{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T15:30:47Z","timestamp":1787671847855,"version":"build-2736575974"},"reference-count":41,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008460","name":"National Center for Complementary and Integrative Health","doi-asserted-by":"publisher","award":["K24 AT009893"],"award-info":[{"award-number":["K24 AT009893"]}],"id":[{"id":"10.13039\/100008460","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000038","name":"U.S. Food and Drug Administration","doi-asserted-by":"publisher","award":["R01FD004814\u201001A2"],"award-info":[{"award-number":["R01FD004814\u201001A2"]}],"id":[{"id":"10.13039\/100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["K23HL173694"],"award-info":[{"award-number":["K23HL173694"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["1K23HL140142"],"award-info":[{"award-number":["1K23HL140142"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["1K23HL140142\u201003S1"],"award-info":[{"award-number":["1K23HL140142\u201003S1"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp;amp; Cancer"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Secretory phospholipase A\n                      <jats:sub>2<\/jats:sub>\n                      (sPLA\n                      <jats:sub>2<\/jats:sub>\n                      ) is an inflammatory mediator linked to acute chest syndrome (ACS) in sickle cell disease (SCD), a serious complication that can develop during an acute vaso\u2010occlusive pain episode (VOE). Plasma sPLA\n                      <jats:sub>2<\/jats:sub>\n                      levels have been proposed as a potential biomarker for predicting ACS onset.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To assess serial plasma sPLA\n                      <jats:sub>2<\/jats:sub>\n                      levels in 105 pediatric patients hospitalized for SCD\u2010VOE and determine the effects of arginine therapy compared to placebo.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Procedures<\/jats:title>\n                    <jats:p>\n                      This is a pharmacokinetics\/pharmacodynamics and randomized controlled trial of intravenous arginine therapy. Statistical methods included\n                      <jats:italic>t<\/jats:italic>\n                      \u2010tests, chi\u2010square, and correlation analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Mean age was 12.7 \u00b1 3.7 years, 48% were male, 67% had Hb\u2010SS, and 70% were prescribed hydroxyurea. Using a previously established SCD\u2010specific cutoff of 48\u00a0ng\/mL, presenting sPLA\n                      <jats:sub>2<\/jats:sub>\n                      levels were elevated in 33% of patients (mean sPLA\n                      <jats:sub>2<\/jats:sub>\n                      level 85.7 \u00b1 32.9\u00a0ng\/mL). SPLA\n                      <jats:sub>2<\/jats:sub>\n                      elevation in the emergency department was more common in patients with ACS compared to those without ACS (64%\u00a0vs. 30%;\n                      <jats:italic>p<\/jats:italic>\n                      = 0.02; negative predictive value of 94%). Peak sPLA\n                      <jats:sub>2<\/jats:sub>\n                      levels were significantly higher in febrile (\n                      <jats:italic>n<\/jats:italic>\n                      = 34) versus afebrile patients (\n                      <jats:italic>n<\/jats:italic>\n                      = 71;101.0 \u00b1 45.3 vs. 48.7 \u00b1 35.4\u00a0ng\/mL;\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.0001). Among subjects with elevated baseline sPLA\n                      <jats:sub>2<\/jats:sub>\n                      , arginine therapy resulted in a significant reduction in sPLA\n                      <jats:sub>2<\/jats:sub>\n                      levels by discharge compared to placebo (\u221227.8 \u00b1 38.1\u00a0ng\/mL;\n                      <jats:italic>p<\/jats:italic>\n                      = 0.002;\n                      <jats:italic>n<\/jats:italic>\n                      = 23\u00a0vs. \u221215.0 \u00b1 41.2\u00a0ng\/mL;\n                      <jats:italic>p<\/jats:italic>\n                      = 0.23;\n                      <jats:italic>n<\/jats:italic>\n                      = 12).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      SPLA\n                      <jats:sub>2<\/jats:sub>\n                      is an underutilized biomarker of ACS given accumulating evidence of its role. In particular, low levels may identify patients at low risk for ACS. Arginine therapy may modulate inflammation in patients with SCD during VOE and\/or ACS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>ClinicalTrials.gov identifiers: NCT02447874; NCT02536170<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/1545-5017.70615","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T13:21:22Z","timestamp":1785849682000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Secretory Phospholipase A\n                    <sub>2<\/sub>\n                    in Patients With Sickle Cell Disease Hospitalized for Vaso\u2010Occlusive Pain Episodes"],"prefix":"10.1002","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9780-9589","authenticated-orcid":false,"given":"Rawan","family":"Korman","sequence":"first","affiliation":[{"name":"Department of Pediatrics Emory University School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Yasmine","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Emory University School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6685-2902","authenticated-orcid":false,"given":"Dunia","family":"Hatabah","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Emory University School of Medicine  Atlanta Georgia 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