tbuckley/cabot-search huggingface dataset:
Into the clinic: Talimogene laherparepvec (T-VEC), a first-in-class intratumoral oncolytic viral therapy
Authors: Hasan Rehman, Ann W. Silk, Michael P. Kane, Howard L. Kaufman
Journal: Journal for ImmunoTherapy of Cancer (2016)

With the recent regulatory approval of Talimogene laherparepvec (T-VEC) for the treatment of advanced of melanoma in the United States, Europe and Australia, oncolytic virus immunotherapy has earned its place in the clinic. However, the adoption of T-VEC by the U.S. oncology community has been slow, and so far has been largely limited to specialized cancer centers. Limiting factors include the intratumoral route of administration, which is unfamiliar to medical oncologists, biosafety concerns related to the use of a live virus in the clinic, and the explosion of other therapeutic strategies now available for the treatment of advanced melanoma. Herein, we review the development of T-VEC, and suggest how it fits into the in the current clinical treatment paradigm, and provide pearls for drug preparation, administration, and monitoring of response to therapy.
P0735 : Assessment of baseline viral load cut-off for shortened ledipasvir/sofosbuvir therapy by widely used HCVRNA assays
Authors: J. Vermehren, B. Maasoumy, S. Chevaliez, J.J. Feld, G. Cloherty, J.-M. Pawlotsky, C. Sarrazin, H. Wedemeyer
Journal: Journal of Hepatology (2015)
MRI monitoring of monocytes to detect immune stimulating treatment response in brain tumor
Authors: Runze Yang, Susobhan Sarkar, Daniel J. Korchinski, Ying Wu, V. Wee. Yong, Jeff F. Dunn
Journal: Neuro-Oncology (2016)

Glioblastoma (GBM) is an aggressive brain cancer with a poor prognosis. The use of immune therapies to treat GBM has become a promising avenue of research. It was shown that amphotericin B (Amp B) can stimulate the innate immune system and suppress the growth of brain tumor initiating cells (BTICs). However, it is not feasible to use histopathology to determine immune activation in patients. We developed an MRI technique that can rapidly detect a therapeutic response in animals treated with drugs that stimulate innate immunity. Ultra-small iron oxide nanoparticles (USPIOs) are MRI contrast agents that have been widely used for cell tracking. We hypothesized that the increased monocyte infiltration into brain tumors due to Amp B can be detected using USPIO-MRI, providing an indicator of early drug response.We implanted human BTICs into severe combined immunodeficient mice and allowed the tumor to establish before treating the animals with either Amp B or vehicle and then imaged them using MRI with USPIO (ferumoxytol) contrast.After 7 days of treatment, there was a significantly decreased T2* in the tumor of Amp B but not vehicle animals, suggesting that USPIO is carried into the tumor by monocytes. We validated our MRI results with histopathology and confirmed that Amp B-treated animals had significantly higher levels of macrophage/microglia that were colocalized with iron staining in their brain tumor compared with vehicle mice.USPIO-MRI is a promising method of rapidly assessing the efficacy of anticancer drugs that stimulate innate immunity.
Detection of Therapeutically Targetable Driver and Resistance Mutations in Lung Cancer Patients by Next-Generation Sequencing of Cell-Free Circulating Tumor DNA
Authors: Jeffrey C. Thompson, Stephanie S. Yee, Andrea B. Troxel, Samantha L. Savitch, Ryan Fan, David Balli, David B. Lieberman, Jennifer D. Morrissette, Tracey L. Evans, Joshua Bauml, Charu Aggarwal, John A. Kosteva, Evan Alley, Christine Ciunci, Roger B. Cohen, Stephen Bagley, Susan Stonehouse-Lee, Victoria E. Sherry, Elizabeth Gilbert, Corey Langer, Anil Vachani, Erica L. Carpenter
Journal: Clinical Cancer Research (2016)

The expanding number of targeted therapeutics for non-small cell lung cancer (NSCLC) necessitates real-time tumor genotyping, yet tissue biopsies are difficult to perform serially and often yield inadequate DNA for next-generation sequencing (NGS). We evaluated the feasibility of using cell-free circulating tumor DNA (ctDNA) NGS as a complement or alternative to tissue NGS.A total of 112 plasma samples obtained from a consecutive study of 102 prospectively enrolled patients with advanced NSCLC were subjected to ultra-deep sequencing of up to 70 genes and matched with tissue samples, when possible.We detected 275 alterations in 45 genes, and at least one alteration in the ctDNA for 86 of 102 patients (84%), with EGFR variants being most common. ctDNA NGS detected 50 driver and 12 resistance mutations, and mutations in 22 additional genes for which experimental therapies, including clinical trials, are available. Although ctDNA NGS was completed for 102 consecutive patients, tissue sequencing was only successful for 50 patients (49%). Actionable EGFR mutations were detected in 24 tissue and 19 ctDNA samples, yielding concordance of 79%, with a shorter time interval between tissue and blood collection associated with increased concordance (P = 0.038). ctDNA sequencing identified eight patients harboring a resistance mutation who developed progressive disease while on targeted therapy, and for whom tissue sequencing was not possible.Therapeutically targetable driver and resistance mutations can be detected by ctDNA NGS, even when tissue is unavailable, thus allowing more accurate diagnosis, improved patient management, and serial sampling to monitor disease progression and clonal evolution. Clin Cancer Res; 22(23); 5772-82. ©2016 AACR.
Postoperative accelerated radiotherapy (POPART) versus conventional postoperative radiotherapy (CPORT) in squamous cell head and neck cancer: A multicenter prospective randomized study of the Dutch Head and Neck Cooperative Study Group.
Authors: J. A. Langendijk, J. H. Kaanders, P. Doornaert, F. R. Burlage, P. L. van den Ende, S. B. Oei, R. B. Keus, S. Nuyts, C. R. Leemans, C. H. Terhaard
Journal: Journal of Clinical Oncology (2010)

5508 Background: In head and neck squamous cell carcinoma (HNSCC), the overall treatment time of radiation (OTT) is significantly associated with locoregional control (LRC), which is consistent with rapid repopulation of cancer clonogens during radiotherapy. However, the importance of the OTT in the postoperative setting is less clear. Therefore, the main objective of this phase III study was to determine the value of reduction of the OTT of postoperative radiotherapy in high risk patients primarily treated with surgery. Methods: Patients with HNSCC treated with curative surgery and with high risk factors for locoregional recurrence (i.e., positive surgical margins and/or extranodal spread) were randomly assigned to receive either standard postoperative radiotherapy (SPORT) at 2 Gy/fraction/day, 5 days/week to 66 Gy/33 fractions/7 weeks or postoperative accelerated radiotherapy (POPART) with 2 Gy/fraction/day, 5 days per week, to 20 Gy followed by 1.8 Gy/fraction/day and 1.3 Gy/fraction per day to a boost field as a second daily treatment to 66.5 Gy/40 fractions/5 weeks.The primary endpoint was locoregional tumor control (LRC). Secondary endpoints were overall survival, acute and late toxicity and quality of life. Results: From December 2004 to October 2008, 148 patients were enrolled in the study (74 pts for SPORT and 74 pts for POPART). The two study-arms were well balanced with regard to the most important prognostic factors. No significant differences were noted with regard to acute and late toxicity, although there was a trend towards more use of pain medication among patients treated with POPART. At 3 years, the locoregional control rate was 77% after POPART compared to 76% with SPORT (HR: 0.86, CI 0.42-1.76; p=0.68). The 3-year overall survival rate was 71% with POPART compared to 63% with SPORT (HR:0.93, CI 0.54-1.61; p=0.81). Conclusions: A reduction in the OTT of postoperative radiotherapy in patients with HNSCC with adverse factors for locoregional failure does not improve outcome in terms of locoregional control and overall survival. No significant financial relationships to disclose.
Close Follow-up in Children With Acute Otitis Media Initially Managed Without Antimicrobials
Authors: Johanna M. Uitti, Paula A. Tähtinen, Miia K. Laine, Aino Ruohola
Journal: JAMA Pediatrics (2016)

This study examines whether close follow-up with reexamination is needed for children with acute otitis media initially managed without antimicrobial agents who have symptomatic improvement during the first week.
Impact of delaying initiation of adjuvant chemotherapy in breast cancer patients.
Authors: Debora De Melo Gagliato, Ana M. Gonzalez-Angulo, Xiudong Lei, Sharon Hermes Giordano, Richard L. Theriault, Vicente Valero, Gabriel N. Hortobagyi, Mariana Chavez-Mac Gregor
Journal: Journal of Clinical Oncology (2013)

1022 Background: The survival benefit of adjuvant chemotherapy in breast cancer is well established. However, the optimal timing to initiation of chemotherapy after definitive surgery is unknown. We evaluated the association between time to initiation of chemotherapy and survival outcomes according to breast cancer subtype and stage at diagnosis. Methods: Women diagnosed with stage I–III breast cancer between 1997-2011 who received adjuvant chemotherapy at our institution were included. Patients were categorized according to time from definitive surgery to adjuvant chemotherapy into one of three groups: ≤ 30 days, 31–60 days and more than 60 days. Descriptive statistics, Kaplan-Meier statistics and Cox proportional hazards models were used. Results: Among the 6,827 patients included, the 5-year Overall Survival (OS), Relapse-Free Survival (RFS) and Distant Relapse-Free Survival (DRFS) estimates were similar for the different time-to-chemotherapy categories. Among patients with stage I, there was no association between outcome and time to initiation of chemotherapy. Patients with stage II disease experienced an 18% and 22% increase in risk of RFS (HR 1.18; p=0.038) and DRFS (HR 1.22; p=0.02), when systemic treatment was started &gt;60 days from surgery. Patients with stage III disease that started adjuvant chemotherapy &gt;60 days after surgery had a 70% increase in the risk of death (HR 1.7; p=0.002), a 32% increase risk of relapse (HR 1.32; p=0.046) and a 34% increase risk of distant relapse (HR 1.34; p=0.044). Time to chemotherapy did not have a significant effect on outcome among Hormone Receptor (HR)-positive patients. Patients with triple negative (TNBC) and HER2-positive tumors treated with trastuzumab who started chemotherapy &gt;60 days after surgery had lower 5 year-OS estimates (HR 1.52; p=0.016 and HR 2.62; p=0.005, respectively). Conclusions: Time to chemotherapy did not influence survival outcomes in the overall population. However, patients with stage III, TNBC and HER2-positive tumors treated with trastuzumab, experienced worse outcomes when chemotherapy was delayed. Among patients with tumors with aggressive biology and more advanced stages at diagnosis, early initiation of therapy should be favored.
Clinical Use of a Von Willebrand Factor with a Low FVIII Content in Von Willebrand Disease Patients Undergoing Surgical Procedures or Deliveries: Results From 5 Prospective Multicenter Studies
Authors: Annie Borel-Derlon, Augusto B. Federici, Jenny Goudemand, Catherine Chatelanaz, Celine Henriet, Françoise Bridey
Journal: Blood (2011)
Molecular Pathways: Interleukin-35 in Autoimmunity and Cancer
Authors: Yuliya Pylayeva-Gupta
Journal: Clinical Cancer Research (2016)

Abstract Immunosuppressive functions conferred by regulatory cytokines are important for maintaining homeostasis in immune responses. IL35 has recently emerged as a novel regulator of immune responses. Once thought to be specifically expressed by T regulatory cells, induction of IL35 expression has now been detected in multiple cell types in a variety of diseases, prompting research into regulation of its expression, signaling specificity, target cell populations, and functional outputs. Recent studies have revealed that by directing de novo generation of regulatory T and B cells and inhibiting T effector responses, IL35 plays an important role in the development of autoimmune diseases and cancer. IL35 is overexpressed in a variety of cancers and may exert its function both on antitumor immune responses as well as directly on tumor cells. As such, IL35 is rapidly emerging as a promising biomarker and an attractive cancer therapy target. Clin Cancer Res; 22(20); 4973–8. ©2016 AACR.
Bortezomib, Thalidomide and Dexamethasone (VTD) Is Superior to Bortezomib, Cyclophosphamide and Dexamethasone (VCD) Prior to Autologous Stem Cell Transplantation for Patients with De Novo Multiple Myeloma. Results of the Prospective IFM 2013-04 Trial
Authors: Philippe Moreau, Cyrille Hulin, Margaret MACRO, Denis Caillot, Carine Chaleteix, Murielle Roussel, Laurent Garderet, Bruno Royer, Sabine Brechignac, Mourad Tiab, Mathieu Puyade, Martine Escoffre, Anne-Marie Stoppa, Thierry Facon, Brigitte Pégourie, Driss Chaoui, Arnaud Jaccard, Borhane Slama, Gerald Marit, Kamel Laribi, Pascal Godmer, Odile Luycx, Jean Claude Eisenmann, Olivier Allangha, Sylvie Glaisner, Mamoun Dib, Carla Araujo, Jean Fontan, Karim Belhadj, Marc Wetterwald, Veronique Dorvaux, Jean-Paul Fermand, Philippe Rodon, Brigitte Kolb, Pascal Lenain, Lucie Planche, Laetitia Biron, Helene Caillon, Herve Avet-Loiseau, Thomas Dejoie, Michel Attal
Journal: Blood (2015)
Noncoding somatic and inherited single-nucleotide variants converge to promote ESR1 expression in breast cancer
Authors: Swneke D Bailey, Kinjal Desai, Ken J Kron, Parisa Mazrooei, Nicholas A Sinnott-Armstrong, Aislinn E Treloar, Mark Dowar, Kelsie L Thu, David W Cescon, Jennifer Silvester, S Y Cindy Yang, Xue Wu, Rossanna C Pezo, Benjamin Haibe-Kains, Tak W Mak, Philippe L Bedard, Trevor J Pugh, Richard C Sallari, Mathieu Lupien
Journal: Nature Genetics (2016)
Progressive multifocal leucoencephalopathy and psoriasis
Authors: O.E. Molloy, C.C. Foley, A. Lally, B. Moriarty, P. Collins, J. O'Gorman, C.F. de Gascun, B. Kirby
Journal: British Journal of Dermatology (2016)

Progressive multifocal leucoencephalopathy (PML) is a progressive demyelinating inflammatory process in which oligodendrocytes are affected by the John Cunningham polyoma virus (JCV). John Cunningham virus infection occurs in childhood and up to 70% of adults have detectable antibodies.

This article is protected by copyright. All rights reserved.
The MDM2 Inhibitor NVP-CGM097 Is Highly Active in a Randomized Preclinical Trial of B-Cell Acute Lymphoblastic Leukemia Patient Derived Xenografts
Authors: Elizabeth C Townsend, Tiffany DeSouza, Mark A. Murakami, Joan Montero, Kristen Stevenson, Amanda L Christie, Alexandra N Christodolou, Una Vojinovic, Nadja Kopp, Patrizia Barzaghi-Rinaudo, Masato Murakami, Anthony Letai, Sebastien Jeay, Jens Wuerthner, Ensar Halilovic, David M. Weinstock
Journal: Blood (2015)
Validating the Patient's "Fitness" Criteria Proposed to Guide Treatment Decision in Elderly AML: a Multicenter Study on a Population-Based Series of 362 Patients By the Network "Rete Ematologica Lombarda" (REL)
Authors: Erika Borlenghi, Chiara Pagani, Claudia Basilico, Massimo Bernardi, Nicola Fracchiolla, Francesca Guidotti, Laura Marbello, Andrea Ferrario, Carlo Messina, Emanuele Ravano, Cinzia Lamorgese, Marta Petullà, Giuseppe Rossi
Journal: Blood (2014)
Together, we reach new heights: Swiss Sports Medicine Society (SGSM/SSMS) joins<i>BJSM</i>
Authors: Susi Kriemler, Andre Leumann, Boris Gojanovic
Journal: British Journal of Sports Medicine (2016)

The small but fine Swiss Sports Medicine Society (SSMS) has been in existence since 1949 and has about 800 members. Most of our members are general practitioners with an interest in sports medicine, and also orthopaedic surgeons, physical medicine and rehabilitation specialists or public health experts who focus on ‘exercise is medicine—and prevention’. Since 1999 sports medicine in Switzerland has been a medical subspecialty that can be achieved by every physician with a medical specialty certification. 24 course days over a period of 1–2 years, a written and oral examination at the end of these and the mandatory 6-month internship in a sports medicine centre of excellence allows a high standard for our ‘Swiss Sports Medicine Physician’ label. These physicians ultimately govern positions as leaders of Swiss Olympic medical centres and bases, become chief medical officers for our national sporting federations or promote ‘exercise is medicine’ in their daily practice.

In 2015, our general assembly unanimously welcomed the proposal to become a …
2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines
Authors: Jose Luis Zamorano, Patrizio Lancellotti, Daniel Rodriguez Muñoz, Victor Aboyans, Riccardo Asteggiano, Maurizio Galderisi, Gilbert Habib, Daniel J. Lenihan, Gregory Y. H. Lip, Alexander R. Lyon, Teresa Lopez Fernandez, Dania Mohty, Massimo F. Piepoli, Juan Tamargo, Adam Torbicki, Thomas M. Suter, Jose Luis Zamorano, Victor Aboyans, Stephan Achenbach, Stefan Agewall, Lina Badimon, Gonzalo Barón‐Esquivias, Helmut Baumgartner, Jeroen J. Bax, Héctor Bueno, Scipione Carerj, Veronica Dean, Çetin Erol, Donna Fitzsimons, Oliver Gaemperli, Paulus Kirchhof, Philippe Kolh, Patrizio Lancellotti, Gregory Y. H. Lip, Petros Nihoyannopoulos, Massimo F. Piepoli, Piotr Ponikowski, Marco Roffi, Adam Torbicki, António Vaz Carneiro, Stephan Windecker
Journal: European Journal of Heart Failure (2016)
Microfluidics-Based Pathogen Detection: A Highly Sensitive Molecular Detection Platform for Robust and Facile Diagnosis of Middle East Respiratory Syndrome (MERS) Corona Virus (Adv. Healthcare Mater. 17/2016)
Authors: Il Young Jung, Jae Bem You, Bo Ram Choi, Ji Su Kim, Hyun Kyung Lee, Bora Jang, Han Saem Jeong, Kyuri Lee, Sung Gap Im, Hyukjin Lee
Journal: Advanced Healthcare Materials (2016)

H. Lee and co-workers demonstrate a definitive molecular diagnosis platform (DhITACT-TR) for rapid and accurate detection of MERS coronavirus on page 2168. DhITACT-TR offers a robust diagnosis of target RNA pathogens in pseudo-serum specimens with minimum liquid handling as compared to conventional PCR analysis. In addition, a definitive diagnostic result can be achieved within 30 min by an optical detection.
The Potential Role of Ferritin in Relation to Inflammatory and Metabolic Syndrome Biomarkers in Patients Undergoing Total Joint Arthroplasty of the Hip or Knee
Authors: Christopher Wanderling, Jeffrey Liles, Peter Carlsgaard, Jennifer Saluk, Daneyal Syed, Schnettler Timothy, Nil Guler, William Hopkinson, Debra Hoppensteadt, Jawed Fareed
Journal: Blood (2015)
Contingent Fees and Malpractice
Authors: Robert F. McCabe
Journal: JAMA (1972)

To the Editor.—  I read, with much interest, Van Zante's LETTER with regard to contingent legal fees. The contingent fee system is certainly less than perfect. I feel sure that all attorneys would prefer to be paid on the basis of time spent and not on result accomplished. However, the contingent fee opens the courts to all who have been wronged, regardless of their ability to pay, and is far superior to the system which was suggested by Van Zante in his LETTER. The system he suggests closely follows the procedure in England where contingent fees are illegal.  The contingent fee system does deter baseless claims. I can think of no better way to prevent the institution of a meritless claim than to tell the lawyer that he will not be paid for his time and effort and may well be obligated to pay for the preparation of the case
Antibody-Interferon-Alpha Fusion Protein Therapy for the Treatment of B-Cell Non-Hodgkin Lymphoma: Enhanced ADCC, Inhibition of Proliferation, and In Vivo Eradication of CD20+ Human Lymphomas
Authors: John M. Timmerman, Kristopher K Steward, Reiko E Yamada, Patricia A Young, Dena M. Minning, Raj K Sachdev, Michael J Gresser, Sanjay D Khare, Sherie L Morrison
Journal: Blood (2015)
Performance of expressed prostatic secretion assays in prediction of surgical pathology outcomes in patients undergoing radical prostatectomy.
Authors: C. M. Whelan, J. P. Clark, T. G. Wilson, D. Y. Josephson, M. H. Kawachi, L. E. Crocitto, D. D. Smith, S. S. Smith
Journal: Journal of Clinical Oncology (2010)

4645 Background: Prostate cells released into expressed prostatic secretions (EPS) during prostatic massage are easily collected and analyzed. Prior work has shown EPS to perform well as a noninvasive test to predict prostate biopsy outcomes. We evaluate the utility of EPS biomarkers to predict surgical pathology outcomes in patients undergoing radical prostatectomy. Methods: We collected EPS specimens in a blinded prospective study from 138 men undergoing radical prostatectomy for prostate cancer. Specimens were obtained in the operating room under general anesthesia before commencing with radical prostatectomy. Specimens were analyzed for expression of GADH, PC3, Type III and VI TMPRSS2:ERG gene fusions using quantitative PCR. Their characteristic performance for predicting extracapsular extension (ECE) and Gleason sum on surgical pathology specimens was evaluated. These were compared to pre-biopsy PSA, biopsy Gleason sum and digital rectal exam (DRE) findings as predictors of surgical pathology outcomes. Results: The addition of GADH, PCA3, and TMPRSS fusion assays to prostate specific antigen (PSA), DRE, and biopsy gleason sum to predict ECE improved the area under the curve value (AUC) from .810, 95% CI 0.742-0.879; to .838, 95% CI 0.772-0.904. At 80% specificity for ECE, the baseline sensitivity using only DRE, PSA and biopsy Gleason sum was 66%. However, when TMPRSS2:ERG type III, type III+VI or PCA3 were added as predictors, the sensitivity was 71%, 71%, and 75% respectively. Based on these data, this test provides a 95% negative predictive value, compared to 93% for PSA, DRE and biopsy Gleason sum alone. Conclusions: The combination of biopsy Gleason sum and PSA correlate strongly with ECE. The addition of TMPRSS2:ERG and PCA3 markers as predictors improves the sensitivity and negative predictive value in predicting ECE. No significant financial relationships to disclose.
On the Neuroendocrinopathy of Critical Illness. Perspectives for Feeding and Novel Treatments
Authors: Greet Van den Berghe
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Section:ChooseTop of pageAbstract <<The GH AxisThe Pituitary–Thyroid Axi...The Pituitary–Adrenocorti...Reconciliation with Resul...ConclusionsReferencesCITING ARTICLES
Success in Meeting the Primary Endpoint in Phase III Trials: A Comparison of Industry and Cooperative Group Trials
Authors: Benjamin Djulbegovic, Ambuj Kumar, Branko Miladinovic, Asmita Mhaskar, Tea Reljic, Sanja Galeb, Rahul Mhaskar, Hozo Iztok, Dongsheng Tu, Heather Stanton, Christopher M Booth, Ralph M. Meyer
Journal: Blood (2011)