tbuckley/cabot-search huggingface dataset:
Patient-reported outcomes for performance measurement: Multi-institution challenges.
Authors: Constance Barysauskas, Kristen K. McNiff, Stephen Flaherty, Mary Ellen Morba, Tracy E. Spinks, Terry Fisher, Barbara Jagels, Neil E. Martin
Journal: Journal of Clinical Oncology (2017)

211 Background: Patient-reported outcomes (PROs) are self-reported measures of a patient’s health or healthcare experience. PRO utilization is driven by the movement toward patient-centered care and emerging evidence which suggests patients (pts) more involved in their care experience better outcomes. The infrastructure to capture PROs is evolving and PROs are now used for performance measurement (PM). PRO-PMs assess the quality of healthcare for improvement and/or accountability; but implementation is challenging. Success of PRO-PM requires identification of pts, ongoing data collection and data aggregation across institutions. The Alliance of Dedicated Cancer Centers (ADCC) identified challenges of PRO use for PM. Methods: The validated tool, Expanded Prostate Cancer Index Composite, evaluating pt function and bother from treatment (trt), administered to new localized prostate pts at three independent cancer centers was retrospectively collected. Surveys administered before and after trt measured change from trt. Results: Institutions implementing PROs following local standards resulted in a high degree of variation. The aggregated data presented challenges in identifying eligible pt populations who received surveys before and after trt within a timeframe. We identified a pragmatic and meaningful pt population and survey implementation window. Pts were stratified by center and trt modality for analysis. Conclusions: The aggregation of dissimilar data sources led to the identification of institution implementation and data capture differences, however, the ADCC identified variation for PRO measure development. Clear guidance, policies and procedures are essential to ensure adequate homogeneity and reduced variability, to assure meaningful PM and reduce confounding by institution. [Table: see text]
Advanced endometrial cancer patients: Who responds to standard chemotherapy?
Authors: Cara Amanda Mathews, Murali Jayaraman, Eric Thomas, Erin Tuller, Danny Dhanasekaran, D. Scott McMeekin
Journal: Journal of Clinical Oncology (2014)

e16542 Background: The treatment for advanced stage endometrial cancer is toxic, only some women benefit from therapy, and there is no predictive model to determine who will respond and benefit from chemotherapy versus those who will not. The aim of this study was to evaluate 10 biomarkers relevant to endometrial cancer (ER, PR, Akt-P, Bcl-2, PTEN, p53, EphA-2, ErbB-2, Bax, and B-catenin) to explore for associations between biomarkers and response to therapy. Methods: Immunohistochemical staining of tissue microarrays was performed on 49 archived histopathology specimens from women undergoing surgery for advanced endometrial cancer and initially treated with chemotherapy alone. Digital software was used to measure the intensity and percentage of tissue stained for each biomarker, which was analyzed as categorical data applying cutpoints previously defined in the literature. Clinical data was collected, including progression free (PFS) and overall survival (OS). Using Chi-square analysis and estimation of risk ratios, biomarker positivity was compared between responders and non-responder to chemotherapy. Results: Poor prognostic factors such as advanced stage, serous histology type, and residual disease at the completion of surgery were all validated within this cohort. Median follow-up was 48 months. There were no statistically significant associations between any of the ten biomarkers and response to chemotherapy, although a trend was suggested for Bax, which had an overall expression of 37% within the population. The cumulative incidence of patients responding to chemotherapy was 1.84 (CI 1.08-3.14, p=0.06) times higher among those who were Bax (+) versus those who were Bax (-). Further analysis of the Bax biomarker showed that it was associated with advanced stage cancer (p=0.02) but not with residual disease (p=1.0), type I versus type II tumor (p=0.45), or serous histology type (p=0.60). Conclusions: Further investigation is necessary to evaluate specific biomarkers and develop a predictive model for chemotherapy response in advanced endometrial cancer. Bax is a potential biomarker for future analysis and appears to add additional information to prognosis beyond traditional surgicopathologic factors.
Abstract 319: Adrenergic Hormones Regulate Cardiac Metabolic Health During Embryogenesis
Authors: Candice Baker, Kingsley Osuala, Steven Ebert
Journal: Circulation Research (2012)

The adrenergic hormones, norepinephrine (NE) and epinephrine (EPI), are critically important during embryogenesis and cardiovascular development, yet their specific mechanisms of action remain mysterious. Disruption of the dopamine β-hydroxylase (Dbh) gene results in an inability to produce NE and EPI, which leads to death in utero between embryonic days 10.5 (E10.5) and E15.5 from apparent heart failure. To determine genes differentially expressed by the loss of adrenergic hormones, Affymetrix® GeneChip microarray analysis revealed 23 genes (of the 22,000 analyzed) that are significantly altered 2-fold or greater in E10.5 Dbh -/- hearts. Of these altered genes, 31% (7 of 23) are linked to metabolic regulation. The gene encoding for NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 2, Ndufb2 , for example, is a subunit of the mitochondrial complex 1, and displayed a 2.1-fold change in Dbh -/- embryonic hearts. This led us to investigate the metabolic health of these Dbh -/- embryos. Initially, we measured adenosine triphosphate (ATP) and adenosine diphosphate (ADP) levels in E9.5, E10.5, and E11.5 embryos from Dbh -/- , Dbh +/- , and Dbh +/+ mice. At E9.5, ATP concentrations were similar in Dbh -/- , Dbh +/- , and Dbh +/+ embryos ( p &gt;0.7, n=6), but began to decline in the Dbh -/- embryos at E10.5 compared to Dbh +/- and Dbh +/+ embryos ( p &lt;0.02, n=5). By E11.5, ATP concentrations were markedly decreased in Dbh -/- embryos, while ADP levels were increased 5-fold relative to Dbh +/+ controls. This resulted in a significant ( p &lt;0.01, n=4) and drastic (nearly 50-fold) difference in ATP/ADP ratio (0.4 ± 0.1) in Dbh -/- compared with Dbh +/+ control embryos (20.7 ± 4.1) at E11.5. Despite this dramatic difference in energy levels, all embryos appeared grossly normal, had similar heart rates, and displayed no significant differences in caspase 3 or 7 cleavage activity. Thus, the energy deficiency observed in Dbh -/- embryos did not appear to be associated with preceding signs of distress or demise. These results suggest that adrenergic hormones play an important role in regulating energy production during a critical phase of early development that roughly coincides with the transition from embryonic to fetal stages when increased energy utilization is needed.
Photodynamic Therapy: Au Nanoclusters and Photosensitizer Dual Loaded Spatiotemporal Controllable Liposomal Nanocomposites Enhance Tumor Photodynamic Therapy Effect by Inhibiting Thioredoxin Reductase (Adv. Healthcare Mater. 7/2017)
Authors: Fuping Gao, Weiping Zheng, Liang Gao, Pengju Cai, Ru Liu, Yaling Wang, Qing Yuan, Yuliang Zhao, Xueyun Gao
Journal: Advanced Healthcare Materials (2017)

Au nanoclusters and Clorine 6 (Ce6) co-loaded spatio-temporal controllable pH-sensitive liposomal nanocomposites are internalized by tumor cells via endocytosis are described by Fuping Gao, Xueyun Gao, and co-workers in article number 1601453. Au nanoclusters and Ce6 are burst and quickly released into cytoplasm under the acidic environment of lysosomes. This way, Au nanoclusters effectively inhibit TrxR in cytoplasm, weaken cell protection mechanisms to photodynamic therapy (PDT) and improve the photodynamic induced intracellular reactive oxygen species, ultimately enhance the effect of PDT.
Half of patients with learning disability miss out on annual GP health check
Authors: Susan Mayor
Journal: BMJ (2017)

Less than half of patients in England known to their GP as having a learning disability receive annual learning disability health checks, a report has shown.1

NHS Digital’s report analysed 2015-16 data on patients with and without learning disabilities from more than half of general practices in England to identify potential differences in treatment and health status. Some 57% of all registered patients were represented in the dataset, including 146 005 people with a learning disability and 32 491 016 with none.

Results showed that, …
Anti-obesity effect of a novel caffeine-loaded dissolving microneedle patch in high-fat diet-induced obese C57BL/6J mice
Authors: Manita Dangol, Suyong Kim, Cheng Guo Li, Shayan Fakhraei Lahiji, Mingyu Jang, Yonghao Ma, Inyoung Huh, Hyungil Jung
Journal: Journal of Controlled Release (2017)
Clinical Significance of Androgen Receptor Splice Variant-7 mRNA Detection in Circulating Tumor Cells of Men With Metastatic Castration-Resistant Prostate Cancer Treated With First- and Second-Line Abiraterone and Enzalutamide
Authors: Emmanuel S. Antonarakis, Changxue Lu, Brandon Luber, Hao Wang, Yan Chen, Yezi Zhu, John L. Silberstein, Maritza N. Taylor, Benjamin L. Maughan, Samuel R. Denmeade, Kenneth J. Pienta, Channing J. Paller, Michael A. Carducci, Mario A. Eisenberger, Jun Luo
Journal: Journal of Clinical Oncology (2017)

Purpose We reported previously that the detection of androgen receptor splice variant-7 (AR-V7) mRNA in circulating tumor cells (CTCs) correlated with poor outcomes from the use of abiraterone and enzalutamide in patients with castration-resistant prostate cancer (CRPC). Here, we expanded our cohort size to better characterize the prognostic significance of AR-V7 in this setting. Methods We prospectively enrolled 202 patients with CRPC starting abiraterone or enzalutamide and investigated the prognostic value of CTC detection (+ v –) and AR-V7 detection (+ v –) using a CTC-based AR-V7 mRNA assay. We examined ≥ 50% prostate-specific antigen (PSA) responses, PSA progression-free survival, clinical and radiologic progression-free survival, and overall survival. We constructed multivariable models adjusting for PSA, Gleason sum, number of prior hormone therapies, prior abiraterone or enzalutamide use, prior taxane use, presence of visceral metastases, and Eastern Cooperative Oncology Group score. We also separately examined the first-line and second-line novel hormonal therapy (NHT) settings. Results Median follow-up times were 15.0, 21.7, and 14.6 months for CTC–, CTC+/AR-V7– and CTC+/AR-V7+ patients, respectively. CTC+/AR-V7+ patients were more likely to have Gleason scores ≥ 8 ( P = .05), metastatic disease at diagnosis ( P = .01), higher PSA ( P &lt; .01), prior abiraterone or enzalutamide use ( P = .03), prior taxane use ( P = .02), and Eastern Cooperative Oncology Group ≥ 1 ( P = .01). Outcomes for the overall cohort (and separately for the first-line and second-line NHT cohorts) were best for CTC– patients, intermediate for CTC+/AR-V7– patients, and worse for CTC+/AR-V7+ patients. These correlations remained significant in multivariable models. Conclusion This expanded analysis further characterizes the importance of CTC-based AR-V7 mRNA detection in predicting outcomes in patients with CRPC receiving first- and second-line NHT and, to the best of our knowledge, is the first to suggest that this assay be interpreted using three separate prognostic categories: CTC–, CTC+/AR-V7–, and CTC+/AR-V7+.
Immunoreactivity to SOX-1, -2, -3 and ZIC2 antigens and correlation to survival in small cell lung cancer (SCLC)
Authors: L. C. Chen, B. Vural, Z. Ustuner, P. Saip, U. Ozbek, M. Gonen, L. Old, Y.-T. Chen, A. Gure
Journal: Journal of Clinical Oncology (2004)

7159 Background: Previous serological analysis of SCLC cell lines identified members of the SOX Group B (SOX-1, -2, -3, -21) and ZIC2 proteins as highly immunogenic tumor antigens. SOX1, -2, and -3 are expressed in normal adult brain, testis and prostate as well as in many SCLC cell lines. ZIC2 is expressed in normal brain and testis and is detected in tumor cell lines (9/11 SCLC, 10/12 melanoma, 7/7 NSCLC) as well as in colon, breast, head and neck, lung, bladder, sarcoma and melanoma tumor tissues. We assessed the prevalence and titers of the antibody response to these proteins and their correlation with survival in a group of SCLC patients. Methods: Serum samples from 70 SCLC patients were tested for SOX and ZIC2 immunoreactivity using a plaque assay. Titers of immunoreactive samples were determined by 10-fold serial dilutions. Clinical characteristics and survival were analyzed with respect to immunoreactivity and statistical analysis performed. Results: Of 70 SCLC patient sera tested, 25.7% were seropositive for SOX1, 21.4% for SOX2, 10.0% for SOX3, and 15.7% for ZIC2 with titers as high as106. Antibody response was seen in 14/30 limited stage patients and 10/25 extensive stage patients. Analysis of 40 patients with complete clinical data showed a statistically significant survival advantage in patients with immunoreactivity to SOX3 and/or ZIC2 (p=0.0175). A trend towards longer survival in patients seropositive for any of the four proteins was also observed although it did not reach statistical significance. Conclusions: In this group of SCLC patients, there is a high incidence of immunoreactivity to SOX-1, -2, -3 and ZIC2. SOX3 immunoreactivity was associated with high titer SOX1 and SOX2 immunoreactivity. Seroreactivity to SOX Group B and ZIC2 is associated with prolonged survival in these patients without clinically evident paraneoplastic neurologic syndromes. The presence of these antibodies may be a marker of a more indolent course of this disease and may be of interest as a vaccine target. No significant financial relationships to disclose.
Myocardial Reparative Properties of Cardiac Mesenchymal Cells Isolated on the Basis of Adherence
Authors: Marcin Wysoczynski, Yiru Guo, Joseph B. Moore, Senthilkumar Muthusamy, Qianhong Li, Marjan Nasr, Hong Li, Yibing Nong, Wenjian Wu, Alex A. Tomlin, Xiaoping Zhu, Gregory Hunt, Anna M. Gumpert, Michael J. Book, Abdur Khan, Xian-Liang Tang, Roberto Bolli
Journal: Journal of the American College of Cardiology (2017)
FOLFOX4 in metastatic colorectal cancer (MCRC) patients who progressed after infusional 5-FU/irinotecan based combination regimens
Authors: F. Dane, P. F. Yumuk, N. S. Turhal, M. Ekenel, G. Basaran, M. S. Iyikesici, C. Tecimer
Journal: Journal of Clinical Oncology (2004)

3729 Background: Irinotecan based regimens are the standard 1st line treatment for MCRC because the other promising agent oxaliplatin is commercially unavailable in Turkey. Oxaliplatin, 5-FU and calcium leucovorine (FOLFOX4) has been reported to be one of the promising treatment options for irinotecan resistant tumors. We want to report our experience of the patients who received FOLFOX4 after progression on irinotecan based combination chemotherapy. Methods: All patients (n=17) with MCRC who received FOLFOX4 were collected retrospectively. Results: Nine (52.9%) patients were male and median age was 59 years (range 50–73). Two (11.8%) had stage II, 8 (47.1%) had stage III disease before relapse and 7 (41.2%) had stage IV disease at presentation. Median time to progression (TTP) on 1st line chemotherapy for metastatic disease was 6 months. Twelve patients (70.6%) received FOLFOX4 as 2nd line and 5 patients (29.4%) as 3rd line treatment. The TTP was 3 months and median overall survival (OS) was 22 months. There was no statistically significant difference in TTP or OS in between the patients who got FOLFOX4 as 2nd versus 3rd line treatment. TTP was 3 months (95% CI: 2–4) and 4±1 months (95% CI: 3–5) respectively, p=0.48. OS was 32±5 months (95% CI: 23–41) and 19±3 months (95% CI: 14–24) respectively, p=0.146. Conclusion: The benefit of FOLFOX4 in metastatic colorectal cancer patients who progresses after infusional 5-FU and irinotecan containing combination regimens is limited. No significant financial relationships to disclose.
Post-discharge venous thromboembolism prophylaxis for surgical oncology patients.
Authors: Ashlie Nadler, Mary Ellen Morba, Jesse Pezzella, Jeffrey M. Farma
Journal: Journal of Clinical Oncology (2017)

79 Background: A number of guidelines have been proposed for prolonged venous thromboembolism (VTE) prophylaxis following hospital discharge for cancer patients undergoing major abdominal or pelvic surgery. However, there is disparity in how closely these guidelines are followed. The purpose of this study was to examine the administration and complications of post-discharge chemical VTE prophylaxis (pdVTE) at an institutional level among surgical oncology patients to help inform policy creation. Methods: A retrospective study at a tertiary referral cancer center was performed. Data was analyzed for patients undergoing surgery in 2015. Chi-square tests were performed. Results: Of 566 colorectal, urologic, and gynecologic surgical oncology procedures performed in 2015, 24% (137) were discharged with a prescription for enoxaparin for pdVTE. An additional 24 patients were already on another form of anticoagulation at the time of discharge. Of the patients discharged on pdVTE, 77% (105) had the prescriptions filled. The compliance rate of those patients was 96% (101). The rate of VTE was 3.5% for all patients. There was a significantly greater rate of VTE amongst patients that received pdVTE (10.4%) compared to those who did not (1.6%) (OR 7.20, CI 2.80-18.46, p &lt; 0.001). For each subspecialty, there was also a significantly greater rate of VTE amongst patients that received pdVTE (p &lt; 0.001). Conclusions: There is a very low rate of pdVTE administration despite current guidelines. Identifying patients who received pdVTE appears to identify patients at high risk for VTE rather than the benefits of pdVTE. Institutional policies regarding prolonged VTE prophylaxis should be implemented to target high-risk patients and to ensure appropriate prescribing practices. [Table: see text]
Systematic CT Methodology for the Evaluation of Subclinical Leaflet Thrombosis
Authors: Hasan Jilaihawi, Federico M. Asch, Eric Manasse, Carlos E. Ruiz, Vladimir Jelnin, Mohammad Kashif, Hiroyuki Kawamori, Yoshio Maeno, Yoshio Kazuno, Nobuyuki Takahashi, Richard Olson, Joe Alkhatib, Daniel Berman, John Friedman, Norman Gellada, Tarun Chakravarty, Raj R. Makkar
Journal: JACC. Cardiovascular imaging (2017)
Worry about recurrence and patient preferences for provider roles in collaborative breast cancer care.
Authors: Lauren P. Wallner, Nancy K. Janz, Yun Li, Christopher Ryan Friese, Kevin C. Ward, Ann S. Hamilton, Steven J. Katz, Sarah T. Hawley
Journal: Journal of Clinical Oncology (2017)

158 Background: Prior studies have shown that worry about recurrence is a common problem during cancer treatment and survivorship and may be associated with symptom response and surveillance after primary treatment. However, whether worry about recurrence influences patient preferences for which provider to see for their continuing care remains unknown. Methods: A random sample of patients newly diagnosed with breast cancer in 2014-15 as reported to the Georgia and Los Angeles SEER registries were surveyed approximately 6 months after diagnosis (N = 2,502, 70% response rate). Frequency of worry about recurrence was defined by asking women to indicate on a 5-pt scale how often they worried about their cancer coming back in the past month (not at all-always) and was then dichotomized as frequent worry (sometimes/often/almost always) vs. less worry (almost never/rarely). Patient preferences for which provider manages certain aspects of care after treatment were ascertained for: follow-up mammograms, screening for other cancers, general preventive care, and treatment of comorbidities. Response categories included primary care clinician (PCP), cancer doctors, either or both. The associations between patient-reported worry about recurrence with preferences for provider roles were assessed using multinomial logistic regression. Results: In this sample, 37% of women reported worrying frequently about recurrence. Controlling for patient and clinical factors, women who reported more frequent worry (vs. less worry) were more likely to prefer to see both clinicians (vs. PCP only) for mammograms (OR: 2.3, 95%CI: 1.5, 3.6), screening for other cancers (OR: 2.3, 95%CI: 1.5, 3.5), general preventive care (OR: 1.6, 95%CI: 1.1, 2.3) and comorbidity care (OR: 1.5, 95%CI: 1.03, 2.2). Conclusions: Frequent worry about recurrence was common in this sample of women with favorable prognosis breast cancer. More frequent worry about breast cancer recurrence was associated with stronger preferences for seeing both PCPs and oncologists for continuing care after treatment. Assessing and managing worry about recurrence early in survivorship may improve collaborative cancer care and reduce duplicated services after treatment.
Treatment of Severe Hypercholesterolemia in a Woman With Advanced Primary Sclerosing Cholangitis
Authors: Changting Xiao, Robert A. Hegele, Gary F. Lewis
Journal: JAMA Cardiology (2017)

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