A Tool to Estimate Risk of 30-day Mortality and Complications After Hip Fracture Surgery: Accurate Enough for Some but Not All Purposes? A Study From the ACS-NSQIP Database.

BACKGROUND: Surgical repair of hip fracture carries substantial short-term risks of mortality and complications. The risk-reward calculus for most patients with hip fractures favors surgical repair. However, some patients have low prefracture functioning, frailty, and/or very high risk of postoperative mortality, making the choice between surgical and nonsurgical management more difficult. The importance of high-quality informed consent and shared decision-making for frail patients with hip fracture has recently been demonstrated. A tool to accurately estimate patient-specific risks of surgery could improve these processes. QUESTIONS/PURPOSES: With this study, we sought (1) to develop, validate, and estimate the overall accuracy (C-index) of risk prediction models for 30-day mortality and complications after hip fracture surgery; (2) to evaluate the accuracy (sensitivity, specificity, and false discovery rates) of risk prediction thresholds for identifying very high-risk patients; and (3) to implement the models in an accessible web calculator. METHODS: In this comparative study, preoperative demographics, comorbidities, and preoperatively known operative variables were extracted for all 82,168 patients aged 18 years and older undergoing surgery for hip fracture in the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) between 2011 and 2017. Eighty-two percent (66,994 of 82,168 ) of patients were at least 70 years old, 21% (17,007 of 82,168 ) were at least 90 years old, 70% (57,260 of 82,168 ) were female, and 79% (65,301 of 82,168 ) were White. A total of 5% (4260 of 82,168) of patients died within 30 days of surgery, and 8% (6786 of 82,168) experienced a major complication. The ACS-NSQIP database was chosen for its clinically abstracted and reliable data from more than 600 hospitals on important surgical outcomes, as well as rich characterization of preoperative demographic and clinical predictors for demographically diverse patients. Using all the preoperative variables in the ACS-NSQIP dataset, least absolute shrinkage and selection operator (LASSO) logistic regression, a type of machine learning that selects variables to optimize accuracy and parsimony, was used to develop and validate models to predict two primary outcomes: 30-day postoperative mortality and any 30-day major complications. Major complications were defined by the occurrence of ACS-NSQIP complications including: on a ventilator longer than 48 hours, intraoperative or postoperative unplanned intubation, septic shock, deep incisional surgical site infection (SSI), organ/space SSI, wound disruption, sepsis, intraoperative or postoperative myocardial infarction, intraoperative or postoperative cardiac arrest requiring cardiopulmonary resuscitation, acute renal failure needing dialysis, pulmonary embolism, stroke/cerebral vascular accident, and return to the operating room. Secondary outcomes were six clusters of complications recently developed and increasingly used for the development of surgical risk models, namely: (1) pulmonary complications, (2) infectious complications, (3) cardiac events, (4) renal complications, (5) venous thromboembolic events, and (6) neurological events. Tenfold cross-validation was used to assess overall model accuracy with C-indexes, a measure of how well models discriminate patients who experience an outcome from those who do not. Using the models, the predicted risk of outcomes for each patient were used to estimate the accuracy (sensitivity, specificity, and false discovery rates) of a wide range of predicted risk thresholds. We then implemented the prediction models into a web-accessible risk calculator. RESULTS: The 30-day mortality and major complication models had good to fair discrimination (C-indexes of 0.76 and 0.64, respectively) and good calibration throughout the range of predicted risk. Thresholds of predicted risk to identify patients at very high risk of 30-day mortality had high specificity but also high false discovery rates. For example, a 30-day mortality predicted risk threshold of 15% resulted in 97% specificity, meaning 97% of patients who lived longer than 30 days were below that risk threshold. However, this threshold had a false discovery rate of 78%, meaning 78% of patients above that threshold survived longer than 30 days and might have benefitted from surgery. The tool is available here: https://s-spire-clintools.shinyapps.io/hip_deploy/ . CONCLUSION: The models of mortality and complications we developed may be accurate enough for some uses, especially personalizing informed consent and shared decision-making with patient-specific risk estimates. However, the high false discovery rate suggests the models should not be used to restrict access to surgery for high-risk patients. Deciding which measures of accuracy to prioritize and what is "accurate enough" depends on the clinical question and use of the predictions. Discrimination and calibration are commonly used measures of overall model accuracy but may be poorly suited to certain clinical questions and applications. Clinically, overall accuracy may not be as important as knowing how accurate and useful specific values of predicted risk are for specific purposes.Level of Evidence Level III, therapeutic study.

What Factors Lead to Racial Disparities in Outcomes After Total Knee Arthroplasty?

Total knee arthroplasty (TKA) is one of the most commonly performed, major elective surgeries in the USA. African American TKA patients on average experience worse clinical outcomes than whites, including lower improvements in patient-reported outcomes and higher rates of complications, hospital readmissions, and reoperations. The mechanisms leading to these racial health disparities are unclear, but likely involve patient, provider, healthcare system, and societal factors. Lower physical and mental health at baseline, lower social support, provider bias, lower rates of health insurance coverage, higher utilization of lower quality hospitals, and systemic racism may contribute to the inferior outcomes that African Americans experience. Limited evidence suggests that improving the quality of surgical care can offset these factors and lead to a reduction in outcome disparities.

Hepatitis C infection and complication rates after total shoulder arthroplasty in United States veterans.

BACKGROUND: Few studies have evaluated the effect of hepatitis C (HCV) on primary total shoulder arthroplasty (TSA). Our purpose was to determine if HCV infection is associated with increased complication rates after TSA in United States (US) veterans and, secondarily, to determine if preoperative HCV treatment with direct-acting antivirals (DAAs) affects postoperative complication rates. METHODS: US Department of Veterans Affairs (VA) data sets were used to retrospectively identify patients without HCV, patients with untreated HCV, and patients with HCV treated with DAAs who underwent TSA from 2014 to 2019. Medical and surgical complications were assessed using International Classification of Diseases codes. Complication rates between patients with HCV (treated and untreated) and patients without HCV and between HCV-treated patients and HCV-untreated patients were compared at 90 days and 1 year after surgery. RESULTS: We identified 5774 primary TSAs that were performed at VA hospitals between 2014 and 2019. A minority (9.5%) of TSA patients had HCV, 23.4% of whom were treated preoperatively with DAAs. On multivariate analysis, HCV patients had increased odds of 1-year medical complications (odds ratio, 1.39; 95% confidence interval, 1.06-1.81, P = .016), when compared with patients without HCV. No statistically significant difference in complication rates was observed between HCV-treated and HCV-untreated patients. DISCUSSION: US veterans with a history of HCV are at an increased risk of developing medical but not surgical complications within the first year after TSA. Larger studies are necessary to evaluate the effects of DAA treatment on complication rates.

Comparison of Periarticular Infiltration and Combination Delivery of Local Anesthetics for Reducing Pain and Opioid Consumption after Total Knee Arthroplasty.

Surgical-site delivery of local anesthetics decreases pain and opioid consumption after total knee arthroplasty (TKA). The optimal route of administration is unknown. We compared local anesthetic delivery using periarticular soft-tissue infiltration to delivery using a combination of preimplantation immersion and intra-articular injection (combination treatment). The records of patients who underwent unilateral, cemented, primary TKA with spinal anesthesia and adductor canal blocks at a single Veterans Affairs Medical Center were retrospectively reviewed. Three subgroups were compared, including controls who did not receive additional local anesthetics, patients who received periarticular infiltration, and patients who received combination treatment. Mean daily pain scores and mean 24-hour opioid consumption on postoperative days (PODs) 0 and 1 were calculated, and analysis of variance was used to assess for significant differences. Factors that were associated with lower pain scores and opioid consumption were then identified using multivariate stepwise regression. There were 26 controls, 25 periarticular infiltration patients, and 39 combination patients. The periarticular infiltration cohort had significantly lower mean pain scores and opioid consumption than controls on POD 0, but not on POD 1. The combination cohort had significantly lower mean pain scores and opioid consumption than controls on PODs 0 and 1. There were no significant differences between the infiltration and combination groups on either day. Multivariate regression analysis showed that infiltration was associated with significantly decreased opioid consumption on both days and decreased pain on POD 0. Combination treatment was associated with significantly decreased pain and opioid consumption on both days. Both local anesthetic periarticular infiltration and combination treatment are associated with decreased pain and opioid consumption after TKA. The stronger effects of the combination treatment compared with periarticular infiltration on POD 1 suggests that combination delivery may have a longer duration of action.

Can Machine Learning Methods Produce Accurate and Easy-to-Use Preoperative Prediction Models of One-Year Improvements in Pain and Functioning After Knee Arthroplasty?

BACKGROUND: Approximately 15%-20% of total knee arthroplasty (TKA) patients do not experience clinically meaningful improvements. We sought to compare the accuracy and parsimony of several machine learning strategies for developing predictive models of failing to experience minimal clinically important differences in patient-reported outcome measures (PROMs) 1 year after TKA. METHODS: Patients (N = 587) in 3 large Veteran Health Administration facilities completed PROMs before and 1 year after TKA (92% follow-up). Preoperative PROMs and electronic health record data were used to develop and validate models to predict failing to experience at least a minimal clinically important difference in Knee Injury and Osteoarthritis Outcome Score (KOOS) Total, KOOS JR, and KOOS subscales (Pain, Symptoms, Activities of Daily Living, Quality of Life, and recreation). Several machine learning strategies were used for model development. Ten-fold cross-validation and bootstrapping were used to produce measures of overall accuracy (C-statistic, Brier Score). The sensitivity and specificity of various predicted probability cut-points were examined. RESULTS: The most accurate models produced were for the Activities of Daily Living, Pain, Symptoms, and Quality of Life subscales of the KOOS (C-statistics 0.76, 0.72, 0.72, and 0.71, respectively). Strategies varied substantially in terms of the numbers of inputs required to achieve similar accuracy, with none being superior for all outcomes. CONCLUSION: Models produced in this project provide estimates of patient-specific improvements in major outcomes 1 year after TKA. Integrating these models into clinical decision support, informed consent and shared decision making could improve patient selection, education, and satisfaction. LEVEL OF EVIDENCE: Level III, diagnostic study.

Antibiotic-Laden Bone Cement Use and Revision Risk After Primary Total Knee Arthroplasty in U.S. Veterans.

BACKGROUND: It is controversial whether the use of antibiotic-laden bone cement (ALBC) in primary total knee arthroplasty (TKA) affects periprosthetic joint infection (PJI) or revision rates. The impact of ALBC on outcomes of primary TKA have not been previously investigated in U.S. veterans, to our knowledge. The purposes of this study were to quantify utilization of ALBC among U.S. veterans undergoing primary TKA and to determine if ALBC usage is associated with differences in revision TKA rates. METHODS: Patients who had TKA with cement from 2007 to 2015 at U.S. Veterans Health Administration (VHA) hospitals with at least 2 years of follow-up were retrospectively identified. Patients who received high-viscosity Palacos bone cement with or without gentamicin were selected as the final study cohort. Patient demographic and comorbidity data were collected. Revision TKA was the primary outcome. All-cause revisions and revisions for PJI were identified from both VHA and non-VHA hospitals. Unadjusted and adjusted regression analyses were performed to identify variables that were associated with increased revision rates. RESULTS: The study included 15,972 patients who had primary TKA with Palacos bone cement at VHA hospitals from 2007 to 2015. Plain bone cement was used for 4,741 patients and ALBC was used for 11,231 patients. Utilization of ALBC increased from 50.6% in 2007 to 69.4% in 2015. At a mean follow-up of 5 years, TKAs with ALBC had a lower all-cause revision rate than those with plain bone cement (5.3% versus 6.7%; p = 0.0009) and a lower rate of revision for PJI (1.9% versus 2.6%; p = 0.005). On multivariable regression, ALBC use was associated with a lower risk of all-cause revision compared with plain bone cement (hazard ratio [HR]: 0.79, 95% confidence interval [CI]: 0.68 to 0.92; p = 0.0019). Seventy-one primary TKAs needed to be implanted with ALBC to avoid 1 revision TKA. CONCLUSIONS: The utilization of ALBC for primary TKAs performed at VHA hospitals has increased over time and was associated with a lower all-cause revision rate and a lower rate of revision for PJI. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Social Determinants of Health and Patient-Reported Outcomes Following Total Hip and Knee Arthroplasty in Veterans.

BACKGROUND: Social determinants of health (SDOH) are the conditions in which people are born, grow, live, work, and age. They are associated with disparities in outcomes following total joint arthroplasty (TJA). These disparities occur even in equal-access healthcare systems such as the Veterans Health Administration (VHA). Our goal was to determine whether SDOH affect patient-reported outcome measures (PROMs) following TJA in VHA patients. METHODS: Patients scheduled to undergo total hip or knee arthroplasty at VHA Hospitals in Minneapolis, MN, Palo Alto, CA, and San Francisco, CA, prospectively completed PROMs before and 1 year after surgery. PROMs included the Hip disability and Osteoarthritis Outcome Score, the Knee injury and Osteoarthritis Outcome Score, and their Joint Replacement subscores. SDOH included race, ethnicity, marital status, education, and employment status. The level of poverty in each patient's neighborhood was determined. Medical comorbidities were recorded. Univariate and multivariate analyses were performed to determine whether SDOH were significantly associated with PROM improvement after surgery. RESULTS: On multivariate analysis, black race was significantly negatively correlated with knee PROM improvement and Hispanic ethnicity was significantly negatively correlated with hip PROM improvement compared to whites. Higher baseline PROM scores and lower age were significantly associated with lower PROM improvement. Significant associations were also found based on education, gender, comorbidities, and neighborhood poverty. CONCLUSION: Minority VHA patients have lower improvement in PROM scores after TJA than white patients. Further research is required to identify the reasons for these disparities and to design interventions to reduce them.

Comparing Methods to Determine the Minimal Clinically Important Differences in Patient-Reported Outcome Measures for Veterans Undergoing Elective Total Hip or Knee Arthroplasty in Veterans Health Administration Hospitals.

Importance: The minimal clinically important difference (MCID) in a patient-reported outcome measure (PROM) is the smallest change that patients perceive as beneficial. Accurate MCIDs are required when PROMs are used to evaluate the value of surgical interventions. Objective: To use well-defined distribution-based and anchor-based methods to calculate MCIDs in the Hip Disability and Osteoarthritis Outcome Score (HOOS) and in the Knee Injury and Osteoarthritis Outcome Score (KOOS) for veterans undergoing primary total hip arthroplasty or total knee arthroplasty. Design, Setting, and Participants: A prospective cohort study was conducted of 858 patients undergoing total joint replacement between March 16, 2015, and March 9, 2017, at 3 high-complexity Veterans Affairs Medical Centers. Interventions: Patients undergoing total hip arthroplasty or total knee arthroplasty were administered HOOS or KOOS PROMs prior to and 1 year after surgery. The Self-Administered Patient Satisfaction Scale (SAPS) for primary hip or knee arthroplasty was administered at 1-year follow-up as an anchor PROM. Main Outcomes and Measures: The HOOS and KOOS before and 1 year after surgery, change scores (difference between postoperative and preoperative PROM scores), and MCIDs for each measure. For anchor-based methods, receiver operating characteristic curve analysis was performed, including calculation of the area under the curve. Results: The mean (SD) age of the 271 patients who underwent hip arthroplasty was 65.6 (8.3) years, and the mean (SD) age of the 587 patients who underwent knee arthroplasty was 66.1 (8.2) years. There were 547 men in the knee arthroplasty cohort and 256 men in the hip arthroplasty cohort (total, 803 men). There were significant improvements in the mean values of every PROM, with mean (SD) differences greater than 39 for HOOS Joint Replacement (JR) and every hip subscale (HOOS JR, 39.7 [20.2]; pain, 47.6 [20.5]; symptoms, 45.1 [21.5]; activities of daily living, 43.7 [22.1]; recreation, 49.2 [33.5]; quality of life, 50.3 [27.8]) and mean (SD) differences greater than 29 for KOOS JR and every knee subscale (KOOS JR, 30.4 [17.5]; pain, 38.0 [20.4]; symptoms, 29.5 [22.1]; activities of daily living, 34.8 [20.5]; recreation, 34.6 [31.1]; quality of life, 35.2 [26.8]). Different calculation methods yielded a wide range of MCIDs. Distribution-based approaches tended to give lower values than the anchor-based approaches, which gave similar values for most PROMs. Area under the curve values demonstrated good to excellent discrimination for SAPS for nearly all PROMs. Conclusions and Relevance: Minimal clinically important difference estimates can be highly variable depending on the method used. Patient satisfaction measured by SAPS is a suitable anchor for the HOOS and KOOS. This study suggests that the SAPS-anchored MCID values presented here be used in future studies of total hip arthroplasty and total knee arthroplasty for veterans.

Osteocyte dysfunction promotes osteoarthritis through MMP13-dependent suppression of subchondral bone homeostasis.

Osteoarthritis (OA), long considered a primary disorder of articular cartilage, is commonly associated with subchondral bone sclerosis. However, the cellular mechanisms responsible for changes to subchondral bone in OA, and the extent to which these changes are drivers of or a secondary reaction to cartilage degeneration, remain unclear. In knee joints from human patients with end-stage OA, we found evidence of profound defects in osteocyte function. Suppression of osteocyte perilacunar/canalicular remodeling (PLR) was most severe in the medial compartment of OA subchondral bone, with lower protease expression, diminished canalicular networks, and disorganized and hypermineralized extracellular matrix. As a step toward evaluating the causality of PLR suppression in OA, we ablated the PLR enzyme MMP13 in osteocytes while leaving chondrocytic MMP13 intact, using Cre recombinase driven by the 9.6-kb DMP1 promoter. Not only did osteocytic MMP13 deficiency suppress PLR in cortical and subchondral bone, but it also compromised cartilage. Even in the absence of injury, osteocytic MMP13 deficiency was sufficient to reduce cartilage proteoglycan content, change chondrocyte production of collagen II, aggrecan, and MMP13, and increase the incidence of cartilage lesions, consistent with early OA. Thus, in humans and mice, defects in PLR coincide with cartilage defects. Osteocyte-derived MMP13 emerges as a critical regulator of cartilage homeostasis, likely via its effects on PLR. Together, these findings implicate osteocytes in bone-cartilage crosstalk in the joint and suggest a causal role for suppressed perilacunar/canalicular remodeling in osteoarthritis.

Does Implant Choice Affect the Episode Cost of Pertrochanteric Hip Fracture for US Veterans?

OBJECTIVE: To investigate an association between a surgeon's choice of a cephalomedullary nail (CMN) or sliding hip screw (SHS) with the cost of treating a pertrochanteric hip fracture. DESIGN: Multicenter retrospective cohort study. SETTING: US Veterans Health Administration Sierra Pacific Network. PATIENTS/PARTICIPANTS: Two hundred ninety-four consecutive US veterans admitted for a principal diagnosis of an OTA/AO 31A-type pertrochanteric hip fracture of a native hip from 2000 to 2015. INTERVENTION: Internal fixation using a CMN or an SHS. MAIN OUTCOME MEASUREMENTS: Veterans Administration Health Economic Resource Center average national cost estimate of combined acute and postacute care episode cost, excluding implant cost, normalized to 2015 US dollars by the Consumer Price Index. RESULTS: Median episode cost was $8223 lower with a CMN than an SHS (95% confidence interval, $5700-$10,746, P < 0.001) after matching on a propensity score for treatment with a CMN based on age, sex, body mass index, Charlson Comorbidity Index, fracture characteristics, study site, and admission year. A subgroup propensity-matched analysis excluding reverse obliquity pertrochanteric fractures was not sufficiently powered to detect a difference in episode cost (ß = 0.76, P = 0.311). CONCLUSIONS: Implant choice significantly affected the episode cost of care of hip fracture at Veterans Health Administration facilities. LEVEL OF EVIDENCE: Economic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Preoperative Treatment of Hepatitis C Is Associated With Lower Prosthetic Joint Infection Rates in US Veterans.

BACKGROUND: Hepatitis C virus (HCV) is associated with poorer outcomes in total joint arthroplasty (TJA). Recently, oral direct-acting antivirals (DAAs) have become available for HCV curative treatment. The goal of this study is to determine if HCV may be a modifiable risk factor in TJA by comparing postoperative complications among patients with and without preoperative treatment for HCV. METHODS: US Department of Veterans Affairs dataset of all consecutive primary TJAs performed between 2014 and 2018, when DAAs were available, was retrospectively reviewed. HCV-infected patients were identified using International Classification of Diseases, Ninth and Tenth Revision codes and laboratory values. HCV-infected patients treated prior to TJA with DAA were included in the "treated" group. HCV-infected patients untreated preoperatively were assigned to the "untreated" group. Medical and surgical complications up to 1 year postoperatively were identified using International Classification of Diseases, Ninth and Tenth Revision inpatient and outpatient codes. RESULTS: In total, 42,268 patients underwent TJA at Veterans Affairs Hospitals between 2014 and 2018. About 6.0% (n = 2557) of TJA patients had HCV, 17.3% of whom received HCV treatment preoperatively. When evaluating inpatient and outpatient codes, implant infection rates were statistically lower at 90 days and 1 year postoperatively among HCV-treated patients than among those untreated. Odds ratios (ORs) favor lower infection rates in HCV-treated patients (90-day OR: 3.30, P = .045; 1-year OR: 2.16, P = .07). CONCLUSION: Preoperative HCV treatment was associated with lower periprosthetic infection rates among US veterans undergoing TJA. Further investigation is necessary for definitive conclusions.

Freedom From Opioids After Total Knee Arthroplasty.

BACKGROUND: In the United States, opioids are commonly prescribed to treat knee pain after total knee arthroplasty (TKA). While surgery leads to decreased pain in most patients, a sizable minority continue to experience severe pain and consume opioids chronically after TKA. We sought to determine the population-level effect of TKA on opioid consumption by detailing the pattern of opioid prescriptions before and after surgery. METHODS: We retrospectively identified US Veterans Health Administration TKA patients from 2010 to 2015. Outpatient opioid prescriptions were identified from 18 months before to 18 months after surgery, and mean daily opioid doses were calculated. Our primary end point was the achievement of opioid-freedom, defined as a period of at least 6 months without opioids. We compared the percentage of patients who were opioid-free preoperatively to the percentage who were opioid-free 18 months after surgery (no prescriptions after postoperative month 12). We identified factors associated with opioid-freedom. RESULTS: In a cohort of 33,927 patients, 41% were opioid-free in the month before surgery compared to 54% 18 months after surgery (P < .001). Preoperative freedom from opioids (odds ratio, 4.59; 95% confidence interval, 4.34 to 4.85; P < .001) was more strongly associated with postoperative freedom from opioids than patient medical and social factors. CONCLUSION: TKA was associated with an increase in postoperative freedom from opioids. Low preoperative dose of opioids was more strongly associated with postoperative opioid-freedom than patient characteristics, suggesting that opioid prescription patterns are a chief driver of opioid use after surgery. LEVEL OF EVIDENCE III: Retrospective cohort study.

Can Machine Learning Methods Produce Accurate and Easy-to-use Prediction Models of 30-day Complications and Mortality After Knee or Hip Arthroplasty?

BACKGROUND: Existing universal and procedure-specific surgical risk prediction models of death and major complications after elective total joint arthroplasty (TJA) have limitations including poor transparency, poor to modest accuracy, and insufficient validation to establish performance across diverse settings. Thus, the need remains for accurate and validated prediction models for use in preoperative management, informed consent, shared decision-making, and risk adjustment for reimbursement. QUESTIONS/PURPOSES: The purpose of this study was to use machine learning methods and large national databases to develop and validate (both internally and externally) parsimonious risk-prediction models for mortality and complications after TJA. METHODS: Preoperative demographic and clinical variables from all 107,792 nonemergent primary THAs and TKAs in the 2013 to 2014 American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) were evaluated as predictors of 30-day death and major complications. The NSQIP database was chosen for its high-quality data on important outcomes and rich characterization of preoperative demographic and clinical predictors for demographically and geographically diverse patients. Least absolute shrinkage and selection operator (LASSO) regression, a type of machine learning that optimizes accuracy and parsimony, was used for model development. Tenfold validation was used to produce C-statistics, a measure of how well models discriminate patients who experience an outcome from those who do not. External validation, which evaluates the generalizability of the models to new data sources and patient groups, was accomplished using data from the Veterans Affairs Surgical Quality Improvement Program (VASQIP). Models previously developed from VASQIP data were also externally validated using NSQIP data to examine the generalizability of their performance with a different group of patients outside the VASQIP context. RESULTS: The models, developed using LASSO regression with diverse clinical (for example, American Society of Anesthesiologists classification, comorbidities) and demographic (for example, age, gender) inputs, had good accuracy in terms of discriminating the likelihood a patient would experience, within 30 days of arthroplasty, a renal complication (C-statistic, 0.78; 95% confidence interval [CI], 0.76-0.80), death (0.73; 95% CI, 0.70-0.76), or a cardiac complication (0.73; 95% CI, 0.71-0.75) from one who would not. By contrast, the models demonstrated poor accuracy for venous thromboembolism (C-statistic, 0.61; 95% CI, 0.60-0.62) and any complication (C-statistic, 0.64; 95% CI, 0.63-0.65). External validation of the NSQIP- derived models using VASQIP data found them to be robust in terms of predictions about mortality and cardiac complications, but not for predicting renal complications. Models previously developed with VASQIP data had poor accuracy when externally validated with NSQIP data, suggesting they should not be used outside the context of the Veterans Health Administration. CONCLUSIONS: Moderately accurate predictive models of 30-day mortality and cardiac complications after elective primary TJA were developed as well as internally and externally validated. To our knowledge, these are the most accurate and rigorously validated TJA-specific prediction models currently available (http://med.stanford.edu/s-spire/Resources/clinical-tools-.html). Methods to improve these models, including the addition of nonstandard inputs such as natural language processing of preoperative clinical progress notes or radiographs, should be pursued as should the development and validation of models to predict longer term improvements in pain and function. LEVEL OF EVIDENCE: Level III, diagnostic study.

American Joint Replacement Registry Risk Calculator Does Not Predict 90-day Mortality in Veterans Undergoing Total Joint Replacement.

BACKGROUND: The American Joint Replacement Registry (AJRR) Total Joint Risk Calculator uses demographic and clinical parameters to provide risk estimates for 90-day mortality and 2-year periprosthetic joint infection (PJI). The tool is intended to help surgeons counsel their Medicare-eligible patients about their risk of death and PJI after total joint arthroplasty (TJA). However, for a predictive risk model to be useful, it must be accurate when applied to new patients; this has yet to be established for this calculator. QUESTIONS/PURPOSES: To produce accuracy metrics (ie, discrimination, calibration) for the AJRR mortality calculator using data from Medicare-eligible patients undergoing TJA in the Veterans Health Administration (VHA), the largest integrated healthcare system in the United States, where more than 10,000 TJAs are performed annually. METHODS: We used the AJRR calculator to predict risk of death within 90 days of surgery among 31,214 VHA patients older than 64 years of age who underwent primary TJA; data was drawn from the Veterans Affairs Surgical Quality Improvement Project (VASQIP) and VA Corporate Data Warehouse (CDW). We then used VHA mortality data to evaluate the extent to which the AJRR calculator estimates distinguished individuals who died compared with those who did not (C-statistic), and graphically depicted the relationship between estimated risk and observed mortality (calibration). As a secondary evaluation of the calculator, a sample of 39,300 patients younger than 65 years old was assigned to the youngest age group available to the user (65-69 years) as might be done in real-world practice. RESULTS: C-statistics for 90-day mortality for the older samples were 0.62 (95% CI, 0.60-0.64) and for the younger samples they were 0.46 (95% CI, 0.43-0.49), suggesting poor discrimination. Calibration analysis revealed poor correspondence between deciles of predicted risk and observed mortality rates. Poor discrimination and calibration mean that patients who died will frequently have a lower estimated risk of death than surviving patients. CONCLUSIONS: For Medicare-eligible patients receiving TJA in the VA, the AJRR risk calculator had a poor performance in the prediction of 90-day mortality. There are several possible reasons for the model's poor performance. Veterans Health Administration patients, 97% of whom were men, represent only a subset of the broader Medicare population. However, applying the calculator to a subset of the target population should not affect its accuracy. Other reasons for poor performance include a lack of an underlying statistical model in the calculator's implementation and simply the challenge of predicting rare events. External validation in a more representative sample of Medicare patients should be conducted to before assuming this tool is accurate for its intended use. LEVEL OF EVIDENCE: Level I, diagnostic study.

Prediction Models for 30-Day Mortality and Complications After Total Knee and Hip Arthroplasties for Veteran Health Administration Patients With Osteoarthritis.

BACKGROUND: Statistical models to preoperatively predict patients' risk of death and major complications after total joint arthroplasty (TJA) could improve the quality of preoperative management and informed consent. Although risk models for TJA exist, they have limitations including poor transparency and/or unknown or poor performance. Thus, it is currently impossible to know how well currently available models predict short-term complications after TJA, or if newly developed models are more accurate. We sought to develop and conduct cross-validation of predictive risk models, and report details and performance metrics as benchmarks. METHODS: Over 90 preoperative variables were used as candidate predictors of death and major complications within 30 days for Veterans Health Administration patients with osteoarthritis who underwent TJA. Data were split into 3 samples-for selection of model tuning parameters, model development, and cross-validation. C-indexes (discrimination) and calibration plots were produced. RESULTS: A total of 70,569 patients diagnosed with osteoarthritis who received primary TJA were included. C-statistics and bootstrapped confidence intervals for the cross-validation of the boosted regression models were highest for cardiac complications (0.75; 0.71-0.79) and 30-day mortality (0.73; 0.66-0.79) and lowest for deep vein thrombosis (0.59; 0.55-0.64) and return to the operating room (0.60; 0.57-0.63). CONCLUSIONS: Moderately accurate predictive models of 30-day mortality and cardiac complications after TJA in Veterans Health Administration patients were developed and internally cross-validated. By reporting model coefficients and performance metrics, other model developers can test these models on new samples and have a procedure and indication-specific benchmark to surpass.

Repurposing Human Osteoarthritic Cartilage as a Bone Graft Substitute in an Athymic Rat Posterolateral Spinal Fusion Model.

BACKGROUND: Spinal fusion involves both endochondral and intramembranous bone formation. We previously demonstrated that endochondral cartilage grafts that were derived from human osteoarthritic (OA) articular cartilage can be used as a bone graft in mouse models. We hypothesized that OA cartilage could also be recycled and repurposed as a bone graft substitute in a posterolateral lumbar spinal fusion model in athymic rats. METHODS: OA articular cartilage was obtained from the femoral resection of a healthy 60-year-old man undergoing elective total knee arthroplasty. The chondrocytes recovered from this tissue were dedifferentiated in monolayer tissue culture and then transitioned to culture conditions that promote chondrocyte hypertrophy. The resultant cell pellets were then used as bone graft substitute for single-level posterolateral spinal fusion in 5 athymic rats. Decortication alone was used as the control group. Spinal fusion was assessed with manual palpation, micro-computed tomography, and histologic analysis. RESULTS: In the experimental group, micro-computed tomography at 4 and 8 weeks demonstrated bilateral fusion in 4 of 5 animals and unilateral fusion in 1 animal. At 8 weeks, manual palpation and histologic analysis showed direct correlation with the radiographic findings. Animals undergoing decortication alone failed to generate any spinal fusion. The difference in the fusion rate between groups was statistically significant with respect to both unilateral fusion (P = .047) and bilateral fusion (P = .007). CONCLUSIONS: In the absence of additional surgically implanted bone graft, hypertrophic chondrocyte grafts are sufficient for generating single-level posterolateral lumbar fusion in athymic rats. CLINICAL RELEVANCE: This animal study demonstrates that cartilage harvested from OA knees can be used as a bone graft substitute. Commercially available cell-based bone grafts have previously only used mesenchymal stem cells or osteoblast precursor cells.

The Effects of Topical Vancomycin on Mesenchymal Stem Cells: More May Not Be Better.

BACKGROUND: The use of topical vancomycin is increasingly popular in spine surgery. Large retrospective reviews suggest that topical vancomycin provides a cost-effective decrease in post-operative infection. Currently, there is little that is known about the maximum dose that can be applied locally. When 1 gram of vancomycin is mixed into the bone graft and another 1 gram applied freely in a spine wound, the local concentration of antibiotic ranges from 260-2900 µg/mL in the immediate post-op period and 50-730 µg/mL by the second post-operative day. We hypothesized that exuberant doses of vancomycin would be toxic to mesenchymal stem cells (MSCs). METHODS: Bone marrow was obtained from the femoral canal of patients undergoing routine elective total hip arthroplasty. Mesenchymal stem cells were isolated using plastic adhesion. Cells were exposed to a wide range of doses of vancomycin for 24 hours and then assessed for viability. Osteogenic potential was assessed with alizarin red staining. RESULTS: There was dose-dependent cell death with vancomycin use. MSC death was 9.43% at 400 µg/mL (p=0.047), 13.79% at 1600 µg/mL (p=0.0047), 19.35% at 3200 µg/mL (p<0.0001), 24.82% at 6400 µg/mL (p<0.0001) and 51.83% at 12800 µg/mL of vancomycin (p<0.0001) in comparison to the control group containing no vancomycin. CONCLUSIONS: Our in vitro study suggests that vancomycin has toxic effects on hMSCs, a cell population particularly important for bone formation. In the absence of any clinical evidence suggesting that "more vancomycin is better," and our data suggesting that more vancomycin is harmful in vitro, surgeons electing to use topical vancomycin in spine surgery should restrict their use to the doses currently reported in the available published studies unless specific reasons exist otherwise. This study does not establish a contraindication to the use of topical vancomycin, nor does it suggest that pseudarthroses are attributable to vancomycin use.

A Simple Method Associated With Reduced Opioid Consumption After Total Knee Arthroplasty.

BACKGROUND: Most patients experience moderate to severe pain after total knee arthroplasty (TKA). We hypothesized that intraoperative treatment of cut bone surfaces with local anesthetic (preimplantation immersion anesthesia, PIA) would lead to decreased postoperative pain and opioid consumption. METHODS: Records of 76 patients who underwent unilateral, cemented TKA were retrospectively reviewed. For PIA patients, surgical wounds were immersed in local anesthetic solution immediately prior to component implantation. Both PIA (n = 43) and control (n = 33) groups received multimodal pain management, including intra-articular local anesthetic injections. Endpoints were opioid consumption and mean pain scores for postoperative day (POD) 0, 1, and 2. Demographic, medical, and social factors were included in multivariate analyses. RESULTS: PIA patients reported significantly lower mean pain scores than controls on PODs 0 and 1 (both P < .005). Pain scores on POD 2 were similar. PIA patients used 45%-33% less opioids on PODs 0, 1, and 2 (all P < .005). POD 0 pain scores showed a significant interaction between PIA treatment and preoperative opioid use (P = .013). On POD 1, PIA was the only factor associated with lower mean pain scores (P < .001). No factors were significant for POD 2. PIA was the only factor associated with lower postoperative opioid consumption on PODs 0 and 2 (both P < .005). For POD 1, PIA and increasing age (both P ≤ .005) were associated with lower postoperative opioid consumption. CONCLUSION: PIA was associated with significant reductions in opioid use and mean pain scores after TKA.

Preoperative Anemia Independently Predicts 30-Day Complications After Aseptic and Septic Revision Total Joint Arthroplasty.

BACKGROUND: Preoperative anemia is a common, important risk factor for adverse events after joint arthroplasty surgery. It affects 21%-35% patients undergoing total joint arthroplasty. To date, few studies have investigated the effect of preoperative anemia, specifically in revision total joint arthroplasty surgery. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was used to identify patients who underwent revision total joint arthroplasty from 2006 to 2014. We matched 6830 patients undergoing aseptic revision (3415 anemic vs 3415 not anemic) and 2650 patients undergoing septic revision (1325 anemic vs 1325 not anemic). In each cohort, patients were propensity score-matched 1:1 by the presence of preoperative anemia. The inpatient hospitalization data, postoperative complications, as well as demographics and comorbidities were compared between patients with or without anemia who underwent revision total joint arthroplasty. RESULTS: After adjusting for comorbidities via multivariate regression, anemia was associated with an increased risk of overall complications (aseptic: odds ratio [OR], 1.45; 95% confidence interval [CI], 1.24-1.70; P < .001; septic: OR, 2.16; 95% CI, 1.83-2.56; P < .001), deep infection (aseptic: OR, 1.68; 95% CI, 1.19-2.38; P = .003; septic: OR, 1.44; 95% CI, 1.06-1.94; P = .018), mortality (aseptic: OR, 2.18; 95% CI, 1.09-4.36; P = .028; septic: OR, 3.16; 95% CI, 1.03-9.74; P = .045), and increased hospital length of stay (aseptic: adjusted coefficient, 1.02 days; 95% CI, 0.73-1.31; P < .001; septic: adjusted coefficient, 2.04 days; 95% CI, 1.53-2.55; P < .001). CONCLUSION: Preoperative anemia is independently associated with postoperative complications, mortality, and increased length of stay in revision total joint arthroplasty. Further studies are needed to evaluate if preoperative treatment of anemia may modify this risk.

Promoting Endochondral Bone Repair Using Human Osteoarthritic Articular Chondrocytes.

INTRODUCTION: Current tissue engineering strategies to heal critical-size bone defects through direct bone formation are limited by incomplete integration of grafts with host bone and incomplete graft vascularization. An alternative strategy for bone regeneration is the use of cartilage grafts that form bone through endochondral ossification. Endochondral cartilages stimulate angiogenesis and are remodeled into bone, but are found in very small quantities in growth plates and healing fractures. We sought to develop engineered endochondral cartilage grafts using osteoarthritic (OA) articular chondrocytes as a cell source. Such chondrocytes often undergo hypertrophy, which is a characteristic of endochondral cartilages. MATERIALS AND METHODS: We compared the ability of unmodified human OA (hOA) cartilage and cartilage grafts formed in vitro from hOA chondrocytes to undergo endochondral ossification in mice. Scaffold-free engineered chondrocyte grafts were generated by pelleting chondrocytes, followed by culture with transforming growth factor-ß1 (TGF-ß1) and bone morphogenetic protein 4. Samples derived from either primary or passaged chondrocytes were implanted subcutaneously into immunocompromised mice. Grafts derived from passaged chondrocytes from three patients were implanted into critical-size tibial defects in mice. Bone formation was assessed with histology after 4 weeks of implantation. The composition of tibial repair tissue was quantified with histomorphometry. RESULTS: Engineered cartilage grafts generated from passaged OA chondrocytes underwent endochondral ossification after implantation either subcutaneously or in bone. Cartilage grafts integrated with host bone at 15 out of 16 junctions. Grafts variably remodeled into woven bone, with the proportion of bony repair tissue in tibial defects ranging from 22% to 85% (average 48%). Bony repair tissue bridged the tibial defects in half of the animals. In contrast, unmodified OA cartilage and engineered grafts formed from primary chondrocytes did not undergo endochondral ossification in vivo. CONCLUSIONS: hOA chondrocytes can adopt an endochondral phenotype after passaging and TGF-ß superfamily treatment. Engineered endochondral cartilage grafts can integrate with host bone, undergo ossification, and heal critical-size long-bone defects in a mouse model. However, additional methods to further enhance ossification of these grafts are required before the clinical translation of this approach.