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Functional impairments for outcomes in a randomized trial of unruptured brain AVMs.

ABSTRACT: OBJECTIVE:To investigate the effects of medical vs interventional management on functional outcome in A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA). METHODS:We used the initial results of a nonblinded, randomized, controlled, parallel-group trial involving adults ?18 years of age with an unruptured brain arteriovenous malformation (AVM) to compare the effects of medical management (MM) with or without interventional therapy (IT) on functional impairment, defined by a primary outcome of death or symptomatic stroke causing modified Rankin Scale (mRS) score ?2. ARUBA closed recruitment on April 15, 2013. RESULTS:After a median of 33.3 months of follow-up (interquartile range 16.3-49.8 months), of the 223 enrolled in the trial, those in the MM arm were less likely to experience primary outcomes with an mRS score ?2 than those who underwent IT. The results applied for both those as randomized (MM n = 109 vs IT n = 114) (hazard ratio [HR] 0.25, 95% confidence interval [CI] 0.11-0.57, p = 0.001) and as treated (MM n = 125 vs IT n = 98) (HR 0.10, 95% CI 0.04-0.28, p < 0.001). Functional impairment for the outcomes showed no significant difference by Spetzler-Martin grade for MM but was more frequent with increasing grades for IT (p < 0.001). CONCLUSION:Death or stroke with functional impairment in ARUBA after a median follow-up of 33 months was significantly lower for those in the MM arm both as randomized and as treated compared with those with IT. Functional severity of outcomes was lower in the MM arm, regardless of Spetzler-Martin grades. CLINICALTRIALSGOV IDENTIFIER:NCT00389181. CLASSIFICATION OF EVIDENCE:This study provides Class II evidence that for adults with unruptured brain AVMs, interventional management compared to MM increases the risk of disability and death over ?3 years.

SUBMITTER: Mohr JP

PROVIDER: S-EPMC5631171 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Functional impairments for outcomes in a randomized trial of unruptured brain AVMs.

Mohr J P JP Overbey Jessica R JR von Kummer Ruediger R Stefani Marco A MA Libman Richard R Stapf Christian C Parides Michael K MK Pile-Spellman John J Moquete Ellen E Moy Claudia S CS Vicaut Eric E Moskowitz Alan J AJ Harkness Kirsty K Cordonnier Charlotte C Biondi Alessandra A Houdart Emmanuel E Berkefeld Joachim J Klijn Catharina J M CJM Barreau Xavier X Kim Helen H Hartmann Andreas A

Neurology 20170906 14

<h4>Objective</h4>To investigate the effects of medical vs interventional management on functional outcome in A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA).<h4>Methods</h4>We used the initial results of a nonblinded, randomized, controlled, parallel-group trial involving adults ≥18 years of age with an unruptured brain arteriovenous malformation (AVM) to compare the effects of medical management (MM) with or without interventional therapy (IT) on functional impairmen ...[more]

PMID: 28878048

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Project description:BACKGROUND:The management of unruptured brain arteriovenous malformation (AVM) patients remains controversial. Furthermore, curative attempts to treat ruptured AVM patients have not been questioned so far, and there is a lack of prospective data on clinical results according to treatment modality. Endovascular treatment is often used aiming to improve the safety or efficacy of surgery or radiation therapy, but benefits have never been documented in a trial. A care trial context is needed to evaluate interventions at the same time they are practised. METHODS/TRIAL DESIGN:TOBAS is a pragmatic, prospective, multicenter, randomized, controlled trial and registry which offers a care trial context for brain AVM patients, including surgical resection, radiosurgery or endovascular embolization, alone or combined. The study includes two RCTs and a multimodality prospective registry. The objectives of the proposed study are to assess whether preventive interventions (surgery, embolization, radiation therapy, alone or combined), selected by the local treatment team and performed as locally practiced, randomly allocated and compared with conservative management, in unruptured brain AVM patients eligible for active or conservative management, can improve the proportion of patients having an independent outcome (modified Rankin Scale (mRS)?<?3, as assessed by a standardized questionnaire administered by non-masked care personnel) at 10 years. All patients judged ineligible for randomized allocation are to be entered in a multimodal registry. The objective of a nested trial in patients with ruptured or unruptured AVMs to be treated by surgery or radiation therapy, is to assess whether pre-surgical or pre-radiation embolization, randomly allocated and compared with no embolization, can improve the proportion of patients with complete eradication of the AVM, as locally adjudicated, combined with a good clinical outcome (mRS?<?3). The study will require up to 2000 patients in approximately 30 centers or more, followed for 10 years. TOBAS is registered at clinicaltrials.gov: NCT02098252 as of 25 March 2014.

Project description:microRNAs (miRNAs) are a class of non-coding RNAs playing a myriad of important roles in regulating gene expression. Of note, recent work demonstrated a critical role of miRNAs in the genesis and progression of brain arteriovenous malformations (bAVMs). Accordingly, here we examine miRNA signatures related to bAVMs and associated gene expression. In so doing we expound on the potential prognostic, diagnostic, and therapeutic significance of miRNAs in the clinical management of bAVMs. A PRISMA-based literature review was performed using PubMed/Medline database with the following search terms: "brain arteriovenous malformations", "cerebral arteriovenous malformations", "microRNA", and "miRNA". All preclinical and clinical studies written in English, regardless of date, were selected. For our bioinformatic analyses, miRWalk and miRTarBase machine learning algorithms were employed; the Kyoto Encyclopedia of Genes and Genomes (KEGG) database was quired for associated pathways/functions. four studies were ultimately included in the final analyses. Sequencing data consistently revealed the decreased expression of miR-18a in bAVM-endothelial cells, resulting in increased levels of vascular endodermal growth factor (VEGF), Id-1, matrix metalloproteinase, and growth signals. Our analyses also suggest that the downregulation of miR-137 and miR-195* within vascular smooth muscle cells (VSMCs) may foster the activation of inflammation, aberrant angiogenesis, and phenotypic switching. In the peripheral blood, the overexpression of miR-7-5p, miR-629-5p, miR-199a-5p, miR-200b-3p, and let-7b-5p may contribute to endothelial proliferation and nidus development. The machine learning algorithms employed confirmed associations between miRNA-related target networks, vascular rearrangement, and bAVM progression. miRNAs expression appears to be critical in managing bAVMs' post-transcriptional signals. Targets of microRNAs regulate canonical vascular proliferation and reshaping. Although additional scientific evidence is needed, the identification of bAVM miRNA signatures may facilitate the development of novel prognostic/diagnostic tools and molecular therapies for bAVMs.

Dataset Information

Functional impairments for outcomes in a randomized trial of unruptured brain AVMs.

Publications

Functional impairments for outcomes in a randomized trial of unruptured brain AVMs.

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