Is Minimally Invasive Resection of Large Thymoma Appropriate?

BACKGROUND: Current practice patterns suggest open rather than minimally invasive (MIS) approaches for thymomas >4 cm. We hypothesized there would be similar perioperative outcomes and overall survival between open and MIS approaches for large (>4 cm) thymoma resection. METHODS: The National Cancer Database was queried for patients who underwent thymectomy from 2010 to 2020. Surgical approach was characterized as either open or MIS. The primary outcome was overall survival and secondary outcomes were margin status, and length of stay (LOS). Differences between approach cohorts were compared after a 1:1 propensity match. RESULTS: Among 4121 thymectomies, 2474 (60%) were open and 1647 (40%) were MIS. Patients undergoing MIS were older, had fewer comorbidities, and had smaller tumors (median; 4.6 vs 6 cm, P < .001). In the unmatched cohort, MIS and open had similar 90-day mortality (1.1% vs 1.8%, P = .158) and rate of positive margin (25.1% vs 27.9%, P = .109). MIS thymectomy was associated with shorter LOS (2 (1-4) vs 4 (3-6) days, P < .001). Propensity matching reduced the bias between the groups. In this cohort, overall survival was similar between the groups by log-rank test (P = .462) and multivariate cox hazard analysis (HR .882, P = .472). Multivariable regression showed shorter LOS with MIS approach (Coef -1.139, P < .001), and similar odds of positive margin (OR 1.130, P = .150). DISCUSSION: MIS has equivalent oncologic benefit to open resection for large thymomas, but is associated with shorter LOS. When clinically appropriate, MIS thymectomy may be considered a safe alternative to open resection for large thymomas.

Longitudinal association of epicardial and thoracic adipose tissues with coronary and cardiac characteristics in psoriasis.

Background: s: Psoriasis is a disease of systemic inflammation associated with increased cardiometabolic risk. Epicardial adipose tissue (EAT) and thoracic adipose tissue (TAT) are contributing factors for atherosclerosis and cardiac dysfunction. We strove to assess the longitudinal impact of the EAT and TAT on coronary and cardiac characteristics in psoriasis. Methods: The study consisted of 301 patients with baseline coronary computed tomography angiography (CTA), of which 139 had four-year follow up scans. EAT and TAT volumes from non-contrast computed tomography scans were quantified by an automated segmentation framework. Coronary plaque characteristics and left ventricular (LV) mass were quantified by CTA. Results: When stratified by baseline EAT and TAT volume quartiles, a stepwise significant increase in cardiometabolic parameters was observed. EAT and TAT volumes associated with fibro-fatty burden (FFB) (TAT: ρ = 0.394, P < 0.001; EAT: ρ = 0.459, P < 0.001) in adjusted models. Only EAT had a significant four-year time-dependent association with FFB in fully adjusted models (ß = 0.307 P = 0.003), whereas only TAT volume associated with myocardial injury in fully adjusted models (TAT: OR = 1.57 95 % CI = (1.00-2.60); EAT: OR = 1.46 95 % CI = (0.91-2.45). Higher quartiles of EAT and TAT had increased LV mass and developed strong correlation (TAT: ρ = 0.370, P < 0.001; EAT: ρ = 0.512, P < 0.001). Conclusions: Our study is the first to explore how both EAT and TAT volumes associate with increased cardiometabolic risk profile in an inflamed psoriasis cohorts and highlight the need for further studies on its use as a potential prognostic tool for high-risk coronary plaques and cardiac dysfunction.

Computational risk model for predicting 2-year malignancy of pulmonary nodules using demographic and radiographic characteristics.

OBJECTIVES: To determine whether discriminatory performance of a computational risk model in classifying pulmonary lesion malignancy using demographic, radiographic, and clinical characteristics is superior to the opinion of experienced providers. We hypothesized that computational risk models would outperform providers. METHODS: Outcome of malignancy was obtained from selected patients enrolled in the NAVIGATE trial (NCT02410837). Five predictive risk models were developed using an 80:20 train-test split: univariable logistic regression model based solely on provider opinion, multivariable logistic regression model, random forest classifier, extreme gradient boosting model, and artificial neural network. Area under the receiver operating characteristic curve achieved during testing of the predictive models was compared to that of prebiopsy provider opinion baseline using the DeLong test with 10,000 bootstrapped iterations. RESULTS: The cohort included 984 patients, 735 (74.7%) of which were diagnosed with malignancy. Factors associated with malignancy from multivariable logistic regression included age, history of cancer, largest lesion size, lung zone, and positron-emission tomography positivity. Testing area under the receiver operating characteristic curve were 0.830 for provider opinion baseline, 0.770 for provider opinion univariable logistic regression, 0.659 for multivariable logistic regression model, 0.743 for random forest classifier, 0.740 for extreme gradient boosting, and 0.679 for artificial neural network. Provider opinion baseline was determined to be the best predictive classification system. CONCLUSIONS: Computational models predicting malignancy of pulmonary lesions using clinical, demographic, and radiographic characteristics are inferior to provider opinion. This study questions the ability of these models to provide additional insight into patient care. Expert clinician evaluation of pulmonary lesion malignancy is paramount.

Declining Geographic Access to High-Volume Revision Total Hip Arthroplasty Surgeons: A National Medicare Analysis.

BACKGROUND: While trends in the economics of revision THA (revTHA) procedures have been well-described from the standpoint of both hospitals and surgeons, their population-level effects of these trends on patient access are not well-understood. METHODS: The Medicare fee-for-service provider utilization and payment public use files were used to extract data for primary and revTHA for beneficiaries between 2013 and 2019. Primary and revTHA procedures were identified using the Healthcare Common Procedure Coding System code; 27130 for primaries and 27132, 27134, 27137, or 27138 for revisions. Geospatial analyses were performed by aggregating surgeon practice locations at the level of individual counties, hospital service areas, and hospital referral regions. RESULTS: The number of high-volume primary THA surgeons within the Medicare population increased by 17.6% over the study period (3,838 in 2013 to 4,515 in 2019). Conversely, the number of high-volume revTHA surgeons decreased by 36.1% (178 in 2013 to 129 in 2019). Linear regression revealed a significant increase and decrease in high-volume primary (ß = 109.07, P ≤ .001) and revision (ß = -13.04, P = .011) THA surgeons, respectively. Over the study period, the number of counties with at least 1 high-volume primary THA surgeon increased by 6.1% (1,194 to 1,267), while the number of counties with at least 1 high-volume revTHA surgeon decreased by 30.2% (159 to 111). CONCLUSION: The present findings of declining geographic access may represent a consequence of shifting economic incentives and declining reimbursements for the care of complicated revTHA patients.

Association of Apremilast With Vascular Inflammation and Cardiometabolic Function in Patients With Psoriasis: The VIP-A Phase 4, Open-label, Nonrandomized Clinical Trial.

Importance: Psoriasis is an inflammatory condition associated with metabolic and cardiovascular disease. Apremilast, a phosphodiesterase 4 inhibitor, is commonly used for psoriasis and can cause weight loss. Objective: To determine the association between apremilast and aortic vascular inflammation as assessed by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), cardiometabolic markers (primary outcomes at week 16), and abdominal fat composition. Design, Setting, and Participants: A single-arm, open-label, interventional, nonrandomized clinical trial in which the imaging and laboratory outcomes were measured by an investigator who was blinded to time was conducted between April 11, 2017, and August 17, 2021, at 7 dermatology sites in the United States. A total of 101 patients with moderate to severe psoriasis were screened, 70 enrolled, 60 completed week 16, and 39 completed week 52. Intervention: Apremilast, 30 mg, twice daily. Main Outcomes and Measures: Aortic vascular inflammation (measured by FDG-PET/CT), 68 cardiometabolic biomarkers, and abdominal fat composition (measured by CT) at week 16 and week 52 compared with baseline. Results: The mean (SD) age of the 70 patients was 47.5 (14.6) years, 54 were male (77.1%), 4 were Black (5.7%), and 58 were White (82.9%). There was no change in aortic vascular inflammation at week 16 (target to background ratio, -0.02; 95% CI, -0.08 to 0.05; P = .61) or week 52 (target to background ratio, -0.07; 95% CI, -0.15 to 0.01; P = .09) compared with baseline. At week 16, potentially beneficial decreases in interleukin 1b, valine, leucine, isoleucine, fetuin A, and branched-chain amino acids were observed. At week 52 compared with baseline, potentially beneficial decreases in ferritin, ß-hydroxybutyrate, acetone, and ketone bodies, with an increase in apolipoprotein A-1, were observed, but there was a reduction in cholesterol efflux. There was an approximately 5% to 6% reduction in subcutaneous and visceral adiposity at week 16 that was maintained at week 52. Conclusions and Relevance: The findings of this nonrandomized clinical trial suggest that apremilast has a neutral association with aortic vascular inflammation, variable but generally beneficial associations with a subset of cardiometabolic biomarkers, and associations with reductions in visceral and subcutaneous fat, indicating that the drug may have an overall benefit for patients with cardiometabolic disease and psoriasis. Trial Registration: ClinicalTrials.gov Identifier: NCT03082729.

Inflammation, coronary plaque progression, and statin use: A secondary analysis of the Risk Stratification with Image Guidance of HMG CoA Reductase Inhibitor Therapy (RIGHT) study.

BACKGROUND: Statin treatment is a potent lipid-lowering therapy associated with decreased cardiovascular risk and mortality. Recent studies including the PARADIGM trial have demonstrated the impact of statins on promoting calcified coronary plaque. HYPOTHESIS: The degree of systemic inflammation impacts the amount of increase in coronary plaque calcification over 2 years of statin treatment. METHODS: A subgroup of 142 participants was analyzed from the Risk Stratification with Image Guidance of HMG CoA Reductase Inhibitor Therapy (RIGHT) study (NCT01212900), who were on statin treatment and underwent cardiac computed tomography angiography (CCTA) at baseline and 2-year follow-up. This cohort was stratified by baseline median levels of high-sensitivity hs-CRP and analyzed with linear regressions using Stata-17 (StataCorp). RESULTS: In the high versus low hs-CRP group, patients with higher baseline median hs-CRP had increased BMI (median [IQR]; 29 [27-31] vs. 27 [24-28]; p < .001), hypertension (59% vs. 41%; p = .03), and LDL-C levels (97 [77-113] vs. 87 [75-97] mg/dl; p = .01). After 2 years of statin treatment, the high hs-CRP group had significant increase in dense-calcified coronary burden versus the low hs-CRP group (1.27 vs. 0.32 mm2 [100×]; p = .02), beyond adjustment (ß = .2; p = .03). CONCLUSIONS: Statin treatment over 2 years associated with a significant increase in coronary calcification in patients with higher systemic inflammation, as measured by hs-CRP. These findings suggest that systemic inflammation plays a role in coronary calcification and further studies should be performed to better elucidate these findings.

Is Our Science Representative? A Systematic Review of Racial and Ethnic Diversity in Orthopaedic Clinical Trials from 2000 to 2020.

BACKGROUND: A lack of racial and ethnic representation in clinical trials may limit the generalizability of the orthopaedic evidence base as it applies to patients in underrepresented minority populations and perpetuate existing disparities in use, complications, or functional outcomes. Although some commentators have implied the need for mandatory race or ethnicity reporting across all orthopaedic trials, the usefulness of race or ethnic reporting likely depends on the specific topic, prior evidence of disparities, and individualized study hypotheses. QUESTIONS/PURPOSES: In a systematic review, we asked: (1) What proportion of orthopaedic clinical trials report race or ethnicity data, and of studies that do, how many report data regarding social covariates or genomic testing? (2) What trends and associations exist for racial and ethnic reporting among these trials between 2000 and 2020? (3) What is the racial or ethnic representation of United States trial participants compared with that reported in the United States Census? METHODS: We performed a systematic review of randomized controlled trials with human participants published in three leading general-interest orthopaedic journals that focus on clinical research: The Journal of Bone and Joint Surgery, American Volume; Clinical Orthopaedics and Related Research; and Osteoarthritis and Cartilage. We searched the PubMed and Embase databases using the following inclusion criteria: English-language studies, human studies, randomized controlled trials, publication date from 2000 to 2020, and published in Clinical Orthopaedics and Related Research; The Journal of Bone and Joint Surgery, American Volume; or Osteoarthritis and Cartilage. Primary outcome measures included whether studies reported participant race or ethnicity, other social covariates (insurance status, housing or homelessness, education and literacy, transportation, income and employment, and food security and nutrition), and genomic testing. The secondary outcome measure was the racial and ethnic categorical distribution of the trial participants included in the studies reporting race or ethnicity. From our search, 1043 randomized controlled trials with 184,643 enrolled patients met the inclusion criteria. Among these studies, 21% (223 of 1043) had a small (< 50) sample size, 56% (581 of 1043) had a medium (50 to 200) sample size, and 23% (239 of 1043) had a large (> 200) sample size. Fourteen percent (141 of 1043) were based in the Northeast United States, 9.2% (96 of 1043) were in the Midwest, 4.7% (49 of 1043) were in the West, 7.2% (75 of 1043) were in the South, and 65% (682 of 1043) were outside the United States. We calculated the overall proportion of studies meeting the inclusion criteria that reported race or ethnicity. Then among the subset of studies reporting race or ethnicity, we determined the overall rate and distribution of social covariates and genomic testing reporting. We calculated the proportion of studies reporting race or ethnicity that also reported a difference in outcome by race or ethnicity. We calculated the proportion of studies reporting race or ethnicity by each year in the study period. We also calculated the proportions and 95% CIs of individual patients in each racial or ethnic category of the studies meeting the inclusion criteria. RESULTS: During the study period (2000 to 2020), 8.5% (89 of 1043) of studies reported race or ethnicity. Of the trials reporting this factor, 4.5% (four of 89) reported insurance status, 15% (13 of 89) reported income, 4.5% (four of 89) reported housing or homelessness, 18% (16 of 89) reported education and literacy, 0% (0 of 89) reported transportation, and 2.2% (two of 89) reported food security or nutrition of trial participants. Seventy-eight percent (69 of 89) of trials reported no social covariates, while 22% (20 of 89) reported at least one. However, 0% (0 of 89) of trials reported genomic testing. Additionally, 5.6% (five of 89) of these trials reported a difference in outcomes by race or ethnicity. The proportion of studies reporting race or ethnicity increased, on average, by 0.6% annually (95% CI 0.2% to 1.0%; p = 0.02). After controlling for potentially confounding variables such as funding source, we found that studies with an increased sample size were more likely to report data by race or ethnicity; location in North America overall, Europe, Asia, and Australia or New Zealand (compared with the Northeast United States) were less likely to; and specialty-topic studies (compared with general orthopaedics research) were less likely to. Our sample of United States trials contained 18.9% more white participants than that reported in the United States Census (95% CI 18.4% to 19.4%; p < 0.001), 5.0% fewer Black participants (95% CI 4.6% to 5.3%; p < 0.001), 17.0% fewer Hispanic participants (95% CI 16.8% to 17.1%; p < 0.001), 5.3% fewer Asian participants (95% CI 5.2% to 5.4%; p < 0.001), and 7.5% more participants from other groups (95% CI 7.2% to 7.9%; p < 0.001). CONCLUSION: Reporting of race or ethnicity data in orthopaedic clinical trials is low compared with other medical fields, although the proportion of diseases warranting this reporting might be lower in orthopaedics. CLINICAL RELEVANCE: Investigators should initiate discussions about race and ethnicity reporting in the early stages of clinical trial development by surveying available published evidence for relevant health disparities, social determinants, and, when warranted, genomic risk factors. The decision to include or exclude race and ethnicity data in study protocols should be based on specific hypotheses, necessary statistical power, and an appreciation for unmeasured confounding. Future studies should evaluate cost-efficient mechanisms for obtaining baseline social covariate data and investigate researcher perspectives on current administrative workflows and decision-making algorithms for race and ethnicity reporting.

Subclinical Liver Disease Is Associated with Subclinical Atherosclerosis in Psoriasis: Results from Two Observational Studies.

Psoriasis is associated with a higher risk of liver diseases. We investigated the impact of hepatic steatosis (European cohort) and hepatic inflammation (United States cohort) on subclinical atherosclerosis. In the European cohort (n = 76 psoriasis participants and 76 controls), nonalcoholic fatty liver disease, assessed by the sonographic hepatorenal index, was more prevalent in psoriasis than in controls (61% vs. 45%; P = 0.04). Participants with psoriasis with nonalcoholic fatty liver disease had a higher prevalence of subclinical atherosclerosis (ultrasonographic presence of plaque in femoral or carotid arteries) than participants with psoriasis without nonalcoholic fatty liver disease (61% vs. 23%; P = 0.006) and controls with nonalcoholic fatty liver disease (61% vs. 32%; P < 0.05). Sonographic hepatorenal index was a determinant of subclinical atherosclerosis in psoriasis (OR = 3.5; P = 0.01). In the United States cohort (n = 162 participants with psoriasis who underwent positron emission tomography and coronary computed tomography angiography), those with high hepatic 2-[fluorine-18]fluoro-2-deoxy-D-glucose uptake had higher noncalcified (1.3 [0.49 mm2] vs. 1.0 [0.40 mm2]), fibrofatty (0.23 [0.15 mm2] vs. 0.11 [0.087 mm2]), and lipid-rich necrotic core (4.3 [2.3 mm2] vs. 3.0 [1.7 mm2]) coronary burden (all P < 0.001). Hepatic 2-[fluorine-18]fluoro-2-deoxy-D-glucose uptake associated with noncalcified (ß = 0.28; P < 0.001), fibrofatty (ß = 0.49; P < 0.001), and lipid-rich necrotic core (ß = 0.28; P = 0.003) burden. These results show the downstream cardiovascular effects of subclinical liver disease in psoriasis.

The relationship between systemic inflammation and increased left ventricular mass is partly mediated by noncalcified coronary artery disease burden in psoriasis.

OBJECTIVE: Increased left ventricular (LV) mass is an important precursor to heart failure. Inflammation plays an important role in increasing LV mass. However, the contribution of subclinical coronary artery disease (CAD) to the inflammation-LV mass relationship is unknown. In subjects with psoriasis, a chronic inflammatory skin disease, we evaluated if systemic inflammation assessed by plasma glycoprotein A (GlycA) associated with LV mass measured on coronary CT angiography (CCTA). Additionally, we analyzed whether this relationship was mediated by early CAD assessed as noncalcified coronary burden (NCB). METHODS: We performed an observational longitudinal study of 213 subjects with psoriasis free of known cardiovascular disease, 189 of whom were followed over one year. All participants had GlycA measurements by nuclear magnetic resonance spectroscopy and LV mass and NCB quantified by CCTA. RESULTS: The cohort had a mean age of 50.3 (±12.9) years and 59% were male. There was moderate psoriasis severity and low cardiovascular risk. LV mass increased by GlycA tertiles [1st tertile:24.6 g/m2.7(3.8), 2nd tertile:25.5 g/m2.7(3.8), 3rd tertile:27.7 g/m2.7(5.5), p<0.001]. Both GlycA (ß=0.24, p = 0.001) and NCB (ß=0.50, p<0.001) associated with LV mass in models adjusted for age, sex, hypertension, hypertension therapy, lipid therapy, biologic therapy for psoriasis, waist:hip ratio, psoriasis disease duration and severity. In multivariable-adjusted mediation analyses, NCB accounted for 32% of the GlycA-LV mass relationship. Finally, over one year, change in NCB independently associated with change in LV mass (ß=0.25, p = 0.002). CONCLUSIONS: Both systemic inflammation and coronary artery NCB were associated with LV mass beyond cardiovascular risk factors in psoriasis. Furthermore, a substantial proportion of the inflammatory-LV mass relationship was mediated by NCB. These findings underscore the possible contribution of early coronary artery disease to the relationship between systemic inflammation and LV mass.

Abdominal subcutaneous adipose tissue negatively associates with subclinical coronary artery disease in men with psoriasis.

OBJECTIVE: Understand the relationship between abdominal subcutaneous adipose tissue (ASAT) and coronary atherosclerosis defined as noncalcified and lipid-rich necrotic core burden in psoriasis. METHODS: We performed a cross-sectional study of 232 participants (92 women) with psoriasis and without known cardiovascular disease. Participants underwent coronary computed tomography angiography to characterize coronary atherosclerosis burden and low dose abdominal computed tomography to quantify subcutaneous and visceral adipose tissue. Fat depot volumes were first adjusted for each participant's BMI (ASATadjBMI). RESULTS: In women, there was a positive correlation between ASATadjBMI and systemic inflammation as assessed by hs-C-reactive protein (r=0.30; p=.004) and GlycA (r=0.29; p=.007) as well as total cholesterol (r=0.24; p=.02) and low-density lipoprotein cholesterol (r=0.22; p=.04). In men, ASATadjBMI correlated with hs-C-reactive protein (r=0.18; p=.04) and insulin resistance (r=0.17; p=.04). In models fully adjusted for traditional cardiovascular risk factors, ASATadjBMI negatively associated with noncalcified and lipid-rich necrotic core burden in men (ß= -0.17; p=.03, ß= -0.20; p=.03, respectively), but not women (ß= -0.06; p=.57, ß= 0.09; p=.49, respectively) with psoriasis. CONCLUSIONS: For a given BMI, ASAT negatively associated with coronary atherosclerosis burden in male participants with psoriasis. The observed sex-specific effects warrant further study of ASAT in states of chronic inflammation.

Metabolic syndrome and its factors are associated with noncalcified coronary burden in psoriasis: An observational cohort study.

BACKGROUND: Psoriasis is associated with a heightened risk of cardiovascular disease and higher prevalence of metabolic syndrome. OBJECTIVE: Investigate the effect of metabolic syndrome and its factors on early coronary artery disease assessed as noncalcified coronary burden by coronary computed tomography angiography in psoriasis. METHODS: This cross-sectional study consisted of 260 participants with psoriasis and coronary computed tomography angiography characterization. Metabolic syndrome was defined according to the harmonized International Diabetes Federation criteria. RESULTS: Of the 260 participants, 80 had metabolic syndrome (31%). The metabolic syndrome group had a higher burden of cardiometabolic disease, systemic inflammation, noncalcified coronary burden, and high-risk coronary plaque. After adjusting for Framingham risk score, lipid-lowering therapy, and biologic use, metabolic syndrome (ß = .31; P < .001) and its individual factors of waist circumference (ß = .33; P < .001), triglyceride levels (ß = .17; P = .005), blood pressure (ß = .18; P = .005), and fasting glucose (ß = .17; P = .009) were significantly associated with noncalcified coronary burden. After adjusting for all other metabolic syndrome factors, blood pressure and waist circumference remained significantly associated with noncalcified coronary burden. LIMITATIONS: Observational nature with limited ability to control for confounders. CONCLUSIONS: In psoriasis, individuals with metabolic syndrome had more cardiovascular disease risk factors, systemic inflammation, and noncalcified coronary burden. Efforts to increase metabolic syndrome awareness in psoriasis should be undertaken to reduce the heightened cardiovascular disease risk.