The Incidence of Breast Cancer among Disabled Kansans with Medicare

BACKGROUND: Breast cancer disparities by disability status are poorly understood. While previous studies have shown increased odds of late stage at diagnosis, it is unclear whether the incidence of breast cancer varies by disability status. METHODS: To assess cancer incidence and stage at diagnosis among disabled and nondisabled Medicare beneficiaries in Kansas, a retrospective cohort study was conducted using linked Medicare enrollment and Kansas Cancer Registry data from 2007 to 2009. Disability status was determined by the indicator for the original reason for Medicare eligibility. RESULTS: Among the 651,337 Medicare beneficiaries included in the cohort, there were 2,384 cases of breast cancer. The age-adjusted incidence was 313 per 100,000 among female beneficiaries with disabilities and 369 per 100,000 among nondisabled female beneficiaries. The adjusted incidence rate ratio was 0.93 (95% CI 0.73-1.18). When assessing stage at diagnosis, there was no difference in the odds of late stage at diagnosis by disability status (OR = 1.02; 95% CI 0.68-1.50). CONCLUSION: No significant difference in incidence or stage at diagnosis was identified among this cohort. The use of Medicare eligibility to define disability status presented a number of limitations. Future studies should seek alternate definitions of disability to assess disparities in breast cancer incidence, including definitions using Medicare claims data

Cross-Calibration of Stroke Disability Measures: Bayesian Analysis of Longitudinal Ordinal Categorical Data Using Negative Dependence

It is common to assess disability of stroke patients using standardized scales, such as the Rankin Stroke Outcome Scale (RS) and the Barthel Index (BI). The Rankin Scale, which was designed for applications to stroke, is based on assessing directly the global conditions of a patient. The Barthel Index, which was designed for general applications, is based on a series of questions about the patient’s ability to carry out 10 basis activities of daily living. As both scales are commonly used, but few studies use both, translating between scales is important in gaining an overall understanding of the efficacy of alternative treatments, and in developing prognostic models that combine several data sets. The objective of our analysis is to provide a tool for translating between BI and RS. Specifically, we estimate the conditional probability distributions of each given the other. Subjects consisted of 459 individuals who sustained a stroke and who were recruited for the Kansas City Stroke Study from 1995 to 1998. Patients were assessed with BI and RS measures 1, 3 and 6 months after stroke. In addition, we included data from the Framingham study, in the form of cross-classifying patients by RS and coarsely aggregated BI. Our statistical estimation approach is motivated by several goals: (a) overcoming the difficulty presented by the fact that our two sources report data at different resolutions; (b) smoothing the empirical counts to provide estimates of probabilities in regions of the table that are sparsely population; (c) avoiding estimates that would conflict with medical knowledge about the relationship between the two measures and (d) estimating the relationship between RS and BI at three months after the stroke, while borrowing strength from measurements made at one and six months. We address these issues via a Bayesian analysis combining data augmentation and constrained semiparametric inference. Our results provide the basis for (a) comparing and integrating the results of clinical trials using different measures, and (b) integrating clinical trials results into comprehensive decision model for the assessment of long term implications and cost-effectiveness of stroke prevention and acute treatment interventions. In addition, our results indicate that the degree of agreement between the two measures is less strong than commonly reported, and emphasize the importance of trial designs that include multiple assessments of outcome

Acute Stroke, Hematocrit, and Blood Pressure.

A population-based study of the relation between hematocrit and stroke subtype was carried out among 2,077 individuals using the Lehigh Valley Stroke Register. This register identifies all stroke patients admitted to the 8 acute care hospitals serving the Lehigh Valley area of eastern Pennsylvania-western New Jersey. The mean hematocrit was higher in patients with lacunes than with thrombotic or embolic strokes (p = 0.02). However, when blood pressure was also considered the increase in hematocrit in patients with lacunar stroke was significant only when systolic hypertension (greater than or equal to 150 mm Hg) was also present (p = 0.029); no significant difference in hematocrit was found between stroke subtypes in normotensive individuals. Therefore, we cannot exclude the possibility that hypertension interacts with hematocrit in accounting for the observed association with lacunar infarcts. There was no trend for increased in-hospital mortality for stroke patients in either the low (less than or equal to 30, 30-36%) or high (greater than or equal to 47%) hematocrit groups

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusions: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms