Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Three-dimensional modeling of hip DXA scans has been proposed to partition BMD into cortical surface (csBMD) and trabecular “volumetric” (tvBMD). We assessed in a population-based cohort, whether such partitioning contributes to fracture risk assessment compared to aBMD alone. Participants (N = 4908) from the Rotterdam Study comprised 56% women, with a mean age of 67.4 (SD = 10.1) years. Hip DXA scans were analyzed with enCore (GE Lunar) and 3D-Shaper software. Pearson partial correlation was calculated between aBMD, csBMD, and tvBMD at the total hip, femoral neck, and trochanter. Incident fractures were collected from GP or hospital records. During a mean follow-up of 6.8 (SD = 2.5) years, 171 sustained a hip fracture, and 1019 any-type fractures. Fracture risk estimates were determined as hazard ratios (HR) per SD decrease in BMD, from Cox-regression adjusted for multiple confounders. High correlation (r = >.81; p < .001) was observed between aBMD and the modeled 3D parameters, and between csBMD and tvBMD (r = 0.85; p < .001 at the total hip). Lower aBMD was associated with higher incidence of any-type (HR = 1.60, 95% CI: 1.43-1.78) and hip (HR = 2.46, 95% CI: 1.90-3.17) fracture; lower csBMD with increased risk of any-type (HR = 1.44, 95% CI: 1.30-1.60) and hip (csBMD HR = 1.76, 95% CI: 1.39-2.23) fracture; and tvBMD with increased risk of any-type (HR = 1.62, 95% CI: 1.45-1.80) and hip fracture (HR = 2.44, 95% CI: 1.88-3.15). Inclusion of aBMD in models with tvBMD or csBMD resulted in high multicollinearity and unreliable coefficient parameters (VIF > 5). The effect of csBMD was largely attenuated after inclusion of tvBMD in the same model for both any-type (csBMD HR = 0.96, 95% CI: 0.81-1.13; tvBMD HR = 1.67, 95% CI: 1.41-1.98) and hip (csBMD HR = 0.83, 95% CI: 0.58-1.21; tvBMD HR = 2.82, 95% CI: 1.94-4.10) fractures. Similar results were observed at the neck and intertrochanteric regions. DXA-derived 3D modeled parameters are highly correlated to aBMD and do not provide additional value for the estimation of fracture risk beyond aBMD alone.

Hematopoietic stem cell transplantation (HSCT) is a life-saving procedure to treat hematopoietic disorders. Current bone marrow conditioning protocols create space for healthy donor stem cells by employing irradiation and/or chemotherapy, but carry severe toxicities, resulting in significant morbidity, mortality and substantial long-term complications. To develop a low-toxicity solution, we generated a bi-specific T-cell engager (BTCE) that targets CD117, an abundantly expressed receptor on hematopoietic stem and progenitor cells (HSPC) and leukemia-initiating cells (LICs). We show that the CD117×CD3 BTCE efficiently depletes in vitro and in vivo HSPCs and LICs. The CD117×CD3 BTCE was not toxic and facilitates highly efficient engraftment of human allogenic donor CD34+cells in humanized mice, thereby restoring hematopoiesis in vivo in both normal and leukemia-bearing humanized mice. We demonstrate here that a potent CD117×CD3 BTCE enables rapid HSCT in both benign and malignant conditions.

Journal Article Accepted manuscript Linking levels of polyunsaturated fatty acids to acne risk Get access Luba Milena Pardo Luba Milena Pardo Department of Dermatology, Erasmus MC Universitair Medisch Centrum Rotterdam, Rotterdam, the Netherlands Corresponding author: Email: [email protected] https://orcid.org/0000-0003-0684-3175 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljaf094, https://doi-org.libproxy1.nus.edu.sg/10.1093/bjd/ljaf094 Published: 15 March 2025 Article history Received: 09 March 2025 Accepted: 10 March 2025 Published: 15 March 2025