{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T14:32:59Z","timestamp":1780410779478,"version":"3.54.1"},"reference-count":49,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T00:00:00Z","timestamp":1724889600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100022400","name":"Agenzia Nazionale per le Nuove Tecnologie, l\u2019Energia e lo Sviluppo Economico Sostenibile","doi-asserted-by":"publisher","award":["89\/2019 within PNCDI III."],"award-info":[{"award-number":["89\/2019 within PNCDI III."]}],"id":[{"id":"10.13039\/501100022400","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006595","name":"Unitatea Executiva pentru Finantarea Invatamantului Superior, a Cercetarii, Dezvoltarii si Inovarii","doi-asserted-by":"publisher","award":["89\/2019 within PNCDI III."],"award-info":[{"award-number":["89\/2019 within PNCDI III."]}],"id":[{"id":"10.13039\/501100006595","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Infections are a major complication of open fractures and fracture fixation. In this study, an innovative bioactive medical device was used to experimentally treat MRSE-induced osteomyelitis in rabbit tibia. This paper investigates the clinical significance of inflammatory biomarkers (NLR, PLR, MLR and PMR), SII and IL-6 and assesses their role in the development of osteomyelitis. The main objective is to identify the utility of hematological reports derived from neutrophils, leukocytes, monocytes and platelets in the evolution of implant-related osteomyelitis and the estimation of treatment efficiency. In particular, this study compares the response of these inflammatory markers to different treatments in the presence or absence of bioactive materials and\/or topical antibiotics over time. The analysis of the threads showed that NLR, PLR and SII had high values in the acute phase of the disease, so that after chronicization, they decrease. The animals treated with vancomycin nano-functionalized peptide-enriched silk fibroin-coated implants showed lower levels of inflammatory biomarkers compared to the other groups (empty implants and peptide-enriched silk fibroin-coated implants). NLR, PLR and SII, complemented by IL-6 can be used as fairly accurate biomarkers for the diagnosis of osteomyelitis.<\/jats:p>","DOI":"10.1371\/journal.pone.0309145","type":"journal-article","created":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T17:50:15Z","timestamp":1724953815000},"page":"e0309145","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["The clinical significance of inflammatory biomarkers, IL6 cytokine, and systemic immune inflammatory index in rabbit model of acute and chronic Methicillin-resistant Staphylococcus epidermidis-induced osteomyelitis"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6985-5152","authenticated-orcid":true,"given":"Diana-Larisa","family":"Ancu\u021ba","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5230-9718","authenticated-orcid":true,"given":"Arianna Barbara","family":"Lovati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6037-183X","authenticated-orcid":true,"given":"Cristin","family":"Coman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,8,29]]},"reference":[{"issue":"6","key":"pone.0309145.ref001","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.mporth.2010.09.004","article-title":"Osteomyelitis","volume":"24","author":"M McNally","year":"2010","journal-title":"Orthop Trauma"},{"issue":"9","key":"pone.0309145.ref002","first-page":"CD004439","article-title":"Antibiotics for treating chronic osteomyelitis in adults","author":"LO Conterno","year":"2013","journal-title":"The Cochrane database of systematic reviews"},{"key":"pone.0309145.ref003","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.actbio.2019.01.015","article-title":"Implantable antimicrobial biomaterials for local drug delivery in bone infection models","volume":"93","author":"JD Caplin","year":"2019","journal-title":"Acta Biomater"},{"issue":"3","key":"pone.0309145.ref004","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/j.injury.2016.09.019","article-title":"Infection after fracture fixation: Current surgical and microbiological concepts","volume":"49","author":"WJ Metsemakers","year":"2018","journal-title":"Injury"},{"key":"pone.0309145.ref005","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.3389\/fimmu.2019.01724","article-title":"Chronic Implant-Related Bone Infections-Can Immune 452 Modulation be a Therapeutic Strategy?","volume":"10","author":"E Seebach","year":"2019","journal-title":"Frontiers in immunology"},{"issue":"9","key":"pone.0309145.ref006","first-page":"1027","article-title":"Diagnosis and management of osteomyelitis","volume":"84","author":"J Hatzenbuehler","year":"2011","journal-title":"American family physician"},{"issue":"5","key":"pone.0309145.ref007","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.bjid.2013.12.005","article-title":"Recommendations for the treatment of osteomyelitis","volume":"18","author":"Diretrizes Panamericanas para el Tratamiento de las Osteomielitis e Infecciones de Tejidos Blandos Group","year":"2014","journal-title":"Braz J Infect Dis"},{"issue":"5","key":"pone.0309145.ref008","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1016\/j.arth.2018.02.078","article-title":"The 2018 Definition of Periprosthetic Hip and Knee Infection: An Evidence-Based and Validated Criteria","volume":"33","author":"J Parvizi","year":"2018","journal-title":"The Journal of arthroplasty"},{"issue":"7","key":"pone.0309145.ref009","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.1097\/CORR.0000000000000718","article-title":"What are the Optimal Cutoff Values for ESR and CRP to Diagnose Osteomyelitis in Patients with Diabetes-related Foot Infections?","volume":"477","author":"LA Lavery","year":"2019","journal-title":"Clinical orthopaedics and related research"},{"issue":"12","key":"pone.0309145.ref010","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1302\/0301-620X.100B12.BJJ-2018-0586.R1","article-title":"Diagnostic accuracy of serum inflammatory markers in late fracture-related infection: a systematic review and meta-analysis","volume":"100-B","author":"J van den Kieboom","year":"2018","journal-title":"Bone Joint J"},{"key":"pone.0309145.ref011","doi-asserted-by":"crossref","first-page":"9213074","DOI":"10.1155\/2019\/9213074","article-title":"Mean Platelet Volume (MPV): New Perspectives for an Old Marker in the Course and Prognosis of Inflammatory Conditions","volume":"2019","author":"A Korniluk","year":"2019","journal-title":"Mediators of inflammation"},{"issue":"1","key":"pone.0309145.ref012","doi-asserted-by":"crossref","first-page":"47","DOI":"10.2174\/138161211795049804","article-title":"Mean platelet volume: a link between thrombosis and inflammation?","volume":"17","author":"AY Gasparyan","year":"2011","journal-title":"Current pharmaceutical design"},{"key":"pone.0309145.ref013","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.intimp.2018.02.008","article-title":"Relationship between monocytes to lymphocytes ratio and axial spondyloarthritis","volume":"57","author":"Y Huang","year":"2018","journal-title":"International immunopharmacology"},{"key":"pone.0309145.ref014","first-page":"3758068","article-title":"Neutrophil-to-Lymphocyte Ratio, Monocyte-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and Mean Platelet Volume-to-Platelet Count Ratio as Biomarkers in Critically Ill and Injured Patients: Which Ratio to Choose to Predict Outcome and Nature of Bacteremia?","author":"D Djordjevic","year":"2018","journal-title":"Mediators of inflammation"},{"issue":"3","key":"pone.0309145.ref015","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/s15010-016-0972-1","article-title":"Role of neutrophil to lymphocyte and monocyte to lymphocyte ratios in the diagnosis of bacterial infection in patients with fever","volume":"45","author":"A Naess","year":"2017","journal-title":"Infection"},{"key":"pone.0309145.ref016","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1186\/s13104-016-2089-0","article-title":"Use of the neutrophil-to-lymphocyte ratio as a component of a score to predict postoperative mortality after surgery for hip fracture in elderly subjects","volume":"9","author":"P Forget","year":"2016","journal-title":"BMC research notes"},{"issue":"12","key":"pone.0309145.ref017","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1016\/j.kjms.2015.10.010","article-title":"The relation of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and mean platelet volume with the presence and severity of Beh\u00b8cet\u2019s syndrome","volume":"31","author":"S Alan","year":"2015","journal-title":"The Kaohsiung journal of medical sciences"},{"key":"pone.0309145.ref018","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.diabres.2018.08.009","article-title":"The significance of neutrophil-lymphocyte ratio, platelet-lymphocyte ratio and lymphocyte-monocyte ratio in predicting peripheral arterial disease, peripheral neuropathy, osteomyelitis and amputation in diabetic foot infection","volume":"144","author":"T Demirdal","year":"2018","journal-title":"Diabetes Res Clin Pract"},{"issue":"11","key":"pone.0309145.ref019","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.it.2012.07.003","article-title":"Interleukin-6: from an inflammatory marker to a target for inflammatory diseases","volume":"33","author":"M Rincon","year":"2012","journal-title":"Trends Immunol"},{"key":"pone.0309145.ref020","doi-asserted-by":"crossref","first-page":"1912","DOI":"10.1086\/315138","article-title":"Staphylococcus aureus infection of mouse or human osteoblasts induces high levels of IL-6 and IL-12 production","volume":"180","author":"KL Bost","year":"1999","journal-title":"J Infect Dis"},{"key":"pone.0309145.ref021","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/S0035-9203(00)90284-0","article-title":"Local and systemic concentrations of tumour necrosis factor-a, interleukin-6 and interleukin-8 in bacterial osteomyelitis","volume":"94","author":"S Fullilove","year":"2000","journal-title":"Trans R Soc Trop Med Hyg"},{"issue":"4","key":"pone.0309145.ref022","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1016\/S0002-9440(10)63226-9","article-title":"Osteoblasts express the inflammatory cytokine interleukin-6 in a murine model of Staphylococcus aureus osteomyelitis and infected human bone tissue","volume":"164","author":"I Marriott","year":"2004","journal-title":"Am J Pathol"},{"issue":"4","key":"pone.0309145.ref023","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1099\/jmm.0.000952","article-title":"Animal models of orthopedic infections. A review of rabbit models used to induce long bone bacterial infections","volume":"68","author":"M Bottagisio","year":"2019","journal-title":"Journal of medical microbiology"},{"issue":"20","key":"pone.0309145.ref024","doi-asserted-by":"crossref","first-page":"e00378","DOI":"10.1128\/genomeA.00378-17","article-title":"Draft Genome Sequence of Staphylococcus epidermidis Clinical Strain GOI1153754-03-14 Isolated from an Infected Knee Prosthesis","volume":"5","author":"M Bottagisio","year":"2017","journal-title":"Genome Announc"},{"key":"pone.0309145.ref025","doi-asserted-by":"crossref","first-page":"3182","DOI":"10.3390\/nano12183182","article-title":"Antibiotic-Loaded Hyperbranched Polyester Embedded into Peptide-Enriched Silk Fibroin for the Treatment of Orthopedic or Dental Infections","volume":"12","author":"Z Sideratou","year":"2022","journal-title":"Nanomaterials"},{"issue":"2","key":"pone.0309145.ref026","first-page":"85","article-title":"Comparative study of osteomyelitis reproduced on rabbits using human strains of Methicilin\u2014Resistant Staphylococcus aureus (MRSA) and Methicillin\u2014Resistant Staphylococcus epidermidis (MRSE)","volume":"Vol. LXVI","author":"DL Ancu\u021ba","year":"2020","journal-title":"Veterinary Medicine"},{"issue":"1","key":"pone.0309145.ref027","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1055\/s-0038-1676292","article-title":"Copper Bead Therapy in Severe Bone Infection: A Rabbit Tibial Model","volume":"32","author":"CC Surdu-Bob","year":"2019","journal-title":"Veterinary and comparative orthopaedics and traumatology: V.C.O.T"},{"key":"pone.0309145.ref028","doi-asserted-by":"crossref","first-page":"175","DOI":"10.3758\/BF03193146","article-title":"G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences","volume":"39","author":"F Faul","year":"2007","journal-title":"Behav Res Methods"},{"issue":"5","key":"pone.0309145.ref029","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1128\/JCM.03197-13","article-title":"Propionibacterium acnes and Staphylococcus lugdunensis cause pyogenic osteomyelitis in an intramedullary nail model in rabbits","volume":"52","author":"AD Gahukamble","year":"2014","journal-title":"J Clin Microbiol"},{"issue":"10","key":"pone.0309145.ref030","first-page":"837","article-title":"Trends in the epidemiology of osteomyelitis: a population-based study, 1969 to 2009. The Journal of bone and joint surgery","volume":"97","author":"HM Kremers","year":"2015","journal-title":"American volume"},{"key":"pone.0309145.ref031","doi-asserted-by":"crossref","first-page":"879630","DOI":"10.3389\/fvets.2022.879630","article-title":"Role of Animal Models to Advance Research of Bacterial Osteomyelitis","volume":"9","author":"C Billings","year":"2022","journal-title":"Frontiers in veterinary science"},{"issue":"1","key":"pone.0309145.ref032","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1002\/ame2.12149","article-title":"Innovations in osteomyelitis research: A review of animal models","volume":"4","author":"KM Roux","year":"2021","journal-title":"Animal models and experimental medicine"},{"key":"pone.0309145.ref033","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/1749-799X-8-38","article-title":"A rabbit osteomyelitis model for the longitudinal assessment of early post-operative implant infections","volume":"8","author":"JC Odekerken","year":"2013","journal-title":"Journal of orthopedic surgery and research"},{"issue":"5","key":"pone.0309145.ref034","first-page":"4995","article-title":"A rabbit model of implant-related osteomyelitis inoculated with biofilm after open femoral fracture","volume":"14","author":"X Zhang","year":"2017","journal-title":"Experimental and therapeutic medicine"},{"key":"pone.0309145.ref035","first-page":"424652","article-title":"The longitudinal assessment of osteomyelitis development by molecular imaging in a rabbit model","author":"JC Odekerken","year":"2014","journal-title":"BioMed research international"},{"issue":"4","key":"pone.0309145.ref036","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1007\/s00259-015-3221-4","article-title":"The diagnostic value of [(18)F] FDG PET for the detection of chronic osteomyelitis and implant-associated infection","volume":"43","author":"V Wenter","year":"2016","journal-title":"European journal of nuclear medicine and molecular imaging"},{"issue":"2","key":"pone.0309145.ref037","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/s00251-015-0868-8","article-title":"An overview of the lagomorph immune system and its genetic diversity","volume":"68","author":"A Pinheiro","year":"2016","journal-title":"Immunogenetics"},{"issue":"1","key":"pone.0309145.ref038","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1111\/imr.12671","article-title":"Dynamic balance of pro- and anti-inflammatory signals controls disease and limits pathology","volume":"285","author":"JM Cicchese","year":"2018","journal-title":"Immunological reviews"},{"issue":"no. 7","key":"pone.0309145.ref039","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1038\/ni.2921","article-title":"Neutrophils at work","volume":"vol. 15","author":"WM Nauseef","year":"2014","journal-title":"Nature Immunology"},{"key":"pone.0309145.ref040","doi-asserted-by":"crossref","first-page":"400","DOI":"10.3389\/fimmu.2015.00400","article-title":"Recognition of microbial glycolipids by natural killer T cells","volume":"vol. 6","author":"DM Zajonc","year":"2015","journal-title":"Frontiers in Immunology"},{"issue":"1","key":"pone.0309145.ref041","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s13054-014-0731-6","article-title":"The association between the neutrophil-to-lymphocyte ratio and mortality in critical illness: an observational cohort study","volume":"19","author":"JD Salciccioli","year":"2015","journal-title":"Crit Care"},{"issue":"10","key":"pone.0309145.ref042","doi-asserted-by":"crossref","first-page":"e46561","DOI":"10.1371\/journal.pone.0046561","article-title":"The neutrophil-lymphocyte count ratio in patients with community-acquired pneumonia","volume":"7","author":"CP de Jager","year":"2012","journal-title":"PloS one"},{"issue":"4","key":"pone.0309145.ref043","doi-asserted-by":"crossref","first-page":"165","DOI":"10.5152\/eajem.2017.51523","article-title":"Prognostic value of the neutrophil-lymphocyte and platelet\u2013lymphocyte ratios in predicting one-year mortality in patients with hip fractures and aged over 60 years","volume":"16","author":"E Emektar","year":"2017","journal-title":"Eurasian Journal of Emergency Medicine"},{"issue":"no. 1","key":"pone.0309145.ref044","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.1038\/s41598-018-20582-z","article-title":"Panton-Valentine leucocidin associated with S. aureus osteomyelitis activates platelets via neutrophil secretion products","volume":"vol. 8","author":"S Niemann","year":"2018","journal-title":"Scientific Reports"},{"key":"pone.0309145.ref045","doi-asserted-by":"crossref","first-page":"85","DOI":"10.3389\/fcimb.2015.00085","article-title":"Staphylococcus aureus vs. osteoblast: relationship and consequences in osteomyelitis","volume":"vol.5","author":"J Josse","year":"2015","journal-title":"Frontiers in Cellular and Infection Microbiology"},{"key":"pone.0309145.ref046","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1006\/cyto.2002.1039","article-title":"Local levels of in-terleukin -1, -4, -6 and tumor necrosis factor in an experimental model of murine osteomyelitis due to staphylococcus aureus","volume":"19","author":"T Yoshii","year":"2002","journal-title":"Cytokine"},{"issue":"Issue 3","key":"pone.0309145.ref047","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1097\/SHK.0000000000000718","article-title":"Mean Platelet Volume to Platelet Count Ratio as a Promising Predictor of Early Mortality in Severe Sepsis","volume":"Volume 47","author":"GH Oh","year":"2017","journal-title":"SHOCK"},{"issue":"3","key":"pone.0309145.ref048","doi-asserted-by":"crossref","first-page":"e0119437","DOI":"10.1371\/journal.pone.0119437","article-title":"An increase in mean platelet volume from baseline is associated with mortality in patients with severe sepsis or septic shock","volume":"10","author":"CH Kim","year":"2015","journal-title":"PloS one"},{"issue":"1","key":"pone.0309145.ref049","first-page":"24","article-title":"Relationship between C-reactive protein, systemic immune-inflammation index, and routine hemogram-related inflammatory markers in low-grade inflammation","volume":"1","author":"Y Ustundag","year":"2018","journal-title":"Int J Med Biochem"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0309145","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T17:50:39Z","timestamp":1724953839000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0309145"}},"subtitle":[],"editor":[{"given":"Seyed Mostafa","family":"Hosseini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,8,29]]},"references-count":49,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2024,8,29]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0309145","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,29]]}}}