Predictors of Reoperation and Survival Experience (Minimum 1 Year) for Primary Versus Conversion Total Hip Arthroplasty in Young Patients.

BACKGROUND: Total hip arthroplasty (THA), including primary and conversion procedures, is commonly used for many types of joint disease in patients aged below 65 years, though few studies have evaluated THA outcomes in young patients (≤ 40 years old). This study examined a large cohort of patients who underwent THA at a young (≤ 40 years old) age to identify predictors of reoperation and compare survivorship between primary and conversion THAs. METHODS: A retrospective study was conducted on 497 patients who underwent 612 primary and conversion THAs at 40 years old or younger between 1990 and 2020. Medical records were reviewed to collect patient/surgical data. A multivariable logistic regression model identified independent predictors of reoperation, and Kaplan-Meier analysis with log-rank tests was used to compare survival curves by THA type. RESULTS: The median age at surgery (interquartile range) was 31 years (25 to 36). The median follow-up time was 6.6 years (range, 3.8 to 10.5). Conversion THAs had an increased rate of both revisions (12.3 versus 5.6%, P = 0.02) and nonrevision reoperations (8.9 versus 3.2%, P = 0.03) compared to primary THAs. A ceramic-on-ceramic articulation (odds ratio: 5.17; P = 0.03) and a higher estimated blood loss (odds ratio: 1.0007; P = 0.03) were independent predictors of reoperation for primary and conversion THA, respectively. Conversion THAs had a lower 15-year survival (77.8 versus 90.8%, P = 0.009) compared to primary THAs. CONCLUSIONS: Patients ≤ 40 years old who underwent primary and conversion THAs demonstrated an impressive 15-year survival comparable to that of older populations (74 to 93%), while conversion procedures had a higher reoperation rate. Although primary THA may be more ideal, there are promising outcomes for patients who need THA at a younger age than typically implemented, especially for those who are very young (≤ 30 years old).

Predictors of reoperation and survival experience for primary total knee arthroplasty in young patients with degenerative and inflammatory arthritis.

INTRODUCTION: While total knee arthroplasty (TKA) is typically implemented in patients > 65 years old, young patients may need to undergo TKA for pain relief and functional improvement. Current data are limited by older cohorts and short-term survival rates. This study aimed to examine a large sample size of patients with degenerative and inflammatory conditions who underwent primary TKA at a young (≤ 40) age to identify predictors of reoperation, as well 15-year survivorship. MATERIALS AND METHODS: A retrospective study was performed on 77 patients (92 surgeries) who underwent primary TKA at ≤ 40 years old, between January 1990 and January 2020. Patient charts were reviewed and a multivariable logistic regression model identified independent predictors of reoperation. Kaplan-Meier analysis was employed to build survival curves and log-rank tests analyzed survival between groups. RESULTS: Of the 77 patients, the median age at the time of surgery was 35.7 years (IQR: 31.2-38.7) and median follow-up time was 6.88 years. Twenty-one (22.8%) primary TKAs underwent 24 reoperations, most commonly due to stiffness (n = 9, 32.1%) and infection (n = 13, 46.4%) more significantly in the OA group (p = 0.049). There were no independent predictors of reoperation in multivariable analysis, and 15-year revision-free survivorship after TKA did not differ by indication (77.3% for OA/PTOA vs. 96.7% for autoimmune, p = 0.09) or between ≤ 30 and 31-40 year age groups (94.7% vs. 83.6%, p = 0.55). CONCLUSIONS: In this cohort of patients ≤ 40 years old, revision-free survival was comparable to that reported in the literature for older TKA patients with osteoarthritis/autoimmune conditions (81-94% at 15-years). Though nearly a quarter of TKAs required reoperation and causes of secondary surgery differed between degenerative and inflammatory arthritis patients, there were no significant predictors of increased reoperation rate. Very young patients ≤ 30 years old did not have an increased risk of revision compared to those aged 31-40 years.

Giant cell-rich osteosarcoma: A match pair analysis of 11 new cases and literature review of 56 patients.

BACKGROUND: Limited remains known on giant cell-rich osteosarcoma (GCRO) with current studies being case reports or smaller series. This investigation compared GCRO and conventional osteoblastic osteosarcoma (OOS) with regard to demographics and survival. METHODS: An institutional tumor registry was used to identify 11 patients (six males) treated for GCRO. Mean age was 43 years. Staging showed American Joint Committee on Cancer (AJCC) stages IIA in four and IIB in seven patients. Mean follow-up was 14 years. Study initiatives were: (1) Comparison of demographics between GCRO and 167 OOS from our institutional registry, (2) Differences in survival between GCRO and 33 OOS case controls (based on sex and AJCC stage), as well as 10 OOS using an age-based propensity match, and (3) Summary of all GCRO cases reported in the literature. RESULTS: (1) Sex (p = 0.53), grading (p = 0.56), AJCC stage (p = 0.42), and chemotherapeutic response rate (p = 0.67) did not differ between groups. Age was significantly increased in GCRO (p = 0.001). (2) Case-control and propensity-matched groups revealed no difference in disease-free survival, local recurrence, and distant disease-free survival at 2 years (p > 0.05). (3) Mean age of 56 patients (50% males) reported in the literature was 26 years. After merging with our 11 cases, the 2-year disease-free survival was 66%. CONCLUSIONS: GCRO remains a rare disease with high short-term mortality. Although affecting older patients more than conventional osteosarcoma, GCRO should not be viewed as a predictor of survival compared to OOS.

Complete tumor necrosis after neoadjuvant chemotherapy defines good responders in patients with Ewing sarcoma.

BACKGROUND: Survival in patients who have Ewing sarcoma is correlated with postchemotherapy response (tumor necrosis). This treatment response has been categorized as the response rate, similar to what has been used in osteosarcoma. There is controversy regarding whether this is appropriate or whether it should be a dichotomy of complete versus incomplete response, given how important a complete response is for in overall survival of patients with Ewing sarcoma. The purpose of this study was to evaluate the impact that the amount of chemotherapy-induced necrosis has on (1) overall survival, (2) local recurrence-free survival, (3) metastasis-free survival, and (4) event-free survival in patients with Ewing sarcoma. METHODS: In total, 427 patients who had Ewing sarcoma or tumors in the Ewing sarcoma family and received treatment with preoperative chemotherapy and surgery at 10 international institutions were included. Multivariate Cox proportional-hazards analyses were used to assess the associations between tumor necrosis and all four outcomes while controlling for clinical factors identified in bivariate analysis, including age, tumor volume, location, surgical margins, metastatic disease at presentation, and preoperative radiotherapy. RESULTS: Patients who had a complete (100%) tumor response to chemotherapy had increased overall survival (hazard ratio [HR], 0.26; 95% CI, 0.14-0.48; p < .01), recurrence-free survival (HR, 0.40; 95% CI, 0.20-0.82; p = .01), metastasis-free survival (HR, 0.27; 95% CI, 0.15-0.46; p ≤ .01), and event-free survival (HR, 0.26; 95% CI, 0.16-0.41; p ≤ .01) compared with patients who had a partial (0%-99%) response. CONCLUSIONS: Complete tumor necrosis should be the index parameter to grade response to treatment as satisfactory in patients with Ewing sarcoma. Any viable tumor in these patients after neoadjuvant treatment should be of oncologic concern. These findings can affect the design of new clinical trials and the risk-stratified application of conventional or novel treatments.

Manubrium Reconstruction.

To date, there is no standard approach for manubrial reconstruction. We had previously utilized mesh; however, this resulted in breakage, infection, and poor cosmesis. In this case series, we describe our transition to iliac wing autograft reconstruction. We examined 7 patients who underwent manubrial resection and reconstruction: 2 with mesh and methyl methacrylate and 5 with an iliac wing autograft. The outcomes of the autograft patients were overall favorable with no short-term complications or instances of breakage. We conclude that an iliac wing autograft for manubrial reconstruction is feasible and effective alternative to methyl methacrylate mesh.

Selecting the Next Class: The "Virtual Orthopaedic Rotation".

INTRODUCTION: When the COVID-19 pandemic forced the cancellation of visiting subinternships, we pivoted to create a virtual orthopaedic rotation (VOR). The purpose of this study was to assess the effect of the VOR on the residency selection process and determine the role of such a rotation in the future. METHODS: A committee was convened to create a VOR to replace visiting orthopaedic rotations for medical students who are interested in pursuing a career in orthopaedic surgery. The VOR was reviewed and sanctioned by our medical school, but no academic credit was granted. We conducted three 3-week VOR sessions. During each session, virtual rotators participated in regularly scheduled educational conferences and attended an invitation-only daily conference in the evenings that was designed for a medical student audience. In addition, students were paired with faculty and resident mentors in a structured mentorship program. Students' orthopaedic knowledge was assessed using prerotation and postrotation tests. RESULTS: From July to September 2020, 61 students from 37 distinct medical schools participated in the VOR. Notable improvements were observed in prerotation and postrotation orthopaedic knowledge test scores. In postrotation surveys, both students and faculty expressed high satisfaction with the curriculum but less certainty about how well they got to know each other. In the subsequent residency application cycle, 27.9% of the students who participated in the VOR were selected to interview, compared with 8.7% of the total application pool. DISCUSSION: The VOR was a valuable substitute for in-person clinical rotations during the COVID-19 pandemic. Although not likely to be a replacement for conventional away rotations, the VOR is a possible adjunct to in-person clinical rotations in the future.

No Difference Between Hemiarthroplasty and Total Hip Arthroplasty in the Treatment of Pathologic Femoral Neck Fractures.

BACKGROUND: Hemiarthroplasty (HA) and total hip arthroplasty (THA) have been widely discussed as treatment options for displaced osteoporotic femoral neck fractures. Pathologic femoral neck fractures from primary or metastatic tumors are comparatively rare and poorly investigated. The purpose of this study was to compare outcomes, complications, and perioperative survival for HA and THA in the treatment of pathologic femoral neck fractures of neoplastic etiology. METHODS: A multicenter retrospective cohort study identified patients with pathologic femoral neck fractures treated with HA or THA from 2005 to 2018. Demographics, American Society of Anesthesiologists classification, Charlson comorbidity index, Dorr classification, histopathologic diagnosis, and surgical data were compared. The primary outcome was reoperation. Secondary outcomes included 90-day mortality, estimated blood loss, length of stay, periprosthetic fracture, periprosthetic joint infection, and Eastern Cooperative Oncology Group performance status. RESULTS: There were 116 patients with HA and 48 patients with THA, with no differences between groups with regard to American Society of Anesthesiologists classification, Charlson comorbidity index, or Dorr classification. There were no differences between HA and THA in the primary outcome of reoperation (5.2% vs 4.2%, P = 1.00) or secondary outcomes of perioperative 90-day overall mortality (30.2% vs 25.0%, P = .51), estimated blood loss, transfusion rates, length of stay, discharge location, periprosthetic joint infection, periprosthetic fracture, or preoperative or postoperative Eastern Cooperative Oncology Group performance status. CONCLUSIONS: Both HA and THA are viable options for the treatment of patients with pathologic femoral neck fractures and demonstrated no differences in reoperations, complications, perioperative 90-day mortality, or functional outcome scores. LEVEL OF EVIDENCE: Level III.

Diagnoses, treatment, and oncologic outcomes in patients with calcaneal malignances: Case series, systematic literature review, and pooled cohort analysis.

BACKGROUND AND OBJECTIVES: Malignant tumors of the calcaneus are rare but pose a treatment challenge. AIMS: (1) describe the demographics of calcaneal malignancies in a large cohort; (2) describe survival after amputation versus limb-salvage surgery for high-grade tumors. METHODS: Study group: a "pooled" cohort of patients with primary calcaneal malignancies treated at two cancer centers (1984-2015) and systematic literature review. Kaplan-Meier analyses described survival across treatment and diagnostic groups; proportional hazards modeling assessed mortality after amputation versus limb salvage. RESULTS: A total of 131 patients (11 treated at our centers and 120 patients from 53 published studies) with a median 36-month follow-up were included. Diagnoses included Ewing sarcoma (41%), osteosarcoma (30%), and chondrosarcoma (17%); 5-year survival rates were 43%, 73% (70%, high grade only), and 84% (60%, high grade only), respectively. Treatment involved amputation in 52%, limb salvage in 27%, and no surgery in 21%. There was no difference in mortality following limb salvage surgery (vs. amputation) for high-grade tumors (HR 0.38; 95% CI 0.14-1.05), after adjusting for Ewing sarcoma diagnosis (HR 5.15; 95% CI 1.55-17.14), metastatic disease at diagnosis (HR 3.88; 95% CI 1.29-11.64), and age (per-year HR 1.04; 95% CI 1.02-1.07). CONCLUSIONS: Limb salvage is oncologically-feasible for calcaneal malignancies.

Orthopedic telemedicine encounter during the COVID-19 pandemic: A cautionary tale.

The COVID-19 pandemic has necessitated increased use of telemedicine for diagnosis and management of musculoskeletal disorders. We describe the virtual/telemedicine encounter and management of a patient with knee pain initially diagnosed as gonarthrosis but that actually resulted from an impending pathologic fracture of the femur. Definitive diagnosis and treatment occurred only after completion of the impending fracture. The multiple factors making telemedicine encounters challenging which contributed to this outcome are highlighted. Orthopedists need awareness of these challenges and must take steps to mitigate the risk of complications possible with continued increased utilization of telemedicine during this pandemic and beyond.

Clinical characteristics and treatment outcomes in six cases of malignant tenosynovial giant cell tumor: initial experience of molecularly targeted therapy.

BACKGROUND: Although tenosynovial giant cell tumor (TGCT) is classified as a benign tumor, it may undergo malignant transformation and metastasize in extremely rare occasions. High aberrant expression of CSF1 has been implicated in the development of TGCT and recent studies have shown promising activity of several CSF1R inhibitors against benign diffuse-type TGCT; however, little is known about their effects in malignant TGCT. CASE PRESENTATION: Information from six consenting patients (3 men, 3 women) with malignant TGCT presenting to Dana-Farber Cancer Institute for initial or subsequent consultation was collected. Median age at initial diagnosis of TGCT was 49.5 years (range 12-55), and median age at diagnosis of malignant TGCT was 50 years (range 34-55). Two patients developed malignant TGCT de novo, while four other cases showed metachronous malignant transformation. All tumors arose in the lower extremities (3 knee, 2 thigh, 1 hip). Five patients underwent surgery for the primary tumors, and four developed local recurrence. All six patients developed lung metastases, and four of five evaluable tumors developed inguinal and pelvic lymph node metastases. All six patients received systemic therapy. Five patients were treated with at least one tyrosine kinase inhibitor with inhibitory activity against CSF1R; however, only one patient showed clinical benefit (SD or PR). Five patients were treated with conventional cytotoxic agents. Doxorubicin-based treatment showed clinical benefit in all four evaluable patients, and gemcitabine/docetaxel showed clinical benefit in two patients. All six patients died of disease after a median of 21.5 months from diagnosis of malignant TGCT. CONCLUSIONS: This study confirms that TGCT may transform into an aggressive malignant tumor. Lymph node and pulmonary metastases are common. Local recurrence rates are exceedingly high. Conventional cytotoxic chemotherapy showed clinical benefit, whereas tyrosine kinase inhibitors against CSF1R showed limited activity. Given its rarity, a prospective registry of malignant TGCT patients is needed to further understand the entity and to develop effective strategies for systemic treatment.

Localized Adult Ewing Sarcoma: Favorable Outcomes with Alternating Vincristine, Doxorubicin, Cyclophosphamide, and Ifosfamide, Etoposide (VDC/IE)-Based Multimodality Therapy.

BACKGROUND: In children with localized Ewing sarcoma (ES), addition of ifosfamide and etoposide to cyclophosphamide, doxorubicin, and vincristine (VDC/IE) improved 5-year overall survival (OS) to 70%-80%. Prior to delivery of VDC/IE in adults, 5-year OS was <50%. We reviewed our institutional outcomes for adults with ES who received VDC/IE-based treatment. MATERIALS AND METHODS: Between 1997-2013, 67 adults with localized ES were treated with curative intent. Local recurrence-free survival (LRFS), progression-free survival (PFS), and OS were determined using Kaplan-Meier method; comparisons were assessed with log-rank. Proportional hazard models were used to determine predictive factors. RESULTS: All patients received VDC/IE (median 14 cycles.) Local therapy was surgery for 33, radiation therapy for 17, or both for 17. Median follow-up for living patients was 5.2 years. Six patients had disease progression on therapy. Site of first failure was local for three, local and distant for two, and distant for ten. Five-year LRFS was 91%; 5-year LRFS was 96% for nonpelvic disease and 64% for pelvic disease (p = .003). Five-year PFS was 66%, and 5-year OS was 79%. On multivariate analysis, pelvic site had a 3.3 times increased risk of progression (p = .01). CONCLUSION: Survival for adults with localized ES treated with VDC/IE-based multimodality therapy appears to be better than historical data and similar to excellent outcomes in children. Pelvic site of disease remains a predictor of worse outcome. Given the paucity of literature for adult ES, these data help validate VDC/IE-based therapy as an appropriate treatment approach for this rare disease in adults. IMPLICATIONS FOR PRACTICE: Ewing sarcoma (ES) is rare in adults. Treatment approaches for adults have been extrapolated from the pediatric experience, and there is a sense that adults fare less well than children. We reviewed treatment outcomes in adults with localized ES treated with cyclophosphamide, doxorubicin, and vincristine in alternation with ifosfamide and etoposide (VDC/IE) as part of multimodality therapy. Survival outcomes appear to be better than historical data for adults and similar to the excellent outcomes for children. These data help validate VDC/IE-based therapy as an appropriate treatment approach for this rare disease in adults.

Complications After Surgical Management of Proximal Femoral Metastasis: A Retrospective Study of 417 Patients.

BACKGROUND: Proximal femoral fractures resulting from metastatic disease often require surgical management. Few studies have compared surgical techniques, and physicians' preferred strategies vary. This study compared revision and complication rates among surgical strategies. METHODS: The study consisted of a retrospective review of electronic medical records of 417 consecutive patients with proximal femoral metastasis or multiple myeloma who underwent intramedullary nailing (n = 302), endoprosthetic reconstruction (n = 70), and open reduction and internal fixation (n = 45) between 1999 and 2014 at two orthopaedic oncology centers. Primary outcome measures were revisions and 30-day systemic complications. Secondary outcome measures were total estimated blood loss, anesthesia time, duration of hospital admission, and 30-day survival. RESULTS: Revision rates did not differ between strategies (5.3% after intramedullary nailing, 11% after endoprosthetic reconstruction, and 13% after open reduction and internal fixation; P = 0.134). When reasons for revision were assessed separately, fixation failure was most common after open reduction and internal fixation (13% versus 3.0% after intramedullary nailing and none after endoprosthetic reconstruction; P < 0.001), whereas deep infection was most common after endoprosthetic reconstruction (8.6% versus 2.0% after intramedullary nailing and none after open reduction and internal fixation; P = 0.010). Overall systemic complication rates did not differ between strategies (8.3% after intramedullary nailing, 14% after endoprosthetic reconstruction, and 11% after open reduction and internal fixation; P = 0.268). CONCLUSION: Implant-specific complications and their timing should be considered in the choice of surgical strategy. Analysis of secondary outcomes and risk factors for systemic complications could aid in surgical decision making. LEVEL OF EVIDENCE: Therapeutic Level III.

Complications after surgery for metastatic humeral lesions.

BACKGROUND: Knowledge of surgical outcome and its predictors helps inform patients and aids in surgical decision-making. We aimed to assess the outcome-reoperation and systemic complication rate-of surgery for humeral metastases, myeloma, or lymphoma. Our null hypothesis was that there are no factors associated with these outcomes. METHODS: We included 295 consecutive patients in this retrospective study: 134 (45%) proximal, 131 (44%) diaphyseal, and 30 (10%) distal impending or pathologic fractures. Proximal lesions were treated by intramedullary nailing (43%, n = 57), prosthesis (34%, n = 46), plate-screw fixation (22%, n = 30), and a combination (n = 1). Diaphyseal lesions were treated by intramedullary nailing (69%, n = 91), plate-screw fixation (30%, n = 39), and a combination (n = 1). Distal lesions were treated by plate-screw fixation (97%, n = 29) and intramedullary nailing (3.3%, n = 1). RESULTS: We found 25 (8.5%) reoperations, and 17 (5.8%) patients had 18 systemic complications: pneumonia (3.7%, n = 11), pulmonary embolism (1.3%, n = 4), sepsis (0.68%, n = 2), and fat embolism (0.34%, n = 1). No factors were independently associated with reoperation. Logistic regression analysis demonstrated that favorable cancer status (i.e., a higher modified Bauer score: odds ratio, 0.48; 95% confidence interval, 0.29-0.80; P = .005) was independently associated with a decreased systemic complication rate. CONCLUSION: Poor cancer status was an independent predictor of postoperative systemic complications. This could help inform the patient and anticipate postoperative problems.

2015 Marshall Urist Young Investigator Award: Prognostication in Patients With Long Bone Metastases: Does a Boosting Algorithm Improve Survival Estimates?

BACKGROUND: Survival estimation guides surgical decision-making in metastatic bone disease. Traditionally, classic scoring systems, such as the Bauer score, provide survival estimates based on a summary score of prognostic factors. Identification of new factors might improve the accuracy of these models. Additionally, the use of different algorithms--nomograms or boosting algorithms--could further improve accuracy of prognostication relative to classic scoring systems. A nomogram is an extension of a classic scoring system and generates a more-individualized survival probability based on a patient's set of characteristics using a figure. Boosting is a method that automatically trains to classify outcomes by applying classifiers (variables) in a sequential way and subsequently combines them. A boosting algorithm provides survival probabilities based on every possible combination of variables. QUESTIONS/PURPOSES: We wished to (1) assess factors independently associated with decreased survival in patients with metastatic long bone fractures and (2) compare the accuracy of a classic scoring system, nomogram, and boosting algorithms in predicting 30-, 90-, and 365-day survival. METHODS: We included all 927 patients in our retrospective study who underwent surgery for a metastatic long bone fracture at two institutions between January 1999 and December 2013. We included only the first procedure if patients underwent multiple surgical procedures or had more than one fracture. Median followup was 8 months (interquartile range, 3-25 months); 369 of 412 (90%) patients who where alive at 1 year were still in followup. Multivariable Cox regression analysis was used to identify clinical and laboratory factors independently associated with decreased survival. We created a classic scoring system, nomogram, and boosting algorithms based on identified variables. Accuracy of the algorithms was assessed using area under the curve analysis through fivefold cross validation. RESULTS: The following factors were associated with a decreased likelihood of survival after surgical treatment of a metastatic long bone fracture, after controlling for relevant confounding variables: older age (hazard ratio [HR], 1.0; 95% CI, 1.0-1.0; p < 0.001), additional comorbidity (HR, 1.2; 95% CI, 1.0-1.4; p = 0.034), BMI less than 18.5 kg/m(2) (HR, 2.0; 95% CI, 1.2-3.5; p = 0.011), tumor type with poor prognosis (HR, 1.8; 95% CI, 1.6-2.2; p < 0.001), multiple bone metastases (HR, 1.3; 95% CI, 1.1-1.6; p = 0.008), visceral metastases (HR, 1.6; 95% CI, 1.4-1.9; p < 0.001), and lower hemoglobin level (HR, 0.91; 95% CI, 0.87-0.96; p < 0.001). The survival estimates by the nomogram were moderately accurate for predicting 30-day (area under the curve [AUC], 0.72), 90-day (AUC, 0.75), and 365-day (AUC, 0.73) survival and remained stable after correcting for optimism through fivefold cross validation. Boosting algorithms were better predictors of survival on the training datasets, but decreased to a performance level comparable to the nomogram when applied on testing datasets for 30-day (AUC, 0.69), 90-day (AUC, 0.75), and 365-day (AUC, 0.72) survival prediction. Performance of the classic scoring system was lowest for all prediction periods. CONCLUSIONS: Comorbidity status and BMI are newly identified factors associated with decreased survival and should be taken into account when estimating survival. Performance of the boosting algorithms and nomogram were comparable on the testing datasets. However, the nomogram is easier to apply and therefore more useful to aid surgical decision making in clinical practice. LEVEL OF EVIDENCE: Level III, prognostic study.

Are Allogeneic Blood Transfusions Associated With Decreased Survival After Surgery for Long-bone Metastatic Fractures?

BACKGROUND: Previous studies have shown that perioperative blood transfusion increases cancer recurrence and decreases patient survival after resection of primary malignancies. The question arises whether this association also exists in patients with already disseminated disease undergoing surgery for metastatic long-bone fractures. PURPOSES: We sought to determine whether perioperative allogeneic blood transfusion is associated with decreased survival after operative treatment of long-bone metastatic fractures after accounting for clinical, laboratory, and treatment factors. Secondarily, we aimed to identify potential factors that are associated with decreased survival. METHODS: We included 789 patients in our retrospective study who underwent surgery at two institutions for a pathologic or impending metastatic long-bone fracture. We used multivariable Cox proportional hazards regression model analysis to assess the relationship of perioperative allogeneic blood transfusion with survival, and accounted for patient age, sex, comorbidities, BMI, tumor type, fracture type and location, presence of other bone and visceral metastases, previous radiotherapy and systemic therapy, preoperative embolization, preoperative hemoglobin level, treatment type, anesthesia time, blood loss, duration of hospital admission, year of surgery, and hospital. RESULTS: Considering transfusion as an "exposure," and comparing patients who received transfusions with those who did not, we found that blood transfusion was not associated with decreased survival after accounting for all explanatory variables (hazard ratio [HR] 1.06; 95% CI, 0.87-1.30; p = 0.57). Evaluating transfusion in terms of dose-response, we found that patients who received more transfusions had lower survival compared with those who had fewer transfusions after accounting for all explanatory variables (HR per unit of blood transfused, 1.07; 95% CI, 1.02-1.12; p = 0.005). We found that age (HR, 1.02; 95% CI, 1.01-1.02; p < 0.001), comorbidity status (HR, 1.06; 95% CI, 1.01-1.10; p = 0.014), duration of hospital stay (HR, 1.02; 95% CI 1.00-1.03; p = 0.021), tumor type (HR, 1.71; 95% CI, 1.44-2.03; p < 0.001), and visceral metastases (HR, 1.59; 95% CI, 1.34-1.88; p < 0.001) were independently associated with survival. CONCLUSION: We found that exposure to perioperative allogeneic blood transfusion does not decrease survival, with the numbers available. However, our sample size might have been insufficient to reveal a small but potentially relevant effect. Our results do suggest a dose-response relationship; patients who received more transfusions had lower survival compared with those with fewer transfusions. Risk of death increased by 7% per unit of blood transfused. LEVEL OF EVIDENCE: Level III, prognostic study.

Safety and efficacy of radiation dose delivered via iodine-125 brachytherapy mesh implantation for deep cavity sarcomas.

BACKGROUND: Radiation delivered as brachytherapy (BRT) via catheters placed during extremity soft tissue sarcoma (STS) resection results in acceptable local control rates; however, there are limitations in deep cavities. (125)I seeds embedded in mesh provide a flexible BRT platform that may be contoured to irregular deep cavities surfaces, but the risks and benefits are unknown. METHODS: Patients with thoracic, abdominal, pelvic, retroperitoneal, and deep truncal STS undergoing resection and implantation of permanent (125)I mesh BRT at our institution were reviewed. Local recurrence rates within the tumor bed covered by mesh (in field) and postoperative complications were analyzed. RESULTS: Between 2000 and 2010, a total of 46 patients were treated for primary (n = 8, 17 %) or recurrent (n = 38, 83 %) deep cavity STS (median follow-up 34.8 months); 74 % received external-beam radiotherapy for this or a prior presentation. In-field recurrences were observed in 9 patients (19.5 %). Crude cumulative incidences of in-field, regional, and distant recurrences at 5 years were 26.3, 54.2, and 54.1 %, respectively. 5-year overall survival rate was 47.2 %; median survival was 44.0 months. Twenty-two patients (48 %) experienced complications, half of whom (24 %) developed grade III/IV complications requiring percutaneous intervention (n = 6) or reoperation (n = 5) at a median of 35.5 days. There were no postoperative deaths. CONCLUSIONS: To our knowledge, this is the first study to report safety and efficacy for permanent (125)I mesh BRT implantation after resection of deep cavity STS. Local in-field recurrence rates were relatively low in this high-risk population. However, 24 % developed complications requiring intervention. (125)I mesh BRT appears effective, but it should be used with caution.

Investigating osteogenic differentiation in multiple myeloma using a novel 3D bone marrow niche model.

Clonal proliferation of plasma cells within the bone marrow (BM) affects local cells, such as mesenchymal stromal cells (MSCs), leading to osteolysis and fatality in multiple myeloma (MM). Consequently, there is an urgent need to find better mechanisms of inhibiting myeloma growth and osteolytic lesion development. To meet this need and accelerate clinical translation, better models of myeloma within the BM are required. Herein we have developed a clinically relevant, three-dimensional (3D) myeloma BM coculture model that mimics bone cell/cancer cell interactions within the bone microenvironment. The coculture model and clinical samples were used to investigate myeloma growth, osteogenesis inhibition, and myeloma-induced abnormalities in MM-MSCs. This platform demonstrated myeloma support of capillary-like assembly of endothelial cells and cell adhesion-mediated drug resistance (CAM-DR). Also, distinct normal donor (ND)- and MM-MSC miRNA (miR) signatures were identified and used to uncover osteogenic miRs of interest for osteoblast differentiation. More broadly, our 3D platform provides a simple, clinically relevant tool to model cancer growth within the bone-useful for investigating skeletal cancer biology, screening compounds, and exploring osteogenesis. Our identification and efficacy validation of novel bone anabolic miRs in MM opens more opportunities for novel approaches to cancer therapy via stromal miR modulation.

WITHDRAWN: Porous Metal Augments Show Excellent Mid-to-Long Term Survival in Complex Acetabular Reconstruction.

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