The Vascular effects of Infection in Pediatric Stroke (VIPS II) Study

小儿中风感染对血管的影响 (VIPS II) 研究

• 批准号: 10581363
• 负责人: HEATHER J FULLERTON
• 金额: $ 17.34万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10581363
• 关键词: Acute; Address; Adult; Anti-Inflammatory Agents; Antibiotics; Antiviral Agents; Arterial Disorder; Blood Vessels; Blood specimen; Brain Injuries; Chickenpox; Child; Childhood; Childhood stroke; Clinical; Clinical Trials; Common Cold; Custom; Data; Derivation procedure; Detection; Development; Endothelium; Enrollment; Exposure to; Goals; Herpes Labialis; Herpesviridae; Herpesviridae Infections; Heterogeneity; Immune Sera; Immune response; Immunologic Markers; Infection; Inflammation; Inflammation Mediators; Inflammatory; Inflammatory Response; Injury; International; Ischemic Stroke; Knowledge; Lead; Light; Location; Measures; Mediating; Medical; Microbe; Minor; Nucleic acid sequencing; Organism; Pathway interactions; Pharmaceutical Preparations; Pharyngeal structure; Pilot Projects; Play; Predisposition; Prevention; Prevention strategy; Prevention trial; Primary Infection; Process; Recurrence; Risk; Risk Factors; Role; Sampling; Sampling Studies; Serology; Serology test; Serum; Site; Stroke; Stroke prevention; Swab; Techniques; Testing; Thrombophilia; Thrombosis; Time; Update; Upper respiratory tract; Vaccination; Vaccines; Validation; Vascular Diseases; Virus; Work; antimicrobial; case control; cohort; disability; emerging pathogen; follow-up; high risk; inflammatory marker; leukocyte activation; next generation sequencing; pathogen; prevent; stroke risk; stroke therapy

PROJECT SUMMARY/ABSTRACT – updated for supplement Pediatric arterial ischemic stroke afflicts ≈2,000 U.S. children every year, permanently disabling most, yet is poorly understood. The Vascular effects of Infection in Pediatric Stroke (VIPS I) study established an international network of 37 sites that enrolled 355 children with stroke and 354 controls. We discovered: (a) minor clinical infections act as a stroke trigger, while routine childhood vaccinations are protective; (b) almost half of children with stroke have an acute herpesvirus infection (the cause of chicken pox, cold sores, and other common illnesses); and (c) children with stroke have a high risk of recurrent stroke, particularly if they have an arteriopathy. A VIPS pilot study suggests that other common childhood pathogens may also play a role, possibly in combination with herpesviruses. Infection is compelling as a treatable stroke risk factor, with available therapies for both pathogens and downstream inflammatory effects. However, VIPS I findings present a paradox: infection is common, while childhood stroke is uncommon. VIPS II is exploring two potential explanations: (1) the “infection hypothesis”: unusual pathogen strains, or combinations of pathogens, lead to stroke; and (2) the “host response hypothesis”: an unusual inflammatory response to infection leads to stroke. The specific aims are to (1) identify known and novel pathogens in children with stroke, and determine whether different pathogens are seen with arteriopathic versus other stroke types; (2) determine whether children with arteriopathic stroke have a different inflammatory response compared to those with other stroke types; and (3) use data from Aims 1 and 2 to explore different mechanistic pathways from infection, to inflammation, to arteriopathic stroke, and other stroke types. In February 2022, VIPS II completed enrollment of 205 new cases of childhood stroke and 147 controls. For Aim 1, we are using next generation sequencing (NGS) of nucleic acids to detect pathogens in blood samples and throat swabs collected in VIPS II. For Aim 2, we are measuring levels of inflammatory markers in blood samples from cases and controls. We have already studied the samples from VIPS I cases. Using these results, we have refined our list of markers and will now proceed with testing the VIPS II samples. The goal of VIPS II is to gain the knowledge needed to protect children with stroke from additional brain injury. Its results will guide the selection of currently available therapies—such as antimicrobials and anti- inflammatory medications—for a pediatric clinical trial aimed at preventing recurrent stroke.

项目摘要/摘要--为补充而更新 儿童动脉缺血性中风每年困扰≈2,000名美国儿童，其中大多数永久残疾，但仍是 人们对此知之甚少。感染对儿童卒中的血管影响(VIPS I)研究建立了一个 由37个地点组成的国际网络招募了355名中风儿童和354名对照儿童。我们发现： (A)轻微临床感染是中风的诱因，而儿童常规疫苗接种具有保护性；(B) 几乎一半的中风儿童患有急性疱疹病毒感染(水痘、唇疱疹、 以及(C)中风儿童中风复发的风险很高，尤其是在以下情况下 他们有一种动脉病。VIPS的一项初步研究表明，其他常见的儿童病原体也可能 发挥作用，可能与疱疹病毒结合使用。感染作为一种可治疗的中风风险是不可忽视的 因素，以及针对病原体和下游炎症影响的现有治疗方法。然而，VIP I 研究结果呈现了一个悖论：感染很常见，而儿童中风并不常见。VIPS II正在探索 两种可能的解释：(1)“感染假说”：不寻常的病原体菌株，或组合 病原体，导致中风；和(2)“宿主反应假说”：一种不寻常的炎症反应 感染会导致中风。 具体目的是(1)识别中风儿童的已知和新的病原体，并确定 动脉病变与其他卒中类型是否存在不同的病原体；(2)确定 与患有其他疾病的儿童相比，动脉病理性中风儿童的炎症反应不同 中风类型；以及(3)使用来自目标1和目标2的数据来探索感染的不同机制途径， 到炎症，到动脉性中风，和其他中风类型。 2022年2月，VIPS II完成了205例新的儿童中风病例和147例对照的登记。 对于目标1，我们正在使用下一代核酸测序(NGS)来检测血液中的病原体 在VIP中采集样本和咽拭子。对于目标2，我们正在测量炎症标记物的水平 在病例和对照的血液样本中。我们已经研究了贵宾I类病例的样本。vbl.使用 根据这些结果，我们已经改进了我们的标记列表，现在将继续测试VIPS II样本。 VIPS II的目标是获得保护中风儿童免受额外大脑伤害所需的知识 受伤。它的结果将指导目前可用的治疗方法的选择--如抗微生物药物和抗肿瘤药物。 炎症性药物--一项旨在预防中风复发的儿科临床试验。

项目成果

Parvovirus B19 Infection in Children With Arterial Ischemic Stroke.

• DOI: 10.1161/strokeaha.117.018272
• 发表时间: 2017-10
• 期刊: Stroke
• 影响因子: 8.3
• 作者: Fullerton HJ;Luna JM;Wintermark M;Hills NK;Tokarz R;Li Y;Glaser C;DeVeber GA;Lipkin WI;Elkind MSV;VIPS Investigators*
• 通讯作者: VIPS Investigators*

Pediatric Moyamoya Revascularization Perioperative Care: A Modified Delphi Study.

• DOI: 10.1007/s12028-023-01788-0
• 发表时间: 2023-07
• 期刊: Neurocritical care
• 影响因子: 3.5
• 作者: Lisa R. Sun;L. Jordan;E. Smith;P. Aldana;M. Kirschen;K. Guilliams;N. Gupta;G. Steinberg;Christine H. Fox;D. Harrar;Sarah Lee;Melissa G. Chung;Peter Dirks;N. Dlamini;C. Maher;L. Lehman;Sue J. Hong;J. Strahle;Jose A. Pineda;L. Beslow;L. Rasmussen;J. Mailo;J. Piatt;S. Lang;P. Adelson;M. Dewan;A. Mineyko;S. McClugage;S. Vadivelu;M. Dowling;David S. Hersh