tbuckley/cabot-search huggingface dataset:
Complex disease=complex trial? Lessons from a successful trial of anti-IFNα in SLE
Authors: Ronald van Vollenhoven
Journal: Annals of the Rheumatic Diseases (2016)

> ‘All other things being equal, we may assume the superiority of the demonstration which derives from fewer postulates or hypotheses’—Aristotle

Therapeutic options for systemic lupus erythematosus (SLE) are still limited. A number of conventional immunosuppressives are used along with glucocorticoids and antimalarials, but the successes of biological therapies in the arthritides have not been duplicated for SLE. To date, only one biologic succeeded in phase III trials1 ,2 and was approved for use in SLE, but its proper role in the overall management of the patient with SLE has remained incompletely defined.3 Rituximab is used off-label on the strength of many observational studies,4 ,5 but two large trials failed to demonstrate efficacy.6 ,7 A distressingly large number of biologics failed in late-stage trials, where some have completely disappeared from further consideration (the B-cell tolerising oligonucleotide construct abetimus,8 the anti-CD20 monoclonal ocrelizumab9); for some others, the future looks bleak (the BLyS antagonist tabalumab,10 ,11 the anti-CD22 monoclonal epratuzumab) and for yet others, investigators and sponsors are struggling to find the best way forward (the T-cell costimulation blocker abatacept,12 ,13 the BLyS/APRIL antagonist atacicept14 ,15).

The failure of many SLE trials may have been due, at least in part, to the simple fact that the drugs being studied were not very effective, but it has also been suggested that clinical trial methodology for SLE has been suboptimal. Any positive or successful trial could therefore give us the dual benefit of moving the field forward with a new compound, while also providing us with useful lessons for the design of clinical trials.

The interferon (IFN) system has been identified as a key pathway in the immunopathogenesis of SLE.16–22 It was therefore logical to develop specific IFN …
P-159 Regorafenib vs TAS-102 as salvage-line treatment in patients with metastatic colorectal cancer refractory to standard chemotherapies: A multicenter retrospective comparison study
Authors: M. Kotaka, H. Satake, Y. Okita, Y. Hatachi, T. Kotake, H. Hashida, T. Kato, A. Tsuji
Journal: Annals of Oncology (2016)
Two Phase I and Pharmacokinetic Studies of Darinaparsin (Organic Arsenic Compound) in Japanese and Korean Patients with Relapsed or Refractory (R/R) Peripheral T-Cell Lymphoma (PTCL)
Authors: Won-Seog Kim, Michinori Ogura, Toshiki Uchida, Naokuni Uike, Yasunobu Abe, Kenichi Ishizawa, Yoko Okitsu, Kensei Tobinai, Fumiko Nagahama, Yusuke Sonehara, Hirokazu Nagai
Journal: Blood (2015)
Removal of expression of concern: Schiffl H, et al. daily hemodialysis and the outcome of acute renal failure
Authors: Jeffrey M. Drazen, Julie R. Ingelfinger, Gregory D. Curfman
Journal: New England Journal of Medicine (2003)

1965 pril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med 2003;349:1893906. 6. Cohn JN, Tognoni G. A randomized trial of the angiotensinreceptor blocker valsartan in chronic heart failure. N Engl J Med 2001;345:1667-75. 7. McMurray JJ, Ostergren J, Swedberg K, et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial. Lancet 2003;362:767-71. 8. Pitt B, Poole-Wilson PA, Segal R, et al. Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomised trial — the Losartan Heart Failure Survival Study ELITE II. Lancet 2000;355:1582-7. 9. Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001;345:861-9. 10. Dahlof B, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 2002;359:995-1003. Copyright © 2003 Massachusetts Medical Society.
Domestic dog exposure at birth reduces the incidence of atopic dermatitis
Authors: S. Thorsteinsdottir, J. P. Thyssen, J. Stokholm, N. H. Vissing, J. Waage, H. Bisgaard
Journal: Allergy (2016)

Abstract Background While the etiopathogenesis of atopic dermatitis is complex and poorly understood, neonatal exposures are important for disease occurrence. However, the effect of dog exposure on the risk of atopic dermatitis is unresolved. Objective We investigated whether domestic dog exposure affected the risk of atopic dermatitis in children during the first 3 years of life. Methods Copenhagen Prospective Studies on Asthma in Childhood ( COPSAC ) are ongoing prospective clinical birth cohort studies. Data from 411 children born to mothers with asthma ( COPSAC 2000 ) and 700 unselected children ( COPSAC 2010 ) were analyzed following the same protocols at the same research site. Atopic dermatitis was diagnosed prospectively according to the Hanifin–Rajka criteria. Parental history of asthma, eczema, or rhinitis was defined by self‐reported physician diagnosis. In the COPSAC 2000 , maternal specific serum IgE against eight inhalant allergens was sampled after the children's birth and at pregnancy week 24 in the COPSAC 2010 cohort. Associations between dog exposure and atopic dermatitis were analyzed by Cox proportional hazard regression models and adjusted for lifestyle confounders. Results In the COPSAC 2000 and COPSAC 2010 cohorts, the risk of atopic dermatitis was significantly lower in children with domestic dog exposure ( adjusted HR = 0.46 [0.25–0.87], P = 0.02; and adjusted HR = 0.58 [0.36–0.93], P = 0.03, respectively). The risk of atopic dermatitis decreased in a dose‐dependent manner with increasing number of dogs ( adjusted HR = 0.58 [0.38–0.89], P = 0.01) in the COPSAC 2010 . The protective effect was restricted to children born to mothers with atopic disease in the unselected COPSAC 2010 cohort ( adjusted HR = 0.39 [0.19–0.82], P = 0.01), as no effect was observed in children born to mothers without atopic disease ( adjusted HR = 0.92 [0.49–1.73], P = 0.79). Paternal atopic status did not affect the risk of atopic dermatitis. We found no significant interaction between the CD 14 T/T genotype and domestic dog exposure in either cohort ( COPSAC 2000 , P = 0.36; and COPSAC 2010 cohort, P = 0.42). Conclusion Neonatal domestic dog exposure was associated with a strongly reduced risk of atopic dermatitis in two independent birth cohorts and in a dose‐dependent manner. While the mechanisms involved are unclear, our findings raise the question of whether in utero exposures may affect the risk of atopic dermatitis and emphasize the importance of the early environment for disease trajectory.
Création d'un réseau européen pour le diagnostic des maladies virales importées (ENIVD)
Authors: M Niedrig, B Niklasson, G Lloyd, H Schmitz, B LeGuenno
Journal: Eurosurveillance (1998)

L’apparition, ces dernieres annees, d’epidemies de fievre hemorragique dues au virus Ebola au Zaire et au Gabon nous a rappele le fait que des infections graves pouvaient etre importees en Europe tres rapidement. En 1993 et 1994, des reunions sur les pathogenes emergents ou re-emergents (1,2) ont ete organisees par l’Organisation Mondiale de la Sante (OMS) ; elles etaient ciblees sur les problemes lies aux arbovirus et aux virus associes aux fievres hemorragiques et sur la necessite de creer un reseau mondial pour echanger les informations, les reactifs et les methodologies.
La surveillance sentinelle des maladies sexuellement transmissibles en Italie
Authors: M Giuliani, B Suligoi
Journal: Eurosurveillance (1998)

Les declarations obligatoires montrent que l’incidence de la gonococcie et de la syphilis a chute ces 30 dernieres annees en Italie, comme dans d’autres pays developpes (figure 1). Toutefois, durant les annees 80, les taux de declaration annuels en Italie etaient 15 a 50 fois inferieurs a ceux des autres pays europeens, ce qui suggere que les donnees du systeme de declaration obligatoire ne refletaient pas l’incidence reelle des deux maladies. En 1990, une etude retrospective multicentrique comparant les cas declares et les cas diagnostiques dans un echantillon de centres publics specialises dans les maladies sexuellement transmissibles (MST) a confirme une sous-declaration tres importante de ces deux maladies (1).
Low-Dose Paclitaxel Reduces S100A4 Nuclear Import to Inhibit Invasion and Hematogenous Metastasis of Cholangiocarcinoma
Authors: Massimiliano Cadamuro, Gaia Spagnuolo, Luisa Sambado, Stefano Indraccolo, Giorgia Nardo, Antonio Rosato, Simone Brivio, Chiara Caslini, Tommaso Stecca, Marco Massani, Nicolò Bassi, Eugenio Novelli, Carlo Spirli, Luca Fabris, Mario Strazzabosco
Journal: Cancer Research (2016)

Nuclear expression of the calcium-binding protein S100A4 is a biomarker of increased invasiveness in cholangiocarcinoma, a primary liver cancer with scarce treatment opportunities and dismal prognosis. In this study, we provide evidence that targeting S100A4 nuclear import by low-dose paclitaxel, a microtubule-stabilizing agent, inhibits cholangiocarcinoma invasiveness and metastatic spread. Administration of low-dose paclitaxel to established (EGI-1) and primary (CCA-TV3) cholangiocarcinoma cell lines expressing nuclear S100A4 triggered a marked reduction in nuclear expression of S100A4 without modifying its cytoplasmic levels, an effect associated with a significant decrease in cell migration and invasiveness. While low-dose paclitaxel did not affect cellular proliferation, apoptosis, or cytoskeletal integrity, it significantly reduced SUMOylation of S100A4, a critical posttranslational modification that directs its trafficking to the nucleus. This effect of low-dose paclitaxel was reproduced by ginkolic acid, a specific SUMOylation inhibitor. Downregulation of nuclear S100A4 by low-dose paclitaxel was associated with a strong reduction in RhoA and Cdc42 GTPase activity, MT1-MMP expression, and MMP-9 secretion. In an SCID mouse xenograft model, low-dose metronomic paclitaxel treatment decreased lung dissemination of EGI-1 cells without significantly affecting their local tumor growth. In the tumor mass, nuclear S100A4 expression by cholangiocarcinoma cells was significantly reduced, whereas rates of proliferation and apoptosis were unchanged. Overall, our findings highlight nuclear S100A4 as a candidate therapeutic target in cholangiocarcinoma and establish a mechanistic rationale for the use of low-dose paclitaxel in blocking metastatic progression of cholangiocarcinoma. Cancer Res; 76(16); 4775-84. ©2016 AACR.
Cytochemical Studies of Hyperplastic Alveolar Nodules in the Mammary Gland of the C3H/He CRGL Mouse&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Harkness, Mary Nishi, Bern, Howard A., Alfert, Max, Goldstein, Norma O.
Journal: JNCI Journal of the National Cancer Institute (1957)

Journal Article Cytochemical Studies of Hyperplastic Alveolar Nodules in the Mammary Gland of the C3H/He CRGL Mouse Get access Mary Nishi Harkness, Mary Nishi Harkness Department of Zoology and its Cancer Research Genetics Laboratory, University of California, Berkeley, California Search for other works by this author on: Oxford Academic PubMed Google Scholar Howard A. Bern, Howard A. Bern Department of Zoology and its Cancer Research Genetics Laboratory, University of California, Berkeley, California Search for other works by this author on: Oxford Academic PubMed Google Scholar Max Alfert, Max Alfert Department of Zoology and its Cancer Research Genetics Laboratory, University of California, Berkeley, California Search for other works by this author on: Oxford Academic PubMed Google Scholar Norma O. Goldstein Norma O. Goldstein Department of Zoology and its Cancer Research Genetics Laboratory, University of California, Berkeley, California Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 19, Issue 6, December 1957, Pages 1023–1033, https://doi.org/10.1093/jnci/19.6.1023 Published: 01 December 1957 Article history Received: 14 May 1957 Published: 01 December 1957
Adjuvant chemotherapy for residual disease after neoadjuvant chemotherapy for muscle invasive urothelial cancer (MIUC).
Authors: Lauren Christine Harshman, Lillian Werner, Yu-Ning Wong, Evan Y. Yu, Ajjai Shivaram Alva, Simon J. Crabb, Thomas Powles, Jonathan E. Rosenberg, Jack Baniel, Ulka N. Vaishampayan, Dominik R. Berthold, Sylvain Ladoire, Syed A. Hussain, Matthew I. Milowsky, Neeraj Agarwal, Andrea Necchi, Sumanta Kumar Pal, Federica Recine, Joaquim Bellmunt, Matt D. Galsky
Journal: Journal of Clinical Oncology (2015)

4524 Background: Neoadjuvant cisplatin-based chemotherapy (Neo) improves outcomes in MIUC. However, the benefit achieved with Neo correlates with pathologic downstaging and patients with residual disease (RD) remain at high risk for metastatic recurrence. The optimal management of such patients is unknown. We evaluated whether adjuvant chemotherapy (Adj) improves time to recurrence (TTR) in pts with RD after Neo. Methods: Data were captured from 23 sites participating in the Retrospective International Study of Cancers of the Urothelium (RISC). Pts with RD after Neo for UC were identified. Median (med) TTR was estimated by Kaplan-Meier method from 2 mo post-surgery to minimize lead time bias in non-Adj pts. The association between Adj and TTR was assessed using a multivariate Cox regression model. Results: From 11/1989 to 4/2013, 185 pts were identified who had RD despite Neo and had adequate follow-up time for data on Adj. Med follow-up time was 30 mo. 25 pts received Adj while 160 proceeded with surveillance. Both groups had similar performance status and med age at time of Neo. Med time to Adj was 1.5 mo. The majority changed regimens between Neo and Adj. Gemcitabine/cisplatin and dose dense MVAC were the most common regimens used in either setting. Use of Adj significantly correlated with higher path stage (p = 0.003). Med TTR was 17 mo with 95/185 experiencing relapse. After adjusting for path stage, type of Neo and age, Adj pts had a significantly decreased risk of relapse (HR = 0.35, 95% CI: 0.17,0.74). A subset analysis (Adj = 19, surveillance = 50) of pts with residual pathologic T4 and/or N+ after Neo also revealed a significant improvement with Adj: median TTR of 20 mo versus 9 mo, p = 0.02 (HR = 0.43, 95% CI: 0.21,0.89). Conclusions: In this international series, the use of Adj chemo for RD after Neo was rare. While limited by small numbers and the potential selection bias inherent to retrospective analyses, Adj may delay recurrence in pts with residual pT4 or N+ disease despite Neo. Overall survival analysis will be presented.
Tumors Induced by 2-Aeetylamino-fluorene in Virgin and Breeding Females of Five Strains of Rats and in Their Offspring&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: Alexander Symeonidis
Journal: JNCI Journal of the National Cancer Institute (1954)

Journal Article Tumors Induced by 2-Aeetylamino-fluorene in Virgin and Breeding Females of Five Strains of Rats and in Their Offspring Get access Alexander Symeonidis Alexander Symeonidis National Cancer Institute,4Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 15, Issue 3, December 1954, Pages 539–549, https://doi.org/10.1093/jnci/15.3.539 Published: 01 December 1954 Article history Received: 20 July 1954 Published: 01 December 1954
Evaluating the prevalence of cardiovascular risk factors among breast cancer survivors and the outcomes of cardio-oncology referrals by a breast cancer survivorship clinic.
Authors: Jennifer R. Klemp, Lori Ranallo, Catie Knight, Carol J. Fabian, Christie A. Befort
Journal: Journal of Clinical Oncology (2013)

107 Background: Breast cancer survivors have a 4x increased incidence of cardiovascular disease (CVD) compared to women never treated for breast cancer and cardiac events are the 2nd most common cause of death in long-term survivors. Attention to reducing the risk of CVD should be a priority for the long-term care of breast cancer survivors. This study was undertaken to describe cardiovascular risk factors in breast cancer survivors, and the cardio-oncology referral patterns and outcomes from cardio-oncology screening visits. Methods: 356 female breast cancer survivors seen at the University of Kansas Breast Cancer Survivorship Center between 2006 and 2012 who completed an initial intake visit were evaluated for cardiovascular risk factors and referrals to cardio-oncology. An expanded list of cardiovascular factors was used: BMI &gt; 25, Diabetes, HTN, HLD, Current/Past Smoker, Family Hx of MI &lt; 60 years, Exercise &lt; 150 min/wk, Ejection Fraction &lt; 50%, and exposure to cardio-toxic breast cancer treatment. Breast cancer survivors without evidence of metastatic disease were on average 57.8 +/-11.0 years old, underwent standard treatment regimens, and were approximately 7.5 years from their initial diagnosis. Results: 13% were already followed by a cardiologist, 21% were referred to cardio-oncology, and 66% were not referred at their initial survivorship visit. There were significant differences in the average number of risk factors between those not referred to cardio-oncology (4.36 +/-1.89), and those referred to cardio-oncology (5.68+/-1.8), and between those already followed by cardiologist (5.91+/-1.75), p &lt; 0.001 and p &lt; 0.0001, respectively. The most common risk factors were BMI &gt;25, elevated HDL, exercise &lt;150 min/wk, and exposure to an anthracycline. The most common outcomes following a cardio-oncology visit included further diagnostic tests, medication changes, or a return visit. Conclusions: These findings demonstrate the need to determine how to include treatment related risk factors along with traditional cardiovascular risk factors in assessing and managing cardiovascular risk in breast cancer survivors.
A nurse communication training curriculum to integrate oncology and palliative care.
Authors: Elaine Wittenberg, Betty R. Ferrell, Joy Goldsmith, Judith A. Paice
Journal: Journal of Clinical Oncology (2015)

19 Background: Quality nurse communication skills are essential to ensure psychosocial care for patients and families, enabling quality of life topics to be addressed across the cancer trajectory and throughout cancer decision-making. However, many oncology nurses are inadequately trained to address patient and family psychosocial concerns. This study describes the development and implementation of an oncology nurse educational program to improve communication about psychological, social, behavior, and spiritual topics. Methods: This interdisciplinary team of authors wrote and published a communication curriculum known by the acronym COMFORT. The curriculum, emphasizing team communication, teaches nurses how to provide life-altering news, assess patient/family health literacy needs, practice mindful communication, acknowledge family caregivers, and address communication openings and goals. With funding from the National Cancer Institute (R25CA174627), the curriculum covers the continuum of cancer care (diagnosis, treatment, survivorship, recurrence, and end of life) and four national courses are planned over the next four years. A pilot study of the two-day communication training course was conducted at one comprehensive cancer center with 27 oncology nurse leaders. Results: Course participants were predominantly female, averaging 19 years nursing experience and 15 years in oncology, and more than half had daily contact with patients and family. Course evaluations were overwhelmingly positive with high mean scores on clarity of presentation (4.82 out of 5), content quality (4.80), and value to clinicians (4.75). The presentation will include a summary of this innovative oncology nurse communication training curriculum aimed at achieving patient-centered communication across the cancer trajectory. Conclusions: This presentation introduces a communication training curriculum focusing on understanding the patient narrative, including the family caregiver, and to provide psychosocial and spiritual care. Improved communication is essential to quality psychosocial nursing interventions.
PD6-2-2: Genomic profiling of malignant pleural mesothelioma with array-based comparative genomic hybridization
Authors: Tetsuo Taniguchi, Sivasundaram Karnan, Takayuki Fukui, Toshihiko Yokoyama, Hiroyuki Tagawa, Kohei Yokoi, Yuichi Ueda, Tetsuya Mitsudomi, Yoshitsugu Horio, Toyoaki Hida, Yasushi Yatabe, Masao Seto, Yoshitaka Sekido
Journal: Journal of Thoracic Oncology (2007)
Hepaticogastrostomy guided by real-time contrast-enhanced harmonic endoscopic ultrasonography: a novel technique
Authors: Kosuke Minaga, Masayuki Kitano, Tomoe Yoshikawa, Shunsuke Omoto, Ken Kamata, Kentaro Yamao, Masatoshi Kudo
Journal: Endoscopy (2016)

Endoscopic ultrasonography-guided hepaticogastrostomy (EUS-HGS) has recently been developed as an alternative biliary drainage technique for failed endoscopic retrograde cholangiopancreatography (ERCP) [1] [2] [3]. A recent review revealed its overall technical success rate to be 82 % [4], but puncturing the left intrahepatic bile duct (LIBD) is occasionally challenging. Here we present a case in which EUS-HGS was successfully performed under real-time contrast-enhanced harmonic EUS guidance.
Small-cell lung cancer is still a problem.
Authors: D Bergsagel, R Feld
Journal: Journal of Clinical Oncology (1984)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1984.2.11.1189 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 6092553 Small-cell lung cancer is still a problem. D BergsagelxD BergsagelSearch for articles by this author , R FeldxR FeldSearch for articles by this author https://doi.org/10.1200/JCO.1984.2.11.1189 First Page PDF © 1984 by American Society of Clinical Oncology
Margaret McCartney: Our messy divorce from the EU
Authors: Margaret McCartney
Journal: BMJ (2016)

The United Kingdom has voted to leave the European Union. Now comes the messy, expensive divorce, with the pound in freefall. I am heartbroken. The need for a referendum was unclear. And the campaign was rotten from the start. It was full of misinformation, which failed to correct vital statistics and allowed the population to believe unchecked factual biases.

We are betrayed by false allure and the idea that the EU is to blame for everything bad in the UK. But there will be no extra village fetes, bunting, or flat beer in Brexit. What does …
Comparative value of post-remission treatment in cytogenetically normal AML subclassified by NPM1 and FLT3-ITD allelic ratio
Authors: J Versluis, F E M in ‘t Hout, R Devillier, W L J van Putten, M G Manz, M -C Vekemans, M -C Legdeur, J R Passweg, J Maertens, J Kuball, B J Biemond, P J M Valk, B A van der Reijden, G Meloni, H C Schouten, E Vellenga, T Pabst, R Willemze, B Löwenberg, G Ossenkoppele, F Baron, G Huls, J J Cornelissen
Journal: Leukemia (2016)