Small extracellular vesicles from mesenchymal stromal cells: the next therapeutic paradigm for musculoskeletal disorders.

Musculoskeletal disorders are one of the biggest contributors to morbidity and place an enormous burden on the health care system in an aging population. Owing to their immunomodulatory and regenerative properties, mesenchymal stromal/stem cells (MSCs) have demonstrated therapeutic efficacy for treatment of a wide variety of conditions, including musculoskeletal disorders. Although MSCs were originally thought to differentiate and replace injured/diseased tissues, it is now accepted that MSCs mediate tissue repair through secretion of trophic factors, particularly extracellular vesicles (EVs). Endowed with a diverse cargo of bioactive lipids, proteins, nucleic acids and metabolites, MSC-EVs have been shown to elicit diverse cellular responses and interact with many cell types needed in tissue repair. The present review aims to summarize the latest advances in the use of native MSC-EVs for musculoskeletal regeneration, examine the cargo molecules and mechanisms underlying their therapeutic effects, and discuss the progress and challenges in their translation to the clinic.

Trends in surgical management of spinal metastases in a Singaporean tertiary referral center: a 17-year retrospective review.

Introduction: Surgical treatment is increasingly the treatment of choice in cancer patients with epidural spinal cord compression and spinal instability. There has also been an evolution in surgical treatment with the advent of minimally invasive surgical (MIS) techniques and separation surgery. This paper aims to investigate the changes in epidemiology, surgical technique, outcomes and complications in the last 17 years in a tertiary referral center in Singapore. Methods: This is a retrospective study of 383 patients with surgically treated spinal metastases treated between January 2005 to January 2022. Patients were divided into 3 groups, patients treated between 2005 - 2010, 2011-2016, and 2017- 2021. Demographic, oncological, surgical, patient outcome and survival data were collected. Statistical analysis with univariate analysis was performed to compare the groups. Results: There was an increase in surgical treatment (87 vs 105 vs 191). Lung, Breast and prostate cancer were the most common tumor types respectively. There was a significant increase in MIS(p<0.001) and Separation surgery (p<0.001). There was also a significant decrease in mean blood loss (1061ml vs 664 ml vs 594ml) (p<0.001) and total transfusion (562ml vs 349ml vs 239ml) (p<0.001). Group 3 patients were more likely to have improved or normal neurology (p=<0.001) and independent ambulatory status(p=0.012). There was no significant change in overall survival. Conclusion: There has been a significant change in our surgical practice with decreased blood loss, transfusion and improved neurological and functional outcomes. Patients should be managed in a multidisciplinary manner and surgical treatment should be recommended when indicated.

Symptomatic Construct Failure after Metastatic Spine Tumor Surgery.

STUDY DESIGN: Retrospective cohort study. PURPOSE: To evaluate the incidence and presentation of symptomatic failures (SFs) after metastatic spine tumor surgery (MSTS). To identify the associated risk factors. To categorize SFs based on the management in these patients. OVERVIEW OF LITERATURE: Few studies have reported on the incidence (1.9%-16%) and risk factors of SF after MSTS. It is unclear whether all SFs, occurring in MSTS-patients, result in revision surgery. METHODS: We conducted a retrospective analysis on 288 patients (246 for final analysis) who underwent MSTS between 2005-2015. Data collected were demographics and peri/postoperative clinical and radiological features. Early and late radiological SF were defined as presentation before and after 3 months from index surgery, respectively. Univariate and multivariate models of competing risk regression analysis were designed to determine the risk factors for SF with death as a competing event. RESULTS: We observed 14 SFs (5.7%) in 246 patients; 10 (4.1%) underwent revision surgery. Median survival was 13.4 months. The mean age was 58.8 years (range, 21-87 years); 48.4% were women. The median time to failure was 5 months (range, 1-60 months). Patients with SF were categorized into three groups: (1) SF when the primary implant was revised (n=5, 35.7%); (2) peri-construct progression of disease requiring extension (n=5, 35.7%); and (3) SFs that did not warrant revision (n=4, 28.5%). Four patients (28.5%) presented with early failure. SF commonly occurred at the implant-bone interface (9/14) and all patients had a spinal instability neoplastic score (SINS) >7. Thirteen patients (92.8%) who developed failure had fixation spanning junctional regions. Multivariate competing risk regression showed that preoperative Eastern Cooperative Oncology Group score was a significant risk factor for implant failure (adjusted sub-hazard ratio, 7.0; 95% confidence interval, 1.63-30.07; p<0.0009). CONCLUSIONS: The incidence of SF (5.7%) was low in patients undergoing MSTS although these patients did not undergo spinal fusion. Preoperative ambulators involved a 7 times higher risk of failure than non-ambulators. Preoperative SINS >7 and fixations spanning junctional regions were associated with SF. Majority of construct failures occurred at the implant-bone interface.

Factors influencing extended hospital stay in patients undergoing metastatic spine tumour surgery and its impact on survival.

Metastatic spine tumour surgeries (MSTS) are indicated for preservation or restoration of neurological function, to provide mechanical stability and pain alleviation. The goal of MSTS is to improve the quality of life of the patients with spinal metastases and rarely for oncological control which is usually achieved by adjuvant therapies. Hence outcome measures such as length of stay (LOS) and rate of complications after MSTS are important indicators of quality but there is limited literature evidence for the same. We carried out a retrospective study to determine the incidence and the factors influencing normal (nLOS) and extended length of stay (eLOS) after MSTS. Data of 220 consecutive patients who underwent MSTS between 2005 and 2015 were retrieved from hospital electronic records. The preoperative, intraoperative and postoperative variables, discharge destinations as well as socioeconomic factors were analyzed. eLOS defined as positive when the LOS exceeded the 75th percentile for this cohort, was the key outcome indicator. Univariate and multivariate logistic regression analyses were performed to determine the predictive factors of eLOS. The overall median LOS was 7 days (1-30 days) and 55 patients had eLOS (LOS ≥ 11 days). Multivariate analysis revealed that significant variables independently associated with eLOS were instrumentation >9 spinal segmental levels (OR 2.89, 95% CI 1.1-7.5, p = 0.032) and presence of postoperative complications (OR 3.68, 95% CI 1.85-7.30, p < 0.001). Metastatic tumours other than breast, prostate and lung have lesser risk of eLOS (OR 0.31, 95% CI 0.14-0.70, p = 0.004). Survival estimates show that patients with eLOS have shorter survival than patients with nLOS (Crude HR 1.81, 95% CI 1.13-2.89, p = 0.003).

Evolving trends in surgically managed patients with proximal humerus fracture: are we different after ten years?

INTRODUCTION: New knowledge, and improved surgical hardware and fixation techniques have changed surgical management. We review the evolving trends of surgically managed proximal humerus fractures. METHODS: Patients who underwent surgery for proximal humerus fractures from 1 January 2001 to 31 December 2010 were identified from the hospital's electronic diagnosis and operative coding database. Data extracted from the database included patient demographics, comorbidities, clinical and radiological findings, operative techniques, and complications. RESULTS: In total, 95 patients with 97 surgically managed proximal humerus fractures were identified. The median age of the patients was 50 (range 12-85) years, and the male to female ratio was 1.2:1.0. Male patients tended to present at a younger age than female patients (peak age 30-39 years vs. 70-79 years, p < 0.001). Two-part surgical neck fracture was the most common type of fracture (n = 33, 34.0%). Plate osteosynthesis was predominantly used for two- and three-part surgical neck fractures involving the greater tuberosity (p = 0.03, p = 0.0002, respectively). Hemiarthroplasty was commonly performed for four-part fractures (p < 0.001). Wound infections, implant failure, avascular necrosis of the humeral head and nonunion were seen in 8 (8.3%) cases. Minimally invasive plate osteosynthesis (MIPO) had been in use since 2007 (p < 0.001). CONCLUSION: Surgically managed proximal humerus fractures predominantly involved young men following high velocity injury and elderly women following osteoporotic fractures. Open plating was most commonly used for two- and three-part fractures, and hemiarthroplasty for four-part fractures. MIPO techniques have been practised in our institution since 2007.