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1.  Melanoma and immunotherapy bridge 2015 
Nanda, Vashisht G. Y. | Peng, Weiyi | Hwu, Patrick | Davies, Michael A. | Ciliberto, Gennaro | Fattore, Luigi | Malpicci, Debora | Aurisicchio, Luigi | Ascierto, Paolo Antonio | Croce, Carlo M. | Mancini, Rita | Spranger, Stefani | Gajewski, Thomas F. | Wang, Yangyang | Ferrone, Soldano | Vanpouille-Box, Claire | Wennerberg, Erik | Pilones, Karsten A. | Formenti, Silvia C. | Demaria, Sandra | Tang, Haidong | Wang, Yang | Fu, Yang-Xin | Dummer, Reinhard | Puzanov, Igor | Tarhini, Ahmad | Chauvin, Joe-Marc | Pagliano, Ornella | Fourcade, Julien | Sun, Zhaojun | Wang, Hong | Sanders, Cindy | Kirkwood, John M. | Chen, Tseng-hui Timothy | Maurer, Mark | Korman, Alan J. | Zarour, Hassane M. | Stroncek, David F. | Huber, Veronica | Rivoltini, Licia | Thurin, Magdalena | Rau, Tilman | Lugli, Alessandro | Pagès, Franck | Camarero, Jorge | Sancho, Arantxa | Jommi, Claudio | de Coaña, Yago Pico | Wolodarski, Maria | Yoshimoto, Yuya | Gentilcore, Giusy | Poschke, Isabel | Masucci, Giuseppe V. | Hansson, Johan | Kiessling, Rolf | Scognamiglio, Giosuè | Sabbatino, Francesco | Marino, Federica Zito | Anniciello, Anna Maria | Cantile, Monica | Cerrone, Margherita | Scala, Stefania | D’alterio, Crescenzo | Ianaro, Angela | Cirin, Giuseppe | Liguori, Giuseppina | Bott, Gerardo | Chapman, Paul B. | Robert, Caroline | Larkin, James | Haanen, John B. | Ribas, Antoni | Hogg, David | Hamid, Omid | Testori, Alessandro | Lorigan, Paul | Sosman, Jeffrey A. | Flaherty, Keith T. | Yue, Huibin | Coleman, Shelley | Caro, Ivor | Hauschild, Axel | McArthur, Grant A. | Sznol, Mario | Callahan, Margaret K. | Kluger, Harriet | Postow, Michael A. | Gordan, RuthAnn | Segal, Neil H. | Rizvi, Naiyer A. | Lesokhin, Alexander | Atkins, Michael B. | Burke, Matthew M. | Ralabate, Amanda | Rivera, Angel | Kronenberg, Stephanie A. | Agunwamba, Blessing | Ruisi, Mary | Horak, Christine | Jiang, Joel | Wolchok, Jedd | Ascierto, Paolo A. | Liszkay, Gabriella | Maio, Michele | Mandalà, Mario | Demidov, Lev | Stoyakovskiy, Daniil | Thomas, Luc | de la Cruz-Merino, Luis | Atkinson, Victoria | Dutriaux, Caroline | Garbe, Claus | Wongchenko, Matthew | Chang, Ilsung | Koralek, Daniel O. | Rooney, Isabelle | Yan, Yibing | Dréno, Brigitte | Sullivan, Ryan | Patel, Manish | Hodi, Stephen | Amaria, Rodabe | Boasberg, Peter | Wallin, Jeffrey | He, Xian | Cha, Edward | Richie, Nicole | Ballinger, Marcus | Smith, David C. | Bauer, Todd M. | Wasser, Jeffrey S. | Luke, Jason J. | Balmanoukian, Ani S. | Kaufman, David R. | Zhao, Yufan | Maleski, Janet | Leopold, Lance | Gangadhar, Tara C. | Long, Georgina V. | Michielin, Olivier | VanderWalde, Ari | Andtbacka, Robert H. I. | Cebon, Jonathan | Fernandez, Eugenio | Malvehy, Josep | Olszanski, Anthony J. | Gause, Christine | Chen, Lisa | Chou, Jeffrey | Stephen Hodi, F. | Brady, Benjamin | Mortier, Laurent | Hassel, Jessica C. | Rutkowski, Piotr | McNeil, Catriona | Kalinka-Warzocha, Ewa | Lebbé, Celeste | Ny, Lars | Chacon, Matias | Queirolo, Paola | Loquai, Carmen | Cheema, Parneet | Berrocal, Alfonso | Eizmendi, Karmele Mujika | Bar-Sela, Gil | Horak, Christine | Hardy, Helene | Weber, Jeffrey S. | Grob, Jean-Jacques | Marquez-Rodas, Ivan | Schmidt, Henrik | Briscoe, Karen | Baurain, Jean-François | Wolchok, Jedd D. | Pinto, Rosamaria | De Summa, Simona | Garrisi, Vito Michele | Strippoli, Sabino | Azzariti, Amalia | Guida, Gabriella | Guida, Michele | Tommasi, Stefania | Jacquelot, Nicolas | Enot, David | Flament, Caroline | Pitt, Jonathan M. | Vimond, Nadège | Blattner, Carolin | Yamazaki, Takahiro | Roberti, Maria-Paula | Vetizou, Marie | Daillere, Romain | Poirier-Colame, Vichnou | la Semeraro, Michaë | Caignard, Anne | Slingluff, Craig L | Sallusto, Federica | Rusakiewicz, Sylvie | Weide, Benjamin | Marabelle, Aurélien | Kohrt, Holbrook | Dalle, Stéphane | Cavalcanti, Andréa | Kroemer, Guido | Di Giacomo, Anna Maria | Maio, Michaele | Wong, Phillip | Yuan, Jianda | Umansky, Viktor | Eggermont, Alexander | Zitvogel, Laurence | Anna, Passarelli | Marco, Tucci | Stefania, Stucci | Francesco, Mannavola | Mariaelena, Capone | Gabriele, Madonna | Antonio, Ascierto Paolo | Franco, Silvestris | Roberti, María Paula | Enot, David P. | Semeraro, Michaela | Jégou, Sarah | Flores, Camila | Chen, Tseng-hui Timothy | Kwon, Byoung S. | Anderson, Ana Carrizossa | Borg, Christophe | Aubin, François | Ayyoub, Maha | De Presbiteris, Anna Lisa | Cordaro, Fabiola Gilda | Camerlingo, Rosa | Fratangelo, Federica | Mozzillo, Nicola | Pirozzi, Giuseppe | Patriarca, Eduardo J. | Caputo, Emilia | Motti, Maria Letizia | Falcon, Rosaria | Miceli, Roberta | Capone, Mariaelena | Madonna, Gabriele | Mallardo, Domenico | Carrier, Maria Vincenza | Panza, Elisabetta | De Cicco, Paola | Armogida, Chiara | Ercolano, Giuseppe | Botti, Gerardo | Cirino, Giuseppe | Sandru, Angela | Blank, Miri | Balatoni, Timea | Olasz, Judit | Farkas, Emil | Szollar, Andras | Savolt, Akos | Godeny, Maria | Csuka, Orsolya | Horvath, Szabolcs | Eles, Klara | Shoenfeld, Yehuda | Kasler, Miklos | Costantini, Susan | Capone, Francesca | Moradi, Farnaz | Berglund, Pontus | Leandersson, Karin | Linnskog, Rickard | Andersson, Tommy | Prasad, Chandra Prakash | Nigro, Cristiana Lo | Lattanzio, Laura | Wang, Hexiao | Proby, Charlotte | Syed, Nelofer | Occelli, Marcella | Cauchi, Carolina | Merlano, Marco | Harwood, Catherine | Thompson, Alastair | Crook, Tim | Bifulco, Katia | Ingangi, Vincenzo | Minopoli, Michele | Ragone, Concetta | Pessi, Antonello | Mannavola, Francesco | D’Oronzo, Stella | Felici, Claudia | Tucci, Marco | Doronzo, Antonio | Silvestris, Franco | Ferretta, Anna | Guida, Stefania | Maida, Imma | Cocco, Tiziana | Passarelli, Anna | Quaresmini, Davide | Franzese, Ornella | Palermo, Belinda | Di Donna, Cosmo | Sperduti, Isabella | Foddai, MariaLaura | Stabile, Helena | Gismondi, Angela | Santoni, Angela | Nisticò, Paola | Sponghini, Andrea P. | Platini, Francesca | Marra, Elena | Rondonotti, David | Alabiso, Oscar | Fierro, Maria T. | Savoia, Paola | Stratica, Florian | Quaglino, Pietro |  Di Monta, Gianluca | Corrado, Caracò |  Di Marzo, Massimiliano | Ugo, Marone |  Di Cecilia, Maria Luisa | Nicola, Mozzillo | Fusciello, Celeste | Marra, Antonio | Guarrasi, Rosario | Baldi, Carlo | Russo, Rosa |  Di Giulio, Giovanni | Faiola, Vincenzo | Zeppa, Pio | Pepe, Stefano | Gambale, Elisabetta | Carella, Consiglia | Di Paolo, Alessandra | De Tursi, Michele | Marra, Laura | De Murtas, Fara | Sorrentino, Valeria | Voinea, Silviu | Panaitescu, Eugenia | Bolovan, Madalina | Stanciu, Adina | Cinca, Sabin | Botti, Chiara | Aquino, Gabriella | Anniciello, Annamaria | Fortes, Cristina | Mastroeni, Simona | Caggiati, Alessio | Passarelli, Francesca | Zappalà, Alba | Capuano, Maria | Bono, Riccardo | Nudo, Maurizio | Marino, Claudia | Michelozzi, Paola | De Biasio, Valeria | Battarra, Vincenzo C. | Formenti, Silvia | Ascierto, Maria Libera | McMiller, Tracee L. | Berger, Alan E. | Danilova, Ludmila | Anders, Robert A. | Netto, George J. | Xu, Haiying | Pritchard, Theresa S. | Fan, Jinshui | Cheadle, Chris | Cope, Leslie | Drake, Charles G. | Pardoll, Drew M. | Taube, Janis M. | Topalian, Suzanne L. | Gnjatic, Sacha | Nataraj, Sarah | Imai, Naoko | Rahman, Adeeb | Jungbluth, Achim A. | Pan, Linda | Venhaus, Ralph | Park, Andrew | Lehmann, Frédéric F. | Lendvai, Nikoletta | Cohen, Adam D. | Cho, Hearn J. | Daniel, Speiser | Hirsh, Vera
Journal of Translational Medicine  2016;14(Suppl 1):65.
Table of contents
MELANOMA BRIDGE 2015
KEYNOTE SPEAKER PRESENTATIONS
Molecular and immuno-advances
K1 Immunologic and metabolic consequences of PI3K/AKT/mTOR activation in melanoma
Vashisht G. Y. Nanda, Weiyi Peng, Patrick Hwu, Michael A. Davies
K2 Non-mutational adaptive changes in melanoma cells exposed to BRAF and MEK inhibitors help the establishment of drug resistance
Gennaro Ciliberto, Luigi Fattore, Debora Malpicci, Luigi Aurisicchio, Paolo Antonio Ascierto, Carlo M. Croce, Rita Mancini
K3 Tumor-intrinsic beta-catenin signaling mediates tumor-immune avoidance
Stefani Spranger, Thomas F. Gajewski
K4 Intracellular tumor antigens as a source of targets of antibody-based immunotherapy of melanoma
Yangyang Wang, Soldano Ferrone
Combination therapies
K5 Harnessing radiotherapy to improve responses to immunotherapy in cancer
Claire Vanpouille-Box, Erik Wennerberg, Karsten A. Pilones, Silvia C. Formenti, Sandra Demaria
K6 Creating a T cell-inflamed tumor microenvironment overcomes resistance to checkpoint blockade
Haidong Tang, Yang Wang, Yang-Xin Fu
K7 Biomarkers for treatment decisions?
Reinhard Dummer
K8 Combining oncolytic therapies in the era of checkpoint inhibitors
Igor Puzanov
K9 Immune checkpoint blockade for melanoma: should we combine or sequence ipilimumab and PD-1 antibody therapy?
Michael A. Postow
News in immunotherapy
K10 An update on adjuvant and neoadjuvant therapy for melanom
Ahmad Tarhini
K11 Targeting multiple inhibitory receptors in melanoma
Joe-Marc Chauvin, Ornella Pagliano, Julien Fourcade, Zhaojun Sun, Hong Wang, Cindy Sanders, John M. Kirkwood, Tseng-hui Timothy Chen, Mark Maurer, Alan J. Korman, Hassane M. Zarour
K12 Improving adoptive immune therapy using genetically engineered T cells
David F. Stroncek
Tumor microenvironment and biomarkers
K13 Myeloid cells and tumor exosomes: a crosstalk for assessing immunosuppression?
Veronica Huber, Licia Rivoltini
K14 Update on the SITC biomarker taskforce: progress and challenges
Magdalena Thurin
World-wide immunoscore task force: an update
K15 The immunoscore in colorectal cancer highlights the importance of digital scoring systems in surgical pathology
Tilman Rau, Alessandro Lugli
K16 The immunoscore: toward an integrated immunomonitoring from the diagnosis to the follow up of cancer’s patients
Franck Pagès
Economic sustainability of melanoma treatments: regulatory, health technology assessment and market access issues
K17 Nivolumab, the regulatory experience in immunotherapy
Jorge Camarero, Arantxa Sancho
K18 Evidence to optimize access for immunotherapies
Claudio Jommi
ORAL PRESENTATIONS
Molecular and immuno-advances
O1 Ipilimumab treatment results in CD4 T cell activation that is concomitant with a reduction in Tregs and MDSCs
Yago Pico de Coaña, Maria Wolodarski, Yuya Yoshimoto, Giusy Gentilcore, Isabel Poschke, Giuseppe V. Masucci, Johan Hansson, Rolf Kiessling
O2 Evaluation of prognostic and therapeutic potential of COX-2 and PD-L1 in primary and metastatic melanoma
Giosuè Scognamiglio, Francesco Sabbatino, Federica Zito Marino, Anna Maria Anniciello, Monica Cantile, Margherita Cerrone, Stefania Scala, Crescenzo D’alterio, Angela Ianaro, Giuseppe Cirino, Paolo Antonio Ascierto, Giuseppina Liguori, Gerardo Botti
O3 Vemurafenib in patients with BRAFV600 mutation–positive metastatic melanoma: final overall survival results of the BRIM-3 study
Paul B. Chapman, Caroline Robert, James Larkin, John B. Haanen, Antoni Ribas, David Hogg, Omid Hamid, Paolo Antonio Ascierto, Alessandro Testori, Paul Lorigan, Reinhard Dummer, Jeffrey A. Sosman, Keith T. Flaherty, Huibin Yue, Shelley Coleman, Ivor Caro, Axel Hauschild, Grant A. McArthur
O4 Updated survival, response and safety data in a phase 1 dose-finding study (CA209-004) of concurrent nivolumab (NIVO) and ipilimumab (IPI) in advanced melanoma
Mario Sznol, Margaret K. Callahan, Harriet Kluger, Michael A. Postow, RuthAnn Gordan, Neil H. Segal, Naiyer A. Rizvi, Alexander Lesokhin, Michael B. Atkins, John M. Kirkwood, Matthew M. Burke, Amanda Ralabate, Angel Rivera, Stephanie A. Kronenberg, Blessing Agunwamba, Mary Ruisi, Christine Horak, Joel Jiang, Jedd Wolchok
Combination therapies
O5 Efficacy and correlative biomarker analysis of the coBRIM study comparing cobimetinib (COBI) + vemurafenib (VEM) vs placebo (PBO) + VEM in advanced BRAF-mutated melanoma patients (pts)
Paolo A. Ascierto, Grant A. McArthur, James Larkin, Gabriella Liszkay, Michele Maio, Mario Mandalà, Lev Demidov, Daniil Stoyakovskiy, Luc Thomas, Luis de la Cruz-Merino, Victoria Atkinson, Caroline Dutriaux, Claus Garbe, Matthew Wongchenko, Ilsung Chang, Daniel O. Koralek, Isabelle Rooney, Yibing Yan, Antoni Ribas, Brigitte Dréno
O6 Preliminary clinical safety, tolerability and activity results from a Phase Ib study of atezolizumab (anti-PDL1) combined with vemurafenib in BRAFV600-mutant metastatic melanoma
Ryan Sullivan, Omid Hamid, Manish Patel, Stephen Hodi, Rodabe Amaria, Peter Boasberg, Jeffrey Wallin, Xian He, Edward Cha, Nicole Richie, Marcus Ballinger, Patrick Hwu
O7 Preliminary safety and efficacy data from a phase 1/2 study of epacadostat (INCB024360) in combination with pembrolizumab in patients with advanced/metastatic melanoma
Thomas F. Gajewski, Omid Hamid, David C. Smith, Todd M. Bauer, Jeffrey S. Wasser, Jason J. Luke, Ani S. Balmanoukian, David R. Kaufman, Yufan Zhao, Janet Maleski, Lance Leopold, Tara C. Gangadhar
O8 Primary analysis of MASTERKEY-265 phase 1b study of talimogene laherparepvec (T-VEC) and pembrolizumab (pembro) for unresectable stage IIIB-IV melanoma
Reinhard Dummer, Georgina V. Long, Antoni Ribas, Igor Puzanov, Olivier Michielin, Ari VanderWalde, Robert H.I. Andtbacka, Jonathan Cebon, Eugenio Fernandez, Josep Malvehy, Anthony J. Olszanski, Thomas F. Gajewski, John M. Kirkwood, Christine Gause, Lisa Chen, David R. Kaufman, Jeffrey Chou, F. Stephen Hodi
News in immunotherapy
O9 Two-year survival and safety update in patients (pts) with treatment-naïve advanced melanoma (MEL) receiving nivolumab (NIVO) or dacarbazine (DTIC) in CheckMate 066
Victoria Atkinson, Paolo A. Ascierto, Georgina V. Long, Benjamin Brady, Caroline Dutriaux, Michele Maio, Laurent Mortier, Jessica C. Hassel, Piotr Rutkowski, Catriona McNeil, Ewa Kalinka-Warzocha, Celeste Lebbé, Lars Ny, Matias Chacon, Paola Queirolo, Carmen Loquai, Parneet Cheema, Alfonso Berrocal, Karmele Mujika Eizmendi, Luis De La Cruz-Merino, Gil Bar-Sela, Christine Horak, Joel Jiang, Helene Hardy, Caroline Robert
O10 Efficacy and safety of nivolumab (NIVO) in patients (pts) with advanced melanoma (MEL) who were treated beyond progression in CheckMate 066/067
Georgina V. Long, Jeffrey S. Weber, James Larkin, Victoria Atkinson, Jean-Jacques Grob, Reinhard Dummer, Caroline Robert, Ivan Marquez-Rodas, Catriona McNeil, Henrik Schmidt, Karen Briscoe, Jean-François Baurain, F. Stephen Hodi, Jedd D. Wolchok
Tumor microenvironment and biomarkers
O11 New biomarkers for response/resistance to BRAF inhibitor therapy in metastatic melanoma
Rosamaria Pinto, Simona De Summa, Vito Michele Garrisi, Sabino Strippoli, Amalia Azzariti, Gabriella Guida, Michele Guida, Stefania Tommasi
O12 Chemokine receptor patterns in lymphocytes mirror metastatic spreading in melanoma and response to ipilimumab
Nicolas Jacquelot, David Enot, Caroline Flament, Jonathan M. Pitt, Nadège Vimond, Carolin Blattner, Takahiro Yamazaki, Maria-Paula Roberti, Marie Vetizou, Romain Daillere, Vichnou Poirier-Colame, Michaëla Semeraro, Anne Caignard, Craig L Slingluff Jr, Federica Sallusto, Sylvie Rusakiewicz, Benjamin Weide, Aurélien Marabelle, Holbrook Kohrt, Stéphane Dalle, Andréa Cavalcanti, Guido Kroemer, Anna Maria Di Giacomo, Michaele Maio, Phillip Wong, Jianda Yuan, Jedd Wolchok, Viktor Umansky, Alexander Eggermont, Laurence Zitvogel
O13 Serum levels of PD1- and CD28-positive exosomes before Ipilimumab correlate with therapeutic response in metastatic melanoma patients
Passarelli Anna, Tucci Marco, Stucci Stefania, Mannavola Francesco, Capone Mariaelena, Madonna Gabriele, Ascierto Paolo Antonio, Silvestris Franco
O14 Immunological prognostic factors in stage III melanomas
María Paula Roberti, Nicolas Jacquelot, David P Enot, Sylvie Rusakiewicz, Michaela Semeraro, Sarah Jégou, Camila Flores, Lieping Chen, Byoung S. Kwon, Ana Carrizossa Anderson, Caroline Robert, Christophe Borg, Benjamin Weide, François Aubin, Stéphane Dalle, Michele Maio, Jedd D. Wolchok, Holbrook Kohrt, Maha Ayyoub, Guido Kroemer, Aurélien Marabelle, Andréa Cavalcanti, Alexander Eggermont, Laurence Zitvogel
POSTER PRESENTATIONS
Molecular and immuno-advances
P1 Human melanoma cells resistant to B-RAF and MEK inhibition exhibit mesenchymal-like features
Anna Lisa De Presbiteris, Fabiola Gilda Cordaro, Rosa Camerlingo, Federica Fratangelo, Nicola Mozzillo, Giuseppe Pirozzi, Eduardo J. Patriarca, Paolo A. Ascierto, Emilia Caputo
P2 Anti-proliferative and pro-apoptotic effect of ABT888 on melanoma cell lines and its potential role in the treatment of melanoma resistant to B-RAF inhibitors
Federica Fratangelo, Rosa Camerlingo, Emilia Caputo, Maria Letizia Motti, Rosaria Falcone, Roberta Miceli, Mariaelena Capone, Gabriele Madonna, Domenico Mallardo, Maria Vincenza Carriero, Giuseppe Pirozzi and Paolo Antonio Ascierto
P3 Involvement of the L-cysteine/CSE/H2S pathway in human melanoma progression
Elisabetta Panza, Paola De Cicco, Chiara Armogida, Giuseppe Ercolano, Rosa Camerlingo, Giuseppe Pirozzi, Giosuè Scognamiglio, Gerardo Botti, Giuseppe Cirino, Angela Ianaro
P4 Cancer stem cell antigen revealing pattern of antibody variable region genes were defined by immunoglobulin repertoire analysis in patients with malignant melanoma
Beatrix Kotlan, Gabriella Liszkay, Miri Blank, Timea Balatoni, Judit Olasz, Emil Farkas, Andras Szollar, Akos Savolt, Maria Godeny, Orsolya Csuka, Szabolcs Horvath, Klara Eles, Yehuda Shoenfeld and Miklos Kasler
P5 Upregulation of Neuregulin-1 expression is a hallmark of adaptive response to BRAF/MEK inhibitors in melanoma
Debora Malpicci, Luigi Fattore, Susan Costantini, Francesca Capone, Paolo Antonio Ascierto, Rita Mancini, Gennaro Ciliberto
P6 HuR positively regulates migration of HTB63 melanoma cells
Farnaz Moradi, Pontus Berglund, Karin Leandersson, Rickard Linnskog, Tommy Andersson, Chandra Prakash Prasad
P7 Prolyl 4- (C-P4H) hydroxylases have opposing effects in malignant melanoma: implication in prognosis and therapy
Cristiana Lo Nigro, Laura Lattanzio, Hexiao Wang, Charlotte Proby, Nelofer Syed, Marcella Occelli, Carolina Cauchi, Marco Merlano, Catherine Harwood, Alastair Thompson, Tim Crook
P8 Urokinase receptor antagonists: novel agents for the treatment of melanoma
Maria Letizia Motti, Katia Bifulco, Vincenzo Ingangi, Michele Minopoli, Concetta Ragone, Federica Fratangelo, Antonello Pessi, Gennaro Ciliberto, Paolo Antonio Ascierto, Maria Vincenza Carriero
P9 Exosomes released by melanoma cell lines enhance chemotaxis of primary tumor cells
Francesco Mannavola, Stella D’Oronzo, Claudia Felici, Marco Tucci, Antonio Doronzo, Franco Silvestris
P10 New insights in mitochondrial metabolic reprogramming in melanoma
Anna Ferretta, Gabriella Guida, Stefania Guida, Imma Maida, Tiziana Cocco, Sabino Strippoli, Stefania Tommasi, Amalia Azzariti, Michele Guida
P11 Lenalidomide restrains the proliferation in melanoma cells through a negative regulation of their cell cycle
Stella D’Oronzo, Anna Passarelli, Claudia Felici, Marco Tucci, Davide Quaresmini, Franco Silvestris
Combination therapies
P12 Chemoimmunotherapy elicits polyfunctional anti-tumor CD8 + T cells depending on the activation of an AKT pathway sustained by ICOS
Ornella Franzese, Belinda Palermo, Cosmo Di Donna, Isabella Sperduti, MariaLaura Foddai, Helena Stabile, Angela Gismondi, Angela Santoni, Paola Nisticò
P13 Favourable toxicity profile of combined BRAF and MEK inhibitors in metastatic melanoma patients
Andrea P. Sponghini, Francesca Platini, Elena Marra, David Rondonotti, Oscar Alabiso, Maria T. Fierro, Paola Savoia, Florian Stratica, Pietro Quaglino
P14 Electrothermal bipolar vessel sealing system dissection reduces seroma output or time to drain removal following axillary and ilio-inguinal node dissection in melanoma patients: a pilot study
Di Monta Gianluca, Caracò Corrado, Di Marzo Massimiliano, Marone Ugo, Di Cecilia Maria Luisa, Mozzillo Nicola
News in immunotherapy
P15 Clinical and immunological response to ipilimumab in a metastatic melanoma patient with HIV infection
Francesco Sabbatino, Celeste Fusciello1, Antonio Marra, Rosario Guarrasi, Carlo Baldi, Rosa Russo, Di Giulio Giovanni, Vincenzo Faiola, Pio Zeppa, Stefano Pepe
P16 Immunotherapy and hypophysitis: a case report
Elisabetta Gambale, Consiglia Carella, Alessandra Di Paolo, Michele De Tursi
Tumor microenvironment and biomarkers
P17 New immuno- histochemical markers for the differential diagnosis of atypical melanocytic lesions with uncertain malignant potential
Laura Marra, Giosuè Scognamiglio, Monica Cantile, Margherita Cerrone, Fara De Murtas, Valeria Sorrentino, Anna Maria Anniciello, Gerardo Botti
P18 Utility of simultaneous measurement of three serum tumor markers in melanoma patients
Angela Sandru, Silviu Voinea, Eugenia Panaitescu, Madalina Bolovan, Adina Stanciu, Sabin Cinca
P19 The significance of various cut-off levels of melanoma inhibitory activity in evaluation of cutaneous melanoma patients
Angela Sandru, Silviu Voinea, Eugenia Panaitescu, Madalina Bolovan, Adina Stanciu, Sabin Cinca
P20 The long noncoding RNA HOTAIR is associated to metastatic progression of melanoma and it can be identified in the blood of patients with advanced disease
Chiara Botti, Giosuè Scognamiglio, Laura Marra, Gabriella Aquino, Rosaria Falcone, Annamaria Anniciello, Paolo Antonio Ascierto, Gerardo Botti, Monica Cantile
Other
P21 The effect of Sentinel Lymph Node Biopsy in melanoma mortality: timing of dissection
Cristina Fortes, Simona Mastroeni, Alessio Caggiati, Francesca Passarelli, Alba Zappalà, Maria Capuano, Riccardo Bono, Maurizio Nudo, Claudia Marino, Paola Michelozzi
P22 Epidemiological survey on related psychopathology in melanoma
Valeria De Biasio, Vincenzo C. Battarra
IMMUNOTHERAPY BRIDGE
KEYNOTE SPEAKER PRESENTATIONS
Immunotherapy beyond melanoma
K19 Predictor of response to radiation and immunotherapy
Silvia Formenti
K20 Response and resistance to PD-1 pathway blockade: clues from the tumor microenvironment
Maria Libera Ascierto, Tracee L. McMiller, Alan E. Berger, Ludmila Danilova, Robert A. Anders, George J. Netto, Haiying Xu, Theresa S. Pritchard, Jinshui Fan, Chris Cheadle, Leslie Cope, Charles G. Drake, Drew M. Pardoll, Janis M. Taube and Suzanne L. Topalian
K21 Combination immunotherapy with autologous stem cell transplantation, protein immunization, and PBMC reinfusion in myeloma patients
Sacha Gnjatic, Sarah Nataraj, Naoko Imai, Adeeb Rahman, Achim A. Jungbluth, Linda Pan, Ralph Venhaus, Andrew Park, Frédéric F. Lehmann, Nikoletta Lendvai, Adam D. Cohen, and Hearn J. Cho
K22 Anti-cancer immunity despite T cell “exhaustion”
Speiser Daniel
Immunotherapy in oncology (I-O): data from clinical trial
K23 The Checkpoint Inhibitors for the Treatment of Metastatic Non-small Cell Lung Cancer (NSCLC)
Vera Hirsh
doi:10.1186/s12967-016-0791-2
PMCID: PMC4965835  PMID: 27461275
2.  Pharmacy-based Immunization in Rural Communities Strategy (PhICS) 
Background:
Influenza is a major cause of morbidity and mortality in Canada, with up to 7000 influenza-related deaths occurring every year. The elderly and individuals with chronic diseases are at increased risk for influenza-related morbidity and mortality.
Methods:
We conducted a 2-year, community cluster-randomized trial targeting elderly people and at-risk groups to assess the effectiveness of pharmacy-based influenza vaccination clinics on influenza vaccination rates. Small rural communities in interior and northern British Columbia were randomly allocated to the intervention or control. In the intervention communities, pharmacy-based influenza vaccination clinics were held and were promoted to eligible patients using personalized invitations from the pharmacists, invitations distributed opportunistically by a pharmacist to eligible patients presenting to pharmacies during the flu season and community-wide promotion using posters and the local media. The main outcome measure was a difference in the mean influenza vaccination rates. The immunization rates were calculated using the number of immunizations given in each community divided by the population size estimated from the census data.
Results:
Baseline influenza immunization rates in the population ≥65 years of age were the same in the control (n = 10, mean 85.6% [SD 16.6]) and intervention (n = 14, mean 83.8% [SD 16.3]) communities in 2009 (p = 0.79). In 2010, the mean influenza immunization rate was 56.9% (SD 28.0) in the control communities (n = 15) and 80.1% (SD 18.4) in the intervention communities (n = 14) (p = 0.01) for those ≥65 years of age. However, in 2010, for those 2 to 64 years with chronic medical conditions, the immunization rates were lower in the intervention communities (mean 16.3% [SD 7.1]) compared with the control communities (mean 21.2% [SD 5.8]) (p = 0.04).
Conclusion
Clinics were feasible and well attended and they resulted in increased vaccination rates for elderly residents. In contrast, vaccination rates in the younger population with comorbidities remained low and unchanged.
doi:10.1177/1715163513514020
PMCID: PMC3908619  PMID: 24494014
3.  Genomic testing to determine drug response: measuring preferences of the public and patients using Discrete Choice Experiment (DCE) 
Background
The extent to which a genomic test will be used in practice is affected by factors such as ability of the test to correctly predict response to treatment (i.e. sensitivity and specificity of the test), invasiveness of the testing procedure, test cost, and the probability and severity of side effects associated with treatment.
Methods
Using discrete choice experimentation (DCE), we elicited preferences of the public (Sample 1, N = 533 and Sample 2, N = 525) and cancer patients (Sample 3, N = 38) for different attributes of a hypothetical genomic test for guiding cancer treatment. Samples 1 and 3 considered the test/treatment in the context of an aggressive curable cancer (scenario A) while the scenario for sample 2 was based on a non-aggressive incurable cancer (scenario B).
Results
In aggressive curable cancer (scenario A), everything else being equal, the odds ratio (OR) of choosing a test with 95% sensitivity was 1.41 (versus a test with 50% sensitivity) and willingness to pay (WTP) was $1331, on average, for this amount of improvement in test sensitivity. In this scenario, the OR of choosing a test with 95% specificity was 1.24 times that of a test with 50% specificity (WTP = $827). In non-aggressive incurable cancer (scenario B), the OR of choosing a test with 95% sensitivity was 1.65 (WTP = $1344), and the OR of choosing a test with 95% specificity was 1.50 (WTP = $1080). Reducing severity of treatment side effects from severe to mild was associated with large ORs in both scenarios (OR = 2.10 and 2.24 in scenario A and B, respectively). In contrast, patients had a very large preference for 95% sensitivity of the test (OR = 5.23).
Conclusion
The type and prognosis of cancer affected preferences for genomically-guided treatment. In aggressive curable cancer, individuals emphasized more on the sensitivity rather than the specificity of the test. In contrast, for a non-aggressive incurable cancer, individuals put similar emphasis on sensitivity and specificity of the test. While the public expressed strong preference toward lowering severity of side effects, improving sensitivity of the test had by far the largest influence on patients’ decision to use genomic testing.
doi:10.1186/1472-6963-13-454
PMCID: PMC3827922  PMID: 24176050
Pharmacogenomics; Genomic medicine; Personalized medicine; Genetic testing; Discrete choice experiment; Conjoint analysis; Preference elicitation; Cancer treatment
4.  Antibiotic consumption in children prior to diagnosis of asthma 
Background
Asthma is difficult to diagnose in children and at times misdiagnosis of an infection can occur. However, little is known about the magnitude and patterns of antibiotic consumption in children with asthma relative to those without asthma.
Methods
Using population-based data, 128,872 children were identified with at least 6 years of follow-up. The adjusted rate-ratio (RR) of antibiotics dispensed to asthmatic as compared to non-asthmatic children was determined.
Results
At age six, the RR of antibiotic consumption for asthmatics compared to non-asthmatics varied between, 1.66 to 2.32, depending on the year of asthma diagnosis. Of the 18,864 children with asthma at ages 2-8, 52% (n = 9,841) had antibiotics dispensed in the 6 months prior to their index date of asthma diagnosis. The RR of antibiotic consumption in the 1 month prior to asthma diagnosis compared to 5 months prior was 1.66 (95% CI 1.60-1.71). The RR was lower in males compared to females (1.58 vs 1.77), and lower in those who received antibiotics in the first year of life relative to those that did not (1.60 vs. 1.76).
Conclusions
There is higher antibiotic consumption in children with asthma compared to those without asthma. The pattern of antibiotic use suggests that diagnosis guidelines are difficult to follow in young children leading to misdiagnosis and over treatment with antibiotics.
doi:10.1186/1471-2466-11-32
PMCID: PMC3118389  PMID: 21627795
5.  Responses to Comments of Weis 
A response to Weis and Pasipanodya 'Measuring health-related quality of life in tuberculosis: a systemic review - Response'.
doi:10.1186/1477-7525-8-6
PMCID: PMC2821369  PMID: 20074383
6.  Measuring health-related quality of life in tuberculosis: a systematic review 
Introduction
Tuberculosis remains a major public health problem worldwide. In recent years, increasing efforts have been dedicated to assessing the health-related quality of life experienced by people infected with tuberculosis. The objectives of this study were to better understand the impact of tuberculosis and its treatment on people's quality of life, and to review quality of life instruments used in current tuberculosis research.
Methods
A systematic literature search from 1981 to 2008 was performed through a number of electronic databases as well as a manual search. Eligible studies assessed multi-dimensional quality of life in people with tuberculosis disease or infection using standardized instruments. Results of the included studies were summarized qualitatively.
Results
Twelve original studies met our criteria for inclusion. A wide range of quality of life instruments were involved, and the Short-Form 36 was most commonly used. A validated tuberculosis-specific quality of life instrument was not located. The findings showed that tuberculosis had a substantial and encompassing impact on patients' quality of life. Overall, the anti-tuberculosis treatment had a positive effect of improving patients' quality of life; their physical health tended to recover more quickly than the mental well-being. However, after the patients successfully completed treatment and were microbiologically 'cured', their quality of life remained significantly worse than the general population.
Conclusion
Tuberculosis has substantially adverse impacts on patients' quality of life, which persist after microbiological 'cure'. A variety of instruments were used to assess quality of life in tuberculosis and there has been no well-established tuberculosis-specific instrument, making it difficult to fully understand the impact of the illness.
doi:10.1186/1477-7525-7-14
PMCID: PMC2651863  PMID: 19224645
7.  Factors influencing quality of life in patients with active tuberculosis 
Background
With effective treatment strategies, the focus of tuberculosis (TB) management has shifted from the prevention of mortality to the avoidance of morbidity. As such, there should be an increased focus on quality of life (QoL) experienced by individuals being treated for TB. The objective of our study was to identify areas of QoL that are affected by active TB using focus groups and individual interviews.
Methods
English, Cantonese, and Punjabi-speaking subjects with active TB who were receiving treatment were eligible for recruitment into the study. Gender-based focus group sessions were conducted for the inner city participants but individual interviews were conducted for those who came to the main TB clinic or were hospitalized. Facilitators used open-ended questions and participants were asked to discuss their experiences of being diagnosed with tuberculosis, what impact it had on their lives, issues around adherence to anti-TB medications and information pertaining to their experience with side effects to these medications. All data were audio-recorded, transcribed verbatim, and analyzed using constant comparative analysis.
Results
39 patients with active TB participated. The mean age was 46.2 years (SD 18.4) and 62% were male. Most were Canadian-born being either Caucasian or Aboriginal. Four themes emerged from the focus groups and interviews. The first describes issues related to the diagnosis of tuberculosis and sub-themes were identified as 'symptoms', 'health care provision', and 'emotional impact'. The second theme discusses TB medication factors and the sub-themes identified were 'adverse effects', 'ease of administration', and 'adherence'. The third theme describes social support and functioning issues for the individuals with TB. The fourth theme describes health behavior issues for the individuals with TB and the identified sub-themes were "behavior modification" and "TB knowledge."
Conclusion
Despite the ability to cure TB, there remains a significant impact on QOL. Since much attention is spent on preventative or curative mechanisms, the impact of this condition on QoL is often not considered. Attention to the issues experienced by patients being treated for TB may optimize adherence and treatment success.
doi:10.1186/1477-7525-2-58
PMCID: PMC526389  PMID: 15496227
8.  Cost effectiveness analysis of azithromycin and doxycycline for Chlamydia trachomatis infection in women: A Canadian perspective 
OBJECTIVE:
To assess the cost effectiveness of azithromycin versus doxycycline therapy for cervical Chlamydia trachomatis infections in Canada.
DESIGN:
A predictive decision analytic model using previously published clinical and economic evaluations, expert opinion and costs of medical care in Canada.
POPULATION:
A hypothetical cohort of 5000 women followed over 10 years.
INTERVENTIONS:
Two diagnostic strategies were compared, laboratory confirmed diagnosis (LCD) and presumptive diagnosis (PD) of C trachomatis infection. Under each strategy, two treatment alternatives were analyzed, a single 1 g dose of azithromycin and a seven-day course of doxycycline as 100 mg twice daily.
RESULTS:
Despite a fourfold higher acquisition cost, under base case conditions, for both diagnostic strategies, the azithromycin treatment alternative was more cost effective than the doxycycline alternative. For the LCD model, the cost per cure for patients receiving azithromycin was $184.76 compared with $240.59 for patients receiving doxycycline, resulting in an incremental cost of $55.83. For the PD model, the cost per cure for patients treated with azithromycin was $51.48 compared with $51.82, resulting in an incremental cost of $0.34. For the hypothetical cohort of 5000 women, the use of azithromycin translates into a projected annual cost savings of $279,150 and $1,700 for the LCD and PD models, respectively. In one-way sensitivity analyses for the LCD model, no clinically plausible changes in the base case estimates changed the results of the cost effectiveness outcome. In the PD model, clinically plausible changes in the probabilities of doxycycline cure, pelvic inflammatory disease, sequelae and chlamydia infection were found to alter the cost effectiveness outcome.
CONCLUSIONS:
Based on the results from our model, the azithromycin strategy should be employed for the treatment of laboratory confirmed cases. However, for presumptive cases, azithromycin should be used only if the probabilities of C trachomatis and pelvic inflammatory disease are more than 19%, doxycycline effectiveness is less than 78%, or the cost of azithromycin is less than $19.00.
PMCID: PMC3250882  PMID: 22346517
Azithromycin; Chlamydia trachomatis; Doxycycline; Pharmacoeconomics
9.  Genome-wide meta-analyses identify three loci associated with primary biliary cirrhosis 
Nature genetics  2010;42(8):658-660.
A genome-wide association screen for primary biliary cirrhosis risk alleles was performed in an Italian cohort. The results from the Italian cohort replicated IL12A and IL12RB associations, and a combined meta-analysis using a Canadian dataset identified newly associated loci at SPIB (P = 7.9 × 10–11, odds ratio (OR) = 1.46), IRF5-TNPO3 (P = 2.8 × 10–10, OR = 1.63) and 17q12-21 (P = 1.7 × 10–10, OR = 1.38).
doi:10.1038/ng.627
PMCID: PMC3150510  PMID: 20639880
10.  Treatment of focal benign lesions of the bone: MRgFUS and RFA 
The British Journal of Radiology  null;89(1066):20150356.
The objective of this study was to evaluate the role of MR-guided focused ultrasound surgery and radiofrequency ablation in the management of bone and soft-tissue lesions. Musculoskeletal interventional radiology represents an interesting option for the treatment of benign bone and soft-tissue lesions to avoid the invasiveness of surgery and related risks. The imaging techniques now available, besides representing an optimal guide, allow control of the temperature reached in the region of interest, avoiding or minimizing damage to the sensitive structures surrounding the lesion.
doi:10.1259/bjr.20150356
PMCID: PMC5124790  PMID: 27197743
11.  Anaesthetics, steroids and platelet-rich plasma (PRP) in ultrasound-guided musculoskeletal procedures 
The British Journal of Radiology  null;89(1065):20150355.
This review aims to evaluate the role of anaesthetics, steroids and platelet-rich plasma (PRP) employed with ultrasound-guided injection in the management of musculoskeletal pathology of the extremities. Ultrasound-guided injection represents an interesting and minimally invasive solution for the treatment of tendon and joint inflammatory or degenerative diseases. The availability of a variety of new drugs such as hyaluronic acid and PRP provides expansion of the indications and therapeutic possibilities. The clinical results obtained in terms of pain reduction and functional recovery suggest that the use of infiltrative procedures can be a good therapeutic alternative in degenerative and inflammatory joint diseases.
doi:10.1259/bjr.20150355
PMCID: PMC5124907  PMID: 27302491
12.  The sponge microbiome project 
GigaScience  2017;6(10):1-7.
Abstract
Marine sponges (phylum Porifera) are a diverse, phylogenetically deep-branching clade known for forming intimate partnerships with complex communities of microorganisms. To date, 16S rRNA gene sequencing studies have largely utilised different extraction and amplification methodologies to target the microbial communities of a limited number of sponge species, severely limiting comparative analyses of sponge microbial diversity and structure. Here, we provide an extensive and standardised dataset that will facilitate sponge microbiome comparisons across large spatial, temporal, and environmental scales. Samples from marine sponges (n = 3569 specimens), seawater (n = 370), marine sediments (n = 65) and other environments (n = 29) were collected from different locations across the globe. This dataset incorporates at least 268 different sponge species, including several yet unidentified taxa. The V4 region of the 16S rRNA gene was amplified and sequenced from extracted DNA using standardised procedures. Raw sequences (total of 1.1 billion sequences) were processed and clustered with (i) a standard protocol using QIIME closed-reference picking resulting in 39 543 operational taxonomic units (OTU) at 97% sequence identity, (ii) a de novo clustering using Mothur resulting in 518 246 OTUs, and (iii) a new high-resolution Deblur protocol resulting in 83 908 unique bacterial sequences. Abundance tables, representative sequences, taxonomic classifications, and metadata are provided. This dataset represents a comprehensive resource of sponge-associated microbial communities based on 16S rRNA gene sequences that can be used to address overarching hypotheses regarding host-associated prokaryotes, including host specificity, convergent evolution, environmental drivers of microbiome structure, and the sponge-associated rare biosphere.
doi:10.1093/gigascience/gix077
PMCID: PMC5632291
marine sponges; archaea; bacteria; symbiosis; microbiome; 16S rRNA gene; microbial diversity
13.  The validity of the SF-12 and SF-6D instruments in people living with HIV/AIDS in Kenya 
Background
Health-related quality of life (HRQoL) and health state utility value (HSUV) measurements are vital components of healthcare clinical and economic evaluations. Accurate measurement of HSUV and HRQoL require validated instruments. The 12-item Short-Form Health Survey (SF-12) is one of few instruments that can evaluate both HRQoL and HSUV, but its validity has not been assessed in people living with HIV/AIDS (PLWHA) in east Africa, where the burden of HIV is high.
Methods
This cross-sectional study used baseline data from a randomized trial involving PLWHA in Kenya. Data included responses from a translated and adapted SF-12 survey as well as key demographic and clinical data. Construct validity of the survey was examined by testing the SF-12’s ability to distinguish between groups known in advance to have differences in their health based on their disease severity. We classified disease severity based on established definitions from the US Center for Disease Control (CDC) and WHO, as well as a previously studied viral load threshold. T-tests and ANOVA were used to test for differences in HRQoL and HSUV scores. Area under the receive operator curve (AUC) was used to test the discriminative ability of the HRQoL and HSUV instruments.
Results
Differences in physical component scores met the minimum clinically important difference among participants with more advanced HIV when defined by CD4 count (4.3 units) and WHO criteria (compared to stage 1, stages 2, 3 and 4 were 2.0, 7.2 and 9.8 units lower respectively). Mental score differences met the minimum clinically important difference between WHO stage 1 and stage 4 patients (4.4). Differences in the HSUV were statistically lower in more advanced HIV by all three definitions of severity. The AUC showed poor to weak discriminatory ability in most analyses, but had fair discriminatory ability between WHO clinical stage 1 and clinical stage 4 individuals (AUC = 0.71).
Conclusion
Our findings suggest that the Kiswahili translated and adapted version of the SF-12 could be used as an assessment tool for physical health, mental health and HSUV for Kiswahili-speaking PLHWA.
Trial registration
Clinical trials.gov identifier: NCT00830622. Registered 26 January 2009.
doi:10.1186/s12955-017-0708-7
PMCID: PMC5513113
Quality of life; Short-form 12; Kiswahili; HIV; Health state utility; SF6D
14.  Filling the gaps in SARDs research: collection and linkage of administrative health data and self-reported survey data for a general population-based cohort of individuals with and without diagnoses of systemic autoimmune rheumatic disease (SARDs) from British Columbia, Canada 
BMJ Open  2017;7(6):e013977.
Purpose
Systemic autoimmune rheumatic diseases (SARDs) are a group of debilitating autoimmune diseases, including systemic lupus erythematosus and related disorders. Assessing the healthcare and economic burden of SARDs has been challenging: while administrative databases can be used to determine healthcare utilisation and costs with minimal selection and recall bias, other health, sociodemographic and economic data have typically been sourced from highly selected, clinic-based cohorts. To address these gaps, we are collecting self-reported survey data from a general population-based cohort of individuals with and without SARDs and linking it to their longitudinal administrative health data.
Participants
Using administrative data from the province of British Columbia (BC), Canada, we established a population-based cohort of all BC adults receiving care for SARDs during 1996–2010 (n=20 729) and non-SARD individuals randomly selected from the general population. BC Ministry of Health granted us contact information for 12 000 SARD and non-SARD individuals, who were recruited to complete the surveys by mail or online.
Findings to date
Four hundred individuals were initially invited to participate, with 135 (34%) consenting and 127 (94%) submitting the first survey (72% completed online). Sixty-three (49.6%) reported ≥1 SARD diagnosis. The non-SARDs group (n=64) was 92% female with mean age 57.0±11.6 years. The SARDs group (n=63) was 94% female with mean age 56.5±13.1 years. Forty-eight per cent of those with SARDs were current-or-former smokers (mean 10.6±16.2 pack-years), and 33% were overweight or obese (mean body mass index of 24.4±5.3).
Future plans
Health and productivity data collected from the surveys will be linked to participants’ administrative health data from the years 1990–2013, allowing us to determine the healthcare and lost productivity costs of SARDs, and assess the impact of patient-reported variables on utilisation, costs, disability and clinical outcomes. Findings will be disseminated through scientific conferences and peer-reviewed journals.
doi:10.1136/bmjopen-2016-013977
PMCID: PMC5541381  PMID: 28637725
administrative data; data linkage; health economics; statistics and research methods; rheumatic diseases; survey
16.  Consumer preferences for food allergen labeling 
Background
Food allergen labeling is an important tool to reduce risk of exposure and prevent anaphylaxis for individuals with food allergies. Health Canada released a Canadian food allergen labeling regulation (2008) and subsequent update (2012) suggesting that research is needed to guide further iterations of the regulation to improve food allergen labeling and reduce risk of exposure.
Objective
The primary objective of this study was to examine consumer preferences in food labeling for allergy avoidance and anaphylaxis prevention. A secondary objective was to identify whether different subgroups within the consumer population emerged.
Methods
A discrete choice experiment using a fractional factorial design divided into ten different versions with 18 choice-sets per version was developed to examine consumer preferences for different attributes of food labeling.
Results
Three distinct subgroups of Canadian consumers with different allergen considerations and food allergen labeling needs were identified. Overall, preferences for standardized precautionary and safety symbols at little or no increased cost emerged.
Conclusion
While three distinct groups with different preferences were identified, in general the results revealed that the current Canadian food allergen labeling regulation can be improved by enforcing the use of standardized precautionary and safety symbols and educating the public on the use of these symbols.
doi:10.1186/s13223-017-0189-6
PMCID: PMC5379517
Immune system diseases; Hypersensitivity; Hypersensitivity, immediate; Food hypersensitivity; Public health; Health planning; Health services research; Social control; Formal policy; Humans
17.  A rare localization of pure dermoid cyst in the frontal bone 
The Neuroradiology Journal  2016;29(2):130-133.
We report the case of an 84-year-old woman who came to our attention with right palpebral edema associated with pain in the omolateral fronto-orbital region. The patient underwent an MRI scan that revealed a rounded, extracerebral intradiploic cystic lesion with dyshomogeneous signal intensity. Computed tomography (CT) imaging was also performed with reformatted 3D reconstruction. Post-surgical histologic analysis confirmed the diagnosis of intradiploic dermoid cyst. We here report the case and discuss epidemiology, imaging features and work-up of this pathological entity.
doi:10.1177/1971400916631993
PMCID: PMC4978317  PMID: 26915898
Extracerebral dermoid cyst; intradiploic cyst; dermoid cyst; skull
18.  Cost-effectiveness of pharmacist care for managing hypertension in Canada 
Canadian Pharmacists Journal : CPJ  2017;150(3):184-197.
Background:
More than half of all heart disease and stroke are attributable to hypertension, which is associated with approximately 10% of direct medical costs globally. Clinical trial evidence has demonstrated that the benefits of pharmacist intervention, including education, consultation and/or prescribing, can help to reduce blood pressure; a recent Canadian trial found an 18.3 mmHg reduction in systolic blood pressure associated with pharmacist care and prescribing. The objective of this study was to evaluate the economic impact of such an intervention in a Canadian setting.
Methods:
A Markov cost-effectiveness model was developed to extrapolate potential differences in long-term cardiovascular and renal disease outcomes, using Framingham risk equations and other published risk equations. A range of values for systolic blood pressure reduction was considered (7.6-18.3 mmHg) to reflect the range of potential interventions and available evidence. The model incorporated health outcomes, costs and quality of life to estimate an overall incremental cost-effectiveness ratio. Costs considered included direct medical costs as well as the costs associated with implementing the pharmacist intervention strategy.
Results:
For a systolic blood pressure reduction of 18.3 mmHg, the estimated impact is 0.21 fewer cardiovascular events per person and, discounted at 5% per year, 0.3 additional life-years, 0.4 additional quality-adjusted life-years and $6,364 cost savings over a lifetime. Thus, the intervention is economically dominant, being both more effective and cost-saving relative to usual care.
Discussion:
Across a range of one-way and probabilistic sensitivity analyses of key parameters and assumptions, pharmacist intervention remained both effective and cost-saving.
Conclusion:
Comprehensive pharmacist care of hypertension, including patient education and prescribing, has the potential to offer both health benefits and cost savings to Canadians and, as such, has important public health implications.
doi:10.1177/1715163517701109
PMCID: PMC5415065
19.  Cognitive status is a determinant of health resource utilization among individuals with a history of falls: a 12-month prospective cohort study 
Introduction
Although falls are costly there are no prospective data examining factors among fallers that drive health care resource utilization. We identified key determinants of health resource utilization (HRU) at 6 and 12 months among older adults with a history of falls. Specifically, with the increasing recognition that cognitive impairment is associated with increased falls risk, we investigated cognition as a potential driver of health resource utilisation.
Methods
This 12-month prospective cohort study at the Vancouver Falls Prevention Clinic (n=319) included participants with a history of at least one fall in the previous 12 months. Based on their cognitive status, participants were divided into two groups: 1) No Mild Cognitive Impairment (MCI) and 2) MCI. We constructed two linear regression models with HRU at 6 and 12 months as the dependent variables for each model, respectively. Predictors relating to mobility, global cognition, executive functions and cognitive status (MCI versus no MCI) were examined. Age, sex, comorbidities, depression status and activities of daily living were included regardless of statistical significance.
Results
Global cognition, comorbidities, working memory and cognitive status (MCI versus no MCI ascertained using the MoCA) were significant determinants of total HRU at 6 months. The number of medical comorbidities and global cognition were significant determinants of total HRU at 12 months.
Conclusion
MCI status was a determinant of HRU at 6 months among older adults with a history of falls. As such, efforts to minimize health care resource use related to falls, it is important to tailor future interventions to be effective for people with MCI who fall.
Trial Registration
ClinicalTrials.gov Identifier: NCT01022866
doi:10.1007/s00198-015-3350-4
PMCID: PMC4898957  PMID: 26449355 CAMSID: cams5759
falls; cost; health resource utilization; older adults
20.  Economic evaluation of mobile phone text message interventions to improve adherence to HIV therapy in Kenya 
Medicine  2017;96(7):e6078.
Supplemental Digital Content is available in the text
Abstract
Background:
A surge in mobile phone availability has fueled low cost short messaging service (SMS) adherence interventions. Multiple systematic reviews have concluded that some SMS-based interventions are effective at improving antiretroviral therapy (ART) adherence, and they are hypothesized to improve retention in care. The objective of this study was to evaluate the cost-effectiveness of SMS-based adherence interventions and explore the added value of retention benefits.
Methods:
We evaluated the cost-effectiveness of weekly SMS interventions compared to standard care among HIV+ individuals initiating ART for the first time in Kenya. We used an individual level micro-simulation model populated with data from two SMS-intervention trials, an East-African HIV+ cohort and published literature. We estimated average quality adjusted life years (QALY) and lifetime HIV-related costs from a healthcare perspective. We explored a wide range of scenarios and assumptions in one-way and multivariate sensitivity analyses.
Results:
We found that SMS-based adherence interventions were cost-effective by WHO standards, with an incremental cost-effectiveness ratio (ICER) of $1,037/QALY. In the secondary analysis, potential retention benefits improved the cost-effectiveness of SMS intervention (ICER = $864/QALY). In multivariate sensitivity analyses, the interventions remained cost-effective in most analyses, but the ICER was highly sensitive to intervention costs, effectiveness and average cohort CD4 count at ART initiation. SMS interventions remained cost-effective in a test and treat scenario where individuals were assumed to initiate ART upon HIV detection.
Conclusions:
Effective SMS interventions would likely increase the efficiency of ART programs by improving HIV treatment outcomes at relatively low costs, and they could facilitate achievement of the UNAIDS goal of 90% viral suppression among those on ART by 2020.
doi:10.1097/MD.0000000000006078
PMCID: PMC5319505  PMID: 28207516
cost-effectiveness; drug adherence; HIV; implementation science; mHealth; mobile phone; SMS
21.  Growth Hormone Deficiency Is Associated with Worse Cardiac Function, Physical Performance, and Outcome in Chronic Heart Failure: Insights from the T.O.S.CA. GHD Study 
PLoS ONE  2017;12(1):e0170058.
Background
Although mounting evidence supports the concept that growth hormone (GH) deficiency (GHD) affects cardiovascular function, no study has systematically investigated its prevalence and role in a large cohort of chronic heart failure (CHF) patients. Aim of this study is to assess the prevalence of GHD in mild-to-moderate CHF and to explore clinical and functional correlates of GHD.
Methods
One-hundred thirty CHF patients underwent GH provocative test with GHRH+arginine and accordingly categorized into GH-deficiency (GHD, n = 88, age = 61.6±1.1 years, 68% men) and GH-sufficiency (GHS, n = 42, age = 63.6±1.5 years, 81% men) cohorts. Both groups received comprehensive cardiovascular examination and underwent Doppler echocardiography, cardiopulmonary exercise testing, and biochemical and hormonal assay.
Results
GHD was detected in roughly 30% of CHF patients. Compared to GHD, GHS patients showed smaller end-diastolic and end-systolic LV volumes (-28%, p = .008 and -24%, p = .015, respectively), lower LV end-systolic wall stress (-21%, p = .03), higher RV performance (+18% in RV area change, p = .03), lower estimated systolic pulmonary artery pressure (-11%, p = .04), higher peak VO2 (+20%, p = .001) and increased ventilatory efficiency (-12% in VE/VCO2 slope, p = .002). After adjusting for clinical covariates (age, gender, and tertiles of LV ejection fraction, IGF-1, peak VO2, VE/VCO2 slope, and NT-proBNP), logistic multivariate analysis showed that peak VO2 (β = -1.92, SE = 1.67, p = .03), VE/VCO2 slope (β = 2.23, SE = 1.20, p = .02) and NT-proBNP (β = 2.48, SE = 1.02, p = .016), were significantly associated with GHD status. Finally, compared to GHS, GHD cohort showed higher all-cause mortality at median follow-up of 3.5 years (40% vs. 25%, p < .001, respectively), independent of age, sex, NT-proBNP, peak VO2 and LVEF.
Conclusions
GH deficiency identifies a subgroup of CHF patients characterized by impaired functional capacity, LV remodeling and elevated NT-proBNP levels. GHD is also associated with increased all-cause mortality.
doi:10.1371/journal.pone.0170058
PMCID: PMC5240983  PMID: 28095492
22.  Ophiobolin A Induces Autophagy and Activates the Mitochondrial Pathway of Apoptosis in Human Melanoma Cells 
PLoS ONE  2016;11(12):e0167672.
Ophiobolin A, a fungal toxin from Bipolaris species known to affect different cellular processes in plants, has recently been shown to have anti-cancer activity in mammalian cells. In the present study, we investigated the anti-proliferative effect of Ophiobolin A on human melanoma A375 and CHL-1 cell lines. This cellular model was chosen because of the incidence of melanoma malignant tumor on human population and its resistance to chemical treatments. Ophyobolin A strongly reduced cell viability of melanoma cells by affecting mitochondrial functionality. The toxin induced depolarization of mitochondrial membrane potential, reactive oxygen species production and mitochondrial network fragmentation, leading to autophagy induction and ultimately resulting in cell death by activation of the mitochondrial pathway of apoptosis. Finally, a comparative proteomic investigation on A375 cells allowed to identify several Ophiobolin A down-regulated proteins, which are involved in fundamental processes for cell homeostasis and viability.
doi:10.1371/journal.pone.0167672
PMCID: PMC5147944  PMID: 27936075
23.  Association of Biomarkers with Serious Cardiac Adverse Events during Abiraterone Acetate Treatment in Castration Resistant Prostate Cancer 
Translational Oncology  2016;9(6):600-605.
BACKGROUND: Abiraterone acetate is an effective drug for castration-resistant prostate cancer, but cardiac serious adverse events (SAEs) may occur. We studied their association with N-terminal pro–brain natriuretic peptide (NT-proBNP) and troponin T (TnT) during abiraterone therapy. PATIENTS AND METHODS: In a single institution, 17 patients were treated with abiraterone acetate 1 g daily with concomitant prednisone and then switched to dexametasone plus canrenone. Blood samples for PSA, NT-proBNP, and TnT were obtained at baseline and after 1, 3, and 6 months. RESULTS: Five patients (29.4%) experienced G3 to 4 cardiac SAEs after a median of 13 weeks (range, 9-32), including pulmonary edema, heart failure, acute coronary syndrome, sinus bradycardia with syncope, and pulmonary edema. At baseline, 4 weeks, and 3 months, median NT-proBNP and TnT levels were higher in patients with subsequent cardiac SAEs (P= .03 and P= .04 for NT-proBNP and TnT at 3 months, respectively). After switching to dexametasone and introducing canrenone, no additional cardiac SAEs were noted. Overall response rate was 67%. CONCLUSIONS: Our study suggests a higher than expected risk of cardiac SAEs during abiraterone treatment which may well be due to the small sample size and the unrestricted entry criteria. However, baseline and frequent NT-proBNP and TnT monitoring predicted a higher risk for cardiac SAE. Larger studies should confirm our findings.
doi:10.1016/j.tranon.2016.08.001
PMCID: PMC5143350  PMID: 27916295
24.  Effectiveness of a pharmacist-driven intervention in COPD (EPIC): study protocol for a randomized controlled trial 
Trials  2016;17:502.
Background
Patients with chronic obstructive pulmonary disease (COPD) are often nonadherent with medications and have poor inhaler technique. Community pharmacists can help to improve health-related quality of life and overall outcomes in patients with COPD. We aim to measure the effectiveness of a systematic, pharmacist-driven intervention on patients with diagnosed COPD.
Methods/design
This pragmatic, parallel-group, cluster randomized controlled trial is designed to determine the effectiveness of a multifactorial, pharmacist-led intervention on medication adherence, inhaler technique, health-related quality of life, health care resource utilization including COPD exacerbations, and use of medications. Participating pharmacies in Newfoundland and Labrador (NL), Canada will be randomly assigned to either the intervention or the control group. The intervention group will deliver an enhanced form of care that emphasizes COPD management. The control group will provide usual care and a COPD education pamphlet. Included patients will be aged 40 years or older, have a physician-confirmed diagnosis of COPD, and be able to answer questionnaires in English. The primary outcomes are the between-group difference in the change from baseline to 6 months in medication adherence using the Medication Possession Ratio (MPR) and the Morisky Medication Adherence Scale (MMAS-8). The secondary outcomes are also measured from baseline to 6 months, and include the proportion of patients with a clinically significant change in adherence, the proportion of patients defined as having “good adherence,” the mean MPR between groups, quality of life as measured by the St. George’s Respiratory Questionnaire, medication inhalation technique using a pharmacist-scored checklist, health care resource utilization and antibiotic and orally administered corticosteroid use for COPD exacerbations. Differences between groups will be analyzed at the individual patient level while controlling for clustering effect.
Discussion
A pharmacist-led COPD intervention has the potential to improve patient medication adherence, thus increasing quality of life, possibly decreasing pulmonary exacerbations and reducing utilization of acute health care resources. Methods and results taken from this study could be used to enhance the delivery of COPD care by community pharmacists in a real-world setting. This would serve to enhance COPD population health and quality of life.
Trial registration
International Standard Randomized Controlled Trial Number (ISRCTN) ISRCTN78138190, registered on 3 February 2016.
Electronic supplementary material
The online version of this article (doi:10.1186/s13063-016-1623-7) contains supplementary material, which is available to authorized users.
doi:10.1186/s13063-016-1623-7
PMCID: PMC5064938  PMID: 27737686
Chronic obstructive pulmonary disease; Cluster randomized controlled trial; Community pharmacy; Medication adherence; Pharmacist; Pharmacy practice research
25.  Opinions and preferences of British Columbia pharmacists and physicians on medication management services 
Background:
Medication management (MM) services are being provided by pharmacists across Canada in various forms, but pharmacist-physician collaboration is still not a routine practice in most jurisdictions. This survey aimed to gather pharmacists’ and physicians’ opinions and preferences for MM provision.
Methods:
Two parallel, cross-sectional online surveys, including best-worst scaling tasks, were designed for pharmacists and physicians in British Columbia to capture and compare their preferences for a number of attributes of MM.
Results:
Surveys were completed by 119 pharmacists and 146 physicians. Results indicate that pharmacists and physicians had similar opinions on many aspects of MM. Ninety-five percent of pharmacists and 69% of physicians believed that additional health services are needed to help patients optimize the use of their medications. However, the majority of each group felt that they were the most important health care professional in providing this service. Most pharmacists (79%) and some physicians (25%) thought that optimizing use of medications would result in both decreased costs and utilization to the health care system. Both pharmacists and physicians felt that the best attribute of an MM service would be if the services resulted in improved health and medication use for patients. Both groups were motivated by increased remuneration for MM; however, the relative strength of preference for this was higher among physicians. Interestingly, physicians valued improved medication adherence as a result of MM more highly than pharmacists did.
Discussion and Conclusion:
Most pharmacists and physicians agreed that improving patients’ health and medication use would be the best attribute of MM and that there is a need for such services. However, physicians also had strong preferences for being remunerated for participating in MM provision.
doi:10.1177/1715163516671746
PMCID: PMC5330418

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