Does metatarsus primus elevatus really exist in hallux rigidus? A weightbearing CT case–control study
Background Elevated first metatarsal, Metatarsus primus elevatus (MPE), has been a topic of controversy. Recent studies have supported a significantly elevated first metatarsal in hallux rigidus on weight-bearing radiographs (WBR). However, conventional radiographs have limitations for accurate meas...
Gespeichert in:
Veröffentlicht in: | Archives of orthopaedic and trauma surgery 2023-02, Vol.143 (2), p.755-761 |
---|---|
Hauptverfasser: | , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 761 |
---|---|
container_issue | 2 |
container_start_page | 755 |
container_title | Archives of orthopaedic and trauma surgery |
container_volume | 143 |
creator | Lee, Hee Young Mansur, Nacime S. Lalevee, Matthieu Maly, Connor Iehl, Caleb J. Hembree, Walter C. Godoy-Santos, Alexandre de Cesar Netto, Cesar |
description | Background
Elevated first metatarsal, Metatarsus primus elevatus (MPE), has been a topic of controversy. Recent studies have supported a significantly elevated first metatarsal in hallux rigidus on weight-bearing radiographs (WBR). However, conventional radiographs have limitations for accurate measurement. Our objective was to comparatively assess MPE and other variables which can affect the spatial relationship of the forefoot in the HR group compared to controls using weight-bearing CT (WBCT).
Methods
In this single-center, retrospective, case–control study, 25 patients (30 feet) with symptomatic HR and 30 controls were selected. WBCT parameters were measured by two independent investigators. Inter-observer reliabilities were assessed using intra-class correlation coefficients (ICCs). MPE was evaluated by measuring the direct distance between 1st and 2nd metatarsals. Independent t tests were performed to compare the two groups. A threshold of MPE to diagnose HR was calculated using the Receiver Operating Characteristic (ROC) curve.
Results
HR groups had increased hallux valgus angle (HVA) (8.52° in control vs 11.98° in HR) and MPE (2.92 vs 5.09 mm), decreased 1st metatarsal declination angle (21.09° vs 19.07°) 1st/2nd metatarsal declination ratio (87.45 vs 79.71) indicating elevated first metatarsal compared to controls. Dorsal translation of the first metatarsal at the first tarsometatarsal joint was observed in 21 (70%) patients of the HR group when defined as a step-off or discontinuation of the curvature along the first TMT joint. The threshold of MPE for diagnosis of HR was 4.19 mm with 77% sensitivity and 77% specificity.
Conclusion
Our results confirmed a significantly elevated first metatarsal in the HR group compared to controls on WBCT. A MPE greater than 4.19 mm was found to be diagnostic for symptomatic HR. Significant number of patients in the HR group (70%) had dorsal translation of the first metatarsal at the first TMT joint which can contribute to increased MPE.
Clinical relevance
The present study demonstrated significantly increased MPE in HR on WBCT and MPE greater than 4.19 mm on WBCT can be used as a diagnostic threshold for HR. |
doi_str_mv | 10.1007/s00402-021-04168-5 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2571918115</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2775844292</sourcerecordid><originalsourceid>FETCH-LOGICAL-c375t-eca21c2a1af6cfc6c8d677a10a71fd52ddb95217472bcfc54147b4a9c98831b93</originalsourceid><addsrcrecordid>eNp9kcFO3DAQhq0KVCjtC_RQWeLCJcXj2HFyqtACLRISF3q2HGeyBGWTrccB9sY78IY8CV6WQtUDp5nRfPPb-n_GvoL4DkKYQxJCCZkJCZlQUJSZ_sB2QeUqyysotv7pd9gnomshQJaV-Mh2cqWFThe7bH48IvEFRhddoIn4MnSLVLDHGxdTE9D1_YrjXUeRdwO_SuN0x0M375qJfvAjfovd_CrW6EI3zPnskntH-Hj_4MchhrHnFKdm9Zltt64n_PJS99jv05PL2a_s_OLn2ezoPPO50TFD7yR46cC1hW994cumMMaBcAbaRsumqSstwSgj67TXCpSplat8VZY51FW-xw42ussw_pmQol105LHv3YDjRFZqAxWUADqh-_-h1-MUhvQ7K43RpVKykomSG8qHkShga9cOubCyIOw6BruJwaYY7HMMdi397UV6qhfYvJ789T0B-Qag5do1DG9vvyP7BKuVlIE</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2775844292</pqid></control><display><type>article</type><title>Does metatarsus primus elevatus really exist in hallux rigidus? A weightbearing CT case–control study</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><creator>Lee, Hee Young ; Mansur, Nacime S. ; Lalevee, Matthieu ; Maly, Connor ; Iehl, Caleb J. ; Hembree, Walter C. ; Godoy-Santos, Alexandre ; de Cesar Netto, Cesar</creator><creatorcontrib>Lee, Hee Young ; Mansur, Nacime S. ; Lalevee, Matthieu ; Maly, Connor ; Iehl, Caleb J. ; Hembree, Walter C. ; Godoy-Santos, Alexandre ; de Cesar Netto, Cesar</creatorcontrib><description>Background
Elevated first metatarsal, Metatarsus primus elevatus (MPE), has been a topic of controversy. Recent studies have supported a significantly elevated first metatarsal in hallux rigidus on weight-bearing radiographs (WBR). However, conventional radiographs have limitations for accurate measurement. Our objective was to comparatively assess MPE and other variables which can affect the spatial relationship of the forefoot in the HR group compared to controls using weight-bearing CT (WBCT).
Methods
In this single-center, retrospective, case–control study, 25 patients (30 feet) with symptomatic HR and 30 controls were selected. WBCT parameters were measured by two independent investigators. Inter-observer reliabilities were assessed using intra-class correlation coefficients (ICCs). MPE was evaluated by measuring the direct distance between 1st and 2nd metatarsals. Independent t tests were performed to compare the two groups. A threshold of MPE to diagnose HR was calculated using the Receiver Operating Characteristic (ROC) curve.
Results
HR groups had increased hallux valgus angle (HVA) (8.52° in control vs 11.98° in HR) and MPE (2.92 vs 5.09 mm), decreased 1st metatarsal declination angle (21.09° vs 19.07°) 1st/2nd metatarsal declination ratio (87.45 vs 79.71) indicating elevated first metatarsal compared to controls. Dorsal translation of the first metatarsal at the first tarsometatarsal joint was observed in 21 (70%) patients of the HR group when defined as a step-off or discontinuation of the curvature along the first TMT joint. The threshold of MPE for diagnosis of HR was 4.19 mm with 77% sensitivity and 77% specificity.
Conclusion
Our results confirmed a significantly elevated first metatarsal in the HR group compared to controls on WBCT. A MPE greater than 4.19 mm was found to be diagnostic for symptomatic HR. Significant number of patients in the HR group (70%) had dorsal translation of the first metatarsal at the first TMT joint which can contribute to increased MPE.
Clinical relevance
The present study demonstrated significantly increased MPE in HR on WBCT and MPE greater than 4.19 mm on WBCT can be used as a diagnostic threshold for HR.</description><identifier>ISSN: 1434-3916</identifier><identifier>ISSN: 0936-8051</identifier><identifier>EISSN: 1434-3916</identifier><identifier>DOI: 10.1007/s00402-021-04168-5</identifier><identifier>PMID: 34505168</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Ankle ; Case-Control Studies ; Hallux Rigidus - diagnostic imaging ; Hallux Valgus ; Humans ; Medicine ; Medicine & Public Health ; Metatarsal Bones - diagnostic imaging ; Metatarsus ; Orthopaedic Surgery ; Orthopedics ; Retrospective Studies ; Statistical analysis ; Surgery ; Tomography, X-Ray Computed ; Trauma ; Weight-Bearing</subject><ispartof>Archives of orthopaedic and trauma surgery, 2023-02, Vol.143 (2), p.755-761</ispartof><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021</rights><rights>2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.</rights><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-eca21c2a1af6cfc6c8d677a10a71fd52ddb95217472bcfc54147b4a9c98831b93</citedby><cites>FETCH-LOGICAL-c375t-eca21c2a1af6cfc6c8d677a10a71fd52ddb95217472bcfc54147b4a9c98831b93</cites><orcidid>0000-0003-4179-9501</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/s00402-021-04168-5$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00402-021-04168-5$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34505168$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Hee Young</creatorcontrib><creatorcontrib>Mansur, Nacime S.</creatorcontrib><creatorcontrib>Lalevee, Matthieu</creatorcontrib><creatorcontrib>Maly, Connor</creatorcontrib><creatorcontrib>Iehl, Caleb J.</creatorcontrib><creatorcontrib>Hembree, Walter C.</creatorcontrib><creatorcontrib>Godoy-Santos, Alexandre</creatorcontrib><creatorcontrib>de Cesar Netto, Cesar</creatorcontrib><title>Does metatarsus primus elevatus really exist in hallux rigidus? A weightbearing CT case–control study</title><title>Archives of orthopaedic and trauma surgery</title><addtitle>Arch Orthop Trauma Surg</addtitle><addtitle>Arch Orthop Trauma Surg</addtitle><description>Background
Elevated first metatarsal, Metatarsus primus elevatus (MPE), has been a topic of controversy. Recent studies have supported a significantly elevated first metatarsal in hallux rigidus on weight-bearing radiographs (WBR). However, conventional radiographs have limitations for accurate measurement. Our objective was to comparatively assess MPE and other variables which can affect the spatial relationship of the forefoot in the HR group compared to controls using weight-bearing CT (WBCT).
Methods
In this single-center, retrospective, case–control study, 25 patients (30 feet) with symptomatic HR and 30 controls were selected. WBCT parameters were measured by two independent investigators. Inter-observer reliabilities were assessed using intra-class correlation coefficients (ICCs). MPE was evaluated by measuring the direct distance between 1st and 2nd metatarsals. Independent t tests were performed to compare the two groups. A threshold of MPE to diagnose HR was calculated using the Receiver Operating Characteristic (ROC) curve.
Results
HR groups had increased hallux valgus angle (HVA) (8.52° in control vs 11.98° in HR) and MPE (2.92 vs 5.09 mm), decreased 1st metatarsal declination angle (21.09° vs 19.07°) 1st/2nd metatarsal declination ratio (87.45 vs 79.71) indicating elevated first metatarsal compared to controls. Dorsal translation of the first metatarsal at the first tarsometatarsal joint was observed in 21 (70%) patients of the HR group when defined as a step-off or discontinuation of the curvature along the first TMT joint. The threshold of MPE for diagnosis of HR was 4.19 mm with 77% sensitivity and 77% specificity.
Conclusion
Our results confirmed a significantly elevated first metatarsal in the HR group compared to controls on WBCT. A MPE greater than 4.19 mm was found to be diagnostic for symptomatic HR. Significant number of patients in the HR group (70%) had dorsal translation of the first metatarsal at the first TMT joint which can contribute to increased MPE.
Clinical relevance
The present study demonstrated significantly increased MPE in HR on WBCT and MPE greater than 4.19 mm on WBCT can be used as a diagnostic threshold for HR.</description><subject>Ankle</subject><subject>Case-Control Studies</subject><subject>Hallux Rigidus - diagnostic imaging</subject><subject>Hallux Valgus</subject><subject>Humans</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metatarsal Bones - diagnostic imaging</subject><subject>Metatarsus</subject><subject>Orthopaedic Surgery</subject><subject>Orthopedics</subject><subject>Retrospective Studies</subject><subject>Statistical analysis</subject><subject>Surgery</subject><subject>Tomography, X-Ray Computed</subject><subject>Trauma</subject><subject>Weight-Bearing</subject><issn>1434-3916</issn><issn>0936-8051</issn><issn>1434-3916</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kcFO3DAQhq0KVCjtC_RQWeLCJcXj2HFyqtACLRISF3q2HGeyBGWTrccB9sY78IY8CV6WQtUDp5nRfPPb-n_GvoL4DkKYQxJCCZkJCZlQUJSZ_sB2QeUqyysotv7pd9gnomshQJaV-Mh2cqWFThe7bH48IvEFRhddoIn4MnSLVLDHGxdTE9D1_YrjXUeRdwO_SuN0x0M375qJfvAjfovd_CrW6EI3zPnskntH-Hj_4MchhrHnFKdm9Zltt64n_PJS99jv05PL2a_s_OLn2ezoPPO50TFD7yR46cC1hW994cumMMaBcAbaRsumqSstwSgj67TXCpSplat8VZY51FW-xw42ussw_pmQol105LHv3YDjRFZqAxWUADqh-_-h1-MUhvQ7K43RpVKykomSG8qHkShga9cOubCyIOw6BruJwaYY7HMMdi397UV6qhfYvJ789T0B-Qag5do1DG9vvyP7BKuVlIE</recordid><startdate>20230201</startdate><enddate>20230201</enddate><creator>Lee, Hee Young</creator><creator>Mansur, Nacime S.</creator><creator>Lalevee, Matthieu</creator><creator>Maly, Connor</creator><creator>Iehl, Caleb J.</creator><creator>Hembree, Walter C.</creator><creator>Godoy-Santos, Alexandre</creator><creator>de Cesar Netto, Cesar</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>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>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-4179-9501</orcidid></search><sort><creationdate>20230201</creationdate><title>Does metatarsus primus elevatus really exist in hallux rigidus? A weightbearing CT case–control study</title><author>Lee, Hee Young ; Mansur, Nacime S. ; Lalevee, Matthieu ; Maly, Connor ; Iehl, Caleb J. ; Hembree, Walter C. ; Godoy-Santos, Alexandre ; de Cesar Netto, Cesar</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-eca21c2a1af6cfc6c8d677a10a71fd52ddb95217472bcfc54147b4a9c98831b93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Ankle</topic><topic>Case-Control Studies</topic><topic>Hallux Rigidus - diagnostic imaging</topic><topic>Hallux Valgus</topic><topic>Humans</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metatarsal Bones - diagnostic imaging</topic><topic>Metatarsus</topic><topic>Orthopaedic Surgery</topic><topic>Orthopedics</topic><topic>Retrospective Studies</topic><topic>Statistical analysis</topic><topic>Surgery</topic><topic>Tomography, X-Ray Computed</topic><topic>Trauma</topic><topic>Weight-Bearing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, Hee Young</creatorcontrib><creatorcontrib>Mansur, Nacime S.</creatorcontrib><creatorcontrib>Lalevee, Matthieu</creatorcontrib><creatorcontrib>Maly, Connor</creatorcontrib><creatorcontrib>Iehl, Caleb J.</creatorcontrib><creatorcontrib>Hembree, Walter C.</creatorcontrib><creatorcontrib>Godoy-Santos, Alexandre</creatorcontrib><creatorcontrib>de Cesar Netto, Cesar</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>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>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>Archives of orthopaedic and trauma surgery</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, Hee Young</au><au>Mansur, Nacime S.</au><au>Lalevee, Matthieu</au><au>Maly, Connor</au><au>Iehl, Caleb J.</au><au>Hembree, Walter C.</au><au>Godoy-Santos, Alexandre</au><au>de Cesar Netto, Cesar</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Does metatarsus primus elevatus really exist in hallux rigidus? A weightbearing CT case–control study</atitle><jtitle>Archives of orthopaedic and trauma surgery</jtitle><stitle>Arch Orthop Trauma Surg</stitle><addtitle>Arch Orthop Trauma Surg</addtitle><date>2023-02-01</date><risdate>2023</risdate><volume>143</volume><issue>2</issue><spage>755</spage><epage>761</epage><pages>755-761</pages><issn>1434-3916</issn><issn>0936-8051</issn><eissn>1434-3916</eissn><abstract>Background
Elevated first metatarsal, Metatarsus primus elevatus (MPE), has been a topic of controversy. Recent studies have supported a significantly elevated first metatarsal in hallux rigidus on weight-bearing radiographs (WBR). However, conventional radiographs have limitations for accurate measurement. Our objective was to comparatively assess MPE and other variables which can affect the spatial relationship of the forefoot in the HR group compared to controls using weight-bearing CT (WBCT).
Methods
In this single-center, retrospective, case–control study, 25 patients (30 feet) with symptomatic HR and 30 controls were selected. WBCT parameters were measured by two independent investigators. Inter-observer reliabilities were assessed using intra-class correlation coefficients (ICCs). MPE was evaluated by measuring the direct distance between 1st and 2nd metatarsals. Independent t tests were performed to compare the two groups. A threshold of MPE to diagnose HR was calculated using the Receiver Operating Characteristic (ROC) curve.
Results
HR groups had increased hallux valgus angle (HVA) (8.52° in control vs 11.98° in HR) and MPE (2.92 vs 5.09 mm), decreased 1st metatarsal declination angle (21.09° vs 19.07°) 1st/2nd metatarsal declination ratio (87.45 vs 79.71) indicating elevated first metatarsal compared to controls. Dorsal translation of the first metatarsal at the first tarsometatarsal joint was observed in 21 (70%) patients of the HR group when defined as a step-off or discontinuation of the curvature along the first TMT joint. The threshold of MPE for diagnosis of HR was 4.19 mm with 77% sensitivity and 77% specificity.
Conclusion
Our results confirmed a significantly elevated first metatarsal in the HR group compared to controls on WBCT. A MPE greater than 4.19 mm was found to be diagnostic for symptomatic HR. Significant number of patients in the HR group (70%) had dorsal translation of the first metatarsal at the first TMT joint which can contribute to increased MPE.
Clinical relevance
The present study demonstrated significantly increased MPE in HR on WBCT and MPE greater than 4.19 mm on WBCT can be used as a diagnostic threshold for HR.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>34505168</pmid><doi>10.1007/s00402-021-04168-5</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0003-4179-9501</orcidid></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1434-3916 |
ispartof | Archives of orthopaedic and trauma surgery, 2023-02, Vol.143 (2), p.755-761 |
issn | 1434-3916 0936-8051 1434-3916 |
language | eng |
recordid | cdi_proquest_miscellaneous_2571918115 |
source | MEDLINE; Springer Nature - Complete Springer Journals |
subjects | Ankle Case-Control Studies Hallux Rigidus - diagnostic imaging Hallux Valgus Humans Medicine Medicine & Public Health Metatarsal Bones - diagnostic imaging Metatarsus Orthopaedic Surgery Orthopedics Retrospective Studies Statistical analysis Surgery Tomography, X-Ray Computed Trauma Weight-Bearing |
title | Does metatarsus primus elevatus really exist in hallux rigidus? A weightbearing CT case–control study |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-02T15%3A30%3A04IST&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=Does%20metatarsus%20primus%20elevatus%20really%20exist%20in%20hallux%20rigidus?%20A%20weightbearing%20CT%20case%E2%80%93control%20study&rft.jtitle=Archives%20of%20orthopaedic%20and%20trauma%20surgery&rft.au=Lee,%20Hee%20Young&rft.date=2023-02-01&rft.volume=143&rft.issue=2&rft.spage=755&rft.epage=761&rft.pages=755-761&rft.issn=1434-3916&rft.eissn=1434-3916&rft_id=info:doi/10.1007/s00402-021-04168-5&rft_dat=%3Cproquest_cross%3E2775844292%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=2775844292&rft_id=info:pmid/34505168&rfr_iscdi=true |