{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T22:37:43Z","timestamp":1777675063356,"version":"3.51.4"},"reference-count":43,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objectives: Early recognition of septic shock among patients with sepsis remains clinically important, particularly in settings where risk stratification relies on routinely available indicators. This study aimed to identify patient-related factors associated with septic shock, with particular emphasis on comorbidities, and to examine early changes in selected inflammatory markers during the first 72 h after diagnosis. Methods: This study included 106 intensive care patients diagnosed with sepsis or septic shock according to Sepsis-3 criteria. Baseline demographic, clinical, and laboratory characteristics were compared between groups using univariate tests. Candidate predictors were then evaluated using a LASSO-assisted logistic regression model. Longitudinal changes in inflammatory markers were analyzed using linear mixed-effects models. Results: Among baseline inflammatory markers, only procalcitonin was significantly higher in patients with septic shock than in those with sepsis. In the final logistic regression model, higher procalcitonin levels were associated with greater odds of septic shock, whereas gastrointestinal comorbidity was associated with lower odds. Patients older than 75 years also had significantly higher odds of septic shock. The model showed satisfactory discrimination (AUC = 0.795). During the first 72 h, only neutrophil percentage demonstrated a significantly different temporal pattern between groups. Conclusions: Early recognition of septic shock may benefit from combining routine biomarkers with patient-related clinical characteristics rather than relying on isolated laboratory measurements alone. Procalcitonin, older age, gastrointestinal comorbidity, and early neutrophil dynamics emerged as the most informative signals, although these findings require validation in larger multicenter cohorts.<\/jats:p>","DOI":"10.3390\/diagnostics16091334","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T07:43:51Z","timestamp":1777448631000},"page":"1334","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comorbidities, Routine Biomarkers and Early Septic Shock Occurrence in Patients with Sepsis: A Retrospective Longitudinal Study"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2634-9342","authenticated-orcid":false,"given":"Jasna","family":"Petrovi\u0107","sequence":"first","affiliation":[{"name":"Centar Valjevo, University Singidunum, Danijelova 23, 11000 Belgrade, Serbia"},{"name":"Intensive Care Unit, Department of Anesthesia, General Hospital \u201cValjevo\u201d, Obrena Nikoli\u0107a 5, 14000 Valjevo, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/S0140-6736(19)32989-7","article-title":"Global, Regional, and National Sepsis Incidence and Mortality, 1990\u20132017: Analysis for the Global Burden of Disease Study","volume":"395","author":"Rudd","year":"2020","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","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":"ref_3","doi-asserted-by":"crossref","first-page":"1644","DOI":"10.1378\/chest.101.6.1644","article-title":"Definitions for Sepsis and Organ Failure and Guidelines for the Use of Innovative Therapies in Sepsis","volume":"101","author":"Bone","year":"1992","journal-title":"Chest"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1097\/01.CCM.0000050454.01978.3B","article-title":"2001 SCCM\/ESICM\/ACCP\/ATS\/SIS International Sepsis Definitions Conference","volume":"31","author":"Levy","year":"2003","journal-title":"Crit. Care Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1001\/jama.2016.0289","article-title":"Developing a New Definition and Assessing New Clinical Criteria for Septic Shock: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)","volume":"315","author":"Phillips","year":"2016","journal-title":"JAMA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e31895","DOI":"10.1097\/MD.0000000000031895","article-title":"Clinical Usefulness of Biomarkers for Diagnosis and Prediction of Prognosis in Sepsis and Septic Shock","volume":"101","author":"Lee","year":"2022","journal-title":"Medicine"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1186\/s13054-020-02993-5","article-title":"Biomarkers of Sepsis: Time for a Reappraisal","volume":"24","author":"Pierrakos","year":"2020","journal-title":"Crit. Care"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Hung, S.K., Lan, H.M., Han, S.T., Wu, C.C., and Chen, K.F. (2020). Current Evidence and Limitation of Biomarkers for Detecting Sepsis and Systemic Infection. Biomedicines, 8.","DOI":"10.3390\/biomedicines8110494"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Spoto, S., Lupoi, D.M., Valeriani, E., Fogolari, M., Locorriere, L., Beretta Anguissola, G., Battifoglia, G., Caputo, D., Coppola, A., and Costantino, S. (2021). Diagnostic Accuracy and Prognostic Value of Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios in Septic Patients Outside the Intensive Care Unit. Medicina, 57.","DOI":"10.3390\/medicina57080811"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1007\/s11845-023-03385-8","article-title":"C-Reactive Protein and Procalcitonin during Course of Sepsis and Septic Shock","volume":"193","author":"Schupp","year":"2024","journal-title":"Ir. J. Med. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"912","DOI":"10.7754\/Clin.Lab.2022.220812","article-title":"The Neutrophil-to-Lymphocyte-Ratio as Diagnostic and Prognostic Tool in Sepsis and Septic Shock","volume":"69","author":"Schupp","year":"2023","journal-title":"Clin. Lab."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1177\/0300060518822404","article-title":"Prognostic Significance of PCT and CRP Evaluation for Adult ICU Patients with Sepsis and Septic Shock: Retrospective Analysis of 59 Cases","volume":"47","author":"Cui","year":"2019","journal-title":"J. Int. Med. Res."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Kang, C., Choi, S., Jang, E.J., Joo, S., Jeong, J.H., Oh, S.Y., Ryu, H.G., and Lee, H. (2024). Prevalence and Outcomes of Chronic Comorbid Conditions in Patients with Sepsis in Korea: A Nationwide Cohort Study from 2011 to 2016. BMC Infect. Dis., 24.","DOI":"10.1186\/s12879-024-09081-x"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2576","DOI":"10.1097\/01.CCM.0000239114.50519.0E","article-title":"The Role of Infection and Comorbidity: Factors That Influence Disparities in Sepsis","volume":"34","author":"Esper","year":"2006","journal-title":"Crit. Care Med."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Le\u00f3n, A.L., Hoyos, N.A., Barrera, L.I., De La Rosa, G., Dennis, R., Due\u00f1as, C., Granados, M., Londo\u00f1o, D., Rodr\u00edguez, F.A., and Molina, F.J. (2013). Clinical Course of Sepsis, Severe Sepsis, and Septic Shock in a Cohort of Infected Patients from Ten Colombian Hospitals. BMC Infect. Dis., 13.","DOI":"10.1186\/1471-2334-13-345"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Oliveira, A.M., Oliveira, A., Vidal, R., and Gon\u00e7alves-Pereira, J. (2024). Infectious Foci, Comorbidities and Its Influence on the Outcomes of Septic Critically Ill Patients. Microorganisms, 12.","DOI":"10.3390\/microorganisms12081705"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"456","DOI":"10.3390\/epidemiologia5030032","article-title":"The Global Burden of Sepsis and Septic Shock","volume":"5","author":"Sangiorgio","year":"2024","journal-title":"Epidemiologia"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Wu, H., Cao, T., Ji, T., Luo, Y., Huang, J., and Ma, K. (2024). Predictive Value of the Neutrophil-to-Lymphocyte Ratio in the Prognosis and Risk of Death for Adult Sepsis Patients: A Meta-Analysis. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1336456"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Ljungstr\u00f6m, L., Pernestig, A.K., Jacobsson, G., Andersson, R., Usener, B., and Tilevik, D. (2017). Diagnostic Accuracy of Procalcitonin, Neutrophil-Lymphocyte Count Ratio, C-Reactive Protein, and Lactate in Patients with Suspected Bacterial Sepsis. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0181704"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Agnello, L., Giglio, R.V., Bivona, G., Scazzone, C., Gambino, C.M., Iacona, A., Ciaccio, A.M., Lo Sasso, B., and Ciaccio, M. (2021). The Value of a Complete Blood Count (CBC) for Sepsis Diagnosis and Prognosis. Diagnostics, 11.","DOI":"10.3390\/diagnostics11101881"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5852","DOI":"10.1002\/jcb.27870","article-title":"The Diagnostic Accuracy of Procalcitonin and C-Reactive Protein for Sepsis: A Systematic Review and Meta-Analysis","volume":"120","author":"Tan","year":"2019","journal-title":"J. Cell. Biochem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/S1473-3099(12)70323-7","article-title":"Procalcitonin as a Diagnostic Marker for Sepsis: A Systematic Review and Meta-Analysis","volume":"13","author":"Wacker","year":"2013","journal-title":"Lancet Infect. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Agnello, L., and Ciaccio, M. (2023). Biomarkers of Sepsis. Diagnostics, 13.","DOI":"10.3390\/diagnostics13030435"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1089\/sur.2017.307","article-title":"Procalcitonin: Usefulness in Acute Care Surgery and Trauma","volume":"19","author":"Parli","year":"2018","journal-title":"Surg. Infect."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s13613-023-01233-7","article-title":"The Critically Ill Older Patient with Sepsis: A Narrative Review","volume":"14","author":"Ibarz","year":"2024","journal-title":"Ann. Intensive Care"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Mart\u00edn, S., P\u00e9rez, A., and Aldecoa, C. (2017). Sepsis and Immunosenescence in the Elderly Patient: A Review. Front. Med., 4.","DOI":"10.3389\/fmed.2017.00020"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1111\/imr.12499","article-title":"The Immune System\u2019s Role in Sepsis Progression, Resolution, and Long-Term Outcome","volume":"274","author":"Delano","year":"2016","journal-title":"Immunol. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.molmed.2013.08.004","article-title":"Redefining the Gut as the Motor of Critical Illness","volume":"20","author":"Mittal","year":"2014","journal-title":"Trends Mol. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/S2468-1253(16)30119-4","article-title":"The Role of the Gut Microbiota in Sepsis","volume":"2","author":"Haak","year":"2017","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"S264","DOI":"10.1093\/infdis\/jiaa682","article-title":"Sepsis and the Microbiome: A Vicious Cycle","volume":"223","author":"Miller","year":"2021","journal-title":"J. Infect. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"L\u00f3pez-Collazo, E., and del Fresno, C. (2024). Endotoxin Tolerance and Trained Immunity: Breaking down Immunological Memory Barriers. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1393283"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1126\/science.aaf1098","article-title":"Trained Immunity: A Program of Innate Immune Memory in Health and Disease","volume":"352","author":"Netea","year":"2016","journal-title":"Science"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1016\/j.cell.2019.07.033","article-title":"GDF15 Is an Inflammation-Induced Central Mediator of Tissue Tolerance","volume":"178","author":"Luan","year":"2019","journal-title":"Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s13098-022-00803-2","article-title":"Impact of Diabetes Mellitus on Outcomes of Patients with Sepsis: An Updated Systematic Review and Meta-Analysis","volume":"14","author":"Jiang","year":"2022","journal-title":"Diabetol. Metab. Syndr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1007\/s00592-021-01728-4","article-title":"Type 2 Diabetes Mellitus and Sepsis: State of the Art, Certainties and Missing Evidence","volume":"58","author":"Costantini","year":"2021","journal-title":"Acta Diabetol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e8371","DOI":"10.1097\/MD.0000000000008371","article-title":"Factors Associated with Severe Sepsis or Septic Shock in Complicated Pyelonephritis","volume":"96","author":"Sena","year":"2017","journal-title":"Medicine"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"477","DOI":"10.21037\/atm.2020.03.95","article-title":"Risk Factors for Uroseptic Shock in Hospitalized Patients Aged over 80 Years with Urinary Tract Infection","volume":"8","author":"Hsiao","year":"2020","journal-title":"Ann. Transl. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1007\/s00345-024-04979-2","article-title":"Urosepsis 30-Day Mortality, Morbidity, and Their Risk Factors: SERPENS Study, a Prospective, Observational Multi-Center Study","volume":"42","author":"Tandogdu","year":"2024","journal-title":"World J. Urol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"E1063","DOI":"10.1097\/CCM.0000000000005337","article-title":"Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021","volume":"49","author":"Evans","year":"2021","journal-title":"Crit. Care Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e195","DOI":"10.1111\/ijlh.13845","article-title":"Monocyte Distribution Width Kinetic after Surgery","volume":"44","author":"Agnello","year":"2022","journal-title":"Int. J. Lab. Hematol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.cca.2022.06.013","article-title":"Time-Dependent Stability of Monocyte Distribution Width (MDW)","volume":"533","author":"Agnello","year":"2022","journal-title":"Clin. Chim. Acta"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"117214","DOI":"10.1016\/j.cca.2022.117214","article-title":"Monocyte Distribution Width (MDW) as a Biomarker of Sepsis: An Evidenced-Based Laboratory Medicine Approach","volume":"540","author":"Ciaccio","year":"2023","journal-title":"Clin. Chim. Acta"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"117511","DOI":"10.1016\/j.cca.2023.117511","article-title":"Monocyte Distribution Width (MDW) in Sepsis","volume":"548","author":"Agnello","year":"2023","journal-title":"Clin. Chim. Acta"}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/9\/1334\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T08:14:39Z","timestamp":1777450479000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/9\/1334"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,29]]},"references-count":43,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["diagnostics16091334"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics16091334","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,29]]}}}