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The aims were to evaluate the differences between pediatric patients with MIS-C and sepsis and to develop a score to distinguish both entities. This was a retrospective study that compared demographic, clinical, diagnostic, and therapeutic data of pediatric patients with MIS-C (cohort 2020\u20132022) and sepsis (cohorts 2010\u20132014 and 2017\u20132018) admitted to a Pediatric Intensive Care Unit (PICU) of a tertiary care hospital. A diagnostic score was developed with variables that differentiated the two conditions. Twenty-nine patients with MIS-C were identified, who were matched 1:3 with patients with sepsis (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200987). Patients with MIS-C were older (10 vs. 4\u00a0years old), and the majority were male (69%). Clinical characteristics that demonstrated differences were prolonged fever and signs and symptoms affecting skin-mucosa and gastrointestinal system. Leukocytes, PCT, and ferritin were higher in sepsis, while thrombocytopenia, lymphopenia, and elevated fibrinogen and adrenomedullin (biomarker with a role for the detection of invasive infections) were more frequent in MIS-C. MIS-C patients presented greater myocardial dysfunction (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). Five criteria were selected and included in the MISSEP score after fitting them into a multivariate logistic regression model: fever\u2009&gt;\u200948\u00a0hours (20 points), thrombocytopenia\u2009&lt;\u2009150\u2009\u00d7\u200910\n                    <jats:sup>3<\/jats:sup>\n                    \/\u00b5L (6 points), abdominal pain (15 points), conjunctival erythema (11 points), and Vasoactive Inotropic Score (VIS)\u2009&gt;\u200910 (7 points). The cutoff\u2009&gt;\u200925 points allowed to discriminate MIS-C from sepsis with a sensitivity of 0.89 and specificity of 0.95.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:italic>\u00a0 \u00a0 \u00a0Conclusion<\/jats:italic>\n                    : MIS-C phenotype overlaps with sepsis. MISSEP score could be useful to distinguish between both entities and direct specific treatment.\n                    <jats:table-wrap>\n                      <jats:table>\n                        <jats:tbody>\n                          <jats:tr>\n                            <jats:td colspan=\"2\">\n                              <jats:bold>What is Known:<\/jats:bold>\n                              <jats:italic>\u2022 Differential diagnosis between Multisystem Inflammatory Syndrome in Children (MIS-C) and other causes of systemic inflammatory response such as sepsis is complex.<\/jats:italic>\n                              <jats:italic>\u2022 It is essential to establish an accurate initial diagnosis and early specific treatment in both cases of MIS-C and sepsis to improve the prognosis of these patients.<\/jats:italic>\n                            <\/jats:td>\n                          <\/jats:tr>\n                          <jats:tr>\n                            <jats:td colspan=\"2\">\n                              <jats:bold>What is New:<\/jats:bold>\n                              <jats:italic>\u2022 Patients with MIS-C are older and have characteristic symptoms of prolonged fever, gastrointestinal symptoms, skin-mucosal involvement, and greater myocardial dysfunction, compared to patients with sepsis.<\/jats:italic>\n                              <jats:italic>\u2022 The use of diagnostic scores, such as the MISSEP score, can be very useful to distinguish between the two entities and help direct specific treatment.<\/jats:italic>\n                            <\/jats:td>\n                          <\/jats:tr>\n                        <\/jats:tbody>\n                      <\/jats:table>\n                    <\/jats:table-wrap>\n                  <\/jats:p>","DOI":"10.1007\/s00431-023-05168-w","type":"journal-article","created":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T00:01:41Z","timestamp":1694044901000},"page":"5109-5118","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Multisystem inflammatory syndrome in children (MIS-C) and sepsis differentiation by a clinical and analytical score: MISSEP score"],"prefix":"10.1007","volume":"182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0938-2554","authenticated-orcid":false,"given":"Mar\u00eda","family":"Hern\u00e1ndez-Garc\u00eda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elies","family":"Roldan-Berengue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9127-5939","authenticated-orcid":false,"given":"Carmina","family":"Guitart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2752-7481","authenticated-orcid":false,"given":"M\u00f2nica","family":"Girona-Alarc\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7419-8158","authenticated-orcid":false,"given":"Guillermo","family":"Arg\u00fcello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9939-7383","authenticated-orcid":false,"given":"Rosa","family":"Pino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3104-675X","authenticated-orcid":false,"given":"Mariona","family":"F. de Sevilla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3483-528X","authenticated-orcid":false,"given":"Juan Jos\u00e9","family":"Garc\u00eda-Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2041-4425","authenticated-orcid":false,"given":"Iolanda","family":"Jordan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,9,7]]},"reference":[{"issue":"7","key":"5168_CR1","doi-asserted-by":"publisher","first-page":"2019","DOI":"10.1007\/s00431-021-03993-5","volume":"180","author":"L Hoste","year":"2021","unstructured":"Hoste L, Van Paemel R, Haerynck F (2021) Multisystem inflammatory syndrome in children related to COVID-19: a systematic review. 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