Plasma Adiponectin, clinical factors, and patient outcomes during the acute respiratory distress syndrome
Adiponectin (APN) is an anti-inflammatory hormone derived from adipose tissue that attenuates acute lung injury in rodents. In this study, we investigated the association between circulating APN and outcomes among patients with acute respiratory distress syndrome (ARDS). We performed a retrospective...
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| description | Adiponectin (APN) is an anti-inflammatory hormone derived from adipose tissue that attenuates acute lung injury in rodents. In this study, we investigated the association between circulating APN and outcomes among patients with acute respiratory distress syndrome (ARDS).
We performed a retrospective cohort study using data and plasma samples from participants in the multicenter ARDS Network Fluid and Catheter Treatment Trial.
Plasma APN concentrations were measured in 816 (81.6%) trial participants at baseline and in 568 (56.8%) subjects at both baseline and day 7 after enrollment. Clinical factors associated with baseline APN levels in multivariable-adjusted models included sex, body mass index, past medical history of cirrhosis, and central venous pressure (model R2 = 9.7%). We did not observe an association between baseline APN and either severity of illness (APACHE III) or extent of lung injury (Lung Injury Score). Among patients who received right heart catheterization (n = 384), baseline APN was inversely related to mean pulmonary artery pressure (β = -0.015, R2 1.5%, p = 0.02); however, this association did not persist in multivariable models (β = -0.009, R2 0.5%, p = 0.20). Neither baseline APN levels [HR per quartile1.04 (95% CI 0.91-1.18), p = 0.61], nor change in APN level from baseline to day 7 [HR 1.04 (95% CI 0.89-1.23), p = 0.62)] were associated with 60 day mortality in Cox proportional hazards regression models. However, subgroup analysis identified an association between APN and mortality among patients who developed ARDS from extra-pulmonary etiologies [HR per quartile 1.31 (95% CI 1.08-1.57)]. APN levels did not correlate with mortality among patients developing ARDS in association with direct pulmonary injury [HR 0.96 (95% CI 0.83-1.13)], pinteraction = 0.016.
Plasma APN levels did not correlate with disease severity or mortality in a large cohort of patients with ARDS. However, higher APN levels were associated with increased mortality among patients developing ARDS from extra-pulmonary etiologies. |
| doi_str_mv | 10.1371/journal.pone.0108561 |
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We performed a retrospective cohort study using data and plasma samples from participants in the multicenter ARDS Network Fluid and Catheter Treatment Trial.
Plasma APN concentrations were measured in 816 (81.6%) trial participants at baseline and in 568 (56.8%) subjects at both baseline and day 7 after enrollment. Clinical factors associated with baseline APN levels in multivariable-adjusted models included sex, body mass index, past medical history of cirrhosis, and central venous pressure (model R2 = 9.7%). We did not observe an association between baseline APN and either severity of illness (APACHE III) or extent of lung injury (Lung Injury Score). Among patients who received right heart catheterization (n = 384), baseline APN was inversely related to mean pulmonary artery pressure (β = -0.015, R2 1.5%, p = 0.02); however, this association did not persist in multivariable models (β = -0.009, R2 0.5%, p = 0.20). Neither baseline APN levels [HR per quartile1.04 (95% CI 0.91-1.18), p = 0.61], nor change in APN level from baseline to day 7 [HR 1.04 (95% CI 0.89-1.23), p = 0.62)] were associated with 60 day mortality in Cox proportional hazards regression models. However, subgroup analysis identified an association between APN and mortality among patients who developed ARDS from extra-pulmonary etiologies [HR per quartile 1.31 (95% CI 1.08-1.57)]. APN levels did not correlate with mortality among patients developing ARDS in association with direct pulmonary injury [HR 0.96 (95% CI 0.83-1.13)], pinteraction = 0.016.
Plasma APN levels did not correlate with disease severity or mortality in a large cohort of patients with ARDS. However, higher APN levels were associated with increased mortality among patients developing ARDS from extra-pulmonary etiologies.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0108561</identifier><identifier>PMID: 25259893</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adiponectin ; Adiponectin - blood ; Adipose tissue ; Adult ; Aged ; APACHE ; Biology and Life Sciences ; Body mass ; Body mass index ; Body size ; Cardiac Catheterization ; Catheterization ; Catheters ; Cirrhosis ; Etiology ; Female ; Hazard identification ; Health risk assessment ; Heart ; Humans ; Inflammation ; Injuries ; Liver cirrhosis ; Lungs ; Male ; Medical instruments ; Medicine and Health Sciences ; Middle Aged ; Mortality ; Patients ; Pressure ; Prognosis ; Pulmonary artery ; Regression analysis ; Regression models ; Respiratory distress syndrome ; Respiratory Distress Syndrome - blood ; Respiratory Distress Syndrome - diagnosis ; Respiratory Distress Syndrome - mortality ; Respiratory Distress Syndrome - therapy ; Respiratory therapy ; Retrospective Studies ; Rodents ; Severity of Illness Index ; Studies ; Survival Rate ; Treatment Outcome</subject><ispartof>PloS one, 2014-09, Vol.9 (9), p.e108561-e108561</ispartof><rights>2014 Walkey et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 Walkey et al 2014 Walkey et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c662t-8a2a20e4403467fc7344158598cbdb09e9e7ef66f4acfd7d41c602f6ce7b4f613</citedby><cites>FETCH-LOGICAL-c662t-8a2a20e4403467fc7344158598cbdb09e9e7ef66f4acfd7d41c602f6ce7b4f613</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4178176/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4178176/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25259893$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Karhausen, Jörn</contributor><creatorcontrib>Walkey, Allan J</creatorcontrib><creatorcontrib>Demissie, Serkalem</creatorcontrib><creatorcontrib>Shah, Dilip</creatorcontrib><creatorcontrib>Romero, Freddy</creatorcontrib><creatorcontrib>Puklin, Leah</creatorcontrib><creatorcontrib>Summer, Ross S</creatorcontrib><title>Plasma Adiponectin, clinical factors, and patient outcomes during the acute respiratory distress syndrome</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Adiponectin (APN) is an anti-inflammatory hormone derived from adipose tissue that attenuates acute lung injury in rodents. In this study, we investigated the association between circulating APN and outcomes among patients with acute respiratory distress syndrome (ARDS).
We performed a retrospective cohort study using data and plasma samples from participants in the multicenter ARDS Network Fluid and Catheter Treatment Trial.
Plasma APN concentrations were measured in 816 (81.6%) trial participants at baseline and in 568 (56.8%) subjects at both baseline and day 7 after enrollment. Clinical factors associated with baseline APN levels in multivariable-adjusted models included sex, body mass index, past medical history of cirrhosis, and central venous pressure (model R2 = 9.7%). We did not observe an association between baseline APN and either severity of illness (APACHE III) or extent of lung injury (Lung Injury Score). Among patients who received right heart catheterization (n = 384), baseline APN was inversely related to mean pulmonary artery pressure (β = -0.015, R2 1.5%, p = 0.02); however, this association did not persist in multivariable models (β = -0.009, R2 0.5%, p = 0.20). Neither baseline APN levels [HR per quartile1.04 (95% CI 0.91-1.18), p = 0.61], nor change in APN level from baseline to day 7 [HR 1.04 (95% CI 0.89-1.23), p = 0.62)] were associated with 60 day mortality in Cox proportional hazards regression models. However, subgroup analysis identified an association between APN and mortality among patients who developed ARDS from extra-pulmonary etiologies [HR per quartile 1.31 (95% CI 1.08-1.57)]. APN levels did not correlate with mortality among patients developing ARDS in association with direct pulmonary injury [HR 0.96 (95% CI 0.83-1.13)], pinteraction = 0.016.
Plasma APN levels did not correlate with disease severity or mortality in a large cohort of patients with ARDS. However, higher APN levels were associated with increased mortality among patients developing ARDS from extra-pulmonary etiologies.</description><subject>Adiponectin</subject><subject>Adiponectin - blood</subject><subject>Adipose tissue</subject><subject>Adult</subject><subject>Aged</subject><subject>APACHE</subject><subject>Biology and Life Sciences</subject><subject>Body mass</subject><subject>Body mass index</subject><subject>Body size</subject><subject>Cardiac Catheterization</subject><subject>Catheterization</subject><subject>Catheters</subject><subject>Cirrhosis</subject><subject>Etiology</subject><subject>Female</subject><subject>Hazard identification</subject><subject>Health risk assessment</subject><subject>Heart</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Injuries</subject><subject>Liver cirrhosis</subject><subject>Lungs</subject><subject>Male</subject><subject>Medical instruments</subject><subject>Medicine and Health Sciences</subject><subject>Middle Aged</subject><subject>Mortality</subject><subject>Patients</subject><subject>Pressure</subject><subject>Prognosis</subject><subject>Pulmonary artery</subject><subject>Regression analysis</subject><subject>Regression models</subject><subject>Respiratory distress syndrome</subject><subject>Respiratory Distress Syndrome - blood</subject><subject>Respiratory Distress Syndrome - diagnosis</subject><subject>Respiratory Distress Syndrome - mortality</subject><subject>Respiratory Distress Syndrome - therapy</subject><subject>Respiratory therapy</subject><subject>Retrospective Studies</subject><subject>Rodents</subject><subject>Severity of Illness Index</subject><subject>Studies</subject><subject>Survival Rate</subject><subject>Treatment Outcome</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNptUstuFDEQHCEQCYE_QGCJC4fsYntsz8wlUhTxiBQJDnC2evzYeOWxF9uDtH-PNzuJEsTJr6rq6nY1zVuC16TtyKdtnFMAv97FYNaY4J4L8qw5JUNLV4Li9vmj_UnzKuctxrzthXjZnFBO-dAP7WnjfnjIE6BL7Q5CqrhwjpR3wSnwyIIqMeVzBEGjHRRnQkFxLipOJiM9Jxc2qNwaBGouBiWTdy5BpeyRdrnUc0Z5H3Sq-NfNCws-mzfLetb8-vL559W31c33r9dXlzcrJQQtqx4oUGwYwy0TnVVdyxjhfbWrRj3iwQymM1YIy0BZ3WlGlMDUCmW6kVlB2rPm_VF352OWy5SyJFxwMWDKaEVcHxE6wlbukpsg7WUEJ-8uYtpISMUpbySF3nbYYjVixhQhw9AL6DiM1ljMGVSti6XaPE5GqzqgBP6J6NOX4G7lJv6RjHQ96UQV-LgIpPh7NrnIyWVlvIdg4nznW_Rk4IxV6Id_oP_vjh1RKsWck7EPZgiWh-Tcs-Thw-WSnEp797iRB9J9VNq_l4fD8Q</recordid><startdate>20140926</startdate><enddate>20140926</enddate><creator>Walkey, Allan J</creator><creator>Demissie, Serkalem</creator><creator>Shah, Dilip</creator><creator>Romero, Freddy</creator><creator>Puklin, Leah</creator><creator>Summer, Ross S</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20140926</creationdate><title>Plasma Adiponectin, clinical factors, and patient outcomes during the acute respiratory distress syndrome</title><author>Walkey, Allan J ; Demissie, Serkalem ; Shah, Dilip ; Romero, Freddy ; Puklin, Leah ; Summer, Ross S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c662t-8a2a20e4403467fc7344158598cbdb09e9e7ef66f4acfd7d41c602f6ce7b4f613</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adiponectin</topic><topic>Adiponectin - 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diagnosis</topic><topic>Respiratory Distress Syndrome - mortality</topic><topic>Respiratory Distress Syndrome - therapy</topic><topic>Respiratory therapy</topic><topic>Retrospective Studies</topic><topic>Rodents</topic><topic>Severity of Illness Index</topic><topic>Studies</topic><topic>Survival Rate</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Walkey, Allan J</creatorcontrib><creatorcontrib>Demissie, Serkalem</creatorcontrib><creatorcontrib>Shah, Dilip</creatorcontrib><creatorcontrib>Romero, Freddy</creatorcontrib><creatorcontrib>Puklin, Leah</creatorcontrib><creatorcontrib>Summer, Ross S</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>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</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>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Walkey, Allan J</au><au>Demissie, Serkalem</au><au>Shah, Dilip</au><au>Romero, Freddy</au><au>Puklin, Leah</au><au>Summer, Ross S</au><au>Karhausen, Jörn</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Plasma Adiponectin, clinical factors, and patient outcomes during the acute respiratory distress syndrome</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-09-26</date><risdate>2014</risdate><volume>9</volume><issue>9</issue><spage>e108561</spage><epage>e108561</epage><pages>e108561-e108561</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Adiponectin (APN) is an anti-inflammatory hormone derived from adipose tissue that attenuates acute lung injury in rodents. In this study, we investigated the association between circulating APN and outcomes among patients with acute respiratory distress syndrome (ARDS).
We performed a retrospective cohort study using data and plasma samples from participants in the multicenter ARDS Network Fluid and Catheter Treatment Trial.
Plasma APN concentrations were measured in 816 (81.6%) trial participants at baseline and in 568 (56.8%) subjects at both baseline and day 7 after enrollment. Clinical factors associated with baseline APN levels in multivariable-adjusted models included sex, body mass index, past medical history of cirrhosis, and central venous pressure (model R2 = 9.7%). We did not observe an association between baseline APN and either severity of illness (APACHE III) or extent of lung injury (Lung Injury Score). Among patients who received right heart catheterization (n = 384), baseline APN was inversely related to mean pulmonary artery pressure (β = -0.015, R2 1.5%, p = 0.02); however, this association did not persist in multivariable models (β = -0.009, R2 0.5%, p = 0.20). Neither baseline APN levels [HR per quartile1.04 (95% CI 0.91-1.18), p = 0.61], nor change in APN level from baseline to day 7 [HR 1.04 (95% CI 0.89-1.23), p = 0.62)] were associated with 60 day mortality in Cox proportional hazards regression models. However, subgroup analysis identified an association between APN and mortality among patients who developed ARDS from extra-pulmonary etiologies [HR per quartile 1.31 (95% CI 1.08-1.57)]. APN levels did not correlate with mortality among patients developing ARDS in association with direct pulmonary injury [HR 0.96 (95% CI 0.83-1.13)], pinteraction = 0.016.
Plasma APN levels did not correlate with disease severity or mortality in a large cohort of patients with ARDS. However, higher APN levels were associated with increased mortality among patients developing ARDS from extra-pulmonary etiologies.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25259893</pmid><doi>10.1371/journal.pone.0108561</doi><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adiponectin Adiponectin - blood Adipose tissue Adult Aged APACHE Biology and Life Sciences Body mass Body mass index Body size Cardiac Catheterization Catheterization Catheters Cirrhosis Etiology Female Hazard identification Health risk assessment Heart Humans Inflammation Injuries Liver cirrhosis Lungs Male Medical instruments Medicine and Health Sciences Middle Aged Mortality Patients Pressure Prognosis Pulmonary artery Regression analysis Regression models Respiratory distress syndrome Respiratory Distress Syndrome - blood Respiratory Distress Syndrome - diagnosis Respiratory Distress Syndrome - mortality Respiratory Distress Syndrome - therapy Respiratory therapy Retrospective Studies Rodents Severity of Illness Index Studies Survival Rate Treatment Outcome |
| title | Plasma Adiponectin, clinical factors, and patient outcomes during the acute respiratory distress syndrome |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-22T15%3A19%3A36IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Plasma%20Adiponectin,%20clinical%20factors,%20and%20patient%20outcomes%20during%20the%20acute%20respiratory%20distress%20syndrome&rft.jtitle=PloS%20one&rft.au=Walkey,%20Allan%20J&rft.date=2014-09-26&rft.volume=9&rft.issue=9&rft.spage=e108561&rft.epage=e108561&rft.pages=e108561-e108561&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0108561&rft_dat=%3Cproquest_plos_%3E1566819544%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1565690242&rft_id=info:pmid/25259893&rft_doaj_id=oai_doaj_org_article_2a8f70f0cb044c119986a75abfef054a&rfr_iscdi=true |