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Objective: Chinese Americans are a fast‐growing immigrant group with worse rheumatic disease outcomes compared to white populations and frequently use traditional Chinese medicine (TCM). Whether TCM use is associated with lower adherence to Western rheumatic medications is unknown. The present study was undertaken to examine adherence to Western medications for systemic rheumatic diseases in the Chinese American immigrant population and its association with TCM use. Methods: Chinese Americans actively treated for a systemic rheumatic disease were recruited from 2 Chinatown clinics. Sociodemographic, TCM use, and clinical data were gathered. Self‐reported health status was assessed using Patient‐Reported Outcome Measurement Information System short forms. Adherence was stratified using the 8‐item Morisky Medication Adherence Scale. Factors independently associated with high adherence were identified using multivariable logistic regression. Results: Of 230 subjects, the median age was 55 years (range 20–97 years), 65% were female, 71% had a high school education or less, 70% were enrolled in Medicaid, and 22% reported fluency in English. The most common rheumatic diagnoses were rheumatoid arthritis (41%), systemic lupus erythematosus (17%), and seronegative spondyloarthropathies (15%). One‐half reported TCM use in the past year, and 28% reported high adherence to Western rheumatic medications. In multivariable analysis, high adherence was associated with TCM use (odds ratio [OR] 3.96, P < 0.001), being married (OR 3.69, P = 0.004), medication regimen complexity (OR 1.13, P = 0.004), and older age (OR 1.06, P < 0.001), and was negatively associated with anxiety (OR 0.94, P = 0.001). Conclusion: While adherence to Western rheumatic medications was low in this cohort, interestingly, it was higher among TCM users compared to nonusers. TCM use appears to represent a complementary rather than an alternate approach to disease management for these patients. Future studies should evaluate whether TCM use is associated with better disease outcomes. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the longitudinal responsiveness (sensitivity to change) of the Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health Short Form (PROMIS10) in outpatients with systemic lupus erythematosus (SLE).Methods: Outpatients with SLE who were receiving care at an academic medical center completed the PROMIS10 at 2 visits that were a minimum of 1 month apart. Responsiveness of the PROMIS10 global physical and mental health domains to Patient-Reported improvement or deterioration of health status was evaluated, as measured by standard validated instruments. Effect sizes of changes in PROMIS10 scores between visits were evaluated using Kruskal-Wallis testing.Results: A total of 223 SLE patients enrolled and completed baseline surveys, with 186 (83.4%) completing a second set of questionnaires. The PROMIS10 demonstrated mild-to-moderate responsiveness to Patient-Reported improvement (effect size 0.29) and worsening (effect sizes -0.27 and -0.54) of health status for both global physical health and global mental health. Changes in the PROMIS10 correlated poorly with changes in physician-reported measures of disease activity.Conclusion: The PROMIS10 showed responsiveness over time to Patient-Reported changes in SLE health status, but not physician-assessed changes. These data suggest that the PROMIS10 can be used to efficiently measure and monitor important aspects of the SLE patient experience that are not captured by standard physician-derived metrics. Further studies are needed to evaluate the role of the PROMIS10 in optimizing longitudinal disease management in SLE and to determine its responsiveness in other chronic health conditions. [ABSTRACT FROM AUTHOR]

Objective: To determine whether racial disparities in total knee replacement (TKR) failure are explained by poverty.Methods: Black and white New York state residents, enrolled in a prospective single-institution TKR registry January 1, 2008 to February 6, 2012, who underwent primary unilateral TKR (n = 4,062) were linked to the New York Statewide Planning and Research Cooperative System database (January 1, 2008 to December 31, 2014) to capture revisions performed at outside institutions. Patients were linked by geocoded addresses to residential census tracts. Multivariable Cox regression was used to assess predictors of TKR revision. Multivariable logistic regression was used to analyze predictors of TKR failure, defined as TKR revision in New York state ≤2 years after surgery, or as Hospital for Special Surgery (HSS) TKR quality of life score "not improved" or "worsened" 2 years after surgery.Results: The mean ± SD age was 68.4 ± 10 years, 64% of patients were female, 8% lived in census tracts with >20% of the population under the poverty line, and 9% were black. Median follow-up time was 5.3 years. A total of 3% of patients (122 of 4,062) required revision a median 454 days (interquartile range 215-829) after surgery. TKR revision risk was higher in blacks than whites, with a hazard ratio of 1.69 (95% confidence interval 1.01-2.81), but in multivariable analysis, only younger age, male sex, and constrained prosthesis were predictors of TKR revision. TKR failure occurred in 200 of 2,832 cases (7%) with 2-year surveys. Risk factors for TKR failure were non-osteoarthritis TKR indication, low surgeon volume, and low HSS Expectations Survey score, but not black race. Community poverty was not associated with TKR revision or failure.Conclusion: There was a trend toward higher TKR revision risk in blacks, but poverty did not modify the relationship between race and TKR revision or failure. [ABSTRACT FROM AUTHOR]

Objective: Patients with rheumatoid arthritis (RA) in clinical remission may have subclinical synovial inflammation. This study was undertaken to determine the proportion of patients with RA in remission or with low disease activity at the time of arthroplasty who had histologic or transcriptional evidence of synovitis, and to identify clinical features that distinguished patients as having subclinical synovitis. Methods: We compared Disease Activity Score in 28 joints (DAS28) to synovial histologic features in 135 patients with RA undergoing arthroplasty. We also compared DAS28 scores to RNA‐Seq data in a subset of 35 patients. Results: Fourteen percent of patients met DAS28 criteria for clinical remission (DAS28 <2.6), and another 15% met criteria for low disease activity (DAS28 <3.2). Histologic analysis of synovium revealed synovitis in 27% and 31% of samples from patients in remission and patients with low disease activity, respectively. Patients with low disease activity and synovitis also exhibited increased C‐reactive protein (CRP) (P = 0.0006) and increased anti–cyclic citrullinated peptide (anti‐CCP) antibody levels (P = 0.03) compared to patients without synovitis. Compared to patients with a "low inflammatory synovium" subtype, 183 genes were differentially expressed in the synovium of patients with subclinical synovitis. The majority of these genes (86%) were also differentially expressed in the synovium of patients with clinically active disease (DAS28 ≥3.2). Conclusion: Thirty‐one percent of patients with low clinical disease activity exhibited histologic evidence of subclinical synovitis, which was associated with increased CRP and anti‐CCP levels. Our findings suggest that synovial gene expression signatures of clinical synovitis are present in patients with subclinical synovitis. [ABSTRACT FROM AUTHOR]

Objective: Total knee arthroplasty (TKA) outcomes are worse for patients from poor neighborhoods, but whether education mitigates the effect of poverty is not known. We assessed the interaction between education and poverty on 2-year Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function.Methods: Patient-level variables from an institutional registry were linked to US Census Bureau data (census tract [CT] level). Statistical models including patient and CT-level variables were constructed within multilevel frameworks. Linear mixed-effects models with separate random intercepts for each CT were used to assess the interaction between education and poverty at the individual and community level on WOMAC scores.Results: Of 3,970 TKA patients, 2,438 (61%) had some college or more. Having no college was associated with worse pain and function at baseline and 2 years (P = 0.0001). Living in a poor neighborhood (>20% below poverty line) was associated with worse 2-year pain (P = 0.02) and function (P = 0.006). There was a strong interaction between individual education and community poverty with WOMAC scores at 2 years. Patients without college living in poor communities had pain scores that were ~10 points worse than those with some college (83.4% versus 75.7%; P < 0.0001); in wealthy communities, college was associated with a 1-point difference in pain. Function was similar.Conclusion: In poor communities, those without college attain 2-year WOMAC scores that are 10 points worse than those with some college; education has no impact on TKA outcomes in wealthy communities. How education protects those in impoverished communities warrants further study. [ABSTRACT FROM AUTHOR]

Objective: In this study, we sought to refine histologic scoring of rheumatoid arthritis (RA) synovial tissue by training with gene expression data and machine learning. Methods: Twenty histologic features were assessed in 129 synovial tissue samples (n = 123 RA patients and n = 6 osteoarthritis [OA] patients). Consensus clustering was performed on gene expression data from a subset of 45 synovial samples. Support vector machine learning was used to predict gene expression subtypes, using histologic data as the input. Corresponding clinical data were compared across subtypes. Results: Consensus clustering of gene expression data revealed 3 distinct synovial subtypes, including a high inflammatory subtype characterized by extensive infiltration of leukocytes, a low inflammatory subtype characterized by enrichment in pathways including transforming growth factor β, glycoproteins, and neuronal genes, and a mixed subtype. Machine learning applied to histologic features, with gene expression subtypes serving as labels, generated an algorithm for the scoring of histologic features. Patients with the high inflammatory synovial subtype exhibited higher levels of markers of systemic inflammation and autoantibodies. C‐reactive protein (CRP) levels were significantly correlated with the severity of pain in the high inflammatory subgroup but not in the others. Conclusion: Gene expression analysis of RA and OA synovial tissue revealed 3 distinct synovial subtypes. These labels were used to generate a histologic scoring algorithm in which the histologic scores were found to be associated with parameters of systemic inflammation, including the erythrocyte sedimentation rate, CRP level, and autoantibody levels. Comparison of gene expression patterns to clinical features revealed a potentially clinically important distinction: mechanisms of pain may differ in patients with different synovial subtypes. [ABSTRACT FROM AUTHOR]

Objective: To assess the safety and efficacy of treatment with belimumab in patients with early diffuse cutaneous systemic sclerosis (dcSSc) treated with background mycophenolate mofetil (MMF). Methods: In this 52‐week, investigator‐initiated, single‐center, double‐blind, placebo‐controlled, pilot study, 20 patients with dcSSc recently started on MMF were randomized 1:1 to additionally receive belimumab at 10 mg/kg intravenously or placebo. We assessed safety, efficacy, and differential gene expression. Results: In the belimumab group, the median modified Rodnan skin thickness score (MRSS) decreased from 27 (interquartile range [IQR] 26.5, 31) to 18 (IQR 11, 23) (P = 0.039). In the placebo group, the median MRSS decreased from 28 (IQR 22, 28) to 21 (IQR 14, 25) (P = 0.023). The median change in MRSS was –10 (IQR –13, –9) in the belimumab group and –3.0 (IQR –15, –1) in the placebo group (P = 0.411). There were no significant differences between the groups in the number of adverse events (AEs). A significant decrease in expression of B cell signaling and profibrotic genes and pathways was observed in patients with improved MRSS in the belimumab group but not in the placebo group. Conclusion: Patients in both treatment groups experienced significant improvements in MRSS. The median difference was greater in the belimumab group but did not achieve statistical significance in this small pilot study. AEs were similar between the groups. Changes in gene expression were consistent with mechanism of action and showed that clinical response to treatment with belimumab is associated with a significant decrease in profibrotic genes and pathways. Additional studies are needed to determine the role of belimumab in the treatment of dcSSc. [ABSTRACT FROM AUTHOR]

Outcome-based sampling is an efficient study design for rare conditions, such as glioblastoma. It is often used in conjunction with matching, for increased efficiency and to potentially avoid bias due to confounding. A study was conducted at the Massachusetts General Hospital that involved retrospective sampling of glioblastoma patients with respect to multiple-ordered disease states, as defined by three categories of overall survival time. To analyze such studies, we posit an adjacent categories logit model and exploit its allowance for prospective analysis of a retrospectively sampled study and its advantageous removal of set and level specific nuisance parameters through conditioning on sufficient statistics. This framework allows for any sampling design and is not limited to one level of disease within each set, such as in previous publications. We describe how this ordinal conditional model can be fit using standard conditional logistic regression procedures. We consider an alternative pseudo-likelihood approach that potentially offers robustness under partial model misspecification at the expense of slight loss of efficiency under correct model specification for small sample sizes. We apply our methods to the Massachusetts General Hospital glioblastoma study. [ABSTRACT FROM AUTHOR]

Objective The aim of the study was to determine the relationship of various thoracic fat depots with the presence and extent of coronary artery plaque and circulating biomarkers. Methods In 342 patients (52 ± 11 years, 61% male, BMI 29.1 ± 5.9 kg/m2) with coronary computed tomography (CT), angiography, we measured the fat volume in four thoracic depots (pericoronary, epicardial, periaortic, extracardiac), assessed coronary plaque, and determined the circulating levels of C-reactive protein, tumor necrosis factor alpha, plasminogen activator inhibitor-1, monocyte chemoattractant protein-1, and adiponectin. The extent of coronary plaque was classified into three groups: 0, 1−3, and >3 segments. Results Patients with plaque ( n =169, 49%) had higher volumes of all four fat depots as compared to patients without plaque (all P < 0.01), despite similar BMI ( P = 0.18). Extracardiac fat was most strongly correlated with BMI ( r = 0.45, P < 0.001), while pericoronary fat was least ( r = 0.21, P < 0.001). Only pericoronary fat remained associated with coronary plaque in adjusted analyses. Inflammatory biomarkers showed a positive correlation with pericoronary fat (all P < 0.0001), whereas adiponectin was not associated with this fat compartment ( P = 0.60) and showed a negative correlation with all other fat depots (all P < 0.001). Conclusions Pericoronary fat is independently associated with coronary artery disease (CAD). Its correlation with inflammatory biomarkers suggests that while systemic inflammation plays a role in the pathogenesis of CAD, there are additional local effects that may exist. [ABSTRACT FROM AUTHOR]

BACKGROUND Histologic response to chemotherapy has been shown to be an independent prognostic factor in patients with osteosarcoma and Ewing sarcoma. However, in patients with soft tissue sarcoma (STS), the prognostic impact of histologic response to chemotherapy is less clear. In the current study, the authors sought to determine the prognostic significance of treatment-induced pathologic necrosis in patients receiving neoadjuvant chemoradiotherapy for STS. METHODS Between 1989 and 2011, a total of 113 patients with grade 2 or 3 (graded according to the National Cancer Institute grading system using 3 tiers) extremity or truncal STS were identified who received neoadjuvant interdigitated chemoradiotherapy according to protocol followed by surgery. The extent of tumor necrosis in the resected specimens was quantified and correlated with outcome. RESULTS The median tumor necrosis rate was 90%, and 103 patients (91%) received all 3 cycles of planned neoadjuvant chemotherapy. The likelihood of achieving ≥95% necrosis was not related to the number of preoperative cycles of chemotherapy received but was found to be related to tumor histology (62% for malignant fibrous histiocytoma vs 0% for synovial sarcoma [ P<.001]; 56% for myxoid liposarcoma vs 0% for synovial sarcoma [ P = .002]). At a median follow-up of 6 years, there were no statistically significant differences noted in the 5-year local control, disease-specific survival, and overall survival rates for patients with ≥95% necrosis (50 patients; 44%) and <95% necrosis (63 patients; 56%), even when stratifying by histology. CONCLUSIONS In a homogeneous population of patients with high-grade extremity and truncal STS who were treated with neoadjuvant chemoradiotherapy, the extent of pathologic tumor necrosis did not correlate with outcome. Cancer 2014;120:3676-3682. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND Early identification of mutations may guide patients with metastatic colorectal cancer toward targeted therapies that may be life prolonging. The authors assessed tumor genotype correlations with clinical characteristics to determine whether mutational profiling can account for clinical similarities, differences, and outcomes. METHODS Under Institutional Review Board approval, 222 patients with metastatic colon adenocarcinoma (n = 158) and rectal adenocarcinoma (n = 64) who underwent clinical tumor genotyping were reviewed. Multiplexed tumor genotyping screened for >150 mutations across 15 commonly mutated cancer genes. The chi-square test was used to assess genotype frequency by tumor site and additional clinical characteristics. Cox multivariate analysis was used to assess the impact of genotype on overall survival. RESULTS Broad-based tumor genotyping revealed clinical and anatomic differences that could be linked to gene mutations. NRAS mutations were associated with rectal cancer versus colon cancer (12.5% vs 0.6%; P < .001) and with age ≥56 years (7% vs 0.9%; P = .02). Conversely, v-raf murine sarcoma viral oncogene homolog B ( BRAF) mutations were associated with colon cancer (13% vs 3%; P = .024) and older age (15.8% vs 4.6%; P = .006). TP53 mutations were associated with rectal cancer (30% vs 18%; P = .048), younger age (14% vs 28.7%; P = .007), and men (26.4% vs 14%; P = .03). Lung metastases were associated with PIK3CA mutations (23% vs 8.7%; P = .004). Only mutations in BRAF were independently associated with decreased overall survival (hazard ratio, 2.4; 95% confidence interval, 1.09-5.27; P = .029). CONCLUSIONS The current study suggests that underlying molecular profiles can differ between colon and rectal cancers. Further investigation is warranted to assess whether the differences identified are important in determining the optimal treatment course for these patients. Cancer 2014;120:1482-1490. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]

Aims Galectin-3 is a prognostic heart failure (HF) biomarker that may mediate cardiac fibrosis. We examined the value of serial galectin-3 measurement for prognosis and response to therapy in chronic HF. Methods and results A total of 151 subjects with LV systolic dysfunction (LVSD) were followed through 908 visits over 10 ± 3 months. The amount of time spent with a galectin-3 level ≤ 20.0 ng/mL and changes between baseline and subsequent values were considered across visits, and used to assess risk for adverse cardiovascular (CV) events and associations with LV remodelling. Medication effects on galectin-3 were examined. Median galectin-3 values at baseline, 3 months, and 6 months were higher in patients with CV events (21.7 vs. 18.4 ng/mL, P = 0.03; 21.7 vs. 16.5 ng/mL, P = 0.03; 23.2 vs. 16.0 ng/mL, P = 0.007). Galectin-3 concentration changed in 35.2% of subjects during study procedures; time spent at ≤ 20.0 ng/mL was significantly associated with a lower rate of CV events, independently predicted fewer CV events even adjusted for relevant variables including study allocation, NT-proBNP, and renal function [odds ratio (OR) = 0.90; P = 0.05], and predicted increase in LV ejection fraction (OR = 1.20; P = 0.04). Serial galectin-3 measurement at 6 months added prognostic value beyond the baseline level (P = 0.02). There were no significant effects of medications on galectin-3 levels. Conclusion In chronic HF due to LVSD, serial galectin-3 measurement adds incremental prognostic information and predicts LV remodelling. In this study, HF therapies had no clear effects on galectin-3 levels. [ABSTRACT FROM AUTHOR]

Introduction: Strength measures with reduced variability and higher sensitivity could improve efficiency in clinical trials of amyotrophic lateral sclerosis (ALS). The Accurate Test of Limb Isometric Strength (ATLIS) was developed to precisely and conveniently measure force in 12 muscle groups. In this study we evaluate the reliability and validity of the ATLIS testing protocol. Methods: Twenty healthy adults and 10 patients with ALS were tested twice by the same or by different evaluators to determine test-retest and interrater reliability. Twenty healthy adults were examined using ATLIS and a well-validated strength testing protocol (TQNE) to assess criterion-based validity. Results: Mean absolute variation between tests was 8.6%, and intraclass correlation coefficients for each muscle group were high (range 0.82-0.99). The Pearson correlation coefficient of mean ATLIS and TQNE scores was 0.90. A subject survey demonstrated high user acceptance of ATLIS. Conclusions: ATLIS is convenient for patients and evaluators, produces precise strength measurements, and is easily moved between examining rooms. Muscle Nerve 45: 81-85, 2012 [ABSTRACT FROM AUTHOR]

BACKGROUND: Myeloma survival varies markedly with International Staging System classification, presence of cytogenetic abnormalities, and, especially, gene expression profiling-based risk and delTP53 status, whose collective impact has not been examined in the context of specific therapies. METHODS: The authors examined overall survival (OS), event-free survival (EFS), and complete response duration (CRD) in Total Therapy 2 with randomization to a control or thalidomide arm and in Total Therapy 3 with added bortezomib. Among 612 patients with complete data sets, multivariate analyses were used to investigate the relative contributions to OS, EFS, and CRD of International Staging System stage, cytogenetic abnormalities, and gene expression profiling-derived risk and delTP53 status, in the context of the 3 Total Therapy regimens. RESULTS: Whereas gene expression profiling risk segregated outcomes within all 3 International Staging System stages, International Staging System 3 conferred inferior prognosis only in low-risk myeloma, whereas the grave prognosis of high-risk disease was International Staging System-independent. After adjusting for gene expression profiling-defined high risk and delTP53 in multivariate analysis, International Staging System 3 and cytogenetic abnormalities both retained independent adverse implications for OS, EFS, and CRD. Among the 86% with low-risk disease, cytogenetic abnormalities and delTP53 both affected all 3 endpoints negatively, whereas the International Staging System 3 effect was limited to OS. Total Therapy 3 improved survival outcomes beyond results obtained with Total Therapy 2. CONCLUSIONS: In the genomic era, standard laboratory variables, such as International Staging System stage and presence of cytogenetic abnormalities, continue to impact survival after adjusting for gene expression profiling risk and delTP53 status, providing a basis for stratification in our current practice of gene expression profiling risk-based treatment assignment. [ABSTRACT FROM AUTHOR]

The article focuses on the immunoglobulin (Ig) isotypes in multiple myeloma. It highlights the Ig heavy and light chain isotypes prognostically relevant baseline laboratory features. It also features the protocols for newly diagnosed patients with symptomatic or progressive disease. Various phenotypes with baseline prognostic features were also discussed by the author.