Loading…
Gaining a new angle on pancreas cancer: A pre-operative thrombelastographic parameter predicts recurrence and survival among patients with resected periampullary and pancreatic adenocarcinoma
It has previously been demonstrated that Thrombelastography(TEG) angle may be associated with recurrence and survival in pancreas cancer in a cohort of patients operated on at the University of Colorado in 2016–2017. Now approaching 10 years of follow-up, we revisit these associations and strengthen...
Saved in:
Published in: | The American journal of surgery 2024-12, Vol.238, p.115820, Article 115820 |
---|---|
Main Authors: | , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
cited_by | |
---|---|
cites | cdi_FETCH-LOGICAL-c271t-4b2f2c5eb66daf4000f8023340a2149136e752f7eba011c688ca081ffeab82743 |
container_end_page | |
container_issue | |
container_start_page | 115820 |
container_title | The American journal of surgery |
container_volume | 238 |
creator | Schulick, Alexander C. Moore, Hunter B. Franco, Salvador Rodriguez Jiang, Jessie G. Edil, Barish H. Schulick, Richard D. Nydam, Trevor L. McCarter, Martin D. Del Chiaro, Marco Gleisner, Ana |
description | It has previously been demonstrated that Thrombelastography(TEG) angle may be associated with recurrence and survival in pancreas cancer in a cohort of patients operated on at the University of Colorado in 2016–2017. Now approaching 10 years of follow-up, we revisit these associations and strengthen these claims with multivariate analysis.
Retrospective chart review was performed. Statistical analysis was conducted using STATA. Receiver operating characteristic(ROC) curves identified the performance of angle for predicting recurrence&survival. Unadjusted and adjusted cox regression models were used to identify significant predictors of these outcomes.
47 patients were included with median follow-up of 29.6 months. ROC curves for angle predicting recurrence and survival identified a cutoff of 44.5°. KM curves demonstrated that patients above the cutoff were more likely to recur(90%vs46 %,p = 0.001) and less likely to survive(16%vs56 %,p = 0.001). Angle remained significant on multivariate analyses (HR recurrence:3.64[1.32–10.25],HR survival:3.80[1.38–10.46]).
TEG angle is independently associated with disease recurrence and overall survival in pancreas cancer. This may be identifying virulent tumor biology, but further studies are required. A prospective study is underway.
•TEG may be used to predict clinical outcomes in pancreas cancer.•TEG Angle ≥44.5° is associated with greater recurrence risk.•Angle ≥44.5° is also associated with lower overall survival.•It remains an independent predictor on multivariate analysis. |
doi_str_mv | 10.1016/j.amjsurg.2024.115820 |
format | article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_3085116269</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0002961024003726</els_id><sourcerecordid>3085116269</sourcerecordid><originalsourceid>FETCH-LOGICAL-c271t-4b2f2c5eb66daf4000f8023340a2149136e752f7eba011c688ca081ffeab82743</originalsourceid><addsrcrecordid>eNqFUctu1DAUjRCIDoVPAFliwyaDH0nGYYOqCgpSJTawtm6cmxmPEjvYzlT9uv4adzpDF2xY2ZbOy-cUxVvB14KL5uN-DdM-LXG7llxWayFqLfmzYiX0pi2F1up5seKcy7JtBL8oXqW0p6cQlXpZXKiW162q-Kp4uAHnnd8yYB7vGPjtiCx4NoO3ESExSxeMn9gVmyOWYcYI2R2Q5V0MU4cjpBy2Eeads0SKMGHGeMT2zubEItolRiQN0u4ZBT64A4wMpkCmM2mhJ9idyzvCJrQZe0YmDqZ5GUeI94-8c5xMJtCjDxaidT5M8Lp4McCY8M35vCx-ff3y8_pbefvj5vv11W1p5UbksurkIG2NXdP0MFTUxKC5VFQBSFG1QjW4qeWwwQ6oI9tobYFrMQwInZabSl0WH066cwy_F0zZTC5ZpIQew5KM4roWopFNS9D3_0D3YYme0hkllNBCVY-C9QllY0gp4mDm6Cb6rxHcHBc2e3Ne2BwXNqeFiffurL50E_ZPrL-TEuDzCYBUx8FhNMm64wC9ozGy6YP7j8UfFnG-mQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3131813474</pqid></control><display><type>article</type><title>Gaining a new angle on pancreas cancer: A pre-operative thrombelastographic parameter predicts recurrence and survival among patients with resected periampullary and pancreatic adenocarcinoma</title><source>ScienceDirect Journals</source><creator>Schulick, Alexander C. ; Moore, Hunter B. ; Franco, Salvador Rodriguez ; Jiang, Jessie G. ; Edil, Barish H. ; Schulick, Richard D. ; Nydam, Trevor L. ; McCarter, Martin D. ; Del Chiaro, Marco ; Gleisner, Ana</creator><creatorcontrib>Schulick, Alexander C. ; Moore, Hunter B. ; Franco, Salvador Rodriguez ; Jiang, Jessie G. ; Edil, Barish H. ; Schulick, Richard D. ; Nydam, Trevor L. ; McCarter, Martin D. ; Del Chiaro, Marco ; Gleisner, Ana</creatorcontrib><description>It has previously been demonstrated that Thrombelastography(TEG) angle may be associated with recurrence and survival in pancreas cancer in a cohort of patients operated on at the University of Colorado in 2016–2017. Now approaching 10 years of follow-up, we revisit these associations and strengthen these claims with multivariate analysis.
Retrospective chart review was performed. Statistical analysis was conducted using STATA. Receiver operating characteristic(ROC) curves identified the performance of angle for predicting recurrence&survival. Unadjusted and adjusted cox regression models were used to identify significant predictors of these outcomes.
47 patients were included with median follow-up of 29.6 months. ROC curves for angle predicting recurrence and survival identified a cutoff of 44.5°. KM curves demonstrated that patients above the cutoff were more likely to recur(90%vs46 %,p = 0.001) and less likely to survive(16%vs56 %,p = 0.001). Angle remained significant on multivariate analyses (HR recurrence:3.64[1.32–10.25],HR survival:3.80[1.38–10.46]).
TEG angle is independently associated with disease recurrence and overall survival in pancreas cancer. This may be identifying virulent tumor biology, but further studies are required. A prospective study is underway.
•TEG may be used to predict clinical outcomes in pancreas cancer.•TEG Angle ≥44.5° is associated with greater recurrence risk.•Angle ≥44.5° is also associated with lower overall survival.•It remains an independent predictor on multivariate analysis.</description><identifier>ISSN: 0002-9610</identifier><identifier>ISSN: 1879-1883</identifier><identifier>EISSN: 1879-1883</identifier><identifier>DOI: 10.1016/j.amjsurg.2024.115820</identifier><identifier>PMID: 39059340</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adenocarcinoma ; Adenocarcinoma - blood ; Adenocarcinoma - mortality ; Adenocarcinoma - pathology ; Adenocarcinoma - surgery ; Aged ; Ampulla of Vater - pathology ; Ampulla of Vater - surgery ; Biomarkers ; Cancer ; Chemotherapy ; FDA approval ; Female ; Humans ; Lymphatic system ; Male ; Middle Aged ; Multivariate analysis ; Neoplasm Recurrence, Local - blood ; Neoplasm Recurrence, Local - epidemiology ; Pancreas ; Pancreatectomy ; Pancreatic cancer ; Pancreatic Neoplasms - blood ; Pancreatic Neoplasms - mortality ; Pancreatic Neoplasms - pathology ; Pancreatic Neoplasms - surgery ; Patients ; Performance evaluation ; Predictive Value of Tests ; Regression analysis ; Regression models ; Retrospective Studies ; ROC Curve ; Statistical analysis ; Statistical methods ; Surgery ; Survival ; Survival Rate ; Thrombelastography ; Tumors</subject><ispartof>The American journal of surgery, 2024-12, Vol.238, p.115820, Article 115820</ispartof><rights>2024 Elsevier Inc.</rights><rights>Copyright © 2024 Elsevier Inc. All rights reserved.</rights><rights>2024. Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c271t-4b2f2c5eb66daf4000f8023340a2149136e752f7eba011c688ca081ffeab82743</cites><orcidid>0000-0001-9275-6267</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27922,27923</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39059340$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Schulick, Alexander C.</creatorcontrib><creatorcontrib>Moore, Hunter B.</creatorcontrib><creatorcontrib>Franco, Salvador Rodriguez</creatorcontrib><creatorcontrib>Jiang, Jessie G.</creatorcontrib><creatorcontrib>Edil, Barish H.</creatorcontrib><creatorcontrib>Schulick, Richard D.</creatorcontrib><creatorcontrib>Nydam, Trevor L.</creatorcontrib><creatorcontrib>McCarter, Martin D.</creatorcontrib><creatorcontrib>Del Chiaro, Marco</creatorcontrib><creatorcontrib>Gleisner, Ana</creatorcontrib><title>Gaining a new angle on pancreas cancer: A pre-operative thrombelastographic parameter predicts recurrence and survival among patients with resected periampullary and pancreatic adenocarcinoma</title><title>The American journal of surgery</title><addtitle>Am J Surg</addtitle><description>It has previously been demonstrated that Thrombelastography(TEG) angle may be associated with recurrence and survival in pancreas cancer in a cohort of patients operated on at the University of Colorado in 2016–2017. Now approaching 10 years of follow-up, we revisit these associations and strengthen these claims with multivariate analysis.
Retrospective chart review was performed. Statistical analysis was conducted using STATA. Receiver operating characteristic(ROC) curves identified the performance of angle for predicting recurrence&survival. Unadjusted and adjusted cox regression models were used to identify significant predictors of these outcomes.
47 patients were included with median follow-up of 29.6 months. ROC curves for angle predicting recurrence and survival identified a cutoff of 44.5°. KM curves demonstrated that patients above the cutoff were more likely to recur(90%vs46 %,p = 0.001) and less likely to survive(16%vs56 %,p = 0.001). Angle remained significant on multivariate analyses (HR recurrence:3.64[1.32–10.25],HR survival:3.80[1.38–10.46]).
TEG angle is independently associated with disease recurrence and overall survival in pancreas cancer. This may be identifying virulent tumor biology, but further studies are required. A prospective study is underway.
•TEG may be used to predict clinical outcomes in pancreas cancer.•TEG Angle ≥44.5° is associated with greater recurrence risk.•Angle ≥44.5° is also associated with lower overall survival.•It remains an independent predictor on multivariate analysis.</description><subject>Adenocarcinoma</subject><subject>Adenocarcinoma - blood</subject><subject>Adenocarcinoma - mortality</subject><subject>Adenocarcinoma - pathology</subject><subject>Adenocarcinoma - surgery</subject><subject>Aged</subject><subject>Ampulla of Vater - pathology</subject><subject>Ampulla of Vater - surgery</subject><subject>Biomarkers</subject><subject>Cancer</subject><subject>Chemotherapy</subject><subject>FDA approval</subject><subject>Female</subject><subject>Humans</subject><subject>Lymphatic system</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Multivariate analysis</subject><subject>Neoplasm Recurrence, Local - blood</subject><subject>Neoplasm Recurrence, Local - epidemiology</subject><subject>Pancreas</subject><subject>Pancreatectomy</subject><subject>Pancreatic cancer</subject><subject>Pancreatic Neoplasms - blood</subject><subject>Pancreatic Neoplasms - mortality</subject><subject>Pancreatic Neoplasms - pathology</subject><subject>Pancreatic Neoplasms - surgery</subject><subject>Patients</subject><subject>Performance evaluation</subject><subject>Predictive Value of Tests</subject><subject>Regression analysis</subject><subject>Regression models</subject><subject>Retrospective Studies</subject><subject>ROC Curve</subject><subject>Statistical analysis</subject><subject>Statistical methods</subject><subject>Surgery</subject><subject>Survival</subject><subject>Survival Rate</subject><subject>Thrombelastography</subject><subject>Tumors</subject><issn>0002-9610</issn><issn>1879-1883</issn><issn>1879-1883</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNqFUctu1DAUjRCIDoVPAFliwyaDH0nGYYOqCgpSJTawtm6cmxmPEjvYzlT9uv4adzpDF2xY2ZbOy-cUxVvB14KL5uN-DdM-LXG7llxWayFqLfmzYiX0pi2F1up5seKcy7JtBL8oXqW0p6cQlXpZXKiW162q-Kp4uAHnnd8yYB7vGPjtiCx4NoO3ESExSxeMn9gVmyOWYcYI2R2Q5V0MU4cjpBy2Eeads0SKMGHGeMT2zubEItolRiQN0u4ZBT64A4wMpkCmM2mhJ9idyzvCJrQZe0YmDqZ5GUeI94-8c5xMJtCjDxaidT5M8Lp4McCY8M35vCx-ff3y8_pbefvj5vv11W1p5UbksurkIG2NXdP0MFTUxKC5VFQBSFG1QjW4qeWwwQ6oI9tobYFrMQwInZabSl0WH066cwy_F0zZTC5ZpIQew5KM4roWopFNS9D3_0D3YYme0hkllNBCVY-C9QllY0gp4mDm6Cb6rxHcHBc2e3Ne2BwXNqeFiffurL50E_ZPrL-TEuDzCYBUx8FhNMm64wC9ozGy6YP7j8UfFnG-mQ</recordid><startdate>202412</startdate><enddate>202412</enddate><creator>Schulick, Alexander C.</creator><creator>Moore, Hunter B.</creator><creator>Franco, Salvador Rodriguez</creator><creator>Jiang, Jessie G.</creator><creator>Edil, Barish H.</creator><creator>Schulick, Richard D.</creator><creator>Nydam, Trevor L.</creator><creator>McCarter, Martin D.</creator><creator>Del Chiaro, Marco</creator><creator>Gleisner, Ana</creator><general>Elsevier Inc</general><general>Elsevier Limited</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>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-9275-6267</orcidid></search><sort><creationdate>202412</creationdate><title>Gaining a new angle on pancreas cancer: A pre-operative thrombelastographic parameter predicts recurrence and survival among patients with resected periampullary and pancreatic adenocarcinoma</title><author>Schulick, Alexander C. ; Moore, Hunter B. ; Franco, Salvador Rodriguez ; Jiang, Jessie G. ; Edil, Barish H. ; Schulick, Richard D. ; Nydam, Trevor L. ; McCarter, Martin D. ; Del Chiaro, Marco ; Gleisner, Ana</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c271t-4b2f2c5eb66daf4000f8023340a2149136e752f7eba011c688ca081ffeab82743</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adenocarcinoma</topic><topic>Adenocarcinoma - blood</topic><topic>Adenocarcinoma - mortality</topic><topic>Adenocarcinoma - pathology</topic><topic>Adenocarcinoma - surgery</topic><topic>Aged</topic><topic>Ampulla of Vater - pathology</topic><topic>Ampulla of Vater - surgery</topic><topic>Biomarkers</topic><topic>Cancer</topic><topic>Chemotherapy</topic><topic>FDA approval</topic><topic>Female</topic><topic>Humans</topic><topic>Lymphatic system</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Multivariate analysis</topic><topic>Neoplasm Recurrence, Local - blood</topic><topic>Neoplasm Recurrence, Local - epidemiology</topic><topic>Pancreas</topic><topic>Pancreatectomy</topic><topic>Pancreatic cancer</topic><topic>Pancreatic Neoplasms - blood</topic><topic>Pancreatic Neoplasms - mortality</topic><topic>Pancreatic Neoplasms - pathology</topic><topic>Pancreatic Neoplasms - surgery</topic><topic>Patients</topic><topic>Performance evaluation</topic><topic>Predictive Value of Tests</topic><topic>Regression analysis</topic><topic>Regression models</topic><topic>Retrospective Studies</topic><topic>ROC Curve</topic><topic>Statistical analysis</topic><topic>Statistical methods</topic><topic>Surgery</topic><topic>Survival</topic><topic>Survival Rate</topic><topic>Thrombelastography</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schulick, Alexander C.</creatorcontrib><creatorcontrib>Moore, Hunter B.</creatorcontrib><creatorcontrib>Franco, Salvador Rodriguez</creatorcontrib><creatorcontrib>Jiang, Jessie G.</creatorcontrib><creatorcontrib>Edil, Barish H.</creatorcontrib><creatorcontrib>Schulick, Richard D.</creatorcontrib><creatorcontrib>Nydam, Trevor L.</creatorcontrib><creatorcontrib>McCarter, Martin D.</creatorcontrib><creatorcontrib>Del Chiaro, Marco</creatorcontrib><creatorcontrib>Gleisner, Ana</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The American journal of surgery</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Schulick, Alexander C.</au><au>Moore, Hunter B.</au><au>Franco, Salvador Rodriguez</au><au>Jiang, Jessie G.</au><au>Edil, Barish H.</au><au>Schulick, Richard D.</au><au>Nydam, Trevor L.</au><au>McCarter, Martin D.</au><au>Del Chiaro, Marco</au><au>Gleisner, Ana</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Gaining a new angle on pancreas cancer: A pre-operative thrombelastographic parameter predicts recurrence and survival among patients with resected periampullary and pancreatic adenocarcinoma</atitle><jtitle>The American journal of surgery</jtitle><addtitle>Am J Surg</addtitle><date>2024-12</date><risdate>2024</risdate><volume>238</volume><spage>115820</spage><pages>115820-</pages><artnum>115820</artnum><issn>0002-9610</issn><issn>1879-1883</issn><eissn>1879-1883</eissn><abstract>It has previously been demonstrated that Thrombelastography(TEG) angle may be associated with recurrence and survival in pancreas cancer in a cohort of patients operated on at the University of Colorado in 2016–2017. Now approaching 10 years of follow-up, we revisit these associations and strengthen these claims with multivariate analysis.
Retrospective chart review was performed. Statistical analysis was conducted using STATA. Receiver operating characteristic(ROC) curves identified the performance of angle for predicting recurrence&survival. Unadjusted and adjusted cox regression models were used to identify significant predictors of these outcomes.
47 patients were included with median follow-up of 29.6 months. ROC curves for angle predicting recurrence and survival identified a cutoff of 44.5°. KM curves demonstrated that patients above the cutoff were more likely to recur(90%vs46 %,p = 0.001) and less likely to survive(16%vs56 %,p = 0.001). Angle remained significant on multivariate analyses (HR recurrence:3.64[1.32–10.25],HR survival:3.80[1.38–10.46]).
TEG angle is independently associated with disease recurrence and overall survival in pancreas cancer. This may be identifying virulent tumor biology, but further studies are required. A prospective study is underway.
•TEG may be used to predict clinical outcomes in pancreas cancer.•TEG Angle ≥44.5° is associated with greater recurrence risk.•Angle ≥44.5° is also associated with lower overall survival.•It remains an independent predictor on multivariate analysis.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>39059340</pmid><doi>10.1016/j.amjsurg.2024.115820</doi><orcidid>https://orcid.org/0000-0001-9275-6267</orcidid></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0002-9610 |
ispartof | The American journal of surgery, 2024-12, Vol.238, p.115820, Article 115820 |
issn | 0002-9610 1879-1883 1879-1883 |
language | eng |
recordid | cdi_proquest_miscellaneous_3085116269 |
source | ScienceDirect Journals |
subjects | Adenocarcinoma Adenocarcinoma - blood Adenocarcinoma - mortality Adenocarcinoma - pathology Adenocarcinoma - surgery Aged Ampulla of Vater - pathology Ampulla of Vater - surgery Biomarkers Cancer Chemotherapy FDA approval Female Humans Lymphatic system Male Middle Aged Multivariate analysis Neoplasm Recurrence, Local - blood Neoplasm Recurrence, Local - epidemiology Pancreas Pancreatectomy Pancreatic cancer Pancreatic Neoplasms - blood Pancreatic Neoplasms - mortality Pancreatic Neoplasms - pathology Pancreatic Neoplasms - surgery Patients Performance evaluation Predictive Value of Tests Regression analysis Regression models Retrospective Studies ROC Curve Statistical analysis Statistical methods Surgery Survival Survival Rate Thrombelastography Tumors |
title | Gaining a new angle on pancreas cancer: A pre-operative thrombelastographic parameter predicts recurrence and survival among patients with resected periampullary and pancreatic adenocarcinoma |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-14T12%3A52%3A59IST&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=Gaining%20a%20new%20angle%20on%20pancreas%20cancer:%20A%20pre-operative%20thrombelastographic%20parameter%20predicts%20recurrence%20and%20survival%20among%20patients%20with%20resected%20periampullary%20and%20pancreatic%20adenocarcinoma&rft.jtitle=The%20American%20journal%20of%20surgery&rft.au=Schulick,%20Alexander%20C.&rft.date=2024-12&rft.volume=238&rft.spage=115820&rft.pages=115820-&rft.artnum=115820&rft.issn=0002-9610&rft.eissn=1879-1883&rft_id=info:doi/10.1016/j.amjsurg.2024.115820&rft_dat=%3Cproquest_cross%3E3085116269%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c271t-4b2f2c5eb66daf4000f8023340a2149136e752f7eba011c688ca081ffeab82743%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=3131813474&rft_id=info:pmid/39059340&rfr_iscdi=true |