{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T18:46:19Z","timestamp":1777056379821,"version":"3.51.4"},"update-to":[{"DOI":"10.1371\/journal.pntd.0014247","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000}}],"reference-count":30,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Science and Technology Plan of Hainan Province","award":["LCYX202306"],"award-info":[{"award-number":["LCYX202306"]}]},{"name":"Science and Technology Plan of Hainan Province","award":["LCYX202408"],"award-info":[{"award-number":["LCYX202408"]}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20241982"],"award-info":[{"award-number":["BK20241982"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]},{"name":"grants from the Hainan Province Clinical Medical Center"}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To develop and validate a model for early risk stratification of secondary hemophagocytic lymphohistiocytosis (HLH) in patients with severe fever with thrombocytopenia syndrome (SFTS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective cohort included adults with laboratory-confirmed SFTS admitted to The First Affiliated Hospital with Nanjing Medical University between January 2019 and July 2024. Predictor variables were derived from clinical and laboratory data obtained within 3 days after virologic confirmation, corresponding to the predefined early-evaluation window of the study. HLH status (binary outcome) was defined using the entire-course HScore (\u2265170), calculated from the worst available values over the clinical course; HLH-2004 criteria and early-window HScore distributions were summarized descriptively to provide transparent outcome accounting. Twenty-eight candidate predictors entered LASSO with Boruta refinement, and retained variables were used to construct a multivariable logistic model and nomogram. Model performance was evaluated by discrimination, calibration, and decision-curve analysis in the derivation cohort, an internal validation set, and an external cohort of 60 patients from The First Affiliated Hospital with Anhui Medical University.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 249 patients (152 non-HLH, 97 HLH), HLH was associated with higher peak temperature, longer fever, more lymphadenopathy\/splenomegaly and neurological symptoms, and more severe thrombocytopenia, hypertriglyceridemia, hypofibrinogenemia, hyperferritinemia, higher viral load, elevated muscle\/liver enzymes and LDH, and coagulopathy (all p\u2009&lt;\u20090.05). LASSO\u2013Boruta identified six routinely available predictors\u2014peak temperature, splenomegaly, fever duration, triglycerides, fibrinogen, and ferritin. The model showed LR \u03c7\u00b2\u2009=\u2009214.82 (p\u2009&lt;\u20090.0001), R\u00b2\u2009=\u20090.784, C-index\u2009=\u20090.962, Dxy\u2009=\u20090.923, with near-perfect calibration in derivation. In internal validation, discrimination remained near-perfect (AUC 0.997, 95% CI 0.989\u20131.000); mild miscalibration was corrected by intercept-and-slope recalibration, and decision curves showed net benefit across wide thresholds. External validation (n\u2009=\u200960) confirmed excellent discrimination (AUC 0.907, 95% CI 0.835\u20130.980), slight miscalibration resolved by recalibration, and preserved net benefit across most thresholds.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>A simple model based on early clinical and laboratory variables supports risk stratification for HLH in SFTS and may facilitate closer monitoring, repeated HLH assessment, and timely individualized management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pntd.0014247","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T17:45:02Z","timestamp":1776447902000},"page":"e0014247","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Development and validation of an early 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