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Total hip arthroplasty (THA) performed in the setting of fracture is associated with greater case complexity, worse outcomes, and increased costs when compared with THA performed for osteoarthritis. Despite the increased complexity, the work relative value units (wRVUs) assigned to THA may not adequately compensate for this difference in surgical effort and time. The purpose of this study was to determine the wRVU per minute rates and reimbursement in dollars per minute for THA performed for fracture compared with THA performed for osteoarthritis. Data were collected through the National Surgical Quality Improvement Program database from 2006 to 2018 to identify all patients who underwent primary THA for osteoarthritis or for fractures. Total wRVU, operation time, wRVU per minute, and dollars per minute were assessed between the osteoarthritis and fracture cohorts. Bivariate and multivariate analyses were utilized for the study. The mean operation times for primary THA for osteoarthritis and for fractures were 91.96 and 99.43 minutes, respectively (p

Patients will often inquire about the magnitude of height gain after scoliosis surgery. Several published models have attempted to predict height gain using preoperative variables. Many of these models reported good internal validity but have not been validated against an external cohort. We attempted to test the validity of 5 published models against an external cohort from our institution. Models included were Hwang, Van Popta, Spencer, Watanabe, and Sarlak models.We retrospectively queried our institution's records from 2006 to 2019 for patients with adolescent idiopathic scoliosis treated with posterior spinal fusion. We recorded preoperative and postoperative variables including clinical height measurements. We also performed radiographic measurements on preoperative and postoperative radiographic studies. We then tested the ability of the models to predict height gain by evaluating Pearson correlation coefficient, root mean square error, Akaike Information Criterion for each model.A total of 387 patients were included. Mean clinical height gain was 3.1 (±1.7) cm.All models demonstrated a moderate positive Pearson correlation coefficient, except the Hwang model, which demonstrated a weak correlation. The Spencer model was the only model with acceptable root mean square error (≤0.5) and was also the best fitting with the lowest Akaike Information Criterion (-308). The mean differences in height gain predictions between all models except the Hwang model was ≤1 cm.Four of the 5 models demonstrated moderate correlation and had good external validity compared with their development cohorts. Although the Spencer model was the best fitting, the clinical significance of the difference in height predictions compared with other models was low. The Watanabe model was the second best fitting and had the simplest formula, making it the most convenient to use in a clinical setting. We offer a simplified equation to use in a preoperative clinical setting based on this data-ΔHeight (mm)=0.77*(preoperative coronal angle-postoperative coronal angle).Not Applicable.

Background Fixation and arthroplasty remain the mainstays of surgical treatment of degenerative and traumatic shoulder pathology. They also constitute an appreciable sum of Medicare expenditure. With continued concern for declines in Medicare reimbursement across orthopedic surgery, it is important to understand how trends in reimbursement correlate with relative procedure volumes. Our aims were to describe temporal changes in procedure volumes, physician payment, and patient charges for proximal humerus open reduction internal fixation (ORIF) and shoulder arthroplasty. Methods Using Medicare's Physician Fee Schedules from 2012 to 2017, we examined procedure volumes, number of unique surgeons performing, actual submitted patient charges, and surgeon payments from 2012 to 2017 for six shoulder procedures: proximal humerus ORIF (CPT-23615), traumatic hemiarthroplasty (HEMI) (CPT-23616), degenerative HEMI (CPT-23470), primary total shoulder arthroplasty (TSA) (CPT-23472), partial TSA revision (humeral or glenoid component, CPT-23473), and total TSA revision (CPT-23474). The reimbursement ratio was calculated by dividing surgeon payment by patient charges. Growth rates of charges and payment were adjusted for inflation using annual consumer price index inflation rates over the same time period. Results The total number of traumatic and degenerative HEMI cases fell over −60%. Similarly, the number of unique surgeons performing traumatic and degenerative HEMI fell over −53%. In contrast, the number of TSA procedures rose by +70%, whereas partial and total revision TSA rose by +62% and +88%, respectively. The number of unique surgeons rose +28% and over +73% for primary and revision TSA, respectively. There was a large gap (between 3.4 and 4.4 times) between submitted charges and surgeon payment for all years analyzed. After adjusting for inflation, Medicare payment to surgeons decreased for all types of surgery (−6% to −9%) other than ORIF, which increased +10%. Submitted patient charges during this period increased +14% and +9.7% for ORIF and revision TSA (total), respectively, but decreased by −6% for traumatic HEMI. The reimbursement ratio was ≤29% for all procedures analyzed across all years and fell the most for revision TSA (partial and total). Conclusion From 2012 to 2017, there was a sharp decline in the use of shoulder HEMI with a correspondingly high increase in TSA. After accounting for inflation, HEMI and TSA showed appreciable declines in surgeon payment over time, whereas ORIF was the only surgery with increased surgeon payment. Revision TSA saw the largest declines in the reimbursement rate. Physicians and health care policy makers must be aware of these trends to ensure both a sustainable payment infrastructure for surgeons as well as to maintain access to care for these procedures. Level of evidence Level III; Economic Study

S4. E-cadherin induces E- to N-cadherin switching in sarcoma cells.

CDH1 (also known as E-cadherin), an epithelial-specific cell–cell adhesion molecule, plays multiple roles in maintaining adherens junctions, regulating migration and invasion, and mediating intracellular signaling. Downregulation of E-cadherin is a hallmark of epithelial-to-mesenchymal transition (EMT) and correlates with poor prognosis in multiple carcinomas. Conversely, upregulation of E-cadherin is prognostic for improved survival in sarcomas. Yet, despite the prognostic benefit of E-cadherin expression in sarcoma, the mechanistic significance of E-cadherin in sarcomas remains poorly understood. Here, by combining mathematical models with wet-bench experiments, we identify the core regulatory networks mediated by E-cadherin in sarcomas, and decipher their functional consequences. Unlike carcinomas, E-cadherin overexpression in sarcomas does not induce a mesenchymal-to-epithelial transition (MET). However, E-cadherin acts to reduce both anchorage-independent growth and spheroid formation of sarcoma cells. Ectopic E-cadherin expression acts to downregulate phosphorylated CREB1 (p-CREB) and the transcription factor, TBX2, to inhibit anchorage-independent growth. RNAi-mediated knockdown of TBX2 phenocopies the effect of E-cadherin on CREB levels and restores sensitivity to anchorage-independent growth in sarcoma cells. Beyond its signaling role, E-cadherin expression in sarcoma cells can also strengthen cell–cell adhesion and restricts spheroid growth through mechanical action. Together, our results demonstrate that E-cadherin inhibits sarcoma aggressiveness by preventing anchorage-independent growth.Implications:We highlight how E-cadherin can restrict aggressive behavior in sarcomas through both biochemical signaling and biomechanical effects.

S5. Revised E-cad/TBX2 signaling model.

Supplementary Data

S6. A mechanical model relates cell-cell adhesion to spheroid size.

S3. CREB knockdown indicates it is downstream of E-cadherin and TBX2.

S1. E-cadherin over-expression does not alter sarcoma cell growth in monolayer culture.

Introduction: Continuous compression implants (CCI) are a fixation device formed from nitinol, a shape memory alloy. This alloy is durable enough to augment fixation and combined with its small footprint, versatile enough to insert into areas that are too small for K wires or lag screws to hold a provisional fixation. Case Report: We used CCIs to successfully stabilize the transverse segments in three posterior column with posterior wall fractures. Conclusion: CCIs can be used to provisionally reduce posterior column with posterior wall acetabular fractures and stabilize small pelvic bone fragments that may be difficult to hold with lag screws. These cases highlight a novel augmentation of the surgical treatment of posterior column with posterior wall fractures.

Background Total Elbow Arthroplasty (TEA) has demonstrated promising functional outcomes for the treatment of complex distal humerus fractures. In many other joints, arthroplasty for trauma is associated with increased risks for acute postoperative complications. The purpose of this investigation is to identify the in-hospital and 30-day postoperative complications for TEA performed because of distal humerus fracture vs. arthritis, and to determine whether acute fracture is associated with differences in complications after TEA. Methods The American College of Surgeons National Surgical Quality Improvement Program was used to identify patients who underwent TEA from 2006 to 2018. Patients who were diagnosed with distal humerus fractures were identified and compared with patients without acute fracture. Patients without fracture were further divided into those undergoing TEA for Rheumatoid Arthritis (RA) vs. osteoarthritis (OA). Demographic data, length of hospital stay, readmission rate, reoperation rate, and postoperative complications within 30 days were analyzed by univariate analysis. Multivariable logistic regression was used to isolate the effect of acute fracture on postoperative complications and readmission. Results Six hundred fourty-six patients underwent TEA, and 149 (23.1%) had undergone TEA for distal humerus fracture. Patients undergoing TEA for fracture had an overall adverse event rate of 13.42% compared to a complication rate of 12.47% in patients undergoing primary elective TEA (P = .76). On univariate analysis, patients who underwent TEA for fracture were not significantly more likely to require reoperation within 30 days (1.34% vs. 4.63% for RA and 4.11% for OA, P = .24) or require readmission within 30 days (5.37% vs. 4.63% for RA and 4.88% for OA, P = .52). Multivariable logistic analysis found that TEA for fracture was not independently associated with readmission, reoperation, major complications, or minor complications. Increasing age is associated with increased risk of minor complications. Female gender is associated with decreased risk of major complication, and higher ASA classification was associated with increased odds of readmission. Conclusions Acute fracture is not an independent risk factors for major complications, reoperation, or readmissions in patients undergoing TEA. Level of Evidence Level III; Retrospective Case-Control Study.

Introduction: Relative value units (RVUs) are integral to the U.S. physician compensation system used by the Centers for Medicare & Medicaid Services. The use of 'work RVUs' (herein, wRVUs) is intended to reimburse physicians according to the amount of expertise and effort needed to safely and effectively perform a procedure. Our purpose was to determine: 1) the number of wRVUs/hour generated by common sports medicine surgical procedures; and 2) how patient characteristics, surgical approach, and practice setting are associated with the number of wRVUs/hour. This analysis was performed to infer whether wRVUs are assigned appropriately according to the factors on which they are purported to be based.Methods: We queried the American College of Surgeons' National Surgical Quality Improvement Program (NSQIP) database for common sports medicine surgical procedures performed in 2018. Data from 19,877 patients (8,258 women) with a mean age of 48 years (range, 18-90) who underwent a surgical sports medicine procedure were analyzed. Work RVUs and operative time were used to calculate work RVUs/hour for each surgical procedure. Univariate and multivariate analyses were used to assess correlations between patient characteristics and wRVUs/hour.Results: Knee chondroplasty generated the most mean (± standard deviation) wRVUs/hour at 22 ± 0.5, whereas 'open tenodesis of biceps tendon, long head' generated the least at 9.6 ± 0.25 wRVUs/hour. Factors associated with a greater mean number of wRVUs/hour were younger patient age, female sex, arthroscopic approach, and outpatient setting. Arthroscopic procedures also generated more wRVUs/hour than the same procedures performed through an open approach. wRVUs were not correlated with case complexity or surgical time.Conclusion: wRVUs/hour in surgical sports medicine procedures vary widely depending on the procedure type, patient characteristics, surgical approach, and practice setting.

The incidence of anterior cruciate ligament (ACL) reconstruction is increasing in the United States, particularly in the older athlete. Patients who undergo ACL reconstruction are at higher risk for undergoing total knee arthroplasty (TKA) later in life. TKA in patients with prior ACL reconstruction has been associated with longer operative time due in-part to difficulty with exposure and retained hardware. Outcomes after TKA in patients with prior ACL reconstruction are not well defined, with some reports showing increased rate of complications and higher risk of reoperation compared with routine primary TKA, but these results are based on small and nonrandomized cohorts. Future research is needed to determine whether graft choice or fixation technique for ACL reconstruction influences outcomes after subsequent TKA. Furthermore, whether outcomes are affected by choice of TKA implant design for patients with prior ACL reconstruction warrants further study. This review analyzes the epidemiology, operative considerations, and outcomes of TKA following ACL reconstruction.

Swimming is a popular activity with numerous health benefits.Swimming involves complex biomechanical movements that, especially if performed incorrectly, can lead to musculoskeletal injuries.The shoulder is the most commonly affected joint, although lower-extremity and spine injuries have also been reported.

Ongoing concern for declining Medicare payment to surgeons may incentivize surgeons to perform more cases to maintain productivity goals. The authors evaluated trends in physician payment, patient charges, and reimbursement ratios for the most common hand and upper extremity surgical procedures.The authors examined Medicare surgeon payment, patient charges, and surgical volume from 2012 to 2017 for 83 common surgical procedures, incorporating the year-to-year Consumer Price Index to adjust for inflation. The reimbursement ratio was calculated by dividing payment by charge. Weighted (by surgery type and volume) averages were calculated.Total Medicare surgeon payment increased 5.6 percent to $272 million for the studied procedures. Patient charges were seven times greater than payment, growing 24 percent to $1.9 billion. Despite growth of total payment, the average overall weighted payment for a single surgery decreased 3.5 percent. The average weighted patient charge increased 8 percent, whereas the reimbursement ratio decreased 13 percent. A hand surgeon would need to perform three more cases per 100 in 2017 to maintain the same reimbursement received in 2012. After categorizing these 83 surgical procedures, distal radius fixation (3 parts, 21 percent increase;2-part intra-articular, extra-articular, and percutaneous pinning, 17 percent increase), bony trauma proximal to the distal radius (10 percent increase), and upper extremity flap (5 percent increase) were subject to the greatest increases in payment. Payment for forearm fasciotomy (39 percent decrease), endoscopic carpal tunnel release (30 percent decrease), and mass excisions proximal to the wrist (18 percent decrease) decreased the most.From 2012 to 2017, despite a disproportionate increase in procedure charges, Medicare surgeon payment has not decreased substantially; however, total reimbursement is multifactorial and involves multiple sources of revenue and cost.

Background Alcohol use disorder (AUD) is the most prevalent substance use disorder in the United States. However, the current literature on AUD as a preoperative risk factor for Total Shoulder Arthroplasty (TSA) outcomes is limited. The purpose of this study was to identify the association of AUD with revision rates and 90-day postoperative complications in TSA. Methods A retrospective study was conducted using the PearlDiver database. Patients diagnosed with AUD were identified. Patients in remission or with underlying cirrhosis were excluded. Outcomes included 2-year revision, 90-day readmission, 90-day emergency, and 90-day post-operative medical complications. Analysis was performed with univariate chi-squared tests followed by multivariable logistic regression. Results A total of 59,261 patients who underwent TSA for osteoarthritis were identified, with 1522 patients having a diagnosis of AUD. Multivariable logistic regression showed that patients with AUD were more likely to undergo 2-year all-cause revision (OR = 1.49, p = 0.007), 2-year aseptic revision (OR = 1.47, p = 0.014), 90-day hospital readmission (OR = 1.57, p = 0.015), and 90-day transient mental disorder (OR = 2.13, p = 0.026). Conclusions AUD is associated with increased rates of 2-year revision surgery, as well as 90-day readmission and 90-day transient mental disorder following primary TSA for osteoarthritis. These findings may assist orthopedic surgeons in counseling patients with AUD during the pre-operative course.

Periprosthetic infections after total shoulder arthroplasty (TSA) are associated with devastating complications and prolonged treatment. Patients with identified antibiotic allergy (ABX) may be at increased risk for complications because of suboptimal preincisional prophylaxis. This study aims to quantify the risk of postoperative outcomes and complications for patients undergoing TSA with a history of ABX.Retrospective cohort analysis of patient data was conducted using the PearlDiver Patient Records Database. Patients who underwent TSA for osteoarthritis were identified using Current Procedural Terminology and International Classification of Diseases codes and were stratified based on self-reported (1) penicillin, (2) sulfonamide, or (3) other antibiotic allergies. We analyzed patient demographics, comorbidities, 90-day medical complications, and rate of revision at 30 days, 90 days, 1 year, and 2 years.In total, 85,606 patients who underwent TSA for osteoarthritis from 2010 to 2018 were identified, of whom 7,836 (9.15%) had a reported ABX. Univariate analysis found the ABX cohort was younger (67.5 versus 67.7 year; P = 0.042), more often female (67.57% versus 54.79%; P0.001), and more likely to have Elixhauser comorbidities than nonallergic control subjects. Multivariate analysis found patients who reported ABX had increased likelihood of periprosthetic joint infection (PJI) within 30 days (odds ratio [OR]: 3.129), 1 year (OR: 2.016), and 2 years of surgery (OR: 2.221). Patients with reported ABX had increased likelihood of postoperative anemia (OR: 1.126), blood transfusion (OR: 1.238), and readmission (OR: 1.585) within 90 days of surgery. Patients with penicillin allergy had a greater incidence of revision due to PJI at 30 days (OR: 4.811), 90 days (OR: 2.91), 1 year (OR: 2.105), and 2 years (OR: 2.72). Rates of reported ABX increased from 2010 to 2018 (8.60% to 10.91%; P = 0.001) in patients undergoing TSA.Patients undergoing TSA with a history of ABX had a higher risk of readmission, postoperative anemia, blood transfusions, and PJI. These findings support critical assessment and clarification of reported allergies before TSA and possibly the use of preoperative allergy testing.Level 3 therapeutic study.

Ulnar-sided wrist pain can be a diagnostic challenge for clinicians and radiologists. The ulnar wrist has complex morphology and is composed of many small bone and soft tissue structures. Within these structures, a wide variety of pathologic conditions can occur. To successfully diagnose and treat these pathologic conditions, clinicians and radiologists must have a strong understanding of the advanced imaging techniques available to them. In this review, the authors present a brief review of the normal ulnar wrist anatomy, discuss the differential diagnosis of ulnar-sided wrist pain, and examine the indications for different advanced imaging modalities.

Background Recurrent shoulder instability is a debilitating condition that can lead to chronic pain, decreased function, and inability to return to activities or sport. This retrospective epidemiology study was performed to report 90-day postoperative complications and costs of Latarjet, anterior bone block reconstruction, arthroscopic, and open Bankart repair for shoulder instability. Methods Patients 18 years and older who underwent four primary shoulder surgeries from 2010 to 2019 were identified using national claims data. Patient demographics, comorbidities, and 90-day postoperative complications were analyzed using univariate analysis and multivariable logistic regression. Total and itemized 90-day reimbursements were determined for each procedure. Results The 90-day medical and surgery-specific complication rates were highest for anterior bone block reconstruction, followed by Latarjet. Arthroscopic Bankart repair had the highest 90-day costs and primary procedure costs compared to other procedures. Conclusion Anterior bone block reconstruction and Latarjet procedures were associated with the highest rates of 90-day medical and surgery-specific complications, while arthroscopic Bankart repair was associated with the highest costs.

Periprosthetic joint infection (PJI) after total joint arthroplasty is a known risk factor for infection in subsequent joint arthroplasty. The purpose of this study was to determine whether prior nonshoulder PJI contributes to the increased risk of infectious complications, greater healthcare utilization, and increased revision surgery after primary total shoulder arthroplasty (TSA).Patients who underwent primary TSA for osteoarthritis with prior nonshoulder PJI were identified in a national database (PearlDiver Technologies) using Current Procedural Terminology and International Classification of Diseases codes. These patients were propensity matched based on age, sex, Charlson Comorbidity Index, smoking status, and obesity (body mass index30 kg/m2) to a control cohort of patients who underwent primary TSA for osteoarthritis without any prior PJI. Primary outcomes include 1- and 2-year revision rates. Secondary outcomes include healthcare-specific outcomes of readmission, emergency department visits, length of stay, and mortality. Bivariate analysis was conducted using chi-square tests to compare all outcomes and complications between both cohorts.Compared with patients without prior PJI, those with prior PJI had a significantly higher risk of 90-day surgical site infection (7.61% versus 0.56%) and sepsis (1.79% versus 0.56%) after TSA (P0.05 for both). Patients with prior PJI also had a higher risk of 90-day readmission compared with those without prior PJI (3.36% versus 1.23%, P = 0.008). In terms of surgical complications, patients with prior PJI had significantly higher risk of 2-year revision surgery compared with patients without prior PJI (3.36% versus 1.57%, P = 0.034).Prior nonshoulder PJI of any joint increases rates of 90-day surgical site infection, sepsis, and hospital readmission, as well as 2-year all-cause revision after TSA. These results are important for risk-stratifying patients undergoing TSA with prior history of PJI.III.

To compare 90-day postoperative complications, health care use, 2-year and 5-year rates of reoperation and manipulation under anesthesia, and costs at the 30-day, 90-day, and 1-year postoperative intervals following open and arthroscopic rotator cuff repair (RCR).Patients who underwent an open or arthroscopic RCR with minimum 5-year follow-up were identified in a national database (PearlDiver Technologies) using Common Procedural Terminology andIn total, 3,266 patients who underwent open RCR were matched with 3,266 patients who underwent arthroscopic RCR. Compared with patients who underwent arthroscopic RCR, patients who underwent open RCR were at significantly increased risk of 90-day surgical-site infection (0.89% vs 0.34%,Patients undergoing open RCR were at increased risk of 90-day surgical-site infection and MUA both within 2 years and within 5 years of surgery in this study cohort.Level III, retrospective cohort study.

Background: Stabilization methods for distal tibiofibular syndesmotic injuries present risk of malreduction. We compared reduction accuracy and biomechanical properties of a new syndesmotic reduction and stabilization technique using 2 suture buttons placed through a sagittal tunnel in the fibula and across the tibia just proximal to the incisura with those of the conventional method. Methods: Syndesmotic injury was created in 18 fresh-frozen cadaveric lower leg specimens. Nine ankles were repaired with the conventional method and 9 with the new technique. Reduction for the conventional method was performed using thumb pressure under direct visualization and for the new method by tightening both suture buttons passed through the fibular and tibial tunnels. Computed tomography was used to assess reduction accuracy. Torsional resistance, fibular rotation, and fibular translation were evaluated during biomechanical testing. Results: The new technique showed less lateral translation of the fibula on CT measurements after reduction (0.06 ± 0.06 mm) than the conventional method (0.26 ± 0.31 mm), P = .02. The new technique produced less fibular rotation during internal rotation after 0 cycles (new –2.4 ± 1.4 degrees; conventional –5.0 ± 1.2 degrees, P = .001), 100 cycles (new –2.1 ± 1.9 degrees; conventional –4.6 ± 1.4 degrees, P = .01), and 500 cycles (new –2.2 ± 1.6 degrees; conventional –5.3 ± 2.5 degrees, P = .01) and during external rotation after 100 cycles (new 3.9 ± 3.3 degrees; conventional 5.9 ± 3.5 degrees, P = .02) and 500 cycles (new 3.3 ± 3.2 degrees; conventional 6.3 ± 2.6 degrees, P = .03). Fixation failed in 3 specimens. Conclusion: The new syndesmotic reduction and fixation technique resulted in more accurate reduction of the fibula in the tibial incisura in the coronal plane and better rotational stability compared with the conventional method. Clinical Relevance: This new technique of syndesmosis reduction and stabilization may be a reliable alternative to current methods.

Case A 78-year-old man was followed for an incidentally found, asymptomatic lesion in his right proximal femur that was unchanged radiographically for 11 years. He developed pain and was believed to have experienced a stress fracture through the lesion. The lesion was biopsied, showing a high-grade pleomorphic sarcoma with an underlying senescent intraosseous lipoma. He was ultimately treated with wide excision and reconstruction of the proximal femur. Conclusion This case highlights the importance of obtaining a tissue diagnosis for lesions that become symptomatic.

Background Identifying preoperative risk factors for complications following total shoulder arthroplasty (TSA) has both clinical and financial implications. The purpose of this study was to determine the influence of different degrees of preoperative INR elevation on complications following TSA. Methods Patients undergoing primary TSA from 2007 to 2018 were identified in a national database. Patients were stratified into 4 cohorts: INR of 1.0 to 1.25, INR of >1.25 to 1.5, and INR of >1.5. Postoperative complications were assessed. Multivariate logistic regressions were performed to adjust for differences in demographics and comorbidities among the INR groups. Results Following adjustment and relative to patients with an INR of 1.0–1.25, >1.25–1.5, and >1.5 had 1.6-times, 2.4-times, and 2.8-times higher odds of having postoperative bleeding requiring transfusion, respectively (p 1.25–1.5 and INR of >1.5 had 7.8-times and 7.0-times higher odds of having pulmonary complications, respectively (p Discussion With increasing INR levels, there is an independent and step-wise increase in odd ratios for postoperative complications. Current guidelines for preoperative INR thresholds may need to be adjusted for more predictive risk-stratification for TSA. Level of Evidence III

CDH1 (also known as E-cadherin), an epithelial-specific cell–cell adhesion molecule, plays multiple roles in maintaining adherens junctions, regulating migration and invasion, and mediating intracellular signaling. Downregulation of E-cadherin is a hallmark of epithelial-to-mesenchymal transition (EMT) and correlates with poor prognosis in multiple carcinomas. Conversely, upregulation of E-cadherin is prognostic for improved survival in sarcomas. Yet, despite the prognostic benefit of E-cadherin expression in sarcoma, the mechanistic significance of E-cadherin in sarcomas remains poorly understood. Here, by combining mathematical models with wet-bench experiments, we identify the core regulatory networks mediated by E-cadherin in sarcomas, and decipher their functional consequences. Unlike carcinomas, E-cadherin overexpression in sarcomas does not induce a mesenchymal-to-epithelial transition (MET). However, E-cadherin acts to reduce both anchorage-independent growth and spheroid formation of sarcoma cells. Ectopic E-cadherin expression acts to downregulate phosphorylated CREB1 (p-CREB) and the transcription factor, TBX2, to inhibit anchorage-independent growth. RNAi-mediated knockdown of TBX2 phenocopies the effect of E-cadherin on CREB levels and restores sensitivity to anchorage-independent growth in sarcoma cells. Beyond its signaling role, E-cadherin expression in sarcoma cells can also strengthen cell–cell adhesion and restricts spheroid growth through mechanical action. Together, our results demonstrate that E-cadherin inhibits sarcoma aggressiveness by preventing anchorage-independent growth. Implications: We highlight how E-cadherin can restrict aggressive behavior in sarcomas through both biochemical signaling and biomechanical effects.

For many cancer types, survival is improved when patients receive management at treatment centers that encounter high numbers of patients annually. This correlation may be more important with less common malignancies such as sarcoma. Existing evidence, however, is limited and inconclusive as to whether facility volume may be associated with survival in soft tissue sarcoma.The purpose of this study was to examine the association between facility volume and overall survival in patients with soft tissue sarcoma of the extremities. In investigating this aim, we sought to (1) examine differences in the treatment characteristics of high- and low-volume facilities; (2) estimate the 5-year survival by facility volume; and (3) examine the association between facility volume and of traveling a further distance to a high-volume center and overall survival when controlling for confounding factors.The largest sarcoma patient registry to date is contained within the National Cancer Database (NCDB) and captures70% of new cancer diagnoses annually. We retrospectively analyzed 25,406 patients with soft tissue sarcoma of the extremities in the NCDB from 1998 through 2012. Patients were stratified based on per-year facility sarcoma volume and we used univariate comparisons and multivariate proportional hazards analyses to correlate survival measures with facility volume and various other patient-, tumor-, and treatment-related factors. First, we evaluated long-term survival for all variables using the Kaplan-Meier method with statistical comparisons based on the log-rank test. Multiple patient, tumor, and treatment characteristics were compared between the two facility-volume groups and then included them in the multivariate proportional hazards model. Of the 25,406 patients analyzed, 3310 were treated at high-volume centers (≥ 20 patients annually) and 22,096 were treated at low-volume centers. Patient demographics were generally not different between both patient cohorts, although patients treated at high-volume centers were more likely to have larger and higher grade tumors (64% versus 56% size ≥ 5 cm, 28% versus 14% undifferentiated grade, p0.001).When controlling for patient, tumor, and treatment characteristics in a multivariate proportional hazards analysis, patients treated at high-volume facilities had an overall lower risk of mortality than those treated at low-volume centers (hazard ratio, 0.81 [0.75-0.88], p0.001). Patients treated at high-volume centers were also less likely to have positive margins (odds ratio [OR], 0.59 [0.52-0.68], p0.001) and in patients who received radiation, those treated at high-volume centers were more likely to have radiation before surgery (40.5% versus 21.7%, p0.001); there was no difference in the type of surgery performed (resection versus amputation) (OR, 1.01 [0.84-1.23], p = 0.883).With the largest patient cohort to date, this database review suggests that certain patients with soft tissue sarcoma of the extremities, particularly those with large high-grade tumors, may benefit from treatment at high-volume centers. Further investigation is necessary to help improve the referral of appropriate patients to high-volume sarcoma centers and to increase the treatment capacity of and access to such centers.Level III, therapeutic study.

Case The expandable intramedullary cage (Conventus Orthopaedics) may treat 3- and 4-part proximal humerus fractures. Cage removal for symptomatic avascular necrosis with humeral head collapse requiring conversion to arthroplasty can be challenging because the cage's collapsing mechanism becomes inoperable after fracture consolidation. We present cage explantation followed by reverse total shoulder prosthesis placement in a 54-year-old man who underwent plate/cage fixation for a 3-part proximal humerus fracture 10 months earlier. Conclusion The proximal humeral cage can be extracted safely while preserving adequate bone stock for subsequent arthroplasty. Additional time and exposure are necessary compared with removing a locking plate alone.

Bordetella pertussis is the causative agent of whooping cough. This pathogenic bacterium can obtain the essential nutrient iron using its native alcaligin siderophore and by utilizing xeno-siderophores such as desferrioxamine B, ferrichrome, and enterobactin. Previous genome-wide expression profiling identified an iron repressible B. pertussis gene encoding a periplasmic protein (FbpABp). A previously reported crystal structure shows significant similarity between FbpABp and previously characterized bacterial iron binding proteins, and established its iron-binding ability. Bordetella growth studies determined that FbpABp was required for utilization of not only unchelated iron, but also utilization of iron bound to both native and xeno-siderophores. In this in vitro solution study, we quantified the binding of unchelated ferric iron to FbpABp in the presence of various anions and importantly, we demonstrated that FbpABp binds all the ferric siderophores tested (native and xeno) with μM affinity. In silico modeling augmented solution data. FbpABp was incapable of iron removal from ferric xeno-siderophores in vitro. However, when FbpABp was reacted with native ferric-alcaligin, it elicited a pronounced change in the iron coordination environment, which may signify an early step in FbpABp-mediated iron removal from the native siderophore. To our knowledge, this is the first time the periplasmic component of an iron uptake system has been shown to bind iron directly as Fe(3+) and indirectly as a ferric siderophore complex.

Haptoglobin (Hp) is an abundant and conserved plasma glycoprotein, which binds acellular adult hemoglobin (Hb) dimers with high affinity and facilitates their rapid clearance from circulation after hemolysis. Humans possess three main phenotypes of Hp, designated Hp 1-1, Hp 2-1, and Hp 2-2. These variants exhibit diverse structural configurations and have been reported to be functionally nonequivalent. We have investigated the functional and redox properties of Hb-Hp complexes prepared using commercially fractionated Hp and found that all forms exhibit similar behavior. The rate of Hb dimer binding to Hp occurs with bimolecular rate constants of ~0.9 μM(-1) s(-1), irrespective of the type of Hp assayed. Although Hp binding does accelerate the observed rate of HbO2 autoxidation by dissociating Hb tetramers into dimers, the rate observed for these bound dimers is three- to fourfold slower than that of Hb dimers free in solution. Co-incubation of ferric Hb with any form of Hp inhibits heme loss to below detectable levels. Intrinsic redox potentials (E1/2) of the ferric/ferrous pair of each Hb-Hp complex are similar, varying from +54 to +59 mV (vs NHE), and are essentially the same as reported by us previously for Hb-Hp complexes prepared from unfractionated Hp. All Hb-Hp complexes generate similar high amounts of ferryl Hb after exposure to hydrogen peroxide. Electron paramagnetic resonance data indicate that the yields of protein-based radicals during this process are approximately 4 to 5% and are unaffected by the variant of Hp assayed. These data indicate that the Hp fractions examined are equivalent to one another with respect to Hb binding and associated stability and redox properties and that this result should be taken into account in the design of phenotype-specific Hp therapeutics aimed at countering Hb-mediated vascular disease.