintenance of male fertility.

The generation of viable sperm proceeds through a series of coordinated steps, including germ cell self-renewal, meiotic recombination, and terminal differentiation into functional spermatozoa. The p53 family of transcription factors, including p53, p63, and p73, are critical for many physiological processes, including female fertility, but little is known about their functions in spermatogenesis. Here, we report that deficiency of the TAp73 isoform, but not p53 or ΔNp73, results in male infertility because of severe impairment of spermatogenesis. Mice lacking TAp73 exhibited increased DNA damage and cell death in spermatogonia, disorganized apical ectoplasmic specialization, malformed spermatids, and marked hyperspermia. We demonstrated that TAp73 regulates the mRNA levels of crucial genes involved in germ stem/progenitor cells (CDKN2B), spermatid maturation/spermiogenesis (metalloproteinase and serine proteinase inhibitors), and steroidogenesis (CYP21A2 and progesterone receptor). These alterations of testicular histology and gene expression patterns were specific to TAp73 null mice and not features of mice lacking p53. Our work provides previously unidentified in vivo evidence that TAp73 has a unique role in spermatogenesis that ensures the maintenance of mitotic cells and normal spermiogenesis. These results may have implications for the diagnosis and management of human male infertility.

Headaches: a Review of the Role of Dietary Factors.

Dietary triggers are commonly reported by patients with a variety of headaches, particularly those with migraines. The presence of any specific dietary trigger in migraine patients varies from 10 to 64 % depending on study population and methodology. Some foods trigger headache within an hour while others develop within 12 h post ingestion. Alcohol (especially red wine and beer), chocolate, caffeine, dairy products such as aged cheese, food preservatives with nitrates and nitrites, monosodium glutamate (MSG), and artificial sweeteners such as aspartame have all been studied as migraine triggers in the past. This review focuses the evidence linking these compounds to headache and examines the prevalence of these triggers from prior population-based studies. Recent literature surrounding headache related to fasting and weight loss as well as elimination diets based on serum food antibody testing will also be summarized to help physicians recommend low-risk, non-pharmacological adjunctive therapies for patients with debilitating headaches.

Prognosis after cerebral venous thrombosis: Mortality during initial admission and at 30 days and one year after discharge in a large Canadian population-based cohort.

BACKGROUND: Prognosis following cerebral venous thrombosis (CVT) is more favorable than other stroke types, but longer-term literature is limited, and trends over time are under-explored. OBJECTIVE: Using administrative data, we examined factors associated with mortality in the inpatient setting, at 30 days and at one year following hospital discharge among a large consecutive cohort of Canadian patients with CVT. DESIGN/METHODS: CVT patients from British Columbia (BC), Canada from 2000 to 2017 were identified using ICD diagnosis codes from the BC subset of the Canadian Institute for Health Information's Discharge Abstract Database. Logistic regression was used to investigate factors associated with inpatient mortality and survival analysis with Cox regression was used to explore factors associated with mortality at 30 days and one year. RESULTS: Of 554 incident CVT patients identified, 508 (92 %) survived their index admission. Older age (OR 1.04, 95 % CI 1.03-1.06, p < 0.01) and the presence of seizures (OR 2.31, 95 % CI 1.08-4.94, p = 0.03) or intracranial bleeding (OR 2.28, 95 % CI 1.08-4.85, p = 0.03) were associated with increased odds of inpatient mortality. Mortality after hospital discharge was 3.0 % at 30 days and 9.4 % at one year. Older age (HR 1.05, 95 % CI 1.02-1.08, p < 0.01 at 30 days; HR 1.05, 95 % CI 1.04-1.07, p < 0.01 at 1 year) and having recent or active malignancy (HR 4.17, 95 % CI 1.51-11.52, p < 0.01 at 30 days; HR 4.60, 95 % CI 2.60-8.11, p < 0.01 at 1 year) were significantly associated with higher risks of mortality at 30 days and one year after discharge. There were decreases in inpatient mortality over the study period, but this was offset by higher mortality within 30 days after discharge in the later study epochs. CONCLUSIONS: Among patients discharged with a diagnosis of CVT, one-year mortality was high at 9.4 %. Older age and a history of cancer were associated with higher mortality after discharge.

Endovascular Treatment of Acute Ischemic Stroke After Cardiac Interventions in the United States.

Importance: Ischemic stroke is a serious complication of cardiac intervention, including surgery and percutaneous procedures. Endovascular thrombectomy (EVT) is an effective treatment for ischemic stroke and may be particularly important for cardiac intervention patients who often cannot receive intravenous thrombolysis. Objective: To examine trends in EVT for ischemic stroke during hospitalization of patients with cardiac interventions vs those without in the United States. Design, Setting, and Participants: This cohort study involved a retrospective analysis using data for 4888 US hospitals from the 2016-2020 National Inpatient Sample database. Participants included adults (age ≥18 years) with ischemic stroke (per codes from the International Statistical Classification of Diseases, Tenth Revision, Clinical Modification), who were organized into study groups of hospitalized patients with cardiac interventions vs without. Individuals were excluded from the study if they had either procedure prior to admission, EVT prior to cardiac intervention, EVT more than 3 days after admission or cardiac intervention, or endocarditis. Data were analyzed from April 2023 to October 2023. Exposures: Cardiac intervention during admission. Main Outcomes and Measures: The odds of undergoing EVT by cardiac intervention status were calculated using multivariable logistic regression. Adjustments were made for stroke severity in the subgroup of patients who had a National Institutes of Health Stroke Scale (NIHSS) score documented. As a secondary outcome, the odds of discharge home by EVT status after cardiac intervention were modeled. Results: Among 634 407 hospitalizations, the mean (SD) age of the patients was 69.8 (14.1) years, 318 363 patients (50.2%) were male, and 316 044 (49.8%) were female. A total of 12 093 had a cardiac intervention. An NIHSS score was reported in 218 576 admissions, 216 035 (34.7%) without cardiac intervention and 2541 (21.0%) with cardiac intervention (P < .001). EVT was performed in 23 660 patients (3.8%) without cardiac intervention vs 194 (1.6%) of those with cardiac intervention (P < .001). After adjustment for potential confounders, EVT was less likely to be performed in stroke patients with cardiac intervention vs those without (adjusted odds ratio [aOR], 0.27; 95% CI, 0.23-0.31), which remained consistent after adjusting for NIHSS score (aOR, 0.28; 95% CI, 0.22-0.35). Among individuals with a cardiac intervention, receiving EVT was associated with a 2-fold higher chance of discharge home (aOR, 2.21; 95% CI, 1.14-4.29). Conclusions and Relevance: In this study, patients hospitalized with ischemic stroke and cardiac intervention may be less than half as likely to receive EVT as those without cardiac intervention. Given the known benefit of EVT, there is a need to better understand the reasons for lower rates of EVT in this patient population.

DJ-1, a novel regulator of the tumor suppressor PTEN.

The phosphatidylinositol 3' kinase (PI3'K) pathway, which regulates cell survival, is antagonized by the PTEN tumor suppressor. The regulation of PTEN is unclear. A genetic screen of Drosophila gain-of-function mutants identified DJ-1 as a suppressor of PTEN function. In mammalian cells, DJ-1 underexpression results in decreased phosphorylation of PKB/Akt, while DJ-1 overexpression leads to hyperphosphorylation of PKB/Akt and increased cell survival. In primary breast cancer samples, DJ-1 expression correlates negatively with PTEN immunoreactivity and positively with PKB/Akt hyperphosphorylation. In 19/23 primary non-small cell lung carcinoma samples, DJ-1 expression was increased compared to paired nonneoplastic lung tissue, and correlated positively with relapse incidence. DJ-1 is thus a key negative regulator of PTEN that may be a useful prognostic marker for cancer.

Rates and reasons for hospital readmission after acute ischemic stroke in a US population-based cohort.

Hospital readmissions following stroke are costly and lead to worsened patient outcomes. We examined readmissions rates, diagnoses at readmission, and risk factors associated with readmission following acute ischemic stroke (AIS) in a large United States (US) administrative database. Using the 2019 Nationwide Readmissions Database, we identified adults discharged with AIS (ICD-10-CM I63*) as the principal diagnosis. Survival analysis with Weibull accelerated failure time regression was used to examine variables associated with hospital readmission. In 2019, 273,811 of 285,451 AIS patients survived their initial hospitalization. Of these, 60,831 (22.2%) were readmitted within 2019. Based on Kaplan Meyer analysis, readmission rates were 9.7% within 30 days and 30.5% at 1 year following initial discharge. The most common causes of readmissions were stroke and post stroke sequalae (25.4% of 30-day readmissions, 15.0% of readmissions between 30-364 days), followed by sepsis (10.3% of 30-day readmissions, 9.4% of readmissions between 30-364 days), and acute renal failure (3.2% of 30-day readmissions, 3.0% of readmissions between 30-364 days). After adjusting for multiple patient and hospital-level characteristics, patients at increased risk of readmission were older (71.6 vs. 69.8 years, p<0.001) and had longer initial lengths of stay (7.6 vs. 6.2 day, p<0.001). They more often had modifiable comorbidities, including vascular risk factors (hypertension, diabetes, atrial fibrillation), depression, epilepsy, and drug abuse. Social determinants associated with increased readmission included living in an urban (vs. rural) setting, living in zip-codes with the lowest median income, and having Medicare insurance. All factors were significant at p<0.001. Unplanned hospital readmissions following AIS were high, with the most common reasons for readmission being recurrent stroke and post stroke sequalae, followed by sepsis and acute renal failure. These findings suggest that efforts to reduce readmissions should focus on optimizing secondary stroke and infection prevention, particularly among older socially disadvantaged patients.