Prospective randomised study comparing screw versus helical blade in the treatment of low-energy trochanteric fractures

Purpose: The purpose of this study was to compare femoral head placement, rates of reoperation and cephalic implant cut-out of a screw versus a blade for patients over age 60 with low energy trochanteric fractures (AO/OTA 31-A1, A2, and A3) treated either with sliding hip screw or cephalomedullary nail. Methods: After surgeon selection of either hip screw or nail, hip screw patients were randomised to either a DHS (dynamic hip system screw) or DHS blade (dynamic hip system blade), while nail patients were randomised to either a Gamma3 Trochanteric Nail or a PFNA (proximal femoral nail antirotation). This resulted in a screw group (DHS and Gamma nail), and a blade group (DHS blade and PFNA). Outcome measures included tip-apex distance and zone location of the cephalic implant, as well as reoperation and implant cut-out within the first postoperative year. Results: A total of 335 patients were randomised, 172 to a screw and 163 to a blade. There was no significant difference concerning mean tip-apex distance, percentage of patients with a tip-apex distance >25mm, and patients with a centre-centre position of the cephalic implant. There were 137 patients in the screw group and 132 in the blade group available for follow-up. They did not differ regarding rates of reoperation or cut-out (screw group = 2.9%; blade group = 1.5%). Conclusions: Both a screw and a blade performed equally well in terms of implant placement in the femoral head and outcom

Adipokines correlate with pain in lower limb osteoarthritis: different associations in hip and knee

Purpose: Our aim was to investigate whether serum and synovial-fluid (SF) concentrations of interleukin-6 (IL-6), leptin, adiponectin, resistin or visfatin are associated with joint pain in hip and knee in end-stage osteoarthritis (OA). Methods: A cross-sectional study assessing patients with hip and knee OA undergoing total joint arthroplasty between January and December 2010 was conducted at a large university hospital. Serum and SF cytokine and adipokine concentrations were determined in samples obtained on the day of surgery. The main outcome was pain severity measured pre-operatively using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and visual analogue scale (VAS) pain scores. Results: A total of 206 patients were involved (112 with hip and 94 with knee OA). Median age was 72years [interquartile range (IQR) 66-79], 59% were women. All adipokine levels were significantly higher in the SF of hip joints than in that of knee joints, except for leptin, which tended to be higher in the knee. In both hip and knee OA, median serum concentrations of leptin, adiponectin, resistin and visfatin exceeded those in SF, whereas for IL-6, median concentrations were much higher in SF than in serum. In hip OA, worse pain was significantly associated with high SF concentrations of IL-6, visfatin and leptin; in knee OA, it was associated with high SF leptin and low SF adiponectin concentrations and a low adiponectin-leptin ratio. Conclusion: Our findings support a connection between intra-articular concentrations of several adipokines and severity of preoperative OA pain. However, the specific adipokines differed by joints: in hip OA, pain was associated with IL-6 and visfatin and in knee OA with adiponectin; leptin played a role in both hip and knee OA

Do synovial leptin levels correlate with pain in end stage arthritis?

Purpose: We evaluated whether synovial fluid (SF) leptin concentrations correlate with pain severity in patients with hip or knee endstage osteoarthritis (OA) and whether they mediate the association between increased joint pain and (1) female gender and (2) obesity. Methods: We conducted a cross-sectional study including patients with primary hip and knee OA undergoing joint replacement between January and December 2010. SF leptin concentrations obtained on the day of surgery were assessed. Main outcome was pain severity measured pre-operatively using WOMAC and VAS pain scales. Results: A total of 219 patients were included, 123 hip and 96 knee arthroplasties. Mean age was 72years, 59% were women. Mean SF leptin levels were 22.9 (±25.6) ng/ml in women and 5.4 (±5.9) ng/ml in men. Levels >19.6ng/ml (highest quartile) were significantly associated with increased pain on both WOMAC (mean difference −9.6, 95% CI −15.1 to −4.0) and VAS scale (mean difference 0.8, 95% CI 0.2-1.3). Associations remained unchanged after adjusting for age, co-morbidities, contra-lateral arthritic joint, OA site, and disability. The associations observed between increased pain and female gender or obesity were substantially reduced after adjusting for SF leptin. Conclusion: Joint pain is associated with SF leptin concentrations. Increased pre-operative pain observed in women and obese may be related to high intra-articular leptin level

Epidemiology and outcomes of bone and joint infections in solid organ transplant recipients

Bone and joint infection (BJI) epidemiology and outcomes in solid organ transplant recipients (SOTr) remain largely unknown. We aim to describe BJI in a multi-center cohort of SOTr (Swiss Transplant Cohort Study). All consecutive SOTr with BJI (01.05.2008-31.12.2019) were included. A nested case-control study to identify risk factors for BJI was performed. Among 4482 patients, 61 SOTr with 82 BJI were included, at an incidence of 1.4% (95% CI 1.1-1.7), higher in heart and kidney-pancreas SOTr (Gray's test p < .01). Although BJI were predominately late events (median of 18.5 months post-SOT), most infections occurred during the first year post-transplant in thoracic SOTr. Diabetic foot osteomyelitis was the most frequent infection (38/82, 46.3%), followed by non-vertebral osteomyelitis (26/82, 31.7%). Pathogens included Gram-positive cocci (70/131, 53.4%), Gram-negative bacilli (34/131, 26.0%), and fungi (9/131, 6.9%). BJI predictors included male gender (OR 2.94, 95% CI 1.26-6.89) and diabetes (OR 2.97, 95% CI 1.34-6.56). Treatment failure was observed in 25.9% (21/81) patients and 1-year mortality post-BJI diagnosis was 14.8% (9/61). BJI remain a rare event in SOTr, associated with subtle clinical presentations, high morbidity and relapses, requiring additional studies in the future

Epigenetic Features of Human Mesenchymal Stem Cells Determine Their Permissiveness for Induction of Relevant Transcriptional Changes by SYT-SSX1

BACKGROUND: A characteristic SYT-SSX fusion gene resulting from the chromosomal translocation t(X;18)(p11;q11) is detectable in almost all synovial sarcomas, a malignant soft tissue tumor widely believed to originate from as yet unidentified pluripotent stem cells. The resulting fusion protein has no DNA binding motifs but possesses protein-protein interaction domains that are believed to mediate association with chromatin remodeling complexes. Despite recent advances in the identification of molecules that interact with SYT-SSX and with the corresponding wild type SYT and SSX proteins, the mechanisms whereby the SYT-SSX might contribute to neoplastic transformation remain unclear. Epigenetic deregulation has been suggested to be one possible mechanism. METHODOLOGY/PRINCIPAL FINDINGS: We addressed the effect of SYT/SSX expression on the transcriptome of four independent isolates of primary human bone marrow mesenchymal stem cells (hMSC). We observed transcriptional changes similar to the gene expression signature of synovial sarcoma, principally involving genes whose regulation is linked to epigenetic factors, including imprinted genes, genes with transcription start sites within a CpG island and chromatin related genes. Single population analysis revealed hMSC isolate-specific transcriptional changes involving genes that are important for biological functions of stem cells as well as genes that are considered to be molecular markers of synovial sarcoma including IGF2, EPHRINS, and BCL2. Methylation status analysis of sequences at the H19/IGF2 imprinted locus indicated that distinct epigenetic features characterize hMSC populations and condition the transcriptional effects of SYT-SSX expression. CONCLUSIONS/SIGNIFICANCE: Our observations suggest that epigenetic features may define the cellular microenvironment in which SYT-SSX displays its functional effects

IGF1 Is a Common Target Gene of Ewing's Sarcoma Fusion Proteins in Mesenchymal Progenitor Cells

The EWS-FLI-1 fusion protein is associated with 85-90% of Ewing's sarcoma family tumors (ESFT), the remaining 10-15% of cases expressing chimeric genes encoding EWS or FUS fused to one of several ets transcription factor family members, including ERG-1, FEV, ETV1 and ETV6. ESFT are dependent on insulin-like growth factor-1 (IGF-1) for growth and survival and recent evidence suggests that mesenchymal progenitor/stem cells constitute a candidate ESFT origin. To address the functional relatedness between ESFT-associated fusion proteins, we compared mouse progenitor cell (MPC) permissiveness for EWS-FLI-1, EWS-ERG and FUS-ERG expression and assessed the corresponding expression profile changes. Whereas all MPC isolates tested could stably express EWS-FLI-1, only some sustained stable EWS-ERG expression and none could express FUS-ERG for more than 3-5 days. Only 14% and 4% of the total number of genes that were respectively induced and repressed in MPCs by the three fusion proteins were shared. However, all three fusion proteins, but neither FLI-1 nor ERG-1 alone, activated the IGF1 promoter and induced IGF1 expression. Whereas expression of different ESFT-associated fusion proteins may require distinct cellular microenvironments and induce transcriptome changes of limited similarity, IGF1 induction may provide one common mechanism for their implication in ESFT pathogenesis