tbuckley/cabot-search huggingface dataset:
Androgen deprivation therapy (ADT) and cardiovascular mortality (CVD) in men with early-stage prostate cancer (PC) receiving curative radiation therapy (RT).
Authors: Ashley Hanlon, Steven Fleming, Ann S Hamilton, Michaela Ann Dinan, Chiara Melloni, Michael Roger Harrison, Michel Khouri, Xiao-cheng Wu, J. Frank Wilson, Joseph Lipscomb, Rosemary Donaldson Cress, Roger T Anderson, Gretchen Genevieve Kimmick
Journal: Journal of Clinical Oncology (2018)

127 Background: Combined with RT, ADT is a highly effective and utilized treatment for men with localized PC, but some studies suggest that use of ADT leads to increased CVD. We explored the association between ADT and CVD in men receiving RT for localized PC in the National Program for Cancer Registry’s (NPCR) Breast and Prostate Cancer Patterns of Care (POC) study. Methods: From 7 population-based cancer registries, we constructed a sample of men with localized PC treated with definitive RT, stratified by race/ethnicity. Cases diagnosed in 2004 were followed through 2009. Comorbidity, at or before diagnosis, was quantified using the Adult Comorbidity Evaluation 27; subcategories were combined into CV disease (CVD = myocardial infarction, coronary artery disease, congestive heart failure, arrhythmia), CVD-equivalents (CVE = peripheral artery disease and stroke) and CV-risk factors (CVRF = hypertension, diabetes, obesity). Cause of death was determined from the National Death Index data and linkage with vital statistics data. Rates of CV death, in those receiving RT alone versus RT+ADT, were compared in univariate and multivariable analyses. Results: The sample included 2,413 men with mean age 67.7 years (range 39-94), 54.5% white non-Hispanic, 997 received RT alone and 1,416 received RT+ADT. Five-year CVD was 2.3% with RT alone and 3.4% with RT+ADT. In univariate analysis, the following predicted higher CVD with ADT: age &lt; 60 (OR 1.42, p = 0.04), white (OR 2.06, p = 0.001), divorced/separated/widowed (OR 1.29, p = 0.02), insured by Medicare (OR 1.64, p = 0.04), living in mixed urban-rural area (OR 1.87, p = 0.03), higher education level (OR 1.56, p = 0.05), high socioeconomic status (OR 1.70, p = 0.03), no or mild comorbidity level (OR 2.14, p = 0.05 and OR 1.66, p = 0.02, respectively), low PSA (OR 5.44, p = 0,02), and Gleason score 3 (OR 2.12, p = 0.02). In multivariate analysis, use of ADT did not significantly predict hazard of death from heart disease (HR 1.21, p = 0.28) or PC (HR 0.76, p = 0.34). Conclusions: After controlling for confounding variables, use of ADT was not associated with increased risk of CVD in men receiving radiation as definitive therapy for localized PC.
Engaging breast cancer survivors in their survivorship care.
Authors: Genevieve Chaput, Vanessa DiLalla, Maria Barrette, Tristan Williams, Catherine Courteau, Blythe Fortier-McGill
Journal: Journal of Clinical Oncology (2018)

22 Background: In North America, increasing evidence supports including patients’ in managing their own health as a strategy to improve health-related outcomes. Moreover, publications have emphasized the merit of supportive interventions during the survivorship phase, given their association with improvements in overall quality of life. Breast cancer survivors (BCS) are integral stakeholders of their own health, and ensuring their educational needs are met may positively influence them to become actively involved in their survivorship care. This study’s aimed to evaluate BCS activation levels in their care following an end of treatment educational group intervention (EOT) on what to expect after treatment, including self-management tips. Increased activation levels are consistently associated with improved self-management behaviors and utilization of services. Methods: The Patient Activation Measure (PAM), which evaluates one’s knowledge, skills, beliefs, and confidence for managing health and health care, was voluntarily self-administered to BCS shortly before and immediately following the EOT, and interviewer administered by telephone at 1 and 6 months post EOT, respectively. Data were analyzed with parametric (paired t-tests) and non-parametric (Wilcoxon Signed rank tests) comparisons as appropriate to assess EOT impact on BCS’ activation levels. Floor and ceiling effects were considered present if more than 40% of BCS achieved the highest score possible. Results: The pre and post survey response rate was 92.8%, the 1 month and 6 months delayed post survey response rate were 72.4% and 46.4%, respectively (n = 69). Post EOT, BCS significantly increased their activation levels: t(64) = 4.291, p ≤ 0.001, t(50) = 5.982, p ≤ 0.001 to t(32) = 4.664, p ≤ 0.001 for the post, 1 month and 6-month post surveys, respectively. The effect size of the BCS’ increased activation level in their own health increased incrementally with time from small (d = 0.40), medium (d = 0.65) to large (d = 0.84), for the post, 1 month and 6 month surveys, respectively. Conclusions: Our results indicate a large effect size in BCS activation levels at 6 month post EOT, suggesting a significant increase in BCS’s engagement to take part in their survivorship care and overall health.
The UK is hopelessly smitten with e-cigarettes
Authors: Simon Chapman
Journal: BMJ (2018)

The English smoking cessation community has long framed smoking cessation as needing pharmacological assistance.1 Yet, awkwardly, most ex-smokers have quit without any professional or pharmaceutical assistance when they finally succeed.2

Aveyard et al write, “E-cigarettes seem as effective as NRT [nicotine replacement therapy] in supporting cessation, according to the few trials and appropriately conducted cohort studies,” …
Health-related quality of life in patients with psoriatic and rheumatoid arthritis: data from the prospective multicentre NOR-DMARD study compared with Norwegian general population controls
Authors: Brigitte Michelsen, Till Uhlig, Joseph Sexton, Désirée van der Heijde, Hilde Berner Hammer, Eirik Klami Kristianslund, Ada Wierød, Gunnstein Bakland, Erik Rødevand, Frode Krøll, Jon Håvard Loge, Glenn Haugeberg, Tore K Kvien
Journal: Annals of the Rheumatic Diseases (2018)

Objectives To compare (1) Short Form-36 (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS), scale scores and Short Form-6 dimensions (SF-6D) between patients with rheumatoid arthritis (RA) and patients with psoriatic arthritis (PsA) and Norwegian general population controls and (2) improvements in these measures between patients with RA and PsA. Methods Analyses of covariance were performed to compare SF-36 measures between first-time enrolled patients with RA (n=3898) and PsA (n=1515) from the prospective observational multicentre NORwegian-Disease Modifying Anti-Rheumatic Drug study (6 months follow-up) and general population controls (n=2323). Results In age and gender-adjusted analyses, patients with PsA compared with patients with RA had similar PCS, MCS and SF-6D (p≥0.14), worse vitality and general health, but better physical functioning at 0/6 months (p≤0.03). With additional 28-joint disease activity scores adjustment as a proxy for joint inflammation, PCS, most scale scores and SF-6D were worse in patients with PsA than patients with RA at 0/3/6 months (p≤0.01). PCS was more impaired than MCS both in RA and PsA compared with general population controls (p≤0.001). Mean 3-month and 6-month improvements after disease-modifying anti-rheumatic drug treatment were larger in patients with RA than patients with PsA for bodily pain, vitality and mental health (p≤0.02). Conclusions Health-related quality of life was overall similar in patients with RA and patients with PsA—with a tendency to worse scores in PsA—and worse compared with Norwegian general population controls.
Gut microbiota metabolites, amino acid metabolites and improvements in insulin sensitivity and glucose metabolism: the POUNDS Lost trial
Authors: Yoriko Heianza, Dianjianyi Sun, Xiang Li, Joseph A DiDonato, George A Bray, Frank M Sacks, Lu Qi
Journal: Gut (2018)

Objective Alterations in gut microbiota have been linked to host insulin resistance, diabetes and impaired amino acid metabolism. We investigated whether changes in gut microbiota-dependent metabolite of trimethylamine N-oxide (TMAO) and its nutrient precursors (choline and L-carnitine) were associated with improvements in glucose metabolism and diabetes-related amino acids in a weight-loss diet intervention. Design We included 504 overweight and obese adults who were randomly assigned to one of four energy-reduced diets varying in macronutrient intake. The 6-month changes (Δ) in TMAO, choline and L-carnitine levels after the intervention were calculated. Results Greater decreases in choline and L-carnitine were significantly (p&lt;0.05) associated with greater improvements in fasting insulin concentrations and homeostasis model assessment of insulin resistance (HOMA-IR) at 6 months. The reduction of choline was significantly related to 2-year improvements in glucose and insulin resistance. We found significant linkages between dietary fat intake and ΔTMAO for changes in fasting glucose, insulin and HOMA-IR (p interaction &lt;0.05); a greater increase in TMAO was related to lesser improvements in the outcomes among participants who consumed a high-fat diet. In addition, ΔL-carnitine and Δcholine were significantly related to changes in amino acids (including branched-chain and aromatic amino acids). Interestingly, the associations of ΔTMAO, Δcholine and ΔL-carnitine with diabetes-related traits were independent of the changes in amino acids. Conclusion Our findings underscore the importance of changes in TMAO, choline and L-carnitine in improving insulin sensitivity during a weight-loss intervention for obese patients. Dietary fat intake may modify the associations of TMAO with insulin sensitivity and glucose metabolism. Trial registration number NCT00072995 .
17q21 variant increases the risk of exacerbations in asthmatic children despite inhaled corticosteroids use
Authors: N. Farzan, S. J. Vijverberg, N. Hernandez‐Pacheco, E. H. D. Bel, V. Berce, K. Bønnelykke, H. Bisgaard, E. G. Burchard, G. Canino, J. C. Celedón, F. T. Chew, W. C. Chiang, M. M. Cloutier, E. Forno, B. Francis, D. B. Hawcutt, E. Herrera‐Luis, M. Kabesch, L. Karimi, E. Melén, S. Mukhopadhyay, S. K. Merid, C. N. Palmer, M. Pino‐Yanes, M. Pirmohamed, U. Potočnik, K. Repnik, M. Schieck, A. Sevelsted, Y. Y. Sio, R. L. Smyth, P. Soares, C. Söderhäll, K. G. Tantisira, R. Tavendale, S. M. Tse, S. Turner, K. M. Verhamme, A.‐H. Maitland‐van der Zee
Journal: Allergy (2018)
Usability of an adapted electronic health record (EHR)-based cardiovascular health application in the oncology setting: Perceptions of oncologists and cancer survivors.
Authors: Kathryn E. Weaver, Heidi D. Klepin, Tiffany P. Avery, Zanetta S. Lamar, Nicholas Pajewski, William G Hundley, Brian J Wells, Aimee Johnson, Randi E Foraker
Journal: Journal of Clinical Oncology (2018)

129 Background: Cardiovascular health (CVH) is of increasing concern to cancer survivors and their healthcare providers, since survivors of many early-stage cancers are more likely to die of cardiovascular disease than cancer. Our team adapted an existing EHR-based CVH data visualization application designed for the primary care setting to be used in the community oncology setting. We evaluated the acceptability of the Automated Heart-Health Application (AH-HA) among oncology providers and cancer survivors. Methods: We queried oncologists, physician assistants, and nurse practitioners (n=20) who provide care to survivors regarding their perceived usability of AH-HA. Oncologists’ responses were assessed on a 7-point Likert scale from strongly disagree (1) to strongly agree (7); we categorized responses of 5-7 as “agreeing”. We additionally asked cancer survivors (N=48) for their opinions of AH-HA. Patients’ responses were assessed on a 5-point Likert scale from strongly disagree (1) to strongly agree (5); responses of 4 or 5 were categorized as “agreeing”. Results: The majority (60%) of oncology providers (60% female, 65% medical oncologists) had been practicing for more than 5 years. Breast cancer survivors comprised the majority of the survivor sample (98%). Usability data are presented below. 85% of providers reported they would use the tool most or all of the time when providing survivorship care. 94% of patients thought oncologists should discuss heart health during survivorship care; 69% would like to use AH-HA with their oncologist. Conclusions: These usability data demonstrate acceptability and feasibility of implementing the AH-HA application in oncology practices and suggest that oncology providers and survivors would value the integration of such applications in survivorship care. [Table: see text]
Prognostic implications of residual disease (RD) tumor-infiltrating lymphocytes (TIL) in triple negative breast cancer (TNBC) after neo-adjuvant chemotherapy (NAC).
Authors: Stephen James Luen, Roberto Salgado, Maria Vittoria Dieci, Andrea Vingiani, Giuseppe Curigliano, Rebekah Hubbard, Carlos Castaneda Altamirano, Joselyn Sanchez, Timothy D'Alfonso, Esther Cheng, Miluska Castillo Garcia, Sylvia Adams, Fahad Ahmed, David L. Rimm, Sandra Demaria, William Fraser Symmans, Stefan Michiels, Sherene Loi
Journal: Journal of Clinical Oncology (2018)

571 Background: For primary TNBCs treated with NAC, higher pre-treatment TILs correlate with increased pathological complete response (pCR) rates, better recurrence-free survival (RFS) and overall survival (OS). We evaluated the prognostic value of RD TILs to pathological stage and Residual Cancer Burden (RCB) in predicting survival post NAC. Methods: We combined individual patient data from 4 TNBC patient series treated with NAC who did not achieve pCR. TILs were evaluated on the RD using our previously published method on H&E stained slides. TILs were investigated for associations with yp stage, RCB, RFS and OS using Cox models with stromal TILs as a continuous variable, stratified by series. The likelihood ratio (LR) test was used to evaluate added prognostic value of TILs to standard yp stage and RCB class. Results: In total 376 RD samples were evaluable for TILs. After 6 years median follow-up we observed 193 RFS events and 165 deaths. The median age was 50 years (range 24-83). 62% received combination anthracycline/taxane chemotherapy, and 27% anthracycline alone. For RD stage, 32% were yp node positive; RCB class I/II/III was 11%/50%/39% respectively. The median RD TIL level was 20% (IQR 10-40). TIL levels were significantly lower with increasing yp stage (P < 0.01), but did not differ significantly by RCB class (P = 0.84). Higher RD TILs were significantly associated with improved RFS (HR per 10% increment 0.86; 95%CI 0.79-0.92; P < 0.01) and OS (HR 0.87; 95%CI 0.80-0.94; P < 0.01), but were only significant for RFS in multivariate analysis after adjusting for yp stage (P = 0.03). RCB class was significant for RFS and OS (both P < 0.01). RD TILs added significant prognostic value to RCB class for both RFS and OS (both LR P < 0.01). The positive prognostic effect of RD TILs was of greater magnitude in the lower RCB classes I/II vs. III for both RFS and OS (both interaction P < 0.01). Conclusions: TIL levels in TNBC RD are significantly associated with improved RFS and OS and add further prognostic information to RCB class. The positive prognostic influence of TILs is significantly greater in patients with less RD burden. This data may help refine NAC clinical trial endpoints.
Armonización entre el Sistema de notificación de las infecciones respiratorias agudas en la República Checa y las Redes europeas
Authors: J Kyncl, W J Paget, M Havlickova, B Kriz
Journal: Eurosurveillance (2005)

En Europa, la actividad de los virus respiratorios se detecta cada invierno, aunque el inicio y la amplitud de esta actividad sean practicamente imprevisibles. El impacto de la infeccion gripal y/o de las infecciones respiratorias agudas en los paises europeos esta monitorizado continuamente por varios sistemas de vigilancia. Todas esas fuentes de informacion se utilizan para evaluar la naturaleza y la amplitud de la actividad gripal y de los otros virus respiratorios y proponer recomendaciones sobre la prevencion y el control de la morbilidad y mortalidad debidas a la gripe, tanto al nivel local como al nacional e internacional. El sistema de alerta precoz para un brote de gripe se basa principalmente en la utilizacion de una serie de umbrales. En la Republica Checa, el sistema de notificacion de las infecciones respiratorias agudas (IRA), con un tratamiento automatizado de datos, utiliza un modelo estadistico para la deteccion precoz de tasas anormalmente altas de los indicadores vigilados. Se recogen los datos sobre el numero de IRA, el numero de complicaciones debidas a estas infecciones y la poblacion registrada a traves de las notificaciones de los medicos generales y de los pediatras, distribuyendo los datos en cinco grupos de edad. Para mejorar el sistema de notificacion en la Republica Checa, desde enero de 2004 se recogen en la misma poblacion y por grupos de edad los datos clinicos sobre la incidencia semanal de sindrome gripal (SG). Estos datos corresponden a la definicion de caso de SG adoptada recientemente por la Comision Europea, permitiendo la comparacion con otros paises europeos, especialmente con los que participan a la red EISS (European Influenza Surveillance Scheme).
Phase 2b study of 2 dosing regimens of quizartinib monotherapy in FLT3-ITD–mutated, relapsed or refractory AML
Authors: Jorge E. Cortes, Martin S. Tallman, Gary J. Schiller, Denise Trone, Guy Gammon, Stuart L. Goldberg, Alexander E. Perl, Jean-Pierre Marie, Giovanni Martinelli, Hagop M. Kantarjian, Mark J. Levis
Journal: Blood (2018)
Home-Time After Discharge Among Patients Hospitalized With Heart Failure
Authors: Stephen J. Greene, Emily C. O’Brien, Robert J. Mentz, Nancy Luo, N. Chantelle Hardy, Warren K. Laskey, Paul A. Heidenreich, Chun-Lan Chang, Stuart J. Turner, Clyde W. Yancy, Adrian F. Hernandez, Lesley H. Curtis, Pamela N. Peterson, Gregg C. Fonarow, Bradley G. Hammill
Journal: Journal of the American College of Cardiology (2018)
Immune profiling of pre- and post-treatment breast cancer tissues from the S0800 randomized neoadjuvant trial of weekly nab-paclitaxel with or without bevacizumab and dose dense doxorubicin and cyclophosphamide.
Authors: Xiaotong Li, Sarah Warren, Vasiliki Pelekanou, Vikram Wali, Alessandra Cesano, Mingdong Liu, Patrick Danaher, Nathan Elliott, Zeina A. Nahleh, Daniel F. Hayes, Gabriel N. Hortobagyi, William E. Barlow, Christos Hatzis, Lajos Pusztai
Journal: Journal of Clinical Oncology (2018)

578 Background: We examined changes in the tumor immune microenvironment during neoadjuvant chemotherapy by comparing immune gene mRNA expression, tumor infiltrating lymphocyte (TIL) count and PD-L1 protein expression in pre- and post-treatment tissues. Methods: Paired pre- and post- treatment tumor samples from 60 patients were profiled using the Nanostring Immune Oncology 360 platform to measure the expression of 770 immune-related genes that also allowed us to test 14 immune cell type and 27 previously published prognostic and immuno therapy response predictive gene signatures. All samples were also assessed for TIL counts and PD-L1 protein expression by immunohistochemistry. Gene expression levels were compared by paired t-test with Bonferroni correction. TIL count, PD-L1 protein expression and immune gene signatures were compared using Wilcoxon signed-rank test. Baseline immune markers were correlated with pathologic complete response (pCR) using estrogen receptor (ER) and treatment adjusted logistic regression. Results: TIL counts were significantly lower in post- compared to pre-treatment samples (17% vs 7%, p = 0.013) but stromal PD-L1 protein expression was not significantly different. At baseline, higher TIL count and PD-L1 expression were associated with pCR. High expression of a mast cell metagene was associated with residual disease (RD). No individual genes or VEGF gene signature were associated with benefit from bevacizumab. In patients with RD (n = 45), genes involved with tissue repair and inflammation (DUSP1, EGR1, IL6, ATF3, CD36, CXCL2, CD69, NGFR, KLF2, THBD, DAB2) showed significantly higher expression after therapy while most other immune markers decreased. The T effector, T-reg, MHC-I, MHC-II, IFNgamma, STAT-1 and M1 macrophage gene signatures were all significantly lower in post- versus pre-treatment samples and only the IL8/VEGFR and T-helper gene signatures showed higher expression after therapy. Conclusions: High mast cell gene expression is associated with lower pCR rate. TIL counts and most immune parameters decrease after neoadjuvant chemotherapy.
COX2 and HLA immunohistochemical (IHC) staining in colorectal tumour samples from patients participating in the ASCOLT clinical trial of adjuvant aspirin therapy.
Authors: Eva Segelov, Oliver Sieber, John Whay Kuang Chia, David S Williams
Journal: Journal of Clinical Oncology (2018)

695 Background: ASCOLT is an international Phase III randomized control trial (NCT00565708) investigating the impact of adjuvant aspirin on recurrence and survival after curative resection of colorectal cancer (CRC). Retrospective data suggest that COX2 and HLA Class 1 antigen expression may predict for aspirin benefit (Reimers MS, JAMA internal medicine, 2014;174(5):732-739; and Chan AT, JAMA, 2009;302(6):649-658.) Translational studies aim to confirm putative biomarkers of aspirin sensitivity in this prospective trial. This study reports the IHC assessment of COX2 and HLA in representative samples. Methods: FFPE slides from consenting Australian patients were stained with COX2 and HLA Class 1 antibodies (Chan AT, JAMA, 2009;302(6):649-658.). Digital images were captured using Aperio software. IHC expression was scored by a pathologist (DW) blinded to sample identification. Intensity was assessed semi-quantitatively for each antibody in one area of dominant (primary) intensity and one of secondary intensity in each section. A scale was applied for staining intensity: 0=absent, 1=weak, 2=moderate and 3=strong; and for amount of tumor epithelium stained: 1= 5%-24%, 2= 25%-49%, 3=50%-74% 4= &gt;75%. Normal epithelium, which typically has strong COX2 and HLA staining, was used as internal control. Only tumor epithelium was scored (not inflammatory cells). Results: 90 tumors were stained for both COX2 and HLA Class 1. All tumors showed diffuse staining for both markers, mostly strong, but with many tumors having regions with lesser degrees of expression (Table). Conclusions: COX2 expression was generally strong and HLA Class 1 was more likely to show regions of weak to moderate expression. No significant correlation was detected between COX2 and HLA expression levels. Further pathological analysis is underway and correlations will be made with outcome once trial data has matured in 2020. Clinical trial information: NCT00565708. [Table: see text]