Dickkopf-1 (DKK1) blockade mitigates osteogenesis imperfecta (OI) related bone disease.

BACKGROUND: The current treatment of osteogenesis imperfecta (OI) is imperfect. Our study thus delves into the potential of using Dickkopf-1 antisense (DKK1-AS) to treat OI. METHODS: We analysed serum DKK1 levels and their correlation with lumbar spine and hip T-scores in OI patients. Comparative analyses were conducted involving bone marrow stromal cells (BMSCs) and bone tissues from wild-type mice, untreated OI mice, and OI mice treated with DKK1-ASor DKK1-sense (DKK1-S). RESULTS: Significant inverse correlations were noted between serum DKK1 levels and lumbar spine (correlation coefficient = - 0.679, p = 0.043) as well as hip T-scores (correlation coefficient = - 0.689, p = 0.042) in OI patients. DKK1-AS improved bone mineral density (p = 0.002), trabecular bone volume/total volume fraction (p < 0.001), trabecular separation (p = 0.010), trabecular thickness (p = 0.001), trabecular number (p < 0.001), and cortical thickness (p < 0.001) in OI mice. DKK1-AS enhanced the transcription of collagen 1α1, osteocalcin, runx2, and osterix in BMSC from OI mice (all p < 0.001), resulting in a higher von Kossa-stained matrix area (p < 0.001) in ex vivo osteogenesis assays. DKK1-AS also reduced osteoclast numbers (p < 0.001), increased ß-catenin and T-cell factor 4 immunostaining reactivity (both p < 0.001), enhanced mineral apposition rate and bone formation rate per bone surface (both p < 0.001), and decreased osteoclast area (p < 0.001) in OI mice. DKK1-AS upregulated osteoprotegerin and downregulated nuclear factor-kappa B ligand transcription (both p < 0.001). Bone tissues from OI mice treated with DKK1-AS exhibited significantly higher breaking force compared to untreated OI mice (p < 0.001). CONCLUSIONS: Our study elucidates that DKK1-AS has the capability to enhance bone mechanical properties, restore the transcription of osteogenic genes, promote osteogenesis, and inhibit osteoclastogenesis in OI mice.

Combination of Sarcopenia and Anemia Predicts Worse Outcome in Elderly Patients With Diffuse Large B-Cell Lymphoma.

BACKGROUND/AIM: In diffuse large B-cell lymphoma (DLBCL), sarcopenia is associated with increased side-effects of chemotherapy and poor survival, especially in elderly patients. Anemia, a complex condition resulting from cancer itself and inflammation, might have a correlation with loss of muscle mass and might also indicate a worse outcome. In this study, we aimed to investigate the association of the skeletal muscle index (SMI) at the third lumbar vertebra (L3) with hemoglobin (Hb) levels and its predictive value for the outcome of DLBCL. PATIENTS AND METHODS: The study included patients, aged 70 or older, newly diagnosed with DLBCL who received immunochemotherapy. Sex-specific L3-SMI was measured by computed tomography, and Hb levels before treatment were recorded. The Kaplan-Meier method and Cox regression model were used to analyze survival and prognostic factors. RESULTS: Anemia was correlated with a low SMI. The presence of either low L3-SMI or anemia (Hb <10.5 g/l) indicated a poor prognosis for both progression-free and overall survival. A novel score combining L3-SMI, and Hb and lactate dehydrogenase levels as independent predictive factors was proposed for treatment response, progression-free and overall survival after adjusting for International Prognostic Index. CONCLUSION: This study highlights the importance of sarcopenia and anemia in patients with DLBCL, particularly in the elderly population. The proposed novel score combining L3-SMI, Hb, and lactate dehydrogenase may provide additional prognostic information for patients with DLBCL, aiding in treatment decisions and management.

Mechanical failure of articulating polymethylmethacrylate (PMMA) spacers in two-stage revision hip arthroplasty: the risk factors and the impact on interim function.

BACKGROUND: This study aimed to investigate the risk factors for mechanical failure of cement spacers and the impact on hip function after two-stage exchange arthroplasty for periprosthetic joint infection (PJI). METHODS: Thirty-one patients (19 males and 12 females) with hip PJIs underwent resection arthroplasty and implantation of cement spacers from January 2014 to December 2015. Patients who encountered spacer-associated mechanical complications in the interim period (14 of 31) were compared with those without complications (17 of 31). Complications were defined as spacer dislocation, spacer fracture, spacer fracture with dislocation, and femoral fracture during or following spacer implantation. Hip functional outcome was assessed using the Harris hip score (HHS). Treatment success was defined according to the following criteria: (1) no symptoms or signs indicative of infection; (2) no PJI-related mortality; and (3) no subsequent surgical intervention for infection after reimplantation surgery. Multivariate logistic regression and Kaplan-Meier survival curves were used for analysis. RESULTS: Fourteen patients (14/31 = 45%) suffered at least one spacer-related complication within the interim period. The development of spacer complications was associated with a younger age (odds ratio [OR] 0.91, 95% confidence interval [CI] 0.83-1.00, p = 0.045) and chronic PJI (OR 14.7, 95% CI 1.19-182, p = 0.036). Patients with spacer complications also had a lower median HHS (37 vs. 60, p < 0.001) before reimplantation in comparison to those without spacer complications. After reimplantation, the two groups had a similar median HHS (90 vs. 89, p = 0.945). Two patients did not undergo reimplantation due to extensive comorbidities, and subsequently retained the antibiotic spacer for definitive treatment. The 2-year treatment success rate was 84.6% in the spacer-complication group and 87.5% in the non-spacer-complication group (p = 0.81). CONCLUSION: There was a high complication rate for articulating PMMA spacers during the interim period of two-stage revision total hip arthroplasty. A young age and chronic infection were the primary risk factors associated with mechanical complications. Patients at high risk of spacer-related mechanical complications should be advised accordingly by surgeons. Knowing the possible risk factors, surgeons should educate patients thoroughly to avoid spacer complications, thereby increasing patient satisfaction in the interim stage. LEVEL OF EVIDENCE: Prognostic Level III.