Evidence map›Paper›PMID 33007039›Full record

ArticlePloS one2020

Brief Report: Hydroxychloroquine does not induce hemolytic anemia or organ damage in a "humanized" G6PD A- mouse model.

Benjamin E Zuchelkowski, Ling Wang, Sebastien Gingras, Qinzi Xu, Minying Yang, Darrell Triulzi, Grier P Page, Victor R Gordeuk, Daniel B Kim-Shapiro, Janet S Lee and 1 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.3field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Increased Neutrophil HResearch square · 2024
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 4 institutions in 1 country.

Benjamin E ZuchelkowskiDepartment of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America.ORCID 0000-0002-0747-292X
Ling WangDepartment of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America.
Sebastien GingrasDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America.
Qinzi XuPittsburgh Heart, Lung, Blood and Vascular Medicine Institute, Pittsburgh, PA, United States of America.
Minying YangPittsburgh Heart, Lung, Blood and Vascular Medicine Institute, Pittsburgh, PA, United States of America.
Darrell TriulziDepartment of Pathology, Division of Transfusion Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America.
Grier P PageRTI International, Research Triangle Park, Durham, NC, United States of America.
Victor R GordeukDivision of Hematology and Oncology, University of Illinois at Chicago School of Medicine, Chicago, IL, United States of America.
Daniel B Kim-ShapiroDepartment of Physics, Wake Forest University, Winston-Salem, NC, United States of America.
Janet S LeeDepartment of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America.
Mark T GladwinDepartment of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America.
University of Pittsburgh · USRTI International · USUniversity of Illinois Chicago · USWake Forest University · US

Funding

Storage Lesion in Banked Blood Due to Disruption of Nitric Oxide HomeostasisR01HL098032 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Mark T Gladwin · 2009 to 2026
$12.5M
Mechanisms of host protection against pathogen-secreted proteases in acute lung injuryR01HL136143 · NHLBI · WASHINGTON UNIVERSITY · PI LEE, JANET SOJUNG · 2017 to 2024
$4.4M
The role of ACOD1 in immunomodulation in intrapulmonary Klebsiella pneumoniae infectionR01HL142084 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHEN, KONG · 2018 to 2021
$2.4M
NHLBI NIH HHS R01 HL098032NHLBI NIH HHS R01 HL136143NHLBI NIH HHS R01 HL142084NIH HHS 5R01HL098032
6 · The paper itself

Abstract

backgroundHydroxychloroquine (HCQ) is widely used in the treatment of malaria, rheumatologic disease such as lupus, and most recently, COVID-19. These uses raise concerns about its safe use in the setting of glucose-6-phosphate dehydrogenase (G6PD) deficiency, especially as 11% of African American men carry the G6PD A- variant. However, limited data exist regarding the safety of HCQ in this population. STUDY DESIGN AND

methodsRecently, we created a novel "humanized" mouse model containing the G6PD deficiency A- variant (Val68Met) using CRISPR technology. We tested the effects of high-dose HCQ administration over 5 days on hemolysis in our novel G6PD A- mice. In addition to standard hematologic parameters including plasma hemoglobin, erythrocyte methemoglobin, and reticulocytes, hepatic and renal function were assessed after HCQ.

resultsResidual erythrocyte G6PD activity in G6PD A- mice was ~6% compared to wild-type (WT) littermates. Importantly, we found no evidence of clinically significant intravascular hemolysis, methemoglobinemia, or organ damage in response to high-dose HCQ.

conclusionsThough the effects of high doses over prolonged periods was not assessed, this study provides early, novel safety data of the use of HCQ in the setting of G6PD deficiency secondary to G6PD A-. In addition to novel safety data for HCQ, to our knowledge, we are the first to present the creation of a "humanized" murine model of G6PD deficiency.

Indexed as

Disease Models, AnimalAnimalsBlack or African AmericanCoronavirus InfectionsCOVID-19COVID-19 Drug TreatmentGlucosephosphate Dehydrogenase DeficiencyHumansHydroxychloroquineMaleMicePandemicsPneumonia, ViralHydroxychloroquine

Identifiers

PMID33007039
PMCPMC7531777
OpenAlexW3090863674

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.