{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T16:11:04Z","timestamp":1778602264008,"version":"3.51.4"},"reference-count":32,"publisher":"Walter de Gruyter GmbH","issue":"3","license":[{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100021914","name":"Grand Challenges in Global Health","doi-asserted-by":"publisher","award":["GCE-India\/R5\/2019\/007"],"award-info":[{"award-number":["GCE-India\/R5\/2019\/007"]}],"id":[{"id":"10.13039\/100021914","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_jpm-2025-0342_abs_001\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To evaluate diagnostic accuracy of urinary immune biomarkers (IBM) for late-onset sepsis (LOS) in very preterm infants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jpm-2025-0342_abs_002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This multicenter, prospective diagnostic accuracy study, included preterm infants\u00a0&lt;32\u00a0weeks of gestation and birth weight\u00a0&lt;1,500\u202fg, needing evaluation for suspected LOS. Urine samples obtained concurrent to blood culture and sepsis screen were evaluated for interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) levels using enzyme immunoassay. Positive blood and\/or CSF culture served as reference standards. Receiver operating characteristic curves were used to evaluate performance of urinary IBM for detection of LOS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jpm-2025-0342_abs_003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>During September 2021\u2013September 2023, we evaluated 136 preterm, very low birth weight infants (mean gestational age: 28.2\u00a0weeks, mean birth weight: 933\u202fg) for sepsis after 72\u202fh of postnatal age and prior to 37\u00a0weeks postmenstrual age. Twenty four infants had culture-positive sepsis. Median IL-8 and MCP-1 levels in neonates with LOS were 86.5\u202fpg\/mL and 230.2\u202fpg\/mL and those in non-infected neonates were 66.5\u202fpg\/mL and 212.1\u202fpg\/mL. Urinary IL-8 had sensitivity and specificity of 42 and 51\u202f% [AUC: 0.46 (0.35\u20130.57)] and urinary MCP-1 had sensitivity and specificity of 46 and 53\u202f% [AUC: 0.49 (0.38\u20130.60)] for detection of LOS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jpm-2025-0342_abs_004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Urinary IL-8 and MCP-1 had low sensitivity and specificity for diagnosis of LOS in very preterm infants. These findings underscore the need to establish reference ranges for urinary IBM in preterm neonates.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/jpm-2025-0342","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T02:59:48Z","timestamp":1759805988000},"page":"630-636","source":"Crossref","is-referenced-by-count":0,"title":["Urinary immune biomarkers for late-onset sepsis in preterm very low birth weight neonates\u00a0\u2013 a diagnostic accuracy study"],"prefix":"10.1515","volume":"54","author":[{"given":"Gayatri","family":"Morajker","sequence":"first","affiliation":[{"name":"Department of Neonatology , Surya Hospital , Mumbai , Maharashtra , India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashwini Ankush","family":"Patil","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Technology , Institute of Chemical Technology , Mumbai , Maharashtra , India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prashanth","family":"Ranya Raghavendra","sequence":"additional","affiliation":[{"name":"Department of Neonatology , Seth GS Medical College and KEM Hospital , Mumbai , Maharashtra , India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anuja","family":"Datar","sequence":"additional","affiliation":[{"name":"Department of Neonatology , Surya Hospital , Mumbai , Maharashtra , India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sruthi","family":"Nair","sequence":"additional","affiliation":[{"name":"Department of Neonatology , Seth GS Medical College and KEM Hospital , Mumbai , Maharashtra , India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prajakta","family":"Dandekar Jain","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Technology , Institute of Chemical Technology , Mumbai , Maharashtra , India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haribalakrishna","family":"Balasubramanian","sequence":"additional","affiliation":[{"name":"Department of Neonatology , Surya Hospital , Mumbai , Maharashtra , India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anitha","family":"Haribalakrishna","sequence":"additional","affiliation":[{"name":"Department of Neonatology , Seth GS Medical College and KEM Hospital , Mumbai , Maharashtra , India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Medha","family":"Goyal","sequence":"additional","affiliation":[{"name":"Department of Neonatology , Seth GS Medical College and KEM Hospital , Mumbai , Maharashtra , India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nandkishor S.","family":"Kabra","sequence":"additional","affiliation":[{"name":"Department of Neonatology , Surya Hospital , Mumbai , Maharashtra , India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2025,10,7]]},"reference":[{"key":"2026051215133583363_j_jpm-2025-0342_ref_001","doi-asserted-by":"crossref","unstructured":"Hornik, CP, Fort, P, Clark, RH, Watt, K, Benjamin, DK, Smith, PB, et al.. 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J Infect Dis 1999;180:904\u20137. https:\/\/doi.org\/10.1086\/314960.","DOI":"10.1086\/314960"},{"key":"2026051215133583363_j_jpm-2025-0342_ref_025","unstructured":"Miklaszewska, M, Korohodai, P, Kwinta, P, Tomasik, T, Zachwieja, K, Klich, B, et al.. Clinical validity of urinary interleukin 18 and interleukin 6 determinations in preterm newborns. Przegl Lek 2015;72:589\u201396."},{"key":"2026051215133583363_j_jpm-2025-0342_ref_026","doi-asserted-by":"crossref","unstructured":"Krzemie\u0144, G, Szmigielska, A, Turczyn, A, Pa\u0144czyk-Tomaszewska, M. Urine interleukin-6, interleukin-8 and transforming growth factor \u03b21 in infants with urinary tract infection and asymptomatic bacteriuria. Cent Eur J Immunol 2016;41:260\u20137. https:\/\/doi.org\/10.5114\/ceji.2016.63125.","DOI":"10.5114\/ceji.2016.63125"},{"key":"2026051215133583363_j_jpm-2025-0342_ref_027","doi-asserted-by":"crossref","unstructured":"Bentlin, MR, de Souza Rugolo, LMS, J\u00fanior, AR, Hashimoto, M, Lyra, JC. 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