{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T03:07:24Z","timestamp":1790996844915,"version":"4.1.0"},"reference-count":20,"publisher":"BMJ","issue":"8","license":[{"start":{"date-parts":[[2021,8,8]],"date-time":"2021-08-08T00:00:00Z","timestamp":1628380800000},"content-version":"unspecified","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"National Institutes of Health\/Center for Research Resources, Colorado Clinical Translational Science Institute","award":["UL1 RR025780"],"award-info":[{"award-number":["UL1 RR025780"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2021,7,26]]},"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      It is widely assumed that\n                      <jats:bold>s<\/jats:bold>\n                      epsis is a life-threatening systemic inflammation caused by a dysregulated host response to infection mediated by an increase in multiple proinflammatory cytokines. The levels of key proinflammatory cytokines tumour necrosis factor, interleukin-1\u03b2 and interferon \u03b3 are poorly characterised during sepsis. We believe this project will produce a \u2018gold-standard\u2019 document to which other reports on cytokine levels will be compared. The objective of this systematic review will be to identify key cytokine circulating levels in patients with sepsis and assess the association between these levels and morbidity and mortality outcomes related to sepsis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>We would include reports of any design except for case reports. Sepsis patients will comprise those with a diagnosis of sepsis, severe sepsis or septic shock. The primary exposure is levels of three proinflammatory cytokines. The primary outcome is mortality at 28 or 30 days. Study subjects can be of any age, sex or ethnicity. Studies will be restricted to the English language. Medline, Embase, Cochrane Library and Web of Science Core Collection will be searched for eligible studies. A database search will include studies from 1985 to May 2020. Two reviewers will independently screen and select studies, assess methodological quality and extract data. A meta-analysis will be performed, if possible, and the Grading of Recommendations Assessment Development and Evaluation Summary of Findings presented.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>Formal ethical approval is not required as data will be extracted from existing literature. This systematic review will be disseminated through a peer-reviewed publication and at conference meetings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PROSPERO registration number<\/jats:title>\n                    <jats:p>CRD42020179800.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2020-048476","type":"journal-article","created":{"date-parts":[[2021,8,9]],"date-time":"2021-08-09T14:17:44Z","timestamp":1628518664000},"page":"e048476","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":25,"title":["Association between cytokine levels, sepsis severity and clinical outcomes in sepsis: a quantitative systematic review protocol"],"prefix":"10.1136","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6175-299X","authenticated-orcid":false,"given":"Amal","family":"Gharamti","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, American University of Beirut, Beirut, Lebanon"},{"name":"Yale School of Medicine, Department of Internal Medicine, Waterbury Hospital, Waterbury, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Samara","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Monzon","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sias","family":"Scherger","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen","family":"DeSanto","sequence":"additional","affiliation":[{"name":"Health Sciences Library, University of Colorado Denver, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Sillau","sequence":"additional","affiliation":[{"name":"Neurolgy, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8757-643X","authenticated-orcid":false,"given":"Carlos","family":"Franco-Paredes","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA"},{"name":"Department of Medicine, Hospital Infantil de M\u00e9xico Federico Gomez, Mexico City, Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7363-8652","authenticated-orcid":false,"given":"Andr\u00e9s","family":"Henao-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1392-3475","authenticated-orcid":false,"given":"Leland","family":"Shapiro","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA"},{"name":"Department of Medicine, Rocky Mountain Regional VA Medical Center, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2021,8,9]]},"reference":[{"key":"2025121411374003000_11.8.e048476.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32989-7"},{"key":"2025121411374003000_11.8.e048476.2","unstructured":"Torio C , Moore B . 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