Osteoarticular infections (OAI) are a common cause of morbidity in children, and as opposed to adults is usually caused by haematogenous spread. The bacteriology of OAI in children is not well described in the South African context, therefore this study was designed to determine the bacteriology of OAI in our population. All patients that underwent surgery for the treatment of OAI over a 3-year period were identified and those with positive cultures where organisms were identified from tissue, pus, fluid or blood were included. Duplicate cultures from the same patient were excluded if the organism and antibiotic susceptibility profile was the same. Patients were categorised according to age and class of infection (Septic arthritis, acute osteomyelitis, fracture related infection, post-operative sepsis and chronic osteomyelitis) and organisms were stratified according to these categories. We identified 132 organisms from 123 samples collected from 86 patients. Most cultured organisms were from children older than 3-years with acute haematogenous septic arthritis, osteomyelitis, or both. Methicillin sensitive Staphylococcus aureus accounted for 56% (74/132) of organisms cultured. There were no cases of MRSA. The Enterobacterales accounted for 17% (22/132) of organisms cultured, mostly in the fracture related and post-operative infection groups. Of these, 6 each were extended spectrum B-lactamase producers and AmpC producers. There were no carbapenemase producing Enterobacterales. Kingella kingae was not isolated in any patient. Methicillin sensitive S. aureus is the most common infecting organism in paediatric OAI and an anti-staphylococcal penicillin such as cloxacillin or flucloxacillin is the most appropriate empiric treatment for haematogenous OAI in our environment. In fracture related or post-operative infections, Enterobacterales were more frequently cultured, and treatment should be guided by culture and susceptibility results

Aims. Degenerative cervical spondylosis (DCS) is a common musculoskeletal disease that encompasses a wide range of progressive degenerative changes and affects all components of the cervical spine. DCS imposes very large social and economic burdens. However, its genetic basis remains elusive. Methods. Predicted whole-blood and skeletal muscle gene expression and genome-wide association study (GWAS) data from a DCS database were integrated, and functional summary-based imputation (FUSION) software was used on the integrated data. A transcriptome-wide association study (TWAS) was conducted using FUSION software to assess the association between predicted gene expression and DCS risk. The TWAS-identified genes were verified via comparison with differentially expressed genes (DEGs) in DCS RNA expression profiles in the Gene Expression Omnibus (GEO) (Accession Number: GSE153761). The Functional Mapping and Annotation (FUMA) tool for genome-wide association studies and Meta tools were used for gene functional enrichment and annotation analysis. Results. The TWAS detected 420 DCS genes with p < 0.05 in skeletal muscle, such as ribosomal protein S15A (RPS15A) (PTWAS = 0.001), and 110 genes in whole blood, such as selectin L (SELL) (PTWAS = 0.001). Comparison with the DCS RNA expression profile identified 12 common genes, including Apelin Receptor (APLNR) (PTWAS = 0.001, PDEG = 0.025). In total, 148 DCS-enriched Gene Ontology (GO) terms were identified, such as mast cell degranulation (GO:0043303); 15 DCS-enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were identified, such as the sphingolipid signalling pathway (ko04071). Nine terms, such as degradation of the extracellular matrix (R-HSA-1474228), were common to the TWAS enrichment results and the RNA expression profile. Conclusion. Our results identify putative susceptibility genes; these findings provide new ideas for exploration of the genetic mechanism of DCS development and new targets for preclinical intervention and clinical treatment. Cite this article: Bone Joint Res 2023;12(1):80–90

Aim. Empiric antibiotic therapy for suspected pyogenic spondylodiscitis (SD) should be initiated immediately with severely ill patients and may also be necessary for culture-negative SD. The aim of this study was to infer an appropriate empiric antibiotic regimen by analyzing the antimicrobial susceptibility of isolated pathogens from microbiologically proven pyogenic spondylodiscitis. Method. We performed a retrospective review of adult patients with clinically proven SD treated at our level 1 trauma center between 2013 and 2020. Demographic data, radiologic findings, and treatment modalities were evaluated. The appropriateness of empiric antibiotic regimens was assessed based on the antibiograms of the isolated pathogens. Anamneses were used to distinguish between community-acquired (CA) and healthcare-associated (HA) pathogens, which included cases that had a hospital stay or invasive intervention in the past 6 months. Results. A total of 155 patients (male: N=88; female: N=67; mean age 66.1 ± 12.4 years) with SD were identified. In n= 74 (47.7%) cases, the infections were associated with the healthcare system (HA). N=34 (21.9%) patients suffered from sepsis. The lumbar spine was involved in 47.1% of the cases, the thoracic spine in 37.3%, and the cervical spine in 7.8%. In 7.8% of the cases, SD occurred in multiple spinal segments. N=96 (62.0%) patients were treated surgically. The mean hospital stay was 36.4 ± 36.3 days. Antibiograms of n=45 patients (HA: N=22; CA: N=23) could be retrospectively evaluated: The most frequently identified pathogens were Staphylococcus aureus (46.7%), Coagulase-negative Staphylococci (17.8%), Enterobacteriaceae (15.6%) and Streptococcus species (15.6%). Overall, 82.2% (HA: 68.2%; CA: 95.5%) of the isolated pathogens were sensitive to piperacillin/tazobactam, 77.8% (HA: 81.8%; CA: 72.2%) to vancomycin, 64.4% (HA: 68.2%; CA: 59.1%) to clindamycin, and 55.6% (HA: 36.4%; CA: 72.7%) to ceftriaxone. To a combination of vancomycin plus meropenem 97.8% of pathogens were sensitive (HA: 95.5%; CA: 100.0%), to vancomycin plus ciprofloxacin 91.1% (HA: 86.4%; CA: 95.7%), and to vancomycin plus cefotaxime 93.3% (HA: 90.9%; CA: 95.7%). In 14 cases, empiric antibiosis was adjusted based on the results of the antibiogram. Conclusions. Antibiotic resistance of CA SD pathogens differed significantly from HA SD. The identification of the pathogen and the analysis of its susceptibility guides the antibiotic therapy. Vancomycin in combination with a carbapenem, broad-spectrum cephalosporin, or fluoroquinolone may be appropriate for empiric treatment of HA SD

Heterotopic ossification (HO) is lamellar bone formation that occurs within tissues that do not normally have properties of ossification. The pathoaetiology of HO is poorly understood. We conducted a genome wide association study to better understand the genetic architecture of HO. 891 patients of European descent (410 HO cases) following THA for primary osteoarthritis were recruited from the UK. HO was assessed from plain AP radiographs of the pelvis. Genomic DNA was extracted, genotyped using the Illumina 610 beadchip and referenced using the 1000 Genome Project panel. HO susceptibility case-control analysis and an evaluation of disease severity in those with HO was undertaken using SNPTESTv2.3.0 on>10 million variants. We tested variants most strongly associated with HO in an independent UK THA replication cohort comprising 209 cases and 211 controls. The datasets were meta-analysed using PLINK. In the discovery cohort 70 signals with an index variant at p<9×10–5 were suggestively associated with HO susceptibility. The strongest signal lay just downstream of the gene ARHGAP18 (rs59084763, effect allele frequency (EAF) 0.19, OR1.87 [1.48–2.38], p=2.48×10–8), the second strongest signal lay within the long non-coding (LNC) RNA gene CASC20 (rs11699612, EAF 0.25, OR1.73 [1.1.40–2.16, p=9.3×10–8). In the discovery cohort 73 signals with an index variant at p<9×10–5 were associated with HO severity. At replication, 12 of the leading 14 susceptibility signals showed a concordant direction of allelic effect and 5 replicated at nominal significance. Following meta-analysis, the lead replicating susceptibility signal was the CASC20 variant rs11699612 (p=2.71×10–11). We identify consistent replicating association of variation within the LNC RNA CASC20 with HO susceptibility after THA. Although the function of CASC20 is currently unknown, possible mechanisms include transcriptional, post-transcriptional and epigenetic regulation of downstream target genes. The work presented here provides new avenues for the development of novel predictive and therapeutic approaches towards HO

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. 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®

Background and methods: Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity in children, with a prevalence of 1–2%. The disease generally displays complex inheritance. Various family studies have produced many first reports of AIS susceptibility regions, but confirmation of these is lacking. In the present study we investigated extension of our own data, and reproducibility of other published results, by testing linkage in a new collection of fifty-four AIS families. Altogether fifteen candidate regions were evaluated in a two-stage design. Results: Strongest results were obtained for linkage to microsatellite loci within a candidate region of proximal 8q previously identified by chromosomal breakpoint mapping. Although positive lod scores were obtained for other regions, none exhibited significance less than or equal to P = .05. Lod scores remained stable after analysis of an independent panel of SNP loci in the 8q candidate region and were strengthened with inclusion of additional affected family members (multipoint NPL = 3.02, P = 0.001). Two SNPs near the peak of linkage produced evidence of association to AIS susceptibility. Both SNPs are found within plausible candidate genes for AIS susceptibility. Conclusion: These results support linkage of the 8q11-8q13 region to AIS susceptibility. Bashiardes et al. previously described a chromosomal break in the 8q11 region that disrupted the gamma-1- syntrophin (SNTG1) gene and segregated with AIS in an extended kindred. In that study, possible rare splice site mutations were identified an additional affected family and one sporadic case. The peak of linkage and association detected in this study appears to be distinct from the SNTG1 gene. This suggests the possibility that more than one gene in the region may contribute to disease. A more detailed analysis of the region encompassing this linkage peak, and the SNTG1 gene, is warranted in larger family collections

Introduction. Periprosthetic infection (PJI) after primary total knee arthroplasty (TKA) remains a challenging issue affecting 1–2% of cases. Locally delivered prophylactic antibiotics, including tobramycin or gentamicin mixed in polymethylmethacrylate (PMMA) bone cement and vancomycin powder, are increasingly used despite a lack of high quality evidence for either practice. In this study, we report the antibiotic susceptibility of organisms recovered in culture from patients with acute prosthetic joint infection after primary TKA to gentamicin, tobramycin and vancomycin. Methods. Using a retrospective database of all primary TKA performed at a single institution between January, 1 2014 and July 1, 2018, we identified 18 cases of acute PJI after primary TKA, as defined by the Musculoskeletal Infection Society 2011 guidelines as less than 3 months from symptoms or index surgery to presentation. The use of antibiotic bone cement during the index procedure and time to surgical management of the infection were recorded. Fluid cultures and tissue cultures were obtained intraoperatively at the time of revision. The organisms from positive cultures underwent MIC testing to gentamicin, tobramycin and vancomycin using a gradient diffusion method (ETEST). MIC breakpoints for susceptibility were based on Clinical and Laboratory Standards Institute definitions. Results. 18 cases of PJI after TKA were identified, including 4 polymicrobial infections (22.2%) (Table 1). Average time to revision for infection was 38 days (range: 6–84 days). 34.8% of bacterial isolates were resistant to gentamicin, 39.1% were resistant to tobramycin and 17.4% were resistant to vancomycin. Of the 8 bacterial isolates resistant to gentamicin, 7 (87.5%) were susceptible tobramycin. Of the 9 bacterial isolates resistant to tobramycin, (88.9%) were susceptible to vancomycin. One bacterial isolate, a Fusobacterium nucleatum from a polymicrobial infection was resistant to gentamicin, tobramycin and vancomycin. Conclusion. Over one third of bacteria causing acute PJI after primary TKA were resistant to the aminoglycosides pre-mixed in commercially available bone cements. All but one of the bacteria resistant to gentamicin and tobramycin were susceptible to vancomycin. The addition of vancomycin to bone cement or as powder in the surgical field has the potential to expand antibiotic coverage to include most organisms responsible for acute PJI after TKA. For figures, tables, or references, please contact authors directly

INTRODUCTION. Prosthetic joint related-infections (PJRI) are severe complications in orthopaedic surgery. Staphylococcus aureus and Staphylococcus epidermidis are the most commonly isolated pathogens from implants (1). The variable antimicrobial susceptibility found in these microorganisms, makes it necessary to perform individual susceptibility studies in order to select the best antibiotic combination for clinical management (2). MATERIAL AND METHODS. 35 staphylococcal strains (17 S. aureus, 18 S. epidermidis) were isolated from PJRI using a previously described sonication protocol (3). Biofilm-producing collection strains S. aureus 15981 (4) and S. epidermidis ATCC 35984 were also included in the study. In vitro susceptibility was evaluated against 7 antimicrobial agents: rifampin, vancomycin, ciprofloxacin, cotrimoxazole, cloxacillin, clindamycin, and daptomycin. Minimal Inhibitory Concentration (MIC) assays were determined according to EUCAST recommendations and breakpoints (5). Minimal Bactericidal Concentration (MBC) was also calculated by colony counting after plating the well contents. RESULTS. Antibiotic susceptibility assay results are shown in tables 1 and 2. It is especially remarkable the high number of meticillin-resistant S. aureus (MRSA) strains. Cotrimoxazole and clindamycin showed better results for S. aureus. Rifampin, vancomycin, and daptomycin showed a very good activity, although some resistant strains were detected for the first two. MBC values showed a strain-dependant activity of rifampin and vancomycin. Only daptomycin showed bactericidal activity against all the tested strains. DISCUSSION & CONCLUSIONS. The treatment of PJRI is still a challenge due to the variable antibiotic susceptibility and the growing number of multidrug-resistant strains. The high number of MRSA detected in our study, makes it necessary to search other antibiotics as an alternative to vancomycin, the traditional elective treatment. The high in vitro activity of daptomycin against the tested strains suggests that it could be an important alternative according to other promising results (6). Rifampin associated with other antimicrobials and cotrimoxazole, with a good in vitro activity against most MRSA strains, could be other potential strategies (7, 8)

Anatomical variation of Lisfranc mortise has been implicated in the susceptibility of Lisfranc fracture-dislocation. We investigated whether the variations in the dimensions of second metatarsal base makes the joint vulnerable to fracture dislocation. Patients and Methods: 31 normal (group A) and 23 injured (group B) foot x-rays were compared. The average age of patients was 33(range 16–64) years. Routine AP and 45 degree oblique foot x-rays were used to measure second metatarsal parameters such as L (length of second metatarsal) were measured on x-rays in both groups. Additionally D (height of base of second metatarsal in sagittal plane of foot) was measured in CT scans. Statistical analysis was performed to test the viability of the null hypothesis that states that the relationship of second metatarsal length and height at the base does not correlate with increased susceptibility of Lisfranc injury. Similar analyses of the relevant parameters at the second metatarsal mortice were also calculated. Results: Mean values of D, L and D/L were obtained in both groups. Statistically the value of D/L was found to be significantly different between injured group and normal group, with a P value of 0.03, while the values of length of second metatarsal itself was not significantly different between two groups (P=0.15). However, no significant correlation was noticed using other parameters of the second metatarsal mortice. Conclusion: Previously shallowness of the second metatarsal mortice was shown to be significantly correlated with increased risk of Lisfranc injury. However, this study suggests that dimensions of second metatarsal such as, depth/length of the second metatarsal significantly increase the risk of Lisfranc injury. In other words more slender metatarsal dimensions at its base carry increased risk to Lisfranc injury. Thus, anatomical variation at the base of the second metatarsal makes the Lisfranc joint susceptible to injury

Objectives. Given the function of adiponectin (ADIPOQ) on the inflammatory condition of obesity and osteoarthritis (OA), we hypothesized that the ADIPOQ gene might be a candidate gene for a marker of susceptibility to OA. Methods. We systematically screened three tagging polymorphisms (rs182052, rs2082940 and rs6773957) in the ADIPOQ gene, and evaluated the association between the genetic variants and OA risk in a case-controlled study that included 196 OA patients and 442 controls in a northern Chinese population. Genotyping was performed using the Sequenom MassARRAY iPLEX platform. Results. The single nucleotide polymorphism (SNP) rs182052 was found to be potentially associated with knee OA risk (additive model: odds ratio = 1.38; 95% confidence interval 1.07 to 1.76; p = 0.012). Furthermore, a non-significant association was observed for rs182052 and body mass index with regard to OA risk in interaction analyses (p = 0.063). Similarly, no significant interaction was detected for rs182052 and age with regard to OA risk (p = 0.614). Conclusion. These findings suggest that the SNP rs182052 in the ADIPOQ gene may potentially modify individual susceptibility to knee OA in the Chinese population. Further studies are warranted to investigate our findings in more depth. Cite this article: L. Jiang, X. Zhu, J. Rong, B. Xing, S. Wang, A. Liu, M. Chu, G. Huang. Obesity, osteoarthritis and genetic risk: The rs182052 polymorphism in the ADIPOQ gene is potentially associated with risk of knee osteoarthritis. Bone Joint Res 2018;7:494–500. DOI: 10.1302/2046-3758.77.BJR-2017-0274.R1

Objectives. The objective of this study was to investigate the association of four single-nucleotide polymorphisms (SNPs) of the cannabinoid receptor 2 (CNR2) gene, gene-obesity interaction, and haplotype combination with osteoporosis (OP) susceptibility. Methods. Chinese patients with OP were recruited between March 2011 and December 2015 from our hospital. In this study, a total of 1267 post-menopausal female patients (631 OP patients and 636 control patients) were selected. The mean age of all subjects was 69.2 years (sd 15.8). A generalized multifactor dimensionality reduction (GMDR) model and logistic regression model were used to examine the interaction between SNP and obesity on OP. For OP patient-control haplotype analyses, the SHEsis online haplotype analysis software (. http://analysis.bio-x.cn/. ) was employed. Results. The logistic regression model revealed that the C allele of rs2501431 and the G allele of rs3003336 were associated with increased OP risk, compared with those with wild genotype. However, no significant correlations were found when analyzing the association of rs4237 and rs2229579 with OP risk. The GMDR analysis suggested that the interaction model composed of two factors, rs3003336 and abdominal obesity (AO), was the best model with statistical significance (p-value from sign test (P. sign. ) = 0.012), indicating a potential gene-environment interaction between rs3003336 and AO. Overall, the two-locus models had a cross-validation consistency of 10/10 and had a testing accuracy of 0.641. Abdominally obese subjects with the AG or GG genotype have the highest OP risk, compared with subjects with the AA genotype and normal waist circumference (WC) (odds ratio (OR) 2.23, 95% confidence interval (CI) 1.54 to 3.51). Haplotype analysis also indicated that the haplotype containing the rs3003336-G and rs2501431-C alleles was associated with a statistically increased OP risk. Conclusion. Our results suggested that the C allele of rs2501431 and the G allele of rs3003336 of the CNR2 gene, interaction between rs3003336 and AO, and the haplotype containing the rs3003336-G and rs2501431-C alleles were all associated with increased OP risk. Cite this article: Bone Joint Res 2019;8:544–549

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

The first aim of the study was to investigate if bacteria were implicated in non-union of fractures of the tibia and femur, which had been treated with intramedullary nailing. The second aim was to evaluate the antimicrobial susceptibility of bacteria isolated from the retrieved intramedullary nails. Forty intramedullary nails removed from tibial and femoral fractures were retrieved for the purpose of the study. Twenty of these nails were from fractures, which had successfully united and 20 were removed from fractures which had failed to unite prior to further operative intervention. There was no evidence of clinical infection in either of the two groups. The nails were subjected to ultrasound in the research laboratory to dislodge adherent bacteria formed as biofilm from the surface of the nail. Using both standard culture techniques and non-culture techniques (Immunofluorescence microscopy and PCR analysis) any dislodged bacteria were isolated and identified. Isolated bacteria were tested for antimicrobial susceptibility to commonly used antibiotics in orthopaedic practice according to NCCLS guidelines. Bacteria were detected in 15 out of 20 [75%] of the nails removed from fractures, which had developed a non-union, and in 5 out of 20 [25%] of fractures that had united, using both standard culture techniques and non-culture techniques. The bacterial isolates identified were mainly Staphylococcus epidermidis and the Gram-positive anaerobe Proprionibacterium acnes. Vancomycin was the most effective antibiotic, with 2 out of 34 [6%] isolates being resistant. Erythromycin was the least effective, with 21 out of 34 [62%] isolates being resistant. Based on overall Minimum Bactericidal Concentrations at which 90% of all strains were killed, Vancomycin was the most active bactericidal agent tested followed in decreasing order by fucidic acid, ciprofloxacin, gentamicin, cefamandole and erythromycin. Bacteria were detected more commonly in the fracture non-union group than in the union group [p< 0.01]. Of the antibiotic agents tested Vancomycin was the most effective and Erythromycin was the least effective

Introduction. Hip Osteoarthritis (HOA) is a highly heterogeneous disease with potentially different genetic aetiologies. Thus far, few genetic variants have been robustly associated with broad definitions of HOA. We aimed to identify novel HOA susceptibility variants by examining a set of more homogeneous, radiographically-derived endophenotypes relating to anatomic pattern of joint involvement and bone remodelling response in HOA. Materials, Methods and Results. Individuals with HOA and AP-hip radiographs (n=2,109) were selected from the arcOGEN study, genotyped on 2 platforms. The most arthritic hip per patient was categorised using Bombelli's classification (atrophic/normotrophic/hypertrophic), and for pattern of joint space narrowing (superior/medial-axial/concentric). Following 1000-Genomes-Project-based imputation and stringent quality control over 7 million variants were tested for association with each phenotype under the additive model. Fixed-effects meta-analysis was used to combine the results from the two GWA studies. In the discovery GWAS of atrophic HOA vs cases with non-atrophic HOA a strong signal (rs16869403, OR[95% CI]=2.47[1.81–3.38], p=1.53×10. −8. ) was detected in the G protein-coupled receptor, GPR98. Polymorphisms in GPR98 have been associated with osteoporotic fracture and low bone mineral density and GPR98 knockout mice have a low bone mass phenotype. The meta-analysis of medial joint space narrowing showed strong association with variants in LRCH1 (rs754106, OR[95% CI]=1.46[1.26–1.68], P=2.85×10. −7. ) previously associated with OA but with conflicting replication evidence, and BMP1 (chr8:22065846, OR[95% CI]=3.36[2.12–5.33], P=2.6×10. −7. ) which induces bone and cartilage development. None of these variants showed significant evidence for association when broadly classified HOA cases were compared to population-based controls from the arcOGEN GWAS. Conclusion. Through comprehensive examination of radiographically-derived, HOA-related phenotypes we have identified several promising signals that point to novel biologically plausible genes for HOA. Our results indicate that, in a heterogeneous disease like OA the study of narrower phenotype definitions closer to the biology of the disease has the potential to enhance power to detect OA-relevant associations

Objectives. Previous genome-wide association studies (GWAS) have reported significant association of the single nucleotide polymorphism (SNP) rs8044769 in the fat mass and obesity-associated gene (FTO) with osteoarthritis (OA) risk in European populations. However, these findings have not been confirmed in Chinese populations. Methods. We systematically genotyped rs8044769 and evaluated the association between the genetic variants and OA risk in a case-controlled study including 196 OA cases and 442 controls in a northern Chinese population. Genotyping was performed using the Sequenom MassARRAY iPLEX platform. Results. We found that the variant T allele of rs8044769 showed no significant association of OA risk (p = 0.791), or association with body mass index (BMI) (pmeta = 0.786) in an additive genetic model. However, we detected a significant interaction between rs8044769 genotypes and BMI on OA risk (p = 0.037), as well as a borderline interaction between rs8044769 genotypes and age on OA risk (p = 0.062). Conclusions. Our findings indicate that rs8044769 in the FTO gene may not modify individual susceptibility to OA or increased BMI in the Chinese population. Further studies are warranted to validate and extend our findings. Cite this article: Prof L. Jiang. No association of the single nucleotide polymorphism rs8044769 in the fat mass and obesity-associated gene with knee osteoarthritis risk and body mass index: A population-based study in China. Bone Joint Res 2016;5:169–174. DOI: 10.1302/2046-3758.55.2000589

Introduction. Adolescent idiopathic scoliosis (AIS) is the most common paediatric spinal deformity, affecting about 3% of school-aged children worldwide. This disorder occurs in otherwise healthy children who bear no obvious deficiencies in the components of the spinal column itself. The cause of AIS is poorly understood, as is implied by the name. Lesions of the bony composition of the vertebrae, the vertebral endplates, the paraspinous muscles, or the neurological system each have been proposed to explain disease pathogenesis. Progress has been hampered by the absence of an obvious AIS animal model. Consequently we have used genetic studies in human populations to identify factors underlying AIS susceptibility. The complex inheritance and population frequency of AIS suggest that many genetic factors are involved in this disease. To search comprehensively for such factors we previously undertook the first genome-wide association study (GWAS) of AIS susceptibility in a cohort of 419 families in Texas, USA. We found that chromosome 3 SNPs in the proximity of the CHL1 gene yielded strongest results, which we replicated in additional cohorts (rs10510181 OR 1·49, 95% CI 1·29–173, p=2·58×10–8). CHL1 is of interest because it encodes an axon guidance protein and is functionally related to the ROBO3 gene that causes hereditary gaze palsy with progressive scoliosis (HGPPS), a rare disease marked by severe scoliosis. Here we expanded the study to 702 Texas families. Methods. We tested more than 327 000 single-nucleotide polymorphisms (SNPs) across all human autosomes for association with disease. Results. Results of the study in 702 Texas families yielded evidence for association with SNPs in a second axon guidance gene, DSCAM, which encodes a protein in the same structural and functional class with Chl1 and Robo3 (rs2222973 combined OR 0·59, 95% CI 0·48–0·74; p=1·46×10–6). We additionally found AIS associations with loci in CNTNAP2, whose protein product interacts directly with L1 and Robo class proteins and participates in axon pathfinding. Conclusions. These data support genetic variation in axon guidance genes as risk factors in AIS. Our results provide new insight into disease pathogenesis and suggest that late-onset scoliosis may be correlated with secondary neurological development

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

To determine the effect of normal human ageing on neutrophil function and to assess the contribution that any decline may play in the increased susceptibility of elderly patients to bacterial infections following minor trauma. Furthermore, to determine any contribution, of trauma, to further neutrophil decline in these elderly patients. Phagocytic index, CD16 (FcγRIIIB) and CD11b (CR3) expression were determined in neutrophils isolated from the peripheral blood of 15 healthy young (average age 26. 5 yrs, range 23–35 yrs; 8 male, 7 female) and elderly (average age 72. 9 yrs, range 65–71 yrs; 8 male, 7 female) volunteers. CD11b levels were unaltered, but phagocytic index and CD16 expression were both significantly reduced (p< 0. 05 and p< 0. 001 respectively) in the elderly group. CD16 levels were monitored in a large volunteer group and were found to correlate with phagocytic index. To determine whether trauma produces additional compromise to neutrophil function in the elderly, peripheral blood neutrophils from individuals (average age 82. 5 yrs, range 65–96 yrs; 7 male, 21 female) during neutrophilia, post-trauma, due to fracture of the femur, were analysed as described above. Patients with chronic inflammatory disease, diabetes or kidney disease, or who were receiving steroid medication, were excluded. The data showed that neutrophil CD16 expression was significantly reduced in the elderly group (p< 0. 05), furthermore following fracture of the neck of femur superoxide generation is significantly reduced. Patient follow up revealed that 17 (60. 8 %) of these patients subsequently acquired bacterial infections (including wound), within 4 weeks of trauma. Normal human ageing was accompanied by a decline in neutrophil phagocytic ability and this may be in part due to reduced levels of the Fcγ receptor CD16. The reduced neutrophil CD16 expression accompanied by reduced superoxide generation in the elderly trauma patients may significantly undermine their ability to combat bacterial infections and contribute to increased incidence of post-traumatic infections in the elderly

Purpose: Operative site infections can have catastrophic consequences after orthopaedic surgery. Prevention is particularly difficult due to the large number of factors involved. We describe here an exceptional epidemic of meti-R Staphylococcus aureus (MRSA) operative site infections whose source was successfully identified and eradicated. Material and methods: The epidemic affected seven patients who underwent orthopaedic surgery during a thirteen-month period. All patients developed acute MRSA operative site infection. The epidemic nature of the infections was confirmed by the bacteriological study which identified the causal germ as a specific MRSA strain very different from strains generally identified in hospital infections. The causal strain was sensitive to quinolones and resistant to amikacin. Antibiotic therapy prescribed in all cases was combined with surgical lavage in four patients. Search was undertaken to identify an environmental or human source. An audit of the operating theatre was performed and nasal swabs were obtained from all personnel present at the last operation complicated by operative site infection. One non-medical assistant was found to be a carrier of the same MRSA strain incriminated as the cause of the epidemic. Nasal application of mupirocin successfully eradicated the carrier-state. No new case of operative site infection was noted for more than fourteen months. Discussion: Operative site infections in orthopaedic surgery led to longer inpatient care and can compromise functional outcome. These nosocomial infections have a significant impact on mortality and constitute a major cost burden for hospitals. Prevention, control and treatment of MRSA nosocomial infections is a major challenge in hospitals throughout the world. Most operative site infections are caused by direct contamination during the operation. This epidemic highlights the importance of strict application of rigorous preventive measures not only by the surgical team but also by all healthcare workers and hospital personnel in general. Conclusion: The specific antibiotic susceptibility pattern of a Staphylococcus aureus strain incriminated in several operating site infections enabled identification of the source of the epidemic and its eradication