Development of Machine Learning Models for Predicting the 1-Year Risk of Reoperation After Lower Limb Oncological Resection and Endoprosthetic Reconstruction Based on Data From the PARITY Trial.

BACKGROUND: Oncological resection and reconstruction involving the lower extremities commonly lead to reoperations that impact patient outcomes and healthcare resources. This study aimed to develop a machine learning (ML) model to predict this reoperation risk. METHODS: This study was conducted according to TRIPOD + AI. Data from the PARITY trial was used to develop ML models to predict the 1-year reoperation risk following lower extremity oncological resection and reconstruction. Six ML algorithms were tuned and calibrated based on fivefold cross-validation. The best-performing model was identified using classification and calibration metrics. RESULTS: The polynomial support vector machine (SVM) model was chosen as the best-performing model. During internal validation, the SVM exhibited an AUC-ROC of 0.73 and a Brier score of 0.17. Using an optimal threshold that balances all quadrants of the confusion matrix, the SVM exhibited a sensitivity of 0.45 and a specificity of 0.81. Using a high-sensitivity threshold, the SVM exhibited a sensitivity of 0.68 and a specificity of 0.68. Total operative time was the most important feature for reoperation risk prediction. CONCLUSION: The models may facilitate reoperation risk stratification, allowing for better patient counseling and for physicians to implement measures that reduce surgical risks.

Neoadjuvant Chemotherapy and Endoprosthetic Reconstruction for Lower Extremity Sarcomas: Does Timing Impact Complication Rates?

INTRODUCTION: Sarcoma patients undergoing surgical resection and endoprosthetic reconstruction often receive neoadjuvant chemotherapy (NACT). The objective of the current study was to determine if the timing of NACT impacts the rates of surgical site infections (SSI) and reoperations. METHODS: This study was a secondary analysis of the recently published Prophylactic Antibiotic Regimens in Tumor Surgery trial. Patients who underwent NACT, tumor resection, and endoprosthetic reconstruction for a bone or soft tissue sarcoma were included. Multivariate Cox proportional hazards regression models were created to evaluate if NACT timing was predictive of SSI or reoperations. RESULTS: Overall, 216 patients from 39 clinical sites were included in the analysis. The most common diagnosis was osteosarcoma (75%), followed by Ewing's sarcoma (16%). The median time from completion of NACT to surgery was 24 days (interquartile range 15-42 days). Eighty-five (39%) patients underwent surgery within 3 weeks of completing NACT, 78 (36%) underwent surgery 3-6 weeks after completing NACT, and 53 (22%) patients underwent surgery > 6 weeks after completion of NACT. The timing of NACT did not impact SSI rates or reoperation rates. Longer operative time was an independent predictor of both SSI [hazard ratio (HR) per hour of 1.21, 95% confidence interval (CI) 1.07-1.40; p = 0.002] and reoperation rates (HR of 1.15 per hour, 95% CI 1.03-1.28; p = 0.014). CONCLUSION: The timing of surgery following NACT varied considerably. Chemotherapy timing did not impact SSI or reoperations in patients undergoing surgical resection and endoprosthetic reconstruction in sarcoma patients.

Prevalence of gender-based and sexual harassment within orthopedic surgery in Canada.

BACKGROUND: Gender-based and sexual harassment are prevalent in the medical profession. We aimed to quantify the prevalence of such behaviours within orthopedic surgery in Canada and to identify any risk factors for experiencing gender-based or sexual harassment in the workplace. METHODS: In collaboration with the Canadian Orthopaedic Association, we conducted a Canada-wide email questionnaire survey in June 2019 of all orthopedic surgeons registered with the Canadian Orthopaedic Association and the Canadian Orthopaedic Residents' Association. The development of our questionnaire was informed by a review of the literature and published surveys on gender-based and sexual harassment, and consultation with researchers in intimate partner violence. We conducted a multivariable logistic regression analysis to identify risk factors for harassment. RESULTS: Of the 1783 surgeons invited to participate, 465 returned the questionnaire (response rate 26.1%); the response rate was 48.1% for females and 22.1% for males. Overall, 331/433 respondents (76.4%, 95% confidence interval [CI] 72%-80%) and 315/423 respondents (74.5%, 95% CI 70%-78%) reported having experienced at least 1 occurrence of gender-based and sexual harassment, respectively. Women were significantly more likely than men to have experienced both gender-based and sexual harassment (odds ratio [OR] 16.2, 95% CI 4.8-54.0, and OR 2.2, 95% CI 1.2-4.0, respectively). Respondents who identified as nonwhite were significantly less likely than those who identified as white to have experienced gender-based harassment (OR 0.5, 95% CI 0.3-0.99). CONCLUSION: The prevalence of gender-based and sexual harassment is high within Canadian orthopedic surgery, and women are at highest risk for experiencing harassment. The results may provide the impetus for orthopedic societies to develop action plans and to re-examine and enforce policies to address these damaging behaviours appropriately.

Which Bone-Modifying Agent is Associated with Better Outcomes in Patients with Skeletal Metastases from Lung Cancer? A Systematic Review and Network Meta-analysis.

BACKGROUND: Lung cancer is one of the most commonly diagnosed cancers and is the leading cause of cancer-related deaths. Metastatic bone disease occurs in 20% to 40% of patients with lung cancer, and these patients often present with pain or skeletal-related events (SREs) that are associated with decreased survival. Bone-modifying agents such as denosumab or bisphosphonates are routinely used; however, to our knowledge, there has been no quantitative synthesis of randomized controlled trial data to determine the most effective pharmacologic treatment of metastatic bone disease because of lung cancer. QUESTIONS/PURPOSES: We aimed to perform a network meta-analysis of randomized trials to identify the bone-modifying agent that is associated with the (1) highest overall survival, (2) longest time to SRE, (3) lowest SRE incidence, and (4) greatest likelihood of pain resolution. METHODS: We conducted our study according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol and pre-registered the analysis on PROSPERO (ID: CRD42019124364). We performed a librarian-assisted search of MEDLINE, PubMed, EMBASE, Cochrane Library, and Chinese databases including China National Knowledge Infrastructure and Wanfang Data. We included randomized controlled trials reporting outcomes specifically for patients with lung cancer treated with a bisphosphonate or denosumab. SREs included pathologic fractures, spinal cord compression, hypercalcemia of malignancy, or pain resulting in surgical intervention or radiation therapy. We excluded trials exclusively reporting surrogate outcomes such as changes in bone turnover markers. Screening, data extraction, risk of bias evaluation, and Grading of Recommendations Assessment, Development, and Evaluation evaluations were performed in duplicate. We included 131 randomized controlled trials that evaluated 11,105 patients with skeletal metastases from lung cancer. The network meta-analysis was performed using a frequentist model and the R statistical software. Results are reported as relative risks or mean differences, and the I2 value is reported for heterogeneity. The P-score, a measure of ranking certainty that accounts for standard error, is reported for each outcome. Heterogeneity in the network was considered moderate for overall survival and time to SRE, mild for the incidence of SRE, and low for pain resolution. RESULTS: For overall survival, denosumab was ranked above zoledronic acid and estimated to confer a mean of 3.3 months (95% CI 0.3-6.3) of increased overall survival compared with untreated patients (P-score = 89%). For the time to SRE, denosumab was ranked first with a mean of 9.1 additional SRE-free months (95% CI 6.7-11.5) compared with untreated patients (P-score = 99%), while zoledronic acid conferred an additional 4.8 SRE-free months (95% CI 3.6-6.1). Reduction in the incidence of SREs was not different between patients treated with denosumab (relative risk 0.54; 95% CI 0.33-0.87) and those treated with zoledronic acid (relative risk 0.56; 95% CI 0.46-0.67). Patients treated with the combination of ibandronate and systemic therapy were more likely to experience successful pain resolution than untreated patients (relative risk 2.4; 95% CI 1.8-3.2). CONCLUSION: In this comprehensive synthesis of all available randomized controlled trial evidence guiding the pharmacologic treatment of bone metastases from lung cancer, denosumab was ranked above zoledronic acid for overall survival and time to SRE and was not different for reducing the incidence of SRE. Both were superior to no treatment for each of these outcomes. Given this, we encourage physicians to consider the use of denosumab or zoledronic acid in treating this patient population. The combination of ibandronate and systemic therapy was the most effective at reducing pain because of metastases. No cost-effectiveness analysis has yet been performed for denosumab and zoledronic acid on patients with metastatic lung cancer, and this represents an avenue for future research. LEVEL OF EVIDENCE: Level I, therapeutic study.

Management of infected extremity endoprostheses: a systematic review.

BACKGROUND: Endoprosthetic reconstructions have become increasingly common in the setting of significant bone loss. Indications include revision arthroplasty, trauma, and reconstruction in the setting of primary malignancies or bony metastases. Although the use of endoprostheses has several advantages, they carry a high risk of infection. The purpose of this review is to determine the success rates of surgical management of infected endoprostheses. METHODS: The authors searched databases for relevant studies and screened in duplicate. Data extracted included overall infection rate, timing of infection, follow-up, isolated pathogen and operative treatment strategy, and subsequent failure rate. The overall quality of the evidence with the Methodological Index for non-randomized studies criteria. RESULTS: A total of 16 studies and 647 patients met the inclusion criteria. 400 patients had operative management and reported outcomes. Failure rates of patients undergoing debridement, antibiotics, and implant retention (DAIR) were 55.1%. Failure rates of patients who underwent one-stage revision were 45.5%. Failure rates of patients undergoing two-stage revision were 27.3%. Failure occurred at 31.4 months (range, 0-228) postoperatively. CONCLUSIONS: Rates of periprosthetic joint infection remain high in endoprosthetic reconstructions. Although DAIR procedures were found to have a low success rate, they remain a reasonable option in acute infections given the morbidity of staged revisions. There is a lack of comparative data in the current literature and the heterogeneity and low level of evidence does not allow for between group comparisons of results.

Causes and Frequencies of Reoperations After Endoprosthetic Reconstructions for Extremity Tumor Surgery: A Systematic Review.

BACKGROUND: Excision of bone tumors and endoprosthetic reconstruction allow patients early weightbearing and a potential functional advantage compared with amputation. These reconstructions do not restore the limb to normal status, however, and patients are subject to complications that may result in revision or loss of the limb. Because better understanding of these complications based on current information might help the patient and surgeon in decision-making, we undertook a systematic review of studies published on this topic. QUESTIONS/PURPOSES: (1) What are the primary modes and proportion of failure of tumor endoprostheses in patients undergoing reconstruction after excision of primary extremity bone sarcomas? METHODS: We systematically searched MEDLINE, Embase, and the Cochrane Library for all studies published from April 15, 1998, to April 15, 2018. Three reviewers independently reviewed studies reporting endoprosthetic reconstruction survival and events requiring revision for primary extremity bone tumors treated with endoprosthetic reconstruction for inclusion and performed independent data extraction. We excluded all studies with fewer than five patients, any systematic review/meta-analyses, and any study not reporting on primary extremity bone tumors. All discrepancies were resolved by the study's senior author. Data extracted from included studies were any reoperation event for wound dehiscence, any operative fixation for a pathologic fracture, and any revision of the primary endoprosthesis for implant wear or breakage, deep infection not amenable to prosthesis retention, or for local recurrence. We assessed the overall quality of the evidence with the Methodological Index for Non-Randomized Studies (MINORS) approach with a higher MINORS score representative of a more methodologically rigorous study with a total possible score of 16 points for noncomparative and 24 points for comparative studies. Forty-nine studies met criteria for inclusion from an initial search return of 904 studies, of which no studies were randomized controlled trials. From a total patient population of 2721, there was a mean followup of 93 months (range, 1-516 months) with loss to followup or death occurring in 447 of 2118 (21%) patients with six studies not providing loss to followup data. The mean MINORS score was 14 for prospective studies and 11 for retrospective studies. RESULTS: Overall, there were 1283 reoperations among the 2721 (47%) patients. Reoperation for mechanical endoprosthetic events (soft tissue dehiscence or periarticular soft tissue instability, aseptic loosening, or implant wear/fracture) occurred in 907 of 2721 (33%) patients. Aseptic loosening occurred at a mean of 75 months (range, 1-376 months) in 212 of 315 patients (67%). Deep infection requiring removal of the initial prosthesis occurred in 247 of 2721 (9%) patients with deep infection occurring at a mean of 24 months (range, 1-372 months) in the 190 infections (77%) with time to infection data available. Local recurrence rates requiring revision or amputation occurred in 129 (5%) of all patients. There was an overall primary endoprosthesis survival rate without any surgical reintervention of 63% among reporting studies at a mean of 79 months followup. CONCLUSIONS: Failures of endoprosthetic reconstructions after extremity tumor surgery are common, most often resulting from implant wear or fracture, aseptic loosening, and infection. Importantly, the aggregated data are the first to attempt to quantify the time to specific complication types within this patient population. Deep infection not amenable to endoprosthesis retention appears to occur approximately 2 years postoperatively in most patients, with aseptic loosening occurring most commonly at 75 months. Although endoprosthetic reconstruction is one of the most common forms of reconstruction after bone tumor resection, the quality of published evidence regarding this procedure is of low quality with high loss to followup and data quality limiting interstudy analysis. The quality of the evidence is low with high loss to followup and inconsistent reporting of times to reintervention events. Although the most common modes of endoprosthetic failure in this population are well known, creation of quality prospective, collaborative databases would assist in clarifying and informing important elements of the followup process for these patients. LEVEL OF EVIDENCE: Level IV, therapeutic study.

The Pediatric Toronto Extremity Salvage Score (pTESS): Validation of a Self-reported Functional Outcomes Tool for Children with Extremity Tumors.

BACKGROUND: The physical function of children with sarcoma after surgery has not been studied explicitly. This paucity of research is partly because of the lack of a sufficiently sensitive pediatric functional measure. The goal of this study was to establish and validate a standardized measure of physical function in pediatric patients with extremity tumors. QUESTIONS/PURPOSES: (1) What is the best format and content for new upper- and lower-extremity measures of physical function in the pediatric population? (2) Do the new measures exhibit floor and/or ceiling effects, internal consistency, and test-retest reliability? (3) Are the new measures valid? METHODS: In Phase 1, interviews with 17 consecutive children and adolescents with bone tumors were conducted to modify the format and content of draft versions of the pediatric Toronto Extremity Salvage Score (pTESS). In Phase 2, the pTESS was formally translated into French. In Phase 3, 122 participants between 7 and 17.9 years old with malignant or benign-aggressive bone tumors completed the limb-specific measure on two occasions. Older adolescents also completed the adult TESS. Floor and ceiling effects, internal consistency, test-retest reliability, and validity were evaluated. RESULTS: Feedback from interviews resulted in the removal, addition, and modification of draft items, and the pTESS-Leg and pTESS-Arm questionnaires were finalized. Both versions exhibited no floor or ceiling effects and high internal consistency (α > 0.92). The test-retest reliability was excellent for the pTESS-Leg (intraclass correlation coefficient [ICC] = 0.94; 95% CI, 0.90-0.97) and good for the pTESS-Arm (ICC = 0.86; 95% CI, 0.61-0.96). Known-group validity (ability to discriminate between groups) was demonstrated by lower mean pTESS-Leg scores for participants using gait aids or braces (mean = 68; SD = 21) than for those who did not (mean = 87; SD = 11; p < 0.001). There was no significant difference between pTESS arm scores among respondents using a brace (n = 5; mean = 73; SD = 11) and those without (n = 22; mean = 83; SD = 19; p = 0.13). To evaluate construct validity, we tested a priori hypotheses. The duration since chemotherapy correlated moderately with higher pTESS-Leg scores (r = 0.4; p < 0.001) but not with pTESS-Arm scores (r = 0.1; p = 0.80), and the duration since tumor resection correlated moderately with higher pTESS-Leg scores (r = 0.4; p < 0.001) but not pTESS-Arm scores (r = 0.2; p = 0.4). Higher VAS scores (that is, it was harder to do things) antecorrelated with both pTESS versions (pTESS-Leg: r = -0.7; p < 0.001; pTESS-Arm: r = -0.8; p < 0.001). To assess criterion validity, we compared the pTESS with the current "gold standard" (adult TESS). Among adolescents, strong correlations were observed between the TESS and pTESS-Leg (r = 0.97, p < 0.001) and pTESS-Arm (r = 0.9, p = 0.007). CONCLUSIONS: Both pTESS versions exhibited no floor or ceiling effects and had high internal consistency. The pTESS-Leg demonstrated excellent reliability and validity, and the pTESS-Arm demonstrated good reliability and reasonable validity. The pTESS is recommended for cross-sectional evaluation of self-reported physical function in pediatric patients with bone tumors. LEVEL OF EVIDENCE: Level II, outcome measurement development.

Published intimate partner violence studies often differ from their trial registration records.

INTRODUCTION: Registering study protocols in a trial registry is important for methodologic transparency and reducing selective reporting bias. The objective of this investigation was to determine whether published studies of intimate partner violence (IPV) that had been registered matched the registration record on key study design elements. METHODS: We systematically searched three trial registries to identify registered IPV studies and the published literature for the associated publication. Two authors independently determined for each study whether key study elements in the registry matched those in the published paper. RESULTS: We included 66 studies published between 2006 and 2017. Nearly half (29/66, 44%) were registered after study completion. Many (26/66, 39%) had discrepancies regarding the primary outcome, and nearly two-thirds (42/66, 64%) had discrepancies in secondary outcomes. Discrepancies in study design were less frequent (13/66, 20%). However, large changes in sample size (26/66, 39%) and discrepancies in funding source (28/66, 42%) were frequently observed. CONCLUSIONS: Trial registries are important tools for research transparency and identifying and preventing outcome switching and selective outcome reporting bias. Published IPV studies often differ from their records in trial registries. Researchers should pay close attention to the accuracy of trial registry records.

Moving Forward Through Consensus: A Modified Delphi Approach to Determine the Top Research Priorities in Orthopaedic Oncology.

BACKGROUND: Several challenges presently impede the conduct of prospective clinical studies in orthopaedic oncology, including limited financial resources to support their associated costs and inadequate patient volume at most single institutions. This study was conducted to prioritize research questions within the field so that the Musculoskeletal Tumor Society (MSTS), and other relevant professional societies, can direct the limited human and fiscal resources available to address the priorities that the stakeholders involved believe will have the most meaningful impact on orthopaedic oncology patient care. QUESTIONS/PURPOSES: The purpose of this study was to use a formal consensus-based approach involving clinician-scientists and other stakeholders to identify the top priority research questions for future international prospective clinical studies in orthopaedic oncology. METHODS: A three-step modified Delphi process involving multiple stakeholder groups (including orthopaedic oncologists, research personnel, funding agency representation, and patient representation) was conducted. First, we sent an electronic questionnaire to all participants to solicit clinically relevant research questions (61 participants; 54% of the original 114 individuals invited to participate returned the questionnaires). Then, participants rated the candidate research questions using a 5-point Likert scale for five criteria (60 participants; 53% of the original group participated in this portion of the process). Research questions that met a priori consensus thresholds progressed for consideration to an in-person consensus meeting, which was attended by 44 participants (39% of the original group; 12 countries were represented at this meeting). After the consensus panel's discussion, members individually assigned scores to each question using a 9-point Likert scale. Research questions that met preset criteria advanced to final ranking, and panel members individually ranked their top three priority research questions, resulting in a final overall ranking of research priorities. RESULTS: A total of 73 candidate research questions advanced to the consensus meeting. In the end, the consensus panel identified four research priorities: (1) Does less intensive surveillance of patients with sarcoma affect survival? (2) What are the survival outcomes over time for orthopaedic oncology implants? (3) Does resection versus stabilization improve oncologic and functional outcomes in oligometastatic bone disease? (4) What is the natural history of untreated fibromatosis? CONCLUSIONS: The results of this study will assist in developing a long-term research strategy for the MSTS and, possibly, the orthopaedic oncology field as a whole. Furthermore, the results of this study can assist researchers in guiding their research efforts and in providing a justified rationale to funding agencies when requesting the resources necessary to support future collaborative research studies that address the identified orthopaedic oncology priorities.

Has the Level of Evidence of Podium Presentations at the Musculoskeletal Tumor Society Annual Meeting Changed Over Time?

BACKGROUND: Level of evidence (LOE) framework is a tool with which to categorize clinical studies based on their likelihood to be influenced by bias. Improvements in LOE have been demonstrated throughout orthopaedics, prompting our evaluation of orthopaedic oncology research LOE to determine if it has changed in kind. QUESTIONS/PURPOSES: (1) Has the LOE presented at the Musculoskeletal Tumor Society (MSTS) annual meeting improved over time? (2) Over the past decade, how do the MSTS and Orthopaedic Trauma Association (OTA) annual meetings compare regarding LOE overall and for the subset of therapeutic studies? METHODS: We reviewed abstracts from MSTS and OTA annual meeting podium presentations from 2005 to 2014. Three independent reviewers evaluated a total of 1222 abstracts for study type and LOE; there were 577 abstracts from MSTS and 645 from OTA. Changes in the distributions of study type and LOE over time were evaluated by Pearson chi-square test. RESULTS: There was no change over time in MSTS LOE for all study types (p = 0.13) and therapeutic (p = 0.36) study types during the reviewed decade. In contrast, OTA LOE increased over this time for all study types (p < 0.01). The proportion of Level I therapeutic studies was higher at the OTA than the MSTS (3% [14 of 413] versus 0.5% [two of 387], respectively), whereas the proportion of Level IV studies was lower at the OTA than the MSTS (32% [134 of 413] versus 75% [292 of 387], respectively) during the reviewed decade. The proportion of controlled therapeutic studies (LOE I through III) versus uncontrolled studies (LOE IV) increased over time at OTA (p < 0.021), but not at MSTS (p = 0.10). CONCLUSIONS: Uncontrolled case series continue to dominate the MSTS scientific program, limiting progress in evidence-based clinical care. Techniques used by the OTA to improve LOE may be emulated by the MSTS. These techniques focus on broad participation in multicenter collaborations that are designed in a comprehensive manner and answer a pragmatic clinical question.

Chronology of the Radiographic Appearances of the Calcium Sulfate-Calcium Phosphate Synthetic Bone Graft Composite Following Resection of Bone Tumors: A Follow-up Study of Postoperative Appearances.

PURPOSE: The objective of the study was to characterize the radiographic appearance of graft resorption and new bone incorporation into a postresection defect of the calcium-sulfate calcium-phosphate synthetic bone graft composite following resection of benign bone tumours. METHODS: Twenty-five patients who underwent treatment with the CaSO4/CaPO4 synthetic graft following bone tumour resection were retrospectively identified from our oncology database. Postoperative radiographs were assessed for: 1) combined partial graft resorption and ingrowth at the graft site; 2) complete graft resorption with complete incorporation of new bone into the defect. After chronologically grouping radiographs, the volume of graft material used to fill bony defects, radiographic evidence of complications, and patterns of resorption were recorded. RESULTS: Partial resorption of graft material/partial ingrowth of new bone was seen in 21 patients at 2.5 months postoperatively. Complete resorption of graft with complete new bone incorporation at the graft site was seen in 94% of cases (15 of 16) by 10 months after surgery. Mean time to complete incorporation of new bone was 6.7 months. Time to resorption of the graft with new bone ingrowth was found to be related to the volume of graft used with smaller volumes showing earlier resorption. For all cases demonstrating resorption (21 of 21), the pattern observed was peripheral to central. Five patients developed complications, including tumour recurrence, cyst formation, and graft site infection. CONCLUSION: Our study suggests a characteristic time and volume related radiographic pattern of resorption and new bone ingrowth with the CaSO4/CaPO4 synthetic graft. Findings that deviate from this pattern may represent complication and warrant additional follow-up.

The epigenetic regulation of SOX9 by miR-145 in human chondrosarcoma.

Chondrosarcoma is the most common primary bone malignancy in the adult population with a high rate of pulmonary metastasis. Chondrosarcoma is managed with surgical excision as the tumors do not respond well to conventional chemotherapy or radiation therapy. Thus, there exists a dire need to develop systemic treatment options to target chondrosarcoma cells for metastatic spread. We hypothesized that the expression of miR-145 is low in chondrosarcoma, leading to decreased transcriptional control of SOX9 (the master regulator of chondrogenesis), and downstream activation of the transcription factor ETV5. We have previously shown that ETV5 activates MMP-2 expression in chondrosarcoma, which in turn increases local bone matrix resorption. In this study, we confirm high expression of SOX9 in human chondrosarcoma using real-time PCR, Western blotting, and immunofluorescence. An ETV5 promoter-reporter plasmid was transfected into chondrosarcoma cells to determine if SOX9 directly regulates the expression of ETV5. Co-transfection of the ETV5 promoter-plasmid with SOX9 lentivirus significantly increased the luciferase activity derived from the ETV5 promoter, from which the regulatory relationship between SOX9 and ETV5 is established. MiR-145 was found to be down-regulated in chondrosarcoma cell lines, patient samples, and further confirmed with a public sarcoma database. After stable miR-145 lentiviral transfection, the subsequent mRNA expression levels of SOX9, ETV5, and MMP-2 were significantly decreased in chondrosarcoma cells. The results generated by this study may have important clinical significance in the treatment of patients with chondrosarcoma in that targeted miRNA may have the potential to downregulate the upstream activators of proteases such as MMP-2.

Intrawound vancomycin to prevent infections after spine surgery: a systematic review and meta-analysis.

PURPOSE: Post-operative spine surgical site infections are associated with substantial morbidity, mortality, and economic burden. Intrawound vancomycin may prevent infections after spine surgery, but recent studies have reported conflicting results. The objectives of this systematic review and meta-analysis were to determine: (1) In patients undergoing spine surgery, does the application of intrawound vancomycin lead to reduced rates of post-operative surgical site infections? (2) Are there differences in the estimates of effect between observational studies and randomized trials? (3) What adverse events are reported in the literature? METHODS: All published comparative studies of intrawound vancomycin in spine surgery were included. Two reviewers independently screened eligible articles and assessed study quality. Observational studies and randomized trials were pooled separately using a random-effects model. RESULTS: Eight observational studies and one randomized controlled trial met the inclusion criteria. Across observational studies, the odds of infection with intrawound vancomycin was 0.19 times the odds of infection without intrawound vancomycin (95 % CI 0.08-0.47, p = 0.0003, I (2) = 52 %). The single randomized controlled trial produced a conflicting result (OR 0.96, 95 % CI 0.34-2.66, p = 0.93). There were no adverse events attributable to intrawound vancomycin. The quality of the evidence was low or very low. CONCLUSIONS: There is a lack of high-quality evidence to inform the use of intrawound vancomycin in spine surgery. Surgeons should be cautious before widely adopting this intervention and should be vigilant in monitoring for adverse effects. Further investigation with additional randomized controlled trials is justified.