Longitudinal measurement of serum cartilage oligomeric matrix protein can detect the progression of cartilage degeneration in anterior cruciate ligament reconstruction patients.

Background/objective: Cartilage oligomeric matrix protein (COMP) has utility as a diagnostic marker for osteoarthritis (OA). Our previous study revealed that the serum COMP level can be used to detect early cartilage change in non-OA patients with anterior cruciate ligament (ACL)-deficiency. However, there are still no studies on detecting the progression of cartilage degeneration in early OA. The aim of present study was to investigate whether serum COMP can detect the progression of cartilage degeneration after ACL reconstruction in non-OA patients. Methods: Patients without cartilage degeneration of early OA at ACL reconstruction and whose serum COMP levels could be measured were included in the study. Cartilage degeneration of early OA were defined as International Cartilage Repair Society (ICRS) grade 1 to 4 in more than 2 compartments or ICRS grade 2 to 4 in 1 compartment. The patients were divided into two groups: those who had cartilage degeneration of early OA at second-look arthroscopy (cartilage degeneration progression group) and those who did not (non-progression group), and the serum COMP values between the two groups were compared. Results: Thirty-one patients were included. There were 8 cases (25.8 %) in progression group and 23 cases (74.2 %) in non-progression group. There were significant differences between the two groups regarding age and change in serum COMP level. In terms of the rate of change in COMP, an increase of more than 1.24-fold was the cut-off value for detecting the progression of cartilage degeneration. Conclusions: In this study, the increase in serum COMP levels was significantly greater in progressed cartilage degeneration group than non-progression group after ACL reconstruction. Longitudinal serum COMP measurement could detect the progression of cartilage degeneration. Level of evidence: Level Ⅲ, retrospective comparative study.

Long-Term Physical Stability of Amorphous Solid Dispersions: Comparison of Detection Powers of Common Evaluation Methods for Spray-Dried and Hot-Melt Extruded Formulations.

Although physical stability can be a critical issue during the development of amorphous solid dispersions (ASDs), there are no established protocols to predict/detect their physical stability. In this study, we have prepared fenofibrate ASDs using two representative manufacturing methods, hot-melt extrusion and spray-drying, to investigate their physical stability for one year. Intentionally unstable ASDs were designed to compare the detection power of each evaluation method, including X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and dissolution study. Each method did not provide the same judgment results on physical stability in some cases because of their different evaluation principles and sensitivity, which has been well-comprehended only for one-component glass. This study revealed that the detection powers of each evaluation method significantly depended on the manufacturing methods. DSC was an effective method to detect a small amount of crystals for both types of ASDs in a quantitative manner. Although the sensitivity of XRPD was always lower compared to that of DSC, interpretation of the data was the easiest. SEM was very effective for observing the crystallization of the small amount of drug for hot-melt extruded products, as the drug crystal vividly appeared on the large grains. The dissolution performance of spray-dried products could change even without any indication of physical change including crystallization. The advantage/disadvantage and complemental roles of each evaluation method are discussed for deeper understanding on the physical stability data of ASDs.