tbuckley/cabot-search huggingface dataset:
Cancer control in Latin America (LA) and the Caribbean: 2015 update.
Authors: Diego Touya, Jessica St. Louis, Alexandra Bukowski, Rossana Esther Ruiz Mendoza, Carmen Herrero Vincent, Abraham Hernandez Blanquisett, Kathrin Strasser-Weippl, David Collingridge, Paul E. Goss
Journal: Journal of Clinical Oncology (2016)

e13096 Background: More than 100 million people in LA will be > 60 yrs of age by 2020. Age, smoke exposure and infectious causes of cancer (HPV, Hepatitis B, and H. pylori) will continue to drive the burden of cancer in the region. Cancer mortality rates in LA are approximately twice those of the United States. These sobering statistics were emphasized in our 2013 LA Cancer Commission (Lancet Oncol 2013; 14: 391–436) and therein we made suggestions to address obstacles to cancer control. In our recent 2015 update (Lancet Oncol 2015;16: 1405–38), we identified key steps being taken to address the burgeoning burden of cancer in the region. Methods: For a year, a multinational team of 25 co-authors gathered and synthesized information from the English, Spanish, and Portuguese literature from public records and government databases on LA cancer control efforts. Results: We reportsignificant progress since 2013. Important advances have included: increases in some countries percentage of gross national product spent on health and cancer care; measures to alleviate fragmented health systems and moves toward universal health care (UHC) together with key shifts in health policy; regional attempts to widen provision of cancer care personnel; implementation of health technology assessments to evaluate cost-effectiveness of cancer control; introduction of palliative care programs and; improvement in design and implementation of cancer registries and national cancer plans. Conclusions: Although LA has shown substantial progress in cancer control, the region needs to continue to prioritize UHC to alleviate inequalities, and to seek cost-saving measures to alleviate the current cancer burden. We recommend urgent attention to smoke exposure (tobacco and stove-top) and cancer-causing infections to improve survival rates and quality of life of cancer patients in general in the region, and to avoid widespread future socioeconomic hardship cancer may cause in LA countries.
A combination of histology and CK19 mRNA transcripts in sentinel lymph nodes for axillary lymph node staging and prognostication in patients with breast cancer.
Authors: Takayuki Kinoshita, Sho Shino, Shin Takayama, Kenjiro Jimbo, Sota Asaga
Journal: Journal of Clinical Oncology (2016)

1055 Background: The ACOSOG Z0011 study revealed that ALND can be omitted without changing prognosis in selected breast cancer patients even if they have SLN metastasis. However, determining the total number of positive axillary lymph nodes is still important for deciding on the postoperative treatment . To address this issue, we developed the National Cancer Center SLN metastatic score (NCS score) based on a detailed evaluation of SLNs in patients with breast cancer using a combination of histology and one-step nucleic acid amplification (OSNA) measuring CK19 mRNA . Methods: 1176 patients were diagnosed with primary breast cancer ( cTis–3 N0) at our institution based on a combination of histology and OSNA for SLNs. Of these, 323 patients who underwent additional ALND for positive SLN metastases were included in this study. Each SLN was divided and tested with histology and OSNA. Histology classified as macrometastasis, micrometastasis, and isolated tumor cells, which were assigned 3, 2, and 1 points, respectively. Whereas, OSNA classified as 2+, 1+, and +I, which were assigned 3, 2, and 1 points, respectively. In each patient, the sum of histology and OSNA points for all SLNs was defined as the NCS score. We compared the performance of the NCS score to other clinical factors in predicting N2 status ( ≥ 4 metastatic LNs ) and RFS using ROC curve analysis with the area under the ROC curve (AUC) and odds ratios (ORs). Results: The NCS score and OSNA result performed better on predicting N2 status (AUC = 0.920 and 0.824) than cT stage, pT stage, ly and pathology findings, respectively. NSC score and OSNA result were both significantly correlated with RFS in the 323 patients ( p = 0.0040 and p = 0.0026 ), suggesting that they are good prognostic factors for metastasis. In these 323 patients, NSC score and OSNA result were also significantly correlated with RFS in ER-negative patients ( p = 0.0241 and p = 0.0050) and triple-negative patients ( p = 0.0459 and p = 0.0132 ), indicating that they are exceptionally good prognostic factors for distant recurrence. Conclusions: NCS score and maximum OSNA copy number are factors for predicting number of metastatic lymph nodes, and prognosis.
Uncommon sites for metastasis of neuroendocrine tumor in adults
Authors: R. Srirajaskanthan, K. Desai, A. Jayaratnam, E. Carras, C. Toumpanakis, T. Meyer, M. Caplin
Journal: Journal of Clinical Oncology (2009)

e15683 Background: Neuroendocrine tumours are relatively slow growing tumours. They often present with significant metastatic disease affecting liver, lymph nodes, lungs and bone. However tumour masses may be found at unusual/uncommon sites e.g. breast, orbital soft tissue and the heart raising the possibility of this being metastatic focus or presence of another primary tumour. Detection of these sites could have a significant impact on the available treatment options. Aim: to determine the most appropriate imaging modality and type of tumour metastases. Methods: We reviewed 300 consecutive clinic patients. We identified 18 patients with metastasis at uncommon sites i.e. breast, orbital and cardiac. We retrospectively evaluated clinical notes and recent radiological investigations of these patients. To characterise these lesions additional investigations included cross sectional imaging, PET imaging ( 68 Gallium DOTA Octreotate PET and 18 F- FDG PET) and histological evaluation of the metastasis where appropriate. Patients with breast metastasis underwent bilateral mammogram, patients with peri-ocular involvement underwent MRI of the brain and the orbit. Results: 18 patients had tumour masses at uncommon sites. Of these 15 masses were in the breast; 4 were in the orbital muscles and 2 patients had pericardial metastasis. Of the 15 patients with breast lesions 12 had confirmed neuroendocrine tumour metastases and 3 had breast cancer. It should be noted that breast cancer lesions were positive on the 68 Gallium Octreotate PET imaging. One patient who had a defined metastasis in the pericardium showed avid uptake on the 68 Gallium DOTA Octreotate PET and scan and cardiac MRI, the other patient had pericardial metastases confirmed at post mortem. Conclusions: Clear knowledge of these uncommon sites of metastasis is useful in terms of arranging further investigations and excluding other cancers. It is also important to realise that although somatostatin receptor scintigraphy especially 68 Gallium DOTA Octreotate PET is very useful in detecting NET metastasis, it may also show avid uptake in patients with breast cancer and hence histological evaluation of these lesions are important. Undoubtedly within our cohort of patients and generally there is an under-diagnosis of lesions in uncommon sites. No significant financial relationships to disclose.
Abstract 117: TWEAK (Tumor Necrosis Factor-Like Weak Inducer of Apoptosis) Impedes Healing After Myocardial Infarction in Mice
Authors: Christina Pachel, Helga Wagner, Barbara Bayer, Charlotte Dienesch, Sandra Umbenhauer, Denise Mathes, Wolfram Heitzmann, Steffen Salzmann, Georg Ertl, Harald Wajant, Stefan Frantz
Journal: Circulation Research (2012)

Introduction: TNF-related weak inducer of apoptosis (TWEAK) triggers multiple cellular responses involved in left ventricular remodelling after myocardial infarction (MI), including cytokine production, inflammation, and wound healing. We therefore hypothesized that TWEAK-Fn14 interactions improve wound healing after experimental MI. Methods/Results: We investigated the effects of exogenous TWEAK by applying (1) cross-linked TWEAK - activating the classical NF-kB-signalling pathway, (2) TWEAK and (3) human serum albumin-tagged (HSA)-TWEAK - both activating the alternative NFkB-signalling pathway, or (4) placebo after the induction of experimental MI. Treatment with TWEAK and HSA-TWEAK surprisingly resulted in significantly higher mortality after MI (survival, placebo vs. TWEAK vs. HSA-TWEAK, 66.7 (10 of 15) vs. 14.3 (4 of 26) vs. 7.1 % (1 of 19)) due to cardiac ruptures in the TWEAK- and HSA-TWEAK groups. Ruptures were not related to changes in cardiac architecture since left ventricular dimensions as measured by echocardiography were identical between HSA-TWEAK and the placebo group three days after MI, a time point where cardiac ruptures had not taken place yet. We rule out direct remodelling defects, since MMP9 mRNA expression and proteolytic activity (gelatine zymography), and collagen1α1 mRNA expression were not altered between the groups. HSA-TWEAK induced an exaggerated inflammatory response: Infiltration of neutrophils into the border zone was significantly increased as assessed by immunohistochemistry (placebo vs. HSA-TWEAK, 297.91 vs. 455.75 neutrophils/ mm2, p &lt; 0.001). FACS-Analysis showed a significant up-regulation of CD45+-cells in the infarcted area (CD45+-cells, placebo vs. HSA-TWEAK, 4.52 vs. 9.38 %, p &lt; 0.05). This was associated with the up-regulation of genes important for the recruitment (MIP2, MCP-1 and MCP-5) and differentiation (IL5, IL12 and IFN-γ) of leukocytes (pg/ml, placebo vs. HSA-TWEAK: p &lt; 0.05: MIP2, 1.41 vs. 7.83; IL5, 4.13 vs. 18.75; p &lt; 0.001: MCP-1, N.D. vs. 28.72; MCP-5, N.D. vs. 7.36; IL12, 2.07 vs. 44.51; IFN-γ, N.D. vs. 7.47). Conclusion: Treatment with TWEAK reduces survival after experimental MI due to left ventricular rupture. This may be mediated by an exaggerated inflammatory response.
First line trastuzumab-based therapy in HER2-positive metastatic breast cancer patients (MBC) presenting with de novo or recurrent disease.
Authors: Francesca Poggio, Matteo Lambertini, Arlindo Rebelo Ferreira, Fabio Puglisi, Antonio Bernardo, Elena Poletto, Federico Sottotetti, Emanuela Risi, Antonella Lai, Elisa Zanardi, Valentina Sini, Serena Ziliani, Gabriele Minuti, Chiara Dellepiane, Donatella Grasso, Andrea Fontana, Silvia Mura, Paolo Pronzato, Lucia Del Mastro
Journal: Journal of Clinical Oncology (2015)

e11575 Background: Approximately 5-10% of breast cancer (BC) patients have metastases at the time of diagnosis (de novo stage IV), suggesting distinct biological and clinical implications as compared to those relapsing after prior treatment for early stage BC (recurrent disease). We evaluated the patterns of care and clinical outcomes of HER2-positive MBC receiving first line trastuzumab-based therapy, according to the type of metastatic presentation. Methods: This is a retrospective cohort study conducted in 14 Italian centers within the GIM (Gruppo Italiano Mammella: Italian Breast Group). Consecutive patients undergoing first-line trastuzumab-based therapy were eligible for the study. Analyses were performed according to the type of presentation of metastatic disease (de novo or recurrent). Dichotomous clinical outcomes were analyzed using logistic regression and time-to-event outcomes using Cox proportional hazards models controlling for relevant demographic, clinicopathologic and therapy characteristics. All data were analyzed using Stata 12.3 (StataCorp LP). Results: A total of 416 MBC patients were included, 113 (27.1%) with de novo stage IV and 303 (72.8%) with recurrent disease. Overall survival (OS) and progression-free survival (PFS) median follow-up were 2.59 years (1.56 – 4.41) and 1.11 years (0.63 – 2.17), respectively. In patients with de novo stage IV disease and in those with recurrent disease the following outcomes were observed, respectively: objective response rate (complete response [CR] + partial response), 163 pts (67.1%) vs 72 pts (72.0%) (adjusted OR = 0.90; 95% CI 0.34–2.38; p = .833); clinical benefit rate (CR + partial response + stable disease), 76 pts (76.0%) vs 187 pts (77.0%) (adjusted OR = 1.21; 95% CI 0.40–3.64; p = .731); median PFS, 14.4 months vs 14.7 months (adjusted HR = 1.21; 95% CI 0.79–1.86;p = .380); median OS, 55.9 months vs 49.0 months (adjusted HR = 1.26; 95% CI 0.71 – 2.23; p = .439). Conclusions: The study shows that clinical outcomes of HER2-positive MBC patients with de novo stage IV disease do not differ significantly from those of patients with recurrent disease.
ACC/AHA 2006 Guideline Update on Perioperative Cardiovascular Evaluation for Noncardiac Surgery: Focused Update on Perioperative Beta-Blocker Therapy
Authors: Lee A. Fleisher, Joshua A. Beckman, Kenneth A. Brown, Hugh Calkins, Elliott Chaikof, Kirsten E. Fleischmann, William K. Freeman, James B. Froehlich, Edward K. Kasper, Judy R. Kersten, Barbara Riegel, John F. Robb, Sidney C. Smith, Alice K. Jacobs, Cynthia D. Adams, Jeffrey L. Anderson, Elliott M. Antman, David P. Faxon, Valentin Fuster, Jonathan L. Halperin, Loren F. Hiratzka, Sharon A. Hunt, Bruce W. Lytle, Rick Nishimura, Richard L. Page, Barbara Riegel
Journal: Circulation (2006)
Abstract 202: Genetic Ablation of Interleukin-18 Does Not Attenuate Hypobaric Hypoxia-Induced Right Ventricular Dysfunction
Authors: Danielle R Bruns, Peter M Buttrick, Lori A Walker
Journal: Circulation Research (2015)

Interleukin-18 (IL-18), a pro-inflammatory cytokine, has been implicated in pathogenic left ventricular hypertrophy and is elevated in plasma of heart failure patients. However, IL-18 blockade strategies in animal models of heart disease have been conflicting. Accordingly, the purpose of these experiments was to determine whether genetic ablation of IL-18 would protect male and female mice against hypobaric hypoxia-induced right ventricular (RV) dysfunction. We hypothesized that IL-18 knockout mice (KO) would be protected while wild type (WT) mice would show significant right ventricular dysfunction in response to exposure to hypobaric hypoxia (HH). KO and WT mice were exposed to HH for 7 weeks, and control (CO) mice were exposed to normoxic, ambient air. Following echocardiography, the RV was dissected and flash frozen for biochemical analyses. 7 week HH exposure trended toward an increase in IL-18 mRNA (p=0.08) in RV from WT mice. However, contrary to our hypothesis, IL-18 KO mice were not protected against HH-induced RV dysfunction, as evidenced by higher RV weights, elevated RV systolic pressure, and increased RV anterior wall thickness compared to normoxic KO mice. Importantly, these measurements were not significantly different from WT HH mice. Biochemical analyses suggest HH RV underwent early remodeling, as no changes were observed at the molecular level in the RV of HH mice compared to CO in either KO or WT animals. Compensatory upregulation of the other pro-inflammatory cytokines IL-2 and SDF-1 may have contributed to the lack of protection in IL-18 KO animals. These data suggest IL-18 signaling is not necessary for hypobaric hypoxia induced RV dysfunction, and blockade of IL-18 is not a viable therapeutic strategy in this model.
Acute coronary syndrome as a possible immune-related adverse event in a lung cancer patient achieving a complete response to anti-PD-1 immune checkpoint antibody
Authors: Y. Tomita, D. Sueta, Y. Kakiuchi, S. Saeki, K. Saruwatari, S. Sakata, T. Jodai, Y. Migiyama, K. Akaike, S. Hirosako, K. Fujisue, S. Yamamura, S. Miyazaki, S. Takashio, Y. Izumiya, K. Nakamura, K. Tsujita, H. Ichiyasu, K. Fujii
Journal: Annals of Oncology (2017)
Rare Copy Number Variants in NRXN1 and CNTN6 Increase Risk for Tourette Syndrome
Authors: Alden Y. Huang, Dongmei Yu, Lea K. Davis, Jae Hoon Sul, Fotis Tsetsos, Vasily Ramensky, Ivette Zelaya, Eliana Marisa Ramos, Lisa Osiecki, Jason A. Chen, Lauren M. McGrath, Cornelia Illmann, Paul Sandor, Cathy L. Barr, Marco Grados, Harvey S. Singer, Markus M. Nöthen, Johannes Hebebrand, Robert A. King, Yves Dion, Guy Rouleau, Cathy L. Budman, Christel Depienne, Yulia Worbe, Andreas Hartmann, Kirsten R. Müller-Vahl, Manfred Stuhrmann, Harald Aschauer, Mara Stamenkovic, Monika Schloegelhofer, Anastasios Konstantinidis, Gholson J. Lyon, William M. McMahon, Csaba Barta, Zsanett Tarnok, Peter Nagy, James R. Batterson, Renata Rizzo, Danielle C. Cath, Tomasz Wolanczyk, Cheston Berlin, Irene A. Malaty, Michael S. Okun, Douglas W. Woods, Elliott Rees, Carlos N. Pato, Michele T. Pato, James A. Knowles, Danielle Posthuma, David L. Pauls, Nancy J. Cox, Benjamin M. Neale, Nelson B. Freimer, Peristera Paschou, Carol A. Mathews, Jeremiah M. Scharf, Giovanni Coppola, Ruth D. Bruun, Sylvain Chouinard, Sabrina Darrow, Erica Greenberg, Matthew E. Hirschtritt, Roger Kurlan, James F. Leckman, Mary M. Robertson, Jan Smit
Journal: Neuron (2017)
Nonreproducibility of Preclinical Research
Authors: Peter G. Goldschmidt
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Beyond maximum grade: A novel method to assess toxicity over time in clinical trials of targeted therapy in lymphoma.
Authors: Gita Thanarajasingam, Pamela J. Atherton, Levi Pederson, Paul J Novotny, Thomas Matthew Habermann, Jeff A. Sloan, Axel Grothey, Shaji Kumar, Thomas E. Witzig
Journal: Journal of Clinical Oncology (2016)

7546 Background: As more targeted, chronically administered therapies are developed in lymphoma, evaluation of adverse events (AEs) over time is increasingly relevant. Limited reports of high grade AEs do not provide adequate clinically relevant information on AE time profile and do not describe longer lasting, low grade AEs that may occur at substantial expense to a patient’s quality of life. We developed a new approach to AE analysis, the Toxicity over Time (ToxT, Thanarajasingam et al, Lancet Oncology 2016, in press), a standardized package of graphical and analytical routines that can depict AEs longitudinally in lymphoma patients on targeted agents. Methods: The analytic capability of ToxT was demonstrated in two completed phase II trials of targeted agents in relapsed or refractory lymphoma at our institution: a trial of single agent everolimus (EVE) (NCT00436618) and a trial of everolimus and panobinostat (EVE+PAN) (NCT00918333). Plots depicting summary statistics or individual patient data over discreet time points were combined with longitudinal techniques (repeated measures modeling, time-to-event and area-under-curve [AUC] analyses). Results: Bar charts visually demonstrate a higher incidence and grade of diarrhea on EVE + PAN starting at cycle 1 that remains consistent over multiple cycles. Stream plots reveal that of multiple toxicities of EVE+PAN, fatigue and diarrhea are the highest grade consistently over multiple cycles. A butterfly plot depicts that cytopenias are worse earlier and improve over time in both studies. Time-to-event analyses display a shorter time to grade 2+ fatigue on EVE+PAN than on EVE (42/93[45%] events vs 76/275[28%] events, hazard ratio 1.67, p = 0.007). AUC analysis depicts that patients on EVE+PAN experienced more chronic low grade fatigue and diarrhea than those on EVE (AUC 4.0 vs 1.3, p < 0.001 for fatigue, AUC 1.9 vs. 1.1, p < 0.006 for diarrhea). Conclusions: Longitudinal AE analysis offers a more complete depiction of toxicity than conventional maximum grade reports for chronically administered targeted therapies. ToxT analyses enhance patient education, guide clinical management and improve patient-centered AE evaluation in lymphoma clinical trials.
Re-Enchanting Medicine
Authors: Lydia S. Dugdale
Journal: JAMA Internal Medicine (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal