{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T10:30:21Z","timestamp":1788517821781,"version":"build-2803163510"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2019,6,12]],"date-time":"2019-06-12T00:00:00Z","timestamp":1560297600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004348","name":"Stockholm County Council","doi-asserted-by":"publisher","award":["20150016"],"award-info":[{"award-number":["20150016"]}],"id":[{"id":"10.13039\/501100004348","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Swedish Children\u2019s Cancer Foundation","award":["PROF06\/001"],"award-info":[{"award-number":["PROF06\/001"]}]},{"name":"Swedish Children\u2019s Cancer Foundation","award":["PR2015\/005"],"award-info":[{"award-number":["PR2015\/005"]}]},{"DOI":"10.13039\/100012538","name":"Swedish Cancer Foundation","doi-asserted-by":"publisher","award":["CAN 2016\/275"],"award-info":[{"award-number":["CAN 2016\/275"]}],"id":[{"id":"10.13039\/100012538","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,5,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Globally, ~500 000 people with severe dengue (SD) require hospitalization yearly; ~12 500 (2.5%) die. Secondary hemophagocytic lymphohistiocytosis (sHLH) is a potentially fatal hyperinflammatory condition for which HLH-directed therapy (as etoposide and dexamethasone) can be life-saving. Prompted by the high mortality in SD and the increasing awareness that patients with SD may develop sHLH, our objectives were to (1) determine the frequency of dengue-HLH in SD, (2) describe clinical features of dengue-HLH, (3) assess mortality rate in SD and dengue-HLH, and (4) identify mortality-associated risk factors in SD.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A 5-year retrospective single-center study in all adult patients with SD admitted to a tertiary intensive care unit in Malaysia.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Thirty-nine of 180 (22%) patients with SD died. Twenty-one of 180 (12%) had HLH defined as an HLH probability \u226570% according to histo score (HScore); 9 (43%) died. Similarly, 12 of 31 (39%) fulfilling \u22654 and 7 of 9 (78%) fulfilling \u22655 HLH-2004 diagnostic criteria died. Peak values of aspartate aminotransferase (AST), alanine aminotransferase, lactate dehydrogenase, and creatinine correlated to fatality (odds ratios [ORs], 2.9, 3.4, 5.8, and 31.9; all P &amp;lt; .0001), as did peak ferritin (OR, 2.5; P = .0028), nadir platelets (OR, 1.9; P = .00068), hepatomegaly (OR, 2.9; P = .012), and increasing age (OR, 1.2; P = .0043). Multivariable logistic regression revealed peak AST (OR, 2.8; P = .0019), peak creatinine (OR, 7.3; P = .0065), and SOFA (Sequential Organ Failure Assessment) score (OR, 1.4; P = .0051) as independent risk factors of death.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Be observant of dengue-HLH due to its high mortality. A prospective study is suggested on prompt HLH-directed therapy in SD patients with hyperinflammation and evolving multiorgan failure at risk of developing dengue-HLH.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciz499","type":"journal-article","created":{"date-parts":[[2019,6,11]],"date-time":"2019-06-11T11:09:25Z","timestamp":1560251365000},"page":"2247-2255","source":"Crossref","is-referenced-by-count":60,"title":["Dengue Infection Complicated by Hemophagocytic Lymphohistiocytosis: Experiences From 180 Patients With Severe Dengue"],"prefix":"10.1093","volume":"70","author":[{"given":"Foong Kee","family":"Kan","sequence":"first","affiliation":[{"name":"Department of Medicine, Hospital Sultanah Aminah, Johor Bahru, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng Cheng","family":"Tan","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Intensive Care, Hospital Sultanah Aminah, Johor Bahru, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Von Bahr Greenwood","sequence":"first","affiliation":[{"name":"Childhood Cancer Research Unit, Department of Women\u2019s and Children\u2019s Health, Karolinska Institute"},{"name":"Theme of Children\u2019s and Women\u2019s Health, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khairil E","family":"Khalid","sequence":"first","affiliation":[{"name":"Department of Medicine, Hospital Sultanah Aminah, Johor Bahru, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Premaa","family":"Supramaniam","sequence":"first","affiliation":[{"name":"Clinical Research Centre, Hospital Sultanah Aminah, Johor Bahru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida","family":"Hed Myrberg","sequence":"first","affiliation":[{"name":"Childhood Cancer Research Unit, Department of Women\u2019s and Children\u2019s Health, Karolinska Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lian Huat","family":"Tan","sequence":"first","affiliation":[{"name":"Sunway Medical Centre, Petaling Jaya, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan-Inge","family":"Henter","sequence":"first","affiliation":[{"name":"Childhood Cancer Research Unit, Department of Women\u2019s and Children\u2019s Health, Karolinska Institute"},{"name":"Theme of Children\u2019s and Women\u2019s Health, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,6,12]]},"reference":[{"key":"2020052309495063500_CIT0001","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1038\/nature12060","article-title":"The global distribution and burden of dengue","volume":"496","author":"Bhatt","year":"2013","journal-title":"Nature"},{"key":"2020052309495063500_CIT0002","author":"World Health Organization"},{"key":"2020052309495063500_CIT0003","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1007\/s00431-006-0258-1","article-title":"Familial and acquired hemophagocytic lymphohistiocytosis","volume":"166","author":"Janka","year":"2007","journal-title":"Eur J Pediatr"},{"key":"2020052309495063500_CIT0004","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1016\/S0140-6736(13)61048-X","article-title":"Adult haemophagocytic syndrome","volume":"383","author":"Ramos-Casals","year":"2014","journal-title":"Lancet"},{"key":"2020052309495063500_CIT0005","doi-asserted-by":"crossref","first-page":"4577","DOI":"10.1182\/blood-2011-06-356261","article-title":"Chemoimmunotherapy for hemophagocytic lymphohistiocytosis: long-term results of the HLH-94 treatment protocol","volume":"118","author":"Trottestam","year":"2011","journal-title":"Blood"},{"key":"2020052309495063500_CIT0006","doi-asserted-by":"crossref","first-page":"2728","DOI":"10.1182\/blood-2017-06-788349","article-title":"Confirmed efficacy of etoposide and dexamethasone in HLH treatment: long term results of the cooperative HLH-2004 study","volume":"130","author":"Bergsten","year":"2017","journal-title":"Blood"},{"key":"2020052309495063500_CIT0007","first-page":"1869","article-title":"Effective control of Epstein-Barr virus-related hemophagocytic lymphohistiocytosis with immunochemotherapy. 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