Risk factors of knee reinjury after anterior cruciate ligament reconstruction.

PURPOSE: This study aimed to investigate whether the return to level I sports, concomitant injuries, foot-related problems, and other factors would increase the risk of knee reinjury after anterior cruciate ligament reconstruction (ACLR). METHODS: This study used a prospective cohort study design. Online enrolment from August 2018 to January 2019 in ACL Community Indonesia recruited 148 patients who had undergone ACLR less than one month prior to injury. Knee injury occurrence after ACLR was diagnosed through a physical examination and positive MRI or arthroscopic findings. RESULTS: During the study, 55 knee reinjuries occurred. The proportional hazards model analysis revealed that the risk of knee reinjury at 12 and 24 months for patients who returned to level I sports (hazards ratio (HR)=3.17 and HR=3.90, respectively) was significantly higher than that of the patients who did not return to sports and that the risk for those who returned to level II/III sports did not significantly increase at 12 or 24 months. Patients with concomitant meniscus injury had a significantly higher risk of knee reinjury at 12 and 24 months (HR=3.33 and HR=2.25, respectively) than those without, and the risk of knee reinjury for patients with concomitant posterior cruciate ligament injury was significantly higher at 12 months (HR=3.05) but not at 24 months. Fewer knee symptoms after ACLR were significantly associated with a lower risk of knee reinjury (HR=0.98) at 12 and 24 months. CONCLUSIONS: The return to level I sports, concomitant meniscus and posterior cruciate ligament injury, and knee symptoms after ACLR may increase the risk of knee reinjury for post-ACLR patients.

The Risk Factors and Preventive Strategies of Poor Knee Functions and Osteoarthritis after Anterior Cruciate Ligament Reconstruction: A Narrative Review.

Anterior cruciate ligament reconstruction (ACLR) is the standard surgical treatment for ACL injury, which typically uses a graft to replace the torn ligament in the knee that uses small incisions with minimally invasive surgery. The optimal knee functions following ACLR depend on rehabilitation processes before and after the surgery. Knee function is the ability of the knee to perform various types of functional movements like walking, squatting, running, jumping, and pivoting where patients expect to achieve maximum knee function or at least more than 80% of its initial condition before the injury to avoid being categorized as poor knee function after ACLR. Patients use patient-reported outcome measures to collect data on their health status and quality of life after ACLR. Post-traumatic osteoarthritis (PTOA) is a type of OA that manifests in local cartilage injury caused by chondrocyte death, and matrix dispersion occurs following a joint injury like ACL injury. Gender, time from injury to surgery, and graft type were considered as risk factors for poor knee function after ACLR, while overweight, meniscus tear, and cartilage defect as risk factors for PTOA. However, age is an internal risk factor for both poor knee function and PTOA following ACLR. This review suggests several strategies to prevent both conditions, including a pre-operative program, comprehensive rehabilitation, body weight control, and return to sport (RTS) consideration based on physical capacity, proper time, and psychological readiness.

Predictors of lower knee function improvement two years after anterior cruciate ligament reconstruction.

OBJECTIVES: The extent to which knee functions improve after anterior cruciate ligament reconstruction (ACLR) varies. This study aimed to determine the factors that affect lower knee function improvement after two years of ACLR. METHODS: The study included 159 patients who underwent ACLR in the Indonesian ACL community between August 2018 and April 2020. The concomitant injury and graft types of ACLR were determined using patients' pre-surgical MRI and medical records. The five subscales of the knee injury and osteoarthritis outcome score (KOOS) were used to evaluate the patient at baseline, first year, and second year following ACLR. A linear mixed-effect model (LMEM) was used to predict the longitudinal improvement models for the five-subscales KOOS score after ACLR. RESULTS: The LMEM predicted lower KOOS subscales scores improvements by 0.5 for QOL, 0.1 for symptom, ADL, and QOL, and 0.2 for sports/recreation, respectively, for a one score increase of age and time from injury to surgery. Male patients had higher KOOS subscale scores with the improvement of pain, symptom, and ADL by 5.7, 5.9, and 6.3 compared to female patients, respectively, while patients with patellar tendon grafts had lower improvement of KOOS score pain by 6.5 compared to hamstring tendon grafts. CONCLUSION: As the age and time from injury to surgery increased, the KOOS subscales scores of QOL and symptoms, ADL, sports/recreation, and QOL decreased. Male patients reported higher KOOS subscales scores for pain, symptoms, and ADL, while patients with patella tendon grafts had a lower improvement in pain score.

Targeting Castration-Resistant Prostate Cancer Using Mesenchymal Stem Cell Exosomes for Therapeutic MicroRNA-let-7c Delivery.

BACKGROUND: Castration-resistant prostate cancer (PCa; CRPC) has a poor response to androgen deprivation therapy and is considered an incurable disease. MicroRNA (miR)-lethal 7c (let-7c) was implied to be a tumor suppressor in PCa, and treatment with exogenous let-7c targets both cancer cells and their associated mesenchymal stem cells (MSCs) to prevent CRPC progression and metastasis. Exosomes are nanometer-sized membrane-bound vesicles which have an absolute predominance in biocompatibility for drug delivery and gene therapy by mediating cell-to-cell communication. By utilizing the intrinsic tumor-targeting property of MSCs, this study aimed to investigate the feasibility of MSC-derived exosomes as an exogenous miR delivery system to target CRPC, using miR let-7c as an example. METHODS: Bioinformatics analysis was performed to observe miR-let-7c expression in clinical samples by utilizing the GEO database. MSC-derived exosomes were collected from a human bone marrow-derived MSC cell line after cell transfection with either a pre-miR negative control or pre-miR-let-7c, and further characterized through nanoparticle tracking analysis and Western blotting. miR-let-7c expression was determined using RT-qPCR, and the phenotypic effects of both naked and MSC-exosome-encapsulated let-7c on CRPC cells (PC3 and CWR22Rv1) were determined by WST-1 cell proliferation assay and wound healing migration assay. RESULTS: miR-let-7c was downregulated in metastatic PCa and high grade group patients. miR-let-7c expression was confirmed to be downregulated in PCa cell lines, with massively decreased in most metastatic CRPC-like cells. Exogenous miR-let-7c can be successfully packaged into MSC exosomes. Treatment with either naked or MSC-exosome-encapsulated miR-let-7c resulted in significant reductions in cell proliferation and migration in CRPC-like PC3 and CWR22Rv1 cells. CONCLUSIONS: MSC-derived exosomes could serve as a therapeutic let-7c delivery system to target CRPC.

Application of Mesenchymal Stem Cells in Targeted Delivery to the Brain: Potential and Challenges of the Extracellular Vesicle-Based Approach for Brain Tumor Treatment.

Treating brain tumors presents enormous challenges, and there are still poor prognoses in both adults and children. Application of novel targets and potential drugs is hindered by the function of the blood-brain barrier, which significantly restricts therapeutic access to the tumor. Mesenchymal stem cells (MSCs) can cross biological barriers, migrate to sites of injuries to exert many healing effects, and be engineered to incorporate different types of cargo, making them an ideal vehicle to transport anti-tumor agents to the central nervous system. Extracellular vesicles (EVs) produced by MSCs (MSC-EVs) have valuable innate properties from parent cells, and are being exploited as cell-free treatments for many neurological diseases. Compared to using MSCs, targeted delivery via MSC-EVs has a better pharmacokinetic profile, yet avoids many critical issues of cell-based systems. As the field of MSC therapeutic applications is quickly expanding, this article aims to give an overall picture for one direction of EV-based targeting of brain tumors, with updates on available techniques, outcomes of experimental models, and critical challenges of this concept.