{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T15:05:07Z","timestamp":1773759907573,"version":"3.50.1"},"reference-count":38,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,3,10]],"date-time":"2024-03-10T00:00:00Z","timestamp":1710028800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004063","name":"Knut och Alice Wallenbergs Stiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004063","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Colorectal Disease"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Previous research has indicated that preoperative beta blocker therapy is associated with a decreased risk of complications after surgery for rectal cancer. This is thought to arise because of the anti\u2010inflammatory activity of the drug. These results need to be reproduced and analyses extended to other drugs with such properties, as this information might be useful in clinical decision\u2010making. The main aim of this work was to replicate previous findings of beta blocker use as a prognostic marker for postoperative leakage. We also investigated whether drug exposure might induce anastomotic leaks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>This is a retrospective multicentre cohort study, comprising 1126 patients who underwent anterior resection for rectal cancer between 2014 and 2018. The use of any preoperative beta blocker was treated as the primary exposure, while anastomotic leakage within 12\u2009months of surgery was the outcome. Secondary exposures comprised angiotensin\u2010converting enzyme inhibitors\/angiotensin receptor blockers, statins and metformin. Using multivariable regression, we performed a replication analysis with a predictive aim for beta blockers only, while adjustment for confounding was done in more causally oriented analyses for all drugs. We estimated incidence rate ratio (IRR) and relative risk (RR) with 95% confidence intervals (CIs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Anastomotic leakage occurred in 20.6% of patients. Preoperative beta blockers were used by 22.7% of the cohort, while the leak distribution was almost identical between exposure groups. In the main replication analysis, no association could be detected (IRR 0.95, 95% CI 0.68\u20131.33). In the causally oriented analyses, only metformin affected the risk of leakage (RR 1.59, 95% Cl 1.31\u20131.92).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>While previous research has suggested that preoperative beta blocker use could be prognostic of anastomotic leakage, this study could not detect any such association. On the contrary, our results indicate that preoperative beta blocker use neither predicts nor causes anastomotic leakage after anterior resection for rectal cancer.<\/jats:p><\/jats:sec>","DOI":"10.1111\/codi.16933","type":"journal-article","created":{"date-parts":[[2024,3,11]],"date-time":"2024-03-11T05:34:49Z","timestamp":1710135289000},"page":"974-986","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Preoperative beta blockers and other drugs in relation to anastomotic leakage after anterior resection for rectal cancer"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-0796-1551","authenticated-orcid":false,"given":"Anders","family":"Gerdin","sequence":"first","affiliation":[{"name":"Department of Surgical and Perioperative Sciences, Surgery Ume\u00e5 University  Ume\u00e5 Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9602-475X","authenticated-orcid":false,"given":"Jennifer","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Surgery, SSORG \u2013 Scandinavian Surgical Outcomes Research Group, Institute of Clinical Sciences, Sahlgrenska Academy University of Gothenburg  Gothenburg Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenny","family":"H\u00e4ggstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Statistics, Ume\u00e5 School of Business, Economics and Statistics Ume\u00e5 University  Ume\u00e5 Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josefin","family":"Segelman","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Surgery, Karolinska Institutet, and Department of Surgery Ersta Hospital  Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Matthiessen","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Medicine and Health \u00d6rebro University  \u00d6rebro Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie\u2010Louise","family":"Lydrup","sequence":"additional","affiliation":[{"name":"Department of Surgery Sk\u00e5ne University Hospital, Malm\u00f6, Lund University  Lund Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Ruteg\u00e5rd","sequence":"additional","affiliation":[{"name":"Department of Surgical and Perioperative Sciences, Surgery Ume\u00e5 University  Ume\u00e5 Sweden"},{"name":"Wallenberg Centre for Molecular Medicine Ume\u00e5 University  Ume\u00e5 Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"The RectoLeak Study Group","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,3,10]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0000000000002429"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/bjs5.50106"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/codi.13771"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/DCR.0000000000002334"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00268-021-06054-y"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/codi.12618"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00423-021-02381-9"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/micr.20197"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2017.194"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0000000000002970"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/0284186X.2017.1332423"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.39335.541782.AD"},{"key":"e_1_2_13_14_1","doi-asserted-by":"crossref","DOI":"10.5195\/jmla.2018.319","article-title":"Research electronic data capture (REDCap)","volume":"106","author":"Patridge EF","year":"2018","journal-title":"J Med Libr Assoc"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/bjs.5679"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/0284186X.2018.1529425"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/bjs.4058"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.surg.2009.10.012"},{"issue":"1","key":"e_1_2_13_19_1","article-title":"Targeted maximum likelihood learning","volume":"2","author":"Laan MJ","year":"2006","journal-title":"Int J Biostat."},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.2202\/1557-4679.1217"},{"issue":"6","key":"e_1_2_13_21_1","first-page":"1887","article-title":"Robust causal inference using directed acyclic graphs: the R package \u2018dagitty\u2019","volume":"45","author":"Textor J","year":"2016","journal-title":"Int J Epidemiol."},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1996.tb02080.x"},{"key":"e_1_2_13_23_1","volume-title":"Flexible imputation of missing data","author":"Sv B","year":"2018"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.1986.10478280"},{"key":"e_1_2_13_25_1","volume-title":"R: a language and environment for statistical computing. R foundation for statistical computing","author":"R Core Team","year":"2022"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v051.i13"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v033.i01"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v045.i03"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1097\/DCR.0000000000001202"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.3109\/0284186X.2014.913101"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bja.2018.02.004"},{"key":"e_1_2_13_32_1","unstructured":"Swedish Colorectal Cancer Registry Interactive Report. 8th of September 2022. Available from:https:\/\/statistik.incanet.se\/kolorektal\/rektum\/"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1213\/ANE.0b013e3181ed114e"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/85.1.109"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.surg.2008.09.013"},{"issue":"4","key":"e_1_2_13_36_1","first-page":"1061","article-title":"Could beta blockade improve outcome after injury by modulating inflammatory profiles?","volume":"64","author":"Friese RS","year":"2008","journal-title":"J Trauma."},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamasurg.2020.0416"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0000000000002653"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/codi.13476"}],"container-title":["Colorectal Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/codi.16933","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,25]],"date-time":"2024-05-25T04:49:43Z","timestamp":1716612583000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/codi.16933"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,10]]},"references-count":38,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,5]]}},"alternative-id":["10.1111\/codi.16933"],"URL":"https:\/\/doi.org\/10.1111\/codi.16933","archive":["Portico"],"relation":{},"ISSN":["1462-8910","1463-1318"],"issn-type":[{"value":"1462-8910","type":"print"},{"value":"1463-1318","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,10]]},"assertion":[{"value":"2022-10-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}