Purpose The Simple Knee Value (SKV) is an outcome score in which patients are asked to grade their knee function as a percentage of that of a normal knee. The primary aim of this study was to validate the SKV by measuring its correlation with existing knee-related PROMs. Methods This was a prospective study conducted at a teaching hospital to assess the SKV's validity. The study enrolled 47 young patients (16-54 years old), 49 older patients (≥ 55 years) and 30 healthy controls. A paper questionnaire consisting of the Lysholm, IKDC, KOOS, WOMAC and SKV was given to subjects three times (enrolment, 1-month preoperative visit and 6 months postoperative visit). The criterion validity of the SKV was determined by correlating it to existing knee PROMs using the Spearman correlation coeicient (S). SKV test-retest reliability was assessed by the intraclass correlation coeicient (ICC) between two time points (initial consultation at enrolment and preoperative visit, relecting the same clinical condition). Responsiveness to change was determined by comparing the SKV scores before and after surgery (enrolment consultation and 6 months postoperative). Discriminative ability was determined by comparing the SKV distribution in patients and controls. Results There was a strong and signiicant correlation between the SKV and the gold standard Lysholm, IKDC, KOOS and WOMAC in the younger patients and the older patients (p < 0.0001). The reliability between the SKV at the initial consultation and before surgery was excellent (ICC 0.862, 95% CI 0.765; 0.921) in the younger patients, and moderate (ICC 0.506, 95% CI 0.265; 0.688) in the older patients. The SKV was responsive to change in both patient groups (p < 0.0001 for the SKV before versus 6 months after surgery). Like the other knee-speciic PROMs (p < 0.0001), the SKV was able to distinguish between patients and controls (p < 0.0001). Conclusions The SKV is valid as it is signiicantly correlated to existing knee PROMs. It is also reliable, responsive to change and discriminating. Its simplicity gives it many advantages and it can be used by physicians in their daily practice. Level of evidence Level II.

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Purpose The pediatric Simple Knee Value (pedi-SKV) is an outcome score in which paediatric patients are asked ‘How would you rate your knee today as a percentage of normal (0% to 100% scale with 100% being normal)?’. The primary aim of this study was to validate the pedi-SKV by measuring its correlation with validated knee function scores used most often in paediatric orthopaedics. Methods This prospective study was conducted at a teaching hospital to evaluate the pedi-SKV’s validity. A total of 44 paediatric patients (ten to 15 years old), were enrolled prior to anterior cruciate ligament reconstruction as well as 17 healthy controls. A survey form consisting of the Lysholm, International Knee Documentation Committee Pediatric Form (Pedi-IKDC) and pedi-SKV was given to subjects twice (enrolment and six months postoperatively). The criterion validity of the pedi-SKV was determined by correlating it to existing knee functional scores. Responsiveness to change was evaluated by comparing the pedi-SKV scores before and after surgery (enrolment visit and six-month postoperative visit). Discriminative ability was evaluated by comparing the pedi-SKV distribution in patients versus controls. Results There was a strong and significant correlation between the pedi-SKV and the Lysholm and Pedi-IKDC (p < 0.0001). The pedi-SKV had a good responsiveness to change (p < 0.0001 for the pedi-SKV before versus six months postoperatively). Like the other knee-specific functional sores (p < 0.0001), the pedi-SKV was able to distinguish between patients and controls (p < 0.0001). Conclusion The pedi-SKV is a valid outcome measure that is strongly correlated with the Lysholm and Pedi-IKDC. This is a novel simple score that can be used by physicians in their daily practice. Level of evidence II

Bone-marrow mesenchymal stromal cells (MSCs) are abnormal in multiple myeloma (MM) and play a critical role by promoting growth, survival and drug resistance of MM cells. We observed higher Toll-like receptor 4 (TLR4) gene expression in MM MSCs than in MSCs from healthy donors. At the clinical level, we highlighted that TLR4 expression in MM MSCs evolves in parallel with the disease stage. Thus, we reasoned that the TLR4 axis is pivotal in MM by increasing the pro-tumor activity of MSCs. Challenging primary MSCs with TLR4 agonists increased the expression of CD54 and interleukin 6, two factors directly implicated in MM MSC-MM cell crosstalk. Then, we evaluated the therapeutic efficacy of a TLR4 antagonist combined or not with conventional treatment in vitro with MSC-MM cell co-culture and in vivo with the Vk*MYC mouse model. Selective inhibition of TLR4 specifically reduced the MM MSC ability to support growth of MM cells in an IL-6-dependent manner and delayed the development of MM in the Vk*MYC mouse model by altering the early disease phase in vivo. For the first time, we demonstrate that specific targeting of the pathological bone-marrow microenvironment via TLR4 signaling could be an innovative approach to alter MM pathology development.

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