Is COVID-19 Infection a Multiorganic Disease? Focus on Extrapulmonary Involvement of SARS-CoV-2.

First described in December 2019 in Wuhan (China), COVID-19 disease rapidly spread worldwide, constituting the biggest pandemic in the last 100 years. Even if SARS-CoV-2, the agent responsible for COVID-19, is mainly associated with pulmonary injury, evidence is growing that this virus can affect many organs, including the heart and vascular endothelial cells, and cause haemostasis, CNS, and kidney and gastrointestinal tract abnormalities that can impact in the disease course and prognosis. In fact, COVID-19 may affect almost all the organs. Hence, SARS-CoV-2 is essentially a systemic infection that can present a large number of clinical manifestations, and it is variable in distribution and severity, which means it is potentially life-threatening. The goal of this comprehensive review paper in the series is to give an overview of non-pulmonary involvement in COVID-19, with a special focus on underlying pathophysiological mechanisms and clinical presentation.

Climate Change and Stroke: A Topical Narrative Review.

The impacts of accumulating atmospheric greenhouse gases on the earth's climate are now well established. As a result, there have been increases in ambient temperatures and resultant higher frequency and duration of temperature extremes and other extreme weather events, which have been linked to a wide range of adverse health outcomes. This topical narrative review provides a summary of published evidence on the links between climate change and stroke. There is consistent evidence of associations between stroke incidence and mortality and increasing ambient temperature and air pollution. Associations have also been shown for changes in barometric pressure, wildfires, and desert dust and sandstorms, but current evidence is limited. Flooding and other extreme weather events appear to primarily cause service disruption, but more direct links to stroke may emerge. Synergies between dietary changes that reduce stroke risk and may also reduce carbon footprint are being explored. We also discuss the impact on vulnerable populations, proposed pathophysiologic mechanisms, mitigation strategies, and current research priorities. In conclusion, climate change increasingly impacts the stroke community, warranting elevated attention.

Environmental factors and stroke: Risk and prevention.

Stroke is a leading cause of death and adult disability globally. In addition to traditional risk factors, environmental risk factors have emerged over the recent past and are becoming increasingly important. The disproportionate rise of stroke incidence in low- and middle-income countries has been attributed, at least in part, to environmental factors. This narrative review provides details on the interplay between the environment and health generally and stroke specifically, covering topics including air pollution, atmospheric brown clouds, desert dust storms, giant wildfires, chemical contamination, biological aggressors, urbanization, and climate change. It also covers some beneficial environmental effects such as can be harnessed from the exposure to green spaces. It concludes with a summary of pragmatic actions that can be taken to help address some of these challenges at individual, community, and political advocacy levels.

More Than 50 Percent Reduction in LDL Cholesterol in Patients With Target LDL <70 mg/dL After a Stroke.

BACKGROUND: Whether a strategy to target an LDL (low-density lipoprotein) cholesterol <70 mg/dL is more effective when LDL is reduced >50% from baseline rather than <50% from baseline has not been investigated. METHODS: The Treat Stroke to Target trial was conducted in France and South Korea in 61 sites between March 2010 and December 2018. Patients with ischemic stroke in the previous 3 months or transient ischemic attack within the previous 15 days and evidence of cerebrovascular or coronary artery atherosclerosis were randomly assigned to a target LDL cholesterol of <70 mg/dL or 100±10 mg/dL, using statin and/or ezetimibe as needed. We used the results of repeated LDL measurements (median, 5 [2-6] per patient) during 3.9 years (interquartile range, 2.1-6.8) of follow-up. The primary outcome was the composite of ischemic stroke, myocardial infarction, new symptoms requiring urgent coronary or carotid revascularization, and vascular death. Cox regression model including lipid-lowering therapy as a time-varying variable, after adjustment for randomization strategy, age, sex, index event (stroke or transient ischemic attack), and time since the index event. RESULTS: Among 2860 patients enrolled, patients in the lower target group who had >50% LDL cholesterol reduction from baseline during the trial had a higher baseline LDL cholesterol and a lower LDL cholesterol achieved as compared to patients who had <50% LDL cholesterol reduction (155±32 and 62 mg/dL versus 121±34 and 74 mg/dL, respectively, P<0.001 for both). In the <70 mg/dL target group, patients with >50% LDL reduction had a significant reduction in the primary outcome as compared to the higher target group (hazard ratio, 0.61 [95% CI, 0.43-0.88]; P=0.007) and patients with <50% LDL reduction from baseline had little reduction (hazard ratio, 0.96 [95% CI, 0.73-1.26]; P=0.75). CONCLUSIONS: In this post hoc analysis of the TST trial, targeting an LDL cholesterol of <70 mg/dL reduced the risk of primary outcome compared with 100±10 mg/dL provided LDL cholesterol reduction from baseline was superior to 50%, thereby suggesting that the magnitude of LDL cholesterol reduction was as important to consider as the target level to achieve. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01252875. URL: https://clinicaltrialsregister.eu; Unique identifier: EUDRACT2009-A01280-57.

Efficiency and effectiveness of intensive multidisciplinary follow-up of patients with stroke/TIA or myocardial infarction compared to usual monitoring: protocol of a pragmatic randomised clinical trial. DiVa (Dijon vascular) study.

INTRODUCTION: The ongoing ageing population is associated with an increase in the number of patients suffering a stroke, transient ischaemic attack (TIA) or myocardial infarction (MI). In these patients, implementing secondary prevention is a critical challenge and new strategies need to be developed to close the gap between clinical practice and evidence-based recommendations. We describe the protocol of a randomised clinical trial that aims to evaluate the efficiency and effectiveness of an intensive multidisciplinary follow-up of patients compared with standard care. METHODS AND ANALYSIS: The DiVa study is a randomised, prospective, controlled, multicentre trial including patients >18 years old with a first or recurrent stroke (ischaemic or haemorrhagic) or TIA, or a type I or II MI, managed in one of the participating hospitals of the study area, with a survival expectancy >12 months. Patients will be randomised with an allocation ratio of 1:1 in two parallel groups: one group assigned to a multidisciplinary, nurse-based and pharmacist-based 2-year follow-up in association with general practitioners, neurologists and cardiologists versus one group with usual follow-up. In each group for each disease (stroke/TIA or MI), 430 patients will be enrolled (total of 1720 patients) over 3 years. The primary outcome will be the incremental cost-utility ratio at 24 months between intensive and standard follow-up in a society perspective. Secondary outcomes will include the incremental cost-utility ratio at 6 and 12 months, the incremental cost-effectiveness ratio at 24 months, reduction at 6, 12 and 24 months of the rates of death, unscheduled rehospitalisation and iatrogenic complications, changes in quality of life, net budgetary impact at 5 years of the intensive follow-up on the national health insurance perspective and analysis of factors having positive or negative effects on the implementation of the project in the study area. ETHICS AND DISSEMINATION: Ethical approval was obtained and all patients receive information about the study and give their consent to participate before randomisation. Results of the main trial and each of the secondary analyses will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT04188457. Registered on 6 December 2019.

Time to onset of cardiovascular and cerebrovascular outcomes after hypertensive disorders of pregnancy: a nationwide, population-based retrospective cohort study.

BACKGROUND: The increased maternal cardiocerebrovascular risk after a pregnancy complicated by hypertensive disorders of pregnancy, is well documented in the literature. Recent evidence has suggested a shorter timeframe for the development of these postnatal outcomes, which could have major clinical implications. OBJECTIVE: This study aimed to determine the risk of and time to onset of maternal cardiovascular and cerebrovascular outcomes after a pregnancy complicated by hypertensive disorders of pregnancy. STUDY DESIGN: This study included 2,227,711 women, without preexisting chronic hypertension, who delivered during the period 2008 to 2010: 37,043 (1.66%) were diagnosed with preeclampsia, 34,220 (1.54%) were diagnosed with gestational hypertension, and 2,156,448 had normotensive pregnancies. Hospitalizations for chronic hypertension, heart failure, coronary heart disease, cerebrovascular disease, and peripheral arterial disease were studied. A classical Cox regression was performed to estimate the average effect of hypertensive disorders of pregnancy over 10 years compared with normotensive pregnancy; moreover, an extended Cox regression was performed with a step function model to estimate the effect of the exposure variable in different time intervals: <1, 1 to 3, 3 to 5, and 5 to 10 years of follow-up. RESULTS: The risk of chronic hypertension after a pregnancy complicated by preeclampsia was 18 times higher in the first year (adjusted hazard ratio, 18.531; 95% confidence interval, 16.520-20.787) to only 5 times higher at 5 to 10 years after birth (adjusted hazard ratio, 4.921; 95% confidence interval, 4.640-5.218). The corresponding risks of women with gestational hypertension were 12 times higher (adjusted hazard ratio, 11.727; 95% confidence interval, 10.257-13.409]) and 6 times higher (adjusted hazard ratio, 5.854; 95% confidence interval, 5.550-6.176), respectively. For other cardiovascular and cerebrovascular outcomes, there was also a significant effect with preeclampsia (heart failure: adjusted hazard ratio, 6.662 [95% confidence interval, 4.547-9.762]; coronary heart disease: adjusted hazard ratio, 3.083 [95% confidence interval, 1.626-5.844]; cerebrovascular disease: adjusted hazard ratio, 3.567 [95% confidence interval, 2.600-4.893]; peripheral arterial disease: adjusted hazard ratio, 4.802 [95% confidence interval, 2.072-11.132]) compared with gestational hypertension in the first year of follow-up. A dose-response effect was evident for the severity of preeclampsia with the averaged 10-year adjusted hazard ratios for developing chronic hypertension after early, preterm, and late preeclampsia being 10, 7, and 6 times higher, respectively. CONCLUSION: The risks of cardiovascular and cerebrovascular outcomes were the highest in the first year after a birth complicated by hypertensive disorders of pregnancy. We found a significant relationship with both the severity of hypertensive disorders of pregnancy and the gestational age of onset suggesting a possible dose-response relationship for the development of cardiovascular and cerebrovascular outcomes. These findings call for an urgent focus on research into effective postnatal screening and cardiocerebrovascular risk prevention for women with hypertensive disorders of pregnancy.

Pre-existing brain damage and association between severity and prior cognitive impairment in ischemic stroke patients.

BACKGROUND: We evaluated whether pre-existing brain damage may explain greater severity in cognitively-impaired patients with ischemic stroke (IS). METHODS: IS patients were retrieved from the population-based registry of Dijon, France. Pre-existing damage (leukoaraiosis, old vascular brain lesions, cortical and central brain atrophy) was assessed on initial CT-scan. Association between prestroke cognitive status defined as no impairment, mild cognitive impairment (MCI), or dementia, and clinical severity at IS onset assessed with the NIHSS score was evaluated using ordinal regression analysis. Mediation analysis was performed to assess pre-existing brain lesions as mediators of the relationship between cognitive status and severity. RESULTS: Among the 916 included patients (mean age 76.8 ± 15.0 years, 54.3% women), those with pre-existing MCI (n = 115, median NIHSS [IQR]: 6 [2-15]) or dementia (n = 147, median NIHSS: 6 [3-15]) had a greater severity than patients without (n = 654, median NIHSS: 3 [1-9]) in univariate analysis (OR=1.69; 95% CI: 1.18-2.42, p = 0.004, and OR=2.06; 95% CI: 1.49-2.84, p < 0.001, respectively). Old cortical lesion (OR=1.53, p = 0.002), central atrophy (OR=1.41, p = 0.005), cortical atrophy (OR=1.90, p < 0.001) and moderate (OR=1.41, p = 0.005) or severe (OR=1.84, p = 0.002) leukoaraiosis were also associated with greater severity. After adjustments, pre-existing MCI (OR=1.52; 95% CI: 1.03-2.26, p = 0.037) or dementia (OR=1.94; 95% CI: 1.32-2.86, p = 0.001) remained associated with higher severity at IS onset, independently of confounding factors including imaging variables. Association between cognitive impairment and severity was not mediated by pre-existing visible brain damages. CONCLUSION: Impaired brain ischemic tolerance in IS patients with prior cognitive impairment could involve other mechanisms than pre-existing visible brain damage.

Asymmetric crying facies in an elderly, when a facial asymmetry is not a facial paralysis but a marker of possible congenital malformations: case report and review of the literature.

BACKGROUND: Facial asymmetry when crying at birth (then called asymmetric crying facies or ACF) or when smiling or speaking loudly in adulthood is the consequence of the agenesis or hypoplasia of the muscle of one of the labial commissures. This developmental disorder of complex mechanism is well known by pediatricians to be a warning sign for underlying developmental disorders of variable severity. CASE REPORT: An 80-year-old man with medical history of renal agenesis was hospitalized for a transient motor deficit of the right face and arm revealing a lacunar stroke. Clinical examination showed an isolated left facial asymmetry upon smiling or talking out loud which had been known since childhood and was not related to the stroke, leading to the diagnosis of ACF. Cardiac ultrasound revealed a patent foramen. Chromosomal investigations could not be performed. DISCUSSION AND CONCLUSION: ACF is a rare disorder that may conceal associated congenital disorders such as heart, skeletal, or renal malformations. Its causing mechanisms are to this day still poorly understood but may include a genetic component as shown by familial cases and the identification of 22q11.2 deletions or trisomy 18 in some patients. Knowledge of this disorder seems highly relevant for adult neurologists, first because of the differential diagnosis with facial palsy, but mostly because it will allow them to screen patients for other congenital disorders such as heart malformations. Conversely, cardiologists and cardiac surgeon may search for an ACF when faced with a patient with a congruent heart defect.

[A territory project for the follow-up of strokes and myocardial infarctions]. / Un projet de territoire pour le suivi des accidents vasculaires cérébraux et des infarctus du myocarde.

The Dijon Vascular Project experiment aims to reduce the risk of unscheduled re-hospitalization for stroke and myocardial infarction. It involves hospital and private healthcare professionals working in the Côte-d'Or and South Haut-Marnais hospital grouping area. Within this system, hospital and private practice nurses are essential links in the patient's circle of care and fundamental contacts for post-stroke or post-MI follow-up: through their interventions, they contribute to preventing the risks of complications and recurrences.

Impact of the First COVID-19 Wave on French Hospitalizations for Myocardial Infarction and Stroke: A Retrospective Cohort Study.

The COVID-19 pandemic modified the management of myocardial infarction (MI) and stroke. We aimed to evaluate the effect of the COVID-19 pandemic on the volume and spatial distribution of hospitalizations for MI and stroke, before, during and after the first nationwide lockdown in France in 2020, compared with 2019. Hospitalization data were extracted from the French National Discharge database. Patient's characteristics were compared according to COVID-19 status. Changes in hospitalization rates over time were measured using interrupted time series analysis. Possible spatial patterns of over or under-hospitalization rates were investigated using Moran's indices. We observed a rapid and significant drop in hospitalizations just before the beginning of the lockdown with a nadir at 36.5% for MI and 31.2% for stroke. Hospitalization volumes returned to those seen in 2019 four weeks after the end of the lockdown, except for MI, which rebounded excessively. Older age, male sex, elevated rate of hypertension, diabetes, obesity and mortality characterized COVID-19 patients. There was no evidence of a change in the spatial pattern of over- or under-hospitalization clusters over the three periods. After a steep drop, only MI showed a significant rebound after the first lockdown with no change in the spatial distribution of hospitalizations.

Yield of Dual Therapy With Statin and Ezetimibe in the Treat Stroke to Target Trial.

BACKGROUND: In atherosclerotic stroke, lipid-lowering treatment with a target LDL (low-density lipoprotein) cholesterol of <70 compared with 100±10 mg/dL reduced the risk of subsequent cardiovascular events. This post hoc analysis explored the relative effects of the combination of statin and ezetimibe (dual therapy) and statin monotherapy in achieving the lower LDL cholesterol target and in reducing the risk of major vascular events, as compared with the higher target group. METHODS: Patients with ischemic stroke in the previous 3 months or transient ischemic attack within the previous 15 days and evidence of cerebrovascular or coronary artery atherosclerosis were randomly assigned to a target LDL cholesterol of <70 or 100±10 mg/dL, using statin and/or ezetimibe as needed. The primary outcome was the composite of ischemic stroke, myocardial infarction, new symptoms requiring urgent coronary or carotid revascularization, and vascular death. Cox regression model including lipid-lowering therapy as a time varying variable, after adjustment for randomization strategy, age, sex, index event (stroke or transient ischemic attack), and time since the index event. RESULTS: Among 2860 patients enrolled, patients who were on dual therapy during the trial in the lower target group had a higher baseline LDL cholesterol as compared to patients on statin monotherapy (141±38 versus 131±36, respectively, P<0.001). In patients on dual therapy and on statin monotherapy, the achieved LDL cholesterol was 66.2 and 64.1 mg/dL respectively, and the primary outcome was reduced during dual therapy as compared with the higher target group (HR, 0.60 [95% CI, 0.39-0.91]; P=0.016) but not during statin monotherapy (HR, 0.92 [95% CI, 0.70-1.20]; P=0.52), with no significant increase in intracranial bleeding. CONCLUSIONS: In the TST trial (Treat Stroke to Target), targeting an LDL cholesterol of < 70 mg/dL with a combination of statin and ezetimibe compared with 100±10 mg/dL consistently reduced the risk of subsequent stroke. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01252875. URL: clinicaltrialsregister.eu; Unique identifier: EUDRACT2009-A01280-57.

Trends of Myocarditis and Endocarditis Cases before, during, and after the First Complete COVID-19-Related Lockdown in 2020 in France.

BACKGROUND: The impact of the COVID-19 pandemic on hospitalization for cardiac infections is not well known. We aimed to evaluate the nationwide trends in hospital stays for myocarditis and endocarditis cases before, during and after the nationwide lockdown for the COVID-19 pandemic in France. We then aimed to describe the proportion of myocarditis and endocarditis patients with and without COVID-19 and their clinical characteristics. METHODS: Hospitalized cases of cardiac infection were extracted from the French National Discharge database, which collects the medical records of all patients discharged from all public and private hospitals in France. Age, sex, and available cardiovascular risk factors were compared between stays with and without COVID-19 during the lockdown. RESULTS: The number of myocarditis cases was 11% higher in 2020, compared to the average of the three prior years. In 2020, 439 of 3727 cases of myocarditis were associated with COVID-19. For endocarditis, there was an increase in cases by 7% in 2020 versus prior years. For endocarditis, 3% (240 of 8128 cases) of patients with endocarditis had COVID-19. For myocarditis, older age, hypertension, diabetes, obesity, and atrial fibrillation were more frequent in patients with COVID-19 than in those without. For endocarditis, only hypertension was more frequent in patients with COVID-19 than in those without. CONCLUSION: Our study reports an increase in hospitalizations for both myocarditis and endocarditis in 2020, possibly related to the COVID-19 pandemic. Interestingly, the trends differ according to the COVID-19 status. Knowledge of the factors associating myocarditis or endocarditis and COVID-19 may improve the quality and the type of monitoring for people with COVID-19, the identification of patients at risk of cardiac infections, and the treatment of COVID-19 patients.

Intracranial Hemorrhage in the TST Trial.

BACKGROUND AND PURPOSE: Although statins are effective in secondary prevention of ischemic stroke, they are also associated with an increase risk of intracranial hemorrhage (ICH) in certain conditions. In the TST trial (Treat Stroke to Target), we prespecified an exploration of the predictors of incident ICH. METHODS: Patients with ischemic stroke in the previous 3 months or transient ischemic attack within the previous 15 days and evidence of cerebrovascular or coronary artery atherosclerosis were randomly assigned in a 1:1 ratio to a target LDL (low-density lipoprotein) cholesterol of <70 mg/dL or 100±10 mg/dL, using statin or ezetimibe. RESULTS: Among 2860 patients enrolled, 31 incident ICH occurred over a median follow-up of 3 years (18 and 13 in the lower and higher target group, 3.21/1000 patient-years [95% CI, 2.38-4.04] and 2.32/1000 patient-years [95% CI, 1.61-3.03], respectively). While there were no baseline predictors of ICH, uncontrolled hypertension (HR, 2.51 [95% CI, 1.01-6.31], P=0.041) and being on anticoagulant (HR, 2.36 [95% CI, 1.00-5.62], P=0.047)] during the trial were significant predictors. On-treatment low LDL cholesterol was not a predictor of ICH. CONCLUSIONS: Targeting an LDL cholesterol of <70 mg/dL compared with 100±10 mg/dL in patients with atherosclerotic ischemic stroke nonsignificantly increased the risk of ICH. Incident ICHs were not associated with low LDL cholesterol. Uncontrolled hypertension and anticoagulant therapy were associated with ICH which has important clinical implications. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01252875; EUDRACT identifier: 2009-A01280-57.

High efficiency and clinical relevance of exome sequencing in the daily practice of neurogenetics.

OBJECTIVE: To assess the efficiency and relevance of clinical exome sequencing (cES) as a first-tier or second-tier test for the diagnosis of progressive neurological disorders in the daily practice of Neurology and Genetic Departments. METHODS: Sixty-seven probands with various progressive neurological disorders (cerebellar ataxias, neuromuscular disorders, spastic paraplegias, movement disorders and individuals with complex phenotypes labelled 'other') were recruited over a 4-year period regardless of their age, gender, familial history and clinical framework. Individuals could have had prior genetic tests as long as it was not cES. cES was performed in a proband-only (60/67) or trio (7/67) strategy depending on available samples and was analysed with an in-house pipeline including software for CNV and mitochondrial-DNA variant detection. RESULTS: In 29/67 individuals, cES identified clearly pathogenic variants leading to a 43% positive yield. When performed as a first-tier test, cES identified pathogenic variants for 53% of individuals (10/19). Difficult cases were solved including double diagnoses within a kindred or identification of a neurodegeneration with brain iron accumulation in a patient with encephalopathy of suspected mitochondrial origin. CONCLUSION: This study shows that cES is a powerful tool for the daily practice of neurogenetics offering an efficient (43%) and appropriate approach for clinically and genetically complex and heterogeneous disorders.

Impact of the first COVID-19 pandemic peak and lockdown on the interventional management of carotid artery stenosis in France.

OBJECTIVE: The aim of this study was to evaluate the impact of the COVID-19 pandemic on the trends of carotid revascularization (endarterectomy [CEA], transfemoral carotid artery stenting [TFCAS]) for symptomatic and asymptomatic carotid stenosis before, during, and after the end of the first lockdown in 2020 in France. METHODS: Nationwide data were provided by the French National Hospital Discharge database (Programme de Médicalisation des Systèmes d'Information). We retrospectively analyzed patients admitted for CEA or TFCAS in all French public and private hospitals during a 9-month period (January-September) in 2017, 2018, 2019, and 2020. Procedures were identified using the French Common Classification of Medical Procedures. Stenoses were considered symptomatic in the presence of stroke and/or transient ischemic attack codes (according to the International Classification of Diseases-Tenth Revision) during the stay, and asymptomatic in the absence of these codes. Hospitalization rates in 2020 were compared with the rates in the same period in the 3 previous years. RESULTS: Between January and September 2020, 12,546 patients were hospitalized for carotid artery surgery (CEA and TFCAS) in France. Compared with the 3 previous years, there was a decrease in hospitalization rates for asymptomatic (-68.9%) and symptomatic (-12.6%) CEA procedures in April, starting at the pandemic peak concomitant with the first national lockdown. This decrease was significant for asymptomatic CEA (P < .001). After the lockdown, while CEA for asymptomatic stenosis returned to usual activity, CEA for symptomatic stenosis presented a significant rebound, up 18.52% in August compared with previous years. Lockdown also had consequences on TFCAS procedures, with fewer interventions for both asymptomatic (-60.53%) and symptomatic stenosis (-16.67%) in April. CONCLUSIONS: This study demonstrates a severe decrease for all interventions during the first peak of the COVID-19 pandemic in France. However, the trends in the postlockdown period were different for the various procedures. These data can be used to anticipate future decisions and organization for cardiovascular care.

Assessment of Clinical Scales for Detection of Large Vessel Occlusion in Ischemic Stroke Patients from the Dijon Stroke Registry.

(1) Background: The limited availability of thrombectomy-capable stroke centres raises questions about pre-hospital triage of patients with suspected stroke (IS) due to large vessel occlusion (LVO). Aims: This study aimed to evaluate the diagnostic accuracy of clinical stroke severity scales available for LVO detection. (2) Methods: Patients with IS were prospectively identified among residents of Dijon, France, using a population-based registry (2013-2017). Clinical signs and arterial imaging data were collected. LVO was defined as an occlusion site affecting the terminal intracranial internal carotid artery, the M1 segment of the middle cerebral artery (MCA), or the basilar artery (restricted definition). A wide definition of LVO also included the M2 segment of the MCA. For each of the 16 evaluated scales, a receiver operator characteristic (ROC) analysis was performed, and the c-statistic representing the area under the ROC curve was evaluated to assess discrimination for predicting LVO. (3) Results: 971 patients were registered, including 123 patients (12.7%) with an LVO according to the restricted definition. The c-statistic for LVO detection ranged between 0.66 and 0.80 according to the different scales, with a sensibility varying from 70% to 98% and a specificity from 33% to 86%. According to the wide definition of LVO (174 patients, 17.9%), the c-statistic was slightly lower, ranging between 0.64 and 0.79. The sensitivity was 59% to 93%, and the specificity was 34% to 89%. (4) Conclusion: The clinical scales failed to combine a high sensitivity and a high specificity to detect LVO. Further studies are needed to determine the best strategy for pre-hospital triage of IS patients.

Cardiovascular Surgical Emergencies in France, before, during and after the First Lockdown for COVID-19 in 2020: A Comparative Nationwide Retrospective Cohort Study.

BACKGROUND: There are still gaps regarding the impact of the nationwide lockdown on non-COVID-19 emergency hospitalizations. This study aims to describe the trends in hospitalizations for cardiovascular surgical emergencies in France, before, during and after the first lockdown. MATERIALS AND METHODS: All adults admitted for mechanical complications of myocardial infarction (MI), aortic dissection, aortic aneurysm rupture, acute and critical limb ischemia, circulatory assistance, heart transplantation and major amputation were included. This retrospective cohort study used the French National Hospital Discharge database. The numbers of hospitalizations per month in 2020 were compared to the previous three years. RESULTS: From January to September 2020, 94,408 cases of the studied conditions were reported versus 103,126 in the same period in 2019 (-8.5%). There was a deep drop in most conditions during the lockdown, except for circulatory assistance, which increased. After the lockdown, mechanical complications of MI and aortic aneurysm rupture increased, and cardiac transplantations declined compared with previous years. CONCLUSION: We confirmed a deep drop in most cardiovascular surgical emergencies during the lockdown. The post-lockdown period was characterized by a small over-recovery for mechanical complications of MI and aortic aneurysm rupture, suggesting that many patients were able to access surgery after the lockdown.

Temporal Trends in the Incidence of Ischemic Stroke in Young Adults: Dijon Stroke Registry.

INTRODUCTION: Stroke is associated with major consequences in terms of socioeconomic impact and lost disability-adjusted life in young victims, thus justifying a careful surveillance of epidemiological trends. This study aimed to assess changes in the incidence of ischemic stroke in young adults over a long period. METHODS: All cases of first-ever ischemic stroke that occurred among adults aged 18-55 years were prospectively recorded using the population-based Dijon Stroke Registry, from 1985 to 2017. Sex-specific annual incidence rates were calculated and were presented according to 6 time periods. Incidence rate ratios (IRRs) were determined to assess sex differences in stroke incidence. RESULTS: Over the whole study period, 4,451 patients suffered a first-ever ischemic stroke. Among these patients, 469 (10.5%) were young adults (median age: 46 years, IQR: 39-50; 53.9% men). Incidence rates rose from the study period 2003 to 2007 compared with previous periods and remained stable thereafter, both in men and women. Hence, incidence per 100,000 per year was globally 11.0 (95% CI: 9.4-12.7) before 2003 and 22.9 (20.3-25.6) thereafter. In individuals aged 18-45 years, incidence rates were 5.4 (4.3-6.9) overall, 4.1 (2.7-6.0) in men, and 6.7 (4.9-9.0) in women, before 2003. After 2003, incidence rates rose to 12.8 (10.7-15.1) overall, 12.0 (9.2-15.4) in men, and 13.6 (10.6-17.0) in women. In this age group, the men/women IRR was 0.78 (95% CI: 0.62-1.26, p = 0.08), although sex differences decreased over time (IRR = 0.62; 95% CI: 0.36-1.02, p = 0.046 before 2003, vs. IRR = 0.88; 95% CI: 0.62-1.26, p = 0.48 after 2003). In individuals aged 45-55 years, incidence rates before 2003 were 47 (37-61) in men and 25 (17-35) in women (IRR = 1.90; 95% CI: 1.24-2.97, p < 0.001), and they increased to 82 (67-100) in men and 46 (35-59) in women (IRR = 1.79; 95% CI: 1.29-2.49, p < 0.001) after 2003. CONCLUSIONS: The incidence of ischemic stroke in young adults increased during the early 2000s and remained stable thereafter. These results highlight the priority need for dedicated prevention strategies for the young to reduce the burden of stroke.

Impact of Lower Versus Higher LDL Cholesterol Targets on Cardiovascular Events After Ischemic Stroke in Patients With Diabetes.

After an ischemic stroke with evidence of atherosclerosis, lipid-lowering treatment with a target LDL cholesterol of <70 mg/dL compared with 100 ± 10 mg/dL reduced the risk of subsequent cardiovascular events. In this analysis, we explored the effect in the subgroup of patients with diabetes compared with the subgroup without, as well as in those with newly diagnosed diabetes. Patients with ischemic stroke in the previous 3 months or transient ischemic attack within the previous 15 days and evidence of cerebrovascular or coronary artery atherosclerosis were randomly assigned at a 1:1 ratio to a target LDL cholesterol of <70 mg/dL or 100 ± 10 mg/dL using statin or ezetimibe. The primary outcome was the composite of ischemic stroke, myocardial infarction, new symptoms requiring urgent coronary or carotid revascularization, and death resulting from vascular disease. We performed a prespecified analysis to evaluate the effect in patients with diabetes. Of 2,860 patients enrolled, 643 had diabetes at baseline, with a mean age of 66.2 years and baseline LDL cholesterol of 127 mg/dL, and were followed for a median of 3 years. The primary composite end point occurred in 27 (8.2%) of 328 patients in the lower-target group and in 44 (14.0%) of 315 patients in the higher-target group (adjusted hazard ratio [HR] 0.56; 95% CI 0.34-0.89; P = 0.016). In patients without diabetes, the HR was 0.87 (95% CI 0.66-1.14; P = 0.31; interaction P = 0.15). In those with diabetes, there were three intracranial hemorrhages in both randomization groups (0.9% vs. 1.0%, respectively). Newly diagnosed diabetes occurred in 98 (9.2%) of 1,070 and in 80 (7.4%) of 1,085 patients in the lower- and higher-target groups, respectively (HR 1.27; 95% CI 0.94-1.71; P = 0.11), and baseline higher HbA1c was the unique multivariable predictor. In conclusion, after an ischemic stroke with evidence of atherosclerosis, targeting an LDL cholesterol of <70 mg/dL compared with 100 ± 10 mg/dL consistently reduced the risk of subsequent stroke and other major vascular events in patients with and without diabetes, but the higher risk in those with diabetes yielded a higher absolute risk reduction, with number needed to treat of 17.

Hospitalizations for Stroke in France During the COVID-19 Pandemic Before, During, and After the National Lockdown.

BACKGROUND AND PURPOSE: In France, the entire population was put under a total lockdown from March 17 to May 11, 2020 during the peak of the coronavirus disease 2019 (COVID-19) pandemic. Whether the lockdown had consequences on the management of medical emergencies such as stroke and transient ischemic attack (TIA) has yet to be fully evaluated. This article describes hospitalization rates for acute stroke in 2 French regions that experienced contrasting rates of COVID-19 infection, before, during, and after the nationwide lockdown (January to June 2020). METHODS: All patients admitted for acute stroke/TIA into all public and private hospitals of the 2 study regions were included. Data were retrieved from the National Hospitalization Database (PMSI). In the most affected region (Grand-Est), the hospitalization rates observed in April 2020 were compared with the rates in the same period in the least affected region (Occitanie) and in the 3 prior years (2017-2019). RESULTS: There was a significant decline in hospitalization rates for stroke/TIA within the region most affected by COVID-19 during the month of April 2020 compared with previous years, while no significant change was seen in the least affected region. After lockdown, we observed a fast rebound in the rate of hospitalization for stroke/TIA in the most affected region, contrasting with a slower rebound in the least affected region. In both regions, patients with COVID-19 stroke more frequently had ischemic stroke, a nonsignificant greater prevalence of diabetes, they were less frequently admitted to stroke units, and mortality was higher than in patients without COVID-19. CONCLUSIONS: Our results demonstrates a significant drop in stroke/TIA hospitalizations and a fast recovery after the end of the French lockdown in the most affected region, while the least affected region saw a nonsignificant drop in stroke/TIA hospitalizations and a slow recovery. These results and recommendations could be used by the health authorities to prepare for future challenges.