tbuckley/cabot-search huggingface dataset:
A randomized, double-blind, multi-center phase III study evaluating paclitaxel with and without RAD001 in patients with gastric or esophagogastric junction carcinoma who have progressed after therapy with a fluoropyrimidine/platinum-containing regimen (RADPAC).
Authors: Sylvie Lorenzen, Jorge Riera Knorrenschild, Claudia Pauligk, Thorsten Oliver Goetze, Susanna Hegewisch-Becker, Jörg Seraphin, Peter C. Thuss-Patience, Hans-Georg Kopp, Tobias Nicolaas Dechow, Arndt Vogel, Kim Barbara Luley, Daniel Pink, Michael Stahl, Frank Kullmann, Holger Frithjof Hebart, Jens T. Siveke, Matthias Egger, Nils Homann, Stephan Probst, Salah-Eddin Al-Batran
Journal: Journal of Clinical Oncology (2017)

4027 Background: There is a need for effective treatments in the second- or further line setting in advanced gastric cancer, especially for new agents. In the current trial we evaluated paclitaxel with RAD001 (everolimus) in patients with gastric carcinoma who have progressed after therapy with a fluoropyrimidine/platinum-containing regimen. Methods: This is a randomized, double-blind, multi-center phase III study. Patients with gastric carcinoma or adenocarcinoma of the esophagogastric junction (EGJ) who have progressed after treatment with a fluoropyrimidine/platinum-containing regimen were randomly assigned to receive Paclitaxel (80 mg/m2) on day 1, 8 and 15 plus placebo (arm A) or RAD001 (10mg daily, arm B) d1-d28, repeated every 28 days as 2 nd , 3 rd or 4 th line therapy. Primary end point was overall survival (OS), secondary endpoints were best overall response, disease control rate, progression free survival (PFS) and toxicity. Results: 300 patients (median age: 62 years; median lines prior therapy: 2; 47.7% of patients had prior taxane therapy) were randomly assigned (Arm A, 150, Arm B, 150). In the intention to treat population, there was no significant difference in median PFS (placebo, 2.07 vs. RAD001, 2.2 months, HR 0.88, p = 0.3) or median OS (placebo, 5.0 vs. RAD001, 6.1 months, HR 0.93, p = 0.54). For patients with prior taxane use, RAD001 improved PFS (placebo 1.8 vs. RAD001, 2.7 months, HR 0.69, p = 0.03) and OS (placebo 3.9 vs. RAD001, 5.8 months, HR 0.73, p = 0.07). Combination of paclitaxel and RAD001 was tolerable, but the RAD001 arm was associated with significantly more grade 3-5 mucositis (13.3% vs. 0.7%; p &lt; 0.001). Conclusions: The addition of RAD001 to paclitaxel/RAD001 did not improve outcomes in pretreated metastatic gastric/EGJ cancer. Of note, activity was seen in the taxane pretreated group. Additional biomarker studies are planned to look for subgroups that may have a benefit. Clinical trial information: 2009-018092-14.
The rumen microbiome: a crucial consideration when optimising milk and meat production and nitrogen utilisation efficiency
Authors: Chloe Matthews, Fiona Crispie, Eva Lewis, Michael Reid, Paul W. O’Toole, Paul D. Cotter
Journal: Gut Microbes (2018)

Methane is generated in the foregut of all ruminant animals by the microorganisms present. Dietary manipulation is regarded as the most effective and most convenient way to reduce methane emissions (and in turn energy loss in the animal) and increase nitrogen utilization efficiency. This review examines the impact of diet on bovine rumen function and outlines what is known about the rumen microbiome. Our understanding of this area has increased significantly in recent years due to the application of omics technologies to determine microbial composition and functionality patterns in the rumen. This information can be combined with data on nutrition, rumen physiology, nitrogen excretion and/or methane emission to provide comprehensive insights into the relationship between rumen microbial activity, nitrogen utilisation efficiency and methane emission, with an ultimate view to the development of new and improved intervention strategies.
Effect of PSA and Gleason score on survival of metastatic prostate cancer.
Authors: Samip R. Master, Runhua Shi
Journal: Journal of Clinical Oncology (2018)

e17042 Background: Prostate-specific antigen (PSA) is used to monitor prostate cancer and rise in PSA is used as a surrogate marker of disease progression. We did a retrospective analysis of the National Cancer database (NCDB) to evaluate the effects of PSA and Gleason score at diagnosis on survival of metastatic prostate cancer patients. Methods: Data was analyzed from 20,532 men registered in the NCDB who were diagnosed with metastatic prostate cancer between 2010 and 2014, and had follow-ups to end of 2014. The primary predictor variables were level of PSA and Gleason Score at diagnosis, and overall survival was the outcome variable. Additional variables addressed and adjusted included age, race, Charlson Comorbidity Index, receipt of chemotherapy and Gleason’s score. Results: The mean age was 76.4 years and SD was 4.9 years. In multivariate analysis, after adjusting for secondary predictor variables, high level PSA of more than 200 and Gleason’s score were statistically significant predictors of overall survival for metastatic prostate cancer. Among the factors analyzed, age, race, co-morbidity index, chemotherapy and Gleason’s score were also found to be significant predictors of survival. Conclusions: High level PSA of > 200 and high Gleason’s score and are significant predictors of shortened survival in patient with metastatic prostate cancer.
Early palliative care: Attitudes and opinions of palliative care physicians.
Authors: Anna Marie Sorensen, Kirsten Wentlandt, Monika K. Krzyzanowska, Lisa W Le, Gary Rodin, Camilla Zimmermann
Journal: Journal of Clinical Oncology (2016)

e21669 Background: Early palliative care (EPC) is increasingly recommended. Recent studies have described oncologists’ barriers to early referral to palliative care. Predictors of early referral included oncologists’ satisfaction with availability of palliative services and palliative services’ acceptance of patients who were receiving chemotherapy. Methods: Palliative care physicians identified by the Canadian Society of Palliative Care Physicians were invited to complete a survey evaluating their attitudes and opinions about EPC by mail and email. Logistic regression was performed on a sample of 257 specialized palliative care (SPC) physicians, (receiving referrals from other physicians) to determine factors associated with receiving early referrals. Backwards likelihood ratio was used to select covariates for the multivariate model (entry p ≤ 0.2). Results: The response rate was 71% (531/747); 48% (257/531) were SPC physicians, the majority of whom (84.4%; 216/256) provide > 50% of their care for cancer patients. The large majority of SPC physicians (93.9%; 229/244) reported that referral to palliative care should ideally be early (at prognosis > 6 months, upon diagnosis of cancer/life-limiting illness, or upon diagnosis of incurable cancer). However, only 20.5% (52/254) reported that the average survival for patients referred to them was > 6 months, and 33.8% (87/256) reported having insufficient resources to provide EPC. Factors associated with receiving early referrals included having a postgraduate degree (OR 2.5, 95% CI 1.1-5.5); providing care mainly for non-cancer patients (4.0, 1.3-12.3); and female sex (2.7, 1.2-6.2). Those agreeing that patients should have stopped all chemotherapy before palliative care referral were less likely to receive early referrals (OR 0.34, 95% CI 0.16-0.73). Conclusions: Although almost all SPC physicians favor EPC, the majority do not receive early referrals. Barriers to earlier integration of palliative care into oncology care appear to be at the receiving as well as the referring end, and include lack of resources as well as a prevailing attitude by a small minority that patients should have stopped all chemotherapy before referral.
From Lifespan to Healthspan
Authors: S. Jay Olshansky
Journal: JAMA (2018)

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Fine and Coarse Particulate Matter Exposures and Associations with Acute Cardiac Events among Participants in a Telemedicine Service: A Case-Crossover Study
Authors: Ronit Nirel, Sara D. Adar, Uri Dayan, Bella Vakulenko-Lagun, Michal Golovner, Ilan Levy, Zvi Alon, Alon Peretz
Journal: Environmental Health Perspectives (2018)

Background: Subclinical cardiovascular changes have been associated with ambient particulate matter (PM) exposures within hours. Although the U.S. Environmental Protection Agency continues to look for additional evidence of effects associated with sub-daily PM exposure, this information is still limited because most studies of clinical events have lacked data on the onset time of symptoms to assess rapid increased risk. Objective: Our objective was to investigate associations between sub-daily exposures to PM and acute cardiac events using telemedicine data. Methods: We conducted a case-crossover study among telemedicine participants ≥50y of age who called a service center for cardiac-related symptoms and were transferred to a hospital in Tel Aviv and Haifa, Israel (2002–2013). Ambient PM2.5 and PM10−2.5 measured by monitors located in each city during the hours before the patient called with symptoms were compared with matched control periods. We investigated the sensitivity of these associations to more accurate symptom onset time and greater certainty of diagnosis. Results: We captured 12,661 calls from 7,617 subscribers experiencing ischemic (19%), arrhythmic (31%), or nonspecific (49%) cardiac events. PM concentrations were associated with small increases in the odds of cardiac events. For example, odds ratios for any cardiac event in association with a 10-μg/m3 increase in 6-h and 24-h average PM2.5 were 1.008 [95% confidence interval (CI): 0.998, 1.018] and 1.006 (95% CI: 0.995, 1.018), respectively, and for PM10−2.5 were 1.003 (95% CI: 1.001, 1.006) and 1.003 (95% CI: 1.000, 1.007), respectively. Associations were stronger when using exposures matched to the call time rather than calendar date and for events with higher certainty of the diagnosis. Conclusions: Our analysis of telemedicine data suggests that risks of cardiac events in telemedicine participants ≥50y of age may increase within hours of PM exposures. https://doi.org/10.1289/EHP2596
Acute leukemia in Puerto Rico: A 5-year retrospective study focusing on cytogenetics mutations.
Authors: Luis Cotto Santana, Deana Hallman
Journal: Journal of Clinical Oncology (2016)

e18533 Background: In Puerto Rico (PR), the University Hospital (UH) has taken care of mostly all adults diagnosed with acute leukemia (AL). A study on incidence, prevalence and survival of AL within the PR population has not been pursued to completion, representing a scientific and clinical need. Methods: This study gathered all clinical and bone marrow findings from adult patients (pts) diagnosed with AL from 2009 to 2013 at the UH. The collected data was statistically analysis using STATA 4.0. Results: Of 247 pts with AL, 187 (76%) were AML, 57 (23%) were ALL and 2 were MPAL. Female to male distribution was homogenous. Regarding age distribution, ages 18-44, 45-64, 65-74, and ≥75 in AML found: 58 (24%), 72 (29%), 44 (18%), and 13 (5%) respectively; and in ALL found: 24 (10%), 22(10%0, 7(3%) and 4(2%), respectively. The 2 MPALs were aged 45-64. Focusing on AML, all received “7+3” (cytarabine/anthracycline) chemotherapy. Of note, 34 (18%) pts were APL. After one induction regimen, 73 (41%) went into a complete remission (CR), 46 (25%) suffered an early death (<30 days), and 68 (36%) had residual disease. Of the CR group, 61 (84%) were <65 y/o. Of the early deaths, 26 (57 %) were <65 y/o. Cytogenetic analysis in shown in Table 1. Conclusions: A total of 247 pts in a 5-year period is significant (~50 pts/year) at a single institution in PR. AML is more prevalent in young to middle-aged adults; although 23% were elderly. Early deaths were 25%, mostly related to infections and poor health. A dismal amount of AMLs (41%) went into CR after one induction, possibly indicating a more resistant leukemia. A significant number (38%) were found to have normal karyotype, of which many suffered early deaths or did not achieve CR, suggesting hidden molecular changes may be of importance. Although we are presenting our preliminary analysis, we hope to have further data in the near future. AML Total (175*) Achieving CR Early deaths Normal Karyotype 67 (36%) 25 (34%) 19 (41%) Single mutations 63 (34%) 32 (44%) 12 (26%) Double mutations 13 (7%) 7 (10%) 3 (7%) Complex mutations ** 32 (17%) 9 (12%) 12 (26%) *12 results were unavailable **defined as ≥ 3 mutations.
Outcome of 91 clear cell sarcoma tumor patients: A retrospective study from the French Sarcoma Group (GSF-GETO).
Authors: Nelly Firmin, Pascaline Boudou-Rouquette, Delphine Duliege, Leonor Chaltiel, Sarah Naomie Dumont, Maud Toulmonde, Sebastien Salas, Isabelle Laure Ray-Coquard, Thibaud Valentin, Sophie Piperno-Neumann, Thomas Ryckewaert, Emmanuelle Bompas, Nicolas Isambert, Jean-Emannuel Kurtz, Christine Le Maignan, Julie Egea, Francois Bertucci, Christophe Perrin, Frederique Larousserie, Christine Chevreau
Journal: Journal of Clinical Oncology (2018)

11552 Background: Clear-Cell Sarcoma (CCS) is a rare soft tissue sarcoma poorly documented, with poor prognosis. Primary objective was to study the characteristics and outcomes of CCS patients (pts). Methods: Retrospective study from the nation-wide French sarcoma network (NetSarc) from 1991 to 2017. Inclusion criterion was CCS central pathological review. Endpoints were local recurrence-free survival (LRFS), metastatic-free survival (MFS), disease-free survival (DFS) and overall survival (OS). Results: 91 pts from 16 centers were included (molecular biology confirmed in 53% pts). Pts were aged 41 years (18-73), 57.1% men. The median tumor size was 4 cm (3-17). Patients were divided in 3 groups: localized (L) (61.5%), locally-advanced (LA) (15.4%), metastatic (M) (23.1%). Presurgical biopsy was performed in 50.7% of pts. All L and LA CCS pts underwent surgery, which was conservative in 70.6% pts. R0 resection was achieved in 71.9% of pts with 42.4% surgical revision to obtain clear margins. After a median follow-up of 6.5 years (95% CI: 4.5-9), 16 (22.9%), 37 (52.9%), 45 (64.3%), 29 (41.4%) events for LRFS, MFS, DFS and OS, were reported. Prognostic factors of the univariate analysis in L and LA pts are presented in Table 1. (Neo)Adjuvant radiotherapy and chemotherapy were performed in 54.4% and 30.9% pts, respectively, with no impact on OS or DFS. The 5-year OS rate for the 91 pts was 53.8% (95% CI: 41.70-64.22). For M pts, median OS was 12.7 months (95% CI: 10.4-21.5). Poor prognostic factors found in univariate analysis were male gender, delay between diagnosis and metastatic stage < 24 months, metastases other than pulmonary, and no surgery for metastatic disease. Conclusions: It's the largest study on CCS since the 1990s, with a large proportion of molecular biology confirmation. Stage, tumor necrosis, tumor size and localization are poor prognosis factors. Endpoint Variable Hazard Ratio (95% CI) p OS Stage Localized 1 0.0128 Locally Advanced 2.76 [1.2 ; 6.37] Tumor Size (mm) < 50 1 0.0171 ≥50 2.82 [1.16 ; 6.85] DFS Stage L 1 0.0253 LA 2.21 [1.08 ; 4.53] Tumor necrosis Yes 1 0.0473 No 2.30 [1.00 ; 5.36] Tumor Size (mm) < 50 1 0.0304 ≥50 2.18 [1.06 ; 4.49] Localization Members 1 0.0335 Other 2.08 [1.04 ; 4.13]
Dupilumab progressively improves systemic and cutaneous abnormalities in patients with atopic dermatitis
Authors: Emma Guttman-Yassky, Robert Bissonnette, Benjamin Ungar, Mayte Suárez-Fariñas, Marius Ardeleanu, Hitokazu Esaki, Maria Suprun, Yeriel Estrada, Hui Xu, Xiangyu Peng, Jonathan I. Silverberg, Alan Menter, James G. Krueger, Rick Zhang, Usman Chaudhry, Brian Swanson, Neil M.H. Graham, Gianluca Pirozzi, George D. Yancopoulos, Jennifer D. D. Hamilton
Journal: Journal of Allergy and Clinical Immunology (2018)

Dupilumab is an IL-4 receptor α mAb inhibiting signaling of IL-4 and IL-13, key drivers of type 2-driven inflammation, as demonstrated by its efficacy in patients with atopic/allergic diseases.This placebo-controlled, double-blind trial (NCT01979016) evaluated the efficacy, safety, and effects of dupilumab on molecular/cellular lesional and nonlesional skin phenotypes and systemic type 2 biomarkers of patients with moderate-to-severe atopic dermatitis (AD).Skin biopsy specimens and blood were evaluated from 54 patients randomized 1:1 to weekly subcutaneous doses of 200 mg of dupilumab or placebo for 16 weeks.Dupilumab (vs placebo) significantly improved clinical signs and symptoms of AD, was well tolerated, and progressively shifted the lesional transcriptome toward a nonlesional phenotype (weeks 4-16). Mean improvements in a meta-analysis-derived AD transcriptome (genes differentially expressed between lesional and nonlesional skin) were 68.8% and 110.8% with dupilumab and -10.5% and 55.0% with placebo (weeks 4 and 16, respectively; P < .001). Dupilumab significantly reduced expression of genes involved in type 2 inflammation (IL13, IL31, CCL17, CCL18, and CCL26), epidermal hyperplasia (keratin 16 [K16] and MKi67), T cells, dendritic cells (ICOS, CD11c, and CTLA4), and TH17/TH22 activity (IL17A, IL-22, and S100As) and concurrently increased expression of epidermal differentiation, barrier, and lipid metabolism genes (filaggrin [FLG], loricrin [LOR], claudins, and ELOVL3). Dupilumab reduced lesional epidermal thickness versus placebo (week 4, P = .001; week 16, P = .0002). Improvements in clinical and histologic measures correlated significantly with modulation of gene expression. Dupilumab also significantly suppressed type 2 serum biomarkers, including CCL17, CCL18, periostin, and total and allergen-specific IgEs.Dupilumab-mediated inhibition of IL-4/IL-13 signaling through IL-4 receptor α blockade significantly and progressively improved disease activity, suppressed cellular/molecular cutaneous markers of inflammation and systemic measures of type 2 inflammation, and reversed AD-associated epidermal abnormalities.
Measles immune status in an inner city pediatric oncology patient cohort during the measles outbreak of 2015.
Authors: Nupur Mittal, Paul Kent, Daniel Urkov, Antonio D Logan, Adam Kidwell
Journal: Journal of Clinical Oncology (2016)

e18228 Background: Survivors of pediatric cancer are at risk of long- term consequences of therapy one of which is loss of pre-existing protective antibodies predisposing them to illnesses such as Measles. Measles in recipients of immunosuppressive chemotherapy has mortality rates up to 50%. Up to 35% of children < 7 Years lose humoral immunity to measles as a result of chemotherapy. Despite the strategies by WHO for improving measles vaccine coverage, the disease still continues to circulate leading to outbreaks in developed countries. In 2015, the US experienced a measles outbreak. 189 cases (40% < 18 years) were reported across 24 states including Illinois. Measles is a highly infectious from 48 hours prior to first symptoms. Our small pediatric oncology practice shares office and floor space with other pediatric practices, placing our patients at risk for infection by measles. Prior to this study, it was not our standard practice to check measles immunity titer prior to initiation of chemotherapy. Methods: Because of the new risk to our patients we chose to check measles protective humoral immune status in our patients from January-June 2015, the period of measles outbreak in USA. Patients under 21 receiving chemotherapy between January 2015 and June 2015 in our department were included in prospective review. We defined immunity according to our lab standards. Results: A total of 30 (15 female) patients were included. Three patients (10%) had non protective measles antibody levels. One of these three patients was previously unimmunized, 2 were < 3 years at diagnosis and had leukemia, one was diagnosed with hepatoblastoma. All came every weekly to the clinic for chemotherapy and thus waited in the shared waiting area. None of the patients developed measles. Conclusions: Measles outbreaks in the US pose a grave threat to immunocompromised children. This danger is increased in the nosocomial setting with shared clinical space. 100% vaccination for all children, stringent isolation strategies in pediatric clinic waiting areas and standard practice of checking measles immune status in all pediatric patients prior to chemotherapy initiation may help prevent this devastating disease in this sensitive population.
Abstract 11076: Tissue Engineered Complementary Endothelial Progenitor Cell Sheet to Reverse Adverse Ventricular Remodeling Following Ischemic Cardiomyopathy
Authors: Yasuhiro Shudo, Pavan Atluri, John W MacArthur, Philip F Hsiao, Elaine C Yang, Alexander S Fairman, Alen Trubelja, Shigeru Miyagawa, Yoshiki Sawa, Joseph Y Woo
Journal: Circulation (2012)

Introduction Endothelial progenitor cell (EPC) has shown in vitro and in vivo potential therapeutic angiogenesis, while there are still limitations related with improper vascular network. It is essential to optimize mature vessels. We hypothesized that EPC co-cultured with smooth muscle cell (SMC), a component of vascular pericyte, might induce robust and functional vessels, together with enhancing the angiogenic performance and preserving the endothelial-pericyte interaction. Methods and Results Primary EPC and SMC of male Wister rats were isolated and cultured. Expression of VEGF, HGF, TGFβ, and SDF1α in the culture supernatant in vitro was significantly greater in co-cultured EPC with SMC, compared to either EPC- or SMC-only, as assessed by ELISA. No significant difference was found in the concentrations of these cytokines between in the supernatant of “co-cultured” dish of both EPCs and SMCs plated together, and “separate-cultured” dish EPCs and SMCs plated onto the different layers using the trans-we...