Larger stem to bone diameter ratio predicts lower cemented endoprosthesis failure.

BACKGROUND AND OBJECTIVES: With continued advances in treatment options, patients with endoprosthetic reconstruction are living longer and consequently relying upon their devices for a longer duration. Major causes of endoprosthesis failure include aseptic loosening and mechanical failure. In the setting of tumor resection, loss of bone stock and use of radiation therapy increase the risk for these complications. As such, considerations of remaining native bone and stem length and diameter may be increasingly important. We asked the following questions: (1) What was the overall rate of endoprosthesis failure at a minimum of 5-year follow-up? (2) Does resection length increase implant failure rates? (3) Does implant size and its ratio to cortical width of bone alter implant failure rates? METHODS: We retrospectively analyzed patient outcomes at a single institution between the years of 1999-2022 who underwent cemented endoprosthetic reconstruction at the hip or knee and identified 150 patients. Of these 150, 55 had a follow-up of greater than 5 years and were used for analysis. Radiographs of these patients at time of surgery were assessed and measured for resection length, bone diameter, stem diameter, and remaining bone length. Resection percentage, and stem to bone diameter ratios were then calculated and their relationship to endoprosthesis failure were analyzed. RESULTS: Patients in this cohort had a mean age of 55.8, and mean follow-up of 59.96 months. There were 78 distal femoral replacements (52%), 16 proximal femoral replacements (10.7%), and 56 proximal tibial replacements (37.3%). There were five patients who experienced aseptic loosening and six patients who experienced mechanical failure. Patients with implant failure had a smaller mean stem to bone diameter (36% vs. 44%; p = 0.002). A stem to bone diameter of 40% appeared to be a breaking point between success and failure in this series, with 90% of patients with implant failure having a stem: bone ratio less than 40%. Stem to bone ratio less than 40% increased risk for failure versus stems that were at least 40% the diameter of bone (6/19 [31.6%] vs. 0/36 [0%]; odds ratio 0.68; p < 0.001). Resection length did not appear to have an impact on the rates of aseptic loosening and mechanical failure in this series. CONCLUSIONS: Data from this series suggests a benefit to using stems with a larger diameter when implanting cemented endoprostheses at the hip or knee. Stems which were less than 40% the diameter of bone were substantially more likely to undergo implant failure.

Exploring novel HIV-1 reverse transcriptase inhibitors with drug-resistant mutants: A double mutant surprise.

HIV-1 reverse transcriptase (RT) remains a key target for HIV drug development. As successful management of the disease requires lifelong treatment, the emergence of resistance mutations is inevitable, making development of new RT inhibitors, which remain effective against resistant variants crucial. To this end, previous computationally guided drug design efforts have resulted in catechol diether compounds, which inhibit wildtype RT with picomolar affinities and appear to be promising preclinical candidates. To confirm that these compounds remain potent against Y181C, a widespread mutation conferring resistance to first generation inhibitors, they were screened against the HIV-1 N119 clinical isolate, reported as a Y181C single mutant. In comparison to a molecular clone with the same mutation, N119 appears less susceptible to inhibition by our preclinical candidate compounds. A more detailed sequencing effort determined that N119 was misidentified and carries V106A in combination with Y181C. While both indolizine and naphthalene substituted catechol diethers are potent against the classical Y181C single mutant, the addition of V106A confers more resistance against the indolizine derivatives than the naphthalene derivatives. Crystal structures presented in this study highlight key features of the naphthyl group, which allow these compounds to remain potent in the double mutant, including stronger interactions with F227 and less reliance on V106 for stabilization of the ethoxy-uracil ring, which makes critical hydrogen bonds with other residues in the binding pocket.

The relative citation ratio (RCR) as a novel bibliometric among 2511 academic orthopedic surgeons.

Objectively measuring research output is important for grant awards, promotion, and tenure, or self-evaluation of productivity. However, certain shortcomings limit common bibliometric indicators. The time- and field-independent relative citation ratio (RCR) was proposed to overcome these limitations. The objective of this study was to determine whether the RCR correlates with academic rank, gender, and PhD degree status among US academic orthopedic surgeons. Full-time faculty surgeons at Accreditation Council for Graduate Medical Education-accredited orthopedic surgery residency programs were included in this study. Mean (mRCR) and weighted (wRCR) RCR scores were collected from the National Institutes of Health iCite database to quantify scholarly "impact" and "production," respectively, and were compared by academic rank, gender, and PhD status. All information was collected from publicly available faculty listings on departmental websites. A total of 2511 orthopedic surgeons from 132 residency programs were assessed. Overall, the median (interquartile range) mRCR score was 1.56 (1.05-2.12) and the median wRCR score was 27.6 (6.97-88.44). Both metrics increased with each successive academic rank, except for department chairs. There was no difference in mRCR between male and female surgeons. Among assistant professors, males had higher wRCR scores. Both metrics were higher among surgeons with a PhD degree. The RCR offers key advantages over other indices, which are reflected in differences in score distributions compared with the widely used h-index. Nevertheless, implementation of the RCR should be preceded with careful consideration of its own limitations.

Covalent Modification of the JH2 Domain of Janus Kinase 2.

Probe molecules that covalently modify the JAK2 pseudokinase domain (JH2) are reported. Selective targeting of JH2 domains over the kinase (JH1) domains is a necessary feature for ligands intended to evaluate JH2 domains as therapeutic targets. The JH2 domains of three Janus kinases (JAK1, JAK2, and TYK2) possess a cysteine residue in the catalytic loop that does not occur in their JH1 domains. Starting from a non-selective kinase binding molecule, computer-aided design directed attachment of substituents terminating in acrylamide warheads to modify Cys675 of JAK2 JH2. Successful covalent attachment was demonstrated first through observation of enhanced binding with increasing incubation time in fluorescence polarization experiments. Covalent binding also increased selectivity to as much as ca. 30-fold for binding the JAK2 JH2 domain over the JH1 domain after a 20-h incubation. Covalency was confirmed through HPLC electrospray quadrupole time-of-flight HRMS experiments, which revealed the expected mass shifts.

Synergistic effects of robotic surgery and IPACK nerve block on reduction of opioid consumption in total knee arthroplasty.

Background: There are numerous strategies to combat postoperative analgesia and expedite recovery after total knee arthroplasty (TKA). The purpose of this study was to determine opioid consumption, length of stay, and functional outcomes after robotic versus standard TKA in the setting of various regional pain modalities. Methods: A consecutive series of patients treated with unilateral primary robotic or standard TKA from January 2018-February 2021 were retrospectively identified. Regional pain modalities included peri-articular injection (PAI), adductor canal block (ACB), and infiltration between popliteal artery and capsule of knee (IPACK). Patient demographics, operative/perioperative variables, and postoperative function were recorded. Daily opiate consumption was calculated as morphine milligram equivalents (MME). Multivariate regression was performed to control for age, sex, and race. Results: After review, 283 patients (177 Females; 106 Males) were included. Robotic TKA patients received IPACK + ACB (36), while standard TKA patients received either ACB (45), IPACK + ACB (167), or PAI (35). Daily inpatient opioid consumption in the standard IPACK + ACB (p = 0.02) and robotic IPACK + ACB groups (p = 0.0001) was significantly lower compared to standard ACB. When combined with IPACK block, robotic procedures synergistically lowered opiate consumption (p = 0.004) compared to standard procedures and led to earlier discharge (p = 0.003). The robotic IPACK + ACB cohort also demonstrated improved early ambulation compared to standard ACB, (p = 0.05), whereas the same benefit was not seen for patients who received IPACK during standard TKA. Conclusions: The utilization of IPACK block decreases inpatient postoperative opioid requirements following TKA. Robotic TKA and IPACK block appeared to have a synergistic effect on opioid consumption and postoperative recovery.

Identifying Patients at Risk for Venous Thromboembolic Events After Isolated Upper Extremity Trauma: A Predictive Scale.

Previous studies have defined risk factors for development of venous thromboembolisms (VTEs) among patients with lower extremity orthopedic trauma. Limited data exist on this risk after upper extremity orthopedic trauma. A total of 269,137 incidents of upper extremity orthopedic trauma (fractures of the clavicle, scapula, humerus, elbow, or lower arm) were identified in the State Inpatient Database for 4 states included in the analysis (California, Florida, New York, and Washington) from 2006 to 2014. These patients were split into 2 cohorts, a derivation cohort (California and New York) and a validation cohort (Florida and Washington). Univariate and multivariate logistic regression analyses of risk factors for VTE within 90 days of discharge in the derivation group were used to develop the Thromboembolic Risk after Upper Extremity Trauma (TRUE-T) scale. Linear regression was used to determine fit of the TRUE-T scale to the 2 cohorts. We found that 2.61% of patients in the derivation cohort and 2.72% of patients in the validation cohort had a VTE within 90 days of discharge. Risk factors associated with increased rates of VTE were age older than 40 years, Medicare payer, anemia, chronic lung disease, coagulopathy, heart failure, malignancy, obesity, renal failure, head injury, chest injury, abdominal injury, rib fracture, humerus fracture, elbow fracture, and closed reduction. Application of the TRUE-T scale to the validation cohort showed an R2 value of 0.88. The patient factors, concomitant injuries, and fracture treatment modalities included in the TRUE-T scale can be used to identify patients at increased risk for VTE after upper extremity orthopedic trauma. [Orthopedics. 2022;45(6):345-352.].

Insights on JAK2 Modulation by Potent, Selective, and Cell-Permeable Pseudokinase-Domain Ligands.

JAK2 is a non-receptor tyrosine kinase that regulates hematopoiesis through the JAK-STAT pathway. The pseudokinase domain (JH2) is an important regulator of the activity of the kinase domain (JH1). V617F mutation in JH2 has been associated with the pathogenesis of various myeloproliferative neoplasms, but JAK2 JH2 has been poorly explored as a pharmacological target. In light of this, we aimed to develop JAK2 JH2 binders that could selectively target JH2 over JH1 and test their capacity to modulate JAK2 activity in cells. Toward this goal, we optimized a diaminotriazole lead compound into potent, selective, and cell-permeable JH2 binders leveraging computational design, synthesis, binding affinity measurements for the JH1, JH2 WT, and JH2 V617F domains, permeability measurements, crystallography, and cell assays. Optimized diaminotriazoles are capable of inhibiting STAT5 phosphorylation in both WT and V617F JAK2 in cells.

Conversion of a False Virtual Screen Hit into Selective JAK2 JH2 Domain Binders Using Convergent Design Strategies.

The Janus kinase 2 (JAK2) pseudokinase domain (JH2) is an ATP-binding domain that regulates the activity of the catalytic tyrosine kinase domain (JH1). Dysregulation of JAK2 JH1 signaling caused by the V617F mutation in JH2 is implicated in various myeloproliferative neoplasms. To explore if JAK2 activity can be modulated by a small molecule binding to the ATP site in JH2, we have developed several ligand series aimed at selectively targeting the JAK2 JH2 domain. We report here the evolution of a false virtual screen hit into a new JAK2 JH2 series. Optimization guided by computational modeling has yielded analogues with nanomolar affinity for the JAK2 JH2 domain and >100-fold selectivity for the JH2 domain over the JH1 domain. A crystal structure for one of the potent compounds bound to JAK2 JH2 clarifies the origins of the strong binding and selectivity. The compounds expand the platform for seeking molecules to regulate JAK2 signaling, including V617F JAK2 hyperactivation.

Structural Studies and Structure Activity Relationships for Novel Computationally Designed Non-nucleoside Inhibitors and Their Interactions With HIV-1 Reverse Transcriptase.

Reverse transcriptase (RT) from the human immunodeficiency virus continues to be an attractive drug target for antiretroviral therapy. June 2022 will commemorate the 30th anniversary of the first Human Immunodeficiency Virus (HIV) RT crystal structure complex that was solved with non-nucleoside reverse transcriptase inhibitor nevirapine. The release of this structure opened opportunities for designing many families of non-nucleoside reverse transcriptase inhibitors (NNRTIs). In paying tribute to the first RT-nevirapine structure, we have developed several compound classes targeting the non-nucleoside inhibitor binding pocket of HIV RT. Extensive analysis of crystal structures of RT in complex with the compounds informed iterations of structure-based drug design. Structures of seven additional complexes were determined and analyzed to summarize key interactions with residues in the non-nucleoside inhibitor binding pocket (NNIBP) of RT. Additional insights comparing structures with antiviral data and results from molecular dynamics simulations elucidate key interactions and dynamics between the nucleotide and non-nucleoside binding sites.

Detection of Elder Abuse Among Orthopedic Patients.

Approximately 10% of US adults experience elder abuse, which often manifests as musculoskeletal and soft tissue injuries. The goal of our study was to determine the rate of elder abuse among orthopedic surgery patients and characterize which patients may be at an increased risk. National Inpatient Sample Healthcare Cost and Utilization Project data from 2001 to 2015 were parsed with the Clinical Classifications Software tool. Patients 60 years and older were identified by International Classification of Diseases, Ninth Revision (ICD-9), code for elder abuse. Primary orthopedic procedures and subsequent inpatient diagnoses and comorbidities were used to develop a binary logistic regression model to predict an elder's risk of abuse. Of a total of 20,532,211 admissions for an orthopedic procedure, 0.010% (2084) were classified as elder abuse. Patients with a classification of abuse more commonly were women (74.8% vs 60.6%) and from the lowest socioeconomic quartile by income (28.5% vs 21.7%). In addition, these patients had hospital stays that were twice as long (10.2 vs 5.3 days) and had higher admission mortality rates (4.4% vs 1.2%). No primary orthopedic procedures were associated with a higher risk of elder abuse. Nonorthopedic diagnoses made during admission that were associated with increased risk of abuse included superficial injury or contusion (odds ratio [OR], 3.252), chronic skin ulcer (OR, 3.119), nutritional deficiency (OR, 3.418), fluid and electrolyte disturbances (OR, 1.729), and delirium or dementia (OR, 2.210). The incidence of elder abuse among orthopedic surgery patients is significantly lower than national estimates. This finding warrants further investigation to determine whether it is a function of underreporting or differences in patient populations, given the 4-fold increase in mortality risk. [Orthopedics. 2022;45(1):50-56.].

Cemented-augmented fixation of metastatic humeral lesions without segmental bone loss results in reliable outcomes.

Background: Treatment of metastatic lesions to the humerus is dependent on patient's pain, lesion size and location, and post-operative functional goals. Surgical options include plate or nail fixation [open reduction internal fixation (ORIF)], or endoprosthetic replacement (EPR), with cement augmentation. The objective of this study was to perform a single institution retrospective analysis of outcomes by method of reconstruction, tumor volume, and pathologic diagnosis. Methods: The records of 229 consecutive patients treated surgically for appendicular metastatic disease from 2005-2018 at our musculoskeletal oncology center were retrospectively reviewed following institutional review board (IRB) approval. Indications for surgical treatment at the humerus included patients who presented with impending and displaced pathologic fractures. Results: Sixty patients (34 male, 26 female) with a mean age of 62.9±12.2 were identified who were treated surgically at the proximal (n=21), diaphyseal (n=29), or distal (n=10) humerus. Forty-nine (82%) patients presented with displaced pathologic fractures. The remaining eleven patients had a mean Mirels score of 9.5. There was no difference in overall complication rate between EPR or ORIF [4/36 (11%) versus 2/24 (8%); P=0.725]. Mean Musculoskeletal Tumor Society (MSTS) scores were 83% for both EPR and ORIF, with no differences in subgroup analyses at the proximal, diaphyseal, or distal humerus. Patients with cortical destruction on anterior posterior (AP) and lateral imaging were at increased risk for mechanical failure [2/6 (33%) versus 0/18 (0%), P=0.015]. Conclusions: In conclusion, when pathologic pattern permits, cement-augmented fixation allows for stabilization of pathologic bone, while minimizing risk of soft-tissue detachment, while EPR resulted in similar outcomes in patients with more extensive bone destruction. Increased tumor volume was associated with lower MSTS scores.

Optimization of Triarylpyridinone Inhibitors of the Main Protease of SARS-CoV-2 to Low-Nanomolar Antiviral Potency.

Non-covalent inhibitors of the main protease (Mpro) of SARS-CoV-2 having a pyridinone core were previously reported with IC50 values as low as 0.018 µM for inhibition of enzymatic activity and EC50 values as low as 0.8 µM for inhibition of viral replication in Vero E6 cells. The series has now been further advanced by consideration of placement of substituted five-membered-ring heterocycles in the S4 pocket of Mpro and N-methylation of a uracil ring. Free energy perturbation calculations provided guidance on the choice of the heterocycles, and protein crystallography confirmed the desired S4 placement. Here we report inhibitors with EC50 values as low as 0.080 µM, while remdesivir yields values of 0.5-2 µM in side-by-side testing with infectious SARS-CoV-2. A key factor in the improvement is enhanced cell permeability, as reflected in PAMPA measurements. Compounds 19 and 21 are particularly promising as potential therapies for COVID-19, featuring IC50 values of 0.044-0.061 µM, EC50 values of ca. 0.1 µM, good aqueous solubility, and no cytotoxicity.

Structure-guided design of a perampanel-derived pharmacophore targeting the SARS-CoV-2 main protease.

There is a clinical need for direct-acting antivirals targeting SARS-CoV-2, the coronavirus responsible for the COVID-19 pandemic, to complement current therapeutic strategies. The main protease (Mpro) is an attractive target for antiviral therapy. However, the vast majority of protease inhibitors described thus far are peptidomimetic and bind to the active-site cysteine via a covalent adduct, which is generally pharmacokinetically unfavorable. We have reported the optimization of an existing FDA-approved chemical scaffold, perampanel, to bind to and inhibit Mpro noncovalently with IC50s in the low-nanomolar range and EC50s in the low-micromolar range. Here, we present nine crystal structures of Mpro bound to a series of perampanel analogs, providing detailed structural insights into their mechanism of action and structure-activity relationship. These insights further reveal strategies for pursuing rational inhibitor design efforts in the context of considerable active-site flexibility and potential resistance mechanisms.

Potent Noncovalent Inhibitors of the Main Protease of SARS-CoV-2 from Molecular Sculpting of the Drug Perampanel Guided by Free Energy Perturbation Calculations.

Starting from our previous finding of 14 known drugs as inhibitors of the main protease (Mpro) of SARS-CoV-2, the virus responsible for COVID-19, we have redesigned the weak hit perampanel to yield multiple noncovalent, nonpeptidic inhibitors with ca. 20 nM IC50 values in a kinetic assay. Free-energy perturbation (FEP) calculations for Mpro-ligand complexes provided valuable guidance on beneficial modifications that rapidly delivered the potent analogues. The design efforts were confirmed and augmented by determination of high-resolution X-ray crystal structures for five analogues bound to Mpro. Results of cell-based antiviral assays further demonstrated the potential of the compounds for treatment of COVID-19. In addition to the possible therapeutic significance, the work clearly demonstrates the power of computational chemistry for drug discovery, especially FEP-guided lead optimization.

Management of Large Segmental Bone Defects at the Knee With Intramedullary Stabilized Antibiotic Spacers During Two-Stage Treatment of Endoprosthetic Joint Infection.

BACKGROUND: Following debridement of infected prostheses that require reconstruction with an endoprosthetic replacement (EPR), instability related to segmental residual bone defects present a challenge in management with 2-stage reimplantation. METHODS: We retrospectively reviewed all patients treated for revision total joint or endoprosthetic infection at the knee from 1998 to 2018. At our institution, patients with skeletal defects >6 cm following explant of prosthesis and debridement (stage 1) were managed with intramedullary nail-stabilized antibiotic spacers. Following stage 1, antimicrobial therapy included 6 weeks of intravenous antibiotics and a minimum of 6 weeks of oral antibiotics. Following resolution of inflammatory markers and negative tissue cultures, reimplantation (stage 2) of an EPR was performed. RESULTS: Twenty-one patients at a mean age of 54 ± 21 years were treated for prosthetic joint infection at the knee. Polymicrobial growth was detected in 38% of cases, followed by coagulase-negative staphylococci (24%) and Staphylococcus aureus (19%). Mean residual skeletal defect after stage 1 treatment was 20 cm. Prosthetic joint infection eradication was achieved in 18 (86%) patients, with a mean Musculoskeletal Tumor Society score of 77% and mean knee range of motion of 100°. Patients with polymicrobial infections had a greater number of surgeries prior to infection (P = .024), and were more likely to require additional debridement prior to EPR (odds ratio 12.0, P = .048). CONCLUSION: Management of large segmental skeletal defects at the knee following explant using intramedullary stabilized antibiotic spacers maintain stability and result in high rates of limb salvage with conversion to an endoprosthesis.

Covalent Inhibition of Wild-Type HIV-1 Reverse Transcriptase Using a Fluorosulfate Warhead.

Covalent inhibitors of wild-type HIV-1 reverse transcriptase (CRTIs) are reported. Three compounds derived from catechol diether non-nucleoside inhibitors (NNRTIs) with addition of a fluorosulfate warhead are demonstrated to covalently modify Tyr181 of HIV-RT. X-ray crystal structures for complexes of the CRTIs with the enzyme are provided, which fully demonstrate the covalent attachment, and confirmation is provided by appropriate mass shifts in ESI-TOF mass spectra. The three CRTIs and six noncovalent analogues are found to be potent inhibitors with both IC50 values for in vitro inhibition of WT RT and EC50 values for cytopathic protection of HIV-1-infected human T-cells in the 5-320 nM range.

Evaluating the Readability of Online Patient Education Materials Related to Orthopedic Oncology.

The internet is increasingly used to access patient education materials. The average American reading level has been found to be that of a 7th- to 8th-grade student, prompting the National Institutes of Health (NIH) and the American Medical Association (AMA) to advise that patient education materials be written between the 4th- to 6th-grade reading level. The purpose of this study was to evaluate the reading level of current patient education materials for the most common musculoskeletal oncological tumors. A Google search was performed with all location filters off to account for geographic variability for patient education materials related to 28 orthopedic primary or secondary tumors. All patient education articles from the first 10 website hits for each tumor type were analyzed. Patient education materials from these websites were evaluated using 8 validated readability scales. Patient resources were found to be written at an average grade level nearly double the NIH and AMA recommendation. Patient education materials for soft tissue chondromas were written at the highest level (14.8±1.9), whereas education materials for chordomas (10.1±1.0) most closely approached national recommendations, despite still being written at a readability level nearly 4 grade levels higher than has been recommended. The Flesch Reading Ease assessment provided a mean score of 46.5±7.7, corresponding with a "difficult to read" result. Current patient education materials regarding oncological musculoskeletal-related patient education materials are written significantly above the recommended reading level. Further modification of these resources is warranted to ensure adequate comprehension and informed decision making in the clinical setting. [Orthopedics. 2021;44(1):38-42.].

Identification of 14 Known Drugs as Inhibitors of the Main Protease of SARS-CoV-2.

A consensus virtual screening protocol has been applied to ca. 2000 approved drugs to seek inhibitors of the main protease (Mpro) of SARS-CoV-2, the virus responsible for COVID-19. 42 drugs emerged as top candidates, and after visual analyses of the predicted structures of their complexes with Mpro, 17 were chosen for evaluation in a kinetic assay for Mpro inhibition. Remarkably 14 of the compounds at 100-µM concentration were found to reduce the enzymatic activity and 5 provided IC50 values below 40 µM: manidipine (4.8 µM), boceprevir (5.4 µM), lercanidipine (16.2 µM), bedaquiline (18.7 µM), and efonidipine (38.5 µM). Structural analyses reveal a common cloverleaf pattern for the binding of the active compounds to the P1, P1', and P2 pockets of Mpro. Further study of the most active compounds in the context of COVID-19 therapy is warranted, while all of the active compounds may provide a foundation for lead optimization to deliver valuable chemotherapeutics to combat the pandemic.

Identification of 14 Known Drugs as Inhibitors of the Main Protease of SARS-CoV-2.

A consensus virtual screening protocol has been applied to ca. 2000 approved drugs to seek inhibitors of the main protease (M pro ) of SARS-CoV-2, the virus responsible for COVID-19. 42 drugs emerged as top candidates, and after visual analyses of the predicted structures of their complexes with M pro , 17 were chosen for evaluation in a kinetic assay for M pro inhibition. Remarkably 14 of the compounds at 100-µM concentration were found to reduce the enzymatic activity and 5 provided IC 50 values below 40 µM: manidipine (4.8 µM), boceprevir (5.4 µM), lercanidipine (16.2 µM), bedaquiline (18.7 µM), and efonidipine (38.5 µM). Structural analyses reveal a common cloverleaf pattern for the binding of the active compounds to the P1, P1', and P2 pockets of M pro . Further study of the most active compounds in the context of COVID-19 therapy is warranted, while all of the active compounds may provide a foundation for lead optimization to deliver valuable chemotherapeutics to combat the pandemic.

An Analysis of Trends in National Residency Matching Program Match Data for Orthopedic Surgery.

Due to electronic residency applications, US Medical Licensing Examination Step 1 scores are frequently used by orthopedic surgery program directors to screen applicants. Prospective applicants therefore often use Step 1 scores as a proxy for specialty competitiveness. The goal of this investigation was two-fold: (1) to determine whether trends in Step 1 scores are indicative of trends in competitiveness of orthopedic surgery and (2) to report the characteristics that optimize a US medical student's match success. A retrospective review of published National Resident Matching Program data from 2009 to 2018 was performed for orthopedic surgery residency applicants. Additional data from the Charting Outcomes reports were used for specific analyses of applicant characteristics. From 2009 to 2018, the number of orthopedic surgery residency positions grew at an annual rate of 1.51% (95% confidence interval [CI], 1.37% to 1.64%; P<.001), accommodating the 1.26% (95% CI, 0.63% to 1.90%; P=.006) annual increase in the number of applicants who ranked orthopedic surgery as their preferred specialty choice (only choice or first choice). There were no significant changes in the applicant-to-position ratio (95% CI, -0.85% to 0.37%; P=.483) or the match rate for US seniors who ranked orthopedic surgery as their preferred choice (95% CI, -0.23% to 0.87%; P=.313). Increases in mean Step 1 scores of matched orthopedic surgery applicants parallel national Step 1 growth trends (0.49% vs 0.44%, respectively). Although orthopedic surgery is currently a competitive specialty to match into, this has been the case since 2009. Increasing Step 1 scores of matched applicants is not unique to orthopedic surgery and should not be misinterpreted as a proxy for increasing competitiveness of the specialty. [Orthopedics. 2020;43(6):e616-e622.].