tbuckley/cabot-search huggingface dataset:
Use of Larynx-Preservation Strategies in the Treatment of Laryngeal Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update
Authors: Arlene A. Forastiere, Nofisat Ismaila, Jan S. Lewin, Cherie Ann Nathan, David J. Adelstein, Avraham Eisbruch, Gail Fass, Susan G. Fisher, Scott A. Laurie, Quynh-Thu Le, Bernard O’Malley, William M. Mendenhall, Snehal Patel, David G. Pfister, Anthony F. Provenzano, Randy Weber, Gregory S. Weinstein, Gregory T. Wolf
Journal: Journal of Clinical Oncology (2017)

Purpose To update the guideline recommendations on the use of larynx-preservation strategies in the treatment of laryngeal cancer. Methods An Expert Panel updated the systematic review of the literature for the period from January 2005 to May 2017. Results The panel confirmed that the use of a larynx-preservation approach for appropriately selected patients does not compromise survival. No larynx-preservation approach offered a survival advantage compared with total laryngectomy and adjuvant therapy as indicated. Changes were supported for the use of endoscopic surgical resection in patients with limited disease (T1, T2) and for initial total laryngectomy in patients with T4a disease or with severe pretreatment laryngeal dysfunction. New recommendations for positron emission tomography imaging for the evaluation of regional nodes after treatment and best measures for evaluating voice and swallowing function were added. Recommendations Patients with T1, T2 laryngeal cancer should be treated initially with intent to preserve the larynx by using endoscopic resection or radiation therapy, with either leading to similar outcomes. For patients with locally advanced (T3, T4) disease, organ-preservation surgery, combined chemotherapy and radiation, or radiation alone offer the potential for larynx preservation without compromising overall survival. For selected patients with extensive T3 or large T4a lesions and/or poor pretreatment laryngeal function, better survival rates and quality of life may be achieved with total laryngectomy. Patients with clinically involved regional cervical nodes (N+) who have a complete clinical and radiologic imaging response after chemoradiation do not require elective neck dissection. All patients should undergo a pretreatment baseline assessment of voice and swallowing function and receive counseling with regard to the potential impact of treatment options on voice, swallowing, and quality of life. Additional information is available at www.asco.org/head-neck-cancer-guidelines and www.asco.org/guidelineswiki .
Response to Comment on Kaul. Mitigating Cardiovascular Risk in Type 2 Diabetes With Antidiabetes Drugs: A Review of Principal Cardiovascular Outcome Results of EMPA-REG OUTCOME, LEADER, and SUSTAIN-6 Trials. Diabetes Care 2017;40:821–831
Authors: Sanjay Kaul
Journal: Diabetes Care (2017)

I would like to thank Dr. Feldman-Billard for her interest in my article (1) and for raising several important issues (2).

First, I agree with the author that the exact mechanism(s) contributing to the increased risk of diabetic retinopathy (DR) with semaglutide (and possibly liraglutide) remain unclear, and potential explanations, among others, include rapid glucose lowering and a direct deleterious effect on the retina.

Second, with regard to the retinopathy outcome in EMPA-REG OUTCOME (BI 10773 [Empagliflozin] Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients), as mentioned previously, the individual component results, but not the composite retinal outcome, were …
A global phase II study of olmutinib (HM61713) in patients with T790M-positive NSCLC after failure of first-line EGFR-TKI
Authors: K. Park, P.A. Jänne, C-J Yu, L. Bazhenova, L. Paz-Ares, E. Baek, O. Han, K.Y. Hong, H. Kwon, Y. Kim, S.R. Kim
Journal: Annals of Oncology (2017)
Keeping GBM in check by targeting CHK1-CIP2A axis.
Authors: Anchit Khanna, Brett Stringer, Bryan Day, Kathleen Ensbey, Han Shen, Andrew Boyd, Kerrie Leanne McDonald, John Pimanda
Journal: Journal of Clinical Oncology (2014)

2036 Background: Checkpoint kinase1 (CHK1) is constitutively active in many human cancers including Glioblastoma (GBM). Unfortunately CHK1 inhibitors, currently in clinical trials, have shown deleterious effects on normal cells, thus limiting their clinical utility. Therefore, identification and targeting of cancer specific effectors of CHK1 signaling, emerges as an attractive therapeutic alternative. Methods: Analysis of 906 gliomapatient samples was done. GBM cell lines (including primary) were used for mechanistic and functional studies. In vivo models of GBM were used to verify the findings. Results: Meta-analysis of key datasets revealed a strong positive correlation for CHK1 and CIP2A expression. By contrast, a negligible correlation was seen in normal samples. Importantly, high mRNA expression of both proteins associated with reduced overall survival in glioma patients and marked for a more aggressive form of the disease. CIP2A amplification, found in 14.72% cases in the REMBRANDT study, was associated with worse overall survival in GBM patients. Inhibition of CHK1, by siRNA and chemicals, resulted in decreased CIP2A expression both in vitro and in vivo. Functionally, both CHK1 and CIP2A promoted viability, clonogenicity and anchorage-independent growth of GBM cells. Strikingly, the CHK1-mediated reduction in the clonogenic potential was partially rescued by exogenous CIP2A expression in GBM cells. Mechanistically, we identify STAT3 as the transcriptional mediator for CHK1-mediated CIP2A regulation. Depletion of STAT3 resulted in decreased CIP2A expression in both, U251MG and primary GBM cells. Further, CHK1 promoted STAT3 phosphorylation in vitro and in vivo. Accordingly, higher CIP2A, pCHK1 and pSTAT3 levels were observed in de novo and patient-derived GBM samples, relative to normal human astrocytes. Analogously, 10- to 15-fold higher CHK1 and CIP2A mRNA expression was seen in the genetically engineered mouse models of human GBM. Finally, using xenograft mouse models we show that both CHK1 inhibitor and CIP2A depletion inhibit GBM growth. Conclusions: These results highlight CHK1 and CIP2A expression as potential diagnostic and prognostic markers in human GBMs and identify CIP2A as a relevant cancer specific therapeutic target.
Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group
Authors: I. Puzanov, A. Diab, K. Abdallah, C. O. Bingham, C. Brogdon, R. Dadu, L. Hamad, S. Kim, M. E. Lacouture, N. R. LeBoeuf, D. Lenihan, C. Onofrei, V. Shannon, R. Sharma, A. W. Silk, D. Skondra, M. E. Suarez-Almazor, Y. Wang, K. Wiley, H. L. Kaufman, M. S. Ernstoff
Journal: Journal for ImmunoTherapy of Cancer (2017)

Cancer immunotherapy has transformed the treatment of cancer. However, increasing use of immune-based therapies, including the widely used class of agents known as immune checkpoint inhibitors, has exposed a discrete group of immune-related adverse events (irAEs). Many of these are driven by the same immunologic mechanisms responsible for the drugs' therapeutic effects, namely blockade of inhibitory mechanisms that suppress the immune system and protect body tissues from an unconstrained acute or chronic immune response. Skin, gut, endocrine, lung and musculoskeletal irAEs are relatively common, whereas cardiovascular, hematologic, renal, neurologic and ophthalmologic irAEs occur much less frequently. The majority of irAEs are mild to moderate in severity; however, serious and occasionally life-threatening irAEs are reported in the literature, and treatment-related deaths occur in up to 2% of patients, varying by ICI. Immunotherapy-related irAEs typically have a delayed onset and prolonged duration compared to adverse events from chemotherapy, and effective management depends on early recognition and prompt intervention with immune suppression and/or immunomodulatory strategies. There is an urgent need for multidisciplinary guidance reflecting broad-based perspectives on how to recognize, report and manage organ-specific toxicities until evidence-based data are available to inform clinical decision-making. The Society for Immunotherapy of Cancer (SITC) established a multidisciplinary Toxicity Management Working Group, which met for a full-day workshop to develop recommendations to standardize management of irAEs. Here we present their consensus recommendations on managing toxicities associated with immune checkpoint inhibitor therapy.
An Unusual Cause of Leg Pain
Authors: Noreen P Kelly, Marie Gerhard-Herman, Akshay S Desai, Amy L Miller, Joseph Loscalzo
Journal: New England Journal of Medicine (2017)

A 67-year-old woman presented to her primary care physician with leg pain. Seven weeks before presentation she noticed a cramping sensation in the thighs and calves that developed after she had walked a couple of blocks and was relieved with rest.
Zika virus in French Polynesia 2013–14: anatomy of a completed outbreak
Authors: Didier Musso, Hervé Bossin, Henri Pierre Mallet, Marianne Besnard, Julien Broult, Laure Baudouin, José Eduardo Levi, Ester C Sabino, Frederic Ghawche, Marion C Lanteri, David Baud
Journal: The Lancet Infectious Diseases (2017)
Platelet Transfusion for Patients With Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update
Authors: Charles A. Schiffer, Kari Bohlke, Meghan Delaney, Heather Hume, Anthony J. Magdalinski, Jeffrey J. McCullough, James L. Omel, John M. Rainey, Paolo Rebulla, Scott D. Rowley, Michael B. Troner, Kenneth C. Anderson
Journal: Journal of Clinical Oncology (2017)

Purpose To provide evidence-based guidance on the use of platelet transfusion in people with cancer. This guideline updates and replaces the previous ASCO platelet transfusion guideline published initially in 2001. Methods ASCO convened an Expert Panel and conducted a systematic review of the medical literature published from September 1, 2014, through October 26, 2016. This review builds on two 2015 systematic reviews that were conducted by the AABB and the International Collaboration for Transfusion Medicine Guidelines. For clinical questions that were not addressed by the AABB and the International Collaboration for Transfusion Medicine Guidelines (the use of leukoreduction and platelet transfusion in solid tumors or chronic, stable severe thrombocytopenia) or that were addressed partially (invasive procedures), the ASCO search extended back to January 2000. Results The updated ASCO review included 24 more recent publications: three clinical practice guidelines, eight systematic reviews, and 13 observational studies. Recommendations The most substantial change to a previous recommendation involved platelet transfusion in the setting of hematopoietic stem-cell transplantation. Based on data from randomized controlled trials, adult patients who undergo autologous stem-cell transplantation at experienced centers may receive a platelet transfusion at the first sign of bleeding, rather than prophylactically. Prophylactic platelet transfusion at defined platelet count thresholds is still recommended for pediatric patients undergoing autologous stem-cell transplantation and for adult and pediatric patients undergoing allogeneic stem-cell transplantation. Other recommendations address platelet transfusion in patients with hematologic malignancies or solid tumors or in those who undergo invasive procedures. Guidance is also provided regarding the production of platelet products, prevention of Rh alloimmunization, and management of refractoriness to platelet transfusion ( www.asco.org/supportive-care-guidelines and www.asco.org/guidelineswiki ).
Une épidémie de listériose associée à la tomme dans le nord-ouest de la Suisse, 2005
Authors: J Bille, D S Blanc, H Schmid, K Boubaker, A Baumgartner, H H Siegrist, M L Tritten, R Lienhard, D Berner, R Anderau, M Treboux, J M Ducommun, R Malinverni, D Genné, P Erard, U Waespi
Journal: Eurosurveillance (2006)

Dix cas de listeriose ont ete declares dans une region (150 000 habitants) du nord-ouest de la Suisse pendant une periode de huit semaines au printemps de l’annee 2005. Il s’agissait de huit patients immunodeprimes atteints de bacteriemie (trois deces), et de deux femmes enceintes ayant subi un avortement septique. Tous les cas etaient dus a un isolat de serotype 1/2a appartenant a deux pulsotypes identifies par PFGE. Les entretiens avec les patients ont permis de decouvrir rapidement qu’un fromage a pâte molle (tomme) fabrique et distribue localement etait la source alimentaire incriminee dans l’epidemie. L. monocytogenes sv 1/2a du meme pulsotype a ete identifie dans les echantillons de ce fromage, ainsi que dans le beurre fabrique par la meme laiterie, en quantites de 1000-10 000 et 10-100 cfu/g, respectivement. Suite a l’interruption immediate de la production, au retrait du produit du marche et a une alerte publique, l’epidemie a pris fin. Neanmoins, deux cas de gastroenterite febrile due aux memes souches ont ete rapportes dans les 10 jours suivant le retrait du fromage. Le fait que ce fromage contamine ait ete distribue dans une zone limitee, la collaboration des medecins locaux, des microbiologistes medicaux et des services de sante alimentaire ont contribue au succes et a la rapidite de l’investigation. 
Cette epidemie de listeriose de faible portee a toutefois souligne l’importance d’un systeme de surveillance basee sur les laboratoires avec un typage rapide, ainsi que de la collaboration entre medecins et microbiologistes.
Abstract 21372: Women Undergoing Coronary Artery Bypass Graft Surgery Do Not Follow Any Recommended Guidelines for Breast Cancer Screening
Authors: Javier E Lopez, Nandini Sarma, Tara Shakeri, Shadi Aminololama-Shakeri
Journal: Circulation (2017)

Introduction: In the United States, 1 in 4 women dies of heart disease. Severe coronary artery disease is usually treated with coronary artery bypass graft (CABG) surgery to prolong a patient’s life span. To maintain the significant survival benefit derived from this procedure, vigilant post-care counseling is performed to prevent further health complications. Current post-CABG care guidelines include counseling on exercise, diet, and medical management but do not explicitly contain recommendations for other primary preventative care. Screening mammography (SM) for primary prevention is an effective measure that reduces women's mortality due to breast cancer by ~30%. Hypothesis: We hypothesize that women change the frequency of screening mammography following CABG surgery. Methods and Results: Using electronic medical record data, we identified a retrospective cohort of 170 women who underwent CABG surgery and SMs between 2002-2012. Recommended guidelines during these years varied between 0.5-1 SM per year (SM/year). The rate of SM/year prior to- and following CABG were calculated. We performed the same analysis on a second cohort of 400 women who underwent a cardiac catheterization (Cath) during the same time period and were found to have preserved heart function without CAD as a control group. The mean (95% CI) age of the CABG women at first screening mammogram, CABG procedure and last follow-up was, respectively, 61 (60-63), 67 (65-68), and 73 (71-74). The median SM/year before CABG procedure was 0.51 compared to 0.28 following CABG procedure (p&lt;0.0001). The median SM/year for Cath women ranged from 0.64 to 0.45 following Cath procedure. Conclusion: Women following CABG have the lowest breast cancer screening rates and are not meeting any recommended screening guidelines for mammography. These results indicate that further study of patient, provider, and/or system-related factors resulting in this change of preventative care is warranted.
Bref résumé de Swedres 2005, rapport sur l’utilisation des antibiotiques et la résistance aux antibiotiques en Suède
Authors: O Cars, B Olsson-Liljequist, K Lundh
Journal: Eurosurveillance (2007)

« Swedres 2005 », le cinquieme rapport sur l’utilisation des antibiotiques et la resistance a ceux-ci chez l’homme en Suede, a ete presente en mai 2006. La consommation d’antibiotiques et les niveaux de resistance en Suede sont relativement faibles par rapport au reste de l’Europe.
Real world use of palliative systemic therapy (tx) in elderly patients (pts) with metastatic colorectal cancer (mCRC) within a UK specialist cancer centre
Authors: S. Khakoo, A. Georgiou, D. Hughes, A. Lanese, C. Baratelli, M. Coakley, S. Shepherd, V. Calamai, K. Kouvelakis, R. Kalaitzaki, A. Ring, I. Chau, D. Watkins, S. Rao, D. Cunningham, N. Starling
Journal: Annals of Oncology (2017)
P226 FRACTION-RCC: a randomized, open-label, adaptive, phase 2 study of nivolumab in combination with other immuno-oncology agents in patients with advanced RCC.
Authors: Corina C Taitt, Robert J Motzer, Toni K Choueiri, Bernard J Escudier, Timothy Kuzel, Michael A Carducci Md, Suresh G. Nair Md, Scott S Tykodi, Sarah Tannenbaum-Dvir, Megan Wind-Rotolo, Katy L Simonsen, Paula M Fracasso
Journal: Journal for ImmunoTherapy of Cancer (2017)
Abstract 229: Increased Afterload Following Myocardial Infarction Promotes Conduction-dependent Arrhythmias That are Unmasked by Hypokalemia
Authors: Lukas J Motloch, Kiotake Ishikawa, Chaoqin Xie, Jun Hu, Jaume Aguero, Kenneth R Fish, Roger J Hajjar, Fadi G Akar
Journal: Circulation Research (2016)

Background-and-Objectives: Arterial hypertension worsens the prognosis of post-myocardial infarction (MI) patients. Its impact on electrophysiological function, however, is unknown. To address this, we developed a new porcine model of post-MI remodeling with chronically increased afterload (MI/iAL). We compared the electrophysiological substrate of this model to that of a standard model of MI without increased afterload and to naïve pigs (Sham). Methods-and-Results: Yorkshire pigs underwent aortic banding 1-month following MI, and were allowed to survive with increased afterload for another 2-months. MI/iAL but not MI or Sham animals exhibited widespread interstitial fibrosis and increased profibrotic gene expression with no major changes in Cx43 expression or localization. Arterially-perfused wedges from MI/iAL but not MI or Sham pigs were prone to pacing-induced VT/VF when challenged with hypokalemia. Investigation of the electrophysiological substrate revealed the dependence of these arrhythmias on impaired conduction and not repolarization. When excitability was reduced with fast pacing and hypokalemia, MI/iAL preparations exhibited conduction velocity (CV) slowing to critical levels never attained in sham or MI preparations before their eventual loss of capture. A steep negative slope of rate-dependent CV slowing was observed exclusively in MI/iAL preparations consistent with a higher safety factor for propagation of slow wavefronts before onset of VT/VF. Conclusions: MI/iAL animals exhibit widespread interstitial fibrosis, a profibrotic gene expression program and marked susceptibility to arrhythmias that are unmasked by hypokalemia. Structural remodeling in MI/iAL produces a substrate that promotes the successful propagation of critically slow wavefronts leading to reentrant arrhythmias.
Heritable Thoracic Aortic Disease Genes in Sporadic Aortic Dissection
Authors: Dong-chuan Guo, Ellen M. Hostetler, Yuxin Fan, Richard J. Kulmacz, Di Zhang, Deborah A. Nickerson, Suzanne M. Leal, Scott A. LeMaire, Ellen S. Regalado, Dianna M. Milewicz
Journal: Journal of the American College of Cardiology (2017)
Use of Fondaparinux Off-Label or Approved Anticoagulants for Management of Heparin-Induced Thrombocytopenia
Authors: Marc Schindewolf, Julia Steindl, Jan Beyer-Westendorf, Sebastian Schellong, Pascal Maria Dohmen, Johannes Brachmann, Katharina Madlener, Bernd Pötzsch, Robert Klamroth, Johannes Hankowitz, Norbert Banik, Sonja Eberle, Markus Michael Müller, Stefan Kropff, Edelgard Lindhoff-Last
Journal: Journal of the American College of Cardiology (2017)
Personal Sound Amplification Products for Hearing Loss
Authors: Manuele Casale, Lorenzo Sabatino, Fabrizio Salvinelli
Journal: JAMA (2017)

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Abstract 21213: Cardiac Secreted Beta-2 Microglobulin Promotes Fibrosis Involving Epidermal Growth Factor Receptor Signaling During Pressure Overload
Authors: Yang Li, Hui Gong
Journal: Circulation (2017)

Plasma Beta-2 microglobulin (β2M) level is inversely associated with glomerular filtration rate (GFR) and ejection fraction (EF) in patients with chronic kidney disease. However, few studies have evaluated roles of β2M in cardiac remodeling induced by hypertension. The present data showed that serum β2M level was increased in patients with hypertension as compared to control group, and it was significantly higher in patients with chronic heart failure than in those with hypertension. Serum β2M level was related to diastolic dysfunction in patients with hypertension and heart failure. During 4 weeks after transverse aortic constriction (TAC) in mice, β2M level in serum or heart tissue increased progressively in time-dependent manner. Cardiomyocyte but not fibroblast secretory β2M was rapidly increased after mechanical stretch (MS) in vitro . Exogenous β2M showed pro-fibrotic effects and enhanced migratory capability in cardiac fibroblasts. Conditional medium (CM) from mechanical stretched cardiomyocytes showed the similar effects in fibroblasts, but these effects were partly abolished by CM from β2M-downregulated-cardiomyocytes subjected to MS. In vivo, AAV9 mediated-knockdown of cardiac β2M greatly improved the cardiac fibrosis and dysfunction induced by TAC. Further analysis indicated that β2M promoted the phosphorylation of p38, smad2/3 and epidermal growth factor receptor (EGFR) in fibroblasts, and inhibition of EGFR attenuated p-p38 and p-smad2/3 levels, and significantly inhibited pro-fibrotic effects in cardiac fibroblasts treated with β2M. The present data demonstrated the importance of β2M as a paracrine pro-fibrotic mediator associated with hypertension or heart failure. It suggests that inhibition of β2M may have the therapeutic potential for the prevention of cardiac fibrosis or the progression of heart failure associated with hypertension.
Comparison of lung diffusing capacity in young elite athletes and their counterparts
Authors: B. Lazovic, M. Zlatkovic-Svenda, J. Grbovic, B. Milenković, S. Sipetic-Grujicic, I. Kopitovic, V. Zugic
Journal: Pulmonology (2017)

The influence of exercise on the pulmonary function is controverse, some studies have reported no sports influence, while the others have found positive correlation.