Risk Factors for All-Cause Early Reoperation Following Tumor Resection and Endoprosthetic Reconstruction: A Secondary Analysis from the PARITY Trial.

BACKGROUND: Oncologic resection and endoprosthetic reconstruction of lower-extremity musculoskeletal tumors are complex procedures fraught with multiple modes of failure. A robust assessment of factors contributing to early reoperation in this population has not been performed in a large prospective cohort. The aim of the present study was to assess risk factors for early reoperation in patients who underwent tumor excision and endoprosthetic reconstruction, with use of data from the Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY) trial. METHODS: Baseline characteristics were assessed, including age, sex, tumor type, tumor location, presence of a soft-tissue mass, diabetes, smoking status, chemotherapy use, and neutropenia. Operative factors were recorded, including operative time, topical antibiotics, silver-coated prosthetics, endoprosthetic fixation, extra-articular resection, length of bone resected, margins, tranexamic acid, postoperative antibiotics, negative-pressure wound therapy, and length of stay. Univariate analysis was utilized to explore the differences between patients who did and did not undergo reoperation within 1 year postoperatively, and a multivariate Cox proportional hazards regression model was utilized to explore the predictors of reoperation within 1 year. RESULTS: A total of 155 (25.7%) of 604 patients underwent ≥1 reoperation. In univariate analysis, tumor type (p < 0.001), presence of a soft-tissue mass (p = 0.045), operative time (p < 0.001), use of negative-pressure wound therapy (p = 0.010), and hospital length of stay (p < 0.001) were all significantly associated with reoperation. On multivariate assessment, tumor type (benign aggressive bone tumor versus primary bone malignancy; hazard ratio [HR], 0.15; 95% confidence interval [CI], 0.04 to 0.63; p = 0.01), operative time (HR per hour, 1.15; 95% CI, 1.10 to 1.23; p < 0.001), and use of negative-pressure wound therapy (HR, 1.93; 95% CI, 1.30 to 2.90; p = 0.002) remained significant predictors of reoperation within 1 year. CONCLUSIONS: Independent variables associated with reoperation within 1 year in patients who underwent tumor resection and endoprosthetic reconstruction included tumor type (benign aggressive bone tumor versus primary bone malignancy), operative time, and use of negative-pressure wound therapy. These results will help to inform patients and surgeons regarding the risk of reoperation by diagnosis and reinforce operative time as a factor influencing reoperation. These results also support further investigation into the use of negative-pressure wound therapy at the time of surgery in this patient population. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

The Impact of Implant Fixation Type on Reoperation Rates Following Endoprosthetic Reconstruction Surgery.

BACKGROUND: Prospective evidence supporting the use of cemented or uncemented implants in endoprosthetic reconstruction is lacking. The present study aimed to determine the effect of cemented fixation compared with uncemented fixation on the rate of all-cause reoperation at 1 year postoperatively. METHODS: This is a secondary analysis of the Prophylactic Antibiotic Regimens In Tumor Surgery (PARITY) trial. A total of 503 patients who underwent surgical excision and endoprosthetic reconstruction of a lower-extremity bone tumor were included in this analysis. A multivariate Cox proportional hazards model was utilized to assess the independent relationship between fixation group and implant survivorship, with all-cause reoperation as the end point. RESULTS: There were 388 cemented implants and 115 uncemented implants. Participants had a mean age of 42.7 years (standard deviation, 22.0 years), and 59% were male. Overall, 131 reoperations were identified over the 1-year follow-up period. There were no significant differences found in all-cause reoperation (hazard ratio [HR], 1.05; 95% confidence interval [CI], 0.70 to 1.57; p = 0.761), septic reoperation, or aseptic reoperation between cemented and uncemented fixation at 1 year postoperatively. The Cox regression analysis demonstrated that total operative time (HR per hour, 1.10; 95% CI, 1.02 to 1.20; p = 0.019) was an independent predictor of reoperation. The risk of reoperation was lower in patients with benign aggressive disease (HR, 0.11; 95% CI, 0.02 to 0.80; p = 0.029) or metastatic bone disease (HR, 0.30; 95% CI, 0.11 to 0.85; p = 0.023). Patients who underwent cemented fixation showed clinically meaningful functional improvement at 1 year postoperatively. CONCLUSIONS: Cemented compared with uncemented fixation has no effect on 1-year all-cause reoperation rates in endoprosthetic reconstruction surgery. Further research is required to investigate the long-term survival of cemented versus uncemented implants. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Patient and Surgical Risk Factors for Surgical Site Infection in Lower-Extremity Oncological Endoprosthetic Reconstruction: A Secondary Analysis of the PARITY Trial Data.

BACKGROUND: The specific risk factors for surgical site infection (SSI) in orthopaedic oncology patients undergoing endoprosthetic reconstruction have not previously been evaluated in a large prospective cohort. In the current study, we aimed to define patient- and procedure-specific risk factors for SSI in patients who underwent surgical excision and endoprosthetic reconstruction for lower-extremity bone or soft-tissue tumors using the prospectively collected data of the Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY) trial. METHODS: PARITY was a multicenter, blinded, randomized controlled trial with a parallel 2-arm design that aimed to determine the effect of a long duration (5 days) versus short duration (24 hours) of postoperative prophylactic antibiotics on the rate of SSI in patients undergoing surgical excision and endoprosthetic reconstruction of the femur or tibia. In this secondary analysis of the PARITY data, a multivariate Cox proportional hazards regression model was constructed to explore predictors of SSI within 1 year postoperatively. RESULTS: A total of 96 (15.9%) of the 604 patients experienced an SSI. Of the 23 variables analyzed in the univariate analysis, 4 variables achieved significance: preoperative diagnosis, operative time, volume of muscle excised, and hospital length of stay (LOS). However, only hospital LOS was found to be independently predictive of SSI in the multivariate regression analysis (hazard ratio per day = 1.03; 95% confidence interval = 1.01 to 1.05; p < 0.001). An omnibus test of model coefficients demonstrated that the model showed significant improvement over the null model (χ2 = 78.04; p < 0.001). No multicollinearity was found. CONCLUSIONS: This secondary analysis of the PARITY study data found that the only independent risk factor for SSI on multivariate analysis was hospital LOS. It may therefore be reasonable for clinicians to consider streamlined discharge plans for orthopaedic oncology patients to potentially reduce the risk of SSI. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Central Adjudication Committee and Clinical Site Investigator Agreement on Outcomes in the PARITY Trial: A Secondary Analysis of the PARITY Trial Data.

BACKGROUND: The detection of a surgical site infection (SSI) in patients with metal implants requires a high degree of clinical acumen. The inherent subjectivity of SSI diagnosis poses a challenge in the design of surgical trials because this subjectivity raises concern for outcome assessment bias. Central Adjudication Committees (CACs) are often utilized to minimize the variability in outcome assessment. Little research has been done to determine the reliability of outcome assessment in trials utilizing a CAC. In the present study, we determined the agreement between the study CAC and the clinical site investigators for the primary and secondary outcome assessments. METHODS: The Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY) trial was a multicenter, blinded, parallel 2-arm, randomized controlled trial that aimed to determine the effect of a 5-day versus 1-day postoperative prophylactic antibiotic regimen on the rate of SSI in patients undergoing surgical excision of tumors in the femur or tibia. The blinded PARITY CAC adjudicated all primary and secondary outcomes identified during the 1-year study follow-up. In the present secondary analysis, the Cohen kappa statistic was utilized to determine the level of agreement. RESULTS: The primary outcome of SSI diagnosis demonstrated a substantial level of agreement between the CAC and the site investigators (0.699; 95% confidence interval [CI], 0.595 to 0.803]). Categorization of the SSI (i.e., superficial, deep, or organ space) showed moderate agreement (0.470; 95% CI, 0.382 to 0.558). Secondary outcomes such as the types of reoperations and the indication for reoperation typically showed substantial to almost perfect agreement, whereas antibiotic-related complications showed fair agreement (0.241; 95% CI, 0.000 to 0.474). CONCLUSIONS: Although there was a substantial level of agreement between the PARITY CAC and site investigators on the diagnosis of an SSI, as well as typically at least substantial agreement on the causes and types of reoperations, there was less agreement regarding the type of SSI and the occurrence of an antibiotic-related complication. Therefore, the CAC appears to have provided value when adjudicating the depth of infection and when determining the causality of medical complications associated with antibiotics. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Evaluation of enamel thickness of mandibular incisors

ABSTRACT Objective: To measure enamel thickness at the proximal surfaces of the mandibular incisors, using micro-computed tomography (micro-CT) scans. Material and Methods: Forty-one single-rooted mandibular incisors were selected and analyzed according to anatomical characteristics, to form three groups: Group 1 - central incisors (n = 18); Group 2 - right lateral incisors (n = 10); and Group 3 - left lateral incisors (n = 13). First, enamel thickness at the proximal contact areas of the mandibular incisors was measured. Second, the mesial and distal surfaces of the lateral incisors were compared. Finally, the relationship between the tooth width and the mean enamel thickness was determined. Each tooth was scanned with a micro-CT scanner, and the image was processed with SCANCO micro-CT onboard analysis software. Results: There were no statistically significant differences in mean enamel thickness between the mesial and distal surfaces for each lateral incisor, or between contralateral lateral incisors. In all surfaces analyzed, the upper zones had statistically significantly thinner enamel (0.52 ± 0.10 mm) when compared to the middle and lower zones (0.60 ± 0.08 mm and 0.59 ± 0.08 mm, respectively). There was no correlation (r =0.07) between enamel thickness of the mandibular incisor and the tooth width. Conclusions: The enamel thickness of the mandibular incisors is similar on the mesial and distal surfaces, with the thinnest layer located at the upper zone.

RESUMO Objetivo: Medir a espessura do esmalte nas superfícies proximais dos incisivos inferiores, usando imagens de microtomografia computadorizada (micro-CT). Material e Métodos: Quarenta e um incisivos inferiores com raiz única foram selecionados e analisados de acordo com as características anatômicas, formando três grupos: Grupo 1 - incisivos centrais (n = 18); Grupo 2 - incisivos laterais direitos (n = 10); e Grupo 3 - incisivos laterais esquerdos (n = 13). Primeiro, foi medida a espessura do esmalte nas áreas de contato proximal dos incisivos inferiores. Em segundo lugar, as faces mesial e distal dos incisivos laterais foram comparadas. Por fim, foi determinada a relação entre a largura do dente e a espessura média do esmalte. Cada dente foi escaneado com um scanner micro-CT, e a imagem foi processada com o software de análise SCANCO micro-CT. Resultados: Não houve diferenças estatisticamente significativas na espessura média do esmalte entre as superfícies mesial e distal de cada incisivo lateral, ou entre os incisivos laterais contralaterais. Em todas as superfícies analisadas, as zonas superiores apresentaram esmalte significativamente mais fino (0,52 ± 0,10 mm) quando comparadas às zonas média e inferior (0,60 ± 0,08 mm e 0,59 ± 0,08 mm, respectivamente). Não houve correlação (r = 0,07) entre a espessura do esmalte do incisivo inferior e a largura do dente. Conclusões: A espessura do esmalte dos incisivos inferiores é semelhante nas faces mesial e distal, com a camada mais fina localizada na zona superior.

Evaluation of maxillary canine and molar movement during the first phase of extraction space closure: a multilevel analysis

ABSTRACT Objective: This study was designed to analyze and compare the cusp and apex movements of the maxillary canines and first molars during canine retraction in the first step of extraction space closure, and to evaluate if these teeth follow a curvilinear (acceleration and/or deceleration) movement rate. Material and Methods: Twenty-five patients (23.3 ± 5.1 years of age) were enrolled. The retraction of the maxillary canines was accomplished using nickel-titanium closed coil springs (100gf) on 0.020-in stainless steel archwire. Oblique cephalograms were traced and superimposed on the anatomic best fit of the maxilla (before the retraction [T0], and after one month [T1], three [T3], five [T5] and seven [T7] months). Statistics was based in a normally distributed data. Multilevel procedures were used to derive polynomials for each of the measurements. Student's t-test and one-way repeated measures ANOVA were conducted. The level of significance of 5% was adopted. Results: Canine cusps and apexes did not follow a quadratic curve regarding horizontal movement (neither accelerate nor decelerate). Canine and molar cusps showed more horizontal movement than apexes (4.80 mm vs. 2.78 mm, and 2.64 mm vs. 2.17 mm, respectively). Conclusions: Canine did not accelerate or decelerate overtime horizontally; the cusps and apexes of the canines and molars showed more horizontal movement and larger rate at the beginning of canine retraction, followed by significantly smaller and constant movement rate after the first month.

RESUMO Objetivo: O objetivo deste estudo foi analisar a movimentação das cúspides e dos ápices de caninos e primeiros molares superiores durante a retração de caninos na primeira fase do fechamento do espaço pós-extração, e avaliar se esses dentes apresentam mudança na taxa de movimentação (aceleração e/ou desaceleração). Material e Métodos: Vinte e cinco pacientes (idade = 23,3 ± 5,1 anos) foram incluídos. A retração dos caninos superiores foi realizada com molas helicoidais fechadas de níquel-titânio (100gf) em arco 0,020" de aço inoxidável. Foram feitos traçados cefalométricos de telerradiografias oblíquas e sobrepostos ao melhor ajuste anatômico da maxila (antes da retração [T0]; após um mês [T1], três meses [T3], cinco meses [T5] e sete meses [T7]). A estatística foi baseada em dados com distribuição normal. Procedimentos multiníveis foram usados para derivar polinômios para cada uma das medidas. Teste t de Student e ANOVA de uma via para medidas repetidas foram realizados, adotando-se um nível de significância de 5%. Resultados: As cúspides e os ápices dos caninos não seguiram uma curva quadrática em relação ao movimento horizontal (sem aceleração ou desaceleração). As cúspides dos caninos e molares apresentaram mais movimento horizontal do que os ápices (4,80 mm vs. 2,78 mm e 2,64 mm vs. 2,17mm, respectivamente). Conclusões: A movimentação horizontal dos caninos não acelerou ou desacelerou ao longo do tempo; as cúspides e os ápices dos caninos e molares apresentaram maior movimento horizontal e maior taxa de movimentação no início da retração dos caninos, seguida por uma taxa de movimentação significativamente menor e constante após o primeiro mês.

Predictors of Functional Recovery among Musculoskeletal Oncology Patients Undergoing Lower Extremity Endoprosthetic Reconstruction.

BACKGROUND AND OBJECTIVES: Functional outcomes are important for oncology patients undergoing lower extremity reconstruction. The objective of the current study was to describe patient reported function after surgery and identify predictors of postoperative function in musculoskeletal oncology patients undergoing lower extremity endoprosthetic reconstruction. METHODS: We performed a cohort study with functional outcome data from the recently completed Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY) trial. We utilized the 100-point Toronto Extremity Salvage Score (TESS), which was administered pre-operatively and at 3, 6 and 12 months post-operatively. Higher scores indicate better physical functioning, and the minimally important difference is 11 points. We calculated mean functional scores at each timepoint after surgery and developed a logistic regression model to explore predictors of failure to achieve excellent post-operative function (TESS ≥ 80) at 1 year after surgery. RESULTS: The 555 patients included in our cohort showed important functional improvement from pre-surgery to 1 year post-surgery (mean difference 14.9 points, 95%CI 12.2 to 17.6; p < 0.001) and 64% achieved excellent post-operative function. Our adjusted regression model found that poor (TESS 0-39) pre-operative function (odds ratio [OR] 3.3, 95%CI 1.6 to 6.6); absolute risk [AR] 24%, 95%CI 8% to 41.2%), older age (OR per 10-year increase from age 12, 1.32, 95%CI 1.17, 1.49; AR 4.5%, 95%CI 2.4% to 6.6%), and patients undergoing reconstruction for soft-tissue sarcomas (OR 2.3, 95%CI 1.03 to 5.01; AR 15.3%, 95%CI 0.4% to 34.4%), were associated with higher odds of failing to achieve an excellent functional outcome at 1-year follow-up. Patients undergoing reconstruction for giant cell tumors were more likely to achieve an excellent functional outcome post-operatively (OR 0.40, 95%CI 0.17 to 0.95; AR -9.9%, 95%CI -14.4% to -0.7%). CONCLUSIONS: The majority of patients with tumors of the lower extremity undergoing endoprosthetic reconstruction achieved excellent function at 1 year after surgery. Older age, poor pre-operative function, and endoprosthetic reconstruction for soft tissue sarcomas were associated with worse outcomes; reconstruction for giant cell tumors was associated with better post-operative function. LEVEL OF EVIDENCE: Therapeutic Level IV.

Tourniquet use in patients undergoing tumour resection and endoprosthetic reconstruction of the knee.

AIMS: The aim of this study was to determine the prevalence and impact of tourniquet use in patients undergoing limb salvage surgery with endoprosthetic reconstruction for a tumour around the knee. METHODS: We retrieved data from the Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY) trial; specifically, differences in baseline characteristics, surgical details, and postoperative functional outcomes between patients who had undergone surgery under tourniquet and those who had not. A linear regression model was created to evaluate the impact of tourniquet use on postoperative Toronto Extremity Salvage Scores (TESSs) while controlling for confounding variables. A negative-binomial regression model was constructed to explore predictors of postoperative length of stay (LOS). RESULTS: Of the 604 patients enrolled in the PARITY trial, 421 had tumours around the knee joint, of whom 225 (53%) underwent surgery under tourniquet. The tourniquet group was younger (p = 0.014), more likely to undergo surgery for a tumour of the tibia, and had shorter operating times by a mean of 50 minutes (95% confidence interval 30 to 72; p < 0.001). The adjusted linear regression model found that the use of a tourniquet, a shorter operating time, and a higher baseline TESS independently predicted better function at both three- and six-month follow-up. The negative-binomial regression model showed that tourniquet use, shorter operating time, younger age, and intraoperative tranexamic acid administration independently predicted a shorter LOS in hospital. CONCLUSION: The results of this study show that in patients undergoing resection of a tumour around the knee and endoprosthetic reconstruction, the use of an intraoperative tourniquet is associated with a shorter operating time, a reduced length of stay in hospital, and a better early functional outcome.Cite this article: Bone Joint J 2022;104-B(10):1168-1173.

Defining Minimally Important Differences in Functional Outcomes in Musculoskeletal Oncology.

BACKGROUND: Functional outcomes are commonly reported in studies of patients undergoing limb-salvage surgery for the treatment of musculoskeletal tumors; however, interpretation requires knowledge of the smallest amount of improvement that is important to patients: the minimally important difference (MID). We established the MIDs for the Musculoskeletal Tumor Society Rating Scale-93 (MSTS-93) and Toronto Extremity Salvage Score (TESS) for patients with bone tumors undergoing lower-extremity endoprosthetic reconstruction. METHODS: This study was a secondary analysis of the recently completed PARITY (Prophylactic Antibiotic Regimens in Tumor Surgery) study. We used MSTS-93 and TESS data from this trial to calculate (1) the anchor-based MIDs with use of an overall function scale and a receiver operating characteristic curve analysis and (2) the distribution-based MIDs based on one-half of the standard deviation of the change scores from baseline to the 12-month follow-up and one-half the standard deviation of baseline scores. RESULTS: Five hundred and ninety-one patients were available for analysis. The Pearson correlation coefficients for the association between changes in MSTS-93 and TESS scores and changes in the external anchor scores were 0.71 and 0.57, indicating high and moderate correlations. The anchor-based MID was 12 points for the MSTS-93 and 11 points for the TESS. Distribution-based MIDs were larger: 16 to 17 points for the MSTS-93 and 14 points for the TESS. CONCLUSIONS: Two methods for determining MIDs for the MSTS-93 and TESS for patients undergoing lower-extremity endoprosthetic reconstruction for musculoskeletal tumors yielded quantitatively different results. We suggest the use of anchor-based MIDs, which are grounded in changes in functional status that are meaningful to patients. These thresholds can facilitate responder analyses and indicate whether significant differences following interventions are clinically important to patients. LEVEL OF EVIDENCE: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

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.

Perpetrators of Gender-Based and Sexual Harassment in the Field of Orthopaedic Surgery.

The prevalence of gender-based and sexual harassment in the field of orthopaedic surgery in Canada is high. Previous research in other jurisdictions has identified the most common perpetrators of harassment to be senior surgeons or directors. We aimed to identify the most frequent perpetrators of gender-based and sexual harassment in orthopaedic surgery in Canada. METHODS: We conducted a Canada-wide survey of all orthopaedic surgeons registered with the Canadian Orthopaedic Association and the Canadian Orthopaedic Residents' Association. The development of our 116-item questionnaire was informed by a review of the literature and other published gender-based and sexual harassment surveys. Descriptive analyses, including frequency counts with associated 95% confidence intervals (CIs), are reported for all data. RESULTS: Of the 465 survey respondents, the median age was 43 years (interquartile range, 35 to 59) and respondents were most commonly male (72%), White (81%), married (77%), and staff orthopaedic surgeons (68%). Peers were identified as the most common perpetrators of gender-based harassment (55%, 95% CI, 50 to 59), and patients were identified as the most common perpetrators of sexual harassment (48%, 95% CI, 43 to 52). Women were more likely to report direct supervisors or patients as the perpetrators of gender-based and sexual harassment, and men reported peers as the most common perpetrators. CONCLUSION: Orthopaedic surgery peers and patients are the most commonly reported perpetrators of gender-based and sexual harassment in Canada. The results of this study may be helpful to institutions in designing and focusing educational programs and/or policies and procedures to help reduce harassment incidents in the training and work environment.

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.

Comparison of Prophylactic Intravenous Antibiotic Regimens After Endoprosthetic Reconstruction for Lower Extremity Bone Tumors: A Randomized Clinical Trial.

IMPORTANCE: The use of perioperative, prophylactic, intravenous antibiotics is standard practice to reduce the risk of surgical site infection after oncologic resection and complex endoprosthetic reconstruction for lower extremity bone tumors. However, evidence guiding the duration of prophylactic treatment remains limited. OBJECTIVE: To assess the effect of a 5-day regimen of postoperative, prophylactic, intravenous antibiotics compared with a 1-day regimen on the rate of surgical site infections within 1 year after surgery. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical superiority trial was performed at 48 clinical sites in 12 countries from January 1, 2013, to October 29, 2019. The trial included patients with a primary bone tumor or a soft tissue sarcoma that had invaded the femur or tibia or oligometastatic bone disease of the femur or tibia with expected survival of at least 1 year who required surgical management by excision and endoprosthetic reconstruction. A total of 611 patients were enrolled, and 7 were excluded for ineligibility. INTERVENTIONS: A 1- or 5-day regimen of postoperative prophylactic intravenous cephalosporin (cefazolin or cefuroxime) that began within 8 hours after skin closure and was administered every 8 hours thereafter. Those randomized to the 1-day regimen received identical saline doses every 8 hours for the remaining 4 days; patients, care providers, and outcomes assessors were blinded to treatment regimen. MAIN OUTCOMES AND MEASURES: The primary outcome in this superiority trial was a surgical site infection (superficial incisional, deep incisional, or organ space) classified according to the criteria established by the Centers for Disease Control and Prevention within 1 year after surgery. Secondary outcomes included antibiotic-related complications, unplanned additional operations, oncologic and functional outcomes, and mortality. RESULTS: Of the 604 patients included in the final analysis (mean [SD] age, 41.2 [21.9] years; 361 [59.8%] male; 114 [18.9%] Asian, 43 [7.1%] Black, 34 [5.6%] Hispanic, 15 [2.5%] Indigenous, 384 [63.8%] White, and 12 [2.0%] other), 293 were randomized to a 5-day regimen and 311 to a 1-day regimen. A surgical site infection occurred in 44 patients (15.0%) allocated to the 5-day regimen and in 52 patients (16.7%) allocated to the 1-day regimen (hazard ratio, 0.93; 95% CI, 0.62-1.40; P = .73). Antibiotic-related complications occurred in 15 patients (5.1%) in the 5-day regimen and in 5 patients (1.6%) allocated to the 1-day regimen (hazard ratio, 3.24; 95% CI, 1.17-8.98; P = .02). Other secondary outcomes did not differ significantly between treatment groups. CONCLUSIONS AND RELEVANCE: This randomized clinical trial did not confirm the superiority of a 5-day regimen of postoperative intravenous antibiotics over a 1-day regimen in preventing surgical site infections after surgery for lower extremity bone tumors that required an endoprosthesis. The 5-day regimen group had significantly more antibiotic-related complications. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01479283.

Published randomized controlled trials of surveillance in cancer patients - a systematic review.

With solid tumor cancer survivorship increasing, the number of patients requiring post-treatment surveillance also continues to increase. This highlights the need for evidence-based cancer surveillance guidelines. Ideally, these guidelines would be based on combined high-quality data from randomized controlled trials (RCTs). We present a systematic review of published cancer surveillance RCTs in which we sought to determine the feasibility of data pooling for guideline development. We carried out a systematic search of medical databases for RCTs in which adult patients with solid tumors that had undergone surgical resection with curative intent and had no metastatic disease at presentation, were randomized to different surveillance regimens that assessed effectiveness on overall survival (OS). We extracted study characteristics and primary and secondary outcomes, and assessed risk of bias and validity of evidence with standardized checklist tools. Our search yielded 32,216 articles for review and 18 distinct RCTs were included in the systematic review. The 18 trials resulted in 23 comparisons of surveillance regimens. There was a highlevel of variation between RCTs, including the study populations evaluated, interventions assessed and follow-up periods for the primary outcome. Most studies evaluated colorectal cancer patients (11/18, [61%]). The risk of bias and validity of evidence were variable and inconsistent across studies. This review demonstrated that there is tremendous heterogeneity among RCTs that evaluate effectiveness of different postoperative surveillance regimens in cancer patients, rendering the consolidation of data to inform high-quality cancer surveillance guidelines unfeasible. Future RCTs in the field should focus on consistent methodology and primary outcome definition.

Prophylactic Antibiotic Regimens In Tumor Surgery (PARITY): a multi-center randomized controlled study comparing alternative antibiotic regimens in patients undergoing tumor resections with endoprosthetic replacements-a statistical analysis plan.

BACKGROUND: Limb salvage with endoprosthetic reconstruction is the current standard practice for the surgical management of lower extremity bone tumors in skeletally mature patients and typically includes tumor resection followed by the functional limb reconstruction with modular metallic and polyethylene endoprosthetic implants. However, owing to the complexity and length of these procedures, as well as the immunocompromised nature of patients treated with chemotherapy, the risk of surgical site infection (SSI) is high. The primary research objective of the Prophylactic Antibiotic Regimens In Tumor Surgery (PARITY) trial is to assess whether a 5-day regimen of post-operative antibiotics decreases the risk of SSI at 1 year post-operatively compared to a 1-day regimen. This article describes the statistical analysis plan for the PARITY trial. METHODS/DESIGN: The PARITY trial is an ongoing multi-center, blinded parallel two-arm randomized controlled trial (RCT) of 600 participants who have been diagnosed with a primary bone tumor, a soft tissue sarcoma that has invaded the bone or oligometastatic bone disease of the femur or tibia that requires surgical resection and endoprosthetic reconstruction. This article describes the overall analysis principles, including how participants will be included in each analysis, the presentation of results, adjustments for covariates, the primary and secondary outcomes, and their respective analyses. Additionally, we will present the planned sensitivity and sub-group analyses. DISCUSSION: Our prior work has demonstrated (1) high rates of SSI after the treatment of lower extremity tumors by surgical excision and endoprosthetic reconstruction, (2) highly varied opinion and practice among orthopedic oncologists with respect to prophylactic antibiotic regimens, (3) an absence of applicable RCT evidence, (4) extensive support from international investigators to participate in a RCT, and (5) the feasibility of conducting a definitive RCT to evaluate a 5-day regimen of post-operative antibiotics in comparison with a 1-day regimen. TRIAL REGISTRATION: ClinicalTrials.gov NCT01479283 . Registered on 24 November 2011.

Recruitment patterns in a large international randomized controlled trial of perioperative care in cancer patients.

INTRODUCTION: The Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY) randomized controlled trial (RCT) was the first study to prospectively enroll and randomize orthopedic oncology patients in multiple centers internationally. The objective of this study was to describe recruitment patterns, to examine the differences in enrollment across different PARITY sites, and to identify variables associated with differing levels of recruitment. METHODS: Data from this study was obtained from the PARITY trial Methods Center and records of correspondence between the Methods Center and recruiting sites. We performed descriptive statistics to report the recruitment patterns over time. We compared recruitment, time to set up, and time to enroll the first patient between North American and international sites, private and public healthcare models, and the presence or absence of research personnel. Two-tailed non-paired t tests were performed to test average monthly recruitment rates between groups. RESULTS: A total of 602 patients from 36 North American and 12 international sites were recruited from 2013 to 2019. North American sites were able to become fully enrollment-ready at an average of 19.5 months and international sites at an average of 27 months. Once enrolling, international sites were able to enroll 0.59 patients per/month whereas North American sites averaged a monthly recruitment rate of 0.2 patients/month once enrolling. Sites with research personnel reached enrollment-ready status at an average of 19.3 months and sites without research support at an average of 30.3 months. Once enrolling, the recruitment rate was 0.28 patients/month and 0.2 patients per month for sites with and without research support, respectively. Publicly funded sites had a monthly enrollment of 0.4 patients/month whereas privately funded sites had a monthly enrollment rate of 0.17 patients/month. CONCLUSIONS: As a collaborative group, the PARITY investigators increased the pace of recruitment throughout the trial, likely by increasing the number of active sites. The longer time to start-up at international sites may be due to the complex governing regulations of pharmaceutical trials. Nevertheless, international sites should be considered essential as they recruited significantly more patients per month once active. The absence of research support personnel may lead to delays in the time to start-up. The results of the current study will provide guidance for choosing which sites to recruit for participation in future collaborative clinical trials in orthopedic oncology and other surgical specialties. TRIAL REGISTRATION: ClinicalTrials.gov NCT01479283 . Prospectively registered on November 24, 2011.

Willingness of patients with sarcoma to participate in cancer surveillance research: a cross-sectional patient survey.

OBJECTIVES: To determine the proportion of patients with extremity sarcoma who would be willing to participate in a clinical trial in which they would be randomised to one of four different postoperative sarcoma surveillance regimens. Additionally, we assessed patients' perspectives on the burden of cancer care, factors that influence comfort with randomisation and the importance of cancer research. DESIGN: Prospective, cross-sectional patient survey. SETTING: Outpatient sarcoma clinics in Canada, the USA and Spain between May 2017 and April 2020. Survey data were entered into a study-specific database. PARTICIPANTS: Patients with extremity sarcoma who had completed definitive treatment from seven clinics across Canada, the USA and Spain. MAIN OUTCOME MEASURES: The proportion of patients with extremity sarcoma who would be willing to participate in a randomised controlled trial (RCT) that evaluates varying postoperative cancer surveillance regimens. RESULTS: One hundred thirty complete surveys were obtained. Respondents reported a wide range of burdens related to clinical care and surveillance. The majority of patients (85.5%) responded that they would agree to participate in a cancer surveillance RCT if eligible. The most common reason to participate was that they wanted to help future patients. Those that would decline to participate most commonly reported that participating in research would be too much of a burden for them at a time when they are already feeling overwhelmed. However, most patients agreed that cancer research will help doctors better understand and treat cancer. CONCLUSIONS: These results demonstrate that most participants would be willing to participate in an RCT that evaluates varying postoperative cancer surveillance regimens. Participants' motivation for trial participation included altruistic reasons to help future patients and deterrents to trial participation included the overwhelming burden of a cancer diagnosis. These results will help inform the development of patient-centred RCT protocols in sarcoma surveillance research. LEVEL OF EVIDENCE: V.

The subterranean catfish Phreatobius cisternarum provides insights into visual adaptations to the phreatic environment.

Vertebrate eyes share the same general organization, though species have evolved morphological and functional adaptations to diverse environments. Cave-adapted animals are characterized by a variety of features including eye reduction, loss of body pigmentation, and enhanced non-visual sensory systems. Species that live in perpetual darkness have also evolved sensory mechanisms that are independent of light stimuli. The subterranean catfish Phreatobius cisternarum lives in the Amazonian phreatic zone and displays a diversity of morphological features that are similar to those observed in cavefish and appear to be adaptations to life in the dark. Here we combine histological and transcriptome analyses to characterize sensory adaptations of P. cisternarum to the subterranean environment. Histological analysis showed that the vestigial eyes of P. cisternarum contain a rudimentary lens. Transcriptome analysis revealed a repertoire of eleven visual and non-visual opsins and the expression of 36 genes involved in lens development and maintenance. In contrast to other cavefish species, such as Astyanax mexicanus, Phreatichthys andruzzii, Sinocyclocheilus anophthalmus and Sinocyclocheilus microphthalmus, DASPEI neuromast staining patterns did not show an increase in the number of sensory hair cells. Our work reveals unique adaptations in the visual system of P. cisternarum to underground habitats and helps to shed light into troglomorphic attributes of subterranean animals.