Prior to COVID-19, only two human-tropic coronaviruses resulted in epidemics and cerebrovascular disease was rarely reported. Evidence now suggests that 1–6% of hospitalized COVID-19 patients develop ...stroke. According to some reports, stroke risk is more than sevenfold greater in patients with COVID-19 than influenza. Concerningly, outcomes of COVID-19-related stroke are often worse than in stroke patients without COVID-19 from the same cohorts. In this review, we highlight the emerging association between COVID-19 and stroke and discuss putative pathogenetic mechanisms. Etiology of stroke in COVID-19 patients is likely multifactorial, related to coagulopathy, inflammation, platelet activation, and alterations to the vascular endothelium. Significant work remains to be done to better understand the pathogenesis of COVID-19-related stroke and for designing optimal primary and secondary prevention strategies.
Growing comparisons of COVID-19 positive and COVID-19 negative stroke cohorts support an association between COVID-19 and stroke.COVID-19-related stroke can be severe and has impacted young patients and minimally symptomatic individuals, as well as patients with traditional cerebrovascular risk factors and severe disease.When compared with stroke patients without COVID-19, morbidity and mortality are much worse in patients with stroke and COVID-19.Etiology of COVID-19-related stroke is frequently unknown and the pathogenesis may be related to coagulopathy, inflammation, endotheliopathy, and platelet activation.Anticoagulation may benefit those hospitalized with severe COVID-19, including those diagnosed with stroke.
Sex Differences in Post-Stroke Depression in the Elderly Mayman, Naomi A.; Tuhrim, Stanley; Jette, Nathalie ...
Journal of stroke and cerebrovascular diseases,
September 2021, 2021-09-00, 20210901, Letnik:
30, Številka:
9
Journal Article
Recenzirano
Post-stroke depression (PSD) occurs in approximately one-third of ischemic stroke patients. However, there is conflicting evidence on sex differences in PSD. We sought to assess sex differences in ...risk and time course of PSD in US ischemic stroke (IS) patients. We hypothesized that women are at greater risk of PSD than men, and that a greater proportion of women experience PSD in the acute post-stroke phase.
We conducted a retrospective cohort study of 100% de-identified data for US Medicare beneficiaries admitted for ischemic stroke from July 1, 2016 to December 31, 2017. We calculated Kaplan-Meier unadjusted cumulative risk of depression, stratified by sex, up to 1.5 years following index admission. We performed Cox regression to report the hazard ratio (HR) for diagnosis of depression up to 1.5 years post-stroke in females vs. males, adjusting for patient demographics, comorbidities, length of stay, and acute stroke interventions.
In elderly stroke patients, females (n=90,474) were 20% more likely to develop PSD than males (n=84,427) in adjusted models. Cumulative risk of depression was consistently elevated for females throughout 1.5 years of follow-up (0.2055 95% CI 0.2013–0.2097 vs. 0.1690 95% CI 0.1639–0.1741 (log-rank p < 0.0001). HR for PSD in females vs. males remained significant in fully adjusted analysis at 1.20 (95% CI 1.17-1.23, p < 0.0001).
Over 1.5 years of follow-up, female stroke patients had significantly greater hazard of developing PSD, highlighting the need for long-term depression screening in this population and further investigation of underlying reasons for sex differences.
We sought to comprehensively evaluate predictors of poststroke depression (PSD) in the United States and to compare PSD to post-myocardial infarction (MI) depression to determine whether ischemic ...stroke uniquely elevates risk of depression.
This is a retrospective cohort study of 100% deidentified inpatient, outpatient, and subacute nursing Medicare data from 2016 to 2017 for US patients ≥65 years of age from July 1, 2016, to December 31, 2017. We calculated Kaplan-Meier unadjusted cumulative risk of depression up to 1.5 years after the index admission. We performed Cox regression to report the hazard ratio for diagnosis of depression up to 1.5 years after stroke vs MI and independent predictors of PSD, and we controlled for patient demographics, comorbid conditions, length of stay, and acute stroke interventions.
In fully adjusted models, patients with stroke (n = 174,901) were ≈50% more likely than patients with MI (n = 193,418) to develop depression during the 1.5-year follow-up period (Kaplan-Meier cumulative risk 0.1596 ± 0.001 in patients with stroke vs 0.0973 ± 0.000778 in patients with MI, log-rank
< 0.0001). History of anxiety was the strongest predictor of PSD, while discharge home was most protective. Female patients, White patients, and patients <75 years of age were more likely to be diagnosed with depression after stroke.
Despite the similarities between MI and stroke, patients with stroke were significantly more likely to develop depression. There were several predictors of PSD, most significantly history of anxiety. Our findings lend credibility to a stroke-specific process causing depression and highlight the need for consistent depression screening in all patients with stroke.
Abstract only Introduction: Post-stroke depression (PSD) occurs commonly following stroke and is associated with worse outcomes and higher mortality. Previous research has not identified consistent ...predictors of PSD, and debate remains about whether PSD differs from other types of depression, including depression following other ischemic vascular events. Objective: We sought to comprehensively evaluate predictors of PSD in the US population and compare the hazard of developing PSD to post-myocardial infarction (MI) depression. Methods: Retrospective cohort study of 100% de-identified inpatient, outpatient, and subacute nursing Medicare data from 2016-2017 for US patients aged ≥65 years from July 1, 2016 to December 31, 2017. We calculated Kaplan-Meier unadjusted cumulative risk of depression up to 1.5 years following index admission. We performed Cox regression to report the hazard ratio for diagnosis of depression up to 1.5 years post-stroke vs. MI, as well as independent predictors of PSD, and controlled for patient demographics, comorbidities, length of stay and acute stroke interventions. Results: In fully adjusted models, stroke patients (n=174,901) were approximately 50% more likely than MI patients (n=193,418) to develop depression during the 1.5-year follow-up period (Kaplan-Meier cumulative risk 0.1596 ± 0.001 in stroke patients versus 0.0973 ± 0.000778 in MI patients, log-rank p<0.0001). History of anxiety was the strongest predictor of PSD, while discharge home was most protective. Female patients, White patients, and patients younger than 75 years were more likely to be diagnosed with depression post-stroke. Conclusions: Despite the similarities between MI and stroke, patients who suffer from stroke were significantly more likely to develop depression. There were several predictors of post-stroke depression, most significantly history of anxiety. Our findings lend credibility to a stroke-specific process causing depression and highlight the need for consistent depression screening in all stroke patients.
Abstract only Introduction: Post-stroke depression (PSD) occurs in approximately one-third of ischemic stroke patients. However, there is conflicting evidence on sex differences in PSD. Objective: We ...sought to assess sex differences in risk and time course of PSD in US ischemic stroke (IS) patients. We hypothesized that women are at greater risk of PSD than men, and that a greater proportion of women experience PSD in the acute post-stroke phase. Methods: Retrospective cohort study of 100% de-identified data for US Medicare beneficiaries ≥65 years admitted for ischemic stroke from July 1, 2016 to December 31, 2017. We calculated Kaplan-Meier unadjusted cumulative risk of depression, stratified by sex, up to 1.5 years following index admission. We performed Cox regression to report the hazard ratio (HR) for diagnosis of depression up to 1.5 years post-stroke in males vs. females, adjusting for patient demographics, comorbidities, length of stay, and acute stroke interventions. Results: Female stroke patients (n=90,474) were 20% more likely to develop PSD than males (n=84,427) in adjusted models. Cumulative risk of depression was consistently elevated for females throughout 1.5 years of follow-up (0.2055 95% CI 0.2013-0.2097 vs. 0.1690 95% CI 0.1639-0.1741 (log-rank p<0.0001). HR for PSD in females vs. males remained significant in fully adjusted analysis at 1.20 (95% CI 1.17-1.23, p<0.0001). Conclusions: Over 1.5 years of follow-up, female stroke patients had significantly greater hazard of developing PSD, highlighting the need for long-term depression screening in this population and further investigation of underlying reasons for sex differences.
BACKGROUND AND PURPOSE:Coronavirus disease 2019 (COVID-19) has been associated with an increased incidence of thrombotic events, including stroke. However, characteristics and outcomes of COVID-19 ...patients with stroke are not well known.
METHODS:We conducted a retrospective observational study of risk factors, stroke characteristics, and short-term outcomes in a large health system in New York City. We included consecutively admitted patients with acute cerebrovascular events from March 1, 2020 through April 30, 2020. Data were stratified by COVID-19 status, and demographic variables, medical comorbidities, stroke characteristics, imaging results, and in-hospital outcomes were examined. Among COVID-19-positive patients, we also summarized laboratory test results.
RESULTS:Of 277 patients with stroke, 105 (38.0%) were COVID-19-positive. Compared with COVID-19-negative patients, COVID-19-positive patients were more likely to have a cryptogenic (51.8% versus 22.3%, P<0.0001) stroke cause and were more likely to suffer ischemic stroke in the temporal (P=0.02), parietal (P=0.002), occipital (P=0.002), and cerebellar (P=0.028) regions. In COVID-19-positive patients, mean coagulation markers were slightly elevated (prothrombin time 15.4±3.6 seconds, partial thromboplastin time 38.6±24.5 seconds, and international normalized ratio 1.4±1.3). Outcomes were worse among COVID-19-positive patients, including longer length of stay (P<0.0001), greater percentage requiring intensive care unit care (P=0.017), and greater rate of neurological worsening during admission (P<0.0001); additionally, more COVID-19-positive patients suffered in-hospital death (33% versus 12.9%, P<0.0001).
CONCLUSIONS:Baseline characteristics in patients with stroke were similar comparing those with and without COVID-19. However, COVID-19-positive patients were more likely to experience stroke in a lobar location, more commonly had a cryptogenic cause, and had worse outcomes.
We developed a screening assay in which luciferized ID8 expressing OVA was cocultured with transgenic CD8
T cells specifically recognizing the model antigen in an H-2b-restricted manner. The assay ...was screened with a small-molecule library to identify compounds that inhibit or enhance T cell-mediated killing of tumor cells. Erlotinib, an EGFR inhibitor, was the top compound that enhanced T-cell killing of tumor cells. Subsequent experiments with erlotinib and additional EGFR inhibitors validated the screen results. EGFR inhibitors increased both basal and IFNγ-induced MHC class-I presentation, which enhanced recognition and lysis of tumor cell targets by CD8
cytotoxic T lymphocytes. The ID8 cell line was also transduced to constitutively express Cas9, and a pooled CRISPR screen, utilizing the same target tumor cell/T-cell assay, identified single-guide (sg)RNAs targeting
that sensitized tumor cells to T cell-mediated killing. Combination of PD-1 blockade with EGFR inhibition showed significant synergistic efficacy in a syngeneic model, further validating EGFR inhibitors as immunomodulatory agents that enhance checkpoint blockade. This assay can be screened in high-throughput with small-molecule libraries and genome-wide CRISPR/Cas9 libraries to identify both compounds and target genes, respectively, that enhance or inhibit T-cell recognition and killing of tumor cells. Retrospective analyses of squamous-cell head and neck cancer (SCCHN) patients treated with the combination of afatinib and pembrolizumab demonstrated a rate of clinical activity exceeding that of each single agent. Prospective clinical trials evaluating the combination of an EGFR inhibitor and PD-1 blockade should be conducted.
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