Cone-Beam CT of the Extremities in Clinical Practice.

Cone-beam CT (CBCT) is a promising tool with increasing applications in musculoskeletal imaging due to its ability to provide thin-section CT images of the appendicular skeleton and introduce weight bearing, which accounts for loading forces that typically interact with and affect this anatomy. CBCT devices include an x-ray source directly opposite a digital silicon detector panel that performs a single rotation around an object of interest, obtaining thin-section images. Currently, the majority of research has been focused on the utility of CBCT with foot and ankle pathologic abnormalities, due to the complex architectural arrangement of the tarsal bones and weight-bearing nature of the lower extremities. Associated software can provide a variety of options for image reconstruction, including metal artifact reduction, three-dimensional biometric measurements, and digitally reconstructed radiographs. Advancements in this technology have allowed imaging of the knee, hip, hand, and elbow. As more data are published, it is becoming evident that CBCT provides many additional benefits, including fast imaging time, low radiation dose, lower cost, and small equipment footprint. These benefits allow placement of CBCT units outside of the traditional radiology department, including the orthopedic clinic setting. These technologic developments have motivated clinicians to define the scope of CBCT for diagnostics, surgical planning, and longitudinal imaging. As efforts are made to create standardized protocol and measurements, the current understanding and surgical approach for various orthopedic pathologic conditions will continue to shift, with the hope of improving outcomes. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

Large Variation in Listed Chargemaster Price for Total Joint Arthroplasty Among Top Orthopaedic Hospitals in the United States.

BACKGROUND: Chargemasters are lists of all services offered by a hospital and their associated cost. This study analyzes chargemaster data to determine price differences among different hospitals for total joint arthroplasty. METHODS: In May 2020, the chargemaster data for highly rated orthopaedic hospitals were accessed, and the diagnostic-related group (DRG) codes related to primary and revision total joint arthroplasty were analyzed (DRGs 466, 467, 468, 469, and 470). The prices listed for each hospital were averaged, and descriptive statistics were calculated. Furthermore, Medicare reimbursement was collected. A subanalysis was performed to determine relationships between geographic and demographic information. RESULTS: The median price for a major hip or knee joint arthroplasty without complications was $68,016 (range: $39,927 to $195,264). The median price of a revision of hip or knee arthroplasty without complications was $90,966 (range: $58,967 to $247,715). The cost of living in the city in which the hospitals are located was weakly correlated with procedure pricing, whereas the median income had no notable relationship to chargemaster pricing. CONCLUSION: The published cost of DRG codes in arthroplasty is widely variable among the top 20 US orthopaedic hospitals, with little correlation to the cost of living or median income of the area.

Orthopaedic Shoulder and Elbow Fellowship Directors in the United States Have Substantial Research Output but Lack Diversity.

Purpose: To investigate the characteristics of shoulder and elbow fellowship directors (FDs). Methods: FDs for shoulder and elbow fellowship programs in the United States were identified. Demographic, educational, and professional background data were collected from available curricula vitarum, institutional biographies, and the Scopus database. Data collected included age, sex, race/ethnicity, training locations, graduation years, advanced degrees, current institutional information, and personal research H-index. Results: Thirty current orthopaedic shoulder and elbow FDs were identified. The mean Scopus H-index was 25.5. The mean age of FDs was 52.1 years. In total, 29 FDs (96.7%) were male and 1 (3.3%) was female. In addition, 25 of the 30 (83.3%) were White (83.3%), 4 were Asian, and 1 (3.3%) was Hispanic. Two (6.7%) had a military affiliation. Mean time from fellowship training graduation to FD appointment was 13.5 years. Mean number of years as FD was 6.1 years, whereas the number of years tenure with an FD-affiliated institution was 13.0 years. Mean calendar years for completion of orthopaedic residency training and fellowship training were 1998 and 2000, respectively. The residencies that produced the most future FDs were Hospital of the University of Pennsylvania (n = 2) and University of Nebraska Medical Center/Creighton University Health Foundation (n = 2). The fellowship that produced the most future FDs was Columbia University (n = 6). Moderate correlation was found between age and Scopus H-index (r = 0.48; P = .04) and years as FD and Scopus H-index (r = 0.42; P = .03). Conclusions: Women and minorities are under-represented in leadership positions in shoulder and elbow surgery. Shoulder and elbow FDs have the highest H-index of any subspecialty reported in the orthopaedic literature. Research productivity is an important qualification when considering the characteristics of shoulder and elbow FDs. Clinical Relevance: Fellowship directors can have a profound influence on current and future orthopaedic surgeons. It is important to identify the traits that characterize current fellowship directors to have a better understanding of who we choose as leaders in our field.

Investigation of Fellowship Leadership in Orthopaedic Musculoskeletal Oncology.

INTRODUCTION: The purpose of this study was to determine the objective characteristics of orthopaedic musculoskeletal oncology fellowship directors (FDs) by concentrating on the demographics, academic background, institutional history, research experience, and professional affiliations of these leaders. METHODS: Data were collected for each FD through institutional biographies or publicly available curriculum vitae. The data collected for each FD included demographic, professional, and research information. RESULTS: Of the 19 FDs, 15 (78.9%) were male, and 4 (21.1%) were female. The mean age for all FDs was 49.2 ± 9.1 years. Most FDs were White (n = 16; 84.2%). The mean Scopus H-index, total number of citations, and total number of publications among all 19 FDs were 21.6 ± 13.8, 2,290.6 ± 2,709.0, and 84.0 ± 54.7, respectively. The mean number of years serving in the FD role was 7.1 ± 9.1 years, and the mean number of years that the FD was employed at his/her current institution was 11.1 ± 8.1 years. CONCLUSION: This study shows that orthopaedic musculoskeletal oncology FDs were mainly White (84.2%), male (78.9%), and in their late 40s; have filled their role as FD for an average of 7.1 years; and are very productive in research.

Publicly Available Pricing Information for Orthopaedic Upper Extremity Procedures in the United States Lacks Transparency and Consistency Between Major Hospitals.

Purpose: The purpose of this study was to assess the price variation of various Medicare severity diagnosis-related group codes for orthopaedic upper extremity procedures for the top 20 orthopaedic hospitals using chargemaster price listings from each hospital. Methods: The top 20 orthopaedic hospitals in the United States were determined by querying the U.S. News and World Report's 2020 orthopaedic hospital ranking. This report ranks orthopaedic hospitals according to 4 major domains: outcomes, structure, process/expert opinion, and patient experience. Chargemaster data for the top 20 orthopaedic hospitals was compiled from their websites. Five DRG codes that represented orthopaedic upper extremity procedures were selected, and the pricing information for each was extracted from hospital chargemasters. The median income and cost-of-living index were also compiled for the county that each hospital is located in so that pricing data could be compared to economic measures through regression analysis. Results: Of the top 20 orthopaedic hospitals, 18 had publicly available pricing information in DRG format on their websites. The DRG code with the highest pricing variability was Hand Injury Procedures (DRG 906; range, $12,832-$253,633). The procedure with the least pricing variability was Hand or Wrist Procedures (DRG 514; range, $24,533-$128,403). Additionally, only the cost of living index was a statistically significant predictor of procedure pricing with a weak correlation. Conclusion: Hospital chargemaster listings are lacking in 2 major areas: true price transparency and standardization/consistency between hospitals. Chargemaster data are often difficult to find, confusing to patients, and inaccurate. Additionally, the price range for a single DRG code can also vary substantially depending on the hospital. It is possible that hospitals located in areas with high costs of living and median incomes would charge higher prices, but these factors were not found to support this hypothesis.

Robotic-Assisted Total Knee Arthroplasty Allows for Trainee Involvement and Teaching Without Lengthening Operative Time.

BACKGROUND: Robot-assisted total knee arthroplasty (RA-TKA) is more accurate than mechanical total knee arthroplasty (M-TKA) and can provide real-time feedback about alignment and soft-tissue balancing that may be helpful in trainee education. However, both robotic-assist and trainee involvement potentially increase the surgical time. This study sought to evaluate whether RA-TKA procedures were longer than M-TKA procedures and whether trainee participation added additional surgical time. METHODS: This retrospective cohort study reviewed 220 consecutive primary TKAs (110 M-TKA and 110 RA-TKA) performed by an orthopedic trainee under supervision or performed by the consultant surgeon with an assistant present. For M-TKAs, a measured resection technique was used. For all RA-TKAs, the MAKO robotic system (Stryker, USA) was used. Tourniquet time was measured from inflation immediately prior to skin incision to deflation after placement of the final polyethylene insert. Procedures performed by a consulting surgeon with a surgical assist were used as controls for procedures performed by the trainee. In trainee-conducted procedures, the trainee is responsible for performing all critical aspects of the procedure while the consulting surgeon provides supervision and acts as first assist. RESULTS: 103 M-TKA and 96 RA-TKA were included. Tourniquet time was significantly longer for RA-TKAs vs M-TKAs (100 vs 89 minutes, P < .0001). However, there were no significant differences in tourniquet times between surgery performed by a trainee vs the consulting surgeon with surgical assist for either M-TKA (P = .3452) or RA-TKA (P = .6724). CONCLUSIONS: While RA-TKA takes longer, orthopedic trainees do not add additional time. Trainees at all stages of postgraduate learning can be educated in the use of robotic technology and potentially benefit from real-time feedback without further compromising surgical efficiency or increasing patient risk.

Trends in the Neurosurgical Workforce and Implications in Providing for an Aging Population.

BACKGROUND: The United States is projected to face increasing physician-workforce shortages. However, the shortage in the neurosurgical workforce has not yet been characterized. In the present study, we outlined the current state of the neurosurgical workforce by quantifying the divide between the number of practicing neurosurgeons and the U.S. METHODS: The Medicare Physician National Medicare database was queried from 2014 to 2019 to obtain the numbers of practicing neurosurgeons, which were compared with the population counts from the U.S. Census data. RESULTS: From 2014 to 2019, the total increase in neurosurgeons per capita was 9.4%. The Northeast neurosurgeons per capita rate (NPCR) increased by 17.1%, the South NPCR by 3.4%, the Midwest NPCR by 13.3%, and the West NPCR by 12.5%. In all regions, except for the West, the surgeon per capita ratio had decreased from 2017 to 2019. The greatest increase in the number of surgeons was 2018 to 2019 (n = 214). In 2014, the states with the lowest NPCRs were Vermont, Arkansas, and New Mexico. In 2019, these included Nevada, New Mexico, and Vermont. As of 2020, 56.6% of the neurosurgeons had practiced for >20 years. CONCLUSIONS: Although the national NPCR has slowly increased during the past 5 years, a more recent decrease occurred within the last 3 years. Additionally, with almost 57% of surgeons having been practicing for >20 years, concern exists regarding whether current practices can sustain increasing patient needs. The results from the present study indicate that further investigation is warranted regarding the factors contributing to this shortage and the steps that can be taken to increase the production of well-trained neurosurgeons.

Orthopaedic Sports Medicine Fellowship Directors Are Predominantly White Men With a High Degree of Research Productivity.

PURPOSE: To determine the objective characteristics of fellowship directors (FDs) in orthopaedic sports medicine by focusing on the demographics, academic background, institutional history, research experience, and professional affiliations of FDs in this field. METHODS: Data was collected for each FD via institutional biographies or publicly available curriculum vitae (CV). The data collected for each FD included age, gender, race/ethnicity, previous training institutions, residency and fellowship graduation years, additional advanced degrees, military affiliation, institutional loyalty, year hired by current institution, career timeline, Scopus H-index, number of publications, and total number of citations. RESULTS: Of the 88 FDs, 87 (98.9%) were male and 1 (1.1%) was female. The mean age for all FDs was 54.7 years (± 9.1 standard deviation). The majority of FDs were White (n = 80; 90.9%). The mean Scopus H-index, total number of publications, and total number of citations were 22.5 ± 16.6, 90.0 ± 91.6, and 2773.9 ± 3962.9, respectively. On average, it took 9.5 ± 7.3 years from fellowship graduation until FD appointment. Additionally, the mean number of years of employment or affiliation with the current institution was 17.2 ± 9.4, and the mean number of years in an FD role was 10.9 ± 9.3. CONCLUSION: Orthopaedic sports medicine fellowship directors are largely distinguished by their high level of research productivity and accomplishment. Additionally, orthopaedic training pedigree seems to play a role in FD role attainment, with a handful of orthopaedic residency and sports medicine fellowship programs producing a large percentage of current FDs. Finally, FDs are overwhelmingly white males with little female or minority representation. CLINICAL RELEVANCE: This study outlines some of the most important characteristics among orthopaedic sports medicine fellowship directors and identifies racial and gender disparities within this population of leaders that may have detrimental effects on the field as a whole.

Workforce Trends in Spinal Surgery: Geographic Distribution and Primary Specialty Characteristics from 2012 to 2017.

OBJECTIVE: Although both neurosurgeons and orthopedic surgeons specialize in spinal care, it is not clear how this increased demand for spine surgeons has affected these fields. In this study, we aim to characterize the total number, geographic distribution, and procedural rate of laminectomies of spine surgeons by their primary specialty from 2012 to 2017. METHODS: Neurosurgical and orthopedic data from 2012 to 2017 were obtained from the Medicare Provider Utilization Database. The databases were filtered by the primary specialty to include "Neurosurgeons" and "Orthopedic surgery." To select specifically for spine surgeons, the 203 Healthcare Common Procedure Coding System codes relating to spinal procedures were chosen as additional filters. RESULTS: Between 2012 and 2017, the total number of spine surgeons in the United States increased by 9.6% from 3,861 to 4,241 total surgeons. The South experienced the largest percentage increase in spine surgeons from 1,584 surgeons in 2012 to 1,769 in 2017 (11.7%). Over this 5-year span, neurosurgeons performed a greater share of both cervical and lumbar laminectomies, but orthopedic spine surgeons saw a greater increase in procedural growth (+87.2% cervical and +16.7% lumbar). CONCLUSIONS: There is relatively slow growth in the workforce of spinal surgery, with orthopedic spine specialists outpacing the growth seen in neurosurgical spine. This growth is seen at different rates across different regions in the U.S., with the South experiencing the highest rate of growth. Finally, although neurologic surgery performs more laminectomies in both the lumbar and cervical region, orthopedic surgeons are quickly increasing their proportion of performed procedures.

Can NFL Combine Results be Used to Estimate NFL Defensive Players Longevity?

The National Football League Scouting Combine is an annual event held to evaluate football players. The results of the combine are used to identify talent and player potential. Our study aims to examine the relationship between combine drill performance (e.g., speed, power, agility, explosiveness) and career longevity. We performed a retrospective review of The National Football League combine test results for all defensive players from 2005-2015 to determine the association of each player's combine test results with career longevity. The position that had the most significant associations for 1-year status was linebackers, with weight, 10-yard dash, 20-yard dash, 40-yard dash, broad jump, 3-cone drill, and shuttle being significantly associated with 1-year roster status. The position that had the most significant associations for 5-year status was cornerbacks, with weight, 10-yard dash, 20-yard dash, 40-yard dash, 3-cone drill, and shuttle being significantly associated with 1-year roster status. The least number of significant associations was found for safeties, with no drill being associated with 1-year roster status and only height and shuttle time significantly associated with 5-year career longevity. Our study demonstrates the utility of the combine results to help estimate the career longevity of NFL defensive players.

A significant association between C5 nerve sheath tumors and new postoperative weakness.

OBJECTIVE: The objective of this study was to determine if patients with nerve sheath tumors affecting the C5 spinal nerve are at greater risk for postoperative weakness than those with similar tumors affecting other spinal nerves contributing to the brachial plexus. METHODS: A retrospective chart review (1998-2020)identified patients with pathologically confirmed schwannomas or neurofibromas from the C5 to T1 nerves. Patients with plexiform nerve sheath tumors, tumors involving more than 1 nerve, and malignant peripheral nerve sheath tumors were excluded. Collected variables included basic demographics, tumor dimensions, its location relative to the dura, involved nerve level, surgical approach, extent of resection, presenting symptoms, postoperative neurological deficits, and recurrence rate. RESULTS: Forty-six patients (23 men, 23 women) were identified for inclusion in the study with an average age of 47 ± 17 years, BMI of 28 ± 5 kg/m2, and follow-up of 32 ± 45 months. Thirty-nine patients (85%) had schwannomas and 7 (15%) had neurofibromas. Tumors involved the C5 (n = 12), C6 (n = 11), C7 (n = 14), C8 (n = 6), and T1 (n = 3) nerves. Multivariable logistic regression analysis with an area under the curve of 0.85 demonstrated C5 tumor level as an independent predictor of new postoperative weakness (odds ratio 7.4, p = 0.028). Of those patients with new postoperative weakness, 75% improved and 50% experienced complete resolution of their motor deficits. CONCLUSIONS: Patients with C5 nerve sheath tumor resections are at higher odds of new postoperative weakness. This may be due to the predominant single innervation of shoulder muscle targets in contrast to other upper extremity muscles that receive input from 2 or more spinal nerves. These findings are important for clinical decision-making and preoperative patient counseling.

Lower Hounsfield Units at the Upper Instrumented Vertebrae are Significantly Associated With Proximal Junctional Kyphosis and Failure Near the Thoracolumbar Junction.

BACKGROUND: Low bone mineral density (BMD) on dual energy x-ray absorptiometry (DXA) is likely a risk factor for proximal junctional kyphosis (PJK) and proximal junctional failure (PJF). However, prior instrumentation and degenerative changes can preclude a lumbar BMD measurement. Hounsfield units (HU) represent an alternative method to estimate BMD via targeted measurements at the intended operative levels. OBJECTIVE: To determine if patients with lower HU at the upper instrumented vertebrae (UIV) and vertebral body superior to the UIV (UIV + 1) are at greater risk for PJK and PJF. METHODS: A retrospective chart review identified patients at least 50 yr of age who underwent instrumented lumbar fusion with pelvic fixation, a UIV from T10 to L2, and a preoperative computed tomography (CT) encompassing the UIV. HU were measured at the UIV, UIV + 1, and the L3-L4 vertebral bodies. RESULTS: A total of 150 patients (80 women and 70 men) were included with an average age of 66 yr and average follow-up of 32 mo. Multivariable logistic regression analysis with an area under the curve (AUC) of 0.89 demonstrated HU at the UIV/UIV + 1 as the only independent predictor of PJK/PJF with an odds ratio of 0.94 (P-value = .031) for a change in a single HU. Patients with HU at UIV/UIV + 1 of <110 (n = 35), 110 to 160 (n = 73), and >160 (n = 42) had a rate of PJK/PJF of 63%, 27%, and 12%, respectively (P-value < .001). CONCLUSION: Patients with lower HU at the UIV and UIV + 1 were significantly associated with PJK and PJF, with an optimal cutoff of 122 HU that maximizes sensitivity and specificity.

Increasing severity of anemia is associated with poorer 30-day outcomes for total shoulder arthroplasty.

BACKGROUND: Total shoulder arthroplasty (TSA) has increased in utilization over the past several decades. Anemia is a common preoperative condition among patients undergoing TSA and has been associated with poorer outcomes in other surgical procedures. To the best of our knowledge, no study has analyzed the association between anemia severity and TSA outcomes. Therefore, the purpose of this study is to determine the effects that increasing severity of anemia may have on the postoperative outcomes in patients receiving primary TSA. METHODS: A retrospective analysis was performed using the American College of Surgeons National Surgery Quality Improvement Project database from the years 2015 to 2018. Current Procedure Terminology code 23472 was used to identify all primary TSA procedures recorded during this time frame. Patients with greater than 38% preoperative hematocrit (HCT) were classified as having normal HCT levels. Patients with HCT values between 33% and 38% were classified as having mild anemia. All patients with less than 33% HCT were classified as having moderate/severe anemia. Patient demographic information, preoperative risk factors, and postoperative outcomes were compared among the 3 cohorts. A multivariate logistic regression including demographic factors and comorbidities was performed to determine whether increasing severity of anemia is independently associated with poorer postoperative outcomes. RESULTS: Of the 15,185 patients included in this study, 11,404 had normal HCT levels, 2962 patients were mildly anemic, and 819 patients had moderate to severe anemia. With increasing severity of anemia, there was an increased average hospital length of stay (1.6 vs. 2.1 vs. 3.0 days, P < .001), rate of readmissions (2.3% vs. 4.8% vs. 7.0%, P < .001), and rate of all reoperations (1.1% vs. 1.8% vs. 3.1%, P < .001). There was a statistically significant increase in both minor (1.9% vs. 2.7% vs. 4.4%, P < .001) and major (1.2% vs. 2.4% vs. 4.3%, P < .001) postoperative complication rates as well. Multivariate analysis identified anemia as an independent predictor of readmissions, reoperations, minor complications, and major complications. CONCLUSION: We found increasing severity of anemia to be associated with progressively worse 30-day postoperative outcomes. This is consistent with the outcomes found for increasing severity of anemia in patients receiving other total joint procedures. Using preoperative HCT levels may be a useful tool for predicting the risk of postoperative complications in patients undergoing TSA. This information could be used to further optimize patient selection for primary TSA.

Comparison of Two-level Cervical Disc Replacement Versus Two-level Anterior Cervical Discectomy and Fusion in the Outpatient Setting.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The aim of this study was to evaluate the safety of two-level cervical disc replacement (CDR) in the outpatient setting. SUMMARY OF BACKGROUND DATA: Despite growing interest in CDR, limited data exist evaluating the safety of two-level CDR in the outpatient setting. METHODS: The National Surgical Quality Improvement Program (NSQIP) database was queried for all two-level anterior cervical discectomy and fusion (ACDF) and CDR procedures between 2015 and 2018. Demographics, comorbidities, and 30-day postoperative complication rates of outpatient two-level CDR were compared to those of inpatient two-level CDR and outpatient two-level ACDF. Radiographic data are not available in the NSQIP. RESULTS: A total of 403 outpatient CDRs were compared to 408 inpatient CDRs and 4134 outpatient ACDFs. Outpatient CDR patients were older and more likely to have pulmonary comorbidities compared to inpatient CDR (P < 0.03). Outpatient CDR patients were less likely to have an American Society of Anesthesiologists class ≥2 and have hypertension compared to outpatient ACDF patients (P < 0.0001). Outpatient CDR had a lower 30-day readmission rate (0.5% vs. 2.5%, P = 0.02) and lower 30-day reoperation rate (0% vs. 1%, P = 0.047) compared to inpatient CDR. Outpatient CDR had a lower readmission rate (0.5% vs. 2.1%, P = 0.03) compared to outpatient ACDF, but there was no difference in reoperation rates between the two procedures (0% vs. 0.8%, P = 0.07). Outpatient CDR had an overall complication rate of 0.2%, inpatient CDR had a complication rate of 0.9%, and outpatient ACDF had a complication rate of 1.3%. These differences were not significant. CONCLUSION: To our knowledge, this is the largest multicenter study examining the safety of two-level outpatient CDR procedures. Outpatient two-level CDR was associated with similarly safe outcomes when compared to inpatient two-level CDR and outpatient two-level ACDF. This suggests that two-level CDR can be performed safely in the outpatient setting.Level of Evidence: 3.

Orthopaedic Foot and Ankle Surgery Fellowship Directors Are Typically White Men in Their Early 50s With Strong Achievements in Research.

PURPOSE: To determine the objective characteristics of orthopaedic foot and ankle fellowship directors (FDs) by concentrating on the demographic characteristics, academic background, institutional history, research experience, and professional affiliations of these leaders. METHODS: Data for each FD were collected by searching institutional biographies, personal websites, or publicly available curricula vitae. Data collection included the following variables: age, sex, race/ethnicity, previous training institutions, residency and fellowship graduation years, advanced degrees, military affiliation, institutional loyalty, year hired, FD career timeline, total number of publications, total number of citations, and h-index. RESULTS: Of the 47 FDs, 44 (93.6%) were men and 3 (6.4%) were women. The mean age was 50.8 ± 9.4 years. Most orthopaedic foot and ankle FDs were white (n = 42, 89.4%), followed by Asian (n = 4, 8.5%) and black or African American (n = 1, 2.1%). The mean Scopus h-index, total number of publications, and total number of citations for all foot and ankle FDs were 13.3 ± 9.5, 47.5 ± 45.8, and 898.1 ± 1,040.3, respectively. Among all foot and ankle FDs, the mean tenure in the FD position was 5.8 ± 4.6 years. CONCLUSIONS: Orthopaedic foot and ankle FDs are primarily white men in their 50s, with minimal female and minority representations. These FDs are distinguished by their high level of research productivity. Additionally, orthopaedic foot and ankle training backgrounds seem to play an important role, given that most of the appointed FDs trained in only a few select programs. CLINICAL RELEVANCE: This study outlines some of the most important characteristics among foot and ankle FDs and identifies important disparities within this population of leaders that may have detrimental effects on the field.

Orthopaedic Group Practice Size Is Increasing.

PURPOSE: To analyze recent trends in orthopaedic surgery consolidation and quantify these changes temporally and geographically from 2012 to 2020. METHODS: We performed a retrospective cross-sectional analysis of orthopaedic surgeon practice size in the United States using 2012 and 2020 data obtained from the Physician Compare database. RESULTS: Although we observed an increase from 21,216 unique orthopaedic surgeons in 2012 to 21,553 in 2020 (1.6% increase), the number of practices experienced a large decrease from 7,299 practices in 2012 to 5,829 in 2020 (20.1% decrease). The proportion of orthopaedic surgeons working in solo practices decreased from 13.2% (2,790) in 2012 to 7.4% (1,595) in 2020, and the proportion of orthopaedic surgeons working in groups sized 2 to 24 decreased from 35.3% (7,482) in 2012 to 22.2% (4,775) in 2020. In contrast, groups sized 25 to 99 have grown from 20.7% (4,387) of all orthopaedic surgeons to 23.4% (5,048) in 2020. Groups sized 100 to 499 have increased from 16.9% (3,593) in 2012 to 24.1% (5,190) in 2020, whereas groups sized 500 or greater have grown from 14% (2,964) in 2012 to 22.9% (4,945) in 2020. The number of unique group practices showed a significant decrease in the number of solo groups, which comprised 43.8% (3,200) of the total number of individual practices in 2012, decreasing to 32% (1,886) in 2020. All other groups increased in number and proportionally from 2012 to 2020. CONCLUSIONS: This study shows that over the period from 2012 to 2020, there has been a substantial trend of orthopaedic surgeons shifting to increasing practice sizes, potentially indicating that more orthopaedic surgeons are working for large health care organizations rather than small independent practices. CLINICAL RELEVANCE: The impact of these changes should be examined to determine large-scale effects on patient care, payment models, access, and outcomes, along with physician compensation, lifestyle, and satisfaction.

Redirecting extracellular proteases to molecularly guide radiosensitizing drugs to tumors.

Patients with advanced cancers are treated with combined radiotherapy and chemotherapy, however curability is poor and treatment side effects severe. Drugs sensitizing tumors to radiotherapy have been developed to improve cell kill, but tumor specificity remains challenging. To achieve tumor selectivity of small molecule radiosensitizers, we tested as a strategy active tumor targeting using peptide-based drug conjugates. We attached an inhibitor of the DNA damage response to antibody or cell penetrating peptides. Antibody drug conjugates honed in on tumor overexpressed cell surface receptors with high specificity but lacked efficacy when conjugated to the DNA damage checkpoint kinase inhibitor AZD7762. As an alternative approach, we synthesized activatable cell penetrating peptide scaffolds that accumulated within tumors based on matrix metalloproteinase cleavage. While matrix metalloproteinases are integral to tumor progression, they have proven therapeutically elusive. We harnessed these pro-tumorigenic extracellular proteases to spatially guide radiosensitizer drug delivery using cleavable activatable cell penetrating peptides. Here, we tested the potential of these two drug delivery platforms targeting distinct tumor compartments in combination with radiotherapy and demonstrate the advantages of protease triggered cell penetrating peptide scaffolds over antibody drug conjugates to deliver small molecule amine radiosensitizers.

Precision Chemoradiotherapy for HER2 Tumors Using Antibody Conjugates of an Auristatin Derivative with Reduced Cell Permeability.

The most successful therapeutic strategies for locally advanced cancers continue to combine decades-old classical radiosensitizing chemotherapies with radiotherapy. Molecular targeted radiosensitizers offer the potential to improve the therapeutic ratio by increasing tumor-specific kill while minimizing drug delivery and toxicity to surrounding normal tissue. Auristatins are a potent class of anti-tubulins that sensitize cells to ionizing radiation damage and are chemically amenable to antibody conjugation. To achieve tumor-selective radiosensitization, we synthesized and tested anti-HER2 antibody-drug conjugates of two auristatin derivatives with ionizing radiation. Monomethyl auristatin E (MMAE) and monomethyl auristatin F (MMAF) were attached to the anti-HER2 antibodies trastuzumab and pertuzumab through a cleavable linker. While MMAE is cell permeable, MMAF has limited cell permeability as free drug resulting in diminished cytotoxicity and radiosensitization. However, when attached to trastuzumab or pertuzumab, MMAF was as efficacious as MMAE in blocking HER2-expressing tumor cells in G2-M. Moreover, MMAF anti-HER2 conjugates selectively killed and radiosensitized HER2-rich tumor cells. Importantly, when conjugated to targeting antibody, MMAF had the advantage of decreased bystander and off-target effects compared with MMAE. In murine xenograft models, MMAF anti-HER2 antibody conjugates had less drug accumulated in the normal tissue surrounding tumors compared with MMAE. Therapeutically, systemically injected MMAF anti-HER2 conjugates combined with focal ionizing radiation increased tumor control and improved survival of mice with HER2-rich tumor xenografts. In summary, our results demonstrate the potential of cell-impermeable radiosensitizing warheads to improve the therapeutic ratio of radiotherapy by leveraging antibody-drug conjugate technology.