Hip resurfacing may be a useful surgical procedure when patient selection is correct and only implants with superior performance are used. In order to establish a body of evidence in relation to hip resurfacing, pseudotumour formation and its genetic predisposition, we performed a case-control study investigating the role of HLA genotype in the development of pseudotumour around MoM hip resurfacings. All metal-on-metal (MoM) hip resurfacings performed in the history of the institution were assessed. A total of 392 hip resurfacings were performed by 12 surgeons between February 1st 2005 and October 31st 2007. In all cases, pseudotumour was confirmed in the preoperative setting on Metal Artefact Reduction Sequencing (MARS) MRI. Controls were matched by implant (ASR or BHR) and absence of pseudotumour was confirmed on MRI. Blood samples from all cases and controls underwent genetic analysis using Next Generation Sequencing (NGS) assessing for the following alleles of 11 HLA loci (A, B, C, DRB1, DRB3/4/5, DQA1, DQB1, DPB1, DPA1). Statistical significance was determined using a Fisher's exact test or Chi-Squared test given the small sample size to quantify the clinical association between HLA genotype and the need for revision surgery due to pseudotumour. Both groups were matched for implant type (55% ASR, 45% BHR in both the case and control groups). According to the ALVAL histological classification described by Kurmis et al., the majority of cases (63%, n=10) were found to have group 2 histological findings. Four cases (25%) had group 3 histological findings and 2 (12%) patients had group 4 findings. Of the 11 HLA loci analysed, 2 were significantly associated with a higher risk of pseudotumour formation (DQB1*05:03:01 and DRB1*14:54:01) and 4 were noted to be protective against pseudotumour formation (DQA1*03:01:01, DRB1*04:04:01, C*01:02:01, B*27:05:02). These findings further develop the knowledge base around specific HLA genotypes and their role in the development of pseudotumour formation in MoM hip resurfacing. Specifically, the two alleles at higher risk of pseudotumour formation (DQB1*05:03:01 and DRB1*14:54:01) in MoM hip resurfacing should be noted, particularly as patient-specific genotype-dependent surgical treatments continue to develop in the future

Total joint replacement (TJR) is by far the most effective therapy for end-stage OA patients. Most of patients achieve joint pain reduction and function improvement following to TJR, however up to 22% of them either do not improve or deteriorate after surgery. The aim of this study was to identify genetic variants to be associated with poor outcome of TJR in primary OA patients by a genome-wide association approach (GWAS). Study participants were primary OA patients from the Newfoundland Osteoarthritis Study (NFOAS) that comprised total knee or hip replacement and recruited before 2016 in St. John's, NL. DNA samples were extracted from patients' blood. Study participants completed their pre-operation and 3.99±1.38 years post-surgery outcome assessment using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). DNA samples were genotyped using the genome-wide Illumina HumanOmni2.58 genotyping microarray containing 2.4 million SNPs. Pre-association quality control filtering was conducted for the raw genotyping data using PLINK 1.7 program, and genotype imputation was performed using the IMPUTE2 algorithm with multiple population reference data from 1000 Genome Project. The imputed data with ∼3.1 million variants was used to test the association with non-responders to TJR using the additive genetic model. Eighty three primary OA patients (44 responders and 39 non-responders) were included in the analysis. Association analysis detected three chromosomal regions on chr5, 7, and 8 to be significantly associated with non-responding to pain. The top SNPs at these loci are intergenic variants that include SNP (rs17118094, p=4.4×10-5) on chr5. This SNP is adjacent to SGCD gene that plays an important role in muscular strength and maintenance. Another associated SNP (rs71572810, p=4.7×10-5) is nearby IMMP2L gene on chr7. This gene is reported to be associated with behavioral abnormalities. Finally, SNP (rs6992938, p=5.8×10-5) on chr8 is located downstream of TRPA1 gene that is known to have a central role in the pain response to endogenous inflammatory mediators. Three loci were also found to be significantly associated with non-responding to function. The lead variant in the locus on chr1 is an intergenic SNP (rs9729377, p=1.7×10-5) falling between CTBS and MCOLN2 genes. CTBS gene is associated with TNF-α, a cytokine that stimulate the inflammation acute phase reaction, and MCOLN2 gene plays a role in the chemokine secretion and macrophage migration in the innate immune response. Other top SNPs in loci on chr2 and 10 harbor CCDC93, INSIG2, and KLF6 genes that are associated with heel bone mineral density, hypercholesterolemia, obesity and BMI. To our knowledge, this project is the first study that investigated the association between genetic factors and TJR non-responders. Our results demonstrated that genes related to muscle strength, behavioral trait, pain response, and inflammation play a significant role in poor outcome of TJR, warranting further investigation

Osteoarthritis (OA) is the most common form of arthritis and one of the ten most disabling diseases in developed countries. Total joint replacement (TJR) is considered by far as the most effective treatment for end-stage OA patients. The majority of patients achieve symptomatic improvement following TJR. However, about 22% of the TJR patients either do not improve or deteriorate after surgery. Several potential non-genetic predictors for the TJR outcome have been investigated. However, the results were either inconclusive or had very limited predictive power. The aim of this study was to identify genetic variants for the poor outcome of TJR in primary OA patients by a genome-wide association study (GWAS). Study participants were total knee or hip replacement patients due to primary OA who were recruited to the Newfoundland Osteoarthritis Study (NFOAS) before 2017. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was used to assess pain and functional impairment pre- and 3.99±1.38 years post-surgery. Two non-responder classification criteria were used in our study. One was defined by an absolute WOMAC change score. Participants with a change score less than 7/20 points for pain were considered as pain non-responders; and those with less than 22/68 points for function were classified as function non-responders. The second one was the Outcome Measures in Arthritis Clinical Trials and the Osteoarthritis Research Society International (OMERACT-OARSI) criteria. Blood DNA samples were genotyped using the Illumina GWAS microarrays genotyping platform. The quality control (QC) filtering was performed on GWAS data before the association of the genetic variants with non-responders to TJR was tested using the GenABEL package in R with adjustment for the relatedness of the study population and using the commonly accepted GWAS significance threshold p < 5*10. −8. to control multiple testing. In total, 316 knee and 122 hip OA patients (mean age 65.45±7.62 years, and 58% females) passed the QC check. These study participants included 368 responders and 56 non-responders to pain, and 364 responders and 68 non-responders to function based on the absolute WOMAC point score change classification. While 377 responders and 56 non-responders to pain, and 366 responders and 71 non-responders to function were identified by the OMERACT-OARSI classification criteria. Interestingly, the same results were obtained by both classification methods, and we found that the G allele of rs4797006 was significantly associated with pain non-responders with odds ratio (OR) of 5.12 (p<7.27×10. -10. ). This SNP is in intron one of the melanocortin receptor 5 (MC5R) gene on chr18. This gene plays central roles in immune response, pain sensitivity, and negative regulation of inflammatory response to antigenic stimulus. The A allele of rs200752023 was associated with function non-responders with OR of 4.41 (p<3.29×10. -8. ). The SNP is located in intron three of the RNA Binding Fox-1 Homolog 3 (RBFOX3) gene on chr17 which has been associated with numerous neurological disorders. Our data suggested that two chromosomal regions are associated with TJR poor outcomes and could be the novel targets for developing strategies to improve the outcome of the TJR

While total joint replacement (TJR) is considered as an effective intervention to relieve pain and restore joint function for end-stage osteoarthritis (OA) patients, a significant proportion of the patients are dissatisfied with their surgery outcomes. The aim of this study was to identify genetic factors that can predict patients who do or do not benefit from these surgical procedures by a genome-wide association study (GWAS). Study participants were derived from the Newfoundland Osteoarthritis Study (NFOAS) which consisted of 1086 TJR patients. Non-responders to TJR was defined as patients who did not reach the minimum clinically important difference (MCID) based on the self administered Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) in terms of pain reduction or function improvment. DNA was extracted from the blood samples of the study participants and genotyped by Illumina GWAS genotyping platform. Over two million single nucleotide polymorphisms (SNPs) across the genome were genotyped and tested for assocition with non-responders. 39 non-responders and 44 age, sex, and BMI matched responders were included in this study. Four chromosome regions on chromosomes 5, 7, 8, and 12 were suggested to be associated with non-responders with p < 1 0–5. The most promising one was on chromosome 5 with the lead SNP rs17118094 (p=1.7×10–6) which can classify 72% of non-responders accurately. The discriminatory power of this SNP alone is very promising as indicated by an area under the curve (AUC) of 0.72 with 95% confidence interval of 0.63 to 0.81, which is much better than any previously studied predictors mentioned above. All the patients who carry two copies of the G allele (minor allele) of rs17118094 were non-responders and 75% of those who carry one copy of the G allele were non-responders. The discriminatory ability of the lead SNPs on chromosomes 7 and 12 were comparable to the one on chromosome 5 with an AUC of 0.74, and 88% of patients who carry two copies of the A allele of rs10244798 on chromosome 7 were non-responders. Similarly, 88% of patients who carry two copies of the C allele of rs10773476 on chromosome 12 were non-responders. While the discriminatory ability of rs9643244 on chromosome 8 was poor with an AUC of 0.26, its strong association with non-responders warrants a further investigation in the region. The study identified four genomic regions harboring genetic factors for non-responders to TJR. The lead SNPs in those regions have great discriminatory ability to predict non-responders and could be used to create a genetic prediction model for clinical unitilty and application

Aim. Previous studies had indicated that interleukin-1 beta (IL-1β) gene single nucleotide polymorphisms (SNPs) associate with different inflammatory diseases. However, potential links between these polymorphisms and susceptibility to extremity chronic osteomyelitis (COM) in Chinese population remain unclear. This study aimed to investigate relationships between IL-1β gene polymorphisms (rs16944, rs1143627, rs1143634 and rs2853550) and the risk of developing extremity COM in Chinese population. Method. Altogether 233 extremity COM patients and 200 healthy controls were genotyped for the four tag SNPs of the IL-1β gene using the SNapShot genotyping method. Comparisons were performed regarding genotype distribution, mutant allele frequency and four genetic models (dominant, recessive, homozygous and heterozygous models) of the 4 SNPs between the two groups. Results. Significant associations were identified between rs16944 polymorphism and the risk of developing COM by dominant model (P = 0.026, OR = 1.698, 95% CI 1.065–2.707) and heterozygous model (P = 0.030, OR = 1.733, 95% CI 1.055 – 2.847). Although no statistical differences were found of rs1143627 polymorphism between the two groups, there existed a trend that rs1143627 may be linked to an elevated risk of developing COM by outcomes of dominant (P = 0.061), homozygous (P = 0.080) and heterozygous (P = 0.095) models. However, no statistical correlations were found between rs1143634 and rs2853550 polymorphisms and susceptibility to COM in Chinese population. Conclusions. To our knowledge, we reported for the first time that IL-1β gene rs16944 polymorphism may contribute to the increased susceptibility to extremity COM in Chinese population, with genotype of AG as a risk factor

Aim. Cyclooxygenase-2 (COX-2) enzyme is one of the major mediators during inflammation reactions, and COX-2 gene polymorphisms of rs20417 and rs689466 have been reported to be associated with several inflammatory diseases. However, potential links between the two polymorphisms and risk of developing post-traumatic osteomyelitis remain unclear. The present study aimed to investigate associations between the rs20417 and rs689466 polymorphisms and susceptibility to post-traumatic osteomyelitis in Chinese population. Methods. A total of 189 patients with definite diagnosis of post-traumatic osteomyelitis and 220 healthy controls were genotyped for rs20417 and rs689466 using the genotyping method*. Chi-square test was used to compare differences of genotype distributions as well as outcomes of five different genetic models between the two groups. Results. Significant association was found between rs689466 and post-traumatic osteomyelitis by recessive model (GG vs. AA + AG) (OR = 1.74, 95% CI: 1.098–2.755, P =0.018). Although no statistical differences were identified of rs689466 between the two groups by allele model (P = .098) or homozygous model (P = 0.084), outcomes revealed a tendency that allele G may be a risk factor and people of GG genotype may be in a higher risk to develop post-traumatic osteomyelitis in Chinese population. However, no significant link was found between rs20417 and susceptibility to post-traumatic osteomyelitis in this Chinese cohort. Conclusions. To our knowledge, we reported for the first time that COX-2 gene polymorphism rs689466 may contribute to the increased susceptibility to post-traumatic osteomyelitis in Chinese population. *SNaPshot®

Aim. Periprosthetic joint infection (PJI) is one of the most serious and frequent complications in prosthetic surgery. Despite significant improvements in the criteria for diagnosis of PJI, the diagnostic workflow remains complex and, sometimes, inconclusive. Host immune factors hold great potential as diagnostic biomarkers in bone and joint infections. We have recently reported that the synovial concentration of the humoral pattern recognition molecule long pentraxin 3 (PTX3) is a sensitive and specific marker of PJI in total hip and knee arthroplasty patients (THA and TKA) undergoing revision surgery [1]. However, the contribution to risk and diagnosis of PJI of the genetic variation in PTX3 and inflammatory genes that are known to affect its expression (IL-1b, IL-6, IL-10, and IL-17A) has not been addressed. Therefore, we assessed these relationships in a cohort of THA and TKA patients who underwent prosthesis revision by focusing on a panel of single nucleotide polymorphisms (SNPs) in the PTX3, IL-1β, IL-6, IL-10 and IL-17A genes. Method. A case-control retrospective study was conducted on an historic cohort of patients that received THA or TKA revision and were diagnosed with PJI (cases) or aseptic complications (controls) [1]. Samples of saliva were collected from 93 subjects and used for extraction of genomic DNA to perform genotyping of the PTX3, IL-1β, IL-6, IL-10 and IL-17A polymorphisms. Moreover, whenever available, samples of synovial fluid and plasma [1] were used to measure the concentration of the IL-1β, IL-10, and IL-6 proteins by immunoassay. Uni-and multivariate analyses were performed to evaluate the relationships between genetic, biochemical, and clinical variables. Results. The rs3024491 (IL-10) and rs2853550 (IL-1b) SNPs were found to be strongly associated with the risk of PJI. The synovial levels of PTX3, IL-1β, IL-10, and IL-6 were higher in cases than in controls, and a clear correlation emerged between the synovial concentration of PTX3 and IL-1b in cases only. Also, we identified a causal relationship between rs2853550, synovial concentration of IL-1b and that of PTX3 (that is induced by IL-1b). Conclusions. Our findings suggest that SNPs in the IL-10 and IL-1b genes could be used for early identification of THA and TKA patients with high risk of PJI. It is therefore conceivable that integrating genetic data into current diagnostic criteria would improve diagnosis of PJI

Aim. To determine whether rep-PCR genotyping can improve the diagnosis of coagulase-negative staphylococci(CoNS)bone and joint infection relative to the standard method based on phenotypic identification. Method. Observational study comparing diagnostic tests (January 2011-March 2015), including all orthopaedic surgery patients with clinically suspected infection and ≥2 surgical specimens culture-positive for CoNS. Data collection included epidemiologic and clinical information, current clinical signs of suspected infection, and microbiological information. Each CoNS strain was analyzed by both methods (phenotyping, VITEK and API;and genotyping, rep-PCR). In accordance with current IDSA guidelines, CoNS strains identified as identical in ≥2 samples within the same surgical episode were considered pathogenic. The results of the two techniques were compared and statistically analyzed. Results. 255 CoNS isolates from 52 surgical episodes with suspected infection in 42 patients (55% male, mean age 61.5±20.6 years) were included. The patients' Charlson comorbidity index was 0.7±1.1. Implanted material was present in 79% of episodes and the surgical site had undergone previous surgery in 93%. CoNS infection was diagnosed by phenotyping in 73% of patients (mean, 2.2±1.3 different strains identified per episode)and 77% by rep-PCR analysis(mean, 1.8±0.6 different strains per episode). The kappa index of concordance was 0.59±0.14 (p<0.01). In patients in whom CoNS was considered not a cause of infection by phenotyping, 37% were considered infective agents by genotyping, accounting for 10%of the total. Conclusions. The two diagnostic methods showed moderate agreement in the diagnosis of postoperative bone and joint infection. Rep-PCR had a somewhat higher capacity for identifying CoNS strains. Rep-PCR could be of value as a complementary technique to phenotyping when the latter technique identifies CoNS strains as being non-pathogenic

Toll-like receptors (TLRs) are crucial components of the immune system that recognize microbial infection and trigger anti-microbial host defense responses. Gram positive bacteria are causative factors of bone infections, as they alter the balance of coordinated activities during bone remodeling, stimulating osteoclastogenesis. The aim of the study was to investigate whether genetic variation in TLR2 and TLR4 genes predisposes to bone infections’ susceptibility. One hundred and twenty patients with bone infections (osteomyelitis) and 200 healthy controls were genotyped for two single nucleotide polymorphisms (SNPs), R753Q [A/G] in TLR2 gene and T399I [C/T] in TLR4 gene. DNA was extracted from whole blood and the above SNPs were typed with PCR-RFLP (Polymerase Chain Reaction- Restriction Fragment Length Polymorphism) method for genotype identification. All patients were infected by Gram-positive bacteria, predominantly Staphylococcus aureus. Statistical analysis was carried out using the chi-square test. We observed a significantly increased frequency in patients carrying the GA genotype of TLR2 R753Q polymorphism compared to controls (p<0.05). We also found that the A allele was more common in patients than in controls. All individuals carrying the A allele were heterozygous for this variant, while homozygous mutant individuals were not detected in the patients and the control group. In contrast, we found that the TLR4 T399I [C/T] SNP was similarly distributed among the two groups (patients and controls). The mechanism through which TLR2 mediates its effect in bone infections is under investigation. A significant difference was observed in the genotype frequency of TLR2 R753Q [A/G] polymorphism in patients, suggesting that genetic variability in TLR2 gene may be associated with susceptibility to osteomyelitis in response to bacterial invasion in the bone

Aim. Previous studies have indicated that TNF-α and lymphotoxin-α (LTA) gene polymorphisms associate with the development of several different inflammatory diseases. However, potential associations of such gene polymorphisms with the susceptibility to extremity chronic osteomyelitis remain unknown. This study aimed to investigate potential links between TNF-α gene polymorphisms (rs1800629, rs361525, rs1799964, rs1800630, rs1799724 and rs1800750) and LTA gene polymorphism (rs909253) and the risk of developing extremity chronic osteomyelitis in Chinese population. Method. A total of 233 patients with extremity chronic osteomyelitis and 200 healthy controls were genotyped for the above 7 polymorphisms of TNF-α and LTA genes using the genotyping method*. Results. Significant difference was found regarding the genotype distribution of rs909253 between patients and healthy controls (P = 0.002). The mutant allele C frequency of rs909253 in patient group was significantly higher than that in control group (P = 0.001). Significant associations were identified between rs909253 and the risk of developing chronic osteomyelitis by dominant model (P = 0.040), recessive model (P = 0.002) and homozygous model (P = 0.001). Additionally, the mutant allele T frequency in rs1799964 in patient group was significantly higher than that in control group (P = 0.035). Significant link was found between rs1799964 and susceptibility to chronic osteomyelitis by recessive model (P = 0.048). However, no significant outcomes were identified regarding other TNF-α gene polymorphisms between the two groups. Conclusions. The present study demonstrated that rs909253 and rs1799964 polymorphisms may associate with the risk of developing chronic osteomyelitis in Chinese population. *SNaPshot

Introduction. This study was to investigate the association of developmental dysplasia of the hip (DDH) and primary protrusion acetabuli (PPA) with Vitamin D receptor polymorphisms TaqI and FokI and oestrogen receptor polymorphisms Pvu II and XbaI. Methods. 45 patients with DDH and 20 patients with PPA were included in the study. Healthy controls (n=101) aged 18-60 years were recruited from the same geographical area. The control subjects had a normal acetabular morphology based on a recent pelvic radiograph performed for an unrelated cause. DNA was obtained from all the subjects from peripheral blood. Genotype frequencies were compared in the three groups. The relationship between the genotype and morphology of the hip joint, severity of the disease, age at onset of disease and gender were examined. Results. The oestrogen receptor XbaI wild-type genotype (XX, compared with Xx and xx combined) was more common in the DDH group (55.8%) than controls (37.9%), though this just failed to achieve statistical significance (p=0.053, odds ratio=2.1, 95% CI=0.9-4.6). In the DDH group, homozygosity for the mutant TaqI Vitamin D receptor t allele was associated with higher acetabular index (Mann-Whitney U-test, p= 0.03). Pvu II pp oestrogen receptor genotype was associated with low centre edge angle (p=0.07). Conclusion. This study suggests a possible correlation between gene polymorphism in the oestrogen and vitamin D receptors and susceptibility to, and severity of DDH. The TaqI vitamin D receptor polymorphisms may be associated with abnormal acetabular morphology leading to DDH while the XbaI oestrogen receptor XX genotype may be associated with increased risk of developing DDH. No such correlations were found in the group with PPA

The Osteoprotegerin/RANK/RANKL system has been implicated in the biological cascade of events initiated by particulate wear debris and bacterial infection resulting in periprosthetic bone loss around loosened total hip arthroplasties (THA). Individual responses to such stimuli may be dictated by genetic variation and we have studied the effect of single nucleotide polymorphisms (SNPs) within these genes. We performed a case control study of the Osteoprotegerin, RANK and RANKL genes for possible association with deep sepsis or aseptic loosening. All patients included in the study were Caucasian and had had a cemented Charnley THA and polyethylene acetabular cup. Cases consisted of 91 patients with early aseptic loosening and 71 patients with microbiological evidence at surgery of deep infection. Controls consisted of 150 THAs that were clinically asymptomatic for over 10 years and demonstrated no radiographic features of aseptic loosening. DNA samples from all individuals were genotyped using Taqman allelic discrimination. The A allele (p<0.001) and homozygous genotype A/A (p<0.001) for the OPG-163 SNP were highly associated with aseptic failure. Additionally, the RANK-575 (C/T SNP) T allele (p=0.004) and T/T genotype (p=0.008) frequencies were associated with aseptic failure. No statistically significant relationship was found between aseptic loosening and the OPG- 245 or OPG-1181 SNPs. When the septic group was compared to controls, the frequency of the A allele (p<0.001) and homozygous genotype A/A (p<0.001) for the OPG-163 SNP were statistically significant. No statistically significant relationship was found between septic failure and the OPG- 245, OPG-1181 or RANK-575 SNPs. Aseptic loosening and possibly deep infection of THA may be under genetic influence to candidate susceptibility genes. SNP markers may serve as predictors of implant survival and aid pharmacogenomic prevention of THA failure

INTRODUCTION. Since the recall of some metal on metal (MoM) THR bearings, surgeons have seen patients with pain, elevated Co and Cr levels and adverse local tissue reactions (ALTR). While many variables may contribute to THR MoM failures, many times these variables are not present in patients who present with symptoms. We investigate the possible genetic predilection of a group of patients who were revised after MoM THR surgery for pain, high Co/Cr levels and ALTR. METHODS. IRB approval was obtained prior to our study. We have analyzed 19 control (asymptomatic MoM THR patients > 6 years after surgery) and 19 disease (revised MoM THR for high metal ions and ALTR). The 38 sample intensity files were subject to sample Quality Control (QC) using Contrast QC (< 0.4) with an Affymetrix Genotyping Console. The resulting 38 sample files with genotype calls were loaded and further analyzed using the Association Workflow in Partek Genomics Suite 6.6 (Partek, Missouri). Hardy-Weinberg equilibrium test was performed on the single nucleotide polymorphism (SNP) level. The difference between the observed and expected frequencies of each allele at each locus were tested by Fisher's exact test and χ2 test. To get the working SNP list, two filters were used: (1) a SNP no-call rate should be less than 5%, and (2) minor allele frequency of a SNP should be greater than 5%. After filtering, association analysis of the SNPS with disease was done using Chi. 2. Test. In this study, χ. 2. statistic was used to assess the difference in allele frequencies between the control and disease samples. The value of χ2 statistic, degrees of freedom, and the associated p-value for each SNP were calculated. Dot Plot was used to visualize the genotypes of all samples. To measure the non-random association of alleles at different loci, Linkage Disequilibrium analysis was performed using the neighborhood size of 20 and statistic r. 2. The resulting correlations show the value of r. 2. for SNPs. The r. 2. = 1 means that two SNPs are tightly associated. RESULTS. We found that several SNPs are linked to the revision disease group that showed evidence of metal sensitivity. Among them, a strong association in the disease group was found in a SNP called MS1. In the disease group 17/19 patients were either heterozygous or recessive homozygous for MS1, with 17/19 asymptomatic patients were of the homozygous dominant MS1 isoform. Based on the Linkage Disequilibrum analysis results, several other SNPs were also fund to be strongly correlated with the disease group (Fig 1). The controls had an average Co level of 2.4 and Cr level of 1.3 while the disease group 18 and 10.4 respectively. CONCLUSIONS. This study found a strong genetic relationship in a gene we designate as MS1 where the homozygous recessive and heterozygous isoform genotypes were found in the disease group of revised MoM THRs. A strong correlation of several SNPs was also found. This may be a good predictor of failures and an avenue for personalized choice of implants in the future. For figures/tables, please contact authors directly.

Aim. Although there are no treatment guidelines for Propionibacterium acnes (PA) bone and joint infections (Corvec et al Acta Orthopedica 2016), these infections can be treated with a combination of fluoroquinolones and rifampicin. Rifampicin resistance have already been reported either in in vitro selected mutants or clinical isolates (Furustrand et al JAC 2013, Anaerobe 2015). Minimal inhibitory concentrations of levofloxacin (LVX) ranging from 0,12 to 0.5mg/L are regularly observed but resistance has not yet been investigated. We investigated the in vitro emergence of LVX resistance and characterized the mutations involved in gyrA gene. Method. The strain of PA ATCC11827 (MIC LVF = 0.25 mg/L) was used. The frequency of mutation was determined after inoculation of 108 PA on blood agar containing concentrations of 2 to 128 times the MIC incubated for 7 days in anaerobiosis at 35 ° C. The emergence of high-level of resistance was also studied from the low-level mutants after a second exposure. For the resistant mutants, the gyrA and parC genes were sequenced and compared to the PA reference sequences. Results. The mutation frequency was 3.8 cfu × 10–8 (8×MIC) and 1.6 cfu × 10–7 (4×MIC), respectively. A low or high-level resistance to LVX was observed. MICs varied between 0.75 and> 32 mg/L and were stable after three subcultures. 87 mutants were studied including 40 with a mutation in gyrA gene. 10 different genotypes could be demonstrated with either high-level resistance: G99 (n = 4), G99 D (n = 3), D100N (n = 1), S101 L (n = 14), S101W N = 5) or low-level resistance D100H (n=1), D100G (n=1), A102P (n=5), D105 H (n = 4), D105 G (n = 2). Substitution 101 always leads to a high level of resistance. No mutation was found in parC gene. Conclusions. To our knowledge, this is the first description of the emergence of LVX resistance in PA. The MIC increases from sensitivity to low or high-level resistance. This resistance is stable and associated exclusively with mutations in the gyrA gene. Six different positions give rise to ten different genotypes. The passage from a low to a high-level resistance is done mainly by the selection of the mutation at position 101. Finally, some mutants do not exhibit mutations in QRDRs, suggesting the existence of an efflux system

Tenomodulin (Tnmd) is the best known mature tendon factor for tendon and ligament tissues with reported important regulatory roles1. In addition, Tnmd C-terminal cysteine-rich domain has been descibed to exert anti-angiogenic functions in in vitro angiogenic assays as well as in vivo models of tendon injury and age-associated cardiac valve diseases1, 2. Interestingly, Tnmd expresson in the intervertebral disc (IVD), which is normally avascular tissue, has been also suggested3. Hence, the purpose of this study was first, to map the exact expression pattern of Tnmd during IVD development and aging and second, by implementing Tnmd-knockout mouse model, to examine if Tnmd plays a role in IVD homeostasis. Histological analyses (hematoxylin/eosin, Safranin O, CD31 for endothelium, TUNEL for apoptosis and type X collagen and Runx2 for hypetrophy) were performed on Tnmd −/−, Tnmd −/− and chondromodulin I Chmd 1 −/− (Tnmd only homolog) double knockout and wild type mice WT (n = three to five) to examine IVD degeneration. Real time PCR was implemented to explore gene expression chnages in annulus fibrous (AF) between Tnmd −/− and WT mice. In addition, outer AF (OAF) cells were isolated from both genotypes to further determine cellular phenotype and assess effects on co-culture with human umbical vein endothelial cells (HUVECs). Statistical differences between two groups were determined with t-test. In multiple comparisons, one-way ANOVA was followed by Bonferroni post-hoc correction. Tnmd was expressed in a temporal manner in OAF and to very low extent in NP. Tnmd −/− mice exhibited more rapid progression of age-related IVD degeneration. These signs included smaller collagen fibril diameter, reduced multiple IVD- and tendon/ligament-related gene expression, induced angiogenesis and inflamatory cell infiltration in OAF as well as more hypertrophic-like chondrocytes in the NP. In addition, Tnmd−/− Chm1 −/− mice displayes not only accelerated IVD phenotpye, but also ectopic bone formation in the IVD. Lastly, the abscence of Tnmd in OAF-derived cells significantly promoted HUVECs migratory capacity. These findings provide clear evidence that Tnmd plays a critical role in IVD homeostasis

Aims

Sickle cell disease (SCD) is an autosomal recessive inherited condition that presents with a number of clinical manifestations that include musculoskeletal manifestations (MM). MM may present differently in different individuals and settings and the predictors are not well known. Herein, we aimed at determining the predictors of MM in patients with SCD at the University Teaching Hospital, Lusaka, Zambia.

Aims

This study aimed to assess the performance of an automated multiplex polymerase chain reaction (mPCR) technique for rapid diagnosis of native joint septic arthritis

Aims

Tuberculosis (TB) infection of bones and joints accounts for 6.7% of TB cases in England, and is associated with significant morbidity and disability. Public Health England reports that patients with TB experience delays in diagnosis and treatment. Our aims were to determine the demographics, presentation and investigation of patients with a TB infection of bones and joints, to help doctors assessing potential cases and to identify avoidable delays.

We compared the use of broth culture medium for samples taken in theatre with the standard practice of placing tissue samples in universal containers. A total of 67 consecutive patients had standard multiple samples of deep tissue harvested at surgery and distributed equally in theatre either to standard universal containers or to broth culture medium. These samples were cultured by direct and enrichment methods. The addition of broth in theatre to standard practice led to an increase in sensitivity from 83% to 95% and an increase in negative predictive value from 77% to 91%. Placing tissue samples directly into broth in the operating theatre is a simple, inexpensive way to increase the sensitivity of cultures from infected patients, and does not appear to compromise the specificity of these cultures.

Cite this article: Bone Joint J 2014;96-B:1566–70.

Little information is available about several important aspects of the treatment of melioidosis osteomyelitis and septic arthritis.

We undertook a retrospective review of 50 patients with these conditions in an attempt to determine the effect of location of the disease, type of surgical intervention and duration of antibiotic treatment on outcome, particularly complications and relapse.

We found that there was a 27.5% risk of osteomyelitis of the adjacent bone in patients with septic arthritis in the lower limb. Patients with septic arthritis and osteomyelitis of an adjacent bone were in hospital significantly longer (p = 0.001), needed more operations (p = 0.031) and had a significantly higher rate of complications and re-presentation (p = 0.048).

More than half the patients (61%), most particularly those with multifocal bone and joint involvement, and those with septic arthritis and osteomyelitis of an adjacent bone who were treated operatively, needed more visits to theatre.

Cite this article: Bone Joint J 2015;97-B:277–82.