Clinical Characteristics Of Traumatic Osteomyelitis And Association Between Interferon ? Single Nucleotide Polymorphism And Risk Of Development Of The Disease

Osteomyelitis is a heterogeneous disease no matter in its pathophysiology,clinical presentation,or management.A classification for osteomyelitis has been proposed by Waldvogel in 1970 based on the source of infection:traumatic osteomyelitis caused by local spreading from a contiguous focus of infection;diabetic osteomyelitis secondary to vascular insufficiency(more likely to develop in the diabetic foot);and haematogenous osteomyelitis derived from a condition of bacteraemia.Along with advances in treatment of severe trauma has helped to increase the survival rate following traumatic injury,which has been accompanied by an increased occurrence of traumatic osteomyelitis.Up till now,traumatic osteomyelitis has always been a great challenge to doctors due to its complex in treatment,long disease course,high risk of therapeutic failure even after long-term therapy,high rate of recurrence,and high incidence of disability.Traumatic osteomyelitis as such also imposes great economic and psychological burdens on its patients,health-care system and the society.Therefore,investigations regarding pathogenesis of the disease should be strengthened to better solve these problems.The present study was undertaken to review the clinical characteristics of traumatic osteomyelitis,investigate diagnostic values of different inflammatory biomarkers and analysis the association of single nucleotide polymorphism with risk of developing traumatic osteomyelitis:Part One:Clinical Characteristics of Traumatic OsteomyelitisGreat differences were found regarding the clinical characteristics of traumatic osteomyelitis among previous studies,which are probably associated with geography,ethnicity,economy,culture and race.Moreover,many of these studies are limited to selected subsets of patients,as defined by age,anatomical location or infecting organisms.At the same time,sample size is a great challenge for accurate understanding of the disease.As advances are made in the management of osteomyelitis,the epidemiology of the condition appears to have evolved over time.Thus we need comprehensive clinical characteristics studies describing the entire spectrum of traumatic osteomyelitis in China.Diagnosis of traumatic osteomyelitis is on the basis of clinical signs and medical history,imaging tests,laboratory tests and histopathological tests.As an important aspect of laboratory tests,change of serum levels of inflammatory biomarkers plays an important role in initial judgment of infection.Most of previous studies which reported diagnostic roles of inflammatory markers for osteoarticular infections were focused on acute phase infections or periprosthetic joint infections.Limited studies reported these aspects in patients with traumatic osteomyelitis.In addition,few studies addressed serum interleukin-6(IL-6),tumor necrosis factor-a(TNF-a)and erum amyloid A(SAA)for diagnosis of traumatic osteomyelitis.Objectives:To review clinical characteristics of traumatic osteomyelitis and compare the clinical features between orthopaedic implant-associated traumatic osteomyelitis(OITO)and non-orthopaedic implant-associated traumatic osteomyelitis(NOITO)in a single center in Southern China.To review the diagnostic values of preoperative serum levels of WBC,ESR,CRP,PCT,IL-6,TNF-a and SAA for traumatic osteomyelitis.Methods:Clinical data were collected in patients who had attend to the Department of Orthopaedics and Traumatology,Nanfang Hospital between January 2010 and December 2016 with definite diagnosis of extremity traumatic osteomyelitis.Making statistical analysis of preoperative serum levels of these biomarkers.Results:Search outcome shows there are 605 osteomyelitis patients and 421 patients with traumatic osteomyelitis(69.59%)was included in this study.The OITO and NOITO is 259(61.52%)and 162(38.48%)respectively.The sex ratio(M/F)is 4.69:1.The sex ratio is higher in the OITO than in the NOITO(?2 = 5.033,P = 0.025).The average age of traumatic osteomyelitis patients is 37.13±16.268 year-old.The most common nature of trauma is open injury(267,63.42%)and the traffic trauma is the most frequent etiopathology(141,33.49%).Single site infection accounted for 85.75%(361 cases),with the most common site of tibia(178 cases,49.31%),femur(81 cases,22.44%)and calcaneus(42 cases,11.63%).The positive rate of intraoperative culture was 63.91%(216/338),80.09%(173/216)of which was monomicrobial infection.The most frequently detected pathogen was Staphylococcus aureus(57 cases,32.93%),followed by Pseudomonas aeruginosa(45 cases,26.01%),Enterococcus faecalis(9 cases,5.20%)and Escherichia coli(9 cases,5.20%)in monomicrobial infection.OITO and NOITO have significant difference in the distribution of pathogen(?2 = 43.155,P=0.019).Amputation rate in traumatic osteomyelitis patients was 4.99%and the rate was significantly higher in NOITO than OITO patients(?? 10.136,P = 0.001).A total of 420 patients with 347 males and 73 females were included for the review of diagnostic values of preoperative serum levels.Of all the 7 inflammatory markers,TNF-a achieved the highest positive rate(65.48%,129/197),successively by IL-6(57.49%,119/207)?ESR(56.71%,207/365)?SAA(53.04%,61/115)?CRP(46.03%,174/378)?PCT(36.36%,84/231)?WBC(13.81%,58/420).The difference between OITON and OITO in positive rate was not significant(P>0.05).Male patients had a higher serum level of WBC(6.98 vs.6.41,P = 0.002)and CRP(4.70 vs,3.76,P ?0.008)than female,however,the ESR(18.00 vs.30.00,P = 0.002)and PCT(0.040 vs.0.030,P = 0.014)serum level were significantly lower than female.Patients over 60 years had significantly lower values of WBC(6.42 vs.6.95,P = 0.042)than those below 60 years.OITON and OITO did not make any difference in all these biomarkers about the serum level(P>0.05).Patients with multiple sites infection had statistically higher levels of ESR(P = 0.038)and PCT(P = 0.026)than those with a single infection site.In addition,patients with positive culture outcomes had significantly higher values of CRP(P = 0.027),IL-6(P = 0.002)and TNF-a(P = 0.010)than those with negative outcomes.Among patients with positive culture outcomes,polymicrobial infections had significantly lower values of CRP(P = 0.039)than those with monomicrobial infections.Moreover,significant greater level were found between patients with a medical history of open injury and those with closed injury in TNF-?level(P = 0.014).Conslusions:The most frequent type of chronic osteomyelitis in southern of China was traumatic osteomyelitis,which favored males and mostly caused by open injury and during road accidents.The infection site was frequently located in lower limbs.Monomicrobial infection was the most common infection type,with Staphylococcus aureus as the most frequently detected pathogen.Amputation rate in traumatic osteomyelitis patients was 4.99%.Significant differences were identified regarding sex ratio,nature of trauma,distribution of single site infection,proportion of monomicrobial infection and amputation rate between the two types of traumatic osteomyelitis.Histopathological examination has the possibility to be false negative in the diagnose of traumatic osteomyelitis.TNF-a,IL-6 and ESR were more valuable biomarkers for assisted diagnosis of traumatic osteomyelitis.However,diagnostic value of serum WBC is limited.The difference between OITO and OITON is not significant neither in positive rates of inflammatory markers nor the serum level.Sex,age,number of infect sites,culture outcome,number of pathogen and open injury may influence the serum levels of the inflammatory biomarkers.Part Two:Association of Interferon ? SNP and Susceptibility to the Development of Trauma OsteomyelitisPrevious studies have explored pathogenesis of chronic osteomyelitis from perspective of single nucleotide polymorphism(SNP).Currently,there still lacks reports for potential SNP associations with traumatic osteomyelitis in Chinese population.Based on traumatic osteomyelitis is the major osteomyelitis type in China,potential geographical and ethnical differences from European population,we inferred that different SNP outcomes may exist between Chinese population and western populations.Objectives:To investigate associations between Interferon y SNP(rs2430561)and the risk of developing traumatic osteomyelitis after trauma.Methods:This study was designed as a case-control study.Patients were those with definite diagnosis of traumatic osteomyelitis,who had attended to the Department of Orthopaedics and Traumatology,Nanfang Hospital between August 2013 and October 2015.Healthy controls were individuals without any abnormalities after thorough examination in the physical examination center.After informed consent signed,all the participants received collection of 2 ml peripheral blood through intermedian cubital vein.Using the SNaPshot method to conduct SNP genotyping.The Chi-square or Fisher exact tests were used to compare the frequencies of genotypes between the two groups,with corresponding odds ratios(ORs)and 95%confidence intervals(CIs).Statistical analysis was conducted using the SPSS 20.0 software(SPSS Inc,Chicago,IL).A P value of<0.05 was defined as statistical significance.Results:A total of 389 participants with 189 patients and 200 healthy controls were included.Similar sex distribution(?2 = 3.536,P = 0.06)and median age(Z =-0.169,P=0.866)were identified between the two groups.Statistical analysis outcomes revealed no statistical difference was found regarding genotype distribution of IFN-y polymorphism rs2430561 gene between the patients with traumatic osteomyelitis and healthy controls(P = 0.055),the frequency of mutant allele A was significantly higher in the patient group than that in the healthy controls(P = 0.013).Additionally,significant links were identified between IFN-y gene polymorphism(rs2430561)and the risk of developing traumatic osteomyelitis by dominant model(P = 0.017)and heterozygous model(P = 0.029).Conclusions:Significant associations are found between IFN-? gene polymorphism rs2430561 and the risk of developing traumatic osteomyelitis in Chinese population.The mutant allele A may be a risk factor of traumatic osteomyelitis and people with genotype of AT of gene site may be a group with a higher risk of developing traumatic osteomyelitis after injury.