tbuckley/cabot-search huggingface dataset:
Efficacy and safety of CD19-targeted 19-28z CAR modified T cells in adult patients with relapsed or refractory B-ALL.
Authors: Jae Hong Park, Isabelle Riviere, Xiuyan Wang, Yvette Bernal, Terence Purdon, Elizabeth Halton, Kevin Joseph Curran, Craig Steven Sauter, Michel Sadelain, Renier J. Brentjens
Journal: Journal of Clinical Oncology (2015)

7010 Background: Adult patients (pts) with relapsed or refractory (R/R) acute lymphoblastic leukemia (ALL) have dismal prognosis. We previously reported high anti-tumor activity of autologous T cells genetically modified to express 19-28z chimeric antigen receptor (CAR) targeting CD19 in adult pts with ALL. Herein, we report the long-term outcome of our phase I trial in adults with R/R ALL (NCT01044069). Methods: Adult pts with R/R B-ALL underwent leukapheresis, and T cells were transduced with a gammaretroviral vector encoding a CAR construct composed of anti-CD19 scFv linked to CD28 and CD3ζ signaling domains (19-28z). All pts received conditioning chemotherapy followed by 1–3x106 19-28z CAR T cells/kg. Results: 33 pts have been treated, and 32 pts are evaluable for response. The median age was 54 years (range, 22-74). 12 pts (36%) had Ph+ ALL, 11 pts (33%) had prior allogeneic stem cell transplant (allo-SCT), and 14 pts (42%) had ≥ 3 prior lines of therapy. At the time of CAR T cell infusion, 16 had morphologic disease ( > 5% blasts in BM) and the remaining 16 pts had minimal residual disease (MRD). 13/16 pts with morphologic disease (81%) and 16/16 pts with MRD (100%) were in complete remission (CR) after 19-28z CAR T cell infusion, yielding an overall CR rate of 91% (29/32). Of the 28 MRD evaluable patients, MRD negative CR rate was 82%. 11 pts underwent allo-SCT following the CAR T cells. As of 1/25/15, the median follow-up was 5.1 months (range, 1.0-37.6+), with 14 pts having ≥ 6 months of follow-up. 6-month overall survival (OS) rate of all patients was 58% (95% CI: 36-74). Among the pts who achieved CR, OS rate at 6 months for pts who had allo-SCT vs. no allo-SCT following CAR T cells was 70% (95% CI: 33-89) vs. 61% (95% CI: 29-82; p = 0.30). Severe cytokine release syndrome (sCRS) requiring vasopressors or mechanical ventilation for hypoxia was observed in 7 patients, effectively managed with IL-6R inhibitor and/or corticosteroids. Conclusions: 19-28z CAR T cells can induce a high CR rate of 91% in adult patients with R/R ALL. The risk of sCRS correlates with disease burden and can be effectively managed. These findings strongly support the use of 19-28z CAR T cells in adults with R/R ALL and warrants investigation in a phase II trial. Clinical trial information: NCT01044069.
Abstract P343: Comparison of Two-stage and One-stage Meta-analyses: An Example of eGFR-Cardiovascular Mortality Association (for CKD-PC collaborators)
Authors: Yingying Sang, Kunihiro Matsushita, Bakhtawar K Mahmoodi, Brad C Astor, Josef Coresh, Mark Woodward
Journal: Circulation (2012)

Purpose: Individual participant data (IPD) meta-analysis provides precise statistical estimates. Two approaches to meta-analyze IPD are currently used. The 1-stage approach fits a regression model to a pooled dataset including all studies. The 2-stage approach fits models in individual studies and meta-analyzes the estimates. However, their comparability has not been well described. We compare these methods for eGFR-cardiovascular mortality association in the CKD Prognosis Consortium (CKD-PC). Methods: For the 1-stage method, we fitted a Cox stratified model, allowing each study to have a unique baseline hazard but assuming a common hazard ratio (HR) for eGFR across studies. For the 2-stage method, we first fitted a Cox model in each study, and then meta-analyzed HRs using a fixed-effect (assuming one true HR for eGFR across studies) and a random-effects (allowing some variance of true HR) model. eGFR was fitted as linear splines in all models. Results: In a sample of 18 of 46 cohorts joining CKD-PC (191,276 participants and 8,732 cardiovascular deaths [CHD, stroke, or heart failure]), these methods gave nearly identical estimates except for the width of the confidence intervals ( Figure ). The 95% CIs were wider as methods made fewer assumptions - narrowest for 1-stage method, slightly wider for the fixed-effect 2-stage and wider for the random-effects 2-stage method. Conclusion: The two-stage and one-stage meta-analyses provided nearly identical estimates for the eGFR-cardiovascular mortality relationship. The random-effects 2-stage method will provide conservative estimates with wider 95% CIs but this is necessary in the presence of heterogeneity.
66P Predictive markers of clinical progressive disease during neoadjuvant chemotherapy in early triple negative breast cancers
Authors: T. Nishikawa, Y. Tanabe, H. Tsuda, M. Yoshida, T. Shimoi, A. Shimomura, M. Kodaira, M. Yunokawa, K. Yonemori, C. Shimizu, Y. Fujiwara, K. Tamura
Journal: Annals of Oncology (2015)
Growth in children with pulmonary arterial hypertension: a longitudinal retrospective multiregistry study
Authors: Mark-Jan Ploegstra, D Dunbar Ivy, Jeremy G Wheeler, Monika Brand, Maurice Beghetti, Erika B Rosenzweig, Tilman Humpl, Xavier Iriart, Erwan Muros-Le Rouzic, Damien Bonnet, Rolf M F Berger
Journal: The Lancet Respiratory Medicine (2016)
Liver DNA Bound In Vivo With Aflatoxin B&lt;sub&gt;1&lt;/sub&gt; as a Measure of Hepatocarcinoma Initiation' in Rainbow Trout&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: M Whitham, J E Nixon, R O Sinnhuber
Journal: JNCI Journal of the National Cancer Institute (1982)

The in vivo binding of aflatoxin B1 (AFB1) to liver DNA was measured in rainbow trout subjected to various regimens and in coho salmon to determine if binding would correlate with tumor incidence and initiation of hepatocellular carcinoma. Establishment of time-course binding parameters showed no significant difference between 4, 12, 24, or 48 hours. Doses of 5, 25, 100, and 300 micrograms AFB1/kg body weight produced an almost linear increase in binding with increasing dose. Compared to that of controls, AFB1-DNA binding was twofold lower in beta-naphthoflavone-treated trout and twentyfold lower in coho salmon. These two comparisons reflected a decrease in the effective activation and binding of AFB1, correlated with tumor incidence, and are believed to correlate with a decrease in the initiation of hepatocellular carcinoma. AFB1 binding was not significantly altered by dietary protein or cyclopropenoid fatty acids, which are thought to increase hepatocellular carcinoma incidence through promotional effects. The data were consistent with the view that in vivo binding of AFB1 to liver DNA is a measure of cancer inititation by AFB1 and correlated with the incidence of hepatocellular carcinoma in salmonid fish.
Zero Pain Is Not the Goal
Authors: Thomas H. Lee
Journal: JAMA (2016)

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Association of Multiple Biomarkers of Iron Metabolism and Type 2 Diabetes: The EPIC-InterAct Study
Authors: Clara Podmore, Karina Meidtner, Matthias B. Schulze, Robert A. Scott, Anna Ramond, Adam S. Butterworth, Emanuele Di Angelantonio, John Danesh, Larraitz Arriola, Aurelio Barricarte, Heiner Boeing, Françoise Clavel-Chapelon, Amanda J. Cross, Christina C. Dahm, Guy Fagherazzi, Paul W. Franks, Diana Gavrila, Sara Grioni, Marc J. Gunter, Gaelle Gusto, Paula Jakszyn, Verena Katzke, Timothy J. Key, Tilman Kühn, Amalia Mattiello, Peter M. Nilsson, Anja Olsen, Kim Overvad, Domenico Palli, J. Ramón Quirós, Olov Rolandsson, Carlotta Sacerdote, Emilio Sánchez-Cantalejo, Nadia Slimani, Ivonne Sluijs, Annemieke M.W. Spijkerman, Anne Tjonneland, Rosario Tumino, Daphne L. van der A, Yvonne T. van der Schouw, Edith J.M. Feskens, Nita G. Forouhi, Stephen J. Sharp, Elio Riboli, Claudia Langenberg, Nicholas J. Wareham
Journal: Diabetes Care (2016)

OBJECTIVE Observational studies show an association between ferritin and type 2 diabetes (T2D), suggesting a role of high iron stores in T2D development. However, ferritin is influenced by factors other than iron stores, which is less the case for other biomarkers of iron metabolism. We investigated associations of ferritin, transferrin saturation (TSAT), serum iron, and transferrin with T2D incidence to clarify the role of iron in the pathogenesis of T2D. RESEARCH DESIGN AND METHODS The European Prospective Investigation into Cancer and Nutrition–InterAct study includes 12,403 incident T2D cases and a representative subcohort of 16,154 individuals from a European cohort with 3.99 million person-years of follow-up. We studied the prospective association of ferritin, TSAT, serum iron, and transferrin with incident T2D in 11,052 cases and a random subcohort of 15,182 individuals and assessed whether these associations differed by subgroups of the population. RESULTS Higher levels of ferritin and transferrin were associated with a higher risk of T2D (hazard ratio [HR] [95% CI] in men and women, respectively: 1.07 [1.01–1.12] and 1.12 [1.05–1.19] per 100 μg/L higher ferritin level; 1.11 [1.00–1.24] and 1.22 [1.12–1.33] per 0.5 g/L higher transferrin level) after adjustment for age, center, BMI, physical activity, smoking status, education, hs-CRP, alanine aminotransferase, and γ-glutamyl transferase. Elevated TSAT (≥45% vs. &amp;lt;45%) was associated with a lower risk of T2D in women (0.68 [0.54–0.86]) but was not statistically significantly associated in men (0.90 [0.75–1.08]). Serum iron was not associated with T2D. The association of ferritin with T2D was stronger among leaner individuals (Pinteraction &amp;lt; 0.01). CONCLUSIONS The pattern of association of TSAT and transferrin with T2D suggests that the underlying relationship between iron stores and T2D is more complex than the simple link suggested by the association of ferritin with T2D.
A New Form Of Therapeutic Resistance: Drug Glucuronidation Regulated By The Sonic Hedgehog Factor Gli1
Authors: Hiba A Zahreddine, Biljana Culjkovic-Kraljacic, Sarit Assouline, Abdellatif Amri, Patrick Gendron, Andrea A. Romeo, Stephen Morris, James Jaquith, Gregory Cormack, Eftihia Cocolakis, Julie Bergeron, Leandro Cerchietti, Brian Leber, Wilson H. Miller, Katherine LB. Borden
Journal: Blood (2013)
Competing mortality in advanced head and neck cancer: A population-based study.
Authors: B. S. Rose, S. K. Nath, S. Lu, L. K. Mell
Journal: Journal of Clinical Oncology (2010)

5578 Background: Competing (noncancer) mortality (CM) is a common event in head/neck cancer (HNC) that complicates the interpretation of treatment effects. Population-based models are needed to estimate the impact of CM on power of HNC clinical trials. Methods: We analyzed 22,729 patients diagnosed with advanced nonmetastatic HNC between 1993 and 2004 using SEER data. We identified factors associated with cancer-specific mortality (CSM) and CM using the Fine-Gray proportional hazards model with backward stepwise regression. Risk scores for CM were derived from coefficient estimates and values of covariates retained in the model. The model was validated using bootstrap and split sample techniques. Power estimates assumed exponential hazards, 500 patients accrued over 3 years, 2 years follow-up, hazard ratio (HR) for all-cause mortality (ACM) of 0.67, and primary endpoint (PE) evaluation at 5 years. The HR for competing risk power estimates (0.63) was calibrated such that power was equivalent in the low CM risk tertile for both competing risk (using CSM as the PE) and standard methods (using ACM as the PE). Results: Median follow-up for surviving patients was 59 months. The 5-year cumulative incidence of ACM, CSM, and CM were 57%, 45%, and 12%, respectively. Risk factors for increasing CM were male sex (subdistribution HR [SHR] 1.17; 95% CI, 1.08-1.27), black race (SHR 1.12; 95%, CI 1.02- 1.24), low socioeconomic status (SHR 1.07; 95% CI, .99-1.16), age (SHR 1.04; 95% CI, 1.04-1.04), unmarried (SHR 1.27; 95% CI 1.19-1.37), grade 1-2 tumor (SHR 1.08; 95% CI 1.01-1.17), larynx subsite (SHR 1.15; 95% CI 1.07-1.24), and nonsurgical treatment (SHR 1.18; 95% CI 1.10-1.26). The 5-year cumulative incidence of CM for patients at low, medium, and high risk was 9%, 11%, and 17%, respectively. The Table shows that power is overestimated with standard methods as the risk for CM increases. Conclusions: Multiple demographic and tumor characteristics affect CM risk in the population, suggesting that competing risk methods should be considered for power calculation in HNC clinical trials. CM risk group 5-year cumulative incidence Power Additional patientsrequired (%) ACM CM ACM Competing risks Low 57% 9% 80% 80% 0 Medium 53% 11% 77% 74% 34 (7%) High 62% 17% 84% 78% 74 (15%) No significant financial relationships to disclose.
Global prevalence of antibiotic resistance in paediatric urinary tract infections caused by<i>Escherichia coli</i>and association with routine use of antibiotics in primary care: systematic review and meta-analysis
Authors: Ashley Bryce, Alastair D Hay, Isabel F Lane, Hannah V Thornton, Mandy Wootton, Céire Costelloe
Journal: BMJ (2016)

<b>Objectives</b>&nbsp;To systematically review studies investigating the prevalence of antibiotic resistance in urinary tract infections caused by <i>Escherichia coli</i> in children and, when appropriate, to meta-analyse the relation between previous antibiotics prescribed in primary care and resistance. <b>Design and data analysis</b>&nbsp;Systematic review and meta-analysis. Pooled percentage prevalence of resistance to the most commonly used antibiotics in children in primary care, stratified by the OECD (Organisation for Economic Co-operation and Development) status of the study country. Random effects meta-analysis was used to quantify the association between previous exposure to antibiotics in primary care and resistance. <b>Data sources</b>&nbsp;Observational and experimental studies identified through Medline, Embase, Cochrane, and ISI Web of Knowledge databases, searched for articles published up to October 2015. <b>Eligibility criteria for selecting studies</b>&nbsp;Studies were eligible if they investigated and reported resistance in community acquired urinary tract infection in children and young people aged 0-17. Electronic searches with MeSH terms and text words identified 3115 papers. Two independent reviewers assessed study quality and performed data extraction. <b>Results</b>&nbsp;58 observational studies investigated 77 783 <i>E coli</i> isolates in urine. In studies from OECD countries, the pooled prevalence of resistance was 53.4% (95% confidence interval 46.0% to 60.8%) for ampicillin, 23.6% (13.9% to 32.3%) for trimethoprim, 8.2% (7.9% to 9.6%) for co-amoxiclav, and 2.1% (0.8 to 4.4%) for ciprofloxacin; nitrofurantoin was the lowest at 1.3% (0.8% to 1.7%). Resistance in studies in countries outside the OECD was significantly higher: 79.8% (73.0% to 87.7%) for ampicillin, 60.3% (40.9% to 79.0%) for co-amoxiclav, 26.8% (11.1% to 43.0%) for ciprofloxacin, and 17.0% (9.8% to 24.2%) for nitrofurantoin. There was evidence that bacterial isolates from the urinary tract from individual children who had received previous prescriptions for antibiotics in primary care were more likely to be resistant to antibiotics, and this increased risk could persist for up to six months (odds ratio 13.23, 95% confidence interval 7.84 to 22.31). <b>Conclusions</b>&nbsp;Prevalence of resistance to commonly prescribed antibiotics in primary care in children with urinary tract infections caused by <i>E coli</i> is high, particularly in countries outside the OECD, where one possible explanation is the availability of antibiotics over the counter. This could render some antibiotics ineffective as first line treatments for urinary tract infection. Routine use of antibiotics in primary care contributes to antimicrobial resistance in children, which can persist for up to six months after treatment.
Lymphoproliferative diseases in immunocompromised hosts: the role of Epstein-Barr virus.
Authors: A F List, F A Greco, L B Vogler
Journal: Journal of Clinical Oncology (1987)

Epstein-Barr virus (EBV) is a ubiquitous transforming virus of the herpes group showing tropism for B lymphocytes. Primary infection in normal hosts results in a transient lymphoproliferative disorder, acute infectious mononucleosis (IM), that is restricted by cytotoxic and suppressive lymphocytes. However, in the immunodeficient host, EBV-induced lymphoproliferation may behave in a biologically malignant fashion. Patients with primary immunodeficiencies and those with immune incompetence resulting from suppressive therapy in allograft transplantation or infection with human immunodeficiency virus (HIV) have EBV-related illness ranging from fulminant mononucleosis and invasive polyclonal B cell hyperplasia to monoclonal B cell malignancies. While the direct link between EBV and malignant B cell proliferation in these patients has not been elucidated, the association has been increasingly recognized with improved techniques of viral detection. Clinical management can be guided by the location and extent of tumor, histologic features, and clonality. Regional and node-based polyclonal proliferations may respond to prompt reduction of immunosuppressive therapy and efforts to interrupt the replicative cycle with antiviral agents. Systemic cytotoxic therapy often leads to further immunosuppression and should be reserved for patients with progressive disease, advanced visceral involvement, and monoclonal lymphoid malignancies.
Ocular Rosacea
Authors: Rimvydas Asoklis, Kristina Malysko
Journal: New England Journal of Medicine (2016)

A 58-year-old man presented with recurrent facial flushing and redness, foreign-body sensation, and blurred vision in both eyes. Examination revealed telangiectasia with hyperemia of the eyelid margins, conjunctival hyperemia, and neovascularization of the cornea in both eyes.
Monoclonal Igκ and Igλ Antibodies Minimize Cross-Reactivity With NK Cells In a Multicolor Immunophenotyping Panel
Authors: Emily M. Deal, Margaret S. Inokuma, Xiaoyun Yang, Shou Shye, Manuela Franzblau, Daiva A. Gladding, Oliver Crespo, Hobert Wai
Journal: Blood (2013)
Correlation Between Cancers of the Uterine Cervix and Penis in China
Authors: J Y Li, F P Li, W J Blot, R W Miller, J F Fraumeni
Journal: JNCI Journal of the National Cancer Institute (1982)

A national survey of cancer mortality in the People's Republic of China during 1973--75 revealed concurrent geographic variation for cancers of the uterine cervix and penis, including clustering of both tumors in central parts of the country. The findings are consistent with recent reports from other countries that the cancers tend to aggregate in spouses and with the hypothesis of an etiologic factor in common.
Abstract P312: Macronutrients Intake and Incident Frailty in the Elderly: A Prospective Cohort Study in Spain
Authors: Pilar Guallar-Castillon, Helena Sandoval-Insausti, Raúl F Pérez-Tasigchana, Esther López-García, Esther García-Esquinas, Fernando Rodríguez-Artalejo
Journal: Circulation (2015)

Background and objective:  Higher protein consumption has been independently associated with a lower risk of incident frailty in older women. Nevertheless, no previous prospective study has focused on the potential effects of other macronutrients on the risk of frailty in both men and women. This study examined prospectively the association between dietary macronutrients intake and incident frailty in community-dwelling older adults in Spain.   Methods:  A prospective cohort with 1,822 community-dwelling individuals aged ≥60 years was recruited in 2008-2010 and followed through 2012. At baseline, nutrient intake was measured using a validated computerized face-to-face diet history. In 2012, individuals were contacted to detect incident frailty. According to the Fried9s criteria, frailty was defined by the presence of at least three of the following criteria: low physical activity, slowness, unintentional weight loss (10 pounds or more in a year), muscle weakness (lowest quintile of strength within groups defined by sex and BMI), and self-reported exhaustion. Analyses were performed using logistic regression and adjusted for the main confounders, including total energy intake using the nutrient residual model.   Results:  During 3.5 years of follow-up, 132 persons with incident frailty were identified. When the amount of energy from animal protein intake was substituted for the same amount of energy from carbohydrates, the ORs (95% CI) of frailty by quartiles of animal protein intake were 1.00, 0.74 (0.43-1.28), 0.54 (0.31-0.96), and 0.52 (0.28-0.96); p for trend 0.019. When energy from monounsaturated fatty acids intake was substituted for the same amount of energy from carbohydrates, the results by quartiles of monounsaturated fatty acids intake were: 1.00, 0.59 (0.32-1.08), 0.50 (0.26-0.96), and 0.44 (0.22-0.88); p for trend 0.025. No association was found between intake of vegetal proteins, saturated fats, long-chain ω-3 fatty acids, alfa-linolenic acid, linoleic acid, simple sugars, or polysaccharides and the risk of frailty.   Conclusion:  Animal protein and monounsaturated fatty acids intake were inversely associated with incident frailty in the elderly. Substituting animal protein and monounsaturated fatty acids for carbohydrates in the diet may be an appropriate strategy to reduce frailty in this population.   Founding:  FP7-HEALTH-2012-Proposal No: 305483-2 (FRAILOMIC Initiative), FIS grants PI11/01379 and PI13/288 (Ministry of Health of Spain).
Interleukin-12 (IL-12) Production in Whole Blood Cultures From Human Immunodeficiency Virus-Infected Individuals Studied in Relation to IL-10 and Prostaglandin E2 Production
Authors: Linde Meyaard, Egbert Hovenkamp, Nadine Pakker, Tineke C.T.M. van der Pouw Kraan, Frank Miedema
Journal: Blood (1997)