Cytogenetic evolution predicts a poor prognosis in acute myeloid leukemia patients who relapse after allogeneic hematopoietic stem cell transplantation
Acute myeloid leukemia (AML) patients relapsing after allogeneic hematopoietic stem cell transplantation (allo-HSCT) have a poor prognosis. Cytogenetic evolution (CGE) has been investigated and found to have an important impact on the prognosis of relapsed leukemia, but its impact on AML patients re...
Gespeichert in:
Veröffentlicht in: | Annals of hematology 2023, Vol.102 (1), p.89-97 |
---|---|
Hauptverfasser: | , , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 97 |
---|---|
container_issue | 1 |
container_start_page | 89 |
container_title | Annals of hematology |
container_volume | 102 |
creator | Li, Ruiqi Wang, Ziwei Zhang, Yuesheng Guo, Mengqiao Ni, Xiong Chen, Jie Chen, Li Gao, Lei Gong, Shenglan Tang, Gusheng Yang, Jianmin Wang, Jianmin |
description | Acute myeloid leukemia (AML) patients relapsing after allogeneic hematopoietic stem cell transplantation (allo-HSCT) have a poor prognosis. Cytogenetic evolution (CGE) has been investigated and found to have an important impact on the prognosis of relapsed leukemia, but its impact on AML patients relapsing after transplantation remains controversial. In this study, we analyzed 34 AML patients relapsing after allo-HSCT, among whom 14 developed additional abnormalities in chromosomal karyotype after leukemia recurrence (CGE group) and 20 patients did not (non-CGE group). We found that the cytogenetic characteristics were much more complex at relapse in the CGE group, and the acquisition of aberrations at relapse most commonly involved chromosome 11. The 6-month post-relapse overall survival (PROS) of the CGE group was significantly lower than that of the non-CGE group (21.4% versus 50.0%,
P
= 0.004). The CGE group also showed a trend of worse 2-year OS (7.1% versus 28.6%,
P
= 0.096). In the multivariate analyses, the occurrence of chronic graft-versus-host disease (HR 0.27 [95% CI, 0.11–0.68],
P
= 0.006) and a reduced-intensity FBA conditioning regimen (HR 0.42 [95% CI, 0.18–0.98],
P
= 0.045) were found to be two independent factors for a better PROS, whereas CGE (HR 3.16 [95% CI, 1.42–7.05],
P
= 0.005) was associated with a worse PROS. In conclusion, CGE was associated with a poor prognosis in AML patients who relapsed after allo-HSCT, and the importance of monitoring karyotype changes after transplantation should be noted. |
doi_str_mv | 10.1007/s00277-022-05061-w |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2756669809</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2756669809</sourcerecordid><originalsourceid>FETCH-LOGICAL-c375t-5f48771112330cbbb43a01b73c2b6d5c85fd1935d396a0f97f2c3b3d436085873</originalsourceid><addsrcrecordid>eNp9kc2O0zAUhS0EYkrhBVggS2zYBPzvZIkqfkYaiQ2sI8e56Xhw7GA7VH0SXhe3HRiJBd5YV_e79xz7IPSSkreUEP0uE8K0bghjDZFE0ebwCG2o4KeyFY_RhnS8a2Q9V-hZzneEUNYK9hRdcSUFo0Rs0K_dscQ9BCjOYvgZ_VpcDHhJMDpbMjZ4iTHVOu5DzC5jF7CxawE8H8FHN2IP63eYXQVNcRDqzOE24gTeLBmwmQokbLw_i1SNW5hNiUt0Z8VcYMYWvMclmZAXb0IxJwfP0ZPJ-Awv7u8t-vbxw9fd5-bmy6fr3fubxnItSyMn0WpNKWWcEzsMg-CG0EFzywY1StvKaaQdlyPvlCFTpydm-cBHwRVpZav5Fr257K0v_LFCLv3s8smQCRDX3DMtlVJdW79yi17_g97FNYXqrlKqZiFa1VaKXSibYs4Jpn5Jbjbp2FPSn2LrL7H1Nbb-HFt_qEOv7levwwzj35E_OVWAX4BcW2EP6UH7P2t_A1N3pn0</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2760024868</pqid></control><display><type>article</type><title>Cytogenetic evolution predicts a poor prognosis in acute myeloid leukemia patients who relapse after allogeneic hematopoietic stem cell transplantation</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Li, Ruiqi ; Wang, Ziwei ; Zhang, Yuesheng ; Guo, Mengqiao ; Ni, Xiong ; Chen, Jie ; Chen, Li ; Gao, Lei ; Gong, Shenglan ; Tang, Gusheng ; Yang, Jianmin ; Wang, Jianmin</creator><creatorcontrib>Li, Ruiqi ; Wang, Ziwei ; Zhang, Yuesheng ; Guo, Mengqiao ; Ni, Xiong ; Chen, Jie ; Chen, Li ; Gao, Lei ; Gong, Shenglan ; Tang, Gusheng ; Yang, Jianmin ; Wang, Jianmin</creatorcontrib><description>Acute myeloid leukemia (AML) patients relapsing after allogeneic hematopoietic stem cell transplantation (allo-HSCT) have a poor prognosis. Cytogenetic evolution (CGE) has been investigated and found to have an important impact on the prognosis of relapsed leukemia, but its impact on AML patients relapsing after transplantation remains controversial. In this study, we analyzed 34 AML patients relapsing after allo-HSCT, among whom 14 developed additional abnormalities in chromosomal karyotype after leukemia recurrence (CGE group) and 20 patients did not (non-CGE group). We found that the cytogenetic characteristics were much more complex at relapse in the CGE group, and the acquisition of aberrations at relapse most commonly involved chromosome 11. The 6-month post-relapse overall survival (PROS) of the CGE group was significantly lower than that of the non-CGE group (21.4% versus 50.0%,
P
= 0.004). The CGE group also showed a trend of worse 2-year OS (7.1% versus 28.6%,
P
= 0.096). In the multivariate analyses, the occurrence of chronic graft-versus-host disease (HR 0.27 [95% CI, 0.11–0.68],
P
= 0.006) and a reduced-intensity FBA conditioning regimen (HR 0.42 [95% CI, 0.18–0.98],
P
= 0.045) were found to be two independent factors for a better PROS, whereas CGE (HR 3.16 [95% CI, 1.42–7.05],
P
= 0.005) was associated with a worse PROS. In conclusion, CGE was associated with a poor prognosis in AML patients who relapsed after allo-HSCT, and the importance of monitoring karyotype changes after transplantation should be noted.</description><identifier>ISSN: 0939-5555</identifier><identifier>EISSN: 1432-0584</identifier><identifier>DOI: 10.1007/s00277-022-05061-w</identifier><identifier>PMID: 36542104</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Chronic Disease ; Hematology ; Hematopoietic Stem Cell Transplantation ; Humans ; Karyotyping ; Leukemia ; Leukemia, Myeloid, Acute - genetics ; Leukemia, Myeloid, Acute - therapy ; Medical prognosis ; Medicine ; Medicine & Public Health ; Oncology ; Original Article ; Prognosis ; Recurrence ; Retrospective Studies ; Stem cell transplantation ; Transplantation, Homologous</subject><ispartof>Annals of hematology, 2023, Vol.102 (1), p.89-97</ispartof><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-5f48771112330cbbb43a01b73c2b6d5c85fd1935d396a0f97f2c3b3d436085873</citedby><cites>FETCH-LOGICAL-c375t-5f48771112330cbbb43a01b73c2b6d5c85fd1935d396a0f97f2c3b3d436085873</cites><orcidid>0000-0003-1071-5336</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00277-022-05061-w$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00277-022-05061-w$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27903,27904,41467,42536,51297</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36542104$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Ruiqi</creatorcontrib><creatorcontrib>Wang, Ziwei</creatorcontrib><creatorcontrib>Zhang, Yuesheng</creatorcontrib><creatorcontrib>Guo, Mengqiao</creatorcontrib><creatorcontrib>Ni, Xiong</creatorcontrib><creatorcontrib>Chen, Jie</creatorcontrib><creatorcontrib>Chen, Li</creatorcontrib><creatorcontrib>Gao, Lei</creatorcontrib><creatorcontrib>Gong, Shenglan</creatorcontrib><creatorcontrib>Tang, Gusheng</creatorcontrib><creatorcontrib>Yang, Jianmin</creatorcontrib><creatorcontrib>Wang, Jianmin</creatorcontrib><title>Cytogenetic evolution predicts a poor prognosis in acute myeloid leukemia patients who relapse after allogeneic hematopoietic stem cell transplantation</title><title>Annals of hematology</title><addtitle>Ann Hematol</addtitle><addtitle>Ann Hematol</addtitle><description>Acute myeloid leukemia (AML) patients relapsing after allogeneic hematopoietic stem cell transplantation (allo-HSCT) have a poor prognosis. Cytogenetic evolution (CGE) has been investigated and found to have an important impact on the prognosis of relapsed leukemia, but its impact on AML patients relapsing after transplantation remains controversial. In this study, we analyzed 34 AML patients relapsing after allo-HSCT, among whom 14 developed additional abnormalities in chromosomal karyotype after leukemia recurrence (CGE group) and 20 patients did not (non-CGE group). We found that the cytogenetic characteristics were much more complex at relapse in the CGE group, and the acquisition of aberrations at relapse most commonly involved chromosome 11. The 6-month post-relapse overall survival (PROS) of the CGE group was significantly lower than that of the non-CGE group (21.4% versus 50.0%,
P
= 0.004). The CGE group also showed a trend of worse 2-year OS (7.1% versus 28.6%,
P
= 0.096). In the multivariate analyses, the occurrence of chronic graft-versus-host disease (HR 0.27 [95% CI, 0.11–0.68],
P
= 0.006) and a reduced-intensity FBA conditioning regimen (HR 0.42 [95% CI, 0.18–0.98],
P
= 0.045) were found to be two independent factors for a better PROS, whereas CGE (HR 3.16 [95% CI, 1.42–7.05],
P
= 0.005) was associated with a worse PROS. In conclusion, CGE was associated with a poor prognosis in AML patients who relapsed after allo-HSCT, and the importance of monitoring karyotype changes after transplantation should be noted.</description><subject>Chronic Disease</subject><subject>Hematology</subject><subject>Hematopoietic Stem Cell Transplantation</subject><subject>Humans</subject><subject>Karyotyping</subject><subject>Leukemia</subject><subject>Leukemia, Myeloid, Acute - genetics</subject><subject>Leukemia, Myeloid, Acute - therapy</subject><subject>Medical prognosis</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Oncology</subject><subject>Original Article</subject><subject>Prognosis</subject><subject>Recurrence</subject><subject>Retrospective Studies</subject><subject>Stem cell transplantation</subject><subject>Transplantation, Homologous</subject><issn>0939-5555</issn><issn>1432-0584</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kc2O0zAUhS0EYkrhBVggS2zYBPzvZIkqfkYaiQ2sI8e56Xhw7GA7VH0SXhe3HRiJBd5YV_e79xz7IPSSkreUEP0uE8K0bghjDZFE0ebwCG2o4KeyFY_RhnS8a2Q9V-hZzneEUNYK9hRdcSUFo0Rs0K_dscQ9BCjOYvgZ_VpcDHhJMDpbMjZ4iTHVOu5DzC5jF7CxawE8H8FHN2IP63eYXQVNcRDqzOE24gTeLBmwmQokbLw_i1SNW5hNiUt0Z8VcYMYWvMclmZAXb0IxJwfP0ZPJ-Awv7u8t-vbxw9fd5-bmy6fr3fubxnItSyMn0WpNKWWcEzsMg-CG0EFzywY1StvKaaQdlyPvlCFTpydm-cBHwRVpZav5Fr257K0v_LFCLv3s8smQCRDX3DMtlVJdW79yi17_g97FNYXqrlKqZiFa1VaKXSibYs4Jpn5Jbjbp2FPSn2LrL7H1Nbb-HFt_qEOv7levwwzj35E_OVWAX4BcW2EP6UH7P2t_A1N3pn0</recordid><startdate>2023</startdate><enddate>2023</enddate><creator>Li, Ruiqi</creator><creator>Wang, Ziwei</creator><creator>Zhang, Yuesheng</creator><creator>Guo, Mengqiao</creator><creator>Ni, Xiong</creator><creator>Chen, Jie</creator><creator>Chen, Li</creator><creator>Gao, Lei</creator><creator>Gong, Shenglan</creator><creator>Tang, Gusheng</creator><creator>Yang, Jianmin</creator><creator>Wang, Jianmin</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-1071-5336</orcidid></search><sort><creationdate>2023</creationdate><title>Cytogenetic evolution predicts a poor prognosis in acute myeloid leukemia patients who relapse after allogeneic hematopoietic stem cell transplantation</title><author>Li, Ruiqi ; Wang, Ziwei ; Zhang, Yuesheng ; Guo, Mengqiao ; Ni, Xiong ; Chen, Jie ; Chen, Li ; Gao, Lei ; Gong, Shenglan ; Tang, Gusheng ; Yang, Jianmin ; Wang, Jianmin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-5f48771112330cbbb43a01b73c2b6d5c85fd1935d396a0f97f2c3b3d436085873</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Chronic Disease</topic><topic>Hematology</topic><topic>Hematopoietic Stem Cell Transplantation</topic><topic>Humans</topic><topic>Karyotyping</topic><topic>Leukemia</topic><topic>Leukemia, Myeloid, Acute - genetics</topic><topic>Leukemia, Myeloid, Acute - therapy</topic><topic>Medical prognosis</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Oncology</topic><topic>Original Article</topic><topic>Prognosis</topic><topic>Recurrence</topic><topic>Retrospective Studies</topic><topic>Stem cell transplantation</topic><topic>Transplantation, Homologous</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Ruiqi</creatorcontrib><creatorcontrib>Wang, Ziwei</creatorcontrib><creatorcontrib>Zhang, Yuesheng</creatorcontrib><creatorcontrib>Guo, Mengqiao</creatorcontrib><creatorcontrib>Ni, Xiong</creatorcontrib><creatorcontrib>Chen, Jie</creatorcontrib><creatorcontrib>Chen, Li</creatorcontrib><creatorcontrib>Gao, Lei</creatorcontrib><creatorcontrib>Gong, Shenglan</creatorcontrib><creatorcontrib>Tang, Gusheng</creatorcontrib><creatorcontrib>Yang, Jianmin</creatorcontrib><creatorcontrib>Wang, Jianmin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Annals of hematology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Ruiqi</au><au>Wang, Ziwei</au><au>Zhang, Yuesheng</au><au>Guo, Mengqiao</au><au>Ni, Xiong</au><au>Chen, Jie</au><au>Chen, Li</au><au>Gao, Lei</au><au>Gong, Shenglan</au><au>Tang, Gusheng</au><au>Yang, Jianmin</au><au>Wang, Jianmin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cytogenetic evolution predicts a poor prognosis in acute myeloid leukemia patients who relapse after allogeneic hematopoietic stem cell transplantation</atitle><jtitle>Annals of hematology</jtitle><stitle>Ann Hematol</stitle><addtitle>Ann Hematol</addtitle><date>2023</date><risdate>2023</risdate><volume>102</volume><issue>1</issue><spage>89</spage><epage>97</epage><pages>89-97</pages><issn>0939-5555</issn><eissn>1432-0584</eissn><abstract>Acute myeloid leukemia (AML) patients relapsing after allogeneic hematopoietic stem cell transplantation (allo-HSCT) have a poor prognosis. Cytogenetic evolution (CGE) has been investigated and found to have an important impact on the prognosis of relapsed leukemia, but its impact on AML patients relapsing after transplantation remains controversial. In this study, we analyzed 34 AML patients relapsing after allo-HSCT, among whom 14 developed additional abnormalities in chromosomal karyotype after leukemia recurrence (CGE group) and 20 patients did not (non-CGE group). We found that the cytogenetic characteristics were much more complex at relapse in the CGE group, and the acquisition of aberrations at relapse most commonly involved chromosome 11. The 6-month post-relapse overall survival (PROS) of the CGE group was significantly lower than that of the non-CGE group (21.4% versus 50.0%,
P
= 0.004). The CGE group also showed a trend of worse 2-year OS (7.1% versus 28.6%,
P
= 0.096). In the multivariate analyses, the occurrence of chronic graft-versus-host disease (HR 0.27 [95% CI, 0.11–0.68],
P
= 0.006) and a reduced-intensity FBA conditioning regimen (HR 0.42 [95% CI, 0.18–0.98],
P
= 0.045) were found to be two independent factors for a better PROS, whereas CGE (HR 3.16 [95% CI, 1.42–7.05],
P
= 0.005) was associated with a worse PROS. In conclusion, CGE was associated with a poor prognosis in AML patients who relapsed after allo-HSCT, and the importance of monitoring karyotype changes after transplantation should be noted.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>36542104</pmid><doi>10.1007/s00277-022-05061-w</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0003-1071-5336</orcidid></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0939-5555 |
ispartof | Annals of hematology, 2023, Vol.102 (1), p.89-97 |
issn | 0939-5555 1432-0584 |
language | eng |
recordid | cdi_proquest_miscellaneous_2756669809 |
source | MEDLINE; SpringerLink Journals - AutoHoldings |
subjects | Chronic Disease Hematology Hematopoietic Stem Cell Transplantation Humans Karyotyping Leukemia Leukemia, Myeloid, Acute - genetics Leukemia, Myeloid, Acute - therapy Medical prognosis Medicine Medicine & Public Health Oncology Original Article Prognosis Recurrence Retrospective Studies Stem cell transplantation Transplantation, Homologous |
title | Cytogenetic evolution predicts a poor prognosis in acute myeloid leukemia patients who relapse after allogeneic hematopoietic stem cell transplantation |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-28T00%3A24%3A05IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Cytogenetic%20evolution%20predicts%20a%20poor%20prognosis%20in%20acute%20myeloid%20leukemia%20patients%20who%20relapse%20after%20allogeneic%20hematopoietic%20stem%20cell%20transplantation&rft.jtitle=Annals%20of%20hematology&rft.au=Li,%20Ruiqi&rft.date=2023&rft.volume=102&rft.issue=1&rft.spage=89&rft.epage=97&rft.pages=89-97&rft.issn=0939-5555&rft.eissn=1432-0584&rft_id=info:doi/10.1007/s00277-022-05061-w&rft_dat=%3Cproquest_cross%3E2756669809%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2760024868&rft_id=info:pmid/36542104&rfr_iscdi=true |