An integrative multi-omics analysis to identify candidate DNA methylation biomarkers related to prostate cancer risk

It remains elusive whether some of the associations identified in genome-wide association studies of prostate cancer (PrCa) may be due to regulatory effects of genetic variants on CpG sites, which may further influence expression of PrCa target genes. To search for Cp

Large-scale transcriptome-wide association study identifies new prostate cancer risk regions

Although genome-wide association studies (GWAS) for prostate cancer (PrCa) have identified more than 100 risk regions, most of the risk genes at these regions remain largely unknown. Here we integrate the largest PrCa GWAS (N = 142,392) with gene expression measured in 45 tissues (N = 4458), including normal and tumor prostate, to perform a multi-tissue transcriptome-wide association study (TWAS) for PrCa. We identify 217 genes at 84 independent 1 Mb regions associated with PrCa risk, 9 of which are region

Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma

Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the total number to 23. Integration of information from gene expression, epigenetic profiling and in situ Hi-C data for the 23 risk loci implicate disruption of developmental transcriptional regulators as a basis of MM susceptibility, compatible with altered B-cell differentiation as a key mechanism. Dysregulation of autophagy/apoptosis and cell cycle signalling feature as recurrently perturbed pathways. Our findings provide further insight

Navigation Improves the Survival Rate of Mobile-Bearing Total Knee Arthroplasty by Severe Preoperative Coronal Deformity: A Propensity Matched Case-Control Comparative Study.

The primary hypothesis of this study was that the survival rate over 10 years of total knee arthroplasties (TKAs) implanted with a navigation system was superior to that of TKAs implanted with a conventional technique. The secondary hypothesis was that the severity of the initial coronal deformity had a negative influence on the survival rate. A national, multicentric, retrospective study was performed in France, including eight university or private centers with high volumes in knee surgery. Cases operated on with either a conventional (control group) or a navigated (study group) technique were matched after calculating the propensity score using the logistic regression technique. All patients were contacted after 10 years or more to determine the survival of the TKA. The need for date and cause of revision were noted. The primary end point of the study was the occurrence of a revision for any mechanical reason. Survival curves were calculated using the Kaplan-Meier's technique, with the primary criterion as end point. The influence of the implantation technique was analyzed by a log-rank test at a 5% level of significance. The influence of severity of the preoperative coronal deformity was analyzed using the same technique. A total of 513 cases were included in each group. The survival rates after 13 years were 96.5% in the study group and 92.9% in the control group (not significant). There was no significant difference between both groups for the survival rates after 13 years for small deformity (96.0 vs. 97.0%), but the difference was significant for large deformity (97.0 vs. 89.0%, p = 0.04). The results suggest that the use of a navigation system, allowing a more consistent correction of the preoperative coronal deformity, thus allows a better long-term prosthetic survival in cases with a large initial coronal deformity. A navigation system should be routinely used in cases of initial coronal deformity greater than or equal to 10 degrees, as conventional techniques do not routinely provide satisfactory axial correction in these difficult cases

No difference in 13-year survival after medial pivot or central pivot mobile bearing total knee arthroplasty. A propensity matched comparative analysis.

The present study was designed to evaluate the long-term results (more than 10 years) of mobile bearing total knee arthroplasty (TKA) and to compare the survival of medial pivot axis (MPA) and central pivot axis (CPA) TKAs. The primary hypothesis was that the 10- to 15-year survival rate of MPA TKAs will be better than CPA TKAs. A national, multicenter, retrospective study was performed in France. In this case-control design, 1154 TKAs were paired into the CPA group (control group: 577 cases) and MPA group (study group: 577 cases) based on a logistic regression analysis of age, gender, body mass index and severity of the coronal deformity, defining the propensity score for each case. Final survival information follow-up was obtained for 946 cases (82%). There was no significant difference between the control and study groups for any baseline data. Twenty-two prosthetic revisions (2%) were performed for mechanical reasons during the follow-up period. There was no significant difference between the 13-year survival rates of CPA (98%) and MPA (97%) TKAs. There was no significant difference between groups in their final Oxford and Knee Society scores. Our findings do not support the assumption that medialization of the pivot axis of a mobile bearing TKA improves clinical results or survival. Level III

Diagnostic accuracy of intra-articular C-reactive protein assay in periprosthetic knee joint infection – a preliminary study.

International audienceBackground: Periprosthetic joint infection often raises diagnostic challenges, as the published criteria are heterogeneous. New markers for predicting periprosthetic infection have been evaluated. Here, we assessed one of these markers, C-reactive protein (CRP), in joint fluid.Hypothesis: We hypothesised that intra-articular CRP levels would perform better than serum CRP concentrations in diagnosing knee prosthesis infection.Patients and methods: We prospectively included 30 patients including 10 with native-knee effusions, 11 with prosthetic-knee aseptic effusions, and 11 with prosthetic-knee infection defined using 2011 Musculoskeletal Society criteria. Serum CRP was assayed using turbidimetry or nephelometry and intra-articular CRP using nephelometry. Appropriate statistical tests were performed to compare the three groups; P values 2.78 mg/L suggested possible infection (100% sensitivity and 82% specificity) and a value >5.37 mg/L probable infection (90% sensitivity and 91% specificity).Discussion: Our findings suggest a possible role for intra-articular CRP assay in diagnosing knee prosthesis infection and perhaps periprosthetic infection at any site.Level of evidence: Level III, diagnostic study, development of a diagnostic criterion in consecutive patients comparatively to a reference standar