tbuckley/cabot-search huggingface dataset:
Prognostic factors associated with long term survival in chemotherapy-treated advanced pancreatic cancer: A Canadian multicenter analysis.
Authors: Christina Kim, Shahid Ahmed, Dawn Elizabeth Armstrong, Tayyba Baig, Miguel Cardoso, Yoo-Joung Ko, Shiying Kong, Madison Mackinnon, Brandon Matthew Meyers, Michelle Pratt, Julie Ward, Yuan Xu, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2019)

416 Background: The outcomes of patients (pts) with advanced pancreatic cancer (APC) are poor. With the use of currently available multi-agent regimens, median overall survival (mOS) remains &lt; 12 months. Select pts, however, experience a protracted survival. Little is known about the clinical, pathologic and treatment characteristics associated with long term survival (LTS) in APC. Methods: Pooled individual level data from six Canadian cancer centers of pts diagnosed with APC from 2012 to 2016 who received at least one cycle of chemotherapy (CT) were analyzed. Clinical, pathologic and treatment characteristics, as well as survival, were compared between pts who lived &lt; and ≥ 18 months. Multivariable logistic regression was used to identify independent predictors of survival. Results: Of 455 pts, 96% had metastatic disease and 88 (19%) survived ≥ 18 months. Compared to pts who survived &lt; 18 months, those with LTS had lower WBC (p = 0.0025), CA 19-9 (p &lt; 0.001), ALP (p &lt; 0.001) and LDH (p = 0.007) at baseline. Pts with LTS also had higher albumin (p &lt; 0.001) and BMI (p = 0.0268). In addition, they had better ECOG (p &lt; 0.001) and were more likely to have tumors in the head of the pancreas (p = 0.0204). LTS pts were more likely to have a complete response (CR) or partial response (PR) to 1L CT (p &lt; 0.001). The mOS seen with LTS was 29.2 months, compared to 4.3 months (p &lt; 0.001). On multivariable logistic regression, independent predictors of LTS included: primary tumor in the head of the pancreas (OR 3.42 95% CI 1.2-9.76); experiencing a CR or PR to 1L CT (OR 9.19 95% CI 3.78-22.32); and receipt of 2L doublet CT (OR 2.72 95% CI 1.05 to 7.08). Conversely, factors associated with lower likelihood of LTS included: ECOG ≥ 2 (OR 0.32 95% CI 0.11-0.95); and elevated CA 19-9 (OR 0.43 95% CI 0.21-0.9). Conclusions: A select proportion of pts with APC experience LTS and have clinical features which differentiate them from those without LTS. The use of performance status, primary tumor location, pre-treatment CA 19-9, 2L CT type and radiologic response may help identify LTS and inform discussions regarding treatment and prognosis.
Sequential gemcitabine (G), oxaliplatin (O), and irinotecan (I) based weekly metronomic chemotherapy (MC) regimens for the treatment of metastatic pancreatic cancer (mPC): A community cancer clinic experience.
Authors: Ben M. Chue, Bryce D. La Course
Journal: Journal of Clinical Oncology (2019)

284 Background: mPC has a poor prognosis with a median overall survival (mOS) ranging from 8.5 to 11.1 months (mo) with standard treatment, outlining the need for new innovative treatments. MC regimens utilize lower doses of chemotherapy that are administered more frequently which can maintain dose intensity while reducing toxicity. MC with paclitaxel (P) or nab-paclitaxel (N) may have effects on the tumor microenvironment. Methods: A retrospective analysis of treatment regimens and survival of patients (pts) with biopsy proven mPC who received treatment between August 2004 and August 2018 was performed. Results: 30 pts with biopsy proven mPC were identified. 14 pts received prior chemotherapy. mOS of this cohort was 18.9 mo after diagnosis and 14.2 mo after beginning MC. 70% of pts (21/30) survived longer than 12 mo, 37% (11/30) greater than 24 mo, and 27% (8/30) greater than 30 mo. All MC regimens were given on a weekly basis and included: P 60 mg/m² and G 600 mg/m² (PaG); P 60 mg/m², O 50 mg/m², folinic acid (L) 20 mg/m², and 5-fluorouracil (F) 425 mg/m² (POLF); P 60 mg/m², I 100 mg/m², and cisplatin (C) 20 mg/m² (PIC) or P 60 mg/m², I 100 mg/m², L 20 mg/m², and F 425 mg/m² (PILF). 21 pts received N instead of P at some point during their treatment. PaG, POLF, and PIC or PILF were purposely switched before disease progression after a median length of 13, 11 and 13 weeks respectively. 16 pts received PaG as their first regimen. 12 of these 16 pts then received POLF as their second regimen, and 7 of these 12 pts subsequently received PIC or PILF as their third regimen. These 7 pts had a mOS of 21.7 mo after diagnosis and 19.1 mo after beginning MC. 10 pts were successfully able to receive PaG, POLF, or PIC/PILF more than once. Conclusions: Weekly MC regimens such as PaG, POLF, and PIC/PILF that are given sequentially are an effective treatment for mPC. Switching regimens may prevent the development of chemotherapy resistance, allowing for chemotherapy regimens to be used again in the future. There are limitations of retrospective studies so further investigation of this treatment strategy should be done with a large randomized clinical trial.
Anti-Human CD117 CAR T-Cells Efficiently Eliminate Hematopoietic Stem and CD117-Positive AML Cells
Authors: Renier Myburgh, Jonathan Kiefer, Norman F Russkamp, Alexander Simonis, Surema Pfister, C. Matthias Wilk, Chiara Magnani, Antonia MS Mueller, Burkhard Becher, Maries van den Broek, Dario Neri, Markus G. Manz
Journal: Blood (2018)
Association Between Water Fluoridation and Income-Related Dental Caries of US Children and Adolescents
Authors: Anne E. Sanders, William B. Grider, William R. Maas, John A. Curiel, Gary D. Slade
Journal: JAMA Pediatrics (2019)

and 6′-sialyllactose (probiotic group, 472 [159] μmol/mL; control group, 567 [179] μmol/mL; P = .03).These changes are consistent with a change in select pathways in overall HMO biosynthetic machinery (Figure ,B).Conclusions | Although HMO composition is largely genetically determined, maternal probiotic supplementation during late stages of pregnancy may change the HMO composition in human milk.It is unknown whether the change is specific to the probiotics used in this study, and findings need to be confirmed by other studies.In this case, we hypothesize a shift from 6′-sialylation to 3′-sialylation and toward type-2 core structures in HMOs.Maternal diet, medications, and microbiome may be important factors modulating a mother's colostrum HMO levels that should be considered when assessing biological effects suspected to be mediated by HMO levels.Ultimately,
Abstract P207: Association Between a 20-year CVD-risk Score Based on Modifiable Lifestyles and Total and Cause Specific Mortality Among US Men and Women
Authors: Mercedes Sotos-Prieto, Howard D Sesso, Frank B Hu, Walter C Willett, Stephanie E Chiuve
Journal: Circulation (2017)

Background: The previously validated Healthy Heart Score, based on modifiable health behaviors (diet, physical activity, alcohol intake, smoking, and body weight), effectively predicted the 20-year risk of CVD in mid-adulthood. While these lifestyle behaviors are independently associated with many chronic diseases, it remains unknown whether the Healthy Heart Score may extend to an association with overall mortality risk. Thus, we examined the Healthy Heart Score and total and cause-specific mortality in the Nurses’ Health Study (NHS) and Health Professional Follow-up Study (HPFS). Methods: We conducted a prospective analysis among 58,319 women in the NHS (1984-2010) aged 30-55 y and 30,713 in men in the HPFS (1986-2010) aged 40-75 y free of cancer and CVD at baseline. The Healthy Heart Score was calculated at baseline and included 9 factors that best estimated CVD risk: current smoking, higher BMI, low physical activity, lack of moderate alcohol consumption, low intakes of fruits and vegetables, cereal fiber, and nuts, and high intakes of sugar-sweetened beverages and red and processed meats). Cox proportional hazards models estimated hazard ratios (HR) and 95% confidence intervals (CI) and adjusted for various demographics, medical history, medication use and total energy. Results: During 2,075,504 years of follow-up, there were 19,181 total deaths, including 11,464 in women and 7,717 in men. Compared to participants with the lowest predicted 20-year CVD risk based on the Healthy Heart Score (1 st quintile, median CVD risk: 0.01%), participants with the highest predictive CVD risk (5 th quintile, median CVD risk: 0.03%) had a pooled HR (95%CI) of 2.26 (1.86, 2.13) for total mortality; 2.89 (95 CI%, 1.93, 4.32) for CVD mortality; and 2.55 (95% CI 2.39, 2.72) for cancer mortality. Participants in the 5 th quintile vs . the 1 st quintile of the Healthy Heart Score had also a significantly greater risk of death due to CHD (3.40 [2.20, 5.26]), stroke (1.77 [1.00, 3.14]), lung cancer (6.02 [2.83, 12.79]), breast cancer (1.45 [1.13, 1.85]), colon cancer (1.51 (1.17, 1.94)), respiratory disease (3.94 (1.03, 15.14)), and diabetes (3.63 (2.00, 6.59)). Conclusion: The Healthy Heart Score, comprised of 9 self-reported, modifiable lifestyle predictors of CVD, is strongly associated with a greater risk of all-cause and cause-specific mortality. This risk score is a potentially useful tool for risk assessment and counseling of healthy lifestyles to promote longevity
Treatment sequencing in MPC, insights from a 3˚ care center.
Authors: Ivan Barrera, Jill Ranger, Nooshin Roofigari, Richard Dalfen, Gerald Batist, Petr Kavan
Journal: Journal of Clinical Oncology (2019)

400 Background: Since 2011, options for treatment of metastatic pancreatic cancer (mPC) have improved with the use of nab-paclitaxel plus gemcitabine (n-PGEM) or FOLFIRINOX (FFX) as first line treatments (1LTx). In 2016, Nanoliposomal irinotecan plus 5FU (nal-IRI-5FU) demonstrated efficacy in 2LTx. Yet, optimal sequential Tx has not been established. Methods: We evaluated oncologist-selected Tx algorithms and resultant progression free &amp; overall survival (PFS, OS) for pts with mPC from 2010 and 2018 at the Jewish General Hospital, Montreal, QC. This retrospective study included 203 pts with mPC (33 to 89 years, 54% male). Results: 1LTx included 66 pts on FFX, 60 pts on n-PGEM, and 66 pts on single-agent GEM. The remaining pts received Capecitabine (CAP) or another Tx (N = 11). Mean PFS in FFX, n-PGEM, and GEM groups was 5.07, 5.52, and 4.10 months, respectively (progression was 1˚ or 2˚ disease progression or a change of Tx due to adverse events or intolerance). Only the FFX and GEM groups were significant when compared (p = 0.049). Only 43.8% of pts (N = 89/203) advanced to 2LTx most receiving GEM (N = 27), n-PGEM (N = 21), or FFX (N = 11), PFS 3.87, 7.04, and 2.30 months, respectively. FFX and n-PGEM groups were significant when compared (p=0.011). CAP and nal-IRI-5FU were 2LTx options for 25.8% (N=23/89) and 7.9% (N = 7/89) of pts, respectively. For 30 pts in 3LTx, Txs included: nal-IRI-5FU (N = 8), clinical trials (CT) (N = 7), GEM (N = 5), FFX (N = 4), n-PGEM (N = 2), CAP (N = 2) and Irinotecan (IRI) (N = 2). Only 7 pts received 4LTx: GEM (N = 3), CAP (N = 2), CT (N = 1), and IRI (N = 1). Median OS from start of 1LTx for pts in FFX (N = 60), n-PGEM (N = 41), and GEM (N = 60) groups was 11.42, 9.50, and 6.23 months, respectively. (Excluding pts on ongoing tx and other censored data points). GEM tx was a significant prognostic factor for shorter OS, GEM verus FFX, HR 1.673 (1.165 to 2.402, p = 0.0053), GEM versus n-PGEM, HR 1.511 (1.012 to 2.258, p = 0.0437). No difference in survival was seen between FFX and n-PGEM groups, HR 0.903 (95% CI 0.605-1.349, p = 0.6196). Conclusions: Though FFX and n-PGEM are considered mainstays of 1LTx, GEM was chosen by physicians in ~1/3 of cases despite reduced PFS. Pts on FFX or n-PGEM had better OS compared to GEM alone, as expected. Further investigation into Tx sequencing in this and larger cohorts, is needed.
Long-term Outcomes of Stereotactic Body Radiotherapy for Low-Risk and Intermediate-Risk Prostate Cancer
Authors: Amar U. Kishan, Audrey Dang, Alan J. Katz, Constantine A. Mantz, Sean P. Collins, Nima Aghdam, Fang-I Chu, Irving D. Kaplan, Limor Appelbaum, Donald B. Fuller, Robert M. Meier, D. Andrew Loblaw, Patrick Cheung, Huong T. Pham, Narek Shaverdian, Naomi Jiang, Ye Yuan, Hilary Bagshaw, Nicolas Prionas, Mark K. Buyyounouski, Daniel E. Spratt, Patrick W. Linson, Robert L. Hong, Nicholas G. Nickols, Michael L. Steinberg, Patrick A. Kupelian, Christopher R. King
Journal: JAMA Network Open (2019)

Stereotactic body radiotherapy harnesses improvements in technology to allow the completion of a course of external beam radiotherapy treatment for prostate cancer in the span of 4 to 5 treatment sessions. Although mounting short-term data support this approach, long-term outcomes have been sparsely reported.To assess long-term outcomes after stereotactic body radiotherapy for low-risk and intermediate-risk prostate cancer.This cohort study analyzed individual patient data from 2142 men enrolled in 10 single-institution phase 2 trials and 2 multi-institutional phase 2 trials of stereotactic body radiotherapy for low-risk and intermediate-risk prostate cancer between January 1, 2000, and December 31, 2012. Statistical analysis was performed based on follow-up from January 1, 2013, to May 1, 2018.The cumulative incidence of biochemical recurrence was estimated using a competing risk framework. Physician-scored genitourinary and gastrointestinal toxic event outcomes were defined per each individual study, generally by Radiation Therapy Oncology Group or Common Terminology Criteria for Adverse Events scoring systems. After central review, cumulative incidences of late grade 3 or higher toxic events were estimated using a Kaplan-Meier method.A total of 2142 men (mean [SD] age, 67.9 [9.5] years) were eligible for analysis, of whom 1185 (55.3%) had low-risk disease, 692 (32.3%) had favorable intermediate-risk disease, and 265 (12.4%) had unfavorable intermediate-risk disease. The median follow-up period was 6.9 years (interquartile range, 4.9-8.1 years). Seven-year cumulative rates of biochemical recurrence were 4.5% (95% CI, 3.2%-5.8%) for low-risk disease, 8.6% (95% CI, 6.2%-11.0%) for favorable intermediate-risk disease, 14.9% (95% CI, 9.5%-20.2%) for unfavorable intermediate-risk disease, and 10.2% (95% CI, 8.0%-12.5%) for all intermediate-risk disease. The crude incidence of acute grade 3 or higher genitourinary toxic events was 0.60% (n = 13) and of gastrointestinal toxic events was 0.09% (n = 2), and the 7-year cumulative incidence of late grade 3 or higher genitourinary toxic events was 2.4% (95% CI, 1.8%-3.2%) and of late grade 3 or higher gastrointestinal toxic events was 0.4% (95% CI, 0.2%-0.8%).In this study, stereotactic body radiotherapy for low-risk and intermediate-risk disease was associated with low rates of severe toxic events and high rates of biochemical control. These data suggest that stereotactic body radiotherapy is an appropriate definitive treatment modality for low-risk and intermediate-risk prostate cancer.
Hematopoietic Stem and Progenitor Cell Proliferation and Differentiation Requires the Trithorax Protein Ash2l In Vivo
Authors: Nicolas Chatain, Juliane Lüscher-Firzlaff, Chao-Chung Kuo, Agnieszka Bochyńska, Andrea Ullius, Bernd Denecke, Ivan Costa, Steffen Koschmieder, Bernhard Lüscher
Journal: Blood (2018)
Stim1 Deletion Synthetically Rescues Ezh2-Null Effector T Cells and Alloimmunity
Authors: Ying Wang, Shan He, Yongnian Liu, Robert Hooper, Hongshuang Yu, Yuanyuan Tian, Hongxing Sun, Ran Reshef, Elizabeth O. Hexner, Jonathan Soboloff, Yi Zhang
Journal: Blood (2018)
Dynamic hyperinflation impairs daily life activity in asthma
Authors: Akke-Nynke van der Meer, Kim de Jong, Aranka Hoekstra-Kuik, Elisabeth H. Bel, Anneke ten Brinke
Journal: European Respiratory Journal (2019)

Introduction Dynamic hyperinflation has been documented in asthma, yet its impact on overall health and daily life activities is unclear. We assessed the prevalence of dynamic hyperinflation in moderate to severe asthma and its relationship with the scores of a set of specific and general respiratory health questionnaires. Methods 77 nonsmoking asthma patients (Global Initiative for Asthma steps 4–5) were recruited consecutively and completed five questionnaires: Asthma Control Questionnaire, Clinical COPD (chronic obstructive pulmonary disease) Questionnaire, St George's Respiratory Questionnaire, London Chest Activity of Daily Living scale (LCADL) and Shortness of Breath with Daily Activities (SOBDA). Dynamic hyperinflation was defined as ≥10% reduction in inspiratory capacity induced by standardised metronome-paced tachypnoea. Associations between level of dynamic hyperinflation and questionnaire scores were assessed and adjusted for asthma severity. Results 81% (95% CI 71.7–89.4%) of patients showed dynamic hyperinflation. Higher levels of dynamic hyperinflation were related to poorer scores on all questionnaires (r=0.228–0.385, p&lt;0.05). After adjustment for asthma severity, dynamic hyperinflation remained associated with poorer scores on LCADL (p=0.027) and SOBDA (p=0.031). Conclusion Dynamic hyperinflation is associated with poorer overall health and impaired daily life activities, independent of asthma severity. Because of its major impact on everyday life activities, dynamic hyperinflation is an important target for treatment in asthma.
Abstract P017: Migraine and Cognitive Function: baseline Findings From the Brazilian Longitudinal Study of Adult Health: ELSA-Brasil
Authors: Cristina P Baena, Alessandra Goulart, Itamar Santos, Claudia Suemoto, Paulo Lotufo, Isabela Benseñor
Journal: Circulation (2017)

Background: Migraine and dementia are associated with higher vascular risk and both conditions have been linked with structural brain lesions. However, evidence on the possible association between migraine and cognitive performance is unclear. We aimed to analyze whether migraine is associated with cognitive performance within participants of the Brazilian Longitudinal Study of Adult Health, ELSA-Brasil. Methods: Inthis a cross-sectional analysis, we evaluated all participants without previous stroke, who were not taking medications that could impair cognitive performance and with complete data on cognitive tests or migraine at baseline assessment. Migraine based on International Headache Society classification was used as dependent variable in binary logistic models. The Consortium to Establish a Registry for Alzheimer’s disease scores for word list memory test (CERAD-WLMT), the semantic fluency test (SFT), and the Trail Making Test version B (TMTB) were categorized into poor cognitive performance as defined by a score below mean minus one standard deviation for a participant’s sex, age and educational-level group for memory and fluency tests and as a score above mean plus one standard deviation for the time to perform the Trail Making Test Version B.. Multivariate analyses were adjusted for marital status, alcohol consumption, smoking, physical activity, body-mass index, hypertension, diabetes mellitus and depression. In women we further adjusted for hormone replacement therapy. Results: We analyzed 4993 men(51.6 ±9.2 y) and 5028 women (51.9±8.9y ). Among those, there were 131 men( 2.6 %) and 926 women migraneurs (18.4%). The proportion of participants in the poor cognitive category did not differ significantly between migraneurs and non-migraneurs for men or women in any of the cognitive tests (p&gt;0.072 for all). Fully adjusted OR (95%) for poor performance in men on immediate recall, late recall, recognition, verbal fluency, and TMTB were 1.02(0.60;1.72),1.15(0.69;1.91), 0.86(0.51;1.43), 1.08(0.51;1.43) and 1.75(0.64;1.82) respectively and in women 1.06(0.69; 1.62); 0.89 (0.61;1.29);1.25(0.81;1.95) and 1.72(1.07;2.77) respectively. Conclusion: Migraine was associated with poorer executive function in middle-aged women after multivariate adjustment including HRT. No association was found for middle-aged men, but this may be a consequence of the lower number of men with migraine compared to women.
Abstract 10918: AST-120 Prevents the Progression of Kidney Injury After Myocardial Infarction
Authors: Hideki Fujii, Keiji Kono, Yuriko Yonekura, Kentaro Nakai, Shunsuke Goto, Yusuke Yamashita, Mikio Sugano, Sumie Goto, Ayako Fujieda, Yoshiharu Ito, Shinichi Nishi
Journal: Circulation (2015)

Introduction: Chronic kidney disease (CKD) is a crucial risk factor for cardiovascular disease (CVD), and combined CKD and CVD further increases morbidity and mortality. Therefore, the prevention of kidney injury is essential for the improvement of prognosis of patients with CVD. Among the many factors, increased oxidative stress plays a role for the pathogenesis of CKD and CVD. Hypothesis: AST-120, which is an oral charcoal adsorbent, may prevent kidney injury by reducing one of the uremic toxins, indoxyl sulfate (IS) and oxidative stress in a rat myocardial infarction (MI) model. Methods: At 10 weeks of age, male spontaneously hypertensive rats (SHR) were divided into 3 groups: SHR (n=6), MI (n=8) and MI+AST-120 groups (n=8) and the administration of AST-120 was started at 11 weeks of age. MI was induced by the ligation of the left coronary artery in the MI and MI+AST-120 groups at 10 weeks of age. At 18 weeks of age, rats were sacrificed, and blood and urine analyses, mRNA expression analysis, renal histological analysis, and echocardiography were performed in these groups. Results: At 18 weeks of age, though there were no significant differences in blood pressure and kidney function, serum IS levels and urinary IS excretion were reduced in the AST-120 groups compared to the MI groups. Urinary 8-hydroxydeoxyguanosine (8-OHdG) excretion, serum tissue growth factor beta (TGF-β) levels, serum neutrophil gelatinase-associated lipocalin (NGAL) levels, serum kidney injury molecular-1 (KIM-1) levels and serum,L-type fatty acid binding protein (L-FABP) levels were also decreased in the MI+AST-120 group compared to the other two groups. The mRNA expressions of NADPH oxidase and NF-kappa B, connective tissue growth factor (CTGF) in the kidney were significantly decreased in the MI+AST-120 group compared to the MI group. In vitro data using LCC-PK1 cells also supported the influence of IS on kidney injury. Further immunohistological analysis revealed that intrarenal oxidative stress was reduced by AST-120 administration. Conclusions: Our data showed that IS increased after MI and AST-120 is suggested to have protective effects on kidney injury after MI through the suppression of oxidative stress.
Genome-Wide Association Study (GWAS) Identifies a Significant Acute Myeloid Leukemia (AML) Susceptibility Locus Near BICRA
Authors: Christopher J. Walker, Christopher C. Oakes, Luke K Genutis, Brian Giacopelli, Sandya Liyanarachchi, Deedra Nicolet, Ann-Kathrin Eisfeld, Markus Scholz, Pamela Brock, Jessica Kohlschmidt, Krzysztof Mrózek, Marius Bill, Andrew J. Carroll, Jonathan E. Kolitz, Bayard L. Powell, Eunice S. Wang, Dietger Niederwieser, Richard M. Stone, John C. Byrd, Sebastian Schwind, Albert de la Chapelle, Clara D. Bloomfield
Journal: Blood (2018)
Abstract 16711: Predicting Progression of Heart Failure Using Administrative Data and Medical Records
Authors: Yanting Dong, David Steenhard, Diana Cusano, Maithreyi Ganti, Yun Wei, George Andrews, Vipin Gopal
Journal: Circulation (2017)

Introduction: Heart failure (HF) affects nearly six million Americans. It is the leading cause of hospitalization in people older than age 65. About 50% of people who develop HF die within five yea...