{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T14:45:15Z","timestamp":1793717115828,"version":"4.6.1"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":1678,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2021,6,2]],"date-time":"2021-06-02T00:00:00Z","timestamp":1622592000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Commission for Veterinary specialization of the Vetsuisse Faculty University of Bern"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Endothelial dysfunction might contribute to the development of leptospiral pulmonary hemorrhage syndrome (LPHS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Hypothesis<\/jats:title>\n                    <jats:p>Serum concentrations of markers of endothelial activation and dysfunction are higher in dogs with leptospirosis and correlate with the occurrence of LPHS and a higher case fatality rate.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Animals<\/jats:title>\n                    <jats:p>Clinically healthy dogs (n\u00a0=\u00a031; 10\/31 dogs confirmed healthy based on no detected abnormalities on blood work), dogs with leptospirosis with LPHS (n\u00a0=\u00a017) and without LPHS (n\u00a0=\u00a015), dogs with acute kidney injury not due to leptospirosis (AKI-nL, n\u00a0=\u00a034).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Observational study. Serum concentrations of soluble intercellular adhesion molecule 1 (sICAM-1), vascular endothelial growth factor (VEGF), and angiopoietin-2 (Ang-2) at admission were compared between groups. Correlations with outcome and the accuracy to predict LPHS were examined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Soluble intercellular adhesion molecule (sICAM-1), VEGF, and Ang-2 concentrations were higher in dogs with AKI-nL (sICAM-1 34.7\u00a0ng\/mL, interquartile range [IQR]\u00a0=\u00a024.4-75.5; VEGF 43.1\u00a0pg\/mL, IQR\u00a0=\u00a012.3-79.2; Ang-2 8.5\u00a0ng\/mL, IQR\u00a0=\u00a06.2-12.3), leptospirosis without LPHS (sICAM-1 45.1\u00a0ng\/mL, IQR\u00a0=\u00a030.6-59.0; VEGF 32.4\u00a0pg\/mL, IQR\u00a0=\u00a012.5-62.6; Ang-2 9.6\u00a0ng\/mL, IQR\u00a0=\u00a06.9-19.3), and LPHS (sICAM-1 69.7\u00a0ng\/mL, IQR\u00a0=\u00a042.1-89.1; VEGF 51.8\u00a0pg\/mL, IQR\u00a0=\u00a026.3-96.7; Ang-2 8.0\u00a0ng\/mL, IQR\u00a0=\u00a05.6-12.2) compared to controls (P\u2009&amp;lt;\u2009.001). In dogs with leptospirosis, VEGF and sICAM-1 were higher in nonsurvivors (sICAM-1 89.4\u00a0ng\/mL, IQR\u00a0=\u00a076.5-101.0; VEGF 117.0\u00a0pg\/mL, IQR\u00a0=\u00a090.3-232.4) than survivors (P\u00a0=\u00a0.004) and sICAM-1 predicted the development of LPHS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Soluble intercellular adhesion molecule 1, VEGF, and Ang-2 do not discriminate leptospirosis from AKI-nL. In dogs with leptospirosis, sICAM-1 and VEGF predict outcome and sICAM-1 might identify dogs at risk for LPHS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jvim.16163","type":"journal-article","created":{"date-parts":[[2021,6,2]],"date-time":"2021-06-02T12:36:01Z","timestamp":1622637361000},"page":"1789-1799","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Association of markers of endothelial activation and dysfunction with occurrence and outcome of pulmonary hemorrhage in dogs with leptospirosis"],"prefix":"10.1093","volume":"35","author":[{"given":"Franziska","family":"Sonderegger","sequence":"first","affiliation":[{"name":"Vetsuisse Faculty University of Bern Department Clinical Veterinary Medicine, , Bern,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Nentwig","sequence":"additional","affiliation":[{"name":"EnnetSee Klinik , H\u00fcnenberg,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9296-4509","authenticated-orcid":false,"given":"Ariane","family":"Schweighauser","sequence":"additional","affiliation":[{"name":"Vetsuisse Faculty University of Bern Department Clinical Veterinary Medicine, , Bern,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6693-5365","authenticated-orcid":false,"given":"Thierry","family":"Francey","sequence":"additional","affiliation":[{"name":"Vetsuisse Faculty University of Bern Department Clinical Veterinary Medicine, , Bern,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliane","family":"Marti","sequence":"additional","affiliation":[{"name":"Vetsuisse Faculty University of Bern Department of Clinical Research and Veterinary Public Health (DCR-VPH), , Bern,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelena","family":"Mirkovitch","sequence":"additional","affiliation":[{"name":"Vetsuisse Faculty University of Bern Department of Clinical Research and Veterinary Public Health (DCR-VPH), , Bern,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7316-4423","authenticated-orcid":false,"given":"Simone","family":"Schuller","sequence":"additional","affiliation":[{"name":"Vetsuisse Faculty University of Bern Department Clinical Veterinary Medicine, , Bern,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,7,1]]},"reference":[{"issue":"4","key":"2026020922180723300_jvim16163-bib-0001","doi-asserted-by":"crossref","first-page":"7242","DOI":"10.3390\/ijerph110707242","article-title":"Increasing incidence of canine leptospirosis in Switzerland","volume":"11","author":"Major","year":"2014","journal-title":"Int J Environ Res Public Health"},{"issue":"4","key":"2026020922180723300_jvim16163-bib-0002","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.jinf.2009.12.005","article-title":"Early identification of leptospirosis-associated pulmonary hemorrhage syndrome by use of a validated prediction model","volume":"60","author":"Marotto","year":"2010","journal-title":"J Infect"},{"key":"2026020922180723300_jvim16163-bib-0003","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.cimid.2015.04.002","article-title":"Immunohistochemical detection of IgM and IgG in lung tissue of dogs with leptospiral pulmonary haemorrhage syndrome (LPHS)","volume":"40","author":"Schuller","year":"2015","journal-title":"Comp Immunol Microbiol Infect Dis"},{"issue":"4","key":"2026020922180723300_jvim16163-bib-0004","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1111\/j.1939-1676.2010.0585.x","article-title":"Pulmonary abnormalities in dogs with leptospirosis","volume":"24","author":"Kohn","year":"2010","journal-title":"J Vet Intern Med"},{"issue":"4","key":"2026020922180723300_jvim16163-bib-0005","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1016\/S0002-9440(10)63198-7","article-title":"Alveolar septal deposition of immunoglobulin and complement parallels pulmonary hemorrhage in a guinea pig model of severe pulmonary leptospirosis","volume":"164","author":"Nally","year":"2004","journal-title":"Am J Pathol"},{"issue":"4","key":"2026020922180723300_jvim16163-bib-0006","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1016\/j.humpath.2011.11.017","article-title":"Immune receptors and adhesion molecules in human pulmonary leptospirosis","volume":"43","author":"Del Carlo Bernardi","year":"2012","journal-title":"Hum Pathol"},{"issue":"4","key":"2026020922180723300_jvim16163-bib-0007","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1111\/jvim.14626","article-title":"Hemorrhagic, hemostatic, and thromboelastometric disorders in 35 dogs with a clinical diagnosis of leptospirosis: a prospective study","volume":"31","author":"Barth\u00e9lemy","year":"2017","journal-title":"J Vet Intern Med"},{"issue":"4","key":"2026020922180723300_jvim16163-bib-0008","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/j.1939-1676.2007.tb02921.x","article-title":"Clinicopathologic features and outcome predictors of Leptospira interrogans Australis serogroup infection in dogs: a retrospective study of 20 cases (2001\u20132004)","volume":"21","author":"Mastrorilli","year":"2007","journal-title":"J Vet Intern Med"},{"issue":"4","key":"2026020922180723300_jvim16163-bib-0009","first-page":"1","article-title":"Leptospira interrogans binds to cadherins","volume":"8","author":"Evangelista","year":"2014","journal-title":"PLoS Negl Trop Dis"},{"issue":"4","key":"2026020922180723300_jvim16163-bib-0010","first-page":"1","article-title":"Responses of human endothelial cells to pathogenic and non-pathogenic Leptospira species","volume":"4","author":"Martinez-Lopez","year":"2010","journal-title":"PLoS Negl Trop Dis"},{"issue":"4","key":"2026020922180723300_jvim16163-bib-0011","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.jinf.2009.07.010","article-title":"Lp95, a novel leptospiral protein that binds extracellular matrix components and activates e-selectin on endothelial cells","volume":"59","author":"Atzingen","year":"2009","journal-title":"J Infect"},{"issue":"4","key":"2026020922180723300_jvim16163-bib-0012","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1111\/j.1574-6968.2007.00924.x","article-title":"A novel leptospiral protein increases ICAM-1 and E-selectin expression in human umbilical vein endothelial cells","volume":"276","author":"Vieira","year":"2007","journal-title":"FEMS Microbiol Lett"},{"issue":"4","key":"2026020922180723300_jvim16163-bib-0013","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.micpath.2008.08.004","article-title":"Putative outer membrane proteins of Leptospira interrogans stimulate human umbilical vein endothelial cells (HUVECS) and express during infection","volume":"45","author":"G\u00f3mez","year":"2008","journal-title":"Microb Pathog"},{"issue":"4","key":"2026020922180723300_jvim16163-bib-0014","first-page":"1","article-title":"Leptospira interrogans causes quantitative and morphological disturbances in adherens junctions and other biological groups of proteins in human endothelial cells","volume":"11","author":"Sato","year":"2017","journal-title":"PLoS Negl Trop Dis"},{"issue":"4","key":"2026020922180723300_jvim16163-bib-0015","first-page":"1","article-title":"Increased levels of soluble forms of E-selectin and ICAM-1 adhesion molecules during human leptospirosis","volume":"12","author":"Raffray","year":"2017","journal-title":"PLoS One"},{"issue":"4","key":"2026020922180723300_jvim16163-bib-0016","doi-asserted-by":"crossref","first-page":"611","DOI":"10.4269\/ajtmh.14-0232","article-title":"Endothelial glycocalyx damage is associated with leptospirosis acute kidney injury","volume":"92","author":"Lib\u00f3rio","year":"2015","journal-title":"Am J Trop Med Hyg"},{"issue":"4","key":"2026020922180723300_jvim16163-bib-0017","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1111\/j.1365-2249.2008.03673.x","article-title":"Differential patterns of endothelial and leucocyte activation in \u201ctyphus-like\u201d illnesses in Laos and Thailand","volume":"153","author":"Paris","year":"2008","journal-title":"Clin Exp Immunol"},{"issue":"4","key":"2026020922180723300_jvim16163-bib-0018","first-page":"5","article-title":"Association of Angiopoietin-2 and dimethylarginines with complicated course in patients with leptospirosis","volume":"9","author":"Lukasz","year":"2014","journal-title":"PLoS One"},{"issue":"4","key":"2026020922180723300_jvim16163-bib-0019","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1093\/trstmh\/trv095","article-title":"Cytokines in human leptospirosis","volume":"109","author":"Papa","year":"2015","journal-title":"Trans R Soc Trop Med Hyg"},{"issue":"4","key":"2026020922180723300_jvim16163-bib-0020","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.jinf.2015.05.016","article-title":"Markers of endothelial cell activation and immune activation are increased in patients with severe leptospirosis and associated with disease severity","volume":"71","author":"Goeijenbier","year":"2015","journal-title":"J Infect"},{"issue":"4","key":"2026020922180723300_jvim16163-bib-0021","first-page":"876","article-title":"Immune evasion by pathogenic Leptospira strains: the secretion of proteases that directly cleave complement proteins","volume":"209","author":"Fraga","year":"2013","journal-title":"J Infect Dis"},{"key":"2026020922180723300_jvim16163-bib-0022","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.micpath.2013.04.011","article-title":"Evaluation of the elastinolytic activity and protective effect of Leptallo I, a protein composed by metalloprotease and FA5\/8C domains, from Leptospira interrogans Copenhageni","volume":"61\u201362","author":"Hashimoto","year":"2013","journal-title":"Microb Pathog"},{"issue":"4","key":"2026020922180723300_jvim16163-bib-0023","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1534\/g3.116.038455","article-title":"A missense variant in KCNJ10 in Belgian shepherd dogs affected by spongy degeneration with cerebellar ataxia (SDCA1)","volume":"7","author":"Mauri","year":"2017","journal-title":"G3"},{"key":"2026020922180723300_jvim16163-bib-0024","article-title":"Leptospirosis. OIE Terrestrial Manual"},{"issue":"4","key":"2026020922180723300_jvim16163-bib-0025","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1007\/s10096-010-0991-2","article-title":"Detection and quantification of leptospires in urine of dogs: a maintenance host for the zoonotic disease leptospirosis","volume":"29","author":"Rojas","year":"2010","journal-title":"Eur J Clin Microbiol Infect Dis"},{"issue":"4","key":"2026020922180723300_jvim16163-bib-0026","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1111\/jvim.12146","article-title":"Markers of coagulation activation, endothelial stimulation, and inflammation in dogs with babesiosis","volume":"27","author":"Bari\u0107 Rafaj","year":"2013","journal-title":"J Vet Intern Med"},{"issue":"4","key":"2026020922180723300_jvim16163-bib-0027","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1111\/jvim.15369","article-title":"Evaluation of plasma angiopoietin-2 and vascular endothelial growth factor in healthy dogs and dogs with systemic inflammatory response syndrome or sepsis","volume":"33","author":"K\u00f6nig","year":"2019","journal-title":"J Vet Intern Med"},{"issue":"4","key":"2026020922180723300_jvim16163-bib-0028","doi-asserted-by":"crossref","first-page":"803","DOI":"10.2460\/ajvr.79.8.803","article-title":"Validation of a human angiopoietin-2 ELISA for measurement of angiopoietin-2 concentrations in canine plasma samples and supernatant of primary canine aortic endothelial cell cultures","volume":"79","author":"K\u00f6nig","year":"2018","journal-title":"Am J Vet Res"},{"issue":"4","key":"2026020922180723300_jvim16163-bib-0029","first-page":"255","article-title":"Handling results below the level of detection","volume":"54","author":"Ogden","year":"2010","journal-title":"Ann Occup Hyg"},{"issue":"4","key":"2026020922180723300_jvim16163-bib-0030","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.ejim.2012.10.009","article-title":"Circulating sICAM-1 and sE-Selectin as biomarker of infection and prognosis in patients with systemic inflammatory response syndrome","volume":"24","author":"de Pablo","year":"2013","journal-title":"Eur J Intern Med"},{"key":"2026020922180723300_jvim16163-bib-0031","first-page":"1","article-title":"Mediators of inflammation in acute kidney injury","volume":"2009","author":"Edelstein","year":"2009","journal-title":"Mediators Inflamm"},{"issue":"4","key":"2026020922180723300_jvim16163-bib-0032","doi-asserted-by":"crossref","first-page":"218","DOI":"10.2460\/ajvr.77.2.218","article-title":"Assessment of the expression of biomarkers of uremic inflammation in dogs with renal disease","volume":"77","author":"Nentwig","year":"2016","journal-title":"Am J Vet Res"},{"issue":"4","key":"2026020922180723300_jvim16163-bib-0033","first-page":"1","article-title":"Cytokine response signatures in disease progression and development of severe clinical outcomes for leptospirosis","volume":"7","author":"Reis","year":"2013","journal-title":"PLoS Negl Trop Dis"},{"key":"2026020922180723300_jvim16163-bib-0034","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1590\/S0100-879X2004000400003","article-title":"Genome features of Leptospira interrogans serovar Copenhageni","volume":"37","author":"Nascimento","year":"2004","journal-title":"Braz J Med Biol Res"},{"issue":"4","key":"2026020922180723300_jvim16163-bib-0035","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1038\/86354","article-title":"Leptospiral lipopolysaccharide activates cells through a TLR2-dependent mechanism","volume":"2","author":"Werts","year":"2001","journal-title":"Nat Immunol"},{"key":"2026020922180723300_jvim16163-bib-0036","first-page":"1","article-title":"Commonly used severity scores are not good predictors of mortality in sepsis from severe leptospirosis: a series of ten patients","volume":"2012","author":"Velissaris","year":"2012","journal-title":"Crit Care Res Pract"}],"container-title":["Journal of Veterinary Internal Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jvim.16163","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jvim.16163","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jvim\/article-pdf\/35\/4\/1789\/66652868\/jvim16163.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jvim\/article-pdf\/35\/4\/1789\/66652868\/jvim16163.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T03:30:02Z","timestamp":1770694202000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jvim\/article\/35\/4\/1789\/8447066"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,1]]},"references-count":36,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021,7,1]]}},"URL":"https:\/\/doi.org\/10.1111\/jvim.16163","relation":{},"ISSN":["1939-1676"],"issn-type":[{"value":"1939-1676","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,7]]},"published":{"date-parts":[[2021,7,1]]},"assertion":[{"value":"2020-04-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}