Prognostic Factors in Intra-articular Platelet-Rich Plasma Treatment for Knee Osteoarthritis: A Comparative Analysis of Responders and Nonresponders.

BACKGROUND: Knee osteoarthritis (KOA) is a chronic joint disease affecting activities of daily living (ADL) and quality of life due to pain and limited range of motion, afflicting a large number of patients worldwide. However, it is difficult to prevent the progression of the disease. Therapeutic strategies for KOA aim to maintain ADL and QOL by alleviating pain or managing locomotive function. Recently, intra-articular injection of platelet-rich plasma (PRP) has been gaining attention. In this study, the clinical results of PRP treatment in our institution were reported and compared between responders and non-responders using patient characteristics and imaging data assessed from plain X-rays and magnetic resonance imaging (MRI). METHODS: Participants in the study were KOA patients with varus deformity assessed as grade 2 or higher in the Kellgren-Lawrence classification who received PRP treatment from January 2022 to November 2023 and were followed up for at least three months. PRP was prepared with 27 mL of blood collected from the patient, and 2.7 mL of PRP was prepared using the PEAK©ï¸ŽPRP System from DePuy Synthes (Raynham, MA). Intra-articular injections of PRP were performed under echo-guided procedures, and responders or non-responders were determined using the Osteoarthritis Research Society International Standing Committee for Clinical Trials Response Criteria Initiative (OMERACT-OARSI) criteria evaluated by the Japanese Knee Injury and Osteoarthritis Outcome Score (J-KOOS) at three months after PRP injection. The clinical efficacy of PRP treatment for KOA was assessed in this study, and a dichotomous analysis was performed comparing the responder group and the non-responder group using patient characteristics and assessed data from plain X-ray images and MRI to determine prognostic factors for PRP treatment. RESULTS: The study population included 36 knees with a mean age of 70.6. ± 9.2 years, comprising six knees in men and 30 knees in women. The responder group consisted of 16 knees (44.4%), and the non-responder group consisted of 20 knees (55.6%). J-KOOS subscores at pre-treatment elicited that each subscale in the R group was significantly lower than that in the NR group at pretreatment. A dichotomous analysis for the two groups revealed the distribution of sex and past medical history of hyperlipidemia to be significantly different between the two groups. Multivariable logistic regression analysis showed that the coexistence of hyperlipidemia was the main prognostic factor for the efficacy of PRP therapy. DISCUSSION: In this study, comparisons were conducted between responders and non-responders to estimate prognostic factors for the efficacy of PRP therapy. Surprisingly, responders to the treatment tended to show lower J-KOOS scores and to have hyperlipidemia. A literature review revealed conflicting reports on prognostic factors for PRP therapy in KOA, highlighting the need for further research.

Multifactorial Comparative Analysis of Platelet-Rich Plasma and Serum Prepared Using a Commercially Available Centrifugation Kit.

Background Platelet-rich plasma (PRP) is an autologous product prepared by centrifuging whole blood. PRP is reported to have high tissue repair potential and anti-inflammatory properties. Recently, PRP has become a potential treatment option for osteoarthritis, contributing to pain relief and locomotive improvement. However, the underlying therapeutic mechanisms and key biochemical factors in PRP remain unclear. This study aimed to estimate the major factors for tissue repair involved in PRP treatment by comparing between serum and PRP prepared from the same patients using the Luminex assay. Methodology Blood samples were collected from nine healthy volunteers, and serum and PRP were prepared. PRP was prepared using a PEAK©ï¸Ž PRP SYSTEM kit of DePuy Synthes Mitek Sports Medicine (Raynham, Massachusetts, USA), which is a commercially available PRP preparation kit. The white blood cell count, hemoglobin level, and platelet count were automatically measured for both whole blood and PRP in the hospital's clinical laboratory using the XE-5000™ Automated Hematology System (Sysmex, Kobe, Japan). Comparative analysis of biological factors was then performed using the Luminex assay on serum and PRP. Results PRP was found to have significantly higher white blood cell and platelet counts and lower hemoglobin levels than whole blood. Furthermore, PRP contained significantly higher levels of various factors, including interleukin (IL)-1ra, IL-10, IL-13, C-C motif chemokine ligand (CCL)-2, CCL3, CCL4, CCL8, CCL13, CCL21, C-X-C motif chemokine ligand (CXCL)-10, matrix metalloproteinase (MMP)-3, MMP-9, cluster of differentiation (CD) 40 ligand, vascular endothelial growth factor (VEGF), VEGF-C, platelet-derived growth factor (PDGF)-AB, PDGF-BB, and bone morphogenic protein (BMP)-2. Additionally, IL-1ra and IL-4 showed significant correlations with white blood cell counts in PRP, whereas VEGF had a significant correlation with platelet counts. Conclusions PRP contains various factors in higher quantities than serum. Specifically, the notable increase in the anti-inflammatory cytokine IL-1ra is suggested to play a key role as a major therapeutic mechanism of PRP.

Clinical three-dimensional anatomy of the femur considering navigation-aided surgery of total knee arthroplasty in Japanese patients.

PURPOSE: Few studies exist regarding sagittal alignment describing femur morphology in navigation-aided surgery. This study investigated the three-dimensional (3D) sagittal femoral alignment of the whole femur. METHODS: Seventy-three consecutive patients (59 females, 14 males, mean age: 76.1 years), yielding 140 femurs, were included in this study. A computed-tomography-based patient-specific 3D femur model was used to define a mechanical axis-based reference plane. Proximal and distal femoral axis angles (PFA, DFA) to the reference plane were measured in 3D using custom software. PFA and DFA represent the proximal and distal inclination of the femoral anatomical axis in sagittal plane, respectively. RESULTS: PFA (10.6 ± 1.5°) was greater than DFA (2.6 ± 1.6°; P < 0.0001). DFA in females (2.3 ± 1.4°) was smaller than in males (3.9 ± 1.7°; P < 0.0001). CONCLUSION: This is the first report of measurement of femoral sagittal alignment related to both 3D anatomy and decision making of femoral flexion angle using navigation surgery for total knee arthroplasty. This report shows a robust DFA measurement that could be used as a template for femoral implants flexion angle when performing both conventional and navigated total knee arthroplasty.

Calpain and atherosclerosis.

This review highlights the pro-atherogenic roles of Ca(2+)-sensitive intracellular protease calpains. Among more than ten species of calpain isozymes, µ- and m-calpains have been characterized most extensively. These two isozymes are ubiquitously expressed in mammalian tissues, including blood vessels, and tightly regulate functional molecules in the vascular component cells through limited proteolytic cleavage. Indeed, previous cell-based experiments showed that calpains play significant roles in nitric oxide production in vascular endothelial cells (ECs), maintenance of EC barrier function and angiogenesis for maintaining vascular homeostasis. Recently, we demonstrated that modified-low density lipoprotein (LDL)-induced m-calpain causes hyperpermeability in ECs, leading to the infiltration of monocytes/macrophages and plasma lipids into the intimal spaces (Miyazaki T. et al., Circulation. 2011; 124: 2522-2532). Calpains also mediate oxidized LDL-induced apoptotic death in ECs. In monocytes/macrophages, calpains induce proteolytic degradation of ATP-binding cassette transporter A1 (ABCA1) and G1 (ABCG1), which results in impaired cholesterol efflux and subsequent macrophage foam cell formation. In vascular smooth muscle cells, calpains may be involved in the conversion from contractile phenotype to proliferative phenotype. In hepatocytes, calpains disrupt the biogenesis of high-density lipoprotein via proteolytic degradation of ABCA1. Thus, calpains may serve as novel candidate molecular targets for control of atherosclerosis.

Salusin-ß accelerates inflammatory responses in vascular endothelial cells via NF-κB signaling in LDL receptor-deficient mice in vivo and HUVECs in vitro.

The bioactive peptide salusin-ß is highly expressed in human atheromas; additionally, infusion of antiserum against salusin-ß suppresses the development of atherosclerosis in atherogenic mice. This study examined the roles of salusin-ß in vascular inflammation during atherogenesis. Infusion of antiserum against salusin-ß attenuated the induction of VCAM-1, monocyte chemoattractant protein (MCP)-1, and IL-1ß and as well as nuclear translocation of NF-κB in aortic endothelial cells (ECs) of LDL receptor-deficient mice, which led to the prevention of monocyte adhesion to aortic ECs. In vitro experiments indicated that salusin-ß directly enhances the expression levels of proinflammatory molecules, including VCAM-1, MCP-1, IL-1ß, and NADPH oxidase 2, as well as THP-1 monocyte adhesion to cultured human umbilical vein ECs (HUVECs). Both salusin-ß-induced VCAM-1 induction and monocyte/HUVEC adhesion were suppressed by pharmacological inhibitors of NF-κB, e.g., Bay 11-7682 and curcumin. Furthermore, the VCAM-1 induction was significantly prevented by the phosphatidylinositol 3-kinase (PI3K) inhibitor LY-294002, whereas it was accelerated by the ERK inhibitor, U-0126. Treatment of HUVECs with salusin-ß, but not with salusin-α, accelerated oxidative stress and nuclear translocation of NF-κB as well as phosphorylation and degradation of IκB-α, an endogenous inhibitor of NF-κB. Thus, salusin-ß enhanced monocyte adhesion to vascular ECs through NF-κB-mediated inflammatory responses in ECs, which can be modified by PI3K or ERK signals. These findings are suggestive of a novel role of salusin-ß in atherogenesis.