Utility of D-dimer in total joint arthroplasty

As the number of patients receiving total joint replacements continues to rise,considerable attention has been directed towards the early detection and prevention of postoperative complications.While D-dimer has long been studied as a diagnostic tool in venous thromboembolism(VTE),this assay has recently received considerable attention in the diagnosis of periprosthetic joint infection(PJI).D-dimer values are substantially elevated in the acute postoperative period after total joint arthroplasty,with levels often exceeding the standard institutional cutoff for VTE(500µg/L).The utility of D-dimer in detecting VTE after total joint replacement is currently limited,and more research to assess its value in the setting of contemporary prophylaxis protocols is warranted.Recent literature supports D-dimer as a good to excellent biomarker for the diagnosis of chronic PJI,especially when using serum sample technique.Providers should exercise caution when interpreting D-dimer levels in patients with inflammatory and hypercoagulability disorders,as the diagnostic value is decreased.The updated 2018 Musculoskeletal Infection Society criteria,which includes D-dimer levels>860µg/L as a minor criterion,may be the most accurate for diagnosing chronic PJI to date.Larger prospective trials with transparent lab testing protocols are needed to establish best assay practices and optimal cutoff values for D-dimer in the diagnosis of PJI.This review summarizes the most current literature on the value of D-dimer in total joint arthroplasty and elucidates areas for future progress.

The Polymorphisms in the Vitamin D Receptor Gene and Disease Severity in Sickle Cell Disease

Vitamin D is important in multiple aspects of health and its effects are mediated through the Vitamin D Receptor (VDR). We wanted to test the hypothesis that specific haplotypes of the VDR gene are associated with markers of disease severity, inflammation and bone health in Sickle Cell Disease (SCD). Genotyping was performed on DNA specimens from 1141 study participants in the NIH-funded Silent Infarct Transfusion (SIT) trial. We used the clinical and laboratory data to create separate endothelial dysfunction, vaso-occlusive severity scores and phenotype variables. Seventy-nine Single Nucleotide Polymorphisms (SNP) in the VDR gene and three associated genes—CYP27B1, VD binding protein, retinoid X receptor, were evaluated. The discovery cohort individuals had VDR haplotype information from a prior Genome-Wide Association Study (GWAS). The validation cohort was analyzed for SNPs that were significant in the discovery cohort. The pheno-type data were obtained from the demographic and clinical information of the participants, and were used to create the severity scores, vaso-occlusive score, endothelial dysfunction severity, and overall severity score. Potential gene-gene interactions were analyzed for prediction of disease severity within each severity score. Two SNPs were associated with the overall severity score, 3 SNPs with the endothelial dysfunction severity score and 4 SNPs with the vaso-occlusive severity score. After permutation testing to correct for multiple comparisons, only one of the associations remained significant. SNP rs7965281 was found to be associated with the endothelial dysfunction severity score and remained significant after correcting for multiple comparisons using permutation testing. In the validation cohort, that SNP was again tested for association with each of the severity scores. There was no association with the endothelial or the overall severity score but a trend towards association with the vaso-occlusive severity score (p = 0.02). None of the known functional polymorphisms in the VDR gene were found to have an association with severity in sickle cell disease. Further work analyzing for gene-gene interaction using the same significant SNPs remains to be done in association with inflammatory markers and measure of bone health. Those studies may provide insight on the contribution of VDR polymorphisms to sickle cell disease severity.