H. Gardener, J. Romano, Terry O Derias, C. Gutierrez, N. Asdaghi, Karlon H Johnson, Gillian Gordon Perue, Erika Marulanda, Scott C. Brown, Dianne Foster, T. Rundek
{"title":"Early hospital readmission following stroke: the Florida Stroke Registry","authors":"H. Gardener, J. Romano, Terry O Derias, C. Gutierrez, N. Asdaghi, Karlon H Johnson, Gillian Gordon Perue, Erika Marulanda, Scott C. Brown, Dianne Foster, T. Rundek","doi":"10.3389/fstro.2023.1238442","DOIUrl":"https://doi.org/10.3389/fstro.2023.1238442","url":null,"abstract":"Hospital readmission is an important indicator of poor transition of care post-stroke. Data on characteristics of patients at highest risk for readmission is limited and necessary to inform effective interventions. The goal is to identify risk factors at hospital discharge that predict 30-day readmission in the Florida Stroke Registry (FSR).The study population included 45,877 patients discharged home or to rehabilitation with an ischemic stroke or intracerebral hemorrhage in the FSR between 2017 and 2019. The FSR is a voluntary statewide registry of stroke patients from 167 hospitals using data from Get With the Guideline-Stroke. Readmissions were ascertained by propensity matching FSR with the Florida Agency for Healthcare Administration dataset, which includes all hospital admissions in Florida. The primary outcome was 30-day hospital readmission for any cause, and secondary outcomes were vascular-related and stroke readmissions specifically. Multivariable logistic regression models identified patient characteristics that independently predicted 30-day readmissions, including sociodemographics, stroke clinical characteristics, in-hospital treatment, medical history, discharge status, and hospital characteristics.A hospital readmission within 30 days was experienced in 12% of cases; 6% had a vascular-related readmission, and 3% a recurrent stroke. The following characteristics were independently associated with an increased risk of all-cause readmission: Medicare or Medicaid insurance, large artery atherosclerosis as the stroke mechanism, increased stroke severity, diabetes, atrial fibrillation, peripheral vascular disease, coronary artery disease, prior stroke, chronic renal insufficiency, and depression. The following characteristics were independently associated with a decreased risk of all-cause readmission: ambulation, treated dyslipidemia, tPA treatment, discharge mRS 0–2, and treatment at a comprehensive stroke center.The risk of 30-day hospital readmission was substantial, modifiable, and impacted by insurance status, medical history, stroke etiology and severity, stroke care, and functional status at discharge. These findings can inform strategies to target high-risk patients who can benefit from interventions to improve transitions of care post-stroke.","PeriodicalId":73108,"journal":{"name":"Frontiers in stroke","volume":"51 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87548725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Case report: Ethylene glycol intoxication presenting as a mimic of acute stroke: a report of three cases","authors":"M. Héja, László Oláh","doi":"10.3389/fstro.2023.1233229","DOIUrl":"https://doi.org/10.3389/fstro.2023.1233229","url":null,"abstract":"Stroke is a major cause of death and disability presenting with acute focal neurological symptoms of vascular origin. Several other disorders may cause symptoms similar to a stroke, referred to as stroke mimics. The misdiagnosis of stroke mimics may lead to potentially harmful treatments, including thrombolysis. Intoxication is a rare, but possible, cause of stroke mimic. We present three cases of ethylene glycol poisoning presenting as an acute stroke mimic within the time window of thrombolytic therapy. Two of three patients (a 54-year-old male and a 78-year-old male) had dysarthria, nystagmus, and truncal ataxia on admission. The third patient with a history of chronic alcoholism presented after an epileptic seizure with mixed aphasia and confusion. Non-contrast cerebral computed tomography and computed tomography angiography were negative in all three cases. As stroke could not be excluded in any of the patients, thrombolysis was performed. However, after some hours, two of the three patients developed agitation, somnolence, and hyperventilation. One patient's consciousness deteriorated rapidly, and he became comatose and tetraplegic. A blood gas analysis showed acidosis in two of the three patients, and toxicological screening revealed ethylene glycol intoxication in all three cases. Due to the appropriate treatment, two of the three patients became symptom-free; however, one of the three patients died. Our cases show that ethylene glycol intoxication in its early phase may mimic acute stroke, resulting in unnecessary thrombolytic therapy. Symptoms not characteristic of a stroke, such as hyperventilation, agitation, and disturbance of consciousness, may appear later and warn of intoxication. The final diagnosis of ethylene glycol intoxication can be established by severe metabolic acidosis and toxicological screening. Close monitoring of symptoms might contribute to the early recognition of ethylene glycol intoxication and its effective treatment.","PeriodicalId":73108,"journal":{"name":"Frontiers in stroke","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78596779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
W. Dodd, Devan Patel, K. Motwani, B. Lucke-Wold, K. Hosaka, B. Hoh
{"title":"NLRP3 inflammasome inhibition protects against intracranial aneurysm rupture and alters the phenotype of infiltrating macrophages","authors":"W. Dodd, Devan Patel, K. Motwani, B. Lucke-Wold, K. Hosaka, B. Hoh","doi":"10.3389/fstro.2023.1202137","DOIUrl":"https://doi.org/10.3389/fstro.2023.1202137","url":null,"abstract":"Aneurysmal subarachnoid hemorrhage is a devastating cerebrovascular disease associated with high morbidity and mortality. Macrophage-mediated mural inflammation is a key pathogenic component contributing to aneurysm rupture.To investigate the effect of pharmacological inhibition of the NLRP3 inflammasome on aneurysm rupture.Cerebral aneurysms were induced in C57BL/6 mice with a combination of hypertension and an intracranial dose of elastase. Mice were treated with either 40 mg/kg of MCC950 or saline via intraperitoneal injections. Vascular tissue at the circle of Willis was harvested for analysis via immunofluorescent microscopy or qPCR.NLRP3+ cells are more common in the aneurysm tissue compared to the normal cerebral vasculature. The mRNA expression of the downstream NLRP3 pathway components caspase-1, IL-1β, and GSDMD is also increased in the aneurysm tissue compared to healthy vessels. There was no difference in the aneurysm formation rate between MCC950- and vehicle-treated mice; however, MCC950 treatment significantly reduced aneurysm rupture rate. There was no difference in systemic blood pressure between both groups. MCC950 treatment also extended the symptom-free survival of mice after aneurysm induction. Mechanistically, NLRP3 inhibition decreased the phenotype polarization of infiltrating macrophages without affecting the total number of macrophages in the vessel wall.Our results indicate that the NLRP3 inflammasome contributes to aneurysm rupture and macrophage polarization within the vessel wall. The NLRP3 pathway is a promising therapeutic target for the development of therapeutics to prevent aneurysmal hemorrhagic stroke.","PeriodicalId":73108,"journal":{"name":"Frontiers in stroke","volume":"15 7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82881397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N. Karim, Suzanne Stone, A. Salter, M. Gebreyohanns, Mark D. Johnson, E. Jones
{"title":"Non-English primary language and disparities in stroke outcomes after mechanical thrombectomy: a single institution study","authors":"N. Karim, Suzanne Stone, A. Salter, M. Gebreyohanns, Mark D. Johnson, E. Jones","doi":"10.3389/fstro.2023.1224566","DOIUrl":"https://doi.org/10.3389/fstro.2023.1224566","url":null,"abstract":"Delays in acute treatment of ischemic stroke have been associated with worse outcomes. While having a non-English primary language has not been shown to delay receiving thrombolytic therapy, we assessed whether non-English primary language was associated with worse functional outcomes in patients receiving mechanical thrombectomy (MT).This is a retrospective study of our MT database from two comprehensive stroke centers from January 2016 to May 2021. Primary endpoint was discharge modified Rankin Scale (mRS) 0-2. Differences between English primary language (EPL) and non-English primary language (nEPL) groups were evaluated using an analysis of variance (ANOVA), Kruskal-Wallis and chi square test. Multivariable logistic regression was used to evaluate EPL vs. nEPL patients using data driven models determined by stepwise selection approach.We identified 276 patients receiving MT with 83% EPL and 17% nEPL patients. nEPL patients had higher mean hemoglobin A1c, were less likely to have insurance, and more likely to have symptomatic intracranial hemorrhage compared to EPL patients (Table). We observed a longer median ED arrival to groin puncture time in the nEPL group. No differences were observed in discharge or mRS 0-2 in the univariate or multivariable logistic regression.Despite finding longer ED length of stay among nEPL patients, there was no difference between nEPL and EPL in good functional outcome rates in patients treated with MT.","PeriodicalId":73108,"journal":{"name":"Frontiers in stroke","volume":"39 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88848218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
D. Laskowitz, K. Muir, S. Savitz, L. Wechsler, J. Pilitsis, S. Rahimi, R. Beckman, Vincent Holmes, P. Chen, Laura Juel, Deborah C. Koltai, B. Kolls
{"title":"Methodological considerations in PISCES 3: a randomized, placebo-controlled study of intracerebral stem cells in subjects with disability following an ischemic stroke","authors":"D. Laskowitz, K. Muir, S. Savitz, L. Wechsler, J. Pilitsis, S. Rahimi, R. Beckman, Vincent Holmes, P. Chen, Laura Juel, Deborah C. Koltai, B. Kolls","doi":"10.3389/fstro.2023.1182537","DOIUrl":"https://doi.org/10.3389/fstro.2023.1182537","url":null,"abstract":"At present, there are no medical interventions proven to improve functional recovery in patients with subacute stroke. We hypothesize that the intraparenchymal administration of CTX0E03, a conditionally immortalized neural stem cell line, linked with a standardized rehabilitation therapy regimen for the upper limb, would improve functional outcomes in patients 6–12 months after an index ischemic stroke.PISCES III was designed as a multicenter prospective, sham-controlled, outcome-blinded randomized clinical trial. Eligibility required a qualifying ischemic stroke 6–12 months prior to surgical intervention. Patients must be between 35 and 75 years of age and have residual moderate or moderately severe disability (mRS 3 or 4), with the preservation of some residual upper limb movement. All patients received a standardized regimen of home physical therapy following the intervention.The primary outcome measure is improvement in the modified Rankin Scale (mRS) of disability at 6 months post treatment. Secondary outcomes include assessment of activities of daily living (Barthel Index), functional mobility (Timed Up and Go; Fugl Meyer Assessment), neurological impairment (NIHSS), upper limb function (Chedoke Arm and Hand Inventory), as well as patient related quality of life and global rating scales.PISCES III was designed as a randomized trial directly comparing the effects of intraparenchymal injection of a conditional stem cell line vs. sham procedure in patients with subacute stroke. This is one of the first studies of this type to include a standardized minimum rehabilitation protocol. As there are a limited number of studies evaluating invasive stem cell administration in the chronic setting of CNS injury, study design considerations are discussed.","PeriodicalId":73108,"journal":{"name":"Frontiers in stroke","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75495331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E. J. Layug, A. D. A. O. Apor, Rudolf V. Kuhn, M. Tan
{"title":"Mechanisms of pediatric ischemic strokes in COVID-19: a systematic review","authors":"E. J. Layug, A. D. A. O. Apor, Rudolf V. Kuhn, M. Tan","doi":"10.3389/fstro.2023.1197714","DOIUrl":"https://doi.org/10.3389/fstro.2023.1197714","url":null,"abstract":"Coronavirus disease 2019 (COVID-19) has been shown to cause vasculopathic and hemostatic derangements predisposing to cerebrovascular and thrombotic disorders in adults. Data in children, however, are limited to case reports and series. Given the unique risk factors and potential pathomechanisms in children, it is imperative to characterize stroke in children with COVID-19. Understanding these mechanisms is essential in drafting an appropriate management protocol to improve outcomes in a population where stroke carries higher disability-adjusted life years.A systematic literature search was done in MEDLINE, EMBASE, Web of Science and Google Scholar using the terms “pediatric ischemic stroke,” “cerebral sinovenous thrombosis,” “SARS-CoV-2,” and “COVID-19.” Patient demographics, clinical profile, stroke risk factors, neuroimaging findings, interventions and outcomes were recorded.The search produced 776 records. After preliminary review of titles, abstracts and selected full texts, 52 articles comprising of 74 patients were studied. The cohort has slight female predominance (51.5%), with mean age of 9.2 years (±2SD 5.6). Pediatric ischemic strokes were categorized as arterial ischemic strokes (82.40%), cerebral sinovenous thrombosis (12.20%) and combined arterial and venous strokes (5.41%). Mechanisms of ischemic stroke included thrombophilia (47.3%), vasculopathies (27%) and cardioembolism (6.8%). Twenty cases (27%) had comorbidities predisposing to stroke and only 18.9% met the criteria for multisystem inflammatory syndrome in children (MIS-C). Outcomes ranged from complete recoveries (13/58), residual deficits (35/58), and mortalities (10/58).This study presents a comprehensive summary of the currently available published literature on pediatric ischemic strokes in the background of COVID-19. The clinical profiles and outcomes of patients reviewed support prior hypotheses that the virus can cause both a vasculopathy and induce a derangement in the coagulation system, predisposing to ischemic strokes.This paper's protocol has been registered in PROSPERO with ID number CRD42022315219.","PeriodicalId":73108,"journal":{"name":"Frontiers in stroke","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88284012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Błażej Nowak, P. Rogujski, Raphael G Guzman, P. Walczak, A. Andrzejewska, M. Janowski
{"title":"Animal models of focal ischemic stroke: brain size matters","authors":"Błażej Nowak, P. Rogujski, Raphael G Guzman, P. Walczak, A. Andrzejewska, M. Janowski","doi":"10.3389/fstro.2023.1165231","DOIUrl":"https://doi.org/10.3389/fstro.2023.1165231","url":null,"abstract":"Stroke remains the second leading cause of death worldwide and the third cause of disability-adjusted life-years. Most strokes are ischemic in nature, meaning they are caused by the disruption of cerebral blood flow resulting from obstructed blood vessels. Reperfusion therapies such as thrombolysis with tissue plasminogen activator and endovascular mechanical thrombectomy are very effective and are becoming game changers for eligible patients. Despite these advances, the achieved effects are insufficient from the perspective of the entire population of stroke patients. Therefore, there is an urgent need to expand eligibility for reperfusion therapies and implement adjuvant therapeutic measures. Animal stroke models are at the forefront of these efforts, helping to untangle complex pathophysiology and providing valuable preclinical data to guide further clinical trials. Various stroke models are available, including direct blocking of cerebral arteries or using other means to recapitulate stroke pathophysiology. International advisory boards recommend initial in vivo experiments be performed in smaller animals, such as rodents. However, second testing would be more desirable in larger animals such as cats, pigs, dogs, and non-human primates. Due to larger cerebral volume, gyrencephalization, and higher white/gray matter ratio, large animals are crucial in translational stroke research. Animal stroke models differ in the time and complexity of the stroke induction procedure, the reproducibility rate, the level of similarity to the human condition, and the possibilities for analysis, imaging, and follow-up studies. The choice of the most appropriate stroke model may translate to better bench-to-bedside translation of preclinical stroke research; ideally, this choice should be based solely on scientific merit.","PeriodicalId":73108,"journal":{"name":"Frontiers in stroke","volume":"152 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78691146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L. Yeo, D. Simonato, P. Bhogal, A. Gopinathan, Y. Cunli, Samuel W. Q. Ong, M. Jing, B. Tan, C. Sia, Tom Jia, G. Cester, J. Gabrieli, T. Andersson
{"title":"Direct dotterising or angioplasty of acute stroke due to tandem atherosclerotic occlusions","authors":"L. Yeo, D. Simonato, P. Bhogal, A. Gopinathan, Y. Cunli, Samuel W. Q. Ong, M. Jing, B. Tan, C. Sia, Tom Jia, G. Cester, J. Gabrieli, T. Andersson","doi":"10.3389/fstro.2023.1163106","DOIUrl":"https://doi.org/10.3389/fstro.2023.1163106","url":null,"abstract":"Background Tandem occlusions cause 10–15% of LVO acute ischemic strokes but are difficult to treat endovascularly and frequently excluded from clinical trials. The optimum endovascular method is still debated, however going directly through the carotid occlusion can speed up the procedure and reduce procedural risk by eliminating an exchange maneuver. Method Using retrospective data from three centers, we compared treating atherosclerotic tandem occlusions using a 0.035'-guidewire and direct dotterisation or angioplasty with a peripheral vascular balloon suitable for the wire, vs. the usual technique of an 0.014'wire. We compared the successful recanalization (mTICI 2b-3) rates, 90 days' functional outcomes (mRS 0–2), and puncture-to-recanalization times between both procedures. Results Forty-two consecutive patients with atherosclerotic tandem occlusions were included; 25 were treated with the 0.014'wire technique and 17 with the 0.035'-guidewire and direct dotterisation or angioplasty with a peripheral vascular balloon technique. The direct technique achieved a higher rate of successful recanalization (100 vs. 72%, P = 0.018), better functional outcome (88.4 vs. 48.0%, P = 0.044), and faster procedure times (mean 65.1 mins vs. 114.8 mins, P < 0.001). The number of attempts was similar between both groups (median 2 vs 3 attempts, P = 0.101). There was no significant difference in the complication rate between both groups (5.9 vs. 12.0%, P = 0.462). Conclusion Compared to previous endovascular techniques for treating atherosclerotic tandem occlusions, the direct technique using standard 0.035' guidewires and dotterisation or a peripheral vascular balloon is significantly faster with better outcomes. However, this will require further external validation in larger cohorts.","PeriodicalId":73108,"journal":{"name":"Frontiers in stroke","volume":"45 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90780593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anna C J Kalisvaart, Natasha A. Bahr, F. Colbourne
{"title":"Relationship between edema and intracranial pressure following intracerebral hemorrhage in rat","authors":"Anna C J Kalisvaart, Natasha A. Bahr, F. Colbourne","doi":"10.3389/fstro.2023.1155937","DOIUrl":"https://doi.org/10.3389/fstro.2023.1155937","url":null,"abstract":"Elevated intracranial pressure (ICP) is a potentially fatal consequence of intracerebral hemorrhage (ICH). As the mass of the hematoma and regional edema builds, ICP rises and becomes increasingly variable acutely after stroke. High ICP may worsen cellular injury and edema by impairing local tissue perfusion, fueling a cycle that may ultimately cause fatality through ischemia and brain herniation. Time spent above an ICP of 20 mmHg often predicts a greater risk of death and disability following ICH. Compensatory mechanisms combat rising ICP. Classically, these include cerebrospinal fluid volume loss and cerebrovascular autoregulation, such as a reduction in the volume of venous blood. Additional mechanisms such as brain tissue compliance and skull volume compensation may also contribute. Compensatory compliance mechanisms are limited, and they vary by age and many other factors. Animal models of ICH are widely used to assess these variables and to gauge putative therapeutics. Most often those studies rely upon simple measures of edema, which may not accurately predict ICP data. Thus, we analyzed our past studies characterizing ICP, edema, and tissue compliance responses to striatal ICH in rat, including the collagenase (C-ICH) and whole blood models (WB-ICH). We found that both ICH models raised ICP, with greater effects in the C-ICH model, which may thus better reflect clinical findings of concern. Importantly, measures of edema, such as in the damaged hemisphere, on their own are not predictive of average or peak ICP response within either model, unless assessing across a very wide range of injury severities, or when including non-stroke animals. We caution against using edema data as a surrogate measure of mass effect and ICP following ICH.","PeriodicalId":73108,"journal":{"name":"Frontiers in stroke","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78325876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}