{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T16:31:25Z","timestamp":1792773085780,"version":"4.5.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>Sepsis is a life-threatening organ dysfunction caused by dysregulated host responses to infection. Accessible inflammatory biomarkers may improve early risk stratification for mortality or short-term adverse prognosis in septic patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To systematically evaluate the prognostic associations of four routinely available inflammatory biomarkers (NLR, PLR, PCT, SII) with mortality or short-term adverse prognosis in patients with sepsis and septic shock. Three PROSPERO protocol deviations (CRD420251035190) were documented: the research question, biomarker set, and effect-measure synthesis all changed from the registered protocol.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Ten cohort studies involving 2,412 patients were included. Random-effects meta-analyses were performed, with OR and HR analyzed separately, and continuous and categorical effects synthesized separately.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Two studies reported PCT with endpoint-specific estimates (Wang 2024 mortality OR\u2009=\u20091.957 [1.243\u22123.081]; Li Liang 2024 composite OR\u2009=\u20092.827 [1.694\u20134.718]; not pooled per \u00a72.5). SII showed a significant HR-based association [pooled HR\u2009=\u20091.4112 (1.2568\u20131.5846);\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;lt;\u20090.0001; I\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090.0%; k\u2009=\u20092]. Continuous NLR showed minimal heterogeneity in the primary OR-based synthesis [pooled OR\u2009=\u20091.0146 per unit (1.0098\u20131.0195);\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;lt;\u20090.001; I\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090.0%; k\u2009=\u20092; Ren 2022\u2009+\u2009Song 2025]; the exploratory analysis including the Wang 2024-recalc value yielded OR\u2009=\u20090.9660 [0.9121\u20131.0230]; I\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u200996.3%;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.237. PLR was not significant [pooled OR\u2009=\u20091.7491 (0.9597\u20133.1877);\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.0679; I\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u200995.4%].\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The present meta-analysis does not support strong clinical recommendations. The evidence is hypothesis-generating and should be interpreted with caution due to three major PROSPERO protocol deviations, moderate-to-high risk of bias, small sample sizes for PCT and SII, and substantial heterogeneity for PLR and exploratory NLR. These biomarkers should be interpreted as components of multidimensional risk assessment, not stand-alone prognostic tools.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic Review Registration<\/jats:title>\n                    <jats:p>PROSPERO ID CRD420251035190.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1893289","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:31:49Z","timestamp":1790314309000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Prognostic value of NLR, SII, PCT, and PLR in sepsis and septic shock: a systematic review and meta-analysis"],"prefix":"10.3389","volume":"13","author":[{"given":"Xiangjie","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Emergency, Shandong Provincial Hospital Affiliated to Shandong First Medical University","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Emergency, Shandong Provincial Hospital Affiliated to Shandong First Medical University","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengxia","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Emergency, Shandong Provincial Hospital Affiliated to Shandong First Medical University","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengxia","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Emergency, Shandong Provincial Hospital Affiliated to Shandong First Medical University","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Emergency, Shandong Provincial Hospital Affiliated to Shandong First Medical University","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The third international consensus definitions for sepsis and septic shock (sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"B2","doi-asserted-by":"publisher","first-page":"159","DOI":"10.3238\/arztebl.2016.0159","article-title":"Hospital incidence and mortality rates of sepsis","volume":"113","author":"Fleischmann","year":"2016","journal-title":"Dtsch Arztebl Int"},{"key":"B3","doi-asserted-by":"publisher","first-page":"2235","DOI":"10.1056\/NEJMoa1703058","article-title":"Time to treatment and mortality during mandated emergency care for sepsis","volume":"376","author":"Seymour","year":"2017","journal-title":"N Engl J Med"},{"key":"B4","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/S0140-6736(19)32989-7","article-title":"Global, regional, and national sepsis incidence and mortality, 1990\u20132017","volume":"395","author":"Rudd","year":"2020","journal-title":"Lancet"},{"key":"B5","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1007\/BF01709751","article-title":"The SOFA score to describe organ dysfunction\/failure","volume":"22","author":"Vincent","year":"1996","journal-title":"Intensive Care Med"},{"key":"B6","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1186\/s13054-015-1144-x","article-title":"Reversal of neutrophil-to-lymphocyte count ratio in early versus late death from septic shock","volume":"19","author":"Riche","year":"2015","journal-title":"Crit Care"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1336","DOI":"10.3906\/sag-1901-105","article-title":"Neutrophil to lymphocyte ratio as a predictor of treatment response and mortality in septic shock patients","volume":"49","author":"SARI","year":"2019","journal-title":"Turk J Med Sci"},{"key":"B8","doi-asserted-by":"publisher","first-page":"e084562","DOI":"10.1136\/bmjopen-2024-084562","article-title":"Predictive value of the dynamics of absolute lymphocyte counts for 90-day mortality in ICU sepsis patients","volume":"14","author":"Chen","year":"2024","journal-title":"BMJ Open"},{"key":"B9","doi-asserted-by":"publisher","first-page":"e763","DOI":"10.52225\/narra.v4i2.763","article-title":"Role of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in diagnosing neonatal sepsis","volume":"4","author":"Hasibuan","year":"2024","journal-title":"Narra J"},{"key":"B10","doi-asserted-by":"publisher","first-page":"8","DOI":"10.4103\/tjem.tjem_198_23","article-title":"Clinical significance and prognostic value of NLR, PLR, SII, SIRI, and delta neutrophil index","volume":"24","author":"Islam","year":"2024","journal-title":"Turk J Emerg Med"},{"key":"B11","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1016\/j.diabet.2015.01.001","article-title":"Impact of diabetes on neutrophil-to-lymphocyte ratio and coronary artery disease","volume":"41","author":"Verdoia","year":"2015","journal-title":"Diabetes Metab"},{"key":"B12","doi-asserted-by":"publisher","first-page":"6212","DOI":"10.1158\/1078-0432.CCR-14-0442","article-title":"Systemic immune-inflammation index predicts prognosis after curative resection for hepatocellular carcinoma","volume":"20","author":"Hu","year":"2014","journal-title":"Clin Cancer Res"},{"key":"B13","doi-asserted-by":"publisher","first-page":"e943414","DOI":"10.12659\/MSM.943414","article-title":"Systemic immune-inflammation index as a predictor of short-term mortality risk in sepsis-associated acute kidney injury","volume":"30","author":"Sun","year":"2024","journal-title":"Med Sci Monit"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.17305\/bb.2024.11494","article-title":"Systemic immune-inflammation index and short-term mortality of patients with sepsis: a meta-analysis","volume":"25","author":"Liang","year":"2025","journal-title":"Biomol Biomed"},{"key":"B15","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1177\/09158688211005208","article-title":"Procalcitonin level in the emergency department identifies a high-risk cohort for patients treated for possible sepsis","volume":"28","author":"Lucas","year":"2021","journal-title":"EJIFCC"},{"key":"B16","doi-asserted-by":"publisher","first-page":"584461","DOI":"10.3389\/fnut.2021.584461","article-title":"The PCT to albumin ratio predicts mortality in patients with acute kidney injury caused by abdominal infection-evoked sepsis","volume":"8","author":"Chen","year":"2021","journal-title":"Front Nutr"},{"key":"B17","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1097\/MEJ.0000000000001235","article-title":"Diagnostic performances of procalcitonin and C-reactive protein for sepsis: a systematic review and meta-analysis","volume":"32","author":"Chuang","year":"2025","journal-title":"Eur J Emerg Med"},{"key":"B18","doi-asserted-by":"publisher","first-page":"e357","DOI":"10.1016\/j.jemermed.2024.05.005","article-title":"The combination of systemic immune-inflammation index and serum procalcitonin has high auxiliary predictive value for short-term adverse prognosis in septic shock patients","volume":"67","author":"Liang","year":"2024","journal-title":"J Emerg Med"},{"key":"B19","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/s12890-021-01809-8","article-title":"Risk factor analysis and nomogram for predicting in-hospital mortality in ICU patients with sepsis and lung infection","volume":"22","author":"Ren","year":"2022","journal-title":"BMC Pulm Med"},{"key":"B20","doi-asserted-by":"publisher","first-page":"578","DOI":"10.3760\/cma.j.cn121430-20230703-00486","article-title":"Construction and validation of a nomogram for predicting prognosis of patients with septic shock in emergency medicine","volume":"36","author":"Wang","year":"2024","journal-title":"Zhonghua Wei Zhong Bing Ji Jiu Yi Xue"},{"key":"B21","doi-asserted-by":"publisher","first-page":"106145","DOI":"10.1016\/j.intimp.2019.106145","article-title":"Prognostic value of an inflammatory biomarker-based clinical algorithm in septic patients in the emergency department","volume":"80","author":"Zhao","year":"2020","journal-title":"Int Immunopharmacol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"e022896","DOI":"10.1136\/bmjopen-2018-022896","article-title":"Platelet-to-lymphocyte ratio as a prognostic predictor of mortality for sepsis","volume":"9","author":"Shen","year":"2019","journal-title":"BMJ Open"},{"key":"B23","doi-asserted-by":"publisher","first-page":"3641","DOI":"10.1007\/s10238-023-01029-w","article-title":"Association between admission SII and mortality in critically ill patients with sepsis based on MIMIC-IV","volume":"23","author":"Jiang","year":"2023","journal-title":"Clin Exp Med"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1615\/CritRevImmunol.2024051413","article-title":"The value of SII and T cell subsets in the severity and prognosis of sepsis","volume":"44","author":"Zhou","year":"2024","journal-title":"Crit Rev Immunol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1186\/s12879-024-09516-5","article-title":"NLR, MLR, and PLR associated with 28-day mortality in septic patients with coronary artery disease","volume":"24","author":"Li","year":"2024","journal-title":"BMC Infect Dis"},{"key":"B26","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1186\/s12876-025-04157-7","article-title":"Prognostic value of NLR in septic patients with liver cirrhosis","volume":"25","author":"Song","year":"2025","journal-title":"BMC Gastroenterol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"e44979","DOI":"10.1097\/MD.0000000000044979","article-title":"Prognostic value of serum magnesium and systemic inflammation indices in septic ICU patients aged 85 years and older","volume":"104","author":"Akin Sen","year":"2025","journal-title":"Medicine (Baltimore)"},{"key":"B28","doi-asserted-by":"publisher","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement","volume":"372","author":"Page","year":"2021","journal-title":"Br Med J"},{"key":"B29","doi-asserted-by":"publisher","first-page":"280","DOI":"10.7326\/0003-4819-158-4-201302190-00009","article-title":"Assessing bias in studies of prognostic factors","volume":"158","author":"Hayden","year":"2013","journal-title":"Ann Intern Med"},{"key":"B30","doi-asserted-by":"publisher","first-page":"51","DOI":"10.7326\/M18-1376","article-title":"PROBAST: a tool to assess the risk of bias and applicability of prediction model studies","volume":"170","author":"Wolff","year":"2019","journal-title":"Ann Intern Med"},{"key":"B31","doi-asserted-by":"publisher","first-page":"31","DOI":"10.59556\/japi.73.0791","article-title":"Relationship between procalcitonin, leukocyte count, neutrophil count and NLR in SIRS and sepsis","volume":"73","author":"Zakaria","year":"2025","journal-title":"J Assoc Physicians India"},{"key":"B32","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1186\/s12879-025-10938-y","article-title":"Sepsis-obesity paradox and immune-inflammatory status in elderly and male individuals","volume":"25","author":"Xu","year":"2025","journal-title":"BMC Infect Dis"},{"key":"B33","doi-asserted-by":"publisher","first-page":"755","DOI":"10.3855\/jidc.20063","article-title":"Meta-analysis of CD64, HBP, and PCT in differential diagnosis of sepsis","volume":"19","author":"Xu","year":"2025","journal-title":"J Infect Dev Ctries"},{"key":"B34","doi-asserted-by":"publisher","first-page":"85612","DOI":"10.18632\/oncotarget.20344","article-title":"Predictive value of inflammatory biomarkers for metabolic syndrome and post-PCNL systemic inflammatory response syndrome","volume":"8","author":"Tang","year":"2017","journal-title":"Oncotarget"},{"key":"B35","doi-asserted-by":"publisher","first-page":"2215","DOI":"10.1093\/eurheartj\/ehab158","article-title":"Neutrophil-lymphocyte ratio in immune checkpoint inhibitor-related atherosclerosis","volume":"42","author":"Tang","year":"2021","journal-title":"Eur Heart J"},{"key":"B36","doi-asserted-by":"publisher","first-page":"77","DOI":"10.21037\/tau-20-890","article-title":"Neutrophil-lymphocyte ratio as a diagnostic biomarker for kidney stone prevalence","volume":"10","author":"Zhang","year":"2021","journal-title":"Transl Androl Urol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1186","DOI":"10.1097\/MEG.0000000000001629","article-title":"NLR predicts therapeutic benefit of neoadjuvant TACE in resectable hepatocellular carcinoma","volume":"32","author":"Hong","year":"2020","journal-title":"Eur J Gastroenterol Hepatol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1093\/annonc\/mdu569","article-title":"NLR as a prognostic biomarker in metastatic castration-resistant prostate cancer","volume":"26","author":"van Soest","year":"2015","journal-title":"Ann Oncol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"31738","DOI":"10.1038\/s41598-024-82333-7","article-title":"Nomogram based on NLR and MR diffusion parameters for predicting Ki67 in hepatocellular carcinoma","volume":"14","author":"Wei","year":"2024","journal-title":"Sci Rep"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1999","DOI":"10.1016\/j.juro.2013.06.082","article-title":"Prognostic impact of preoperative NLR in localized nonclear cell renal cell carcinoma","volume":"190","author":"de Martino","year":"2013","journal-title":"J Urol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1","DOI":"10.12968\/hmed.2025.0361","article-title":"Predictive value of neutrophil-to-lymphocyte ratio and systemic immune-inflammation index in the prognosis of sepsis-related acute respiratory distress syndrome","volume":"86","author":"Wen","year":"2025","journal-title":"Br J Hosp Med (Lond)"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1893289\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T14:13:35Z","timestamp":1792764815000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1893289\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,25]]},"references-count":41,"alternative-id":["10.3389\/fmed.2026.1893289"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1893289","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,25]]},"article-number":"1893289"}}