The Association Between Surgeon Volume and Dislocation After Total Hip Arthroplasty: A Nationwide Evaluation of 5,106 Orthopaedic Surgeons.

INTRODUCTION: The relationship between surgeon volume and risk of dislocation after total hip arthroplasty (THA) is debated. This study sought to characterize this association and assess patient outcomes using a nationwide patient and surgeon registry. METHODS: The Premier Healthcare Database was queried for adult primary elective THA patients from January 1, 2016, to December 31, 2019. Annual surgeon volume and 90-day risk of dislocation were modeled using multivariable logistic regression with restricted cubic splines. Bootstrap analysis identified a threshold annual case volume, corresponding to the maximum decrease in dislocation risk. Surgeons with an annual volume greater than the threshold were deemed high volume, and those with an annual volume less than the threshold were low volume. Each surgeon within a given year was treated as a unique entity (surgeon-year unit). 90-day complications of patients treated by high-volume and low-volume surgeons were compared. RESULTS: From 2016 to 2019, 352,131 THAs were performed by 5,106 surgeons. The restricted cubic spline model demonstrated an inverse relationship between risk of dislocation and surgeon volume (threshold: 109 cases per year). A total of 9,967 (87.8%) low-volume surgeon-year units had individual dislocation rates lower than the average of the entire surgeon cohort. Patients treated by high-volume surgeons had decreased risk of dislocation (adjusted odds ratio [aOR], 0.60; 95% CI, 0.54 to 0.67), periprosthetic fracture (aOR, 0.87; 95% CI, 0.76 to 0.99), periprosthetic joint infection (aOR, 0.63; 95% CI, 0.56 to 0.69), readmission (aOR, 0.70; 95% CI, 0.67 to 0.73), and in-hospital death (aOR, 0.60; 95% CI, 0.46 to 0.80). CONCLUSION: While most of the low-volume surgeons had dislocation rates lower than the cohort average, increasing annual surgeon case volume was associated with a reduction in risk of dislocation after primary elective THA. THERAPEUTIC LEVEL OF EVIDENCE: Level IV.

Patients with Hip Osteoarthritis Have a Higher Rate of Spinal Reoperation Following Lumbar Spinal Fusion.

BACKGROUND: Lumbar spinal pathology is known to affect outcomes following total hip arthroplasty (THA). However, the effect of hip osteoarthritis (OA) on outcomes following lumbar fusion has not been well studied. The purpose of this study was to determine the association between hip OA and spinal reoperation following lumbar spinal fusion. METHODS: The 5% Medicare Part B claims database was queried for all patients who underwent primary elective lumbar fusion from 2005 to 2019. Patients were divided into 2 groups: those who underwent elective THA within 1 year after primary lumbar fusion, indicating that they had severe hip OA at the time of lumbar fusion, and those who underwent lumbar fusion with no diagnosed hip OA and no THA during the study period. Exclusion criteria included THA as a result of trauma, revision THA or primary THA in the 5-year period before primary lumbar fusion, <65 years of age, and no enrollment in the database for 5 years before and 1 year after primary lumbar fusion. The primary outcome was spinal reoperation within 1, 3, and 5 years. Multivariable Cox regression was performed with age, sex, diabetes, heart disease, obesity, smoking status, osteoporosis, number of levels fused, use of posterior instrumentation, use of an interbody device, use of bone graft, and surgical approach as covariates. RESULTS: Overall, 1,123 patients (63.4% female; 91.3% White; mean age, 76.8 ± 4.1 years) were included in the hip OA group and 8,893 patients (56.2% female; 91.3% White; mean age, 74.8 ± 4.9 years) were included in the control group. After multivariable analysis, patients with severe hip OA had significantly greater rates of revision surgery at 3 years (odds ratio [OR], 1.61; p < 0.001) and 5 years (OR, 1.87; p < 0.001) after the index lumbar fusion. CONCLUSIONS: Patients with severe hip OA at the time of primary lumbar fusion had a significantly increased risk of spinal reoperation at 3 and 5 years postoperatively. These data provide further evidence to support performing THA prior to lumbar fusion in the unsettled debate regarding which surgery should be prioritized for patients with simultaneous degenerative diseases of the hip and lumbar spine. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Risk Factors Associated with Thromboembolic Complications After total Hip Arthroplasty: An Analysis of 1,129 Pulmonary Emboli.

INTRODUCTION: Venous thromboembolism (VTE) remains a dangerous complication after total hip arthroplasty (THA), despite advances in chemoprophylactic measures. This study aimed to identify risk factors of developing pulmonary embolism (PE) and deep vein thrombosis (DVT) after THA using a modern cohort of patients reflecting contemporary practices. METHODS: The Premier Healthcare Database was queried for primary, elective THAs from January 1st, 2015, to December 31st, 2021. Patients who developed PE or DVT within 90 days of THA were compared with patients who did not develop any postoperative VTE. Differences in patient demographics, comorbidities, hospital factors, perioperative medications, chemoprophylactic agents, and allogeneic blood transfusion were compared between cohorts. Multivariable logistic regression models were used to identify independent risk factors of PE and DVT. In total, 544,298 THAs were identified, of which 1,129 (0.21%) developed a PE and 1,799 (0.33%) developed a DVT. RESULTS: Patients diagnosed with a PE had significantly higher rates of in-hospital death (2.6% vs 0.1%, P < 0.001) compared with those without a PE. Age (adjusted odds ratio: 1.02 per year, 95% confidence interval [CI]: 1.01 to 1.03) and Black race (aOR: 1.52, 95% CI: 1.24 to 1.87) were associated with an increased risk of PE. Comorbidities associated with increased risk of PE included chronic pulmonary disease (aOR: 1.58, 95% CI: 1.36 to 1.84), pulmonary hypertension (aOR: 2.06, 95% CI: 1.39 to 3.04), and history of VTE (aOR: 2.38, 95% CI: 1.98 to 2.86). Allogeneic blood transfusion (aOR: 2.40, 95% CI: 1.88 to 3.06) was also associated with an increased risk of PE while dexamethasone utilization was associated with a reduced risk (aOR: 0.83, 95% CI: 0.73 to 0.95). DISCUSSION: Increasing age; Black race; allogeneic blood transfusion; and comorbidities, including chronic pulmonary disease, pulmonary hypertension, and history of VTE, were independent risk factors of PE after THA. Given the increased mortality associated with PE, patients should be carefully evaluated for these factors and managed with an appropriate chemoprophylactic regimen.

An Updated Estimate of Total Hip and Total Knee Arthroplasty Inpatient Case Volume During the 2020 COVID-19 Pandemic in the United States.

Background: Inpatient total hip arthroplasty (THA) and total knee arthroplasty (TKA) practices were dramatically affected in the United States in 2020 as elective surgeries were paused in response to the COVID-19 pandemic. This study sought to provide an updated estimate of inpatient total joint arthroplasty (TJA) case volumes in the United States in 2020. Methods: A retrospective cohort study was performed by identifying all adult patients who underwent primary, elective TJA from January 1st, 2017 to December 31st, 2020, using the National Inpatient Sample. Monthly and annual case volumes were reported with descriptive statistics. Baseline case volumes were established by taking the average number of monthly cases performed in 2017, 2018, and 2019. These monthly averages were compared to 2020 values. Results: From 2017 to 2019, the average case volume was 1,056,669 cases per year (41.0% THA, 59.0% TKA) and 88,055 cases per month. In 2020, 535,441 cases were identified (45.4% THA, 54.6% TKA), corresponding to a 49.3% reduction from the 2017-2019 annual average. Monthly cases decreased to 4515 in April during the "first wave" of COVID-19, corresponding to a 94.8% decrease from prior years. In June, cases rebounded to 55,520 before decreasing again in July to 50,100 during the "second wave" of COVID-19. During the "third wave," COVID-19 cases decreased month-over-month from October through December (56.5% decrease). Conclusions: This updated estimate identified a 49.3% decrease in inpatient TJA cases in 2020 compared to prior years. This is similar to the 46.5-47.7% decrease in case volume previously reported.

Robotic-Assisted Total Knee Arthroplasty in Obese Patients.

Background: Robotic-assisted systems have gained popularity in total knee arthroplasty (TKA). The purpose of this study was to evaluate operative characteristics and radiographic outcomes of obese patients undergoing robotic-assisted TKA. Methods: A retrospective review of consecutive cases performed by a single surgeon was performed from January 1, 2016, to January 31, 2022. Adult patients with body mass index ≥35 kg/m2 who underwent primary TKA using a computed tomography-assisted robotic system were compared to patients who underwent primary TKA using conventional instrumentation. Demographics, preoperative and postoperative radiographic measurements, and intraoperative outcomes were compared between cohorts. In total, 119 patients were identified, 60 in the robotic-assisted cohort and 59 in the conventional instrumentation cohort. Results: Age, body mass index, and estimated blood loss were not significantly different between the cohorts. The robotic-assisted cohort experienced longer tourniquet times (93.3 vs 75.5 minutes, P < .001). Preoperative hip-knee-ankle angle (HKA) was similar between the robotic-assisted and conventional cohorts (8.4° ± 4.9° vs 9.3° ± 5.3°, P = .335). Postoperative HKA was 2.0° ± 1.4° in the robotic-assisted group and 3.1° ± 3.23° in the conventional group (P = .040). The proportion of patients with postoperative HKA > 3° of varus or valgus was 9 of 60 (15.0%) in the robotic-assisted cohort compared to 18 of 59 (30.5%) using conventional instrumentation (P = .043). Conclusions: Obese patients treated with robotic-assisted TKA had postoperative alignment closer to neutral and fewer postoperative radiographic outliers than patients treated with conventional instrumentation. The results of this study support use of robotic-assisted technologies in TKA, particularly in obese patients.

Intravenous tranexamic acid reduces complications following surgical treatment of pathologic fractures of the lower extremity.

BACKGROUND AND OBJECTIVES: This study aimed to evaluate the postoperative complications associated with administering intravenous (IV) tranexamic acid (TXA) in patients undergoing surgical fixation for neoplastic pathologic fractures of the lower extremities. METHODS: Patients ≥18 years old who underwent surgical intervention for neoplastic pathologic lower extremity fractures from 2015 to 2021 were identified using the Premier Healthcare Database. This cohort was divided by TXA receipt on the index surgery day. Patient demographics, hospital factors, patient comorbidities, and 90-day complications were assessed and compared between the cohorts. RESULTS: From 2015 to 2021, 4497 patients met inclusion criteria (769 TXA[+] and 3728 TXA[-]). Following propensity score matching, patients who received TXA had a significantly shorter length of stay than those who did not (7.6 ± 7.3 days vs. 9.0 ± 15.2, p = 0.036). Between the two cohorts, there were no significant differences in comorbidities. Regarding differences in postoperative complications, TXA(+) patients had significantly decreased odds of deep vein thrombosis (DVT) (1.87% vs. 5.46%; odds ratio [OR]:0.33; 95% confidence interval: 0.17-0.62; p = 0.001). CONCLUSION: Administration of IV TXA may be associated with a decreased risk of postoperative DVT without an increased risk of other complications. Orthopedic surgeons should consider the utilization of IV TXA in patients treated surgically for neoplastic pathologic fractures of the lower extremity.

Dexamethasone-Associated Hyperglycemia is Not Associated With Infectious Complications After Total Joint Arthroplasty in Diabetic Patients.

BACKGROUND: Postoperative infection is a devastating complication of total joint arthroplasty (TJA). Perioperative use of dexamethasone in patients who have diabetes mellitus (DM) remains controversial due to concern for increased infection risk. This study aimed to evaluate the association between dexamethasone and infection risk among patients who have DM undergoing TJA. METHODS: This was a retrospective cohort study conducted on adult patients who underwent primary, elective total knee arthroplasty (TKA) or total hip arthroplasty (THA) between January 2016 and December 2021 using a large national database. We identified 110,568 TJA patients (TKA: 66.6%; THA: 33.4%), 31.0% (34,298) of which had DM. Patients who received perioperative dexamethasone were compared to those who did not. The primary end points were the 90-day risk of postoperative periprosthetic joint infection, surgical site infection (SSI), and other non-SSI (urinary tract infection, pneumonia, sepsis). RESULTS: When modeling the association between dexamethasone exposure and study outcomes while accounting for the interaction between dexamethasone and morning blood glucose levels, dexamethasone administration conferred no increased odds of postoperative periprosthetic joint infection nor SSI in diabetics. However, dexamethasone significantly lowered the adjusted odds of other postoperative infections in diabetic patients (TKA: adjusted odds ratio = 09, 95% confidence interval = 0.8 to 1.0, P = .030; THA: adjusted odds ratio = 0.7, 95% confidence interval = 0.6 to 0.9, P = .001); specifically in patients with morning blood glucose levels between 110 to 248 mg/dL in TKA and ≤ 172 mg/dL in THA. CONCLUSIONS: This study provides strong evidence against withholding dexamethasone in diabetic patients undergoing TJA based on concern for infection. Instead, short-course perioperative dexamethasone reduced infection risk in select patients. The narrative surrounding dexamethasone should shift away from questions about whether dexamethasone is appropriate for diabetic patients, and instead focus on how best to optimize its use.

Total Hip and Total Knee Arthroplasty Outpatient Case Volume During the 2020 COVID-19 Pandemic in New York and California.

BACKGROUND: Inpatient total hip and total knee arthroplasty were substantially impacted by the SARS-CoV-2 (COVID-19) pandemic. We sought to characterize the transition of total joint arthroplasty (TJA) to the outpatient setting in 2 large state health systems during this pandemic. METHODS: Adult patients who underwent primary elective TJA between January 1, 2016 and December 31, 2020 were retrospectively reviewed using the New York Statewide Planning and Research Cooperative System and California Department of Health Care Access and Information datasets. Yearly inpatient and outpatient case volumes and patient demographics, including age, sex, race, and payer coverage, were recorded. Continuous and categorical variables were compared using descriptive statistics. Significance was set at P < .05. RESULTS: In New York during 2020, TJA volume decreased 16% because 22,742 fewer inpatient TJAs were performed. Much of this lost volume (46.6%) was offset by a 166% increase in outpatient TJA. In California during 2020, TJA volume decreased 20% because 34,114 fewer inpatient TJAs were performed. Much of this lost volume (37%) was offset by a 47% increase in outpatient TJA. CONCLUSIONS: This present study demonstrates a marked increase in the proportion of TJA being performed on an outpatient basis in both California and New York. In both states, despite a decrease in overall TJA volume in 2020, outpatient TJA volume increased markedly. LEVEL OF EVIDENCE: Therapeutic Level IV, Retrospective Cohort Study.

Tranexamic Acid Is Safe in Patients with a History of Venous Thromboembolism Undergoing Total Joint Arthroplasty.

BACKGROUND: Tranexamic acid (TXA) is increasingly utilized during total knee arthroplasty (TKA) and total hip arthroplasty (THA) to decrease blood loss; however, there are concerns with regard to potential thromboembolic complications, particularly in high-risk patients. This study sought to define a subset of patients at elevated risk for thromboembolic complications following total joint arthroplasty (TJA) and to compare postoperative outcomes between patients who received TXA and those who did not. METHODS: Patients who underwent primary, elective TJA from 2015 to 2021 were identified in the Premier Healthcare Database. Patients with a history of venous thromboembolism, defined as a history of pulmonary embolism or deep vein thrombosis, were identified and formed the high-risk cohort. Patient demographic characteristics, hospital factors, patient comorbidities, antithrombotic medication use, perioperative blood transfusion, and 90-day complications were assessed and compared between patients who received TXA and those who did not. Univariate regression and multivariable regression were performed to account for potential confounders. RESULTS: The high-risk cohort comprised 70,759 patients who underwent TJA, of whom 46,074 (65.1%) received TXA and 24,685 (34.9%) did not. After controlling for confounding factors, patients in the TXA cohort had similar risks of pulmonary embolism (adjusted odds ratio [OR], 0.90 [95% confidence interval (CI), 0.79 to 1.02]; p = 0.097), stroke (adjusted OR, 0.97 [95% CI, 0.69 to 1.37]; p = 0.867), and myocardial infarction (adjusted OR, 0.93 [95% CI, 0.69 to 1.24]; p = 0.614) compared with patients who did not receive TXA. Patients who received TXA demonstrated decreased risks of transfusion (adjusted OR, 0.42 [95% CI, 0.38 to 0.46]; p < 0.001) and 90-day readmission (adjusted OR, 0.87 [95% CI, 0.80 to 0.94]; p < 0.001). CONCLUSIONS: TXA utilization was not associated with an increased risk of postoperative pulmonary embolism, stroke, or myocardial infarction in patients with a history of venous thromboembolism. Furthermore, patients who received TXA had a decreased risk of transfusion and readmission. This evidence suggests that TXA may be safely utilized among select high-risk patients. LEVEL OF EVIDENCE: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Limited Durability of Extensor Mechanism Reconstruction Following Total Knee Arthroplasty: Mesh and Allograft Show Equivalent Outcomes at Five-Year Follow-Up.

BACKGROUND: Extensor mechanism disruption is a challenging complication following total knee arthroplasty. The purpose of this study was to compare outcomes between patients who received mesh versus allograft extensor mechanism reconstruction. METHODS: All patients who underwent extensor mechanism reconstruction at a single institution were screened. Demographic and surgical variables were recorded, including technique (ie, synthetic mesh versus allograft reconstruction). Patients were assessed for preoperative and postoperative extensor lag, revision, and duration of follow-up. Analyses, including Kaplan-Meier survivorships, were performed to compare mesh to allograft reconstruction. In total, 50 extensor mechanism reconstructions (30 mesh and 20 allograft) were conducted between January 1st, 2001, and December 31st, 2022. RESULTS: There were no differences between the cohorts with respect to revision (26.7 [8 of 30] versus 35.0% [7 of 20], P = .680) or failure defined as above knee amputation or fusion (6.7 [2 of 30] versus 5.0% [1 of 20], P = .808). There were also no differences in time to reoperation (average 27 months [range, 6.7 to 58.8] versus 29 months [range, 1.2 to 84.9], P = .910) or in postoperative extensor lag among patients who did not undergo a reoperation (13 [0 to 50] versus 11° [0 to 30], P = .921). The estimated 5-year Kaplan-Meier survival with extensor mechanism revision as the endpoint was similar between the 2 groups (52.1, 95% confidence interval [CI] = 25.4 to 73.3 versus 55.0%, 95% CI = 23.0 to 78.4%, P = .990). CONCLUSIONS: The purpose of this study was to present the findings of a large cohort of patients who required extensor mechanism reconstruction. Regardless of the reconstruction type, the 5-year outcomes of patients requiring extensor mechanism reconstruction are suboptimal.

Same-Day Total Joint Arthroplasty in the United States From 2016 to 2020: The Impact of the Medicare Inpatient Only List and the COVID-19 Pandemic.

BACKGROUND: Same-day total hip arthroplasty (THA) and total knee arthroplasty (TKA) continue to gain popularity in the United States. The present study sought to quantify recent same-day outpatient trends taking into consideration the COVID-19 pandemic as well as the removal of these procedures from the Medicare inpatient only (IPO) list. METHODS: Patients undergoing primary elective TKA and THA were identified using the Nationwide Ambulatory Surgery Sample and the National Inpatient Sample from January 1, 2016, to December 31, 2020. The same-day cohort included Nationwide Ambulatory Surgery Sample and National Inpatient Sample patients with a length of stay = 0 days. The inpatient cohort included patients with length of stay ≥1 day. National estimates were extrapolated using weight functions. RESULTS: From January 2016 to December 2020, the proportion of same-day TKA increased from 1.2 (719) to 62.4% (31,293) and the proportion of same-day THA increased from 2.0 (599) to 54.5% (18,252). Following removal from the Medicare IPO list, same-day TKAs increased from 3.2% (1,895) in December 2017 to 13.8% (9,269) in January 2018, and same-day THAs increased from 10.7% (4,295) in December 2019 to 22.5% (8,708) in January 2020. Between February and March 2020, same-day TKAs increased from 42.4 (26,148) to 44.4% (16,972) and same-day THAs increased from 28.5 (10,729) to 30.2% (7,409). CONCLUSIONS: The proportion of same-day TKA and THA dramatically increased following removal from the Medicare IPO list and in response to the COVID-19 pandemic. By December 2020, same-day TKA and THA accounted for >50% of all cases performed in the United States.

Development and validation of a novel TNM staging N-classification of oral cavity squamous cell carcinoma.

BACKGROUND: For oral cavity squamous cell carcinoma (OSCC), extent of extranodal extension (ENE) (minor, ≤2 mm; major, >2 mm) is differentially prognostic, whereas limitations exist with the 8th edition of American Joint Committee on Cancer/International Union Against Cancer TNM N-classification (TNM-8-N). METHODS: Resected OSCC patients at four centers were included and extent of ENE was recorded. Thresholds for optimal overall survival (OS) discrimination of lymph node (LN) features were established. After dividing into training and validation sets, two new N-classifications were created using 1) recursive partitioning analysis (RPA), and 2) adjusted hazard ratios (aHRs) and were ranked against TNM-8-N and two published proposals. RESULTS: A total of 1460 patients were included (pN0: 696; pN+: 764). Of the pN+ cases, 135 (18%) had bilateral/contralateral LNs; 126 (17%) and 244 (32%) had minor and major ENE, and two (0.3%) had LN(s) >6 cm without ENE (N3a). LN number (1 and >1 vs. 0: aHRs, 1.92 [95% confidence interval (CI), 1.44-2.55] and 3.21 [95% CI, 2.44-4.22]), size (>3 vs. ≤3 cm: aHR, 1.88 [95% CI, 1.44-2.45]), and ENE extent (major vs. minor: aHR, 1.40 [95% CI, 1.05-1.87]) were associated with OS, whereas presence of contralateral LNs was not (aHR, 1.05 [95% CI, 0.81-1.36]). The aHR proposal provided optimal performance with these changes to TNM-8-N: 1) stratification of ENE extent, 2) elimination of N2c and 6-cm threshold, and 3) stratification of N2b by 3 cm threshold. CONCLUSION: A new N-classification improved staging performance compared to TNM-8-N, by stratifying by ENE extent, eliminating the old N2c category and the 6 cm threshold, and by stratifying multiple nodes by size.

Higher Blood Glucose Levels on the Day of Surgery Are Associated with an Increased Risk of Periprosthetic Joint Infection After Total Hip Arthroplasty.

BACKGROUND: Hyperglycemia has been identified as a risk factor for periprosthetic joint infection (PJI) after total hip arthroplasty (THA). However, there is no consensus with regard to the preoperative blood glucose level (BGL) on the day of the surgical procedure associated with increased risk. We sought to identify preoperative BGL thresholds associated with an increased risk of PJI. METHODS: The Premier Healthcare Database was retrospectively queried for adult patients who underwent primary, elective THA and had a measurement of the preoperative BGL recorded on the day of the surgical procedure (preoperative BGL) from January 1, 2016, to December 31, 2021. The association between preoperative BGL and 90-day PJI risk was modeled using multivariable logistic regression with restricted cubic splines. Patients with and without diabetes with a preoperative BGL associated with 1.5 times greater odds of PJI (high preoperative BGL) were then compared with patients with a normal preoperative BGL. RESULTS: In this study, 90,830 patients who underwent THA and had a recorded preoperative BGL were identified. The preoperative BGL associated with 1.5 times greater odds of PJI was found to be 277 mg/dL in patients with diabetes and 193 mg/dL in patients without diabetes. Compared with the normal preoperative BGL cohort, those with high preoperative BGL had increased odds of PJI (adjusted odds ratio [OR], 2.60 [95% confidence interval (CI), 1.45 to 4.67] for patients with diabetes and 1.66 [95% CI, 1.10 to 2.51] for patients without diabetes) and 90-day readmissions (adjusted OR, 1.92 [95% CI, 1.45 to 2.53] for patients with diabetes and 1.66 [95% CI, 1.37 to 2.00] for patients without diabetes). CONCLUSIONS: Increased preoperative BGL was found to be associated with an increased risk of PJI following primary THA. Surgeons should be aware of patients with diabetes and a preoperative BGL of >277 mg/dL and patients without diabetes but with a preoperative BGL of >193 mg/dL. LEVEL OF EVIDENCE: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

ORFeus: a computational method to detect programmed ribosomal frameshifts and other non-canonical translation events.

BACKGROUND: In canonical protein translation, ribosomes initiate translation at a specific start codon, maintain a single reading frame throughout elongation, and terminate at the first in-frame stop codon. However, ribosomal behavior can deviate at each of these steps, sometimes in a programmed manner. Certain mRNAs contain sequence and structural elements that cause ribosomes to begin translation at alternative start codons, shift reading frame, read through stop codons, or reinitiate on the same mRNA. These processes represent important translational control mechanisms that can allow an mRNA to encode multiple functional protein products or regulate protein expression. The prevalence of these events remains uncertain, due to the difficulty of systematic detection. RESULTS: We have developed a computational model to infer non-canonical translation events from ribosome profiling data. CONCLUSION: ORFeus identifies known examples of alternative open reading frames and recoding events across different organisms and enables transcriptome-wide searches for novel events.

Pharmacokinetic and Ocular Toxicity Evaluation of Latanoprost Ophthalmic Solution, 0.005%, with Preservative Level Reduced to Below the Limit of Quantitation.

Purpose: The systemic and ocular pharmacokinetics (PK), and ocular toxicity of benzalkonium chloride (BAK)-free TearClear latanoprost ophthalmic solution, 0.005% formulation (TC-002) were evaluated. TC-002 is designed to selectively capture BAK at the time of drug administration; therefore, the dose delivered to the eye contains no quantifiable level of preservative. Methods: The systemic and ocular PK of TC-002 were compared to a BAK containing reference listed drug (RLD, Xalatan™) over a 24-h period, after a single topical ocular dose to 1 eye of male Dutch Belted (DB) rabbits (n = 3/timepoint). Latanoprost acid concentrations were measured in plasma and ocular tissues. The ocular toxicity was evaluated in a separate study and included toxicokinetic evaluation of TC-002 after once daily topical ocular dosing into each eye of DB rabbits (n = 8/group) for at least 28 days. Toxicity endpoints included ophthalmic and clinical evaluations, necropsy, and microscopic evaluation of ocular tissues. Results: Average ratios of Cmax values for TC-002/RLD ranged from 0.6 to 1.6, and Cmax and area under the concentration-time curve of last observed concentration (AUClast) exposures to latanoprost acid were similar (<2-fold) between the 2 treatments. In the 28-day study, the Tmax was achieved in both groups in <0.5 h. There were no abnormal ocular findings. Conclusions: TC-002 with no quantifiable preservative or BAK-containing RLD exhibited similar ocular and systemic PK profiles. TC-002 was well tolerated and comparable to RLD. TC-002 retains the safety and PK characteristics of RLD without the added concern of long-term exposure of the eye to preservatives.

Increased Risk of Venous Thromboembolism in Patients with Postoperative Anemia After Total Joint Arthroplasty: Are Transfusions to Blame?

BACKGROUND: The relationship between anemia and the risk of venous thromboembolism (VTE) following total knee arthroplasty (TKA) and total hip arthroplasty (THA) remains unclear. Red blood cell (RBC) transfusions, which have been shown to have thrombogenic effects, may explain conflicting data. This study sought to elucidate the relationship between anemia, RBC transfusions, and VTE following total joint arthroplasty (TJA). METHODS: Using the International Classification of Diseases, Tenth Revision (ICD-10) and Current Procedural Terminology (CPT) codes, the Premier Healthcare Database was queried for all adults who underwent primary elective THA or TKA from January 2015 to December 2020. Patients were classified into 3 cohorts: those who did not have a diagnosis of anemia and did not receive an RBC transfusion (the control group), those with acute blood loss anemia who did not receive a transfusion (the anemia without transfusion group), and those with acute blood loss anemia who did receive a transfusion (the anemia with transfusion group). The primary outcomes assessed were the 90-day rate and risk of deep vein thrombosis (DVT), pulmonary embolism (PE), and aggregate VTE. Analysis of variance and pairwise comparisons were used to compare groups. Multivariable analyses were performed to account for confounding factors. RESULTS: The 1,290,815 patients identified as having undergone TJA included 1,078,507 control patients (83.6%), 198,233 patients who had anemia without transfusion (15.4%), and 14,075 patients who had anemia and transfusion (1.1%). Age, sex, race, length of hospital stay, and hospital costs were significantly different between the 3 groups. After adjusting for confounding factors, there was no difference between the anemia without transfusion group and the control group with regard to DVT (adjusted odds ratio [OR], 0.97 [95% confidence interval (CI), 0.89 to 1.06]; p = 0.500), PE (adjusted OR, 1.04 [95% CI, 0.92 to 1.18]; p = 0.543), and VTE (adjusted OR, 0.99 [95% CI, 0.92 to 1.06]; p = 0.697). However, patients with anemia and transfusion had an increased risk of PE (adjusted OR, 1.83 [95% CI, 1.34 to 2.51]; p < 0.001) and VTE (adjusted OR, 1.39 [95% CI, 1.14 to 1.70]; p = 0.001) compared with patients in the control group. CONCLUSIONS: Patients with acute blood loss anemia who received a transfusion were at increased risk for developing VTE following TJA, whereas patients with anemia who did not receive a transfusion were not. Orthopaedic surgeons need to be aware of the risks of transfusion and individualize the use of transfusions in their patients. LEVEL OF EVIDENCE: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Complications of cryoprobe cryoablation as a surgical adjuvant for the treatment of metastatic carcinoma to bone, benign bone tumors, and soft tissue tumors: A series of 148 patients.

BACKGROUND AND OBJECTIVE: This study describes the complication profile of modern cryoablation utilizing probes as an adjuvant during open surgical treatment of orthopedic tumors. METHODS: A retrospective, single-surgeon study was performed for patients receiving cryoprobe cryoablation. Demographic information, malignancy-related and operative details, and clinical courses were collected. Outcomes assessed included rates of complications, recurrence, and correlations between the number of probes or cryoablation cycles performed. RESULTS: In this 148-patient study, 67.6% had metastatic carcinoma to bone, 27.7% had benign bone tumors, and 4.7% had soft tissue tumors. An average of 3.4 ± 1.7 cryoablation probes were utilized and 1.7 ± 0.6 freezing cycles were performed. The overall cohort aggregate complication rate was 16.9%. These complications included postoperative fracture (3.4%), nerve palsy (2.7%), wound complications (7.4%), and infection (3.4%). The number of cycles and probes was significantly correlated with the incidence of aggregate complications in the overall cohort (Pearson = 0.162, p = 0.049) and metastatic bone cohort (Pearson = 0.222, p = 0.027). There were 13 recurrences. CONCLUSION: This study describes the complication rates involving cryoablation probes used as surgical adjuvants. Greater probe number usage was correlated with increased aggregate complications in patients with metastatic disease to bone; meanwhile, more treatment cycles were associated with increased aggregate complications in the overall cohort.

Complications and Safety of Simultaneous Bilateral Total Knee Arthroplasty: A Patient Characteristic and Comorbidity-Matched Analysis.

BACKGROUND: Total knee arthroplasty (TKA) is a highly successful surgical procedure that decreases pain and improves function. Many patients who undergo TKA may require surgical intervention on both extremities because of bilateral osteoarthritis. The purpose of this study was to evaluate the safety of simultaneous bilateral TKA compared with that of unilateral TKA. METHODS: Patients who underwent unilateral or simultaneous bilateral primary, elective TKA from 2015 to 2020 were identified using the Premier Healthcare Database. Subsequently, the simultaneous bilateral TKA cohort was matched to the unilateral TKA cohort in a 1:6 ratio by age, sex, race, and presence of pertinent comorbidities. Patient characteristics, hospital factors, and comorbidities were compared between the cohorts. The 90-day risks of postoperative complications, readmission, and in-hospital death were assessed. Differences were assessed using univariable regression, and multivariable regression analyses were performed to account for potential confounders. RESULTS: Overall, 21,044 patients who underwent simultaneous bilateral TKA and 126,264 matched patients who underwent unilateral TKA were included. After accounting for confounding factors, patients who underwent simultaneous bilateral TKA demonstrated a significantly increased risk of postoperative complications, including pulmonary embolism (adjusted odds ratio [OR], 2.13 [95% confidence interval (CI), 1.57 to 2.89]; p < 0.001), stroke (adjusted OR, 2.21 [95% CI, 1.42 to 3.42]; p < 0.001), acute blood loss anemia (adjusted OR, 2.06 [95% CI, 1.99 to 2.13]; p < 0.001), and transfusion (adjusted OR, 7.84 [95% CI, 7.16 to 8.59]; p < 0.001). Patients who underwent simultaneous bilateral TKA were at increased risk of 90-day readmission (adjusted OR, 1.35 [95% CI, 1.24 to 1.48]; p < 0.001). CONCLUSIONS: Simultaneous bilateral TKA was associated with increased rates of complications including pulmonary embolism, stroke, and transfusion. Orthopaedic surgeons and patients should consider these potential complications when contemplating simultaneous bilateral TKA. When simultaneous bilateral TKA is pursued, patient counseling and thorough medical optimization should be performed. LEVEL OF EVIDENCE: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Increased Complication Risk Associated With Simultaneous Bilateral Total Hip Arthroplasty: A Contemporary, Matched Cohort Analysis.

BACKGROUND: Simultaneous bilateral total hip arthroplasty (sbTHA) continues to be performed in patients who have bilateral end-stage osteoarthritis. However, few studies have evaluated the risk associated with this practice compared to unilateral total hip arthroplasty (THA). METHODS: Using a large national database, primary, elective sbTHAs, and unilateral THAs were identified from January 1, 2015 to December 31, 2021. The sbTHAs were matched to unilateral THAs at a 1:5 ratio on age, sex, and pertinent comorbidities. Patient characteristics and comorbidities, and hospital factors were compared between both cohorts. Additionally, 90-day risk of postoperative complications, readmissions, and in-hospital deaths were assessed. After matching, 2,913 sbTHAs were compared to 14,565 unilateral THAs with an average age of 58.5 ± 10.0 years. RESULTS: Compared to unilateral patients, sbTHA patients demonstrated higher rates of pulmonary embolism (PE) (0.4 versus 0.2%, P = .002), acute renal failure (1.2 versus 0.7%, P = .007), acute blood loss anemia (30.4 versus 16.7%, P < .001), and need for transfusion (6.6 versus 1.8%, P < .001). After accounting for confounders, sbTHA patients demonstrated increased risk of PE (adjusted odds ratio [aOR]: 3.76, 95% CI: 1.84 to 7.70, P < .001), acute renal failure (aOR: 1.83, 95% CI: 1.23 to 2.72, P = .003), acute blood loss anemia (aOR: 2.3, 95% CI: 2.10 to 2.53, P < .001), and transfusion (aOR: 4.08, 95% CI: 3.35 to 4.98, P < .001) compared to unilateral THA patients. CONCLUSION: The practice of performing sbTHA was associated with an increased risk of PE, acute renal failure, and risk of transfusion. Careful evaluation of patient-specific risk factors is warranted when considering these bilateral procedures.