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Background: Increasing demand for shoulder arthroplasty and an aging population may increase the rate of complications associated with advanced age such as postoperative delirium, but little is known on its burden in this cohort. Purpose: We sought to answer the following questions: (1) What is the epidemiology of postoperative delirium after shoulder arthroplasty? (2) What modifiable risk factors can be identified for postoperative delirium after shoulder arthroplasty? (3) Do risk factors differ in those younger than and in those older than 70 years of age? Methods: In a retrospective nationwide cohort study, we extracted data from the Premier Healthcare database on inpatient total and reverse shoulder arthroplasties from 2006 to 2016. The primary outcome was postoperative delirium; modifiable risk factors of interest were perioperative opioid use (high, medium, or low), peripheral nerve block use, and perioperative prescription medications. Mixed-effects models assessed associations between risk factors and postoperative delirium. Odds ratios and confidence intervals are reported. We applied a cutoff of 70 years of age because it was the median age of the cohort, as well as the age at which we observed that delirium prevalence increased. Results: A total of 92,429 total and reverse shoulder arthroplasties were identified (age range: 14–89 years). Overall delirium prevalence was 3.1% ( n = 2909). Age-specific prevalence of postoperative delirium was lower in patients aged 50 to 70 years and higher in those aged 70 years and older, up to 8% among those older than 88 years. After adjusting for relevant covariates, only long-acting and combined short-acting and long-acting benzodiazepines (compared with no benzodiazepines) were associated with increased odds of postoperative delirium. Corticosteroids were associated with decreased odds of postoperative delirium. Conclusion: Our retrospective cohort study demonstrated that benzodiazepine use and older patient age were significantly associated with postoperative delirium in shoulder arthroplasty patients. The relationship between benzodiazepine use and delirium was particularly notable among those 70 years of age and older. Further investigation is indicated, given the known adverse effects of benzodiazepines in older adults and our findings of higher than expected use of these medications in this surgical cohort.

Despite the extensive literature on racial disparities in care and outcomes after total knee arthroplasty (TKA), data on manipulation under anesthesia (MUA) is lacking. We aimed to determine (1) the relationship between race and rate of (and time to) MUA after TKA, and (2) annual trends in racial differences in MUA from 2013 to 2018.This retrospective cohort study (using 2013-2018 Medicare Limited Data Set claims data) included 836,054 primary TKA patients. The primary outcome was MUA1 year after TKA; time from TKA to MUA in days was also recorded. A mixed-effects multivariable model measured the association between race (White, Black, Other) and odds of MUA. Odds ratios (OR) and 95% confidence intervals (CI) were reported. A Cochran Armitage Trend test was conducted to assess MUA trends over time, stratified by race.MUA after TKA occurred in 1.7%, 3.2% and 2.1% of White, Black, and Other race categories, respectively (SMD = 0.07). After adjustment for covariates, (Black vs White) patients had increased odds of requiring an MUA after TKA: odds ratio (OR) 1.97, 95% confidence intervals (CI) 1.86-2.10, P.0001. Moreover, White (compared to Black) patients had significantly shorter time to MUA after TKA: 60 days (interquartile range [IQR] 46-88) versus 64 days (interquartile range [IQR] 47-96); P.0001. These disparities persisted from 2013 through 2018.Continued racial differences exist for rates and timing of MUA following TKA signifying the continued need for efforts aimed toward understanding and eliminating inequalities that exist in total joint arthroplasty (TJA) care.

Myelofibrosis (MF) is a clonal stem cell neoplasm characterized by abnormal JAK-STAT signaling, chronic inflammation, cytopenias, and risk of transformation to acute leukemia. Despite improvements in the therapeutic options for patients with MF, allogeneic hematopoietic stem cell transplantation remains the only curative treatment. We previously demonstrated multiple immunosuppressive mechanisms in patients with MF, including increased expression of programmed cell death protein 1 (PD-1) on T cells compared with healthy controls. Therefore, we conducted a multicenter, open-label, phase 2, single-arm study of pembrolizumab in patients with Dynamic International Prognostic Scoring System category of intermediate-2 or greater primary, post-essential thrombocythemia or post-polycythemia vera myelofibrosis that were ineligible for or were previously treated with ruxolitinib. The study followed a Simon 2-stage design and enrolled a total of 10 patients, 5 of whom had JAK2V617mutation, 2 had CALR mutation, and 6 had additional mutations. Most patients were previously treated with ruxolitinib. Pembrolizumab treatment was well tolerated, but there were no objective clinical responses, so the study closed after the first stage was completed. However, immune profiling by flow cytometry, T-cell receptor sequencing, and plasma proteomics demonstrated changes in the immune milieu of patients, which suggested improved T-cell responses that can potentially favor antitumor immunity. The fact that these changes were not reflected in a clinical response strongly suggests that combination immunotherapeutic approaches rather than monotherapy may be necessary to reverse the multifactorial mechanisms of immune suppression in myeloproliferative neoplasms. This trial was registered at www.clinicaltrials.gov as #NCT03065400.

Background: Anterior cruciate ligament reconstruction (ACLR) is a commonly performed orthopaedic procedure. The volume and cost of ACLR procedures are increasing annually, but the drivers of these cost increases are not well described. Purpose: To analyze the modifiable drivers of total health care utilization (THU), immediate procedure reimbursement, and surgeon reimbursement for patients undergoing ACLR using a large national commercial insurance database from 2013 to 2017. Study Design: Descriptive epidemiology study. Methods: For this study, the cohort consisted of patients identified in the MarketScan Commercial Claims and Encounters database who underwent outpatient arthroscopic ACLR in the United States from 2013 to 2017. Patients with Current Procedural Terminology code 29888 were included. THU was defined as the sum of any payment related to the ACLR procedure from 90 days preoperatively to 180 days postoperatively. A multivariable model was utilized to describe the patient- and procedure-related drivers of THU, immediate procedure reimbursement, and surgeon reimbursement. Results: There were 34,862 patients identified. On multivariable analysis, the main driver of THU and immediate procedure reimbursement was an outpatient hospital as the surgical setting (US$6789 increase in THU). The main driver of surgeon reimbursement was an out-of-network surgeon (US$1337 increase). Health maintenance organization as the insurance plan type decreased THU, immediate procedure reimbursement, and surgeon reimbursement (US$955, US$108, and US$38 decrease, respectively, compared with preferred provider organization; P < .05 for all). Conclusion: Performing procedures in more cost-efficient ambulatory surgery centers had the largest effect on decreasing health care expenditures for ACLR. Health maintenance organizations aided in cost-optimization efforts as well, but had a minor effect on surgeon reimbursement. Overall, this study increases transparency into what drives reimbursement and serves as a foundation for how to decrease health care expenditures related to ACLR.

BACKGROUND Chronic intestinal failure (CIF) is an ultrarare disease, with an estimated national prevalence of ∼25,000 cases. There is a suspicion of widespread lack of expertise in CIF care, but no formal assessment tool or data exist. We developed and validated a knowledge test in CIF and now report our preliminary results from testing CIF knowledge in a cohort of US gastroenterologists. METHOD We developed a 20-question knowledge test in CIF, covering four key components of IF. After internal testing, refinement, and revision, we administered the test to a convenience sample of experts and nonexperts in IF. We then deployed the validated test to a cohort of 100 US gastroenterologists. RESULTS The test had a Cronbach alpha of 0.74, suggesting a reliable test, with a threshold score to discriminate experts and nonexperts of 13.4 (maximum 20) and with a sensitivity of 81.3% and specificity of 86.4%. The overall mean score of 8.2 for the 100 US gastroenterologists was at the level of nonexperts in our convenience sample. CONCLUSION The preliminary results of our validated knowledge test in IF among a broad group of US gastroenterologists demonstrate lack of knowledge in IF.

PURPOSE: The ASCO Quality Oncology Practice Initiative (QOPI) project was established to evaluate the influence of guideline recommendations on routine clinical practice. METHODS: QOPI provided summary data from 839 unique practices in which data were collected every six months from the Fall of 2015 to the Spring of 2019. From these data, six items were chosen based on their relationship to domains of survivorship. A zero-inflated negative binomial regression model was used to test for trends in QOPI measures adherence rates over time. The models were adjusted for the time period, region, practice-ownership, multispecialty site, fellowship program, and hospital type. RESULTS: Smoking cessation counseling recommended and smoking cessation counseling administered or referred both increased over time, 50%-61% (adjusted incidence rate ratios (IRR), 1.028; 95% CI, 1.016 to 1.040; P < .001) and 34%-49% (adjusted IRR, 1.052; 95% CI, 1.035 to 1.070; P < .001), respectively. Infertility risks discussed before chemotherapy increased from 36% to 53% (adjusted IRR, 1.056; 95% CI, 1.035 to 1.078; P < .001) and fertility options discussed or referred to specialists increased from 23% to 38% (adjusted IRR, 1.074; 95% CI, 1.046 to 1.102; P < .001). Twenty-nine percent documented a positron emission tomography, computed tomography, or bone scan within the first 12 months for women diagnosed with early breast cancer treated for curative intent (adjusted IRR, 1.000; 95% CI, 0.977 to 1.024; P = .971). Tumor marker surveillance within 12 months increased from 78% to 87% (adjusted IRR, 1.018; 95% CI, 1.002 to 1.033; P = .023). CONCLUSION: As scientific evidence to guide cancer survivorship care grows, the role of guideline recommendations permeating clinical practice using quality metrics will become increasingly important.

BACKGROUND An increasing body of evidence demonstrates an association between obstructive sleep apnea (OSA) and adverse perioperative outcomes. However, large-scale data on open colectomies are lacking. Moreover, the interaction of obesity with OSA is unknown. This study examines the impact of OSA, obesity, or a combination of both, on perioperative complications in patients undergoing open colectomy. We hypothesized that while both obesity and OSA individually increase the likelihood for perioperative complications, the overlap of the 2 conditions is associated with the highest risk. METHODS Patients undergoing open colectomies were identified using the national Premier Healthcare claims-based Database (2006-2016; n = 340,047). Multilevel multivariable models and relative excess risk due to interaction (RERI) analysis quantified the impact of OSA, obesity, or both on length and cost of hospitalization, respiratory and cardiac complications, intensive care unit (ICU) admission, mechanical ventilation, and inhospital mortality. RESULTS Nine thousand twenty-eight (2.7%) patients had both OSA and obesity diagnoses; 10,137 (3.0%) had OSA without obesity; and 33,692 (9.9%) had obesity without OSA. Although there were overlapping confidence intervals in the binary outcomes, the risk increase was found highest for OSA with obesity, intermediate for obesity without OSA, and lowest for OSA without obesity. The strongest effects were seen for respiratory complications: odds ratio (OR), 2.41 (2.28-2.56), OR, 1.40 (1.31-1.49), and OR, 1.50 (1.45-1.56), for OSA with obesity, OSA without obesity, and obesity without OSA, respectively (all P < .0001). RERI analysis revealed a supraadditive effect of 0.51 (95% confidence interval [CI], 0.34-0.68) for respiratory complications, 0.11 (-0.04 to 0.26) for cardiac complications, 0.30 (0.14-0.45) for ICU utilization, 0.34 (0.21-0.47) for mechanical ventilation utilization, and 0.26 (0.15-0.37) for mortality in patients with both OSA and obesity, compared to the sum of the conditions' individual risks. Inhospital mortality was significantly higher in patients with both OSA and obesity (OR [CI], 1.21 [1.07-1.38]) but not in the other groups. CONCLUSIONS Both OSA and obesity are individually associated with adverse perioperative outcomes, with a supraadditive effect if both OSA and obesity are present. Interventions, screening, and perioperative precautionary measures should be tailored to the respective risk profile. Moreover, both conditions appear to be underreported compared to the general population, highlighting the need for stringent perioperative screening, documentation, and reporting.

Background With increasing use of tranexamic acid in total hip and knee arthroplasties, safety concerns remain. Using national claims data, this study examined tranexamic acid use in patients with preexisting comorbidities. The hypothesis was that tranexamic acid use is not associated with increased complication risk in hip and knee arthroplasty patients with comorbidities. Methods Among 765,011 total hip/knee arthroplasties (2013 to 2016, Premier Healthcare claims), tranexamic acid use was assessed in three high-risk groups: group I with patients with a history of venous thromboembolism, myocardial infarction, seizures, or ischemic stroke/transient ischemic attack (n = 27,890); group II with renal disease (n = 44,608); and group III with atrial fibrillation (n = 45,952). The coprimary outcomes were blood transfusion and new-onset “composite complications” (venous thromboembolism, myocardial infarction, seizures, and ischemic stroke/transient ischemic attack). Associations between tranexamic acid use and outcomes were measured separately by high-risk group. The odds ratios and Bonferroni-adjusted 99.9% CIs are reported. Results Overall, 404,974 patients (52.9%) received tranexamic acid, with similar frequencies across high-risk groups I (13,004 of 27,890 [46.6%]), II (22,424 of 44,608 [50.3%]), and III (22,379 of 45,952 [48.7%]). Tranexamic acid use was associated with decreased odds of blood transfusion in high-risk groups I (721 of 13,004 [5.5%] vs. 2,293 of 14,886 [15.4%]; odds ratio, 0.307; 99.9% CI, 0.258 to 0.366), group II (2,045 of 22,424 [9.1%] vs. 5,159 of 22,184 [23.3%]; odds ratio, 0.315; 99.9% CI, 0.263 to 0.378), and group III (1,325 of 22,379 [5.9%] vs. 3,773 of 23,573 [16.0%]; odds ratio, 0.321; 99.9% CI, 0.266 to 0.389); all adjusted comparisons P < 0.001. No increased odds of composite complications were observed in high-risk group I (129 of 13,004 [1.0%] vs. 239 of 14,886 [1.6%]; odds ratio, 0.89, 99.9% CI, 0.49 to 1.59), group II (238 of 22,424 [1.1%] vs. 369 of 22,184 [1.7%]; odds ratio, 0.98; 99.9% CI, 0.58 to 1.67), and group III (187 of 22,379 [0.8%] vs. 290 of 23,573 [1.2%]; odds ratio, 0.93; 99.9% CI, 0.54 to 1.61); all adjusted comparisons P > 0.999. Conclusions Although effective in reducing blood transfusions, tranexamic acid is not associated with increased complications, irrespective of patient high-risk status at baseline. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Fluoroquinolone prophylaxis is recommended during induction chemotherapy for patients with acute myeloid leukemia (AML) to reduce risk of neutropenic fever and systemic bacterial infections. We evaluated the effectiveness of primary fluoroquinolone prophylaxis in an area with high fluoroquinolone resistance.We performed a retrospective chart review of newly diagnosed adult AML patients who received frontline therapy at Mount Sinai Hospital in New York, NY, between 2012 and 2019. Primary outcome was development of neutropenic fever. Secondary outcomes were development of systemic bacterial infections and infections with multidrug-resistant organisms and Clostridioides difficile. Infectious outcomes were collected through 6 months after therapy initiation. We estimated the effect of fluoroquinolone prophylaxis with a time-dependent Cox proportional hazards model.Of 121 included patients, 87 received antibiotic prophylaxis and 34 did not. There was no difference in baseline characteristics, although the prophylaxis group had longer neutropenia duration (median 30 vs. 23 days, P = .013). The prophylaxis group had a reduced risk of neutropenic fever (hazard ratio 0.59, P = .039). The prophylaxis group had fewer gram-positive (P = .043) and gram-negative (P = .049) bloodstream infections and fewer clinically documented infections during frontline therapy (P = .005) and follow-up (P = .026). There was no difference in incidence of C. difficile or infection with fluoroquinolone-resistant or multidrug-resistant organisms. There was no mortality difference between groups.In an area with high fluoroquinolone resistance, primary fluoroquinolone prophylaxis in newly diagnosed AML patients reduced the risk of neutropenic fever and systemic bacterial infections without increased antimicrobial resistance. Prospective, randomized studies are needed to confirm these observations.

Introduction Tranexamic acid (TXA) has been shown to reduce blood loss and transfusion risk in various orthopedic surgeries including shoulder arthroplasty. However, concerns still exist regarding its use in patients with a history of thrombotic events. Using national claims data, we aimed to study the safety of TXA administration in shoulder arthroplasty patients with a history of thrombotic events. Methods We used retrospective national claims data (Premier Healthcare) on 71,174 patients who underwent a total or reverse shoulder arthroplasty between 2010 and 2016. TXA use was evaluated specifically within a subgroup of patients with a history of thrombotic events such as myocardial infarction, deep venous thrombosis, pulmonary embolism, transient ischemic attack, or ischemic stroke. Studied outcomes were blood transfusion need, complications (including acute renal failure, new onset myocardial infarction, deep venous thrombosis, pulmonary embolism, transient ischemic attack, or ischemic stroke), and cost and length of hospitalization. Mixed-effects models measured the association between TXA use and outcomes, separately in patients with and without a history of thrombotic events. Odds ratios (OR) or percent change for continuous outcomes with 95% confidence intervals (CI) were reported. Results Overall, TXA was used in 13.7% (n = 9735) of patients, whereas 10.5% (n = 7475) of patients had a history of a thrombotic event. After adjustment for relevant covariates, TXA use (compared with no TXA use) in patients without a history of thrombotic events was associated with decreased odds of blood transfusions (OR, 0.48; CI, 0.24-0.98; P = .0444), whereas no increased odds for complications were observed (OR, 0.83; CI, 0.40-1.76; P = .6354). Similar results were observed in patients with a history of thrombotic events. Moreover, in this subgroup, TXA use was associated with a slight reduction in hospitalization cost (−8.9% CI: −13.1%; −4.6%; P Conclusions Among shoulder arthroplasty patients, TXA use was not associated with increased complication odds, independent of a history of thrombotic events. These findings are in support of wider TXA use.

Medical knowledge is increasing at an exponential rate. At the same time, unexplained variations in practice and patient outcomes and unacceptable rates of medical errors and inefficiencies in health care delivery have emerged. Our Institute for Health Care Delivery Science (I-HDS) began in 2014 as a novel platform to conduct multidisciplinary healthcare delivery research. We followed ten strategies to develop a successful institute with excellence in methodology and strong understanding of the value of team science. Our work was organized around five hubs: 1) Quality/Process Improvement and Systematic Review, 2) Comparative Effectiveness Research, Pragmatic Clinical Trials, and Predictive Analytics, 3) Health Economics and Decision Modeling, 4) Qualitative, Survey, and Mixed Methods, and 5) Training and Mentoring. In the first 5 years of the I-HDS, we have identified opportunities for change in clinical practice through research using our health system’s electronic health record (EHR) data, and designed programs to educate clinicians in the value of research to improve patient care and recognize efficiencies in processes. Testing the value of several model interventions has guided prioritization of evidence-based quality improvements. Some of the changes in practice have already been embedded in the EHR workflow successfully. Development and sustainability of the I-HDS has been fostered by a mix of internal and external funding, including philanthropic foundations. Challenges remain due to the highly competitive funding environment and changes needed to adapt the EHR to healthcare delivery research. Further stakeholder engagement and culture change working with hospital leadership and I-HDS core and affiliate members continues.

The role of anticoagulation (AC) in the management of cirrhotic patients with portal vein thrombosis (PVT) remains unclear. We conducted a retrospective study of cirrhotic patients diagnosed with PVT from 1/1/2000 through 2/1/2019, comparing those who received AC to those who did not. Outcomes included rate of complete radiographic resolution (CRR) of PVT, recanalization of occlusive PVT (RCO), PVT extension, major bleeding, and overall survival (OS). The log-rank test was used to compare Kaplan–Meier distributions of time-to-event outcomes. Multivariable Cox-proportional-hazards modeling was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals. A total of 214 patients were followed for a median 27 months (IQR 12–48). Eighty-six patients (39%) received AC. AC was associated with significantly greater CRR (48% vs. 27%, p = 0.0007), (multivariable HR for CRR with AC; 2.49 (1.54–4.04, p = 0.0002)). AC was also associated with significantly greater RCO (69% vs. 28%, p = 0.0013), (multivariable HR for RCO with AC; 4.86 (1.91–12.37, p = 0.0009)). Rates of major bleeding were similar with and without AC (20% vs. 17%, p = 0.5207), multivariable HR for major bleeding with AC; 1.29 (0.68–2.46, p = 0.4423)). OS rates in the AC and no-AC groups were 83% and 70%, respectively (p = 0.1362), (HR for death with AC; 0.69 (0.38–1.28, p = 0.2441)). Among 75 patients who had CRR, 10 (13%) experienced recurrent PVT during follow-up (none were receiving AC at the time of recurrence). AC appears safe and effective for the treatment of cirrhotic PVT; however, prospective studies to confirm these findings and evaluate additional outcomes are needed.

Introduction Whole brain radiation therapy (WBRT) is widely used to treat patients with brain metastases. However, there is debate regarding its utility in patients with poor prognoses. In this study, we sought to characterize the use of WBRT in the United States, especially in adults aged 55 and above. Material and Methods Patients with brain metastases were identified using the National Cancer Database between 2010 and 2013. The receipt and completion of WBRT with various patient factors were correlated using multivariable logistic regression. Results 28,422 patients with brain metastases were identified, 23,362 of whom were aged 55 or above. 14,845 patients received WBRT and 12,310 patients completed treatment. Among adults aged 55 and above, 11,945 patients received WBRT, and 9812 patients completed treatment. Patients aged 60 and above were less likely to receive WBRT, while those aged 65 and above were less likely to complete WBRT. Discussion These results suggest that WBRT may be over-utilized in the United States, especially among older adults. Better interventions to improve pre-WBRT decision-making in this population are needed to select patients who might derive benefit.

Observational data suggest an acquired prothrombotic state may contribute to the pathophysiology of COVID-19. These data include elevated D-dimers observed among many COVID-19 patients. We present a retrospective analysis of admission D-dimer, and D-dimer trends, among 1065 adult hospitalized COVID-19 patients, across 6 New York Hospitals. The primary outcome was all-cause mortality. Secondary outcomes were intubation and venous thromboembolism (VTE). Three-hundred-thirteen patients (29.4%) died, 319 (30.0%) required intubation, and 30 (2.8%) had diagnosed VTE. Using Cox proportional-hazard modeling, each 1 μg/ml increase in admission D-dimer level was associated with a hazard ratio (HR) of 1.06 (95%CI 1.04–1.08, p, Highlights • We present a retrospective analysis of admission D-dimer, and D-dimer trends, among adults hospitalized for COVID-19. • 1065 inpatients from 6 hospitals were included; outcomes included mortality, intubation, and VTE. • Admission D-dimers and D-dimer trends were associated with outcomes in COVID-19. • However, D-dimer levels and trends were limited prognostic tests in COVID-19. • The role of D-dimer levels in COVID-19 clinical decision making remains unclear.

Bundled payment models may lead to selection of healthier total joint arthroplasty (TJA) candidates resulting in comorbid patients being taken care of in fewer hospitals. We aimed to (1) evaluate hospital-specific TJA comorbidity burden ("casemix") over time and (2) associations with resource utilization.This retrospective cohort study used 2011 and 2016 New York State data (n = 36,078 hip/knee arthroplasties). Comorbidity burden was estimated by the Charlson-Deyo Index; main outcomes were hospitalization cost and nonhome discharge. Hospitals were categorized into those with a decreased, stable (with a 5% buffer), or increased percentage of comorbidity-free patients (Charlson-Deyo = 0) between 2011 and 2016. Mixed-effects models measured the association between Charlson-Deyo Index category and outcomes, by hospital casemix categorization. Odds ratios and 95% confidence intervals (CIs) are reported.Overall, 29 (n = 8810), 37 (n = 16,297), and 46 (n = 10,971) hospitals were categorized into the decreased, stable, and increased Charlson-Deyo = 0 categories, respectively, with median annual TJA volumes of 499, 814, and 393 (P.0001). Multivariable models demonstrated that-in hospitals with a stable patient casemix-increased patient comorbidity was associated with increased hospitalization costs (maximum 21.8%, CI 18.9-24.9, P.0001). However, this effect was moderated (maximum 11.1%, CI 8.0-14.2) in hospitals that took on a more comorbid patient casemix. Similar patterns were observed for nonhome discharge.Most studied hospitals show an increase in comorbidity-free TJA patients, suggestive of patient selection. This redistribution of comorbid patients to select hospitals may not necessarily be a negative development as our results suggest more efficient resource utilization for comorbid patients in such hospitals.

Background Portal vein thrombosis (PVT) is a poorly described complication of inflammatory bowel disease (IBD). We sought to better characterize presentations, compare treatments, and assess outcomes in IBD-related PVT. Methods We conducted a retrospective investigation of IBD-related PVT at our institution. Multivariable Cox proportional hazards modeling was used to estimate adjusted hazard ratios across treatments. Results Sixty-three patients with IBD-related PVT (26 with Crohn disease, 37 with ulcerative colitis) were followed for a median 21 months (interquartile ratio [IQR] = 9-52). Major risk factors included intra-abdominal surgery (60%), IBD flare (33%), and intra-abdominal infection (13%). Primary hematologic thrombophilias were rare and did not impact management. Presentations were generally nonspecific, and diagnosis was incidental. Ninety-two percent of patients (58/63) received anticoagulation (AC), including 23 who received direct oral anticoagulants (DOACs), 22 who received warfarin, and 13 who received enoxaparin. All anticoagulated patients started AC within 3 days of diagnosis. Complete radiographic resolution (CRR) of PVT occurred in 71% of patients. We found that DOACs were associated with higher CRR rates (22/23; 96%) relative to warfarin (12/22; 55%): the hazard ratio of DOACs to warfarin was 4.04 (1.83-8.93; P = 0.0006)). Patients receiving DOACs required shorter courses of AC (median 3.9 months; IQR = 2.7-6.1) than those receiving warfarin (median 8.5 months; IQR = 3.9-NA; P = 0.0190). Incidence of gut ischemia (n = 3), symptomatic portal hypertension (n = 3), major bleeding (n = 4), and death (n = 2) were rare, and no patients receiving DOACs experienced these adverse outcomes. Conclusions We show that early and aggressive use of AC can lead to excellent outcomes in IBD-associated PVT and that DOACs are associated with particularly favorable outcomes in this setting.

Given increasing demand for primary knee arthroplasties, revision surgery is also expected to increase, with periprosthetic joint infection (PJI) a main driver of costs. Recent data on national trends is lacking. We aimed to assess trends in PJI in total knee arthroplasty revisions and hospitalization costs. From the National Inpatient Sample (2003–2016), we extracted data on total knee arthroplasty revisions (n = 782,449). We assessed trends in PJI prevalence and (inflation-adjusted) hospitalization costs (total as well as per-day costs) for all revisions and stratified by hospital teaching status (rural/urban by teaching status), hospital bed size (≤299, 300–499, and ≥500 beds), and hospital region (Northeast, Midwest, South, and West). The Cochran–Armitage trend test (PJI prevalence) and linear regression determined significance of trends. PJI prevalence overall was 25.5% (n = 199,818) with a minor increasing trend: 25.3% (n = 7,828) in 2003 to 28.9% (n = 19,275) in 2016; p

Anagrelide (ANA) is a platelet-specific cytoreductive agent utilized in the guideline-directed management of high-risk essential thrombocythemia. In the context of polycythemia vera (PV), ANA is occasionally employed in clinical practice, although data has not consistently demonstrated a benefit to targeting a platelet goal as a therapeutic endpoint. The aim of the current study was to delineate the patterns of ANA use in PV, and to describe outcomes and toxicities. Within a multi-center cohort of 527 patients with PV, 48 received ANA (9 excluded for absent data). 27 (69.2%) had high-risk PV, 10 (25.6%) had prior thrombosis, and none had extreme thrombocytosis, acquired von Willebrand disease, and/or documented resistance to hydroxyurea. While ANA effectively lowered median platelet count, 43.5% of patients had an unresolved thrombocytosis at time of ANA discontinuation. Treatment-emergent adverse events-including headaches, cardiac palpitations and arrhythmias, nausea, vomiting and/or diarrhea-led to ANA discontinuation in 76.9% of patients. Further, three patients experienced arterial thromboses during a median duration of 27.5 months of ANA therapy. In conclusion, this study highlights ANA's restrictive tolerability profile which, compounded by the absence of clear advantage to strict platelet control in PV, suggests the use of ANA should be limited in this setting.

After the suspension of elective surgeries was lifted in June 2020 in New York State, challenges remained regarding coordination of total joint arthroplasty (TJA) cases. Using the experience from a high-volume health system in New York City, we aimed to describe patterns of care after resumption of elective TJA.We retrospectively assessed 7,699 TJAs performed before and during the COVID-19 pandemic. Perioperative characteristics and clinical outcomes were compared between TJAs based on time period of performance: 1) pre-pandemic (PP, June 8th-December 8th, 2019), 2) initial period post-resumption of elective surgeries (IR, June 8th-September 8th, 2020), and 3) later period post-resumption (LR, September 9th-December 8th, 2020).LOS 2 days (83%, 67%, 70% for PP, IR, LR periods respectively) and discharge rates to post-acute care (PAC) facilities were lower during the pandemic periods (ORDespite decreased LOS and discharge to PAC for TJAs performed during the pandemic, 30-day readmissions did not increase. Given the increased costs and lack of superior functional outcomes associated with discharge to PAC, these findings suggest that discharge to PAC facilities need not return to pre-pandemic levels.

Provider-run "joint classes" educate total joint arthroplasty (TJA) patients on how to best prepare for surgery and maximize recovery. There is no research on potential healthcare inequities in the context of joint classes or on the impact of the recent shift toward telehealth due to coronavirus disease 2019 (COVID-19). Using data from a large metropolitan health system, we aimed to (1) identify demographic patterns in prepandemic joint class attendance and (2) understand the impact of telehealth on attendance.We included data on 3,090 TJA patients from three centers, each with a separately operated joint class. Attendance patterns were assessed prepandemic and after the resumption of elective surgeries when classes transitioned to telehealth. Statistical testing included standardized differences (SD0.1 indicates significance) and a multivariate linear regression.The in-person and telehealth attendance rates were 69.9% and 69.2%, respectively. Joint class attendance was significantly higher for non-White, Hispanic, non-English primary language, Medicaid, and Medicare patients (all SD0.1). Age was a determinant of attendance for telehealth (SD0.1) but not for in-person (SD = 0.04). Contrastingly, physical distance from hospital was significant for in-person (SD0.1) but not for telehealth (SD = 0.06). On a multivariate analysis, distance from hospital (P.05) and telehealth (P.0001) were predictors of failed class attendance.This work highlights the relative importance of joint classes in specific subgroups of patients. Although telehealth attendance was lower, telehealth alleviated barriers to access related to physical distance but increased barriers for older patients. These results can guide providers on preoperative education and the implementation of telehealth.

BACKGROUND: Large-scale data assessing the effect of a prior failed rotator cuff repair (RCR) on the outcome of reverse shoulder arthroplasty (RSA) is currently lacking. Therefore, this study aimed (1) to assess the course of patients undergoing RCR, specifically focusing on the need for conversion to RSA within two years, and (2) to compare outcomes following RSA performed for rotator cuff tears (RCTs) with and without prior RCR. METHODS: This retrospective cohort study included data from the CMS Data Set (2016–2018). For the first study objective, we included patients undergoing an RCR; these were followed for 24 months to identify a conversion to RSA. For the second study objective, we included RSAs for RCTs, stratified by those with and without a prior RCR (preceding 24 months). Outcomes (hospitalization cost, institutional post-acute care discharge, 90-day readmission and health resource utilization up to 6 months post-RSA) were compared between propensity score-matched groups. RESULTS: Out of 33,244 RCRs, 433 (1.3%) patients underwent RSA conversion within two years. Among 7534 RSA cases for RCTs, 245 (3.3%) had an RCR in the preceding two years. In the propensity score analysis, except for a minimal increase in the number of physical rehabilitation visits (RR 1.10; p = 0.0009), no differences were observed between those with and without prior RCR in terms of other RSA outcomes. These included hospitalization cost, discharge to institutional post-acute care facility, 90-day readmission and 6-month post-op cost CONCLUSION: Rotator cuff repair in elderly patients, when utilizing currently employed indication criteria, results in low conversion rates to RSA within 2 years postoperatively. Furthermore, large dataset outcomes after RSA for RCT such as cost, post-acute care discharge, physical rehabilitation, and readmission rates appear not to be negatively affected by the presence of a prior RCR. LEVEL OF EVIDENCE: Level 3 evidence; Retrospective cohort study.

Background: While the comprehensive care for joint replacement (CJR) bundled payment program for total joint replacement (TJR) emphasizes value, concerns persist regarding unintended consequences, primarily hospital selection of healthier, younger patients. Purpose: We sought to assess changes in patient characteristics and outcomes after CJR implementation in New York State. Methods: This retrospective cohort study included primary total hip and total knee arthroplasties from the New York Statewide Planning and Research Cooperative System (SPARCS) database. Procedures performed before (July 2014 to March 2016; n = 58,610) and after (April 2016 to December 2017; n = 78,728) CJR implementation were compared. Primary outcomes were patient characteristics: Deyo-Comorbidity Index and age. Secondary outcomes were increased hospitalization cost, discharge to institutional post-acute care, and prolonged length of stay. A difference-in-differences analysis estimated changes after CJR implementation, comparing CJR to non-CJR hospitals. Results: We found that CJR implementation (in 49 of 144 New York State hospitals) coincided with slightly older and more comorbid TJR recipients. The CJR program coincided with significantly reduced hospitalization cost and discharge to institutional post-acute care but not length of stay. Some CJR effects appear to have affected non-Medicare patients, as well. Conclusion: This retrospective analysis suggests that in New York State, the CJR bundled payment program did not result in hospitals selecting younger and healthier TJR recipients and coincided with decreased costs and fewer discharges to institutional postacute care.

BACKGROUND Hip fracture patients represent various perioperative challenges related to their significant comorbidity burden and the high incidence of morbidity and mortality. As population trend data remain rare, we aimed to investigate nationwide trends in the United States in patient demographics and outcomes in patients after hip fracture repair surgery. METHODS After Institutional Review Board (IRB) approval (IRB#2012-050), data covering hip fracture repair surgeries were extracted from the Premier Healthcare Database (2006-2016). Patient demographics, comorbidities, and complications, as well as anesthesia and surgical details, were analyzed over time. Cochran-Armitage trend tests and simple linear regression assessed significance of (linear) trends. RESULTS Among N = 507,274 hip fracture cases, we observed significant increases in the incidence in preexisting comorbid conditions, particularly the proportion of patients with >3 comorbid conditions (33.9% to 43.4%, respectively; P < .0001). The greatest increase for individual comorbidities was seen for sleep apnea, drug abuse, weight loss, and obesity. Regarding complications, increased rates over time were seen for acute renal failure (from 6.9 to 11.1 per 1000 inpatient days; P < .0001), while significant decreasing trends for mortality, pneumonia, hemorrhage/hematoma, and acute myocardial infarction were recorded. In addition, decreasing trends were observed for the use of neuraxial anesthesia either used as sole anesthetic or combined with general anesthesia (7.3% to 3.6% and 6.3% to 3.4%, respectively; P < .0001). Significantly more patients (31.9% vs 41.3%; P < .0001) were operated on in small rather than medium- and large-sized hospitals. CONCLUSIONS From 2006 to 2016, the overall comorbidity burden increased among patients undergoing hip fracture repair surgery. Throughout this same time period, incidence of postoperative complications either remained constant or declined with the only significant increase observed in acute renal failure. Moreover, use of regional anesthesia decreased over time. This more comorbid patient population represents an increasing burden on the health care system; however, existing preventative measures appear to be effective in minimizing complication rates. Although, given the proposed benefits of regional anesthesia, decreased utilization may be of concern.

BACKGROUND AND PURPOSE Transcranial Doppler (TCD) criteria for cerebrovascular stenosis are only based on velocity with unsatisfactory positive predictive value (PPV) in previous studies. We refined a published scoring system that integrates several characteristics of TCD data in diagnosing middle cerebral artery (MCA) stenosis. METHODS Using the TCD-digital subtraction angiography (DSA) database from Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA) trial, velocity, spectrum pattern, diffuse ratio, and asymmetry ratio were assessed. The cutpoints were defined for each parameter and a point value was assigned to each category within that parameter. A summed score was calculated for each MCA. The accuracy was assessed for different cutpoints in predicting ≥50% MCA stenosis measured by DSA. Logistic regression and C-statistics were used for analysis. RESULTS A total of 114 MCAs were included in vessel-based and 87 patients were included in patient-based analysis. Compared to the velocity-only cutpoints in SONIA, the score results in much improved PPV while negative predictive value (NPV) remains unchanged. The score based on mean velocity (score 0

Introduction Although surgical drains have been used routinely in total knee arthroplasties (TKAs), results from several large trials have led to recommendations against their use. Because national data are lacking, we aimed at assessing utilization patterns of drains and perioperative outcomes in TKA procedures. Methods We included 1,130,124 TKA procedures from the national claims-based Premier Healthcare Database (2006 to 2016). Patients receiving a drain were compared with those who did not. Multivariable multilevel models measured associations between drain use and blood transfusions, postoperative infections, 30-day readmission, and length/cost of hospitalization. Odds ratios and 95% confidence intervals are reported. Propensity score analyses were performed to assess the robustness of results. Results Drain use decreased from 33.0% (n = 22,901 of 69,370) in 2006 to 15.6% (n = 19,418 of 124,440) in 2016 and was particularly higher in large (>500 beds; 27.1%) and nonteaching hospitals (26.9%). After adjustment for relevant covariates, the use of drains (compared with no use) was significantly associated with increases in particularly blood transfusions (odds ratio, 1.27; 95% confidence interval, 1.24 to 1.30 n = 138,306 total transfusions), whereas minimal effects were seen for other outcomes. Propensity score analyses confirmed these results. Discussion Although retrospective, the current study provides an important insight into real-world clinical practice regarding the use of drains. With current evidence not supporting their use in TKA, we found that national utilization is slowly decreasing. Moreover, because drain use is associated with negative outcomes, future studies should focus on drivers of their continued use. Level of evidence Level III, therapeutic study.

Postoperative loss of airway requiring reintubation is a rare but potentially catastrophic complication following anterior cervical discectomy and fusion (ACDF). We sought to identify risk factors asscociated with reintubation within one day following ACDF. Attention was focused on patient demographics, comorbidities, and factors potentially linked to soft tissue swelling and hematoma formation that could compromise the upper airway. We performed a retrospective cohort study of patients who underwent ACDF procedures at a high-volume institution from 2005 to 2014 (n = 3,041), participating hospitals in the National Surgical Quality Improvement Program (NSQIP) (n = 47,425), and Premier Healthcare (n = 233,633) databases from 2006 to 2016. Separate multivariable logistic regression models using the NSQIP and Premier samples were used to identify risk factors for reintubation within one day of ACDF. Odds ratios (OR) and 95% confidence intervals (CI) are reported. Incidence of reintubation within one day of ACDF was 0.19% in the institutional database and 0.21% in NSQIP and Premier databases. Risk factors for reintubation included older age, male sex, high comorbidity burden, procedures performed at large hospitals, non-elective procedures, Medicaid insurance, and use of heparin or more than one anticoagulant. Intravenous or oral steroid use (OR, 0.45; 95% CI, 0.36 to 0.56; P < 0.001) and delayed extubation (OR, 0.28 95% CI, 0.16 to 0.49; P < 0.001) were found to decrease risk of reintubation. Across three complementary data sets, incidence of reintubation within one day of ACDF was approximately 0.20%. Increased risk of reintubation associated with anticoagulant administration suggests upper airway hematoma as an underlying etiology. Steroid administration and delayed extubation may be useful in patients considered to be at higher risk for reintubation.

BackgroundWith an ageing population, the demand for joint arthroplasties and the burden of postoperative delirium is likely to increase. Given the lack of large-scale data, we investigated associations between perioperative risk factors and postoperative delirium in arthroplasty surgery.MethodsThis retrospective population-based cohort study, utilized national claims data from the all-payer Premier Healthcare database containing detailed billing information from >25% nationwide hospitalizations. Patients undergoing elective total hip/knee arthroplasty surgery (2006–2016) were included.The primary outcome was postoperative delirium, while potential risk factors included age, gender, race, insurance type, and modifiable exposures including anesthesia type, opioid prescription dose (low/medium/high), benzodiazepines, meperidine, non-benzodiazepine hypnotics, ketamine, corticosteroids, and gabapentinoids.ResultsAmong 1 694 795 patients’ postoperative delirium was seen in 2.6% (14 785/564 226) of hip and 2.9% (32 384/1 130 569) of knee arthroplasties. Multivariable models revealed that the utilization of long acting (OR 2.10 CI 1.82 to 2.42), combined long/short acting benzodiazepines (OR 1.74 CI 1.56 to 1.94), and gabapentinoids (OR 1.26 CI 1.16 to 1.36) was associated with increased odds of postoperative delirium. Lower odds of postoperative delirium were seen for neuraxial versus general anesthesia (OR 0.81 CI 0.70 to 0.93) and with the utilization of non-steroidal anti-inflammatory drugs (OR 0.85 CI 0.79 to 0.91) as well as cyclooxygenase-2 inhibitors (OR 0.82 CI 0.77 to 0.89). Age-stratified analysis revealed lower odds with high versus low opioid dose (OR 0.86 CI 0.76 to 0.98) in patients >65 years. Findings were consistent between hip and knee arthroplasties.ConclusionsIn this large national cohort, we identified various modifiable risk factors (including anesthesia type and pharmaceutical agents) for postoperative delirium, demonstrating possible prevention pathways.

Epidemiologic and preclinical data suggest isoflavones have anticancer activity in colorectal malignancy prevention and treatment. This is the first clinical trial assessing safety and tolerability of Genistein in combination with chemotherapy in metastatic colorectal cancer. Patients who had histologically confirmed metastatic colorectal cancer and had not received previous treatment were eligible to enroll. Subjects were treated with FOLFOX or FOLFOX–Bevacizumab as per the investigator choice. Genistein was administered orally for 7 days every 2 weeks, beginning 4 days prior to chemotherapy and continuing through days 1–3 of infusional chemotherapy. Primary endpoint was safety and secondary endpoints included cycle 6 response rate, best overall response rate (BOR), and median progression-free survival (PFS). Thirteen patients received chemotherapy with Genistein in this trial. The most common adverse events related to Genistein alone were mild and included headaches, nausea, and hot flashes. One subject was observed to have grade 3 hypertension. No increase in chemotherapy-related adverse events was observed when Genistein was added. BOR and median PFS were 61.5% and 11.5 months, respectively. We observed that adding Genistein to FOLFOX or FOLFOX–Bevacizumab was safe and tolerable. Efficacy results are notable and warrant verification in larger clinical trials. The study was registered at ClinicalTrials.gov Identifier: NCT01985763.

Background and objectivesThe significance of intravenous over oral acetaminophen (APAP) as part of multimodal analgesic protocols is contested, particularly when considering its relatively high price and use in a surgical cohort such as total hip or knee arthroplasty (THA/TKA), which generally tolerates oral medications. This study aims to elucidate APAP’s effectiveness in a large, population-based patient sample.Methods1 039 647 THA/TKA procedures were sampled from the Premier Healthcare claims database 2011–2016. APAP use was categorized by intravenous/oral and use on the day of surgery, postoperative day 1 and thereafter. Outcomes were opioid utilization (in oral morphine equivalents), length and cost of hospitalization, and opioid-related adverse effects (respiratory, gastrointestinal, and naloxone use as a proxy). Mixed-effects models measured the associations between intravenous/oral APAP use and outcomes. Percent (%) change and 95% CIs are reported.ResultsOverall, 23.6% (n=245 454) of patients received intravenous APAP; of these, 56.3% (n=138 180) received just one dose on the day of surgery. After adjustment for relevant covariates, particularly use of >1 dose of intravenous APAP (compared with no use) on postoperative day 1 was associated with −6.0% (CI −7.2% to −4.7%) reduced opioid utilization; this was −10.7% (CI −11.4% to -9.9%) for use of > 1 dose oral APAP on postoperative day 1. Further comparisons regarding other outcomes also favored oral (over intravenous) APAP.ConclusionsThese results do not support the routine use of intravenous APAP in patients undergoing lower joint arthroplasty, especially since oral APAP shows more beneficial outcome patterns.

Background: The demand for total ankle arthroplasty (TAA) and ankle arthrodesis surgery is increasing. Findings from other orthopaedic populations suggest an increasing comorbidity burden among those planned for surgery, however, data on TAA and ankle arthrodesis is limited. The goal of this study is to study the comorbidity burden for TAA and ankle arthrodesis. Hypothesis: Comorbidity burden is associated with higher resource utilization for both TAA and ankle arthrodesis. Patients and Methods: This retrospective cohort study utilized data from the nationwide Premier Healthcare Database (2006-2016) which contains inpatient claims on N=10,085 ankle arthrodesis and N=4,977 TAA procedures. Patients were categorized into Deyo-Charlson comorbidity index (DCCI) groups. Outcomes were cost of hospitalization, length of stay (LOS), total opioid utilization, discharge to a skilled nursing facility (SNF), and 30-day readmission. Mixed-effects models estimated associations between DCCI and outcomes. We report odds ratios (OR, or % change for continuous outcomes) and 95% confidence intervals (CI). Results: In the TAA group, 67.9% of patients were in DCCI category 0 while 22.4%, 6.6%, and 3.1% were in the 1, 2, and >2 DCCI categories, respectively. This was 61.3%, 18.1%, 9.8% and 10.9% in the ankle arthrodesis group. The most common comorbidities were obesity, diabetes mellitus, and chronic pulmonary disease. Particularly in the ankle arthrodesis group, the proportion of patients with comorbidities has increased over time. After adjustment for relevant covariates, patients in the DCCI group >2 (compared to ‘0’) were associated with stepwise effects of up to 77.1% (CI 70.9%; 83.6%) longer length of stay and up to 48.5% (CI 44.0%; 53.2%) higher cost of hospitalization. Discussions: Comorbidity burden is increasing among patients undergoing ankle arthrodesis where it is associated with significantly increased resource utilization. Our data demonstrate the potential impact of patient selection, which may be crucial in optimizing preoperative status. Level of Evidence: III

Background Early identification of glioma molecular phenotypes can lead to understanding of patient prognosis and treatment guidance. We aimed to develop a multiparametric MRI texture analysis model using a combination of conventional and diffusion MRI to predict a wide range of biomarkers in patients with glioma. Methods In this retrospective study, patients were included if they (1) had diagnosis of gliomas with known IDH1, EGFR, MGMT, ATRX, TP53, and PTEN status from surgical pathology and (2) had preoperative MRI including FLAIR, T1c+ and diffusion for radiomic texture analysis. Statistical analysis included logistic regression and receiver-operating characteristic (ROC) curve analysis to determine the optimal model for predicting glioma biomarkers. A comparative analysis between ROCs (conventional only vs conventional + diffusion) was performed. Results From a total of 111 patients included, 91 (82%) were categorized to training and 20 (18%) to test datasets. Constructed cross-validated model using a combination of texture features from conventional and diffusion MRI resulted in overall AUC/accuracy of 1/79% for IDH1, 0.99/80% for ATRX, 0.79/67% for MGMT, and 0.77/66% for EGFR. The addition of diffusion data to conventional MRI features significantly (P < .05) increased predictive performance for IDH1, MGMT, and ATRX. The overall accuracy of the final model in predicting biomarkers in the test group was 80% (IDH1), 70% (ATRX), 70% (MGMT), and 75% (EGFR). Conclusion Addition of MR diffusion to conventional MRI features provides added diagnostic value in preoperative determination of IDH1, MGMT, and ATRX in patients with glioma.

The impact of pre-transplant (SOT) carbapenem-resistant Enterobacterales (CRE) colonization or infection on post-SOT outcomes is unclear. We conducted a multi-center, international, cohort study of SOT recipients, with microbiologically diagnosed CRE colonization and/or infection pre-SOT. Sixty adult SOT recipients were included (liver n = 30, hearts n = 17). Klebsiella pneumoniae (n = 47, 78%) was the most common pre-SOT CRE species. Median time from CRE detection to SOT was 2.32 months (IQR 0.33-10.13). Post-SOT CRE infection occurred in 40% (n = 24/60), at a median of 9 days (IQR 7-17), and most commonly due to K pneumoniae (n = 20/24, 83%). Of those infected, 62% had a surgical site infection, and 46% had bloodstream infection. Patients with post-SOT CRE infection more commonly had a liver transplant (16, 67% vs. 14, 39%; p =.0350) or pre-SOT CRE BSI (11, 46% vs. 7, 19%; p =.03). One-year post-SOT survival was 77%, and those with post-SOT CRE infection had a 50% less chance of survival vs. uninfected (0.86, 95% CI, 0.76-0.97 vs. 0.34, 95% CI 0.08-1.0, p =.0204). Pre-SOT CRE infection or colonization is not an absolute contraindication to SOT and is more common among abdominal SOT recipients, those with pre-SOT CRE BSI, and those with early post-SOT medical and surgical complications.

Enhanced recovery after surgery (ERAS) protocols are increasingly used in orthopedic surgery. Data are lacking on which combinations of ERAS components are (1) the most commonly used and (2) the most effective in terms of outcomes.This retrospective cohort study utilized claims data (Premier Healthcare, n = 1,539,432 total joint arthroplasties, 2006-2016). Eight ERAS components were defined: (A) regional anesthesia, (B) multimodal analgesia, (C) tranexamic acid, (D) antiemetics on day of surgery, (E) early physical therapy, and avoidance of (F) urinary catheters, (G) patient-controlled analgesia, and (H) drains. Outcomes were length of stay, "any complication," and hospitalization cost. Mixed-effects models measured associations between the most common ERAS combinations and outcomes. Odds ratios (ORs) and 95% confidence intervals (CIs) are reported.In 2006-2012 and 2013-2016, the most common ERAS combinations were B/D/E/F/G/H (20%, n = 172,397) and B/C/D/E/F/G/H (17%, n = 120,266), respectively. The only difference between the most commonly used ERAS combinations over the years is the addition of C (addition of tranexamic acid to the protocol). The most pronounced beneficial effects in 2006-2012 were seen for combination A/B/D/E/F/G/H (6% of cases vs less prevalent ERAS combinations) for the outcome of "any complication" (OR 0.87, CI 0.83-0.91, P.0001). In 2013-2016, the strongest effects were seen for combination B/C/D/E/F/G/H (17% of cases) also for the outcome of "any complication" (OR 0.86, CI 0.83-0.89, P.0001). Relatively minor differences existed between ERAS protocols for the other outcomes.Despite varying ERAS protocols, maximum benefits in terms of complication reduction differed minimally. Further study may elucidate the balance between an increasing number of ERAS components and incremental benefits realized.III.