To investigate the effects of senescent osteocytes on bone homeostasis in the progress of age-related osteoporosis and explore the underlying mechanism. In a series of in vitro experiments, we used tert-Butyl hydroperoxide (TBHP) to induce senescence of MLO-Y4 cells successfully, and collected conditioned medium (CM) and senescent MLO-Y4 cell-derived exosomes, which were then applied to MC3T3-E1 cells, separately, to evaluate their effects on osteogenic differentiation. Furthermore, we identified differentially expressed microRNAs (miRNAs) between exosomes from senescent and normal MLO-Y4 cells by high-throughput RNA sequencing. Based on the key miRNAs that were discovered, the underlying mechanism by which senescent osteocytes regulate osteogenic differentiation was explored. Lastly, in the in vivo experiments, the effects of senescent MLO-Y4 cell-derived exosomes on age-related bone loss were evaluated in male SAMP6 mice, which excluded the effects of oestrogen, and the underlying mechanism was confirmed.Aims
Methods
The objective of this study was to evaluate the clinical and radiological outcomes of patients younger than six months of age with developmental dysplasia of the hip (DDH) managed by either a Pavlik harness or Tübingen hip flexion splint. Records of 251 consecutive infants with a mean age of 89 days (SD 47), diagnosed with DDH between January 2015 and December 2018, were retrospectively reviewed. Inclusion criteria for patients with DDH were: younger than 180 days at the time of diagnosis; ultrasound Graf classification of IIc or greater; treatment by Pavlik harness or Tübingen splint; and no prior treatment history. All patients underwent hip ultrasound every seven days during the first three weeks of treatment and subsequently every three to four weeks until completion of treatment. If no signs of improvement were found after three weeks, the Pavlik harness or Tübingen splint was discontinued. Statistical analysis was performed.Aims
Methods
There is a paucity of published Canadian literature comparing lumbar total disc arthroplasty (LDA) to fusion on patient outcomes in degenerative spondylosis. The purpose of this study is to quantify and compare the long-term patient reported outcomes following LDA and matched-fusion procedures. We conducted a matched-cohort study comparing consecutive patients enrolled by CSORN who underwent standalone primary LDA or hybrid techniques for degenerative disk disease between 2015–2019. Fusion patients were included by a primary diagnosis of degenerative disk disease, chief complaint of back pain, who received a primary fusion irrespective of technique. Fusion patients were matched by number of involved levels of surgery to LDA counterparts. Outcome scores and patient satisfaction were assessed preoperatively and 2-years postoperatively. 97 patients (39-female, 58-male) underwent LDA or hybrid construct up to 4 levels. 94 patients (52-female, 42-male) underwent a lumbar fusion were selected based on inclusion criteria. 36 LDA and 57 Fusion patients underwent a 1-level surgery. 39 LDA and 25 Fusion patients underwent 2-level surgery. 18 LDA and 7 Fusion patients underwent 3-level surgery. 4 LDA and 5 Fusion patients underwent a 4-level procedure. Slight differences in average cohort age were found (LDA-43.4yrs, Fusion-49.8yrs, p<0.01). Cohort preoperative-BMI (LDA-27.0kg/m2, Fusion-27.9kg/m2, p=0.29) and total comorbidities (LDA-2.6, Fusion-2.1, p=0.05) demonstrated no clinically significant differences. At 2 year follow-up, no differences were found in ODI improvement (LDA-20.32pts, Fusion-17.02pts, p=0.36), numerical back-pain improvement (LDA-3.5pts, Fusion-3.06pts, p=0.40), numerical leg-pain improvement (LDA-1.67pts, Fusion-1.87pts, p=0.76), and Health Scale improvement (LDA-17.12, Fusion-10.73, p=0.20) between cohorts. Similar positive findings were found in subgroups stratified by number of surgical levels. Satisfaction rate at 2 years was 86.7% and 82.4% for LDA and Fusion patients respectively. There didn't appear to be significant differences in outcomes or satisfaction through 2 years comparing patients who underwent LDA (whether used in isolation or as part of a hybrid construct) for debilitating degenerative disk disease and isolated spinal fusion for back dominant pain.
Ageing-related incompetence becomes a major hurdle for the clinical translation of adult stem cells in the treatment of osteoarthritis (OA). This study aims to investigate the effect of stepwise preconditioning on cellular behaviours in human mesenchymal stem cells (hMSCs) from ageing patients, and to verify their therapeutic effect in an OA animal model. Mesenchymal stem cells (MSCs) were isolated from ageing patients and preconditioned with chondrogenic differentiation medium, followed by normal growth medium. Cellular assays including Bromodeoxyuridine / 5-bromo-2'-deoxyuridine (BrdU), quantitative polymerase chain reaction (q-PCR), β-Gal, Rosette forming, and histological staining were compared in the manipulated human mesenchymal stem cells (hM-MSCs) and their controls. The anterior cruciate ligament transection (ACLT) rabbit models were locally injected with two millions, four millions, or eight millions of hM-MSCs or phosphate-buffered saline (PBS). Osteoarthritis Research Society International (OARSI) scoring was performed to measure the pathological changes in the affected joints after staining. Micro-CT analysis was conducted to determine the microstructural changes in subchondral bone.Aims
Methods
Technology within medicine has great potential to bring about more accessible, efficient, and a higher quality delivery of care. Paediatric supracondylar fractures are the most common elbow fracture in children and at our institution often have high rates of unnecessary long term clinical follow-up, leading to an inefficient use of healthcare and patient resources. This study aims to evaluate patient and clinical factors that significantly predict necessity for further clinical visits following closed reduction and percutaneous pinning. A total of 246 children who underwent closed reduction and percutaneous pinning following supracondylar humerus fractures were prospectively enrolled over a two year period. Patient demographics, perioperative course, goniometric measurements, functional outcome measures, clinical assessment and decision making for further follow up were assessed. Categorical and continuous variables were analyzed and screened for significance via bivariate regression. Significant covariates were used to develop a predictive model through multivariate logistical regression. A probability cut-off was determined on the Receiver Operator Characteristic (ROC) curve using the Youden index to maximize sensitivity and specificity. The regression model performance was then prospectively tested against 22 patients in a blind comparison to evaluate accuracy. 246 paediatrics patients were collected, with 29 cases requiring further follow up past the three month visit. Significant predictive factors for follow up were residual nerve palsy (p < 0 .001) and maximum active flexion angle of injured elbow (p < 0 .001). Insignificant factors included other goniometric measures, subjective evaluations, and functional outcomes scores. The probability of requiring further clinical follow up at the 3 month post-op point can be estimated with the equation: logit(follow-up) = 11.319 + 5.518(nerve palsy) − 0.108(maximum active flexion). Goodness of fit of the model was verified with Nagelkerke R2 = 0.574 and Hosmer & Lemeshow chi-square (p = 0.739). Area Under Curve of the ROC curve was C = 0.919 (SE = 0.035, 95% CI 0.850 – 0.988). Using Youden's Index, a cut-off for probability of follow up was set at 0.094 with the overall sensitivity and specificity maximized to 86.2% and 88% respectively. Using this model and cohort, 194 three month clinic visits would have been deemed medically unnecessary. Preliminary blind prospective testing against the 22 patient cohort demonstrates a model sensitivity and specificity at 100% and 75% respectively, correctly deeming 15 visits unnecessary. Virtual clinics and automated clinical decision making can improve healthcare inefficiencies, unclog clinic wait times, and ultimately enhance quality of care delivery. Our regression model is highly accurate in determining medical necessity for physician examination at the three month visit following supracondylar fracture closed reduction and percutaneous pinning. When applied correctly, there is potential for significant reductions in health care expenditures and in the economic burden on patient families by removing unnecessary visits. In light of positive patient and family receptiveness toward technology, our promising findings and predictive model may pave the way for remote health care delivery, virtual clinics, and automated clinical decision making.
Paediatric supracondylar fractures are the most common elbow fracture in children, and is associated with an 11% incidence of neurologic injury. The goal of this study is to investigate the natural history and outcome of motor nerve recovery following closed reduction and percutaneous pinning of this injury. A total of 246 children who underwent closed reduction and percutaneous pinning following supracondylar humerus fractures were prospectively enrolled over a two year period. Patient demographics (age, weight), Gartland fracture classification, and associated traumatic neurologic injury were collected and analyzed with descriptive statistics. Patients with neurologic palsies were separated based on nerve injury distribution, and followed long term to monitor for neurologic recovery at set time points for follow up. Of the 246 patient cohort, 46 patients (18.6%) sustained a motor nerve palsy (Group 1) and 200 patients (82.4%) did not (Group 2) following elbow injury. Forty three cases involved one nerve palsy, and three cases involved two nerve palsies. No differences were found between patient age (Group 1 – 6.6 years old, Group 2 – 6.2 years old, p = 0.11) or weight (Group 1 – 24.3kg, Group 2 – 24.5kg, p = 0.44). A significantly higher proportion of Gartland type III and IV injuries were found in those with nerve palsies (Group 1 – 93.5%, Group 2 – 59%, p < 0 .001). Thirty four Anterior Interosseous Nerve (AIN) palsies were observed, of which 22 (64.7%) made a full recovery by three month. Refractory AIN injuries requiring longer than three month recovered on average 6.8 months post injury. Ten Posterior Interosseous Nerve (PIN) palsies occurred, of which four (40%) made full recovery at three month. Refractory PIN injuries requiring longer than three month recovered on average 8.4 months post injury. Six ulnar nerve motor palsies occurred, of which zero (0%) made full recovery at three month. Ulnar nerve injuries recovered on average 5.8 months post injury. Neurologic injury occurs significantly higher in Gartland type III and IV paediatric supracondylar fractures. AIN palsies remain the most common, with an expected 65% chance of full recovery by three month. 40% of all PIN palsies are expected to fully recover by three month. Ulnar motor nerve palsies were slowest to recover at 0% by the three month mark, and had an average recovery time of approximately 5.8 months. Our study findings provide further evidence for setting clinical and parental expectations following neurologic injury in paediatric supracondylar elbow fractures.
Bone marrow concentrates are being used to augment soft tissue healing. However, only 0.01% of these cells meet the criteria of a mesenchymal stem cell (MSC), which likely accounts for the variability in reported results. Previous studies using an established rat rotator cuff repair model have demonstrated that bone marrow-derived MSCs had no effect on healing. In this study we evaluated the effect of purified human MSCs on rotator cuff healing in an athymic rat model. Hypothesis: Purified human MSCs added to the repair site will improve biomechanical strength and fibrocartilage formation of the healing tendon. Fifty-two athymic rats underwent unilateral detachment and repair of the supraspinatus tendon with either fibrin glue (control) or fibrin glue with 106 hMSCs (experimental) applied at the repair site. Flow cytometry verified the stem cell phenotype of the cells as CD73+, CD90+, CD105+, CD14-, CD34- and CD45-. Rats were sacrificed at 2 and 4 weeks, with 10 used for biomechanical testing and 3 for histologic analysis from each group. Biomechanical testing revealed a significant increase in failure load (11.5±2.4N vs. 8.5±2.4N, p=0.002) and stiffness (7.1±1.2 N/mm vs. 5.7±2.1 N/mm, p0.17). These data demonstrate the potential for stem cells to augment tendon healing. This is the first study to use purified stem cells, rather than simple bone marrow concentrate. In the future, cell sorting techniques and culture expansion could be used to select and expand the small population of true stem cells in bone marrow. Furthermore, healing could potentially be improved with repeat cell injection at an additional post-operative time point.
We evaluated the long-term outcome of patients with an osteosarcoma who had undergone prior manipulative therapy, a popular treatment in Asia, and investigated its effects on several prognostic factors. Of the 134 patients in this study, 70 (52%) patients had manipulative therapy and 64 (48%) did not. The age, location, and size of tumour were not significantly different between the groups. The five-year overall survival rate was 58% and 92% in the groups with and without manipulative therapy (p = 0.004). Both the primary and overall rates of lung metastasis were significantly higher in the manipulative group (primary: 32% This form of therapy may serve as a mechanism to accelerate the spread of tumour cells, and therefore must be avoided in order to improve the outcome for patients with an osteosarcoma.
