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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Steroid-induced osteonecrosis in severe acute respiratory syndrome: a retrospective analysis of biochemical markers of bone metabolism and corticosteroid therapy</title>
<author><name sortKey="Chan, Michael H M" sort="Chan, Michael H M" uniqKey="Chan M" first="Michael H. M." last="Chan">Michael H. M. Chan</name>
<affiliation><nlm:aff id="aff0005">Departments of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Chan, Paul K S" sort="Chan, Paul K S" uniqKey="Chan P" first="Paul K. S." last="Chan">Paul K. S. Chan</name>
<affiliation><nlm:aff id="aff0010">Departments of Microbiology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Griffith, James F" sort="Griffith, James F" uniqKey="Griffith J" first="James F." last="Griffith">James F. Griffith</name>
<affiliation><nlm:aff id="aff0015">Departments of Diagnostic Radiology and Organ Imaging, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Chan, Iris H S" sort="Chan, Iris H S" uniqKey="Chan I" first="Iris H. S." last="Chan">Iris H. S. Chan</name>
<affiliation><nlm:aff id="aff0005">Departments of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Lit, Lydia C W" sort="Lit, Lydia C W" uniqKey="Lit L" first="Lydia C. W." last="Lit">Lydia C. W. Lit</name>
<affiliation><nlm:aff id="aff0005">Departments of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wong, C K" sort="Wong, C K" uniqKey="Wong C" first="C. K." last="Wong">C. K. Wong</name>
<affiliation><nlm:aff id="aff0005">Departments of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Antonio, Gregory E" sort="Antonio, Gregory E" uniqKey="Antonio G" first="Gregory E." last="Antonio">Gregory E. Antonio</name>
<affiliation><nlm:aff id="aff0015">Departments of Diagnostic Radiology and Organ Imaging, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Liu, Ester Y M" sort="Liu, Ester Y M" uniqKey="Liu E" first="Ester Y. M." last="Liu">Ester Y. M. Liu</name>
<affiliation><nlm:aff id="aff0010">Departments of Microbiology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hui, David S C" sort="Hui, David S C" uniqKey="Hui D" first="David S. C." last="Hui">David S. C. Hui</name>
<affiliation><nlm:aff id="aff0020">Departments of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Suen, Michael W M" sort="Suen, Michael W M" uniqKey="Suen M" first="Michael W. M" last="Suen">Michael W. M Suen</name>
<affiliation><nlm:aff id="aff0025">Department of Pathology, Alice Ho Miu Ling Nethersole Hospital, Tai Po, Hong Kong</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ahuja, Anil T" sort="Ahuja, Anil T" uniqKey="Ahuja A" first="Anil T." last="Ahuja">Anil T. Ahuja</name>
<affiliation><nlm:aff id="aff0015">Departments of Diagnostic Radiology and Organ Imaging, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Y Sung, Joseph J" sort="Y Sung, Joseph J" uniqKey="Y Sung J" first="Joseph J." last="Y. Sung">Joseph J. Y. Sung</name>
<affiliation><nlm:aff id="aff0020">Departments of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="K Lam, Christopher W" sort="K Lam, Christopher W" uniqKey="K Lam C" first="Christopher W." last="K. Lam">Christopher W. K. Lam</name>
<affiliation><nlm:aff id="aff0005">Departments of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong;</nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">16753744</idno>
<idno type="pmc">7131002</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7131002</idno>
<idno type="RBID">PMC:7131002</idno>
<idno type="doi">10.1080/00313020600696231</idno>
<date when="2006">2006</date>
<idno type="wicri:Area/Pmc/Corpus">001422</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001422</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Steroid-induced osteonecrosis in severe acute respiratory syndrome: a retrospective analysis of biochemical markers of bone metabolism and corticosteroid therapy</title>
<author><name sortKey="Chan, Michael H M" sort="Chan, Michael H M" uniqKey="Chan M" first="Michael H. M." last="Chan">Michael H. M. Chan</name>
<affiliation><nlm:aff id="aff0005">Departments of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Chan, Paul K S" sort="Chan, Paul K S" uniqKey="Chan P" first="Paul K. S." last="Chan">Paul K. S. Chan</name>
<affiliation><nlm:aff id="aff0010">Departments of Microbiology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Griffith, James F" sort="Griffith, James F" uniqKey="Griffith J" first="James F." last="Griffith">James F. Griffith</name>
<affiliation><nlm:aff id="aff0015">Departments of Diagnostic Radiology and Organ Imaging, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Chan, Iris H S" sort="Chan, Iris H S" uniqKey="Chan I" first="Iris H. S." last="Chan">Iris H. S. Chan</name>
<affiliation><nlm:aff id="aff0005">Departments of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Lit, Lydia C W" sort="Lit, Lydia C W" uniqKey="Lit L" first="Lydia C. W." last="Lit">Lydia C. W. Lit</name>
<affiliation><nlm:aff id="aff0005">Departments of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wong, C K" sort="Wong, C K" uniqKey="Wong C" first="C. K." last="Wong">C. K. Wong</name>
<affiliation><nlm:aff id="aff0005">Departments of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Antonio, Gregory E" sort="Antonio, Gregory E" uniqKey="Antonio G" first="Gregory E." last="Antonio">Gregory E. Antonio</name>
<affiliation><nlm:aff id="aff0015">Departments of Diagnostic Radiology and Organ Imaging, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Liu, Ester Y M" sort="Liu, Ester Y M" uniqKey="Liu E" first="Ester Y. M." last="Liu">Ester Y. M. Liu</name>
<affiliation><nlm:aff id="aff0010">Departments of Microbiology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hui, David S C" sort="Hui, David S C" uniqKey="Hui D" first="David S. C." last="Hui">David S. C. Hui</name>
<affiliation><nlm:aff id="aff0020">Departments of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Suen, Michael W M" sort="Suen, Michael W M" uniqKey="Suen M" first="Michael W. M" last="Suen">Michael W. M Suen</name>
<affiliation><nlm:aff id="aff0025">Department of Pathology, Alice Ho Miu Ling Nethersole Hospital, Tai Po, Hong Kong</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ahuja, Anil T" sort="Ahuja, Anil T" uniqKey="Ahuja A" first="Anil T." last="Ahuja">Anil T. Ahuja</name>
<affiliation><nlm:aff id="aff0015">Departments of Diagnostic Radiology and Organ Imaging, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Y Sung, Joseph J" sort="Y Sung, Joseph J" uniqKey="Y Sung J" first="Joseph J." last="Y. Sung">Joseph J. Y. Sung</name>
<affiliation><nlm:aff id="aff0020">Departments of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="K Lam, Christopher W" sort="K Lam, Christopher W" uniqKey="K Lam C" first="Christopher W." last="K. Lam">Christopher W. K. Lam</name>
<affiliation><nlm:aff id="aff0005">Departments of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong;</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">Pathology</title>
<idno type="ISSN">0031-3025</idno>
<idno type="eISSN">1465-3931</idno>
<imprint><date when="2006">2006</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><title>Summary</title>
<sec><title>Aim</title>
<p>We investigated the effect of massive doses of corticosteroid therapy on bone metabolism using specific biochemical markers of bone metabolism, and the prevalence of osteonecrosis in severe acute respiratory syndrome (SARS) patients at a university teaching hospital in Hong Kong.</p>
</sec>
<sec><title>Methods</title>
<p>Seventy-one patients with a clinical diagnosis of SARS were studied according to the modified World Health Organization case definition of SARS who were involved in the SARS epidemic between 10 March and 20 June 2003. The clinical diagnosis was confirmed by serological test and/ or molecular analysis. Biochemical markers of bone metabolism were analysed retrospectively using serial clotted blood samples collected from each patient during the course of hospital admission to discharge and subsequent follow-up at out-patient clinic using the arbitrary time periods: (i) Day <10; (ii) Day 28-44; (iii) Day 51-84; and (iv) Day >90 after the onset of fever. Magnetic resonance imaging of the knee and hip joints were performed post-admission to evaluate the prevalence of osteonecrosis amongst these SARS patients. Various risk factors for the development of osteonecrosis were assessed using receiver operating characteristics curve comparison with appropriate test statistics and Spearman’s coefficients of rank correlation with biochemical bone markers.</p>
</sec>
<sec><title>Results</title>
<p>Biochemical markers of bone metabolism showed significant bone resorption as evidenced by a marked increase in serum C-terminal telopeptide concentration (CTx) from Day 28-44 after the onset of fever. With tapering down of corticosteroid dosage, CTx started to return to previous baseline level from Day 51 onwards, while other bone formation markers, serum osteocalcin and bone- specific alkaline phosphatase concentrations (OC and BALP, respectively), started to increase. The latter effect was even more marked after Day >90. Seven patients developed radiological evidence of osteonecrosis. The prevalence of osteonecrosis in this cohort was 9.9%. A total corticosteroid dosage of >1900mg hydrocortisone, >2000 mg methylprednisolone, >13 340 mg hydrocortisone-equivalent corticosteroid therapy, and >18 days on corticosteroid therapy were found to be significant risk factors for the subsequent development of osteonecrosis. There were also significant positive correlations amongst various biochemical bone markers in this patient cohort.</p>
</sec>
<sec><title>Conclusion</title>
<p>Both bone resorption and formation markers were unable to predict the subsequent development of osteonecrosis. The use of high dose of hydrocortisone or methylprednisolone for an extended duration was shown to be a significant risk factor for osteonecrosis. Its prevalence in this cohort is comparable to those reported in the literature for SARS patients with high-dose corticosteroid therapy. The Day 28–44 increase in the serum CTx coincided with the timing of corticosteroid use. The Day >51 increase in serum OC and BALP coincided with the timing of corticosteroid withdrawal.</p>
</sec>
</div>
</front>
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<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Pathology</journal-id>
<journal-id journal-id-type="iso-abbrev">Pathology</journal-id>
<journal-title-group><journal-title>Pathology</journal-title>
</journal-title-group>
<issn pub-type="ppub">0031-3025</issn>
<issn pub-type="epub">1465-3931</issn>
<publisher><publisher-name>Royal College of Pathologists of Australasia. Published by Elsevier B.V.</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">16753744</article-id>
<article-id pub-id-type="pmc">7131002</article-id>
<article-id pub-id-type="publisher-id">S0031-3025(16)33940-X</article-id>
<article-id pub-id-type="doi">10.1080/00313020600696231</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Steroid-induced osteonecrosis in severe acute respiratory syndrome: a retrospective analysis of biochemical markers of bone metabolism and corticosteroid therapy</article-title>
</title-group>
<contrib-group><contrib contrib-type="author" id="aut0005"><name><surname>Chan</surname>
<given-names>Michael H.M.</given-names>
</name>
<xref rid="aff0005" ref-type="aff">*</xref>
</contrib>
<contrib contrib-type="author" id="aut0010"><name><surname>Chan</surname>
<given-names>Paul K.S.</given-names>
</name>
<xref rid="aff0010" ref-type="aff">†</xref>
</contrib>
<contrib contrib-type="author" id="aut0015"><name><surname>Griffith</surname>
<given-names>James F.</given-names>
</name>
<xref rid="aff0015" ref-type="aff">‡</xref>
</contrib>
<contrib contrib-type="author" id="aut0020"><name><surname>Chan</surname>
<given-names>Iris H.S.</given-names>
</name>
<xref rid="aff0005" ref-type="aff">*</xref>
</contrib>
<contrib contrib-type="author" id="aut0025"><name><surname>Lit</surname>
<given-names>Lydia C.W.</given-names>
</name>
<xref rid="aff0005" ref-type="aff">*</xref>
</contrib>
<contrib contrib-type="author" id="aut0030"><name><surname>Wong</surname>
<given-names>C.K.</given-names>
</name>
<xref rid="aff0005" ref-type="aff">*</xref>
</contrib>
<contrib contrib-type="author" id="aut0035"><name><surname>Antonio</surname>
<given-names>Gregory E.</given-names>
</name>
<xref rid="aff0015" ref-type="aff">‡</xref>
</contrib>
<contrib contrib-type="author" id="aut0040"><name><surname>Liu</surname>
<given-names>Ester Y.M.</given-names>
</name>
<xref rid="aff0010" ref-type="aff">†</xref>
</contrib>
<contrib contrib-type="author" id="aut0045"><name><surname>Hui</surname>
<given-names>David S.C.</given-names>
</name>
<xref rid="aff0020" ref-type="aff">§</xref>
</contrib>
<contrib contrib-type="author" id="aut0050"><name><surname>Suen</surname>
<given-names>Michael W.M</given-names>
</name>
<xref rid="aff0025" ref-type="aff">∥</xref>
</contrib>
<contrib contrib-type="author" id="aut0055"><name><surname>Ahuja</surname>
<given-names>Anil T.</given-names>
</name>
<xref rid="aff0015" ref-type="aff">‡</xref>
</contrib>
<contrib contrib-type="author" id="aut0060"><name><surname>Y. Sung</surname>
<given-names>Joseph J.</given-names>
</name>
<xref rid="aff0020" ref-type="aff">§</xref>
</contrib>
<contrib contrib-type="author" id="aut0065"><name><surname>K. Lam</surname>
<given-names>Christopher W.</given-names>
</name>
<email>waikeilam@cuhk.edu.hk</email>
<xref rid="aff0005" ref-type="aff">*</xref>
<xref rid="cor0005" ref-type="corresp">**</xref>
</contrib>
</contrib-group>
<aff id="aff0005"><label>*</label>
Departments of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong;</aff>
<aff id="aff0010"><label>†</label>
Departments of Microbiology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong;</aff>
<aff id="aff0015"><label>‡</label>
Departments of Diagnostic Radiology and Organ Imaging, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong;</aff>
<aff id="aff0020"><label>§</label>
Departments of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong;</aff>
<aff id="aff0025"><label>∥</label>
Department of Pathology, Alice Ho Miu Ling Nethersole Hospital, Tai Po, Hong Kong</aff>
<author-notes><corresp id="cor0005"><label>**</label>
Address for correspondence: Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong. <email>waikeilam@cuhk.edu.hk</email>
</corresp>
</author-notes>
<pub-date pub-type="pmc-release"><day>7</day>
<month>3</month>
<year>2016</year>
</pub-date>
<pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="ppub"><month>6</month>
<year>2006</year>
</pub-date>
<pub-date pub-type="epub"><day>7</day>
<month>3</month>
<year>2016</year>
</pub-date>
<volume>38</volume>
<issue>3</issue>
<fpage>229</fpage>
<lpage>235</lpage>
<history><date date-type="received"><day>5</day>
<month>8</month>
<year>2005</year>
</date>
<date date-type="rev-recd"><day>6</day>
<month>1</month>
<year>2006</year>
</date>
<date date-type="rev-recd"><day>1</day>
<month>2</month>
<year>2006</year>
</date>
<date date-type="accepted"><day>7</day>
<month>2</month>
<year>2006</year>
</date>
</history>
<permissions><copyright-statement>© 2006 Royal College of Pathologists of Australasia</copyright-statement>
<copyright-year>2006</copyright-year>
<license><license-p>Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.</license-p>
</license>
</permissions>
<abstract id="abs0005"><title>Summary</title>
<sec><title>Aim</title>
<p>We investigated the effect of massive doses of corticosteroid therapy on bone metabolism using specific biochemical markers of bone metabolism, and the prevalence of osteonecrosis in severe acute respiratory syndrome (SARS) patients at a university teaching hospital in Hong Kong.</p>
</sec>
<sec><title>Methods</title>
<p>Seventy-one patients with a clinical diagnosis of SARS were studied according to the modified World Health Organization case definition of SARS who were involved in the SARS epidemic between 10 March and 20 June 2003. The clinical diagnosis was confirmed by serological test and/ or molecular analysis. Biochemical markers of bone metabolism were analysed retrospectively using serial clotted blood samples collected from each patient during the course of hospital admission to discharge and subsequent follow-up at out-patient clinic using the arbitrary time periods: (i) Day <10; (ii) Day 28-44; (iii) Day 51-84; and (iv) Day >90 after the onset of fever. Magnetic resonance imaging of the knee and hip joints were performed post-admission to evaluate the prevalence of osteonecrosis amongst these SARS patients. Various risk factors for the development of osteonecrosis were assessed using receiver operating characteristics curve comparison with appropriate test statistics and Spearman’s coefficients of rank correlation with biochemical bone markers.</p>
</sec>
<sec><title>Results</title>
<p>Biochemical markers of bone metabolism showed significant bone resorption as evidenced by a marked increase in serum C-terminal telopeptide concentration (CTx) from Day 28-44 after the onset of fever. With tapering down of corticosteroid dosage, CTx started to return to previous baseline level from Day 51 onwards, while other bone formation markers, serum osteocalcin and bone- specific alkaline phosphatase concentrations (OC and BALP, respectively), started to increase. The latter effect was even more marked after Day >90. Seven patients developed radiological evidence of osteonecrosis. The prevalence of osteonecrosis in this cohort was 9.9%. A total corticosteroid dosage of >1900mg hydrocortisone, >2000 mg methylprednisolone, >13 340 mg hydrocortisone-equivalent corticosteroid therapy, and >18 days on corticosteroid therapy were found to be significant risk factors for the subsequent development of osteonecrosis. There were also significant positive correlations amongst various biochemical bone markers in this patient cohort.</p>
</sec>
<sec><title>Conclusion</title>
<p>Both bone resorption and formation markers were unable to predict the subsequent development of osteonecrosis. The use of high dose of hydrocortisone or methylprednisolone for an extended duration was shown to be a significant risk factor for osteonecrosis. Its prevalence in this cohort is comparable to those reported in the literature for SARS patients with high-dose corticosteroid therapy. The Day 28–44 increase in the serum CTx coincided with the timing of corticosteroid use. The Day >51 increase in serum OC and BALP coincided with the timing of corticosteroid withdrawal.</p>
</sec>
</abstract>
<kwd-group id="kwd0005"><title>Key words</title>
<kwd>Steroid-induced osteonecrosis</kwd>
<kwd>severe acute respiratory syndrome (SARS)</kwd>
<kwd>biochemical markers</kwd>
<kwd>bone metabolism</kwd>
<kwd>corticosteroid therapy</kwd>
</kwd-group>
</article-meta>
</front>
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