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Abstract

Background Objectives

It is unclear whether IV thrombolysis (IVT) outperforms early dual antiplatelet therapy (DAPT) in the acute setting of mild ischemic stroke. The aim of this study was to compare the early safety and efficacy of IVT with that of DAPT.

Methods

Data of mild noncardioembolic stroke patients with admission NIH Stroke Scale (NIHSS) score ≤3 who received IVT or early DAPT in the period 2018–2021 were extracted from a nationwide, prospective stroke unit registry. Study endpoints included symptomatic intracerebral hemorrhage (sICH), early neurologic deterioration ≥4 NIHSS points (END), and 3-month functional outcome by modified Rankin scale (mRS).

Results

A total of 1,195 mild stroke patients treated with IVT and 2,625 patients treated with DAPT were included. IVT patients were younger (68.1 vs 70.8 years), had less hypertension (72.8% vs 83.5%), diabetes (19% vs 28.8%), and a history of myocardial infarction (7.6% vs 9.2%), and slightly higher admission NIHSS scores (median 2 vs median 1) when compared with DAPT patients. After propensity score matching and multivariable adjustment, IVT was associated with sICH (4 [1.2%] vs 0) and END (adjusted odds ratio [aOR] 2.8, 95% CI 1.1–7.5), and there was no difference in mRS 0–1 at 3 months (aOR 1.3, 95% CI 0.7–2.6).

Discussion

This analysis from a prospective nationwide stroke unit network indicates that IVT is not superior to DAPT in the setting of mild noncardioembolic stroke and may eventually be associated with harm. Further research focusing on acute therapy of mild stroke is highly warranted.

Classification of Evidence

This study provides Class III evidence that IVT is not superior to DAPT in patients with acute mild (NIHSS score ≤3) noncardioembolic stroke. The study lacks the statistical precision to exclude clinically important superiority of either therapy.

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Letters to the Editor
20 September 2023
Author Response: IV Thrombolysis vs Early Dual Antiplatelet Therapy in Patients With Mild Noncardioembolic Ischemic Stroke.
Marek Sykora, Neurologist | St. Johns Hospital Vienna, Austria
Julia Ferrari, Neurologist | St. Johns Hospital Vienna, Austria

We thank Pensato et al. for their valuable comments on our article.[1] Agreed, the definition of END and the use of mRS might not be optimally precise for this highly selected stroke population. However, it is not solely the registry structure that didn't allow us to use more granular endpoints, we rather purposely adhered to standard clinical endpoints to secure comparability. DAPT preference in older patients with higher comorbidities and lower NIHSS scores additionally mirrors the presence of a clear selection bias, unavoidable with this type of studies.

1. Sykora M, Krebs S, Miksova D, et al. for Austria Stroke Unit Collaborators. IV Thrombolysis vs Early Dual Antiplatelet Therapy in Patients With Mild Noncardioembolic Ischemic Stroke. Neurology Aug 2023, 101 (9) e933-e939.

Author disclosures are available upon request([email protected]).

19 August 2023
Reader Response: IV Thrombolysis vs Early Dual Antiplatelet Therapy in Patients With Mild Noncardioembolic Ischemic Stroke
Umberto Pensato, Neurologist | IRCCS Humanitas Research Hospital, via Manzoni 56, 20089 Rozzano, Milan, Italy
Stefano Forlivesi, Neurologist | IRCCS Istituto delle Scienze Neurologiche di Bologna, Department of Neurology and Stroke Center, Maggiore Hospital, Bologna, Ita
Andrea Zini, Neurologist | IRCCS Istituto delle Scienze Neurologiche di Bologna, Department of Neurology and Stroke Center, Maggiore Hospital, Bologna, Ita

Sykora et al. [1] showed that intravenous thrombolysis (IVT) was associated with an increased risk of early neurological deterioration (END) and symptomatic intracranial hemorrhage (sICH) compared to dual antiplatelet therapy (DAPT) in a prospective cohort of non-cardioembolic minor ischemic stroke. However, no difference in the 90-day modified Rankin Scale (mRS) was observed. The authors also confirmed these findings in the subgroup analysis exploring small and large vessel disease etiologies. Notably, DAPT was preferred in older patients with higher comorbidities and lower NIHSS scores, reflecting its cultural heritage as a second-class choice in stroke hyperacute management. Conversely, mounting recent evidence supports the ultra-early role of DAPT in minor stroke management by preventing lacunar stroke progression and athero-embolism through micro- and macro-atheroma plaque stabilization, respectively. [2-4]


The authors’ definition of END as ≥4 NIHSS points within 48 hours arguably did not capture the full spectrum of lacunar progression that may present with milder neurological deterioration up to 5 days after symptoms onset.[5] Additionally, a functional-independence scale, such as the mRS, might not be the most appropriate tool to measure the functional outcomes of non-disabling/minimal disabling strokes. Nonetheless, this study represents a critical step forward toward an etiology-driven, complementarily to the severity-driven, stroke hyperacute treatment.


1. Sykora M, Krebs S, Miksova D, et al. IV Thrombolysis vs Early Dual Antiplatelet Therapy in Patients With Mild Noncardioembolic Ischemic Stroke. Neurology 2023.
2. Vynckier J, Maamari B, Grunder L, et al. Early Neurologic Deterioration in Lacunar Stroke: Clinical and Imaging Predictors and Association With Long-term Outcome. Neurology 2021.
3. Chen HS, Cui Y, Zhou ZH, et al. Dual Antiplatelet Therapy vs Alteplase for Patients With Minor Nondisabling Acute Ischemic Stroke: The ARAMIS Randomized Clinical Trial. JAMA 2023;329:2135-44.
4. Bhatia K, Jain V, Aggarwal D, et al. Dual Antiplatelet Therapy Versus Aspirin in Patients With Stroke or Transient Ischemic Attack: Meta-Analysis of Randomized Controlled Trials. Stroke 2021;52:e217-e23.
5. Berberich A, Schneider C, Herweh C, et al. Risk factors associated with progressive lacunar strokes and benefit from dual antiplatelet therapy. Eur J Neurol 2020;27:817-24.

Author disclosures are available upon request([email protected]).

 

 

Information & Authors

Information

Published In

Neurology®
Volume 101Number 9August 29, 2023
Pages: e933-e939
PubMed: 37407270

Publication History

Received: November 15, 2022
Accepted: May 4, 2023
Published online: July 5, 2023
Published in print: August 29, 2023

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Disclosure

The authors report no relevant disclosures. Go to Neurology.org/N for full disclosures.

Study Funding

Research funding was provided by the Austrian Neurological Society and the Austrian Stroke Society.

Authors

Affiliations & Disclosures

From the Department Neurology (M.S., S.K., W.L., J.F.), St. Johns Hospital Vienna; Sigmund Freud University Vienna (M.S., I.B., W.L.); Austrian National Public Health Institute (D.M.), Vienna; Medical University of Graz (T.G., S.F.-H.); Medical University of Vienna (M.M., S.G.); and Medical University of Innsbruck (M.K.), Austria.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
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1.
NONE
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Stefan Krebs, MD
From the Department Neurology (M.S., S.K., W.L., J.F.), St. Johns Hospital Vienna; Sigmund Freud University Vienna (M.S., I.B., W.L.); Austrian National Public Health Institute (D.M.), Vienna; Medical University of Graz (T.G., S.F.-H.); Medical University of Vienna (M.M., S.G.); and Medical University of Innsbruck (M.K.), Austria.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
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1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
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1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
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1.
NONE
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1.
NONE
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1.
NONE
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1.
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From the Department Neurology (M.S., S.K., W.L., J.F.), St. Johns Hospital Vienna; Sigmund Freud University Vienna (M.S., I.B., W.L.); Austrian National Public Health Institute (D.M.), Vienna; Medical University of Graz (T.G., S.F.-H.); Medical University of Vienna (M.M., S.G.); and Medical University of Innsbruck (M.K.), Austria.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
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1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
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1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
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1.
NONE
Research Support, Government Entities:
1.
NONE
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1.
NONE
Research Support, Foundations and Societies:
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Ines Badic
From the Department Neurology (M.S., S.K., W.L., J.F.), St. Johns Hospital Vienna; Sigmund Freud University Vienna (M.S., I.B., W.L.); Austrian National Public Health Institute (D.M.), Vienna; Medical University of Graz (T.G., S.F.-H.); Medical University of Vienna (M.M., S.G.); and Medical University of Innsbruck (M.K.), Austria.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
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1.
NONE
Research Support, Government Entities:
1.
NONE
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1.
NONE
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NONE
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From the Department Neurology (M.S., S.K., W.L., J.F.), St. Johns Hospital Vienna; Sigmund Freud University Vienna (M.S., I.B., W.L.); Austrian National Public Health Institute (D.M.), Vienna; Medical University of Graz (T.G., S.F.-H.); Medical University of Vienna (M.M., S.G.); and Medical University of Innsbruck (M.K.), Austria.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
<br>(1) Boehringer Ingelheim, travel and speaker honoraria,<br><br><br><br><br><br><br><br>(2) Bayer Austria, travel and speaker honoraria<br><br><br><br><br><br><br><br>(3) BMS Pfizer, speaker honoraria<br><br><br><br><br><br><br><br>(4) Alexion, speaker honoraria<br><br><br><br><br><br><br><br>(5) Novartis, speaker honoraria<br><br><br><br><br><br><br><br>(6) Amgen, speaker honoraria<br>
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NONE
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1.
NONE
Consultancies:
1.
NONE
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NONE
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1.
NONE
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NONE
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NONE
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1.
NONE
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NONE
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1.
<br>Austrian Neurological Society,<br><br><br><br><br><br><br><br>Austrian Science Fund<br> Signature: /Thomas Gattringer/ Date: April 24, 2023<br><br>
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Simon Fandler-Höfler, MD https://orcid.org/0000-0001-9043-0378
From the Department Neurology (M.S., S.K., W.L., J.F.), St. Johns Hospital Vienna; Sigmund Freud University Vienna (M.S., I.B., W.L.); Austrian National Public Health Institute (D.M.), Vienna; Medical University of Graz (T.G., S.F.-H.); Medical University of Vienna (M.M., S.G.); and Medical University of Innsbruck (M.K.), Austria.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
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1.
NONE
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Martha Marko, MD
From the Department Neurology (M.S., S.K., W.L., J.F.), St. Johns Hospital Vienna; Sigmund Freud University Vienna (M.S., I.B., W.L.); Austrian National Public Health Institute (D.M.), Vienna; Medical University of Graz (T.G., S.F.-H.); Medical University of Vienna (M.M., S.G.); and Medical University of Innsbruck (M.K.), Austria.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
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1.
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Stefan Greisenegger, MD
From the Department Neurology (M.S., S.K., W.L., J.F.), St. Johns Hospital Vienna; Sigmund Freud University Vienna (M.S., I.B., W.L.); Austrian National Public Health Institute (D.M.), Vienna; Medical University of Graz (T.G., S.F.-H.); Medical University of Vienna (M.M., S.G.); and Medical University of Innsbruck (M.K.), Austria.
Disclosure
Scientific Advisory Boards:
1.
<br>Novartis (Advisory boards)<br>
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
<br>1) Novartis (Speaker Honoraria)<br>2) Daiichi Sankyo (Speaker Honoraria)<br>3) BMS (Speaker Honoraria)<br>
Editorial Boards:
1.
NONE
Patents:
1.
NONE
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1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
<br>Medtronic<br> Signature: Stefan Greisenegger/ Date: 25th April 2023<br><br>
Research Support, Government Entities:
1.
NONE
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1.
NONE
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1.
NONE
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1.
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NONE
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Michael Knoflach, MD
From the Department Neurology (M.S., S.K., W.L., J.F.), St. Johns Hospital Vienna; Sigmund Freud University Vienna (M.S., I.B., W.L.); Austrian National Public Health Institute (D.M.), Vienna; Medical University of Graz (T.G., S.F.-H.); Medical University of Vienna (M.M., S.G.); and Medical University of Innsbruck (M.K.), Austria.
Disclosure
Scientific Advisory Boards:
1.
<br>(1) Tyrolian government (non-profit, no reimbursement): <br>Tyrolian Stroke Pathway<br>(2) MyReha (commercial, no reimbursement): Scientific advisory <br>board<br>(3) Novartis (commercaial, compensation): Advisory board<br>
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
<br>(1) Novartis: Speakes's honoraria<br>
Editorial Boards:
1.
NONE
Patents:
1.
NONE
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1.
NONE
Employment, Commercial Entity:
1.
<br>(1) VASCage, Research Center for Vascular Ageing and Stroke, <br>Innsbruck, Austria - medical and scienctific advisor, 2 years<br>
Consultancies:
1.
NONE
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1.
NONE
Other Activities:
1.
NONE
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1.
NONE
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1.
NONE
Research Support, Government Entities:
1.
<br>(1) Austrian Research Promotion Agency FFG, #843536, <br>Project leader, 2014-2018<br>(2) VASCage (Centre for Promoting Vascular Health in the <br>Ageing Community, project number 868624) of the Austrian <br>Research Promotion Agency FFG (COMET program), PI, since <br>2019<br> Signature: /Michael Knoflach/ Date: 25.04.2023<br><br>
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NONE
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NONE
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Wilfried Lang, MD
From the Department Neurology (M.S., S.K., W.L., J.F.), St. Johns Hospital Vienna; Sigmund Freud University Vienna (M.S., I.B., W.L.); Austrian National Public Health Institute (D.M.), Vienna; Medical University of Graz (T.G., S.F.-H.); Medical University of Vienna (M.M., S.G.); and Medical University of Innsbruck (M.K.), Austria.
Disclosure
Scientific Advisory Boards:
1.
<br>(1) Astra Zeneca, (2) Novartis<br> Signature: /Wilfried Lang/ Date: April 27, 2023<br><br>
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
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NONE
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Julia Ferrari, MD
From the Department Neurology (M.S., S.K., W.L., J.F.), St. Johns Hospital Vienna; Sigmund Freud University Vienna (M.S., I.B., W.L.); Austrian National Public Health Institute (D.M.), Vienna; Medical University of Graz (T.G., S.F.-H.); Medical University of Vienna (M.M., S.G.); and Medical University of Innsbruck (M.K.), Austria.
Disclosure
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Clinical Procedures or Imaging Studies:
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NONE
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NONE
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for Austria Stroke Unit Collaborators
From the Department Neurology (M.S., S.K., W.L., J.F.), St. Johns Hospital Vienna; Sigmund Freud University Vienna (M.S., I.B., W.L.); Austrian National Public Health Institute (D.M.), Vienna; Medical University of Graz (T.G., S.F.-H.); Medical University of Vienna (M.M., S.G.); and Medical University of Innsbruck (M.K.), Austria.

Notes

Correspondence Dr. Sykora [email protected]
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Coinvestigators are listed at links.lww.com/WNL/C959.
Submitted and externally peer reviewed. The handling editor was Editor-in-Chief José Merino, MD, MPhil, FAAN.

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