PP113. NT-Pro-BNP: A predictor of adverse maternal outcomes in hypertensive gestational syndromes?

Abstract Introduction BNP (brain-type natriuretic peptide) is released by cardiomyocytes, as a pro-hormone, in response to parietal stress augmentation and systemic endothelial dysfunction, and then Pro-BNP is cleaved into: NT-Pro-BNP and BNP fragment in 1:1 ratio. BNP is considered an important com...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Pregnancy hypertension 2012-07, Vol.2 (3), p.301-301
Hauptverfasser: Cabo Fustaret, M.C, Escobar, A.M, Illia, R, Uranga, M, Rivas, C, Lobenstein, G, Olejnik, P, Mayer, H, Ramilo, T.P
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 301
container_issue 3
container_start_page 301
container_title Pregnancy hypertension
container_volume 2
creator Cabo Fustaret, M.C
Escobar, A.M
Illia, R
Uranga, M
Rivas, C
Lobenstein, G
Olejnik, P
Mayer, H
Ramilo, T.P
description Abstract Introduction BNP (brain-type natriuretic peptide) is released by cardiomyocytes, as a pro-hormone, in response to parietal stress augmentation and systemic endothelial dysfunction, and then Pro-BNP is cleaved into: NT-Pro-BNP and BNP fragment in 1:1 ratio. BNP is considered an important component of the adaptative mechanism that helps to reduce the load on the myocardium, through systemic vasodilatation, reduction in venous return and reduction in vascular volume. Hypertensive Gestational Syndromes (HGS) are considered to share those mechanisms, but the role of NT-Pro-BNP to evaluate maternal outcomes, is not well defined. Objectives Evaluate the correlation between NT-Pro-BNP: in Normotensive Pregnant Women (NPW) and HGS with established markers of adverse maternal outcomes in HGS. Methods We performed a transversal case–control study to analyze NT-Pro-BNP in 68 patients with HGS vs 80 NPW admitted at a private hospital, and to evaluate its correlation with established clinical and blood markers of maternal outcomes at hospital admission. Patients with renal chronic failure, previous cardiac disease and mola were excluded. We used the Pearson and Kendall correlation test for quantitative variables and the non-parametrical Mann–Whitney test for qualitative variables. Results The average maternal age was: NPW 33.2 years, HGS 33.8 years; average gestational age at delivery: NPW 38.5 weeks, HGS 35.3 weeks; first pregnancy: NPW 36%, HGS 56%; birth average weight: NPW 3351.6 g, HGS 2615.5 g; media NT-Pro-BNP: NPW 59.7 pg/ml, HGS 704.8 pg/ml. None of the NPW had high levels of NT-Pro-BNP. In the HGS group: 57% had preeclampsia, 10% HELLP, 25% gestational hypertension and 8% chronic hypertension. In the HGS media values for: proteinuria 1.5 g/24 h, glutamic-oxalacetic transaminase 86 UI/L, platelets 231,688/mm3 , glutamic-pyruvic transaminase 100 UI/L, uric acid 48 mg/dl, hematocrit 33%, alkaline phosphatase 152 UI/L, lactic dehydrogenase 284 UI/L. In the HGS the following significant correlations were found: for NT-Pro-BNP relation to: proteinuria (0.34 p = 0.001), glutamic–oxalacetic transaminase (0.375 p = 0.001), platelets (−0.353 p = 0.001), glutamic–pyruvic transaminase (0.317 p = 0.001), uric acid (0.398 p = 0.001), hematocrit (−0.183 p = 0.048), gestational age at delivery (−0.29 p = 0.002), birth average weight (−0.23 p = 0.018), cardiac failure ( p = 0.001), number of used anti-hypertensive drugs (0.367 p = 0.004), lactic dehydrogenase (0.65 p
doi_str_mv 10.1016/j.preghy.2012.04.224
format Article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1691287537</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>1_s2_0_S221077891200253X</els_id><sourcerecordid>1691287537</sourcerecordid><originalsourceid>FETCH-LOGICAL-c2626-28d7a45e751dc1847b84b937fcb025d61dcbbddb2df5e519d57009ca369a929a3</originalsourceid><addsrcrecordid>eNqFkU9v1DAQxSNERavSb4CQj1yS2o7_xBxApaKAVLUrtZW4WY49ab0k8WInK-Xb42hLD1zwxZb13puZ3xTFO4Irgok431a7CI9PS0UxoRVmFaXsVXFCKcGllEq-fnk36rg4S2mL82EcN1K8KY6pIJizWpwU7WZDSF2hm_tyE0P55WbzEV2gHO68nUJEoUPG7SEmQIOZII6mR2GebBggIT-ip2UHcYIx-T2gR0iTmXxYRWkZXVxVn98WR53pE5w936fFw9XX-8vv5fXttx-XF9elpYKKkjZOGsZBcuIsaZhsG9aqWna2xZQ7kX_b1rmWuo4DJ8pxibGyphbKKKpMfVp8OOTuYvg951b04JOFvjcjhDlpIhShjeS1zFJ2kNoYUorQ6V30g4mLJlivgPVWHwDrFbDGTGfA2fb-ucLcDuBeTH9xZsGngwDynHsPUSfrYbSZZgQ7aRf8_yr8G2B7P3pr-l-wQNqGed1AnkWn7NF365LXHROKM6T6Z_0Hf7aiWQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1691287537</pqid></control><display><type>article</type><title>PP113. NT-Pro-BNP: A predictor of adverse maternal outcomes in hypertensive gestational syndromes?</title><source>Elsevier ScienceDirect Journals Complete</source><creator>Cabo Fustaret, M.C ; Escobar, A.M ; Illia, R ; Uranga, M ; Rivas, C ; Lobenstein, G ; Olejnik, P ; Mayer, H ; Ramilo, T.P</creator><creatorcontrib>Cabo Fustaret, M.C ; Escobar, A.M ; Illia, R ; Uranga, M ; Rivas, C ; Lobenstein, G ; Olejnik, P ; Mayer, H ; Ramilo, T.P</creatorcontrib><description>Abstract Introduction BNP (brain-type natriuretic peptide) is released by cardiomyocytes, as a pro-hormone, in response to parietal stress augmentation and systemic endothelial dysfunction, and then Pro-BNP is cleaved into: NT-Pro-BNP and BNP fragment in 1:1 ratio. BNP is considered an important component of the adaptative mechanism that helps to reduce the load on the myocardium, through systemic vasodilatation, reduction in venous return and reduction in vascular volume. Hypertensive Gestational Syndromes (HGS) are considered to share those mechanisms, but the role of NT-Pro-BNP to evaluate maternal outcomes, is not well defined. Objectives Evaluate the correlation between NT-Pro-BNP: in Normotensive Pregnant Women (NPW) and HGS with established markers of adverse maternal outcomes in HGS. Methods We performed a transversal case–control study to analyze NT-Pro-BNP in 68 patients with HGS vs 80 NPW admitted at a private hospital, and to evaluate its correlation with established clinical and blood markers of maternal outcomes at hospital admission. Patients with renal chronic failure, previous cardiac disease and mola were excluded. We used the Pearson and Kendall correlation test for quantitative variables and the non-parametrical Mann–Whitney test for qualitative variables. Results The average maternal age was: NPW 33.2 years, HGS 33.8 years; average gestational age at delivery: NPW 38.5 weeks, HGS 35.3 weeks; first pregnancy: NPW 36%, HGS 56%; birth average weight: NPW 3351.6 g, HGS 2615.5 g; media NT-Pro-BNP: NPW 59.7 pg/ml, HGS 704.8 pg/ml. None of the NPW had high levels of NT-Pro-BNP. In the HGS group: 57% had preeclampsia, 10% HELLP, 25% gestational hypertension and 8% chronic hypertension. In the HGS media values for: proteinuria 1.5 g/24 h, glutamic-oxalacetic transaminase 86 UI/L, platelets 231,688/mm3 , glutamic-pyruvic transaminase 100 UI/L, uric acid 48 mg/dl, hematocrit 33%, alkaline phosphatase 152 UI/L, lactic dehydrogenase 284 UI/L. In the HGS the following significant correlations were found: for NT-Pro-BNP relation to: proteinuria (0.34 p = 0.001), glutamic–oxalacetic transaminase (0.375 p = 0.001), platelets (−0.353 p = 0.001), glutamic–pyruvic transaminase (0.317 p = 0.001), uric acid (0.398 p = 0.001), hematocrit (−0.183 p = 0.048), gestational age at delivery (−0.29 p = 0.002), birth average weight (−0.23 p = 0.018), cardiac failure ( p = 0.001), number of used anti-hypertensive drugs (0.367 p = 0.004), lactic dehydrogenase (0.65 p = 0.001). The media NT-Pro-BNP was: 936 pg/ml in preeclampsia , 1909 pg/ml in HELLP, 150 pg/ml in gestational hypertension and 107 pg/ml in chronic hypertension. The highest NT-Pro-BNP level was 12,386 pg/ml in a patient with systolic dysfunction (LVEF: 35%) associated with preeclampsia. After delivery, 13% HGS women had persistent hypertension post-partum, and this did not correlate with the level of NT-Pro-BNP at hospital admission. Conclusion NT-Pro-BNP significantly correlates with established markers of adverse maternal outcomes in HGS, probing to be useful in routine maternal evaluation in this setting.</description><identifier>ISSN: 2210-7789</identifier><identifier>EISSN: 2210-7797</identifier><identifier>DOI: 10.1016/j.preghy.2012.04.224</identifier><identifier>PMID: 26105436</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Cardiovascular ; Obstetrics and Gynecology</subject><ispartof>Pregnancy hypertension, 2012-07, Vol.2 (3), p.301-301</ispartof><rights>2012</rights><rights>Copyright © 2012. Published by Elsevier B.V.</rights><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c2626-28d7a45e751dc1847b84b937fcb025d61dcbbddb2df5e519d57009ca369a929a3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.preghy.2012.04.224$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3541,27915,27916,45986</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26105436$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cabo Fustaret, M.C</creatorcontrib><creatorcontrib>Escobar, A.M</creatorcontrib><creatorcontrib>Illia, R</creatorcontrib><creatorcontrib>Uranga, M</creatorcontrib><creatorcontrib>Rivas, C</creatorcontrib><creatorcontrib>Lobenstein, G</creatorcontrib><creatorcontrib>Olejnik, P</creatorcontrib><creatorcontrib>Mayer, H</creatorcontrib><creatorcontrib>Ramilo, T.P</creatorcontrib><title>PP113. NT-Pro-BNP: A predictor of adverse maternal outcomes in hypertensive gestational syndromes?</title><title>Pregnancy hypertension</title><addtitle>Pregnancy Hypertens</addtitle><description>Abstract Introduction BNP (brain-type natriuretic peptide) is released by cardiomyocytes, as a pro-hormone, in response to parietal stress augmentation and systemic endothelial dysfunction, and then Pro-BNP is cleaved into: NT-Pro-BNP and BNP fragment in 1:1 ratio. BNP is considered an important component of the adaptative mechanism that helps to reduce the load on the myocardium, through systemic vasodilatation, reduction in venous return and reduction in vascular volume. Hypertensive Gestational Syndromes (HGS) are considered to share those mechanisms, but the role of NT-Pro-BNP to evaluate maternal outcomes, is not well defined. Objectives Evaluate the correlation between NT-Pro-BNP: in Normotensive Pregnant Women (NPW) and HGS with established markers of adverse maternal outcomes in HGS. Methods We performed a transversal case–control study to analyze NT-Pro-BNP in 68 patients with HGS vs 80 NPW admitted at a private hospital, and to evaluate its correlation with established clinical and blood markers of maternal outcomes at hospital admission. Patients with renal chronic failure, previous cardiac disease and mola were excluded. We used the Pearson and Kendall correlation test for quantitative variables and the non-parametrical Mann–Whitney test for qualitative variables. Results The average maternal age was: NPW 33.2 years, HGS 33.8 years; average gestational age at delivery: NPW 38.5 weeks, HGS 35.3 weeks; first pregnancy: NPW 36%, HGS 56%; birth average weight: NPW 3351.6 g, HGS 2615.5 g; media NT-Pro-BNP: NPW 59.7 pg/ml, HGS 704.8 pg/ml. None of the NPW had high levels of NT-Pro-BNP. In the HGS group: 57% had preeclampsia, 10% HELLP, 25% gestational hypertension and 8% chronic hypertension. In the HGS media values for: proteinuria 1.5 g/24 h, glutamic-oxalacetic transaminase 86 UI/L, platelets 231,688/mm3 , glutamic-pyruvic transaminase 100 UI/L, uric acid 48 mg/dl, hematocrit 33%, alkaline phosphatase 152 UI/L, lactic dehydrogenase 284 UI/L. In the HGS the following significant correlations were found: for NT-Pro-BNP relation to: proteinuria (0.34 p = 0.001), glutamic–oxalacetic transaminase (0.375 p = 0.001), platelets (−0.353 p = 0.001), glutamic–pyruvic transaminase (0.317 p = 0.001), uric acid (0.398 p = 0.001), hematocrit (−0.183 p = 0.048), gestational age at delivery (−0.29 p = 0.002), birth average weight (−0.23 p = 0.018), cardiac failure ( p = 0.001), number of used anti-hypertensive drugs (0.367 p = 0.004), lactic dehydrogenase (0.65 p = 0.001). The media NT-Pro-BNP was: 936 pg/ml in preeclampsia , 1909 pg/ml in HELLP, 150 pg/ml in gestational hypertension and 107 pg/ml in chronic hypertension. The highest NT-Pro-BNP level was 12,386 pg/ml in a patient with systolic dysfunction (LVEF: 35%) associated with preeclampsia. After delivery, 13% HGS women had persistent hypertension post-partum, and this did not correlate with the level of NT-Pro-BNP at hospital admission. Conclusion NT-Pro-BNP significantly correlates with established markers of adverse maternal outcomes in HGS, probing to be useful in routine maternal evaluation in this setting.</description><subject>Cardiovascular</subject><subject>Obstetrics and Gynecology</subject><issn>2210-7789</issn><issn>2210-7797</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><recordid>eNqFkU9v1DAQxSNERavSb4CQj1yS2o7_xBxApaKAVLUrtZW4WY49ab0k8WInK-Xb42hLD1zwxZb13puZ3xTFO4Irgok431a7CI9PS0UxoRVmFaXsVXFCKcGllEq-fnk36rg4S2mL82EcN1K8KY6pIJizWpwU7WZDSF2hm_tyE0P55WbzEV2gHO68nUJEoUPG7SEmQIOZII6mR2GebBggIT-ip2UHcYIx-T2gR0iTmXxYRWkZXVxVn98WR53pE5w936fFw9XX-8vv5fXttx-XF9elpYKKkjZOGsZBcuIsaZhsG9aqWna2xZQ7kX_b1rmWuo4DJ8pxibGyphbKKKpMfVp8OOTuYvg951b04JOFvjcjhDlpIhShjeS1zFJ2kNoYUorQ6V30g4mLJlivgPVWHwDrFbDGTGfA2fb-ucLcDuBeTH9xZsGngwDynHsPUSfrYbSZZgQ7aRf8_yr8G2B7P3pr-l-wQNqGed1AnkWn7NF365LXHROKM6T6Z_0Hf7aiWQ</recordid><startdate>201207</startdate><enddate>201207</enddate><creator>Cabo Fustaret, M.C</creator><creator>Escobar, A.M</creator><creator>Illia, R</creator><creator>Uranga, M</creator><creator>Rivas, C</creator><creator>Lobenstein, G</creator><creator>Olejnik, P</creator><creator>Mayer, H</creator><creator>Ramilo, T.P</creator><general>Elsevier B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201207</creationdate><title>PP113. NT-Pro-BNP: A predictor of adverse maternal outcomes in hypertensive gestational syndromes?</title><author>Cabo Fustaret, M.C ; Escobar, A.M ; Illia, R ; Uranga, M ; Rivas, C ; Lobenstein, G ; Olejnik, P ; Mayer, H ; Ramilo, T.P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2626-28d7a45e751dc1847b84b937fcb025d61dcbbddb2df5e519d57009ca369a929a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Cardiovascular</topic><topic>Obstetrics and Gynecology</topic><toplevel>online_resources</toplevel><creatorcontrib>Cabo Fustaret, M.C</creatorcontrib><creatorcontrib>Escobar, A.M</creatorcontrib><creatorcontrib>Illia, R</creatorcontrib><creatorcontrib>Uranga, M</creatorcontrib><creatorcontrib>Rivas, C</creatorcontrib><creatorcontrib>Lobenstein, G</creatorcontrib><creatorcontrib>Olejnik, P</creatorcontrib><creatorcontrib>Mayer, H</creatorcontrib><creatorcontrib>Ramilo, T.P</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Pregnancy hypertension</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cabo Fustaret, M.C</au><au>Escobar, A.M</au><au>Illia, R</au><au>Uranga, M</au><au>Rivas, C</au><au>Lobenstein, G</au><au>Olejnik, P</au><au>Mayer, H</au><au>Ramilo, T.P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PP113. NT-Pro-BNP: A predictor of adverse maternal outcomes in hypertensive gestational syndromes?</atitle><jtitle>Pregnancy hypertension</jtitle><addtitle>Pregnancy Hypertens</addtitle><date>2012-07</date><risdate>2012</risdate><volume>2</volume><issue>3</issue><spage>301</spage><epage>301</epage><pages>301-301</pages><issn>2210-7789</issn><eissn>2210-7797</eissn><abstract>Abstract Introduction BNP (brain-type natriuretic peptide) is released by cardiomyocytes, as a pro-hormone, in response to parietal stress augmentation and systemic endothelial dysfunction, and then Pro-BNP is cleaved into: NT-Pro-BNP and BNP fragment in 1:1 ratio. BNP is considered an important component of the adaptative mechanism that helps to reduce the load on the myocardium, through systemic vasodilatation, reduction in venous return and reduction in vascular volume. Hypertensive Gestational Syndromes (HGS) are considered to share those mechanisms, but the role of NT-Pro-BNP to evaluate maternal outcomes, is not well defined. Objectives Evaluate the correlation between NT-Pro-BNP: in Normotensive Pregnant Women (NPW) and HGS with established markers of adverse maternal outcomes in HGS. Methods We performed a transversal case–control study to analyze NT-Pro-BNP in 68 patients with HGS vs 80 NPW admitted at a private hospital, and to evaluate its correlation with established clinical and blood markers of maternal outcomes at hospital admission. Patients with renal chronic failure, previous cardiac disease and mola were excluded. We used the Pearson and Kendall correlation test for quantitative variables and the non-parametrical Mann–Whitney test for qualitative variables. Results The average maternal age was: NPW 33.2 years, HGS 33.8 years; average gestational age at delivery: NPW 38.5 weeks, HGS 35.3 weeks; first pregnancy: NPW 36%, HGS 56%; birth average weight: NPW 3351.6 g, HGS 2615.5 g; media NT-Pro-BNP: NPW 59.7 pg/ml, HGS 704.8 pg/ml. None of the NPW had high levels of NT-Pro-BNP. In the HGS group: 57% had preeclampsia, 10% HELLP, 25% gestational hypertension and 8% chronic hypertension. In the HGS media values for: proteinuria 1.5 g/24 h, glutamic-oxalacetic transaminase 86 UI/L, platelets 231,688/mm3 , glutamic-pyruvic transaminase 100 UI/L, uric acid 48 mg/dl, hematocrit 33%, alkaline phosphatase 152 UI/L, lactic dehydrogenase 284 UI/L. In the HGS the following significant correlations were found: for NT-Pro-BNP relation to: proteinuria (0.34 p = 0.001), glutamic–oxalacetic transaminase (0.375 p = 0.001), platelets (−0.353 p = 0.001), glutamic–pyruvic transaminase (0.317 p = 0.001), uric acid (0.398 p = 0.001), hematocrit (−0.183 p = 0.048), gestational age at delivery (−0.29 p = 0.002), birth average weight (−0.23 p = 0.018), cardiac failure ( p = 0.001), number of used anti-hypertensive drugs (0.367 p = 0.004), lactic dehydrogenase (0.65 p = 0.001). The media NT-Pro-BNP was: 936 pg/ml in preeclampsia , 1909 pg/ml in HELLP, 150 pg/ml in gestational hypertension and 107 pg/ml in chronic hypertension. The highest NT-Pro-BNP level was 12,386 pg/ml in a patient with systolic dysfunction (LVEF: 35%) associated with preeclampsia. After delivery, 13% HGS women had persistent hypertension post-partum, and this did not correlate with the level of NT-Pro-BNP at hospital admission. Conclusion NT-Pro-BNP significantly correlates with established markers of adverse maternal outcomes in HGS, probing to be useful in routine maternal evaluation in this setting.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>26105436</pmid><doi>10.1016/j.preghy.2012.04.224</doi><tpages>1</tpages></addata></record>
fulltext fulltext
identifier ISSN: 2210-7789
ispartof Pregnancy hypertension, 2012-07, Vol.2 (3), p.301-301
issn 2210-7789
2210-7797
language eng
recordid cdi_proquest_miscellaneous_1691287537
source Elsevier ScienceDirect Journals Complete
subjects Cardiovascular
Obstetrics and Gynecology
title PP113. NT-Pro-BNP: A predictor of adverse maternal outcomes in hypertensive gestational syndromes?
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-14T18%3A09%3A16IST&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=PP113.%20NT-Pro-BNP:%20A%20predictor%20of%20adverse%20maternal%20outcomes%20in%20hypertensive%20gestational%20syndromes?&rft.jtitle=Pregnancy%20hypertension&rft.au=Cabo%20Fustaret,%20M.C&rft.date=2012-07&rft.volume=2&rft.issue=3&rft.spage=301&rft.epage=301&rft.pages=301-301&rft.issn=2210-7789&rft.eissn=2210-7797&rft_id=info:doi/10.1016/j.preghy.2012.04.224&rft_dat=%3Cproquest_cross%3E1691287537%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=1691287537&rft_id=info:pmid/26105436&rft_els_id=1_s2_0_S221077891200253X&rfr_iscdi=true