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1. Considerations for resuming global surgery outreach programs during and after the coronavirus disease 2019 (COVID-19) pandemic

Author: Arun K. Gosain, Gazi B. Zibari, Alireza Hamidian Jahromi, Quyen D. Chu, and Jenna R. Stoehr
Subjects: Coronavirus disease 2019 (COVID-19), business.industry, Surgical care, MEDLINE, COVID-19, Medical Missions, 030230 surgery, Global Health, medicine.disease, Article, Outreach, 03 medical and health sciences, Patient population, Local infection, 0302 clinical medicine, General Surgery, 030220 oncology & carcinogenesis, Pandemic, Humans, Medicine, Surgery, Narrative review, Medical emergency, business, Pandemics
Abstract: Background The coronavirus disease 2019 pandemic has disrupted the delivery of safe surgical care worldwide. One specific aspect of global surgical care that has been severely limited is the ability for physicians and trainees to participate in global surgical outreach programs in low- and middle-income countries. Methods A narrative review of the literature regarding global surgical outreach programs during the coronavirus disease 2019 pandemic was performed. Factors that must be considered in the reinstatement of global surgical outreach programs were identified, and suggestions to address them were provided based on the available literature and the experiences of the senior authors. Results As global surgical outreach programs were canceled at the start of the pandemic, many academic surgeons turned to digital solutions to continue to engage with low- and middle-income country partners. With the advent of coronavirus disease 2019 vaccines and improved access to testing and treatment worldwide, the recommencement of global surgical outreach programs may begin to be considered. Important considerations before initiation include vaccine and testing availability for visiting providers, local staff, and patients, local hospital capacity, staff and equipment shortages, and the characteristics of the patient population and visiting providers. Region- and country-specific factors, including local infection rates and concomitant health crises, must also be taken into account. Expansion of digital collaborative efforts may further deepen international connections and promote sustainable models of care. Conclusion With careful consideration, global surgical outreach programs may begin to be safely restarted in the near future. The current article evaluates individual factors that must be considered to safely restart global surgical outreach programs as the coronavirus disease 2019 pandemic is better controlled.
Published: 2021

2. A Possible Distinct Molecular Subtype (Quintuple-Wildtype) of Metastatic Colorectal Cancer in First-Line Anti-EGFR Therapy with Cetuximab Plus FOLFIRI – Palliative Precision Therapy and a Multidisciplinary Treatment Approach: Interim Analysis of the IVOPAK II Trial with Early Results

Author: Jan-Peter Roth, Francesco Vitali, Dagmar Busse, W Schreiner, Susanne Merkel, Robert Stoehr, Arndt Hartmann, Markus Eckstein, Axel Wein, Stephan Kersting, Michael Uder, Peter Anhut, Robert Grützmann, Jürgen Siebler, Nicola Ostermeier, Markus F. Neurath, Kerstin Wolff, and Clemens Neufert
Subjects: Adult, Male, Proto-Oncogene Proteins B-raf, Oncology, Neuroblastoma RAS viral oncogene homolog, Cancer Research, medicine.medical_specialty, Bevacizumab, Class I Phosphatidylinositol 3-Kinases, Receptor, ErbB-2, Colorectal cancer, Population, Leucovorin, Cetuximab, medicine.disease_cause, GTP Phosphohydrolases, Proto-Oncogene Proteins p21(ras), Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Tumor, medicine, Humans, Precision Medicine, education, Aged, education.field_of_study, business.industry, Palliative Care, Membrane Proteins, General Medicine, Middle Aged, medicine.disease, Interim analysis, ErbB Receptors, FOLFIRI, Camptothecin, Female, Fluorouracil, KRAS, Colorectal Neoplasms, business, medicine.drug
Abstract: Objective: The study aimed to prospectively evaluate a new molecular biomarker panel (KRAS, NRAS, BRAF, PIK3CA, and ERBB2) for palliative first-line treatment of colorectal cancer (CRC), including a multidisciplinary treatment approach. The rate of secondary metastasis resections was assessed. Patients and Methods: A total of 40 patients with definitively nonresectable metastatic CRC were enrolled from 10 centers before the interim analysis (June 2019) of the IVOPAK II trial (Interdisciplinary Care with Quality Control in Palliative Treatment of Colorectal Cancer). After determination of 5 molecular biomarkers in the tumor (KRAS, exons 2–4; NRAS, exons 2–4; BRAF V600E; PIK3CA; and ERBB2), patients in the IVOPAK II study received FOLFIRI plus cetuximab for all-RAS/quintuple-wildtype disease and FOLFIRI plus bevacizumab in the case of RAS mutations. The current article presents the early description of the clinical outcome of the interim analysis of IVOPAK II comparing the all-RAS/quintuple-wildtype and RAS-mutations populations, including a multidisciplinary-treated case report of a quintuple-wildtype patient. Results: The quintuple-wildtype population treated with FOLFIRI plus cetuximab in first-line exhibited a significantly higher response rate and enhanced early tumor shrinkage in the interim analysis than the RAS-mutations population, as well as a high rate of secondary metastatic resections. Conclusion: Initial results of this new biomarker panel (quintuple-wildtype) are promising for anti-EGFR therapy with cetuximab plus doublet chemotherapy (FOLFIRI) in first-line treatment of metastatic CRC. These results warrant confirmation with higher case numbers in the IVOPAK II trial.
Published: 2021

3. Outcomes of men with HIV and germ cell cancer: Results from an international collaborative study

Author: Marcus Hentrich, David Pfister, Christian Hoffmann, Markus Bickel, Mark Bower, Andrea Necchi, Annette Dieing, Florian Lesmeister, Massimiliano Berretta, Julia Heinzelbecker, Ivanka Krznaric, Albrecht Stoehr, Vindi Jurinovic, Margarida Brito, Klaus-Peter Dieckmann, Pablo Maroto Rey, Jürgen K. Rockstroh, and Gedske Daugaard
Subjects: Adult, Male, Cart, Cancer Research, medicine.medical_specialty, Adolescent, Human immunodeficiency virus (HIV), HIV Infections, Disease, medicine.disease_cause, Collaborative group, Testicular Neoplasms, Acquired immunodeficiency syndrome (AIDS), Refractory, nonseminoma, Internal medicine, medicine, Humans, HIV-related germ cell cancer, germ cell cancer, business.industry, seminoma, HIV, virus diseases, Seminoma, Neoplasms, Germ Cell and Embryonal, medicine.disease, AIDS, Germ cell cancer, Oncology, Neoplasm Recurrence, Local, business
Abstract: Background: Previous studies have shown that men with HIV and germ cell cancer (HIV-GCC) have inferior overall survival (OS) in comparison with their HIV-negative counterparts. However, little information is available on treatments and outcomes of HIV-GCC in the era of combination antiretroviral therapy (cART). Methods: This study examined men living with HIV who were 18 years old or older and had a diagnosis of histologically proven germ cell cancer (GCC). The primary outcomes were OS and progression-free survival (PFS). Results: Data for 89 men with a total of 92 HIV-GCCs (2 synchronous GCCs and 1 metachronous bilateral GCC) were analyzed; among them were 64 seminomas (70%) and 28 nonseminomas (30%). The median age was 36 years, the median CD4 T-cell count at GCC diagnosis was 420 cells/µL, and 77% of the patients on cART had an HIV RNA load < 500 copies/mL. Stage I disease was found in 44 of 79 gonadal GCCs (56%). Among 45 cases with primary disseminated GCC, 78%, 18%, and 4% were assigned to the good-, intermediate-, and poor-prognosis groups, respectively, of the International Germ Cell Cancer Collaborative Group. Relapses occurred in 14 patients. Overall, 12 of 89 patients (13%) died. The causes of death were refractory GCC (n = 5), an AIDS-defining illness (n = 3), and other causes (n = 4). After a median follow-up of 6.5 years, the 5- and 10-year PFS rates were 81% and 73%, respectively, and the 5- and 10-year OS rates were 91% and 85%, respectively. Conclusions: The 5- and 10-year PFS and OS rates of men with HIV-GCC were similar to those reported for men with HIV-negative GCC. Patients with HIV-GCC should be managed identically to HIV-negative patients. Lay Summary: Men living with HIV are at increased risk for germ cell cancer (GCC). Previous studies have shown that the survival of men with HIV-associated germ cell cancer (HIV-GCC) is poorer than the survival of their HIV-negative counterparts. This study examined the characteristics, treatments, and outcomes of 89 men with HIV-GCC in the era of effective combination antiretroviral therapies. The long-term outcomes of men with HIV-GCC were similar to those reported for men with HIV-negative GCC. Patients with HIV-GCC should be managed identically to HIV-negative patients.
Published: 2021

4. Frequency of microsatellite instability (MSI) in upper tract urothelial carcinoma: comparison of the Bethesda panel and the Idylla MSI assay in a consecutively collected, multi-institutional cohort

Author: Peter Olbert, Bernardo Herrera-Imbroda, Daniel Prieto, Ivan Bièche, Elisa Matas-Rico, Romane Beaurepere, Helge Taubert, Maria Jose Lozano, Markus Eckstein, Robert Stoehr, Arndt Hartmann, Bernd Wullich, Hendrik Heers, Isabel Hierro, Pamela L. Strissel, Yves Allory, Julien Masliah-Planchon, Danijel Sikic, Friederike Kullmann, Veronika Weyerer, Maria Fernanda Lara, Simone Bertz, Thomas van Doeveren, Joost L. Boormans, Sven Wach, Maria Luisa Macias, Reiner Strick, and Urology
Subjects: Oncology, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, business.industry, Concordance, nutritional and metabolic diseases, Microsatellite instability, General Medicine, medicine.disease, Malignancy, digestive system diseases, Lynch syndrome, Pathology and Forensic Medicine, Upper tract, Internal medicine, Cohort, medicine, Biomarker (medicine), DNA mismatch repair, ddc:610, business, neoplasms
Abstract: AimsUpper tract urothelial carcinoma (UTUC) is a rare malignancy with a poor prognosis which occurs sporadically or in few cases results from a genetic disorder called Lynch syndrome. Recently, examination of microsatellite instability (MSI) has gained importance as a biomarker: MSI tumours are associated with a better response to immunomodulative therapies. Limited data are known about the prevalence of MSI in UTUC. New detection methods using the fully automated Idylla MSI Assay facilitate analysis of increased patient numbers.MethodsWe investigated the frequency of MSI in a multi-institutional cohort of 243 consecutively collected UTUC samples using standard methodology (Bethesda panel), along with immunohistochemistry of mismatch repair (MMR) proteins. The same tumour cohort was retested using the Idylla MSI Assay by Biocartis.ResultsUsing standard methodology, 230/243 tumours were detected as microsatellite stable (MSS), 4/243 tumours as MSI and 9/243 samples as invalid. In comparison, the Idylla MSI Assay identified four additional tumours as MSS, equalling 234/243 tumours; 4/243 were classified as MSI and only 5/243 cases as invalid. At the immunohistochemical level, MSI results were supported in all available cases with a loss in MMR proteins. The overall concordance between the standard and the Idylla MSI Assay was 98.35%. Time to result differed between 3 hours for Idylla MSI Assay and 2 days with the standard methodology.ConclusionOur data indicate a low incidence rate of MSI tumours in patients with UTUC. Furthermore, our findings highlight that Idylla MSI Assay can be applied as an alternative method of MSI analysis for UTUC.
Published: 2021

5. A Comparison of Outcomes of Proximal and Distal Anastomosis Sites of the Facial Artery in Head and Neck Reconstruction

Author: Jenna R. Stoehr, Marco F. Ellis, Nicholas R. Curran, and Christopher J. Micallef
Subjects: business.industry, Anastomosis, Surgical, Facial artery, Arteries, General Medicine, Anatomy, Plastic Surgery Procedures, Free Tissue Flaps, Surgical Flaps, Otorhinolaryngology, Head and Neck Neoplasms, medicine.artery, medicine, Humans, Surgery, Obesity, Head and neck, business, Neck, Retrospective Studies, Distal anastomosis
Abstract: Recipient vessel selection in head and neck reconstruction is based on multiple factors, including defect size and location, patient history, and vessel location, diameter, and length. The authors present a comparison of proximal and distal anastomotic sites of the facial artery. A chart review of head and neck reconstructions using the facial artery as a recipient vessel over a 7-year period was conducted. The anastomosis site was identified as distal (at the inferior mandible border) or proximal (at the origin of the artery). The distal site was utilized for both defects of the midface/ scalp and of the mandible/neck, while the proximal site was exclusively used for mandible/neck defects. The following complications were included in the analysis: facial nerve injury, surgical site infection, thrombosis, flap congestion, flap loss, hardware failure, malunion/nonunion, osteomyelitis, sinus/fistula, hematoma, seroma, reoperation, and 90-day mortality. Fifty-four free tissue transfers were performed. The overall complication rate (including major and minor complications) was 53.7%. Anastomosis level did not have a significant impact on complication rate. In addition, there were no significant differences in complication rates for the distal anastomosis site when stratified by defect location. However, obese patients were more likely to have a complication than nonobese patients. This conclusion may reassure surgeons that factors related to anastomosis level, such as vessel diameter and proximity to the zone of injury, have less impact on outcomes than factors like obesity, which may inform preoperative planning, intraoperative decision-making, and postoperative monitoring.
Published: 2021

6. Machine Learning Detects Pan-cancer Ras Pathway Activation in The Cancer Genome Atlas

Author: Gregory P. Way, Francisco Sanchez-Vega, Konnor La, Joshua Armenia, Walid K. Chatila, Augustin Luna, Chris Sander, Andrew D. Cherniack, Marco Mina, Giovanni Ciriello, Nikolaus Schultz, Yolanda Sanchez, Casey S. Greene, Samantha J. Caesar-Johnson, John A. Demchok, Ina Felau, Melpomeni Kasapi, Martin L. Ferguson, Carolyn M. Hutter, Heidi J. Sofia, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jean C. Zenklusen, Jiashan (Julia) Zhang, Sudha Chudamani, Jia Liu, Laxmi Lolla, Rashi Naresh, Todd Pihl, Qiang Sun, Yunhu Wan, Ye Wu, Juok Cho, Timothy DeFreitas, Scott Frazer, Nils Gehlenborg, Gad Getz, David I. Heiman, Jaegil Kim, Michael S. Lawrence, Pei Lin, Sam Meier, Michael S. Noble, Gordon Saksena, Doug Voet, Hailei Zhang, Brady Bernard, Nyasha Chambwe, Varsha Dhankani, Theo Knijnenburg, Roger Kramer, Kalle Leinonen, Yuexin Liu, Michael Miller, Sheila Reynolds, Ilya Shmulevich, Vesteinn Thorsson, Wei Zhang, Rehan Akbani, Bradley M. Broom, Apurva M. Hegde, Zhenlin Ju, Rupa S. Kanchi, Anil Korkut, Jun Li, Han Liang, Shiyun Ling, Wenbin Liu, Yiling Lu, Gordon B. Mills, Kwok-Shing Ng, Arvind Rao, Michael Ryan, Jing Wang, John N. Weinstein, Jiexin Zhang, Adam Abeshouse, Debyani Chakravarty, Ino de Bruijn, Jianjiong Gao, Benjamin E. Gross, Zachary J. Heins, Ritika Kundra, Marc Ladanyi, Moriah G. Nissan, Angelica Ochoa, Sarah M. Phillips, Ed Reznik, Robert Sheridan, S. Onur Sumer, Yichao Sun, Barry S. Taylor, Jioajiao Wang, Hongxin Zhang, Pavana Anur, Myron Peto, Paul Spellman, Christopher Benz, Joshua M. Stuart, Christopher K. Wong, Christina Yau, D. Neil Hayes, Joel S. Parker, Matthew D. Wilkerson, Adrian Ally, Miruna Balasundaram, Reanne Bowlby, Denise Brooks, Rebecca Carlsen, Eric Chuah, Noreen Dhalla, Robert Holt, Steven J.M. Jones, Katayoon Kasaian, Darlene Lee, Yussanne Ma, Marco A. Marra, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Karen Mungall, A. Gordon Robertson, Sara Sadeghi, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Kane Tse, Tina Wong, Ashton C. Berger, Rameen Beroukhim, Carrie Cibulskis, Stacey B. Gabriel, Galen F. Gao, Gavin Ha, Matthew Meyerson, Steven E. Schumacher, Juliann Shih, Melanie H. Kucherlapati, Raju S. Kucherlapati, Stephen Baylin, Leslie Cope, Ludmila Danilova, Moiz S. Bootwalla, Phillip H. Lai, Dennis T. Maglinte, David J. Van Den Berg, Daniel J. Weisenberger, J. Todd Auman, Saianand Balu, Tom Bodenheimer, Cheng Fan, Katherine A. Hoadley, Alan P. Hoyle, Stuart R. Jefferys, Corbin D. Jones, Shaowu Meng, Piotr A. Mieczkowski, Lisle E. Mose, Amy H. Perou, Charles M. Perou, Jeffrey Roach, Yan Shi, Janae V. Simons, Tara Skelly, Matthew G. Soloway, Donghui Tan, Umadevi Veluvolu, Huihui Fan, Toshinori Hinoue, Peter W. Laird, Hui Shen, Wanding Zhou, Michelle Bellair, Kyle Chang, Kyle Covington, Chad J. Creighton, Huyen Dinh, HarshaVardhan Doddapaneni, Lawrence A. Donehower, Jennifer Drummond, Richard A. Gibbs, Robert Glenn, Walker Hale, Yi Han, Jianhong Hu, Viktoriya Korchina, Sandra Lee, Lora Lewis, Wei Li, Xiuping Liu, Margaret Morgan, Donna Morton, Donna Muzny, Jireh Santibanez, Margi Sheth, Eve Shinbrot, Linghua Wang, Min Wang, David A. Wheeler, Liu Xi, Fengmei Zhao, Julian Hess, Elizabeth L. Appelbaum, Matthew Bailey, Matthew G. Cordes, Li Ding, Catrina C. Fronick, Lucinda A. Fulton, Robert S. Fulton, Cyriac Kandoth, Elaine R. Mardis, Michael D. McLellan, Christopher A. Miller, Heather K. Schmidt, Richard K. Wilson, Daniel Crain, Erin Curley, Johanna Gardner, Kevin Lau, David Mallery, Scott Morris, Joseph Paulauskis, Robert Penny, Candace Shelton, Troy Shelton, Mark Sherman, Eric Thompson, Peggy Yena, Jay Bowen, Julie M. Gastier-Foster, Mark Gerken, Kristen M. Leraas, Tara M. Lichtenberg, Nilsa C. Ramirez, Lisa Wise, Erik Zmuda, Niall Corcoran, Tony Costello, Christopher Hovens, Andre L. Carvalho, Ana C. de Carvalho, José H. Fregnani, Adhemar Longatto-Filho, Rui M. Reis, Cristovam Scapulatempo-Neto, Henrique C.S. Silveira, Daniel O. Vidal, Andrew Burnette, Jennifer Eschbacher, Beth Hermes, Ardene Noss, Rosy Singh, Matthew L. Anderson, Patricia D. Castro, Michael Ittmann, David Huntsman, Bernard Kohl, Xuan Le, Richard Thorp, Chris Andry, Elizabeth R. Duffy, Vladimir Lyadov, Oxana Paklina, Galiya Setdikova, Alexey Shabunin, Mikhail Tavobilov, Christopher McPherson, Ronald Warnick, Ross Berkowitz, Daniel Cramer, Colleen Feltmate, Neil Horowitz, Adam Kibel, Michael Muto, Chandrajit P. Raut, Andrei Malykh, Jill S. Barnholtz-Sloan, Wendi Barrett, Karen Devine, Jordonna Fulop, Quinn T. Ostrom, Kristen Shimmel, Yingli Wolinsky, Andrew E. Sloan, Agostino De Rose, Felice Giuliante, Marc Goodman, Beth Y. Karlan, Curt H. Hagedorn, John Eckman, Jodi Harr, Jerome Myers, Kelinda Tucker, Leigh Anne Zach, Brenda Deyarmin, Hai Hu, Leonid Kvecher, Caroline Larson, Richard J. Mural, Stella Somiari, Ales Vicha, Tomas Zelinka, Joseph Bennett, Mary Iacocca, Brenda Rabeno, Patricia Swanson, Mathieu Latour, Louis Lacombe, Bernard Têtu, Alain Bergeron, Mary McGraw, Susan M. Staugaitis, John Chabot, Hanina Hibshoosh, Antonia Sepulveda, Tao Su, Timothy Wang, Olga Potapova, Olga Voronina, Laurence Desjardins, Odette Mariani, Sergio Roman-Roman, Xavier Sastre, Marc-Henri Stern, Feixiong Cheng, Sabina Signoretti, Andrew Berchuck, Darell Bigner, Eric Lipp, Jeffrey Marks, Shannon McCall, Roger McLendon, Angeles Secord, Alexis Sharp, Madhusmita Behera, Daniel J. Brat, Amy Chen, Keith Delman, Seth Force, Fadlo Khuri, Kelly Magliocca, Shishir Maithel, Jeffrey J. Olson, Taofeek Owonikoko, Alan Pickens, Suresh Ramalingam, Dong M. Shin, Gabriel Sica, Erwin G. Van Meir, Hongzheng Zhang, Wil Eijckenboom, Ad Gillis, Esther Korpershoek, Leendert Looijenga, Wolter Oosterhuis, Hans Stoop, Kim E. van Kessel, Ellen C. Zwarthoff, Chiara Calatozzolo, Lucia Cuppini, Stefania Cuzzubbo, Francesco DiMeco, Gaetano Finocchiaro, Luca Mattei, Alessandro Perin, Bianca Pollo, Chu Chen, John Houck, Pawadee Lohavanichbutr, Arndt Hartmann, Christine Stoehr, Robert Stoehr, Helge Taubert, Sven Wach, Bernd Wullich, Witold Kycler, Dawid Murawa, Maciej Wiznerowicz, Ki Chung, W. Jeffrey Edenfield, Julie Martin, Eric Baudin, Glenn Bubley, Raphael Bueno, Assunta De Rienzo, William G. Richards, Steven Kalkanis, Tom Mikkelsen, Houtan Noushmehr, Lisa Scarpace, Nicolas Girard, Marta Aymerich, Elias Campo, Eva Giné, Armando López Guillermo, Nguyen Van Bang, Phan Thi Hanh, Bui Duc Phu, Yufang Tang, Howard Colman, Kimberley Evason, Peter R. Dottino, John A. Martignetti, Hani Gabra, Hartmut Juhl, Teniola Akeredolu, Serghei Stepa, Dave Hoon, Keunsoo Ahn, Koo Jeong Kang, Felix Beuschlein, Anne Breggia, Michael Birrer, Debra Bell, Mitesh Borad, Alan H. Bryce, Erik Castle, Vishal Chandan, John Cheville, John A. Copland, Michael Farnell, Thomas Flotte, Nasra Giama, Thai Ho, Michael Kendrick, Jean-Pierre Kocher, Karla Kopp, Catherine Moser, David Nagorney, Daniel O’Brien, Brian Patrick O’Neill, Tushar Patel, Gloria Petersen, Florencia Que, Michael Rivera, Lewis Roberts, Robert Smallridge, Thomas Smyrk, Melissa Stanton, R. Houston Thompson, Michael Torbenson, Ju Dong Yang, Lizhi Zhang, Fadi Brimo, Jaffer A. Ajani, Ana Maria Angulo Gonzalez, Carmen Behrens, Jolanta Bondaruk, Russell Broaddus, Bogdan Czerniak, Bita Esmaeli, Junya Fujimoto, Jeffrey Gershenwald, Charles Guo, Alexander J. Lazar, Christopher Logothetis, Funda Meric-Bernstam, Cesar Moran, Lois Ramondetta, David Rice, Anil Sood, Pheroze Tamboli, Timothy Thompson, Patricia Troncoso, Anne Tsao, Ignacio Wistuba, Candace Carter, Lauren Haydu, Peter Hersey, Valerie Jakrot, Hojabr Kakavand, Richard Kefford, Kenneth Lee, Georgina Long, Graham Mann, Michael Quinn, Robyn Saw, Richard Scolyer, Kerwin Shannon, Andrew Spillane, Jonathan Stretch, Maria Synott, John Thompson, James Wilmott, Hikmat Al-Ahmadie, Timothy A. Chan, Ronald Ghossein, Anuradha Gopalan, Douglas A. Levine, Victor Reuter, Samuel Singer, Bhuvanesh Singh, Nguyen Viet Tien, Thomas Broudy, Cyrus Mirsaidi, Praveen Nair, Paul Drwiega, Judy Miller, Jennifer Smith, Howard Zaren, Joong-Won Park, Nguyen Phi Hung, Electron Kebebew, W. Marston Linehan, Adam R. Metwalli, Karel Pacak, Peter A. Pinto, Mark Schiffman, Laura S. Schmidt, Cathy D. Vocke, Nicolas Wentzensen, Robert Worrell, Hannah Yang, Marc Moncrieff, Chandra Goparaju, Jonathan Melamed, Harvey Pass, Natalia Botnariuc, Irina Caraman, Mircea Cernat, Inga Chemencedji, Adrian Clipca, Serghei Doruc, Ghenadie Gorincioi, Sergiu Mura, Maria Pirtac, Irina Stancul, Diana Tcaciuc, Monique Albert, Iakovina Alexopoulou, Angel Arnaout, John Bartlett, Jay Engel, Sebastien Gilbert, Jeremy Parfitt, Harman Sekhon, George Thomas, Doris M. Rassl, Robert C. Rintoul, Carlo Bifulco, Raina Tamakawa, Walter Urba, Nicholas Hayward, Henri Timmers, Anna Antenucci, Francesco Facciolo, Gianluca Grazi, Mirella Marino, Roberta Merola, Ronald de Krijger, Anne-Paule Gimenez-Roqueplo, Alain Piché, Simone Chevalier, Ginette McKercher, Kivanc Birsoy, Gene Barnett, Cathy Brewer, Carol Farver, Theresa Naska, Nathan A. Pennell, Daniel Raymond, Cathy Schilero, Kathy Smolenski, Felicia Williams, Carl Morrison, Jeffrey A. Borgia, Michael J. Liptay, Mark Pool, Christopher W. Seder, Kerstin Junker, Larsson Omberg, Mikhail Dinkin, George Manikhas, Domenico Alvaro, Maria Consiglia Bragazzi, Vincenzo Cardinale, Guido Carpino, Eugenio Gaudio, David Chesla, Sandra Cottingham, Michael Dubina, Fedor Moiseenko, Renumathy Dhanasekaran, Karl-Friedrich Becker, Klaus-Peter Janssen, Julia Slotta-Huspenina, Mohamed H. Abdel-Rahman, Dina Aziz, Sue Bell, Colleen M. Cebulla, Amy Davis, Rebecca Duell, J. Bradley Elder, Joe Hilty, Bahavna Kumar, James Lang, Norman L. Lehman, Randy Mandt, Phuong Nguyen, Robert Pilarski, Karan Rai, Lynn Schoenfield, Kelly Senecal, Paul Wakely, Paul Hansen, Ronald Lechan, James Powers, Arthur Tischler, William E. Grizzle, Katherine C. Sexton, Alison Kastl, Joel Henderson, Sima Porten, Jens Waldmann, Martin Fassnacht, Sylvia L. Asa, Dirk Schadendorf, Marta Couce, Markus Graefen, Hartwig Huland, Guido Sauter, Thorsten Schlomm, Ronald Simon, Pierre Tennstedt, Oluwole Olabode, Mark Nelson, Oliver Bathe, Peter R. Carroll, June M. Chan, Philip Disaia, Pat Glenn, Robin K. Kelley, Charles N. Landen, Joanna Phillips, Michael Prados, Jeffry Simko, Karen Smith-McCune, Scott VandenBerg, Kevin Roggin, Ashley Fehrenbach, Ady Kendler, Suzanne Sifri, Ruth Steele, Antonio Jimeno, Francis Carey, Ian Forgie, Massimo Mannelli, Michael Carney, Brenda Hernandez, Benito Campos, Christel Herold-Mende, Christin Jungk, Andreas Unterberg, Andreas von Deimling, Aaron Bossler, Joseph Galbraith, Laura Jacobus, Michael Knudson, Tina Knutson, Deqin Ma, Mohammed Milhem, Rita Sigmund, Andrew K. Godwin, Rashna Madan, Howard G. Rosenthal, Clement Adebamowo, Sally N. Adebamowo, Alex Boussioutas, David Beer, Thomas Giordano, Anne-Marie Mes-Masson, Fred Saad, Therese Bocklage, Lisa Landrum, Robert Mannel, Kathleen Moore, Katherine Moxley, Russel Postier, Joan Walker, Rosemary Zuna, Michael Feldman, Federico Valdivieso, Rajiv Dhir, James Luketich, Edna M. Mora Pinero, Mario Quintero-Aguilo, Carlos Gilberto Carlotti, Jose Sebastião Dos Santos, Rafael Kemp, Ajith Sankarankuty, Daniela Tirapelli, James Catto, Kathy Agnew, Elizabeth Swisher, Jenette Creaney, Bruce Robinson, Carl Simon Shelley, Eryn M. Godwin, Sara Kendall, Cassaundra Shipman, Carol Bradford, Thomas Carey, Andrea Haddad, Jeffey Moyer, Lisa Peterson, Mark Prince, Laura Rozek, Gregory Wolf, Rayleen Bowman, Kwun M. Fong, Ian Yang, Robert Korst, W. Kimryn Rathmell, J. Leigh Fantacone-Campbell, Jeffrey A. Hooke, Albert J. Kovatich, Craig D. Shriver, John DiPersio, Bettina Drake, Ramaswamy Govindan, Sharon Heath, Timothy Ley, Brian Van Tine, Peter Westervelt, Mark A. Rubin, Jung Il Lee, Natália D. Aredes, Armaz Mariamidze, Cancer Genome Atlas Research Network, Caesar-Johnson, S.J., Demchok, J.A., Felau, I., Kasapi, M., Ferguson, M.L., Hutter, C.M., Sofia, H.J., Tarnuzzer, R., Wang, Z., Yang, L., Zenklusen, J.C., Zhang, J.J., Chudamani, S., Liu, J., Lolla, L., Naresh, R., Pihl, T., Sun, Q., Wan, Y., Wu, Y., Cho, J., DeFreitas, T., Frazer, S., Gehlenborg, N., Getz, G., Heiman, D.I., Kim, J., Lawrence, M.S., Lin, P., Meier, S., Noble, M.S., Saksena, G., Voet, D., Zhang, H., Bernard, B., Chambwe, N., Dhankani, V., Knijnenburg, T., Kramer, R., Leinonen, K., Liu, Y., Miller, M., Reynolds, S., Shmulevich, I., Thorsson, V., Zhang, W., Akbani, R., Broom, B.M., Hegde, A.M., Ju, Z., Kanchi, R.S., Korkut, A., Li, J., Liang, H., Ling, S., Liu, W., Lu, Y., Mills, G.B., Ng, K.S., Rao, A., Ryan, M., Wang, J., Weinstein, J.N., Zhang, J., Abeshouse, A., Armenia, J., Chakravarty, D., Chatila, W.K., de Bruijn, I., Gao, J., Gross, B.E., Heins, Z.J., Kundra, R., La, K., Ladanyi, M., Luna, A., Nissan, M.G., Ochoa, A., Phillips, S.M., Reznik, E., Sanchez-Vega, F., Sander, C., Schultz, N., Sheridan, R., Sumer, S.O., Sun, Y., Taylor, B.S., Anur, P., Peto, M., Spellman, P., Benz, C., Stuart, J.M., Wong, C.K., Yau, C., Hayes, D.N., Parker, J.S., Wilkerson, M.D., Ally, A., Balasundaram, M., Bowlby, R., Brooks, D., Carlsen, R., Chuah, E., Dhalla, N., Holt, R., Jones, SJM, Kasaian, K., Lee, D., Ma, Y., Marra, M.A., Mayo, M., Moore, R.A., Mungall, A.J., Mungall, K., Robertson, A.G., Sadeghi, S., Schein, J.E., Sipahimalani, P., Tam, A., Thiessen, N., Tse, K., Wong, T., Berger, A.C., Beroukhim, R., Cherniack, A.D., Cibulskis, C., Gabriel, S.B., Gao, G.F., Ha, G., Meyerson, M., Schumacher, S.E., Shih, J., Kucherlapati, M.H., Kucherlapati, R.S., Baylin, S., Cope, L., Danilova, L., Bootwalla, M.S., Lai, P.H., Maglinte, D.T., Van Den Berg, D.J., Weisenberger, D.J., Auman, J.T., Balu, S., Bodenheimer, T., Fan, C., Hoadley, K.A., Hoyle, A.P., Jefferys, S.R., Jones, C.D., Meng, S., Mieczkowski, P.A., Mose, L.E., Perou, A.H., Perou, C.M., Roach, J., Shi, Y., Simons, J.V., Skelly, T., Soloway, M.G., Tan, D., Veluvolu, U., Fan, H., Hinoue, T., Laird, P.W., Shen, H., Zhou, W., Bellair, M., Chang, K., Covington, K., Creighton, C.J., Dinh, H., Doddapaneni, H., Donehower, L.A., Drummond, J., Gibbs, R.A., Glenn, R., Hale, W., Han, Y., Hu, J., Korchina, V., Lee, S., Lewis, L., Li, W., Liu, X., Morgan, M., Morton, D., Muzny, D., Santibanez, J., Sheth, M., Shinbrot, E., Wang, L., Wang, M., Wheeler, D.A., Xi, L., Zhao, F., Hess, J., Appelbaum, E.L., Bailey, M., Cordes, M.G., Ding, L., Fronick, C.C., Fulton, L.A., Fulton, R.S., Kandoth, C., Mardis, E.R., McLellan, M.D., Miller, C.A., Schmidt, H.K., Wilson, R.K., Crain, D., Curley, E., Gardner, J., Lau, K., Mallery, D., Morris, S., Paulauskis, J., Penny, R., Shelton, C., Shelton, T., Sherman, M., Thompson, E., Yena, P., Bowen, J., Gastier-Foster, J.M., Gerken, M., Leraas, K.M., Lichtenberg, T.M., Ramirez, N.C., Wise, L., Zmuda, E., Corcoran, N., Costello, T., Hovens, C., Carvalho, A.L., de Carvalho, A.C., Fregnani, J.H., Longatto-Filho, A., Reis, R.M., Scapulatempo-Neto, C., Silveira, HCS, Vidal, D.O., Burnette, A., Eschbacher, J., Hermes, B., Noss, A., Singh, R., Anderson, M.L., Castro, P.D., Ittmann, M., Huntsman, D., Kohl, B., Le, X., Thorp, R., Andry, C., Duffy, E.R., Lyadov, V., Paklina, O., Setdikova, G., Shabunin, A., Tavobilov, M., McPherson, C., Warnick, R., Berkowitz, R., Cramer, D., Feltmate, C., Horowitz, N., Kibel, A., Muto, M., Raut, C.P., Malykh, A., Barnholtz-Sloan, J.S., Barrett, W., Devine, K., Fulop, J., Ostrom, Q.T., Shimmel, K., Wolinsky, Y., Sloan, A.E., De Rose, A., Giuliante, F., Goodman, M., Karlan, B.Y., Hagedorn, C.H., Eckman, J., Harr, J., Myers, J., Tucker, K., Zach, L.A., Deyarmin, B., Hu, H., Kvecher, L., Larson, C., Mural, R.J., Somiari, S., Vicha, A., Zelinka, T., Bennett, J., Iacocca, M., Rabeno, B., Swanson, P., Latour, M., Lacombe, L., Têtu, B., Bergeron, A., McGraw, M., Staugaitis, S.M., Chabot, J., Hibshoosh, H., Sepulveda, A., Su, T., Wang, T., Potapova, O., Voronina, O., Desjardins, L., Mariani, O., Roman-Roman, S., Sastre, X., Stern, M.H., Cheng, F., Signoretti, S., Berchuck, A., Bigner, D., Lipp, E., Marks, J., McCall, S., McLendon, R., Secord, A., Sharp, A., Behera, M., Brat, D.J., Chen, A., Delman, K., Force, S., Khuri, F., Magliocca, K., Maithel, S., Olson, J.J., Owonikoko, T., Pickens, A., Ramalingam, S., Shin, D.M., Sica, G., Van Meir, E.G., Eijckenboom, W., Gillis, A., Korpershoek, E., Looijenga, L., Oosterhuis, W., Stoop, H., van Kessel, K.E., Zwarthoff, E.C., Calatozzolo, C., Cuppini, L., Cuzzubbo, S., DiMeco, F., Finocchiaro, G., Mattei, L., Perin, A., Pollo, B., Chen, C., Houck, J., Lohavanichbutr, P., Hartmann, A., Stoehr, C., Stoehr, R., Taubert, H., Wach, S., Wullich, B., Kycler, W., Murawa, D., Wiznerowicz, M., Chung, K., Edenfield, W.J., Martin, J., Baudin, E., Bubley, G., Bueno, R., De Rienzo, A., Richards, W.G., Kalkanis, S., Mikkelsen, T., Noushmehr, H., Scarpace, L., Girard, N., Aymerich, M., Campo, E., Giné, E., Guillermo, A.L., Van Bang, N., Hanh, P.T., Phu, B.D., Tang, Y., Colman, H., Evason, K., Dottino, P.R., Martignetti, J.A., Gabra, H., Juhl, H., Akeredolu, T., Stepa, S., Hoon, D., Ahn, K., Kang, K.J., Beuschlein, F., Breggia, A., Birrer, M., Bell, D., Borad, M., Bryce, A.H., Castle, E., Chandan, V., Cheville, J., Copland, J.A., Farnell, M., Flotte, T., Giama, N., Ho, T., Kendrick, M., Kocher, J.P., Kopp, K., Moser, C., Nagorney, D., O'Brien, D., O'Neill, B.P., Patel, T., Petersen, G., Que, F., Rivera, M., Roberts, L., Smallridge, R., Smyrk, T., Stanton, M., Thompson, R.H., Torbenson, M., Yang, J.D., Zhang, L., Brimo, F., Ajani, J.A., Gonzalez, AMA, Behrens, C., Bondaruk, J., Broaddus, R., Czerniak, B., Esmaeli, B., Fujimoto, J., Gershenwald, J., Guo, C., Lazar, A.J., Logothetis, C., Meric-Bernstam, F., Moran, C., Ramondetta, L., Rice, D., Sood, A., Tamboli, P., Thompson, T., Troncoso, P., Tsao, A., Wistuba, I., Carter, C., Haydu, L., Hersey, P., Jakrot, V., Kakavand, H., Kefford, R., Lee, K., Long, G., Mann, G., Quinn, M., Saw, R., Scolyer, R., Shannon, K., Spillane, A., Stretch, J., Synott, M., Thompson, J., Wilmott, J., Al-Ahmadie, H., Chan, T.A., Ghossein, R., Gopalan, A., Levine, D.A., Reuter, V., Singer, S., Singh, B., Tien, N.V., Broudy, T., Mirsaidi, C., Nair, P., Drwiega, P., Miller, J., Smith, J., Zaren, H., Park, J.W., Hung, N.P., Kebebew, E., Linehan, W.M., Metwalli, A.R., Pacak, K., Pinto, P.A., Schiffman, M., Schmidt, L.S., Vocke, C.D., Wentzensen, N., Worrell, R., Yang, H., Moncrieff, M., Goparaju, C., Melamed, J., Pass, H., Botnariuc, N., Caraman, I., Cernat, M., Chemencedji, I., Clipca, A., Doruc, S., Gorincioi, G., Mura, S., Pirtac, M., Stancul, I., Tcaciuc, D., Albert, M., Alexopoulou, I., Arnaout, A., Bartlett, J., Engel, J., Gilbert, S., Parfitt, J., Sekhon, H., Thomas, G., Rassl, D.M., Rintoul, R.C., Bifulco, C., Tamakawa, R., Urba, W., Hayward, N., Timmers, H., Antenucci, A., Facciolo, F., Grazi, G., Marino, M., Merola, R., de Krijger, R., Gimenez-Roqueplo, A.P., Piché, A., Chevalier, S., McKercher, G., Birsoy, K., Barnett, G., Brewer, C., Farver, C., Naska, T., Pennell, N.A., Raymond, D., Schilero, C., Smolenski, K., Williams, F., Morrison, C., Borgia, J.A., Liptay, M.J., Pool, M., Seder, C.W., Junker, K., Omberg, L., Dinkin, M., Manikhas, G., Alvaro, D., Bragazzi, M.C., Cardinale, V., Carpino, G., Gaudio, E., Chesla, D., Cottingham, S., Dubina, M., Moiseenko, F., Dhanasekaran, R., Becker, K.F., Janssen, K.P., Slotta-Huspenina, J., Abdel-Rahman, M.H., Aziz, D., Bell, S., Cebulla, C.M., Davis, A., Duell, R., Elder, J.B., Hilty, J., Kumar, B., Lang, J., Lehman, N.L., Mandt, R., Nguyen, P., Pilarski, R., Rai, K., Schoenfield, L., Senecal, K., Wakely, P., Hansen, P., Lechan, R., Powers, J., Tischler, A., Grizzle, W.E., Sexton, K.C., Kastl, A., Henderson, J., Porten, S., Waldmann, J., Fassnacht, M., Asa, S.L., Schadendorf, D., Couce, M., Graefen, M., Huland, H., Sauter, G., Schlomm, T., Simon, R., Tennstedt, P., Olabode, O., Nelson, M., Bathe, O., Carroll, P.R., Chan, J.M., Disaia, P., Glenn, P., Kelley, R.K., Landen, C.N., Phillips, J., Prados, M., Simko, J., Smith-McCune, K., VandenBerg, S., Roggin, K., Fehrenbach, A., Kendler, A., Sifri, S., Steele, R., Jimeno, A., Carey, F., Forgie, I., Mannelli, M., Carney, M., Hernandez, B., Campos, B., Herold-Mende, C., Jungk, C., Unterberg, A., von Deimling, A., Bossler, A., Galbraith, J., Jacobus, L., Knudson, M., Knutson, T., Ma, D., Milhem, M., Sigmund, R., Godwin, A.K., Madan, R., Rosenthal, H.G., Adebamowo, C., Adebamowo, S.N., Boussioutas, A., Beer, D., Giordano, T., Mes-Masson, A.M., Saad, F., Bocklage, T., Landrum, L., Mannel, R., Moore, K., Moxley, K., Postier, R., Walker, J., Zuna, R., Feldman, M., Valdivieso, F., Dhir, R., Luketich, J., Pinero, EMM, Quintero-Aguilo, M., Carlotti, C.G., Dos Santos, J.S., Kemp, R., Sankarankuty, A., Tirapelli, D., Catto, J., Agnew, K., Swisher, E., Creaney, J., Robinson, B., Shelley, C.S., Godwin, E.M., Kendall, S., Shipman, C., Bradford, C., Carey, T., Haddad, A., Moyer, J., Peterson, L., Prince, M., Rozek, L., Wolf, G., Bowman, R., Fong, K.M., Yang, I., Korst, R., Rathmell, W.K., Fantacone-Campbell, J.L., Hooke, J.A., Kovatich, A.J., Shriver, C.D., DiPersio, J., Drake, B., Govindan, R., Heath, S., Ley, T., Van Tine, B., Westervelt, P., Rubin, M.A., Lee, J.I., Aredes, N.D., Mariamidze, A., SAIC-F-Frederick, Inc, and Leidos Biomedical Research, Inc.
Subjects: 0301 basic medicine, Neuroblastoma RAS viral oncogene homolog, Genetics and Molecular Biology (all), PATHOGENESIS, pan-cancer, PROTEIN, Cancer Genome Atlas Research Network, medicine.disease_cause, computer.software_genre, Genome, Biochemistry, Transcriptome, Gene expression, HRAS, KRAS, NF1, NRAS, Ras, TCGA, drug sensitivity, machine learning, Neoplasms, PRECISION ONCOLOGY, lcsh:QH301-705.5, Regulation of gene expression, PREVIOUSLY TREATED PATIENTS, 3. Good health, Gene Expression Regulation, Neoplastic, PHASE-II, Life Sciences & Biomedicine, Signal Transduction, Biology, Machine learning, General Biochemistry, Genetics and Molecular Biology, Article, BRAF, 03 medical and health sciences, Cell Line, Tumor, medicine, Biochemistry, Genetics and Molecular Biology (all), Humans, Gene, SIGNATURES, Science & Technology, business.industry, Genome, Human, MUTATIONS, EXPRESSÃO GÊNICA, Cell Biology, SELUMETINIB, GENE, 030104 developmental biology, lcsh:Biology (General), Selumetinib, ras Proteins, Artificial intelligence, business, computer
Abstract: SUMMARY Precision oncology uses genomic evidence to match patients with treatment but often fails to identify all patients who may respond. The transcriptome of these “hidden responders” may reveal responsive molecular states. We describe and evaluate a machine-learning approach to classify aberrant pathway activity in tumors, which may aid in hidden responder identification. The algorithm integrates RNA-seq, copy number, and mutations from 33 different cancer types across The Cancer Genome Atlas (TCGA) PanCanAtlas project to predict aberrant molecular states in tumors. Applied to the Ras pathway, the method detects Ras activation across cancer types and identifies phenocopying variants. The model, trained on human tumors, can predict response to MEK inhibitors in wild-type Ras cell lines. We also present data that suggest that multiple hits in the Ras pathway confer increased Ras activity. The transcriptome is underused in precision oncology and, combined with machine learning, can aid in the identification of hidden responders., In Brief Way et al. develop a machine-learning approach using PanCanAtlas data to detect Ras activation in cancer. Integrating mutation, copy number, and expression data, the authors show that their method detects Ras-activating variants in tumors and sensitivity to MEK inhibitors in cell lines.
Published: 2018

7. The changing characteristics of patients infected with chronic hepatitis C virus from 2014 to 2019: Real‐world data from the German Hepatitis C‐Registry (DHC‐R)

Author: Kristina Lohmann, Dietrich Hüppe, Dennis Hidde, Stefan Mauss, Hartwig Klinker, Albrecht Stoehr, Mark Bondin, Peter Buggisch, Gerlinde Teuber, and Heiner Wedemeyer
Subjects: medicine.medical_specialty, Hepacivirus, Hepatitis C virus, Medizin, medicine.disease_cause, Antiviral Agents, Underserved Population, Virology, Internal medicine, Humans, Medicine, Prospective Studies, Registries, Substance Abuse, Intravenous, Prospective cohort study, Hepatitis, Hepatology, biology, business.industry, Hepatitis C, Hepatitis C, Chronic, Middle Aged, biology.organism_classification, medicine.disease, Infectious Diseases, Cohort, business, Viral hepatitis
Abstract: The number of patients diagnosed with hepatitis C virus (HCV) is markedly higher than the number initiating treatment indicating gaps in the care cascade, likely centred around reaching at-risk populations. Understanding changing characteristics of patients with HCV allows for targeted programs that increase linkage to care. We investigated changes in demographic and clinical characteristics of patients registered in the German Hepatitis C-Registry (DHC-R) from 1 January 2014 to 31 December 2019. The DHC-R is an ongoing, noninterventional, multicentre, prospective, observational cohort registry including 327 German centres. Patient characteristics were analysed over time in 7 phases for all patients completing a screening visit. Overall, 14,357 patients were enrolled. The percentage of treatment-naïve/non-cirrhotic patients increased from 34.4% in phase 1 (1 January–31 December 2014) to 68.2% in phase 7 (1 August–31 December 2019). The proportion of migrants, alcohol users, people who inject drugs, and those receiving opiate substitution therapy increased in later registry phases. Most patients (60.1%) were receiving comedication at baseline. The most prescribed comedications were drugs used to treat opioid dependence which increased from 9.2% in phase 1 to 24.0% in phase 7. The patients’ mean age decreased from 52.3 years in phase 1 to 48.7 years in phase 7. From 2014 to 2019, the proportion of at-risk patients enrolling in the registry increased. To eliminate viral hepatitis as a major public health threat, a continued commitment to engaging underserved populations into the HCV care cascade is needed.
Published: 2021

8. Prognostic impact of molecular muscle-invasive bladder cancer subtyping approaches and correlations with variant histology in a population-based mono-institutional cystectomy cohort

Author: Veronika Weyerer, Fabienne Lange, Sven Wach, Simone Bertz, Markus Eckstein, Helge Taubert, Danijel Sikic, Bernd Wullich, Carol Geppert, Arndt Hartmann, and Robert Stoehr
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, Molecular subtypes, Urology, medicine.medical_treatment, Cystectomy, Cohort Studies, 03 medical and health sciences, Basal (phylogenetics), 0302 clinical medicine, Internal medicine, medicine, Humans, Neoplasm Invasiveness, ddc:610, Correlation of Data, Survival analysis, Carcinoma, Transitional Cell, Bladder cancer, business.industry, GATA3, medicine.disease, Topic Paper, Prognosis, Survival Analysis, Subtyping, Histological variants, 030104 developmental biology, Urinary Bladder Neoplasms, 030220 oncology & carcinogenesis, Immunohistochemistry, Prognostic impact, FOXA1, business, Muscle-invasive bladder cancer
Abstract: Purpose Recently discovered molecular classifications for urothelial bladder cancer appeared to be promising prognostic and predictive biomarkers. The present study was conducted to evaluate the prognostic impact of molecular subtypes assessed by two different methodologies (gene and protein expression), to compare these two approaches and to correlate molecular with histological subtypes in a consecutively collected, mono-institutional muscle-invasive bladder cancer (MIBC) cohort. Methods 193 MIBC were pathologically re-evaluated and molecular subtypes were assessed on mRNA (NanoString technology, modified 21-gene-containing MDACC approach) and protein levels (immuno-histochemical [IHC] analysis of CK5, CK14, CD44, CK20, GATA3 and FOXA1). Descriptive statistical methods and uni-/multi-variable survival models were employed to analyze derived data. Results Neither gene expression nor protein-based subtyping showed significant associations with disease-specific (DSS) or recurrence-free survival (RFS). Agreement between mRNA (reference) and protein-based subtyping amounted 68.6% for basal, 76.1% for luminal and 50.0% for double-negative tumors. Histological subtypes associated with RFS in uni-variable (P = 0.03), but not in multivariable survival analyses. Tumors with variant histology predominantly showed luminal subtypes (gene expression subtyping: 36/55 cases, 65.5%; protein subtyping: 44/55 cases, 80.0%). Squamous differentiation significantly associated with basal subtypes (gene expression subtyping: 44/45 squamous cases, 97.8%; protein subtyping: 36/45 cases, 80.0%). Conclusion In our consecutive cystectomy cohort, neither gene, protein expression-based subtyping, nor histological subtypes associated with DSS or RFS in multi-variably adjusted survival analyses. Application of a limited IHC subtyping marker panel showed high concordance of 83.9% with gene expression-based subtyping, thus underlining the utility for subtyping in pathological routine diagnostics. In addition, histological MIBC subtypes are strong indicators for intrinsic subtypes.
Published: 2021

9. A population pharmacodynamic Markov mixed‐effects model for determining remimazolam‐induced sedation when co‐administered with fentanyl in procedural sedation

Author: Thomas Stoehr, Frank Schippers, Laura Curd, Natalie Delpratt, Virginia D. Schmith, Jie Zhou, Lauren R. L. Lohmer, and Joachim Ossig
Subjects: Male, medicine.drug_class, Sedation, Population, RM1-950, Pain, Procedural, Placebo, Models, Biological, Article, General Biochemistry, Genetics and Molecular Biology, Fentanyl, Benzodiazepines, Pharmacokinetics, medicine, Humans, Computer Simulation, General Pharmacology, Toxicology and Pharmaceutics, Infusions, Intravenous, education, Aged, Clinical Trials as Topic, education.field_of_study, Benzodiazepine, Dose-Response Relationship, Drug, business.industry, Research, General Neuroscience, Age Factors, Drug Synergism, Articles, General Medicine, Middle Aged, Healthy Volunteers, Markov Chains, Biological Variation, Population, Anesthesia, Pharmacodynamics, Female, Therapeutics. Pharmacology, Deep Sedation, medicine.symptom, Public aspects of medicine, RA1-1270, Remimazolam, business, medicine.drug
Abstract: The clinical effects of remimazolam (an investigational, ultra‐short acting benzodiazepine being studied in procedural sedation) were measured using the Modified Observer’s Assessment of Awareness/Sedation Scale (MOAA/S). The objective of this analysis was to develop a population pharmacokinetic/pharmacodynamic model to describe remimazolam‐induced sedation with fentanyl over time in procedural sedation. MOAA/S from 10 clinical phase I–III trials were pooled for analysis, where data were collected after administration of placebo or remimazolam with or without concomitant fentanyl. A Markov model described transition states for 35,356 MOAA/S‐time observations from 1071 subjects. Effect‐compartment models of remimazolam and fentanyl linked plasma concentrations to the Markov model, and drug effects were described using a synergistic maximum effect (Emax) model. Simulations were performed to identify the optimal remimazolam‐fentanyl combination doses in procedural sedation. Fentanyl showed synergistic effects with remimazolam in sedation. Increasing age was related to longer recovery from sedation. Patients with body mass index greater than 25 kg/m2 had ~30% higher rates of distribution from plasma to the effect site (keo), indicating a slightly faster onset of sedation. Simulations showed that remimazolam 5 mg was more appropriate than 4 or 6 mg when administered with fentanyl 50 μg. The model and simulations support that a combination of remimazolam 5 mg with fentanyl 50 μg is an appropriate dosing regimen and the dose of remimazolam does not need to be changed in elderly patients, but some elderly patients may have a longer duration of sedation.
Published: 2021

10. Current Strategies to Identify Patients That Will Benefit from TACE Treatment and Future Directions a Practical Step-by-Step Guide

Author: Fabian Stoehr, Lukas Müller, Roman Kloeckner, Arndt Weinmann, Aline Mähringer-Kunz, and Felix Hahn
Subjects: medicine.medical_specialty, business.industry, practical step-by-step guide, Review, hepatocellular carcinoma, transarterial chemoembolization, Hypervascularity, Disease, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Medicine, 030211 gastroenterology & hepatology, Tumor growth, Liver function, treatment decision support, Stage (cooking), business, Liver cancer, Intensive care medicine, survival prediction, Staging system
Abstract: Treatment of hepatocellular carcinoma (HCC) depends on the stage of disease. In the Western Hemisphere, the Barcelona Clinic Liver Cancer classification (BCLC) is the preferred staging system. Approximately one-third of patients initially present with intermediate-stage disease. For these patients, transarterial chemoembolization (TACE) is the treatment of choice. However, the intermediate-stage comprises a heterogeneous subgroup of patients with considerable differences in tumor burden and liver function. In addition, differences in individual factors that are not captured by the BCLC framework, such as the tumor growth pattern, degree of hypervascularity, and vascular supply, complicate further evaluation of these patients. Due to these differences, not all patients benefit equally from TACE. Several tools and scoring systems have been devised to provide decision-making support. All of these have shown promising initial results but failed external evaluation and have not been translated to the clinic. Nevertheless, criteria for objectifying treatment decisions in daily clinical practice are needed in all stages of disease. Therefore, this review provides a concise practical step-by-step guide on current strategies for patient selection and decision-making, with a focus on TACE, to critically evaluate the existing decision-support tools and provide a summary of the latest updates in the field.
Published: 2021

11. NSD3-NUTM1-rearranged carcinoma of the median neck/thyroid bed developing after recent thyroidectomy for sclerosing mucoepidermoid carcinoma with eosinophilia: report of an extraordinary case

Author: Robert Stoehr, Abbas Agaimy, Sabine Semrau, Arndt Hartmann, Norbert Meidenbauer, Konstantinos Mantsopoulos, and Lars Tögel
Subjects: BRD4, Pathology, medicine.medical_specialty, medicine.medical_treatment, Histogenesis, NSD3, Pathology and Forensic Medicine, Head and neck, Mucoepidermoid carcinoma, Carcinoma, Medicine, Eosinophilia, ddc:610, Molecular Biology, Thyroid gland, business.industry, Brief Report, Thyroid, Thyroidectomy, Sclerosing mucoepidermoid carcinoma with eosinophilia, Neck dissection, NUTM1, Cell Biology, General Medicine, NUT carcinoma, medicine.disease, medicine.anatomical_structure, Midline carcinoma, medicine.symptom, business
Abstract: Sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE) is an exceedingly rare low-grade thyroid malignancy of unknown histogenesis. NUT carcinoma is another rare, highly aggressive neoplasm with predilection for the midline, defined by recurrent NUTM1 fusions. The bromodomain family genes (BRD4 or BRD3) and rarely NSD3, ZNF532, or others are known fusion partners. We describe an extraordinary case of a 42-year-old female with a thyroid SMECE treated by thyroidectomy and neck dissection. She presented 6 months later with extensive midline recurrence encasing/compressing the trachea. Biopsy revealed poorly differentiated carcinoma with abrupt squamous differentiation, suggestive of NUT carcinoma. Immunohistochemistry confirmed expression of monoclonal NUT antibody. Targeted RNA sequencing revealed the NSD3-NUTM1 fusion in the NUT carcinoma, but not in the SMECE. This unique case highlights unusual sequential origin of two exceptionally rare entities at same anatomic site and underlines the necessity of sampling unexpectedly aggressive recurrences of otherwise indolent malignancies.
Published: 2021

12. Deriving internal crown geometric features of Douglas-fir from airborne laser scanning in a realized-gain trial

Author: Yousry A. El-Kassaby, Nicholas C. Coops, Tristan R.H. Goodbody, Francois du Toit, and Michael Stoehr
Subjects: 0106 biological sciences, 010504 meteorology & atmospheric sciences, Laser scanning, business.industry, Crown (botany), Forestry, 15. Life on land, 01 natural sciences, Optics, Environmental science, business, 010606 plant biology & botany, 0105 earth and related environmental sciences, Douglas fir
Abstract: Tree improvement programs are critical to establishing high yield seed sources while maintaining genetic diversity and developing sustainable plantation forests. Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) is commonly used in improvement programs due to its superior strength and stiffness properties. Progeny testing trials in British Columbia (BC), Canada aim to increase stem volume without sacrificing wood quality. As genetically improved stock in BC is entering its fourth generation, wood quality and branch attributes are becoming more important as selection criteria evolve. This study investigates the utility of Airborne Laser Scanning (ALS) to produce metrics that describe branch attributes, and test whether these attributes showed differences in trees of three different genetic gain levels (GL); Wild-Stand (WS), Mid-Gain (MG) and Top-Cross (TC), planted at two different spacings (2.9 m and 4.0 m) in a realized-gain trial. New methods were developed to utilize ALS data to estimate metrics such as branch angle, length and volume using a point clustering approach. The relative impact of GL and spacing on branch attributes were assessed. Spacing was significant for branch angle (2.9 m = 73.53°, 4.0 m = 72.46°), whereas GL (WS = 0.861 m, MG = 0.917 m, TC = 0.948 m) and spacing (2.9 m = 0.884, 4.0 m = 0.942) were significant for length. For all metrics, TC trees at 4.0 m spacing were consistently significantly different whenever GL or the interaction effect was significant. This data provide an insight into how ALS can be used to model branch attributes, whereas the ability to analyse trees by plot, individual tree and individual branch attributes further allows researchers and foresters to maximize the value of ALS data. Findings from this research can be integrated into large-scale programs not just for monitoring trees, but also for identifying new trees that can display attributes associated with larger volumes and increased value.
Published: 2021

13. El poeta viciado: Utz Rachowski como poeta, prisionero político y consejero

Author: Louise Stoehr and Ingo Stoehr
Subjects: Subjectivity, poesía como droga, History, literatura de protest, Metaphor, literatura de protesto, media_common.quotation_subject, lcsh:Literature (General), police state, Prison, prison literature, German, Politics, literatura en la cárcel, poetry as drug, exile, State (polity), poesia como droga, literatura sobre prisão, media_common, Literature, lcsh:French literature - Italian literature - Spanish literature - Portuguese literature, Poetry, business.industry, General Medicine, lcsh:PN1-6790, Tone (literature), language.human_language, protest literature, lcsh:PQ1-3999, language, exilio, exílio, estado policial, business
Abstract: Closely analyzing selected poems, this article traces the major phases of the five-decade-long career of contemporary German poet Utz Rachowski. First, East Germany’s paranoid repressive police force declared five of Rachowski’s poems to be subversive. Second, with his prison poems, Rachowski asserts his subjectivity against objectifying punishments. From this phase onward, the metaphor “poetry is a drug” helps us to understand the role of poetry for Rachowski. Third, his exile led to a sense of loss of home expressed in mature poetry. Finally, taking on responsibility for a dog during his 2012 stay in the United States reconfirmed Rachowski’s belief in trust, giving his poetry new productivity and a gentler tone. Outside his poetic career, Rachowski counsels people who have suffered under the state repressions---Original in English. Analizando algunos poemas escogidos, este artículo rastrea las fases más importantes de la extensa carrera de Utz Rachowski como poeta. En primer lugar, la policía de la Alemania del Este, paranoica y represiva, declaró subversivos cinco poemas de Rachowski. Después, con sus poemas sobre la prisión, Rachowski afirma su subjetividad contra la objetivización del castigo, como su metáfora “la poesía es una droga” nos ayuda a comprender. Más tarde, su exilio le llevó a la experiencia de pérdida del hogar. Finalmente, la fe de Rachowski en la confianza entre individuos se vio reforzada cuando se decidió a responsabilizarse de un perro durante su estancia en Estados Unidos en 2012 y dio a su poesía nueva productividad y un tono más suave.---Original en inglés. Closely analyzing selected poems, this article traces the major phases of the five-decade-long career of contemporary German poet Utz Rachowski. First, East Germany’s paranoid repressive police force declared five of Rachowski’s poems to be subversive. Second, with his prison poems, Rachowski asserts his subjectivity against objectifying punishments. From this phase onward, the metaphor “poetry is a drug” helps us to understand the role of poetry for Rachowski. Third, his exile led to a sense of loss of home expressed in mature poetry. Finally, taking on responsibility for a dog during his 2012 stay in the United States reconfirmed Rachowski’s belief in trust, giving his poetry new productivity and a gentler tone. Outside his poetic career, Rachowski counsels people who have suffered under the state repressions----------------------------------------------------------------------------O POETA VICIADO: UTZ RACHOWSKI COMO POETA, PRISIONEIRO POLÍTICO E CONSELHEIROAtravés da análise de alguns dos poemas de Utz Rachowski, este artigo descreve as principais fases de cinco décadas de sua carreira como poeta. Primeiro, analisamos como a força policial da Alemanha, paranoica e repressiva, declarou que cinco dos poemas de Rachowski eram subversivos. Em seguida, analisamos como os poemas de Rachowski sobre a prisão afirmam sua subjetividade contra a objetivação do castigo, no qual o autor usando a metáfora “a poesia é uma droga” ajuda os leitores a entender seus poemas. Mais adiante analisamos como o exílio levou Rachowski a ter uma sensação de perda, já que o mesmo perdeu o direito de ser livre em seu próprio país. E finalmente, discorremos sobre a fase em que Rachowski cuidou de um cachorro em 2012 nos Estados Unidos, o que o ajudou a restaurar sua confiança em relação à sociedade, dando a suas poesias uma nova produtividade e um tom mais suave.---Original em inglês.
Published: 2019

14. FGFR3 Mutation Status and FGFR3 Expression in a Large Bladder Cancer Cohort Treated by Radical Cystectomy: Implications for Anti-FGFR3 Treatment?†

Author: Hossain Roshani, Laura S. Mertens, Y. Neuzillet, Núria Malats, Geert J.L.H. van Leenders, Markus Eckstein, Wolfgang Otto, Robert Stoehr, Ellen C. Zwarthoff, Damien Pouessel, Katrin Hippe, Yanish Soorojebally, Peter J. Boström, Maximilian Burger, Cheno Abas, Joost L. Boormans, Arndt Hartmann, Mirari Marquez, Michiel S. van der Heijden, Annegien Broeks, Joyce Sanders, Alexandre R. Zlotta, Stefanie Götz, Roman Mayr, Francisco X. Real, Nanor Sirab, Simone Bertz, Bas W.G. van Rhijn, Theo van der Kwast, Bernd Wullich, Tahlita C.M. Zuiverloon, François Radvanyi, Michael A.S. Jewett, Yves Allory, Urology, Pathology, and Graduate School
Subjects: Male, musculoskeletal diseases, congenital, hereditary, and neonatal diseases and abnormalities, Urology, medicine.medical_treatment, Bladder, Mutant, 030232 urology & nephrology, Expression, medicine.disease_cause, Cystectomy, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Humans, Receptor, Fibroblast Growth Factor, Type 3, Medicine, Stage (cooking), Aged, Cancer, Mutation, Bladder cancer, business.industry, Carcinoma in situ, Middle Aged, Fibroblast growth factor receptor 3, Prognosis, medicine.disease, musculoskeletal system, Gene Expression Regulation, Neoplastic, Survival Rate, stomatognathic diseases, Urinary Bladder Neoplasms, FGFR3, 030220 oncology & carcinogenesis, Cancer research, Female, Urothelial carcinoma, business
Abstract: Fibroblast growth factor receptor 3 (FGFR3) is an actionable target in bladder cancer (BC). FGFR3 mutations are common in noninvasive BC and associated with favorable BC prognosis. Overexpression was reported in up to 40% of FGFR3 wild-type muscle-invasive BC. We analyzed FGFR3 mutations, FGFR3, and p53 protein expression and assessed their prognostic value in a cohort of 1000 chemotherapy-naive radical cystectomy specimens. FGFR3 mutations were found in 11%, FGFR3 overexpression was found in 28%, and p53 overexpression was found in 69% of tumors. Among FGFR3 mutant tumors, 73% had FGFR3 overexpression versus 22% among FGFR3 wild-type tumors. FGFR3 mutations were significantly associated with lower pT stage, tumor grade, absence of carcinoma in situ, pN0, low-level p53, and longer disease-specific survival (DSS). FGFR3 overexpression was associated only with lower pT stage and tumor grade. Moreover, FGFR3 overexpression was not associated with DSS in patients with FGFR3 wild-type tumors. In conclusion, FGFR3 mutations identified patients with favorable BC at cystectomy. Our results suggest that FGFR3 mutations have a driver role and are functionally distinct from FGFR3 overexpression. Hence, patients with FGFR3 mutations would be more likely to benefit from anti-FGFR3 therapy. Ideally, further research is needed to test this hypothesis. Patient summary: Oncogenic fibroblast growth factor receptor 3 (FGFR3) mutations are very common in bladder cancer. In this report, we found that these FGFR3 mutations were associated with favorable features and prognosis of bladder cancer compared with patients with FGFR3 overexpressed tumors only. As a consequence, patients with FGFR3 mutant tumors would be more likely to benefit from anti-FGFR3 therapy than patients with FGFR3 protein overexpression only.
Published: 2020

15. Posterior Cranial Vault Distraction (PCVD): Common Complication Rates and Strategies of Prevention and Management

Author: Nikhil K. Murthy, Abbas Hassan, Tord D. Alden, Jenna R. Stoehr, Ava G. Chappell, and Arun K. Gosain
Subjects: medicine.medical_specialty, Osteogenesis, Distraction, Craniosynostosis, Craniosynostoses, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, Distraction, Cranial vault, medicine, Postoperative infection, Humans, Craniofacial, 030223 otorhinolaryngology, Device failure, Surgeons, Cerebrospinal Fluid Leak, Cerebrospinal fluid leak, business.industry, Skull, 030206 dentistry, General Medicine, medicine.disease, Surgery, Otorhinolaryngology, Complication, business
Abstract: Background Posterior cranial vault distraction (PCVD) is a well-established procedure to treat infants with craniosynostosis. Craniofacial surgeons have seen an evolution in the complications following PCVD. This report aims to demonstrate the rates of common complications from PCVD, and to identify strategies for prevention and management of these complications. Methods A formal literature review of studies on postoperative complications from PCVD was conducted to identify the breadth of reported complications from PCVD and rates of occurrence. Results A total of 776 articles were captured by our search strategy. Nineteen original articles met inclusion criteria, with a total of 342 patients. The average rate of reported complications was 25%, range (0%-100%). The most commonly reported complication was postoperative infection (23.7%), followed by cerebrospinal fluid leak (20.3%) and device failure (15.3%). Postoperative infection, device exposure, iatrogenic vascular injury, cerebrospinal fluid leak, and other complications have the potential to disrupt distraction and increase morbidity and mortality. Conclusions By continuing to identify and evaluate complications, prevention strategies can be determined and standardized to decrease complications from PCVD. These efforts uphold the ultimate goal for surgeons involved in the treatment of craniosynostosis: to provide safe, effective surgical care.
Published: 2020

16. Population Pharmacokinetics of Remimazolam in Procedural Sedation With Nonhomogeneously Mixed Arterial and Venous Concentrations

Author: Lauren R. L. Lohmer, Frank Schippers, Thomas Stoehr, Joachim Ossig, Virginia D. Schmith, Jie Zhou, and Laura Curd
Subjects: Male, 030213 general clinical medicine, Datasets as Topic, Pilot Projects, Pain, Procedural, 030226 pharmacology & pharmacy, Benzodiazepines, 0302 clinical medicine, General Pharmacology, Toxicology and Pharmaceutics, Infusions, Intravenous, Aged, 80 and over, Volume of distribution, Clinical Trials as Topic, education.field_of_study, lcsh:Public aspects of medicine, General Neuroscience, Venous Plasma, Articles, General Medicine, Middle Aged, Random effects model, Healthy Volunteers, Cardiology, Female, medicine.symptom, Adult, medicine.medical_specialty, Sedation, Population, Models, Biological, Article, General Biochemistry, Genetics and Molecular Biology, Young Adult, 03 medical and health sciences, Sex Factors, Pharmacokinetics, Internal medicine, Covariate, medicine, Humans, education, Aged, business.industry, Research, lcsh:RM1-950, lcsh:RA1-1270, lcsh:Therapeutics. Pharmacology, Biological Variation, Population, Deep Sedation, Remimazolam, business
Abstract: Remimazolam is an ultra-short acting benzodiazepine under development for procedural sedation and general anesthesia. Population pharmacokinetic analysis (PopPK) was conducted for remimazolam with arterial and venous samples previously, but results were limited by arterial-venous concentration differences and inaccurate central volume of distribution (V1) estimates. A new model was developed to describe covariate effects after accounting for arterial-venous differences. Arterial and venous plasma concentration-time data from 11 clinical trials were pooled for PopPK. Data from two constant-rate infusion studies were used to account for venous-to-arterial (VtoA) ratio within residual error and to accurately estimate V1. V1 and VtoA ratio from the pilot model were applied to the full dataset, where the optimal fixed/random effects and covariates were assessed. VtoA ratio was described using a maximum effect (Emax ) model during infusion and as a constant postdose. V1 was estimated as 4.83 L for a 70 kg subject and interindividual variability (IIV) on V1 could only be estimated in studies with early concentrations. IIV on clearance was low (22.9%). Covariates included effects of sex on clearance (women 10% > men), and race on clearance and steady-state volume of distribution (African Americans 16% < other races). Arterial-venous concentration differences were best described using an Emax model during infusion with a constant ratio after infusion, resulting in low residual error (20.7%). There are no clinically relevant dose adjustments needed for any covariates based on pharmacokinetic differences.
Published: 2020

17. A visual approach to explainable computerized clinical decision support

Author: Alexander Oeser, Jan Gaebel, Steffen Oeltze-Jafra, Marc Streit, Andreas Dietz, Matthaeus Stoehr, and Juliane Müller
Subjects: Knowledge management, Computer science, business.industry, media_common.quotation_subject, General Engineering, Bayesian network, 020207 software engineering, 02 engineering and technology, Certainty, Computer Graphics and Computer-Aided Design, Clinical decision support system, Transparency (behavior), Textual information, Clinical knowledge, Human-Computer Interaction, Visual approach, 0202 electrical engineering, electronic engineering, information engineering, 020201 artificial intelligence & image processing, business, Multiple view, media_common
Abstract: Clinical Decision Support Systems (CDSS) provide assistance to physicians in clinical decision-making. Based on patient-specific evidence items triggering the inferencing process, such as examination findings, and expert-modeled or machine-learned clinical knowledge, these systems provide recommendations in finding the right diagnosis or the optimal therapy. The acceptance of, and the trust in, a CDSS are highly dependent on the transparency of the recommendation’s generation. Physicians must know both the key influences leading to a specific recommendation and the contradictory facts. They must also be aware of the certainty of a recommendation and its potential alternatives. We present a glyph-based, interactive multiple views approach to explainable computerized clinical decision support. Four linked views (1) provide a visual summary of all evidence items and their relevance for the computation result, (2) present linked textual information, such as clinical guidelines or therapy details, (3) show the certainty of the computation result, which includes the recommendation and a set of clinical scores, stagings etc., and (4) facilitate a guided investigation of the reasoning behind the recommendation generation as well as convey the effect of updated evidence items. We demonstrate our approach for a CDSS based on a causal Bayesian network representing the therapy of laryngeal cancer. The approach has been developed in close collaboration with physicians, and was assessed by six expert otolaryngologists as being tailored to physicians’ needs in understanding a CDSS.
Published: 2020

18. Hepatitis C therapy with grazoprevir/elbasvir and glecaprevir/pibrentasvir in patients with advanced chronic kidney disease: data from the German Hepatitis C-Registry (DHC-R)

Author: Christine John, Claus Niederau, Renate Heyne, Albrecht Stoehr, Hartwig Klinker, Gerlinde Teuber, Johannes Wiegand, U Naumann, Yvonne Serfert, Thomas Berg, Stefan Zeuzem, German Hepatitis C-Registry, and K. Stein
Subjects: Cyclopropanes, medicine.medical_specialty, Elbasvir, Aminoisobutyric Acids, Pyrrolidines, Genotype, Proline, Sustained Virologic Response, Lactams, Macrocyclic, Renal function, Hepacivirus, Antiviral Agents, Gastroenterology, chemistry.chemical_compound, Leucine, Quinoxalines, Internal medicine, Ribavirin, medicine, Humans, Prospective Studies, Registries, Renal Insufficiency, Chronic, Benzofurans, Hepatitis, Sulfonamides, Hepatology, business.industry, Imidazoles, Hepatitis C, Glecaprevir, Hepatitis C, Chronic, medicine.disease, Amides, Pibrentasvir, chemistry, Grazoprevir, Benzimidazoles, Drug Therapy, Combination, Carbamates, business
Abstract: Grazoprevir/elbasvir and glecaprevir/pibrentasvir (G/P) are the two preferred treatment options for patients with chronic hepatitis C virus (HCV) infection and a glomerular filtration rate (GFR)30 mL/min. Both therapies have been separately analyzed in different real-life cohorts; however, a direct comparison has not been performed so far. We, therefore, analyzed safety and effectiveness of both regimens in a concerted real-life population.The Germany Hepatitis C-Registry is a prospective national real-world registry. The analysis is based on 2773 patients with documented GFR at baseline treated with grazoprevir/elbasvir (N = 1041), grazoprevir/elbasvir + ribavirin (N = 53) and glecaprevir/pibrentasvir (N = 1679).A total of 93 patients with GFR30 mL/min were treated with grazoprevir/elbasvir (N = 56), grazoprevir/elbasvir + ribavirin (N = 4), and glecaprevir/pibrentasvir (N = 33). They suffered significantly more frequent from diabetes mellitus, hypertension, and coronary heart disease than individuals with GFR30 mL/min and showed the following baseline characteristics: 20.4, 55.9, 3.2, 12.9, and 5.3% were infected with HCV-genotypes 1a, 1b, 2, 3, and 4; 12.9% suffered from liver cirrhosis; 80.1% were treatment-naïve. Baseline characteristics except distribution of HCV-genotype 1b (n = 43/52 treated with grazoprevir/elbasvir) and sustained virologic response rates (SVR12) did not differ significantly between glecaprevir/pibrentasvir (SVR12: 100%) and grazoprevir/elbasvir (SVR12: 97.9%).Fatigue, headache, abdominal discomfort, and arthralgia were the most frequently reported adverse events without a statistical difference between grazoprevir/elbasvir and glecaprevir/pibrentasvir.In patients with chronic hepatitis C and a baseline GFR ≤30 mL/min grazoprevir/elbasvir and glecaprevir/pibrentasvir show an equally favorable safety profile and antiviral efficacy and can both be recommended for real-life use.
Published: 2020

19. Mass Spectrometry Imaging Differentiates Chromophobe Renal Cell Carcinoma and Renal Oncocytoma with High Accuracy

Author: Kerstin Junker, Mark Kriegsmann, Holger Moch, Matthias M. Gaida, Peter Schirmacher, Christine Stoehr, Nadine Maurer, Rita Casadonte, Wilko Weichert, Gunhild Mechtersheimer, Arndt Hartmann, Franziska Erlmeier, Sören-Oliver Deininger, Albrecht Stenzinger, Joerg Kriegsmann, Kristina Schwamborn, Katharina Kriegsmann, Christiane Zgorzelski, University of Zurich, Kriegsmann, Mark, and Kriegsmann, Katharina
Subjects: 0301 basic medicine, Chromophobe Renal Cell Carcinoma, 610 Medicine & health, mass spectrometry imaging, Biology, Cross-validation, Mass spectrometry imaging, Oncocytic renal tumors, 03 medical and health sciences, 0302 clinical medicine, proteomics, 10049 Institute of Pathology and Molecular Pathology, medicine, Renal oncocytoma, chromophobe renal cell carcinoma, business.industry, medicine.disease, Linear discriminant analysis, Random forest, Support vector machine, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, 2730 Oncology, Differential diagnosis, Nuclear medicine, business, renal oncocytoma, Research Paper
Abstract: Background: While subtyping of the majority of malignant chromophobe renal cell carcinoma (cRCC) and benign renal oncocytoma (rO) is possible on morphology alone, additional histochemical, immunohistochemical or molecular investigations are required in a subset of cases. As currently used histochemical and immunohistological stains as well as genetic aberrations show considerable overlap in both tumors, additional techniques are required for differential diagnostics. Mass spectrometry imaging (MSI) combining the detection of multiple peptides with information about their localization in tissue may be a suitable technology to overcome this diagnostic challenge. Patients and Methods: Formalin-fixed paraffin embedded (FFPE) tissue specimens from cRCC (n=71) and rO (n=64) were analyzed by MSI. Data were classified by linear discriminant analysis (LDA), classification and regression trees (CART), k-nearest neighbors (KNN), support vector machine (SVM), and random forest (RF) algorithm with internal cross validation and visualized by t-distributed stochastic neighbor embedding (t-SNE). Most important variables for classification were identified and the classification algorithm was optimized. Results: Applying different machine learning algorithms on all m/z peaks, classification accuracy between cRCC and rO was 85%, 82%, 84%, 77% and 64% for RF, SVM, KNN, CART and LDA. Under the assumption that a reduction of m/z peaks would lead to improved classification accuracy, m/z peaks were ranked based on their variable importance. Reduction to six most important m/z peaks resulted in improved accuracy of 89%, 85%, 85% and 85% for RF, SVM, KNN, and LDA and remained at the level of 77% for CART. t-SNE showed clear separation of cRCC and rO after algorithm improvement. Conclusion: In summary, we acquired MSI data on FFPE tissue specimens of cRCC and rO, performed classification and detected most relevant biomarkers for the differential diagnosis of both diseases. MSI data might be a useful adjunct method in the differential diagnosis of cRCC and rO.
Published: 2020

20. Randomized Crossover Trial to Compare Abuse Liability of Intravenous Remimazolam Versus Intravenous Midazolam and Placebo in Recreational Central Nervous System Depressant Users

Author: Lynn R. Webster, Thomas Stoehr, Marija Pesic, Robert Saunders, Frank Schippers, Shawn L. Searle, and Keith Borkett
Subjects: Adult, Male, Adolescent, Visual Analog Scale, Substance-Related Disorders, medicine.drug_class, Midazolam, Sedation, Placebo, abuse potential, 030226 pharmacology & pharmacy, Benzodiazepines, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Drug tolerance, Recreational Drug Use, medicine, Humans, Hypnotics and Sedatives, Pharmacology (medical), NON COVID ARTICLES, Pharmacology, Benzodiazepine, Cross-Over Studies, business.industry, Central Nervous System Depressants, remimazolam, Middle Aged, randomized clinical trial, Crossover study, Drug class, 030220 oncology & carcinogenesis, Anesthesia, Administration, Intravenous, Female, Amnesia, benzodiazepine, medicine.symptom, business, Remimazolam, Drug Abuse Deterrence, medicine.drug
Abstract: Remimazolam (RMZ) is a new and ultra‐fast‐acting, short‐duration intravenous benzodiazepine, a drug class associated with abuse potential. This trial was designed to compare the abuse potential of remimazolam with placebo and midazolam (MDZ), a well‐characterized member of the same pharmacological class in healthy, recreational drug users 18‐55 years‐of‐age, who demonstrated good drug tolerance and were able to discriminate between midazolam and placebo. At equipotent intravenous doses selected to produce effects ranging from mild/moderate to relatively strong sedation without loss of consciousness (RMZ: 5, 10 mg versus MDZ: 2.5, 5 mg), peak scores (Emax or Emin, respectively) for drug liking, good/bad/any effects, and sedation (drowsiness and relaxation) were significantly greater than placebo for both active drugs and were broadly comparable between RMZ and MDZ. In contrast, areas under the effect‐time curves (TA_AUE) were notably lower for RMZ versus MDZ, particularly for measures of good and any effects, reflecting the shorter duration of action and consistent with the more rapid observed plasma clearance for RMZ versus MDZ and the lack of an active RMZ metabolite. Scores for willingness to take drug again were also lower for RMZ versus MDZ, but not significantly so. We concluded that the abuse potential of RMZ is comparable to or lower than that of MDZ, a drug known to have a low potential for intravenous abuse.
Published: 2020

21. Utilization and effectiveness of elbasvir/grazoprevir and adoption of resistance-associated substitutions testing in real-world treatment of hepatitis C virus genotype 1A infection: results from the German Hepatitis C-Registry

Author: Hartwig Klinker, Karen Martin, Renate Heyne, Christine John, Markus Cornberg, Albrecht Stoehr, Holger Hinrichsen, Veronika Guenther, V Witte, Karl-Georg Simon, and Stefan Zeuzem
Subjects: Cyclopropanes, Male, Sustained Virologic Response, resistance-associated substitution testing, Hepacivirus, nonstructural protein 5A, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, Original Articles: Hepatology, Registries, Sulfonamides, elbasvir and grazoprevir, Imidazoles, virus diseases, Hepatitis C, Middle Aged, Grazoprevir, 030220 oncology & carcinogenesis, Drug Therapy, Combination, 030211 gastroenterology & hepatology, Viral load, medicine.medical_specialty, Elbasvir, Genotype, Antiviral Agents, genotype 1A, 03 medical and health sciences, Quinoxalines, Internal medicine, medicine, Humans, chronic hepatitis C, Elbasvir, Grazoprevir, Benzofurans, direct-acting antiviral agent, Hepatitis, baseline viral load, Hepatology, business.industry, Ribavirin, Hepatitis C, Chronic, medicine.disease, Amides, digestive system diseases, Regimen, chemistry, Carbamates, business
Abstract: Background For treatment of genotype 1a (GT1a) infection with elbasvir/grazoprevir, the German guidelines recommend a differentiated approach depending on baseline viral load (BVL). For low BVL ≤800 000 IU/mL, treatment with 12 weeks elbasvir/grazoprevir should be considered, whereas for high BVL >800 000 IU/mL, this regimen is only recommended in nonstructural protein 5A (NS5A) resistance-associated substitutions (RAS) absence. With present NS5A RAS or when RAS-testing is not available, 16 weeks elbasvir/grazoprevir + ribavirin is preferred. Here, we investigated the adherence to these recommendations and the effectiveness of elbasvir/grazoprevir in a large German Hepatitis C-Registry GT1a cohort. Methods From September 2016 until July 2018, 195 GT1a-infected patients were treated with elbasvir/grazoprevir ± ribavirin for 12-16 weeks. The primary outcome was per protocol SVR12 or SVR24. Results Mean age was 50 years, 89% were male, 19% had cirrhosis, 72% were treatment-naive. Forty-five percent had low BVL ≤800 000 IU/mL, 55% high BVL >800 000 IU/mL, of whom 49 vs. 42% were baseline RAS-tested. Four patients with high (7.7%) and two with low BVL (5%) had NS5A RAS of whom 50% received elbasvir/grazoprevir+ribavirin, respectively. Ninety-four percent of patients with low and 65% with high BVL received elbasvir/grazoprevir without ribavirin. Thirty-five percent of patients with high BVL received ribavirin, mostly without prior RAS-testing. Per protocol sustained virologic response (SVR) by low vs. high BVL was 98.8 and 95.1%. All patients with NS5A RAS achieved SVR. Conclusions In German, real-world most patients received elbasvir/grazoprevir without ribavirin. Ribavirin was mainly added in GT1a patients >800 000 IU/mL, who were not NS5A RAS tested. SVR rates were consistently high and comparable to clinical trial results.
Published: 2020

22. Potential strategy for assessing QT/QTc interval for drugs that produce rapid changes in heart rate: Electrocardiographic assessment of the effects of intravenous remimazolam on cardiac repolarization

Author: Michael D. Thorn, Borje Darpo, Frank Schippers, Robert Kleiman, and Thomas Stoehr
Subjects: medicine.medical_specialty, medicine.drug_class, Sedation, Cardiac repolarization, 030226 pharmacology & pharmacy, QT interval, 03 medical and health sciences, Benzodiazepines, Electrocardiography, 0302 clinical medicine, Double-Blind Method, Heart Rate, Internal medicine, Heart rate, Medicine, Humans, Pharmacology (medical), General anaesthesia, 030212 general & internal medicine, intravenous drug administration, QT interval, QT‐RR hysteresis, Pharmacology, Benzodiazepine, Dose-Response Relationship, Drug, business.industry, Original Articles, Pharmaceutical Preparations, Cardiology, Original Article, medicine.symptom, business, Remimazolam
Abstract: Aims Remimazolam is a new, ultra‐short‐acting benzodiazepine developed for intravenous (IV) use during procedural sedation and in general anaesthesia. Two trials were conducted to characterize its effects on cardiac repolarization. Methods A thorough QT/QTc (TQT) study assessed electrocardiography effects of therapeutic and supratherapeutic doses of remimazolam and midazolam. To investigate whether RR‐QT hysteresis effects due to rapid heart rate changes might have confounded the QTc assessments in the TQT trial, a second trial used continuous IV remimazolam infusion to achieve stable heart rates during periods of stable remimazolam plasma concentration. Results During the TQT, both compounds produced a 10–20‐beats/min increase in heart rate within 30 seconds, persisting for 5–10 minutes. Within 30 seconds, the upper bound of the 2‐sided 90% confidence interval for the placebo‐corrected change from baseline for QTcI (ΔΔQTcI) exceeded 10 ms for both doses of remimazolam (ΔΔQTcI 7.2 [3.2, 11.2] ms for the 10 mg dose and 10.4 [6.5, 14.3] ms for the 20 mg dose) as well as for the 7.5‐mg dose of midazolam (8.2 [4.4, 12.1] ms). At 2 minutes after IV bolus, the upper bound of the 2‐sided 90% confidence interval for ΔΔQTcI exceeded 10 ms only for the remimazolam 20‐mg dose (6.3 [2.3, 10.2] ms). During the second study, during periods of stable heart rate, remimazolam had no clinically significant effect on QTc (peak ΔΔQTcI 3.4 [−1.1, 7.6] ms). Conclusion Remimazolam does not prolong cardiac repolarization (QTc). The methods reported here may allow assessment of the QTc effects of other drugs given by IV bolus.
Published: 2020

23. Time‐to‐Event Modeling for Remimazolam for the Indication of Induction and Maintenance of General Anesthesia

Author: Thomas Stoehr, Frank Schippers, Lauren R. L. Lohmer, Karl Uwe Petersen, and Virginia D. Schmith
Subjects: Adult, Sedation, Kaplan-Meier Estimate, Anesthesia, General, anesthesia, Models, Biological, 030226 pharmacology & pharmacy, Drug Administration Schedule, Time, Benzodiazepines, 03 medical and health sciences, Clinical Trials, Phase II as Topic, 0302 clinical medicine, medicine, Humans, Hypnotics and Sedatives, Pharmacology (medical), Dosing, Aged, Probability, Pharmacology, Dose-Response Relationship, Drug, Proportional hazards model, Cumulative dose, business.industry, remimazolam, Middle Aged, dose‐response, Clinical Trials, Phase III as Topic, Pharmacodynamics, sedation, 030220 oncology & carcinogenesis, Bispectral index, Anesthesia, Linear Models, time‐to‐event analysis, medicine.symptom, Remimazolam, business, Body mass index
Abstract: Remimazolam is an ultra‐short‐acting benzodiazepine being investigated for induction and maintenance of general anesthesia and for procedural sedation. This dose‐response analysis of 4 phase 2‐3 studies evaluated covariates that may impact the pharmacodynamic profile (based on theoretical pharmacokinetic principles) and require dose adjustments in subpopulations, particularly elderly, and if remimazolam has cumulative properties. Covariates affecting the time to loss of consciousness and time to extubation were evaluated using Cox proportional hazards models. Factors affecting steady‐state infusion rate required to produce adequate sedation were evaluated using linear regression. Variability in time to loss of consciousness was explained by induction dose, age, body mass index, and time from initiation of opioids to initiation of remimazolam. The steady‐state infusion rate producing adequate sedation was higher in European than Japanese subjects due to differences in study design. American Society of Anesthesiologists physical status class 3 subjects had a 28% lower maintenance infusion rate than class 1 subjects. Other statistically significant covariates (American Society of Anesthesiologists class 2, estimated glomerular filtration rate, and sex) resulted in small (≤14%), non–clinically relevant differences. Factors affecting time to extubation included the last infusion rate (ie, tapering), the bispectral index score at the end of infusion, and sex. The time to extubation after remimazolam did not increase with increased cumulative dose of remimazolam or duration of surgery. This evaluation of remimazolam's pharmacodynamic profile, in the absence of pharmacokinetic data, informed dosing recommendations and showed that remimazolam does not have cumulative properties in the general anesthesia setting.
Published: 2020

24. Doravirine versus ritonavir-boosted darunavir in antiretroviral-naive adults with HIV-1 (DRIVE-FORWARD): 96-week results of a randomised, double-blind, non-inferiority, phase 3 trial

Author: Jean-Michel Molina, Kathleen Squires, Paul E Sax, Pedro Cahn, Johan Lombaard, Edwin DeJesus, Ming-Tain Lai, Anthony Rodgers, Lisa Lupinacci, Sushma Kumar, Peter Sklar, George J Hanna, Carey Hwang, Elizabeth Anne Martin, Debbie P. Hagins, Olayemi O. Osiyemi, David James Prelutsky, Moti N. Ramgopal, Anthony John Scarsella, Robin Dretler, Christopher J. Bettacchi, James Sims, Patrick G. Clay, Nicholaos C. Bellos, Melanie A. Thompson, Jose Montero, Cheryl K. McDonald, Catherine Creticos, David Shamblaw, Miguel Mogyoros, Antonio E. Terrelonge, Martin Valdes, Karen T. Tashima, William J. Robbins, Franco Antonio Felizarta, Richard A. Elion, Jihad Slim, Sandra S. Win, Sujata N. Lalla-Reddy, Peter Jerome Ruane, Anthony Mills, Jerry L. Cade, Craig A. Dietz, David Scott Rubin, Cynthia Mayer, Juan Carlos Rondon, Paul P. Cook, Eric Daar, Princy N. Kumar, Susan Swindells, Jose Guillermo Castro, Ivan Melendez-Rivera, Javier O. Morales-Ramirez, Lizette Santiago, Jorge L. Santana-Bagur, Marcelo Martins, Pedro Enrique Cahn, Gustavo D. Lopardo, Norma Porteiro, Mark Theo Bloch, David Alfred Baker, Norman Roth, Richard James Moore, Robert James Finlayson, James McMahon, Armin Rieger, Alexander Zoufaly, Sylvia Hartl, Robert Zangerle, Fiona Smaill, Sharon L. Walmsley, Brian Conway, Anita Rachlis, Graham H.R. Smith, Carlos Perez, Alejandro Afani, Maria Isabel Campos, Carolina Eugenia Chahin, Marcelo Wolff Reyes, Jan Gerstoft, Nina Weis, Alex Lund Laursen, Yazdan Yazdanpanah, Laurent Cotte, Francois Raffi, Philippe Morlat, Pierre-Marie Girard, Christine Katlama, Juergen K. Rockstroh, Keikawus Arasteh, Stefan Esser, Albrecht Stoehr, Hans-Juergen Stellbrink, Matthias Stoll, Dirk Schuermann, Gerd Faetkenheuer, Johannes Bogner, Thomas Lutz, Axel Baumgarten, Hans Jaeger, Andrea Gori, Gabriel Coltan, Felicia Constandis, Simona Manuela Erscoiu, Liviu-Jany Prisacariu, Sorin Rugina, Adrian Streinu-Cercel, Vadim Valentinovich Pokrovsky, Natalia V. Zakharova, Andrey Anatolyevich Shuldyakov, Elena Pavlovna Ryamova, Valeriy Viktorovich Kulagin, Olga Aleksandrovna Tsybakova, Elena Orlova-Morozova, Firaya Nagimova, Evgeniy Voronin, Tatyana Evgenyevna Shimonova, Oleg Anatolyevich Kozyrev, Catherine Orrell, Johannes Jurgens Lombaard, Marleen de Jager, Joaquin Portilla Segorb, Josep Mallolas, Maria Jesus Perez Elias, Josep M. Gatell, Jose Ramon Arribas Lopez, Eugenia Negredo Puigmal, Daniel Podzamczer Palter, Federico Pulido Ortega, Jesus Troya Garcia, Ignacio De los Santos Gil, Juan Berenguer Berenguer, Ian G. Williams, Margaret A. Johnson, Gabriel Schembri, Amanda Clarke, Mark Gompels, Julie Meriel Fox, Steven John Taylor, David Harold Dockrell, and Stephen Kegg
Subjects: Adult, Male, 0301 basic medicine, medicine.medical_specialty, Anti-HIV Agents, Pyridones, Epidemiology, Immunology, Phases of clinical research, HIV Infections, Emtricitabine, law.invention, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Randomized controlled trial, Abacavir, law, Virology, Internal medicine, medicine, Humans, 030212 general & internal medicine, Darunavir, Ritonavir, Reverse-transcriptase inhibitor, business.industry, Lamivudine, Middle Aged, Triazoles, 030112 virology, Infectious Diseases, HIV-1, Female, business, medicine.drug
Abstract: Doravirine is a novel, non-nucleoside reverse transcriptase inhibitor that has shown non-inferior efficacy to ritonavir-boosted darunavir, with a superior lipid profile, in adults with HIV who were treatment naive at week 48 in the phase 3 DRIVE-FORWARD trial. Here we present the 96-week data for the study.This randomised, controlled, double-blind, multicentre, non-inferiority, phase 3 study was undertaken at 125 clinical centres in 15 countries. Eligible participants were adults (aged ≥18 years) infected with HIV-1 who were naive to antiretroviral therapy, with a plasma HIV-1 RNA concentration of 1000 copies per mL or higher at screening, and no known resistance to any of the study drugs. Participants were randomly assigned (1:1) using an interactive voice and web response system, stratified by baseline HIV-1 RNA concentration and background nucleoside reverse transcriptase inhibitor therapy, to doravirine (100 mg per day) or ritonavir-boosted darunavir (100 mg ritonavir and 800 mg darunavir per day), both with investigator-selected nucleoside reverse transcriptase inhibitors: emtricitabine and tenofovir disoproxil fumarate or abacavir and lamivudine. Participants and investigators were masked to treatment assignment until week 96. The primary efficacy endpoint was the proportion of participants who had a plasma HIV-1 RNA concentration of less than 50 copies per mL at week 48, which has been reported previously. Here we report the key secondary efficacy endpoint of the proportion of participants who achieved this concentration by week 96, assessed in all participants who received at least one dose of any study drug, regardless of whether it was their randomly assigned treatment. We used a US Food and Drug Administration snapshot approach and a margin of 10 percentage points to define the non-inferiority of doravirine to ritonavir-boosted darunavir at 96 weeks. Key safety endpoints were change in fasting serum lipid concentrations, the incidence of adverse events, and time to discontinuation due to an adverse event, assessed in all participants who received at least one dose of any study medication. This study is registered with ClinicalTrials.gov, NCT02275780, and is closed to accrual.Between Dec 1, 2014, and Oct 20, 2015, 1027 individuals were screened, of whom 769 participants were randomly assigned to doravirine (n=385) or ritonavir-boosted darunavir (n=384), and 383 in both groups were given at least one dose of their allocated treatment. Most participants were male (645 [84%] of 766) and white (560 [73%]), with a mean age of 35·2 years (SD 10·6). 292 participants in the doravirine group and 273 in the darunavir group completed 96 weeks of treatment. At week 96, a higher proportion of the doravirine group (277 [73%] of 383) achieved an HIV-1 RNA concentration of less than 50 copies per mL than did of the darunavir group (248 [66%] of 383; difference 7·1%, 95% CI 0·5-13·7). Responses were similar regardless of baseline characteristics. Treatment-emergent resistance to any study drug occurred in two (1%) of 383 participants in the doravirine group and one (1%) of 383 in the ritonavir-boosted darunavir group. Significant differences were seen between treatment groups in mean changes from baseline in LDL cholesterol (-14·6 mg/dL, 95% CI -18·2 to -11·0) and non-HDL cholesterol (-18·4 mg/dL, -22·5 to -14·3). Frequencies of adverse events were similar between groups. No significant treatment difference (log-rank nominal p=0·063) through week 96 was observed in time to discontinuation due to an adverse event. The most common adverse events (week 0-96) were diarrhoea (65 [17%] in the doravirine group vs 91 [24%] in the ritonavir-boosted darunavir group), nausea (45 [12%] vs 52 [14%]), headache (57 [15%] vs 46 [12%]), and upper respiratory tract infection (51 [13%] vs 30 [8%]). Two participants, one in each group, died during treatment; neither death was considered to be related to study medication.These results through 96 weeks support the efficacy and safety results reported previously for doravirine at 48 weeks, supporting the use of doravirine for the long-term treatment of adults with previously untreated HIV-1 infection.Merck.
Published: 2020

25. Intra-abdominal EWSR1/FUS-CREM-rearranged malignant epithelioid neoplasms: two cases of an emerging aggressive entity with emphasis on misleading immunophenotype

Author: Arndt Hartmann, Robert Stoehr, Björn Konukiewitz, Abbas Agaimy, Atsuko Kasajima, Jan Hinrich Bräsen, Nicole Pfarr, Mike Otto, and Günter Klöppel
Subjects: Male, 0301 basic medicine, Pathology, medicine.medical_specialty, Oncogene Proteins, Fusion, Histiocytoma, Malignant Fibrous, Pathology and Forensic Medicine, Cyclic AMP Response Element Modulator, 03 medical and health sciences, 0302 clinical medicine, Immunophenotyping, Brief Report, RCC, ALK, EWSR1, CREB, CREM, FUS, Primary renal sarcoma, Mesentery, Neuroendocrine, Paraganglioma, Renal cell carcinoma, Biomarkers, Tumor, medicine, Humans, ddc:610, Molecular Biology, ATF1, Angiomatoid fibrous histiocytoma, business.industry, Cell Biology, General Medicine, Middle Aged, medicine.disease, Immunohistochemistry, ddc, 030104 developmental biology, 030220 oncology & carcinogenesis, RNA-Binding Protein FUS, Female, Clear-cell sarcoma, Gene Fusion, RNA-Binding Protein EWS, Differential diagnosis, business, Epithelioid cell
Abstract: CREB family (CREB1, ATF1, and CREM) gene fusions are defining markers in diverse mesenchymal neoplasms (clear cell sarcoma, angiomatoid fibrous histiocytoma, and others). However, neoplasms harboring EWSR1-CREM/FUS-CREM fusions are rare and poorly characterized. We describe two cases (55-year-old male with 7.5 cm renal mass and 32-year-old female with 5.5 cm mesenteric mass) illustrating their misleading immunophenotypes. Histologically, both showed eosinophilic and focally clear epithelioid cells arranged into sheets, nests, and trabeculae. Immunohistochemistry showed ALK, EMA, and AE1/AE3 immunoreactivity suggesting ALK-rearranged renal cell carcinoma (Case 1) and coexpression of keratin, EMA, synaptophysin, and chromogranin-A, suggesting neuroendocrine neoplasm (Case 2). Targeted RNA sequencing revealed EWSR1-CREM (Case 1) and FUS-CREM (Case 2) fusions. These cases add to the spectrum of CREM fusion-positive intra-abdominal epithelioid neoplasms. Their unusual immunophenotype and unexpected sites represent major pitfalls, underline a wide differential diagnosis, and emphasize the value of molecular testing in correctly diagnosing them.
Published: 2022

26. Molecular Composition of Genomic TMPRSS2-ERG Rearrangements in Prostate Cancer

Author: Helge Taubert, Arndt Hartmann, Manuela Krumbholz, Maximilian Burger, Robert Stoehr, Sven Wach, Markus Metzler, Bernd Wullich, and Abbas Agaimy
Subjects: Male, 0301 basic medicine, Oncogene Proteins, Fusion, Article Subject, Clinical Biochemistry, TMPRSS2, Fusion gene, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, Prostate, Cell Line, Tumor, Biomarkers, Tumor, Genetics, Humans, Medicine, Precision Medicine, Child, Molecular Biology, Aged, Repetitive Sequences, Nucleic Acid, Tumor marker, lcsh:R5-920, business.industry, Biochemistry (medical), Breakpoint, Prostatic Neoplasms, General Medicine, Middle Aged, medicine.disease, Leukemia, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cancer research, Sarcoma, lcsh:Medicine (General), business, Cell-Free Nucleic Acids, Neoplasms, Connective and Soft Tissue, Research Article
Abstract: There is increasing interest in the use of cell-free circulating tumor DNA (ctDNA) as a serum marker for therapy assessment in prostate cancer patients. Prostate cancer is characterized by relatively low numbers of mutations, and, in contrast to many other common epithelial cancers, commercially available single nucleotide mutation assays for quantification of ctDNA are insufficient for therapy assessment in this disease. However, prostate cancer shares some similarity with translocation-affected mesenchymal tumors (e.g., leukemia and Ewing sarcoma), which are common in pediatric oncology, where chromosomal translocations are used as biomarkers for quantification of the tumor burden. Approximately 50% of prostate cancers carry a chromosomal translocation resulting in generation of the TMPRSS2-ERG fusion gene, which is unique to the tumor cells of each individual patient because of variability in the fusion breakpoint sites. In the present study, we examined the structural preconditions for TMPRSS2-ERG fusion sites in comparison with mesenchymal tumors in pediatric patients to determine whether the sequence composition is suitable for the establishment of tumor-specific quantification assays in prostate cancer patients. Genomic repeat elements represent potential obstacles to establishment of quantification assays, and we found similar proportions of repeat elements at fusion sites in prostate cancer to those reported for mesenchymal tumors, where genomic fusion sequences are established as biomarkers. Our data support the development of the TMPRSS2-ERG fusion gene as a noninvasive tumor marker for therapy assessment, risk stratification, and relapse detection to improve personalized therapy strategies for patients with prostate cancer.
Published: 2019

27. Physical vapor deposition cluster arrival energy enhances the electrochemical performance of silicon thin-film anodes for Li-ion batteries

Author: Colin Hall, Thushan Pathirana, Robert Kerr, Manrico Fabretto, Bastian Stoehr, Eva Alvarez de Eulate, Mohammed Salah, Sam Rudd, Salah, Mohammed, Pathirana, Thushan, Alvarez De Eulate, Eva, Hall, Colin, Stoehr, Bastian, Rudd, Sam, Kerr, Robert, and Fabretto, Manrico
Subjects: Materials science, business.industry, PVD sputtering, Energy Engineering and Power Technology, Silicon thin film, Electrochemistry, deposition power, Ion, Anode, Physical vapor deposition, Materials Chemistry, Cluster (physics), film stress, Chemical Engineering (miscellaneous), Optoelectronics, electrochemical and cyclability performance, Electrical and Electronic Engineering, lithium diffusion coefficient, business, Energy (signal processing), silicon anodes
Abstract: Silicon is a leading candidate material to replace carbon/graphite, the commonly used anode material in lithium-ion batteries (LIBs), because it has an 11 times higher theoretical specific capacity. However, silicon anodes have two main issues, low electronic conductivity and large volume expansion during cycling, and these issues present challenges in the manufacture of mechanically stable high-electrochemical-performance Si electrodes. Physical vapor deposition (PVD) is an alternative fabrication process that can produce binderless compact Si thin films suitable for microbatteries and thin flexible devices. Despite numerous studies exploring the use of vacuum-based PVD silicon films, no definitive information has been recorded correlating how changes in process parameters affect the properties of the resulting deposited films and how this influences anode performance in Li-ion batteries. In this work, process parameters (i.e., deposition power and gas working pressure) were altered for various Si film deposition trials. Electronic resistivity, electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV), residual film stress, X-ray diffraction (XRD), Raman spectroscopy, Fourier transform infrared (FTIR) spectroscopy, and X-ray photoelectron spectroscopy (XPS) measurements were performed for a thorough physico/chemico analysis of the various films. This information was used to interpret the differences in discharge capacity and capacity retention obtained from the various Si anodes using galvanostatic charge/discharge cycling from assembled coin cells. CV measurements were used to corroborate performance outcomes, as well as to calculate Li-ion diffusion coefficients Refereed/Peer-reviewed
Published: 2021

28. Risk of penile tumor development in Caucasian individuals is independent of the coding variant rs7208422 in the TMC8 (EVER2) gene

Author: Johannes Giedl, Arndt Hartmann, Nadine T. Gaisa, Olaf Wendler, Georg Richter, Robert Stoehr, Bernd Wullich, Valentina Campean, Simone Bertz, and Maximilian Burger
Subjects: Oncology, Sanger sequencing, Cervical cancer, Cancer Research, medicine.medical_specialty, business.industry, Cancer, Articles, medicine.disease, Malignancy, symbols.namesake, Internal medicine, Genotype, medicine, symbols, SNP, Penile cancer, TMC8, business
Abstract: Genetic variation in the transmembrane channel-like (TMC)6/TMC8 region has been linked to β-type human papillomavirus (HPV) infection and squamous cell carcinoma (SCC) of the skin and the head and neck, α-type HPV persistence and progression to cervical cancer. The functional variant rs7208422 of the TMC8 gene was suggested to have a high impact on susceptibility to β-papillomaviruses and their oncogenic potential and to also have an influence on α-type HPV-related disease. The aim of the present study was to evaluate a possible influence of rs7208422 on penile cancer risk, a known α-type HPV-related malignancy. Therefore, the distribution of rs7208422 was determined by direct Sanger sequencing of 104 Caucasian penile SCC cases and compared to data of 3,810 controls taken from the literature. HPV detection was performed by usage of GP5+/6+ primers and subtype-specific PCR. It was observed that the distribution of rs7208422 followed the Hardy-Weinberg equilibrium in both cases and controls. HPV DNA was detected in 39% of the penile SCC cases. Overall, there was no significant difference in the distribution of rs7208422 neither between cases and controls (P=0.726) nor between HPV-positive and -negative penile SCC cases (P=0.747). There was also no association between rs7208422 genotypes and age of disease onset (P=0.740). In conclusion, the present data argue against a significant impact of rs7208422 on the risk for the development of penile SCC in Caucasians. Even in combination with the HPV status, the SNP appears not to influence the risk of penile SCC in HPV-positive cases.
Published: 2021

29. Impact of clinical phenotypes on management and outcomes in European atrial fibrillation patients: a report from the ESC-EHRA EURObservational Research Programme in AF (EORP-AF) General Long-Term Registry

Author: Proietti, M., Vitolo, M., Harrison, S. L., Lane, D. A., Fauchier, L., Marin, F., Nabauer, M., Potpara, T. S., Dan, G. -A., Boriani, G., Lip, G. Y. H., Boriani (Chair), G., Tavazzi, L., Maggioni, A. P., Potpara, T., Kalarus, Z., Ferrari, R., Shantsila, A., Goda, A., Mairesse, G., Shalganov, T., Antoniades, L., Taborsky, M., Riahi, S., Muda, P., Garcia Bolao, I., Piot, O., Etsadashvili, K., Simantirakis, E. N., Haim, M., Azhari, A., Najafian, J., Santini, M., Mirrakhimov, E., Kulzida, K., Erglis, A., Poposka, L., Burg, M. R., Crijns, H., Erkuner, O., Atar, D., Lenarczyk, R., Martins Oliveira, M., Shah, D., Serdechnaya, E., Diker, E., Lane, D., Zera, E., Ekmekciu, U., Paparisto, V., Tase, M., Gjergo, H., Dragoti, J., Ciutea, M., Ahadi, N., el Husseini, Z., Raepers, M., Leroy, J., Haushan, P., Jourdan, A., Lepiece, C., Desteghe, L., Vijgen, J., Koopman, P., Van Genechten, G., Heidbuchel, H., Boussy, T., De Coninck, M., Van Eeckhoutte, H., Bouckaert, N., Friart, A., Boreux, J., Arend, C., Evrard, P., Stefan, L., Hoffer, E., Herzet, J., Massoz, M., Celentano, C., Sprynger, M., Pierard, L., Melon, P., Van Hauwaert, B., Kuppens, C., Faes, D., Van Lier, D., Van Dorpe, A., Gerardy, A., Deceuninck, O., Xhaet, O., Dormal, F., Ballant, E., Blommaert, D., Yakova, D., Hristov, M., Yncheva, T., Stancheva, N., Tisheva, S., Tokmakova, M., Nikolov, F., Gencheva, D., Kunev, B., Stoyanov, M., Marchov, D., Gelev, V., Traykov, V., Kisheva, A., Tsvyatkov, H., Shtereva, R., Bakalska-Georgieva, S., Slavcheva, S., Yotov, Y., Kubickova, M., Marni Joensen, A., Gammelmark, A., Hvilsted Rasmussen, L., Dinesen, P., Krogh Veno, S., Sorensen, B., Korsgaard, A., Andersen, K., Fragtrup Hellum, C., Svenningsen, A., Nyvad, O., Wiggers, P., May, O., Aarup, A., Graversen, B., Jensen, L., Andersen, M., Svejgaard, M., Vester, S., Hansen, S., Lynggaard, V., Ciudad, M., Vettus, R., Maestre, A., Castano, S., Cheggour, S., Poulard, J., Mouquet, V., Leparree, S., Bouet, J., Taieb, J., Doucy, A., Duquenne, H., Furber, A., Dupuis, J., Rautureau, J., Font, M., Damiano, P., Lacrimini, M., Abalea, J., Boismal, S., Menez, T., Mansourati, J., Range, G., Gorka, H., Laure, C., Vassaliere, C., Elbaz, N., Lellouche, N., Djouadi, K., Roubille, F., Dietz, D., Davy, J., Granier, M., Winum, P., Leperchois-Jacquey, C., Kassim, H., Marijon, E., Le Heuzey, J., Fedida, J., Maupain, C., Himbert, C., Gandjbakhch, E., Hidden-Lucet, F., Duthoit, G., Badenco, N., Chastre, T., Waintraub, X., Oudihat, M., Lacoste, J., Stephan, C., Bader, H., Delarche, N., Giry, L., Arnaud, D., Lopez, C., Boury, F., Brunello, I., Lefevre, M., Mingam, R., Haissaguerre, M., Le Bidan, M., Pavin, D., Le Moal, V., Leclercq, C., Beitar, T., Martel, I., Schmid, A., Sadki, N., Romeyer-Bouchard, C., Da Costa, A., Arnault, I., Boyer, M., Piat, C., Lozance, N., Nastevska, S., Doneva, A., Fortomaroska Milevska, B., Sheshoski, B., Petroska, K., Taneska, N., Bakrecheski, N., Lazarovska, K., Jovevska, S., Ristovski, V., Antovski, A., Lazarova, E., Kotlar, I., Taleski, J., Kedev, S., Zlatanovik, N., Jordanova, S., Bajraktarova Proseva, T., Doncovska, S., Maisuradze, D., Esakia, A., Sagirashvili, E., Lartsuliani, K., Natelashvili, N., Gumberidze, N., Gvenetadze, R., Gotonelia, N., Kuridze, N., Papiashvili, G., Menabde, I., Gloggler, S., Napp, A., Lebherz, C., Romero, H., Schmitz, K., Berger, M., Zink, M., Koster, S., Sachse, J., Vonderhagen, E., Soiron, G., Mischke, K., Reith, R., Schneider, M., Rieker, W., Boscher, D., Taschareck, A., Beer, A., Oster, D., Ritter, O., Adamczewski, J., Walter, S., Frommhold, A., Luckner, E., Richter, J., Schellner, M., Landgraf, S., Bartholome, S., Naumann, R., Schoeler, J., Westermeier, D., William, F., Wilhelm, K., Maerkl, M., Oekinghaus, R., Denart, M., Kriete, M., Tebbe, U., Scheibner, T., Gruber, M., Gerlach, A., Beckendorf, C., Anneken, L., Arnold, M., Lengerer, S., Bal, Z., Uecker, C., Fortsch, H., Fechner, S., Mages, V., Martens, E., Methe, H., Schmidt, T., Schaeffer, B., Hoffmann, B., Moser, J., Heitmann, K., Willems, S., Klaus, C., Lange, I., Durak, M., Esen, E., Mibach, F., Mibach, H., Utech, A., Gabelmann, M., Stumm, R., Landle, V., Gartner, C., Goerg, C., Kaul, N., Messer, S., Burkhardt, D., Sander, C., Orthen, R., Kaes, S., Baumer, A., Dodos, F., Barth, A., Schaeffer, G., Gaertner, J., Winkler, J., Fahrig, A., Aring, J., Wenzel, I., Steiner, S., Kliesch, A., Kratz, E., Winter, K., Schneider, P., Haag, A., Mutscher, I., Bosch, R., Taggeselle, J., Meixner, S., Schnabel, A., Shamalla, A., Hotz, H., Korinth, A., Rheinert, C., Mehltretter, G., Schon, B., Schon, N., Starflinger, A., Englmann, E., Baytok, G., Laschinger, T., Ritscher, G., Gerth, A., Dechering, D., Eckardt, L., Kuhlmann, M., Proskynitopoulos, N., Brunn, J., Foth, K., Axthelm, C., Hohensee, H., Eberhard, K., Turbanisch, S., Hassler, N., Koestler, A., Stenzel, G., Kschiwan, D., Schwefer, M., Neiner, S., Hettwer, S., Haeussler-Schuchardt, M., Degenhardt, R., Sennhenn, S., Brendel, M., Stoehr, A., Widjaja, W., Loehndorf, S., Logemann, A., Hoskamp, J., Grundt, J., Block, M., Ulrych, R., Reithmeier, A., Panagopoulos, V., Martignani, C., Bernucci, D., Fantecchi, E., Diemberger, I., Ziacchi, M., Biffi, M., Cimaglia, P., Frisoni, J., Giannini, I., Boni, S., Fumagalli, S., Pupo, S., Di Chiara, A., Mirone, P., Pesce, F., Zoccali, C., Malavasi, V. L., Mussagaliyeva, A., Ahyt, B., Salihova, Z., Koshum-Bayeva, K., Kerimkulova, A., Bairamukova, A., Lurina, B., Zuzans, R., Jegere, S., Mintale, I., Kupics, K., Jubele, K., Kalejs, O., Vanhear, K., Burg, M., Cachia, M., Abela, E., Warwicker, S., Tabone, T., Xuereb, R., Asanovic, D., Drakalovic, D., Vukmirovic, M., Pavlovic, N., Music, L., Bulatovic, N., Boskovic, A., Uiterwaal, H., Bijsterveld, N., De Groot, J., Neefs, J., van den Berg, N., Piersma, F., Wilde, A., Hagens, V., Van Es, J., Van Opstal, J., Van Rennes, B., Verheij, H., Breukers, W., Tjeerdsma, G., Nijmeijer, R., Wegink, D., Binnema, R., Said, S., Philippens, S., van Doorn, W., Szili-Torok, T., Bhagwandien, R., Janse, P., Muskens, A., van Eck, M., Gevers, R., van der Ven, N., Duygun, A., Rahel, B., Meeder, J., Vold, A., Holst Hansen, C., Engset, I., Dyduch-Fejklowicz, B., Koba, E., Cichocka, M., Sokal, A., Kubicius, A., Pruchniewicz, E., Kowalik-Sztylc, A., Czapla, W., Mroz, I., Kozlowski, M., Pawlowski, T., Tendera, M., Winiarska-Filipek, A., Fidyk, A., Slowikowski, A., Haberka, M., Lachor-Broda, M., Biedron, M., Gasior, Z., Kolodziej, M., Janion, M., Gorczyca-Michta, I., Wozakowska-Kaplon, B., Stasiak, M., Jakubowski, P., Ciurus, T., Drozdz, J., Simiera, M., Zajac, P., Wcislo, T., Zycinski, P., Kasprzak, J., Olejnik, A., Harc-Dyl, E., Miarka, J., Pasieka, M., Zieminska-Luc, M., Bujak, W., Sliwinski, A., Grech, A., Morka, J., Petrykowska, K., Prasal, M., Hordynski, G., Feusette, P., Lipski, P., Wester, A., Streb, W., Romanek, J., Wozniak, P., Chlebus, M., Szafarz, P., Stanik, W., Zakrzewski, M., Kazmierczak, J., Przybylska, A., Skorek, E., Blaszczyk, H., Stepien, M., Szabowski, S., Krysiak, W., Szymanska, M., Karasinski, J., Blicharz, J., Skura, M., Halas, K., Michalczyk, L., Orski, Z., Krzyzanowski, K., Skrobowski, A., Zielinski, L., Tomaszewska-Kiecana, M., Dluzniewski, M., Kiliszek, M., Peller, M., Budnik, M., Balsam, P., Opolski, G., Tyminska, A., Ozieranski, K., Wancerz, A., Borowiec, A., Majos, E., Dabrowski, R., Szwed, H., Musialik-Lydka, A., Leopold-Jadczyk, A., Jedrzejczyk-Patej, E., Koziel, M., Mazurek, M., Krzemien-Wolska, K., Starosta, P., Nowalany-Kozielska, E., Orzechowska, A., Szpot, M., Staszel, M., Almeida, S., Pereira, H., Brandao Alves, L., Miranda, R., Ribeiro, L., Costa, F., Morgado, F., Carmo, P., Galvao Santos, P., Bernardo, R., Adragao, P., Ferreira da Silva, G., Peres, M., Alves, M., Leal, M., Cordeiro, A., Magalhaes, P., Fontes, P., Leao, S., Delgado, A., Costa, A., Marmelo, B., Rodrigues, B., Moreira, D., Santos, J., Santos, L., Terchet, A., Darabantiu, D., Mercea, S., Turcin Halka, V., Pop Moldovan, A., Gabor, A., Doka, B., Catanescu, G., Rus, H., Oboroceanu, L., Bobescu, E., Popescu, R., Dan, A., Buzea, A., Daha, I., Dan, G., Neuhoff, I., Baluta, M., Ploesteanu, R., Dumitrache, N., Vintila, M., Daraban, A., Japie, C., Badila, E., Tewelde, H., Hostiuc, M., Frunza, S., Tintea, E., Bartos, D., Ciobanu, A., Popescu, I., Toma, N., Gherghinescu, C., Cretu, D., Patrascu, N., Stoicescu, C., Udroiu, C., Bicescu, G., Vintila, V., Vinereanu, D., Cinteza, M., Rimbas, R., Grecu, M., Cozma, A., Boros, F., Ille, M., Tica, O., Tor, R., Corina, A., Jeewooth, A., Maria, B., Georgiana, C., Natalia, C., Alin, D., Dinu-Andrei, D., Livia, M., Daniela, R., Larisa, R., Umaar, S., Tamara, T., Loachim Popescu, M., Nistor, D., Sus, I., Coborosanu, O., Alina-Ramona, N., Dan, R., Petrescu, L., Ionescu, G., Vacarescu, C., Goanta, E., Mangea, M., Ionac, A., Mornos, C., Cozma, D., Pescariu, S., Solodovnicova, E., Soldatova, I., Shutova, J., Tjuleneva, L., Zubova, T., Uskov, V., Obukhov, D., Rusanova, G., Isakova, N., Odinsova, S., Arhipova, T., Kazakevich, E., Zavyalova, O., Novikova, T., Riabaia, I., Zhigalov, S., Drozdova, E., Luchkina, I., Monogarova, Y., Hegya, D., Rodionova, L., Nevzorova, V., Lusanova, O., Arandjelovic, A., Toncev, D., Milanov, M., Sekularac, N., Zdravkovic, M., Hinic, S., Dimkovic, S., Acimovic, T., Saric, J., Polovina, M., Vujisic-Tesic, B., Nedeljkovic, M., Zlatar, M., Asanin, M., Vasic, V., Popovic, Z., Djikic, D., Sipic, M., Peric, V., Dejanovic, B., Milosevic, N., Stevanovic, A., Andric, A., Pencic, B., Pavlovic-Kleut, M., Celic, V., Pavlovic, M., Petrovic, M., Vuleta, M., Petrovic, N., Simovic, S., Savovic, Z., Milanov, S., Davidovic, G., Iric-Cupic, V., Simonovic, D., Stojanovic, M., Stojanovic, S., Mitic, V., Ilic, V., Petrovic, D., Deljanin Ilic, M., Ilic, S., Stoickov, V., Markovic, S., Kovacevic, S., Garcia Fernandez, A., Perez Cabeza, A., Anguita, M., Tercedor Sanchez, L., Mau, E., Loayssa, J., Ayarra, M., Carpintero, M., Roldan Rabadan, I., Gil Ortega, M., Tello Montoliu, A., Orenes Pinero, E., Manzano Fernandez, S., Romero Aniorte, A., Veliz Martinez, A., Quintana Giner, M., Ballesteros, G., Palacio, M., Alcalde, O., Garcia-Bolao, I., Bertomeu Gonzalez, V., Otero-Ravina, F., Garcia Seara, J., Gonzalez Juanatey, J., Dayal, N., Maziarski, P., Gentil-Baron, P., Koc, M., Onrat, E., Dural, I. E., Yilmaz, K., Ozin, B., Tan Kurklu, S., Atmaca, Y., Canpolat, U., Tokgozoglu, L., Dolu, A. K., Demirtas, B., Sahin, D., Ozcan Celebi, O., Gagirci, G., Turk, U. O., Ari, H., Polat, N., Toprak, N., Sucu, M., Akin Serdar, O., Taha Alper, A., Kepez, A., Yuksel, Y., Uzunselvi, A., Yuksel, S., Sahin, M., Kayapinar, O., Ozcan, T., Kaya, H., Yilmaz, M. B., Kutlu, M., Demir, M., Gibbs, C., Kaminskiene, S., Bryce, M., Skinner, A., Belcher, G., Hunt, J., Stancombe, L., Holbrook, B., Peters, C., Tettersell, S., Senoo, K., Russell, K., Domingos, P., Hussain, S., Partridge, J., Haynes, R., Bahadur, S., Brown, R., Mcmahon, S., Lip, G., Mcdonald, J., Balachandran, K., Singh, R., Garg, S., Desai, H., Davies, K., Goddard, W., Galasko, G., Rahman, I., Chua, Y., Payne, O., Preston, S., Brennan, O., Pedley, L., Whiteside, C., Dickinson, C., Brown, J., Jones, K., Benham, L., Brady, R., Buchanan, L., Ashton, A., Crowther, H., Fairlamb, H., Thornthwaite, S., Relph, C., Mcskeane, A., Poultney, U., Kelsall, N., Rice, P., Wilson, T., Wrigley, M., Kaba, R., Patel, T., Young, E., Law, J., Runnett, C., Thomas, H., Mckie, H., Fuller, J., Pick, S., Sharp, A., Hunt, A., Thorpe, K., Hardman, C., Cusack, E., Adams, L., Hough, M., Keenan, S., Bowring, A., Watts, J., Zaman, J., Goffin, K., Nutt, H., Beerachee, Y., Featherstone, J., Mills, C., Pearson, J., Stephenson, L., Grant, S., Wilson, A., Hawksworth, C., Alam, I., Robinson, M., Ryan, S., Egdell, R., Gibson, E., Holland, M., Leonard, D., Mishra, B., Ahmad, S., Randall, H., Hill, J., Reid, L., George, M., Mckinley, S., Brockway, L., Milligan, W., Sobolewska, J., Muir, J., Tuckis, L., Winstanley, L., Jacob, P., Kaye, S., Morby, L., Jan, A., Sewell, T., Boos, C., Wadams, B., Cope, C., Jefferey, P., Andrews, N., Getty, A., Suttling, A., Turner, C., Hudson, K., Austin, R., Howe, S., Iqbal, R., Gandhi, N., Brophy, K., Mirza, P., Willard, E., Collins, S., Ndlovu, N., Subkovas, E., Karthikeyan, V., Waggett, L., Wood, A., Bolger, A., Stockport, J., Evans, L., Harman, E., Starling, J., Williams, L., Saul, V., Sinha, M., Bell, L., Tudgay, S., Kemp, S., Frost, L., Ingram, T., Loughlin, A., Adams, C., Adams, M., Hurford, F., Owen, C., Miller, C., Donaldson, D., Tivenan, H., Button, H., Nasser, A., Jhagra, O., Stidolph, B., Brown, C., Livingstone, C., Duffy, M., Madgwick, P., Roberts, P., Greenwood, E., Fletcher, L., Beveridge, M., Earles, S., Mckenzie, D., Beacock, D., Dayer, M., Seddon, M., Greenwell, D., Luxton, F., Venn, F., Mills, H., Rewbury, J., James, K., Roberts, K., Tonks, L., Felmeden, D., Taggu, W., Summerhayes, A., Hughes, D., Sutton, J., Felmeden, L., Khan, M., Walker, E., Norris, L., O'Donohoe, L., Mozid, A., Dymond, H., Lloyd-Jones, H., Saunders, G., Simmons, D., Coles, D., Cotterill, D., Beech, S., Kidd, S., Wrigley, B., Petkar, S., Smallwood, A., Jones, R., Radford, E., Milgate, S., Metherell, S., Cottam, V., Buckley, C., Broadley, A., Wood, D., Allison, J., Rennie, K., Balian, L., Howard, L., Pippard, L., Board, S., Pitt-Kerby, T., Proietti M, Vitolo M, Harrison SL, Lane DA, Fauchier L, Marin F, Nabauer M, Potpara TS, Dan GA, Boriani G, Lip GYH, ESC-EHRA EORP-AF Long-Term General Registry Investigators, Diemberger I, Ziacchi M, Frisoni J, Cardiology, ACS - Heart failure & arrhythmias, Graduate School, UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, UCL - SSS/IREC/MONT - Pôle Mont Godinne, and UCL - (MGD) Service de cardiologie
Subjects: Registrie, Research Report, medicine.medical_specialty, Major adverse outcome, Cardiovascular risk factors, Cluster analysis, Risk Factors, Internal medicine, Clinical phenotype, Atrial Fibrillation, Epidemiology, Humans, Medicine, Registries, Cluster analysi, Atrial fibrillation, Clinical management, Clinical phenotypes, Major adverse outcomes, Phenotype, business.industry, Proportional hazards model, Risk Factor, Hazard ratio, General Medicine, medicine.disease, Confidence interval, Cohort, Observational study, business, Research Article, Human
Abstract: Background Epidemiological studies in atrial fibrillation (AF) illustrate that clinical complexity increase the risk of major adverse outcomes. We aimed to describe European AF patients’ clinical phenotypes and analyse the differential clinical course. Methods We performed a hierarchical cluster analysis based on Ward’s Method and Squared Euclidean Distance using 22 clinical binary variables, identifying the optimal number of clusters. We investigated differences in clinical management, use of healthcare resources and outcomes in a cohort of European AF patients from a Europe-wide observational registry. Results A total of 9363 were available for this analysis. We identified three clusters: Cluster 1 (n = 3634; 38.8%) characterized by older patients and prevalent non-cardiac comorbidities; Cluster 2 (n = 2774; 29.6%) characterized by younger patients with low prevalence of comorbidities; Cluster 3 (n = 2955;31.6%) characterized by patients’ prevalent cardiovascular risk factors/comorbidities. Over a mean follow-up of 22.5 months, Cluster 3 had the highest rate of cardiovascular events, all-cause death, and the composite outcome (combining the previous two) compared to Cluster 1 and Cluster 2 (all P < .001). An adjusted Cox regression showed that compared to Cluster 2, Cluster 3 (hazard ratio (HR) 2.87, 95% confidence interval (CI) 2.27–3.62; HR 3.42, 95%CI 2.72–4.31; HR 2.79, 95%CI 2.32–3.35), and Cluster 1 (HR 1.88, 95%CI 1.48–2.38; HR 2.50, 95%CI 1.98–3.15; HR 2.09, 95%CI 1.74–2.51) reported a higher risk for the three outcomes respectively. Conclusions In European AF patients, three main clusters were identified, differentiated by differential presence of comorbidities. Both non-cardiac and cardiac comorbidities clusters were found to be associated with an increased risk of major adverse outcomes.
Published: 2021

30. Immunonutritive Scoring for Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization: Evaluation of the CALLY Index

Author: Maurice Michel, Christoph Düber, Daniel Pinto dos Santos, Simon Johannes Gairing, Aline Mähringer-Kunz, Michael B. Pitton, Friedrich Foerster, Felix Hahn, Fabian Stoehr, Jens Mittler, Roman Kloeckner, Lukas Müller, Peter R. Galle, and Arndt Weinmann
Subjects: Cancer Research, medicine.medical_specialty, Multivariate statistics, Index (economics), Scoring system, Future studies, Multivariate analysis, transarterial chemoembolization, Gastroenterology, Article, risk prediction, Internal medicine, medicine, Overall survival, RC254-282, inflammation index, business.industry, fungi, Univariate, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, hepatocellular carcinoma, medicine.disease, CRP–albumin–lymphocyte ratio, immunoscoring, Oncology, Hepatocellular carcinoma, business
Abstract: The novel CRP–albumin–lymphocyte (CALLY) index is an improved immunonutritive scoring system, based on serum C-reactive protein (CRP), serum albumin, and the lymphocyte count. It has shown promise as a prognostic index for patients with hepatocellular carcinoma (HCC) undergoing resections. This study evaluated the prognostic ability of the CALLY index for patients with HCC undergoing transarterial chemoembolization (TACE). We retrospectively identified 280 treatment-naïve patients with HCC that underwent an initial TACE at our institution, between 2010 and 2020. We compared the CALLY index to established risk factors in univariate and multivariate regression analyses for associations with median overall survival (OS). A low CALLY score was associated with low median OS (low vs. high CALLY: 9.0 vs. 24.0 months, p &lt, 0.001). In the multivariate analysis, the CALLY index remained an independent prognostic predictor (p = 0.008). Furthermore, all factors of the CALLY index reached significance in univariate and in-depth multivariate analyses. However, the concordance index (C-index) of the CALLY index (0.60) was similar to the C-indices of established immunonutritive and inflammation scoring systems (range: 0.54 to 0.63). In conclusion, the CALLY index showed promise as a stratification tool for patients with HCC undergoing TACE. Notably, the CALLY index was not superior to other immunonutritive and inflammation scoring systems in predicting the median OS. Thus, future studies should re-evaluate the mathematical calculation of the index, particularly the contributions of individual parameters.
Published: 2021

31. Considerations for Differentiating the Effects of Intravenous and Topical Tranexamic Acid in Liposuction in Future Research Protocols

Author: Neil A. Fine and Jenna R. Stoehr
Subjects: AcademicSubjects/MED00987, business.industry, Anesthesia, Liposuction, medicine.medical_treatment, General Engineering, Medicine, Body Contouring, business, Letter to the Editor, Tranexamic acid, medicine.drug
Published: 2021

32. An observational cohort study of pelvic floor photobiomodulation for treatment of chronic pelvic pain

Author: Georgine Lamvu, Angela R Stoehr, Neeraj Kohli, and Barry Jarnagin
Subjects: medicine.medical_specialty, medicine.medical_treatment, media_common.quotation_subject, Pelvic Pain, Urination, Cohort Studies, medicine, Humans, Low level laser therapy, media_common, Pain Measurement, Pelvic floor, business.industry, Health Policy, Minimal clinically important difference, Pelvic pain, Pelvic Floor, medicine.anatomical_structure, Cohort, Physical therapy, Defecation, Female, medicine.symptom, Chronic Pain, business, Cohort study
Abstract: Aim: This research is the first to evaluate the effectiveness of trans -vaginal photobiomodulation therapy (TV-PBMT) for chronic pelvic pain. Materials & methods: Observational analysis of 128 women, undergoing TV-PBMT for chronic pelvic pain. Minimal clinically important difference, defined as ≥2-point drop on a 0–10 numeric pain rating scale (NPRS), and effect size Cohen d coefficient, was calculated over nine treatments for overall pain, and pain with activities. Results: Compared with baseline, 64.5% of women showed improvement in overall pain, pain with bowel movement, intercourse, exercise, urination, sitting and vulvar pain (minimal clinically important difference = -2.4, -2.0, -2.4, -2.1, -2.1, -2.0, -3.1; d = 0.9, 0.7, 0.9, 0.7, 0.7, 0.7, 0.9) by treatment 9. Conclusion: In this cohort, TV-PBMT resulted in improvement of pelvic pain without serious adverse events.
Published: 2021

33. Persistent long-term risk of liver related complications in HCV patients after antiviral therapy - Data from the German Hepatitis C-Registry

Author: Thomas Berg, Hartwig Klinker, Gerlinde Teuber, Yvonne Serfert, Albrecht Stoehr, Dietrich Hüppe, Stefan Mauss, M Cornberg, Peter Buggisch, Stefan Zeuzem, Deutsches Hepatitis C-Register Leberstiftungs-GmbH, Khw Böker, K-G Simon, Heinz Hartmann, Heiner Wedemeyer, and Christoph Sarrazin
Subjects: Long term risk, German, medicine.medical_specialty, business.industry, Internal medicine, medicine, Antiviral therapy, language, Hepatitis C, business, medicine.disease, language.human_language
Published: 2021

34. Health related quality of life of patients in opioid substitution therapy at the beginning of hepatitis C treatment - Data from the German Hepatitis C-Registry

Author: D Hepatitis C-Register, U Naumann, Albrecht Stoehr, Peter Buggisch, Stefan Christensen, Norbert Scherbaum, Heiner Wedemeyer, Hartwig Klinker, Renate Heyne, M Specka, Yvonne Serfert, and Ralph Link
Subjects: Health related quality of life, German, medicine.medical_specialty, business.industry, Internal medicine, language, Medicine, Hepatitis C, business, medicine.disease, Opioid substitution therapy, language.human_language
Published: 2021

35. Aiming for HCV elimination - Optimizing DAA therapy by characterisation of patients lost to follow up (LTFU) in a large real world setting - Data from the German Hepatitis C-Registry (DHC-R)

Author: Deutsches Hepatitis C-Register Leberstiftungs-GmbH, Christoph Sarrazin, K. Simon, Yvonne Serfert, Stefan Mauss, Albrecht Stoehr, Peter Buggisch, Uta Merle, S Christensen, Hartwig Klinker, Gerlinde Teuber, and M Cornberg
Subjects: German, Pediatrics, medicine.medical_specialty, business.industry, medicine, language, Hepatitis C, Lost to follow-up, business, medicine.disease, language.human_language, Hcv elimination
Published: 2021

36. An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

Author: Jianfang Liu, Tara Lichtenberg, Katherine A. Hoadley, Laila M. Poisson, Alexander J. Lazar, Andrew D. Cherniack, Albert J. Kovatich, Christopher C. Benz, Douglas A. Levine, Adrian V. Lee, Larsson Omberg, Denise M. Wolf, Craig D. Shriver, Vesteinn Thorsson, Hai Hu, Samantha J. Caesar-Johnson, John A. Demchok, Ina Felau, Melpomeni Kasapi, Martin L. Ferguson, Carolyn M. Hutter, Heidi J. Sofia, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jean C. Zenklusen, Jiashan (Julia) Zhang, Sudha Chudamani, Jia Liu, Laxmi Lolla, Rashi Naresh, Todd Pihl, Qiang Sun, Yunhu Wan, Ye Wu, Juok Cho, Timothy DeFreitas, Scott Frazer, Nils Gehlenborg, Gad Getz, David I. Heiman, Jaegil Kim, Michael S. Lawrence, Pei Lin, Sam Meier, Michael S. Noble, Gordon Saksena, Doug Voet, Hailei Zhang, Brady Bernard, Nyasha Chambwe, Varsha Dhankani, Theo Knijnenburg, Roger Kramer, Kalle Leinonen, Yuexin Liu, Michael Miller, Sheila Reynolds, Ilya Shmulevich, Wei Zhang, Rehan Akbani, Bradley M. Broom, Apurva M. Hegde, Zhenlin Ju, Rupa S. Kanchi, Anil Korkut, Jun Li, Han Liang, Shiyun Ling, Wenbin Liu, Yiling Lu, Gordon B. Mills, Kwok-Shing Ng, Arvind Rao, Michael Ryan, Jing Wang, John N. Weinstein, Jiexin Zhang, Adam Abeshouse, Joshua Armenia, Debyani Chakravarty, Walid K. Chatila, Ino de Bruijn, Jianjiong Gao, Benjamin E. Gross, Zachary J. Heins, Ritika Kundra, Konnor La, Marc Ladanyi, Augustin Luna, Moriah G. Nissan, Angelica Ochoa, Sarah M. Phillips, Ed Reznik, Francisco Sanchez-Vega, Chris Sander, Nikolaus Schultz, Robert Sheridan, S. Onur Sumer, Yichao Sun, Barry S. Taylor, Jioajiao Wang, Hongxin Zhang, Pavana Anur, Myron Peto, Paul Spellman, Christopher Benz, Joshua M. Stuart, Christopher K. Wong, Christina Yau, D. Neil Hayes, Joel S. Parker, Matthew D. Wilkerson, Adrian Ally, Miruna Balasundaram, Reanne Bowlby, Denise Brooks, Rebecca Carlsen, Eric Chuah, Noreen Dhalla, Robert Holt, Steven J.M. Jones, Katayoon Kasaian, Darlene Lee, Yussanne Ma, Marco A. Marra, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Karen Mungall, A. Gordon Robertson, Sara Sadeghi, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Kane Tse, Tina Wong, Ashton C. Berger, Rameen Beroukhim, Carrie Cibulskis, Stacey B. Gabriel, Galen F. Gao, Gavin Ha, Matthew Meyerson, Steven E. Schumacher, Juliann Shih, Melanie H. Kucherlapati, Raju S. Kucherlapati, Stephen Baylin, Leslie Cope, Ludmila Danilova, Moiz S. Bootwalla, Phillip H. Lai, Dennis T. Maglinte, David J. Van Den Berg, Daniel J. Weisenberger, J. Todd Auman, Saianand Balu, Tom Bodenheimer, Cheng Fan, Alan P. Hoyle, Stuart R. Jefferys, Corbin D. Jones, Shaowu Meng, Piotr A. Mieczkowski, Lisle E. Mose, Amy H. Perou, Charles M. Perou, Jeffrey Roach, Yan Shi, Janae V. Simons, Tara Skelly, Matthew G. Soloway, Donghui Tan, Umadevi Veluvolu, Huihui Fan, Toshinori Hinoue, Peter W. Laird, Hui Shen, Wanding Zhou, Michelle Bellair, Kyle Chang, Kyle Covington, Chad J. Creighton, Huyen Dinh, HarshaVardhan Doddapaneni, Lawrence A. Donehower, Jennifer Drummond, Richard A. Gibbs, Robert Glenn, Walker Hale, Yi Han, Jianhong Hu, Viktoriya Korchina, Sandra Lee, Lora Lewis, Wei Li, Xiuping Liu, Margaret Morgan, Donna Morton, Donna Muzny, Jireh Santibanez, Margi Sheth, Eve Shinbro, Linghua Wang, Min Wang, David A. Wheeler, Liu Xi, Fengmei Zhao, Julian Hess, Elizabeth L. Appelbaum, Matthew Bailey, Matthew G. Cordes, Li Ding, Catrina C. Fronick, Lucinda A. Fulton, Robert S. Fulton, Cyriac Kandoth, Elaine R. Mardis, Michael D. McLellan, Christopher A. Miller, Heather K. Schmidt, Richard K. Wilson, Daniel Crain, Erin Curley, Johanna Gardner, Kevin Lau, David Mallery, Scott Morris, Joseph Paulauskis, Robert Penny, Candace Shelton, Troy Shelton, Mark Sherman, Eric Thompson, Peggy Yena, Jay Bowen, Julie M. Gastier-Foster, Mark Gerken, Kristen M. Leraas, Tara M. Lichtenberg, Nilsa C. Ramirez, Lisa Wise, Erik Zmuda, Niall Corcoran, Tony Costello, Christopher Hovens, Andre L. Carvalho, Ana C. de Carvalho, José H. Fregnani, Adhemar Longatto-Filho, Rui M. Reis, Cristovam Scapulatempo-Neto, Henrique C.S. Silveira, Daniel O. Vidal, Andrew Burnette, Jennifer Eschbacher, Beth Hermes, Ardene Noss, Rosy Singh, Matthew L. Anderson, Patricia D. Castro, Michael Ittmann, David Huntsman, Bernard Kohl, Xuan Le, Richard Thorp, Chris Andry, Elizabeth R. Duffy, Vladimir Lyadov, Oxana Paklina, Galiya Setdikova, Alexey Shabunin, Mikhail Tavobilov, Christopher McPherson, Ronald Warnick, Ross Berkowitz, Daniel Cramer, Colleen Feltmate, Neil Horowitz, Adam Kibel, Michael Muto, Chandrajit P. Raut, Andrei Malykh, Jill S. Barnholtz-Sloan, Wendi Barrett, Karen Devine, Jordonna Fulop, Quinn T. Ostrom, Kristen Shimmel, Yingli Wolinsky, Andrew E. Sloan, Agostino De Rose, Felice Giuliante, Marc Goodman, Beth Y. Karlan, Curt H. Hagedorn, John Eckman, Jodi Harr, Jerome Myers, Kelinda Tucker, Leigh Anne Zach, Brenda Deyarmin, Leonid Kvecher, Caroline Larson, Richard J. Mural, Stella Somiari, Ales Vicha, Tomas Zelinka, Joseph Bennett, Mary Iacocca, Brenda Rabeno, Patricia Swanson, Mathieu Latour, Louis Lacombe, Bernard Têtu, Alain Bergeron, Mary McGraw, Susan M. Staugaitis, John Chabot, Hanina Hibshoosh, Antonia Sepulveda, Tao Su, Timothy Wang, Olga Potapova, Olga Voronina, Laurence Desjardins, Odette Mariani, Sergio Roman-Roman, Xavier Sastre, Marc-Henri Stern, Feixiong Cheng, Sabina Signoretti, Andrew Berchuck, Darell Bigner, Eric Lipp, Jeffrey Marks, Shannon McCall, Roger McLendon, Angeles Secord, Alexis Sharp, Madhusmita Behera, Daniel J. Brat, Amy Chen, Keith Delman, Seth Force, Fadlo Khuri, Kelly Magliocca, Shishir Maithel, Jeffrey J. Olson, Taofeek Owonikoko, Alan Pickens, Suresh Ramalingam, Dong M. Shin, Gabriel Sica, Erwin G. Van Meir, Hongzheng Zhang, Wil Eijckenboom, Ad Gillis, Esther Korpershoek, Leendert Looijenga, Wolter Oosterhuis, Hans Stoop, Kim E. van Kessel, Ellen C. Zwarthoff, Chiara Calatozzolo, Lucia Cuppini, Stefania Cuzzubbo, Francesco DiMeco, Gaetano Finocchiaro, Luca Mattei, Alessandro Perin, Bianca Pollo, Chu Chen, John Houck, Pawadee Lohavanichbutr, Arndt Hartmann, Christine Stoehr, Robert Stoehr, Helge Taubert, Sven Wach, Bernd Wullich, Witold Kycler, Dawid Murawa, Maciej Wiznerowicz, Ki Chung, W. Jeffrey Edenfield, Julie Martin, Eric Baudin, Glenn Bubley, Raphael Bueno, Assunta De Rienzo, William G. Richards, Steven Kalkanis, Tom Mikkelsen, Houtan Noushmehr, Lisa Scarpace, Nicolas Girard, Marta Aymerich, Elias Campo, Eva Giné, Armando López Guillermo, Nguyen Van Bang, Phan Thi Hanh, Bui Duc Phu, Yufang Tang, Howard Colman, Kimberley Evason, Peter R. Dottino, John A. Martignetti, Hani Gabra, Hartmut Juhl, Teniola Akeredolu, Serghei Stepa, Dave Hoon, Keunsoo Ahn, Koo Jeong Kang, Felix Beuschlein, Anne Breggia, Michael Birrer, Debra Bell, Mitesh Borad, Alan H. Bryce, Erik Castle, Vishal Chandan, John Cheville, John A. Copland, Michael Farnell, Thomas Flotte, Nasra Giama, Thai Ho, Michael Kendrick, Jean-Pierre Kocher, Karla Kopp, Catherine Moser, David Nagorney, Daniel O’Brien, Brian Patrick O’Neill, Tushar Patel, Gloria Petersen, Florencia Que, Michael Rivera, Lewis Roberts, Robert Smallridge, Thomas Smyrk, Melissa Stanton, R. Houston Thompson, Michael Torbenson, Ju Dong Yang, Lizhi Zhang, Fadi Brimo, Jaffer A. Ajani, Ana Maria Angulo Gonzalez, Carmen Behrens, Jolanta Bondaruk, Russell Broaddus, Bogdan Czerniak, Bita Esmaeli, Junya Fujimoto, Jeffrey Gershenwald, Charles Guo, Christopher Logothetis, Funda Meric-Bernstam, Cesar Moran, Lois Ramondetta, David Rice, Anil Sood, Pheroze Tamboli, Timothy Thompson, Patricia Troncoso, Anne Tsao, Ignacio Wistuba, Candace Carter, Lauren Haydu, Peter Hersey, Valerie Jakrot, Hojabr Kakavand, Richard Kefford, Kenneth Lee, Georgina Long, Graham Mann, Michael Quinn, Robyn Saw, Richard Scolyer, Kerwin Shannon, Andrew Spillane, Jonathan Stretch, Maria Synott, John Thompson, James Wilmott, Hikmat Al-Ahmadie, Timothy A. Chan, Ronald Ghossein, Anuradha Gopalan, Victor Reuter, Samuel Singer, Bhuvanesh Singh, Nguyen Viet Tien, Thomas Broudy, Cyrus Mirsaidi, Praveen Nair, Paul Drwiega, Judy Miller, Jennifer Smith, Howard Zaren, Joong-Won Park, Nguyen Phi Hung, Electron Kebebew, W. Marston Linehan, Adam R. Metwalli, Karel Pacak, Peter A. Pinto, Mark Schiffman, Laura S. Schmidt, Cathy D. Vocke, Nicolas Wentzensen, Robert Worrell, Hannah Yang, Marc Moncrieff, Chandra Goparaju, Jonathan Melamed, Harvey Pass, Natalia Botnariuc, Irina Caraman, Mircea Cernat, Inga Chemencedji, Adrian Clipca, Serghei Doruc, Ghenadie Gorincioi, Sergiu Mura, Maria Pirtac, Irina Stancul, Diana Tcaciuc, Monique Albert, Iakovina Alexopoulou, Angel Arnaout, John Bartlett, Jay Engel, Sebastien Gilbert, Jeremy Parfitt, Harman Sekhon, George Thomas, Doris M. Rassl, Robert C. Rintoul, Carlo Bifulco, Raina Tamakawa, Walter Urba, Nicholas Hayward, Henri Timmers, Anna Antenucci, Francesco Facciolo, Gianluca Grazi, Mirella Marino, Roberta Merola, Ronald de Krijger, Anne-Paule Gimenez-Roqueplo, Alain Piché, Simone Chevalier, Ginette McKercher, Kivanc Birsoy, Gene Barnett, Cathy Brewer, Carol Farver, Theresa Naska, Nathan A. Pennell, Daniel Raymond, Cathy Schilero, Kathy Smolenski, Felicia Williams, Carl Morrison, Jeffrey A. Borgia, Michael J. Liptay, Mark Pool, Christopher W. Seder, Kerstin Junker, Mikhail Dinkin, George Manikhas, Domenico Alvaro, Maria Consiglia Bragazzi, Vincenzo Cardinale, Guido Carpino, Eugenio Gaudio, David Chesla, Sandra Cottingham, Michael Dubina, Fedor Moiseenko, Renumathy Dhanasekaran, Karl-Friedrich Becker, Klaus-Peter Janssen, Julia Slotta-Huspenina, Mohamed H. Abdel-Rahman, Dina Aziz, Sue Bell, Colleen M. Cebulla, Amy Davis, Rebecca Duell, J. Bradley Elder, Joe Hilty, Bahavna Kumar, James Lang, Norman L. Lehman, Randy Mandt, Phuong Nguyen, Robert Pilarski, Karan Rai, Lynn Schoenfield, Kelly Senecal, Paul Wakely, Paul Hansen, Ronald Lechan, James Powers, Arthur Tischler, William E. Grizzle, Katherine C. Sexton, Alison Kastl, Joel Henderson, Sima Porten, Jens Waldmann, Martin Fassnacht, Sylvia L. Asa, Dirk Schadendorf, Marta Couce, Markus Graefen, Hartwig Huland, Guido Sauter, Thorsten Schlomm, Ronald Simon, Pierre Tennstedt, Oluwole Olabode, Mark Nelson, Oliver Bathe, Peter R. Carroll, June M. Chan, Philip Disaia, Pat Glenn, Robin K. Kelley, Charles N. Landen, Joanna Phillips, Michael Prados, Jeffry Simko, Karen Smith-McCune, Scott VandenBerg, Kevin Roggin, Ashley Fehrenbach, Ady Kendler, Suzanne Sifri, Ruth Steele, Antonio Jimeno, Francis Carey, Ian Forgie, Massimo Mannelli, Michael Carney, Brenda Hernandez, Benito Campos, Christel Herold-Mende, Christin Jungk, Andreas Unterberg, Andreas von Deimling, Aaron Bossler, Joseph Galbraith, Laura Jacobus, Michael Knudson, Tina Knutson, Deqin Ma, Mohammed Milhem, Rita Sigmund, Andrew K. Godwin, Rashna Madan, Howard G. Rosenthal, Clement Adebamowo, Sally N. Adebamowo, Alex Boussioutas, David Beer, Thomas Giordano, Anne-Marie Mes-Masson, Fred Saad, Therese Bocklage, Lisa Landrum, Robert Mannel, Kathleen Moore, Katherine Moxley, Russel Postier, Joan Walker, Rosemary Zuna, Michael Feldman, Federico Valdivieso, Rajiv Dhir, James Luketich, Edna M. Mora Pinero, Mario Quintero-Aguilo, Carlos Gilberto Carlotti, Jr, Jose Sebastião Dos Santos, Rafael Kemp, Ajith Sankarankuty, Daniela Tirapelli, James Catto, Kathy Agnew, Elizabeth Swisher, Jenette Creaney, Bruce Robinson, Carl Simon Shelley, Eryn M. Godwin, Sara Kendall, Cassaundra Shipman, Carol Bradford, Thomas Carey, Andrea Haddad, Jeffey Moyer, Lisa Peterson, Mark Prince, Laura Rozek, Gregory Wolf, Rayleen Bowman, Kwun M. Fong, Ian Yang, Robert Korst, W. Kimryn Rathmell, J. Leigh Fantacone-Campbell, Jeffrey A. Hooke, John DiPersio, Bettina Drake, Ramaswamy Govindan, Sharon Heath, Timothy Ley, Brian Van Tine, Peter Westervelt, Mark A. Rubin, Jung Il Lee, Natália D. Aredes, Armaz Mariamidze, Liu J., Lichtenberg T., Hoadley K.A., Poisson L.M., Lazar A.J., Cherniack A.D., Kovatich A.J., Benz C.C., Levine D.A., Lee A.V., Omberg L., Wolf D.M., Shriver C.D., Thorsson V., Caesar-Johnson S.J., Demchok J.A., Felau I., Kasapi M., Ferguson M.L., Hutter C.M., Sofia H.J., Tarnuzzer R., Wang Z., Yang L., Zenklusen J.C., Zhang J.J., Chudamani S., Lolla L., Naresh R., Pihl T., Sun Q., Wan Y., Wu Y., Cho J., DeFreitas T., Frazer S., Gehlenborg N., Getz G., Heiman D.I., Kim J., Lawrence M.S., Lin P., Meier S., Noble M.S., Saksena G., Voet D., Zhang H., Bernard B., Chambwe N., Dhankani V., Knijnenburg T., Kramer R., Leinonen K., Liu Y., Miller M., Reynolds S., Shmulevich I., Zhang W., Akbani R., Broom B.M., Hegde A.M., Ju Z., Kanchi R.S., Korkut A., Li J., Liang H., Ling S., Liu W., Lu Y., Mills G.B., Ng K.-S., Rao A., Ryan M., Wang J., Weinstein J.N., Zhang J., Abeshouse A., Armenia J., Chakravarty D., Chatila W.K., de Bruijn I., Gao J., Gross B.E., Heins Z.J., Kundra R., La K., Ladanyi M., Luna A., Nissan M.G., Ochoa A., Phillips S.M., Reznik E., Sanchez-Vega F., Sander C., Schultz N., Sheridan R., Sumer S.O., Sun Y., Taylor B.S., Anur P., Peto M., Spellman P., Benz C., Stuart J.M., Wong C.K., Yau C., Hayes D.N., Parker J.S., Wilkerson M.D., Ally A., Balasundaram M., Bowlby R., Brooks D., Carlsen R., Chuah E., Dhalla N., Holt R., Jones S.J.M., Kasaian K., Lee D., Ma Y., Marra M.A., Mayo M., Moore R.A., Mungall A.J., Mungall K., Robertson A.G., Sadeghi S., Schein J.E., Sipahimalani P., Tam A., Thiessen N., Tse K., Wong T., Berger A.C., Beroukhim R., Cibulskis C., Gabriel S.B., Gao G.F., Ha G., Meyerson M., Schumacher S.E., Shih J., Kucherlapati M.H., Kucherlapati R.S., Baylin S., Cope L., Danilova L., Bootwalla M.S., Lai P.H., Maglinte D.T., Van Den Berg D.J., Weisenberger D.J., Auman J.T., Balu S., Bodenheimer T., Fan C., Hoyle A.P., Jefferys S.R., Jones C.D., Meng S., Mieczkowski P.A., Mose L.E., Perou A.H., Perou C.M., Roach J., Shi Y., Simons J.V., Skelly T., Soloway M.G., Tan D., Veluvolu U., Fan H., Hinoue T., Laird P.W., Shen H., Zhou W., Bellair M., Chang K., Covington K., Creighton C.J., Dinh H., Doddapaneni H., Donehower L.A., Drummond J., Gibbs R.A., Glenn R., Hale W., Han Y., Hu J., Korchina V., Lee S., Lewis L., Li W., Liu X., Morgan M., Morton D., Muzny D., Santibanez J., Sheth M., Shinbro E., Wang L., Wang M., Wheeler D.A., Xi L., Zhao F., Hess J., Appelbaum E.L., Bailey M., Cordes M.G., Ding L., Fronick C.C., Fulton L.A., Fulton R.S., Kandoth C., Mardis E.R., McLellan M.D., Miller C.A., Schmidt H.K., Wilson R.K., Crain D., Curley E., Gardner J., Lau K., Mallery D., Morris S., Paulauskis J., Penny R., Shelton C., Shelton T., Sherman M., Thompson E., Yena P., Bowen J., Gastier-Foster J.M., Gerken M., Leraas K.M., Lichtenberg T.M., Ramirez N.C., Wise L., Zmuda E., Corcoran N., Costello T., Hovens C., Carvalho A.L., de Carvalho A.C., Fregnani J.H., Longatto-Filho A., Reis R.M., Scapulatempo-Neto C., Silveira H.C.S., Vidal D.O., Burnette A., Eschbacher J., Hermes B., Noss A., Singh R., Anderson M.L., Castro P.D., Ittmann M., Huntsman D., Kohl B., Le X., Thorp R., Andry C., Duffy E.R., Lyadov V., Paklina O., Setdikova G., Shabunin A., Tavobilov M., McPherson C., Warnick R., Berkowitz R., Cramer D., Feltmate C., Horowitz N., Kibel A., Muto M., Raut C.P., Malykh A., Barnholtz-Sloan J.S., Barrett W., Devine K., Fulop J., Ostrom Q.T., Shimmel K., Wolinsky Y., Sloan A.E., De Rose A., Giuliante F., Goodman M., Karlan B.Y., Hagedorn C.H., Eckman J., Harr J., Myers J., Tucker K., Zach L.A., Deyarmin B., Hu H., Kvecher L., Larson C., Mural R.J., Somiari S., Vicha A., Zelinka T., Bennett J., Iacocca M., Rabeno B., Swanson P., Latour M., Lacombe L., Tetu B., Bergeron A., McGraw M., Staugaitis S.M., Chabot J., Hibshoosh H., Sepulveda A., Su T., Wang T., Potapova O., Voronina O., Desjardins L., Mariani O., Roman-Roman S., Sastre X., Stern M.-H., Cheng F., Signoretti S., Berchuck A., Bigner D., Lipp E., Marks J., McCall S., McLendon R., Secord A., Sharp A., Behera M., Brat D.J., Chen A., Delman K., Force S., Khuri F., Magliocca K., Maithel S., Olson J.J., Owonikoko T., Pickens A., Ramalingam S., Shin D.M., Sica G., Van Meir E.G., Eijckenboom W., Gillis A., Korpershoek E., Looijenga L., Oosterhuis W., Stoop H., van Kessel K.E., Zwarthoff E.C., Calatozzolo C., Cuppini L., Cuzzubbo S., DiMeco F., Finocchiaro G., Mattei L., Perin A., Pollo B., Chen C., Houck J., Lohavanichbutr P., Hartmann A., Stoehr C., Stoehr R., Taubert H., Wach S., Wullich B., Kycler W., Murawa D., Wiznerowicz M., Chung K., Edenfield W.J., Martin J., Baudin E., Bubley G., Bueno R., De Rienzo A., Richards W.G., Kalkanis S., Mikkelsen T., Noushmehr H., Scarpace L., Girard N., Aymerich M., Campo E., Gine E., Guillermo A.L., Van Bang N., Hanh P.T., Phu B.D., Tang Y., Colman H., Evason K., Dottino P.R., Martignetti J.A., Gabra H., Juhl H., Akeredolu T., Stepa S., Hoon D., Ahn K., Kang K.J., Beuschlein F., Breggia A., Birrer M., Bell D., Borad M., Bryce A.H., Castle E., Chandan V., Cheville J., Copland J.A., Farnell M., Flotte T., Giama N., Ho T., Kendrick M., Kocher J.-P., Kopp K., Moser C., Nagorney D., O'Brien D., O'Neill B.P., Patel T., Petersen G., Que F., Rivera M., Roberts L., Smallridge R., Smyrk T., Stanton M., Thompson R.H., Torbenson M., Yang J.D., Zhang L., Brimo F., Ajani J.A., Angulo Gonzalez A.M., Behrens C., Bondaruk J., Broaddus R., Czerniak B., Esmaeli B., Fujimoto J., Gershenwald J., Guo C., Logothetis C., Meric-Bernstam F., Moran C., Ramondetta L., Rice D., Sood A., Tamboli P., Thompson T., Troncoso P., Tsao A., Wistuba I., Carter C., Haydu L., Hersey P., Jakrot V., Kakavand H., Kefford R., Lee K., Long G., Mann G., Quinn M., Saw R., Scolyer R., Shannon K., Spillane A., Stretch J., Synott M., Thompson J., Wilmott J., Al-Ahmadie H., Chan T.A., Ghossein R., Gopalan A., Reuter V., Singer S., Singh B., Tien N.V., Broudy T., Mirsaidi C., Nair P., Drwiega P., Miller J., Smith J., Zaren H., Park J.-W., Hung N.P., Kebebew E., Linehan W.M., Metwalli A.R., Pacak K., Pinto P.A., Schiffman M., Schmidt L.S., Vocke C.D., Wentzensen N., Worrell R., Yang H., Moncrieff M., Goparaju C., Melamed J., Pass H., Botnariuc N., Caraman I., Cernat M., Chemencedji I., Clipca A., Doruc S., Gorincioi G., Mura S., Pirtac M., Stancul I., Tcaciuc D., Albert M., Alexopoulou I., Arnaout A., Bartlett J., Engel J., Gilbert S., Parfitt J., Sekhon H., Thomas G., Rassl D.M., Rintoul R.C., Bifulco C., Tamakawa R., Urba W., Hayward N., Timmers H., Antenucci A., Facciolo F., Grazi G., Marino M., Merola R., de Krijger R., Gimenez-Roqueplo A.-P., Piche A., Chevalier S., McKercher G., Birsoy K., Barnett G., Brewer C., Farver C., Naska T., Pennell N.A., Raymond D., Schilero C., Smolenski K., Williams F., Morrison C., Borgia J.A., Liptay M.J., Pool M., Seder C.W., Junker K., Dinkin M., Manikhas G., Alvaro D., Bragazzi M.C., Cardinale V., Carpino G., Gaudio E., Chesla D., Cottingham S., Dubina M., Moiseenko F., Dhanasekaran R., Becker K.-F., Janssen K.-P., Slotta-Huspenina J., Abdel-Rahman M.H., Aziz D., Bell S., Cebulla C.M., Davis A., Duell R., Elder J.B., Hilty J., Kumar B., Lang J., Lehman N.L., Mandt R., Nguyen P., Pilarski R., Rai K., Schoenfield L., Senecal K., Wakely P., Hansen P., Lechan R., Powers J., Tischler A., Grizzle W.E., Sexton K.C., Kastl A., Henderson J., Porten S., Waldmann J., Fassnacht M., Asa S.L., Schadendorf D., Couce M., Graefen M., Huland H., Sauter G., Schlomm T., Simon R., Tennstedt P., Olabode O., Nelson M., Bathe O., Carroll P.R., Chan J.M., Disaia P., Glenn P., Kelley R.K., Landen C.N., Phillips J., Prados M., Simko J., Smith-McCune K., VandenBerg S., Roggin K., Fehrenbach A., Kendler A., Sifri S., Steele R., Jimeno A., Carey F., Forgie I., Mannelli M., Carney M., Hernandez B., Campos B., Herold-Mende C., Jungk C., Unterberg A., von Deimling A., Bossler A., Galbraith J., Jacobus L., Knudson M., Knutson T., Ma D., Milhem M., Sigmund R., Godwin A.K., Madan R., Rosenthal H.G., Adebamowo C., Adebamowo S.N., Boussioutas A., Beer D., Giordano T., Mes-Masson A.-M., Saad F., Bocklage T., Landrum L., Mannel R., Moore K., Moxley K., Postier R., Walker J., Zuna R., Feldman M., Valdivieso F., Dhir R., Luketich J., Mora Pinero E.M., Quintero-Aguilo M., Carlotti C.G., Dos Santos J.S., Kemp R., Sankarankuty A., Tirapelli D., Catto J., Agnew K., Swisher E., Creaney J., Robinson B., Shelley C.S., Godwin E.M., Kendall S., Shipman C., Bradford C., Carey T., Haddad A., Moyer J., Peterson L., Prince M., Rozek L., Wolf G., Bowman R., Fong K.M., Yang I., Korst R., Rathmell W.K., Fantacone-Campbell J.L., Hooke J.A., DiPersio J., Drake B., Govindan R., Heath S., Ley T., Van Tine B., Westervelt P., Rubin M.A., Lee J.I., Aredes N.D., Mariamidze A., SAIC-F-Frederick, Inc, and Leidos Biomedical Research, Inc.
Subjects: 0301 basic medicine, Genetics and Molecular Biology (all), Cancer Genome Atlas Research Network, Kaplan-Meier Estimate, Biochemistry, DEFINITIONS, Neoplasms, Databases, Genetic, SUFFICIENT FOLLOW-UP, LS2_1, LS4_6, 11 Medical and Health Sciences, COMPREHENSIVE GENOMIC CHARACTERIZATION, Cox proportional hazards regression model, TAXA DE SOBREVIVÊNCIA, follow-up time, Genomics, 3. Good health, TIME, Life Sciences & Biomedicine, PROGRESSION-FREE SURVIVAL, Human, Biochemistry & Molecular Biology, overall survival, The Cancer Genome Atlas, Translational research, Computational biology, Biology, clinical data resource, disease-free interval, disease-specific survival, progression-free interval, TCGA, translational research, Article, General Biochemistry, Genetics and Molecular Biology, CLASSIFICATION, NO, 03 medical and health sciences, Annotation, Breast cancer, END-POINTS, medicine, BREAST-CANCER, Humans, Progression-free survival, RECURRENCE, Biochemistry, Genetics and Molecular Biology (all), Proportional Hazards Models, Data collection, Science & Technology, business.industry, MOLECULAR PORTRAITS, Biochemistry, Genetics and Molecular Biology(all), Cancer, Cell Biology, 06 Biological Sciences, medicine.disease, 030104 developmental biology, Analytics, Genomic, Neoplasm, business, The Cancer Genome Atla, Genetics and Molecular Biology(all), Developmental Biology
Abstract: SUMMARY For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale., Graphical abstract In Brief Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types.
Published: 2018

37. The Immune Landscape of Cancer

Author: Vésteinn Thorsson, David L. Gibbs, Scott D. Brown, Denise Wolf, Dante S. Bortone, Tai-Hsien Ou Yang, Eduard Porta-Pardo, Galen F. Gao, Christopher L. Plaisier, James A. Eddy, Elad Ziv, Aedin C. Culhane, Evan O. Paull, I.K. Ashok Sivakumar, Andrew J. Gentles, Raunaq Malhotra, Farshad Farshidfar, Antonio Colaprico, Joel S. Parker, Lisle E. Mose, Nam Sy Vo, Jianfang Liu, Yuexin Liu, Janet Rader, Varsha Dhankani, Sheila M. Reynolds, Reanne Bowlby, Andrea Califano, Andrew D. Cherniack, Dimitris Anastassiou, Davide Bedognetti, Younes Mokrab, Aaron M. Newman, Arvind Rao, Ken Chen, Alexander Krasnitz, Hai Hu, Tathiane M. Malta, Houtan Noushmehr, Chandra Sekhar Pedamallu, Susan Bullman, Akinyemi I. Ojesina, Andrew Lamb, Wanding Zhou, Hui Shen, Toni K. Choueiri, John N. Weinstein, Justin Guinney, Joel Saltz, Robert A. Holt, Charles S. Rabkin, Alexander J. Lazar, Jonathan S. Serody, Elizabeth G. Demicco, Mary L. Disis, Benjamin G. Vincent, Ilya Shmulevich, Samantha J. Caesar-Johnson, John A. Demchok, Ina Felau, Melpomeni Kasapi, Martin L. Ferguson, Carolyn M. Hutter, Heidi J. Sofia, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jean C. Zenklusen, Jiashan (Julia) Zhang, Sudha Chudamani, Jia Liu, Laxmi Lolla, Rashi Naresh, Todd Pihl, Qiang Sun, Yunhu Wan, Ye Wu, Juok Cho, Timothy DeFreitas, Scott Frazer, Nils Gehlenborg, Gad Getz, David I. Heiman, Jaegil Kim, Michael S. Lawrence, Pei Lin, Sam Meier, Michael S. Noble, Gordon Saksena, Doug Voet, Hailei Zhang, Brady Bernard, Nyasha Chambwe, Theo Knijnenburg, Roger Kramer, Kalle Leinonen, Michael Miller, Sheila Reynolds, Vesteinn Thorsson, Wei Zhang, Rehan Akbani, Bradley M. Broom, Apurva M. Hegde, Zhenlin Ju, Rupa S. Kanchi, Anil Korkut, Jun Li, Han Liang, Shiyun Ling, Wenbin Liu, Yiling Lu, Gordon B. Mills, Kwok-Shing Ng, Michael Ryan, Jing Wang, Jiexin Zhang, Adam Abeshouse, Joshua Armenia, Debyani Chakravarty, Walid K. Chatila, Ino de Bruijn, Jianjiong Gao, Benjamin E. Gross, Zachary J. Heins, Ritika Kundra, Konnor La, Marc Ladanyi, Augustin Luna, Moriah G. Nissan, Angelica Ochoa, Sarah M. Phillips, Ed Reznik, Francisco Sanchez-Vega, Chris Sander, Nikolaus Schultz, Robert Sheridan, S. Onur Sumer, Yichao Sun, Barry S. Taylor, Jioajiao Wang, Hongxin Zhang, Pavana Anur, Myron Peto, Paul Spellman, Christopher Benz, Joshua M. Stuart, Christopher K. Wong, Christina Yau, D. Neil Hayes, Matthew D. Wilkerson, Adrian Ally, Miruna Balasundaram, Denise Brooks, Rebecca Carlsen, Eric Chuah, Noreen Dhalla, Robert Holt, Steven J.M. Jones, Katayoon Kasaian, Darlene Lee, Yussanne Ma, Marco A. Marra, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Karen Mungall, A. Gordon Robertson, Sara Sadeghi, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Kane Tse, Tina Wong, Ashton C. Berger, Rameen Beroukhim, Carrie Cibulskis, Stacey B. Gabriel, Gavin Ha, Matthew Meyerson, Steven E. Schumacher, Juliann Shih, Melanie H. Kucherlapati, Raju S. Kucherlapati, Stephen Baylin, Leslie Cope, Ludmila Danilova, Moiz S. Bootwalla, Phillip H. Lai, Dennis T. Maglinte, David J. Van Den Berg, Daniel J. Weisenberger, J. Todd Auman, Saianand Balu, Tom Bodenheimer, Cheng Fan, Katherine A. Hoadley, Alan P. Hoyle, Stuart R. Jefferys, Corbin D. Jones, Shaowu Meng, Piotr A. Mieczkowski, Amy H. Perou, Charles M. Perou, Jeffrey Roach, Yan Shi, Janae V. Simons, Tara Skelly, Matthew G. Soloway, Donghui Tan, Umadevi Veluvolu, Huihui Fan, Toshinori Hinoue, Peter W. Laird, Michelle Bellair, Kyle Chang, Kyle Covington, Chad J. Creighton, Huyen Dinh, HarshaVardhan Doddapaneni, Lawrence A. Donehower, Jennifer Drummond, Richard A. Gibbs, Robert Glenn, Walker Hale, Yi Han, Jianhong Hu, Viktoriya Korchina, Sandra Lee, Lora Lewis, Wei Li, Xiuping Liu, Margaret Morgan, Donna Morton, Donna Muzny, Jireh Santibanez, Margi Sheth, Eve Shinbrot, Linghua Wang, Min Wang, David A. Wheeler, Liu Xi, Fengmei Zhao, Julian Hess, Elizabeth L. Appelbaum, Matthew Bailey, Matthew G. Cordes, Li Ding, Catrina C. Fronick, Lucinda A. Fulton, Robert S. Fulton, Cyriac Kandoth, Elaine R. Mardis, Michael D. McLellan, Christopher A. Miller, Heather K. Schmidt, Richard K. Wilson, Daniel Crain, Erin Curley, Johanna Gardner, Kevin Lau, David Mallery, Scott Morris, Joseph Paulauskis, Robert Penny, Candace Shelton, Troy Shelton, Mark Sherman, Eric Thompson, Peggy Yena, Jay Bowen, Julie M. Gastier-Foster, Mark Gerken, Kristen M. Leraas, Tara M. Lichtenberg, Nilsa C. Ramirez, Lisa Wise, Erik Zmuda, Niall Corcoran, Tony Costello, Christopher Hovens, Andre L. Carvalho, Ana C. de Carvalho, José H. Fregnani, Adhemar Longatto-Filho, Rui M. Reis, Cristovam Scapulatempo-Neto, Henrique C.S. Silveira, Daniel O. Vidal, Andrew Burnette, Jennifer Eschbacher, Beth Hermes, Ardene Noss, Rosy Singh, Matthew L. Anderson, Patricia D. Castro, Michael Ittmann, David Huntsman, Bernard Kohl, Xuan Le, Richard Thorp, Chris Andry, Elizabeth R. Duffy, Vladimir Lyadov, Oxana Paklina, Galiya Setdikova, Alexey Shabunin, Mikhail Tavobilov, Christopher McPherson, Ronald Warnick, Ross Berkowitz, Daniel Cramer, Colleen Feltmate, Neil Horowitz, Adam Kibel, Michael Muto, Chandrajit P. Raut, Andrei Malykh, Jill S. Barnholtz-Sloan, Wendi Barrett, Karen Devine, Jordonna Fulop, Quinn T. Ostrom, Kristen Shimmel, Yingli Wolinsky, Andrew E. Sloan, Agostino De Rose, Felice Giuliante, Marc Goodman, Beth Y. Karlan, Curt H. Hagedorn, John Eckman, Jodi Harr, Jerome Myers, Kelinda Tucker, Leigh Anne Zach, Brenda Deyarmin, Leonid Kvecher, Caroline Larson, Richard J. Mural, Stella Somiari, Ales Vicha, Tomas Zelinka, Joseph Bennett, Mary Iacocca, Brenda Rabeno, Patricia Swanson, Mathieu Latour, Louis Lacombe, Bernard Têtu, Alain Bergeron, Mary McGraw, Susan M. Staugaitis, John Chabot, Hanina Hibshoosh, Antonia Sepulveda, Tao Su, Timothy Wang, Olga Potapova, Olga Voronina, Laurence Desjardins, Odette Mariani, Sergio Roman-Roman, Xavier Sastre, Marc-Henri Stern, Feixiong Cheng, Sabina Signoretti, Andrew Berchuck, Darell Bigner, Eric Lipp, Jeffrey Marks, Shannon McCall, Roger McLendon, Angeles Secord, Alexis Sharp, Madhusmita Behera, Daniel J. Brat, Amy Chen, Keith Delman, Seth Force, Fadlo Khuri, Kelly Magliocca, Shishir Maithel, Jeffrey J. Olson, Taofeek Owonikoko, Alan Pickens, Suresh Ramalingam, Dong M. Shin, Gabriel Sica, Erwin G. Van Meir, Hongzheng Zhang, Wil Eijckenboom, Ad Gillis, Esther Korpershoek, Leendert Looijenga, Wolter Oosterhuis, Hans Stoop, Kim E. van Kessel, Ellen C. Zwarthoff, Chiara Calatozzolo, Lucia Cuppini, Stefania Cuzzubbo, Francesco DiMeco, Gaetano Finocchiaro, Luca Mattei, Alessandro Perin, Bianca Pollo, Chu Chen, John Houck, Pawadee Lohavanichbutr, Arndt Hartmann, Christine Stoehr, Robert Stoehr, Helge Taubert, Sven Wach, Bernd Wullich, Witold Kycler, Dawid Murawa, Maciej Wiznerowicz, Ki Chung, W. Jeffrey Edenfield, Julie Martin, Eric Baudin, Glenn Bubley, Raphael Bueno, Assunta De Rienzo, William G. Richards, Steven Kalkanis, Tom Mikkelsen, Lisa Scarpace, Nicolas Girard, Marta Aymerich, Elias Campo, Eva Giné, Armando López Guillermo, Nguyen Van Bang, Phan Thi Hanh, Bui Duc Phu, Yufang Tang, Howard Colman, Kimberley Evason, Peter R. Dottino, John A. Martignetti, Hani Gabra, Hartmut Juhl, Teniola Akeredolu, Serghei Stepa, Dave Hoon, Keunsoo Ahn, Koo Jeong Kang, Felix Beuschlein, Anne Breggia, Michael Birrer, Debra Bell, Mitesh Borad, Alan H. Bryce, Erik Castle, Vishal Chandan, John Cheville, John A. Copland, Michael Farnell, Thomas Flotte, Nasra Giama, Thai Ho, Michael Kendrick, Jean-Pierre Kocher, Karla Kopp, Catherine Moser, David Nagorney, Daniel O’Brien, Brian Patrick O’Neill, Tushar Patel, Gloria Petersen, Florencia Que, Michael Rivera, Lewis Roberts, Robert Smallridge, Thomas Smyrk, Melissa Stanton, R. Houston Thompson, Michael Torbenson, Ju Dong Yang, Lizhi Zhang, Fadi Brimo, Jaffer A. Ajani, Ana Maria Angulo Gonzalez, Carmen Behrens, Jolanta Bondaruk, Russell Broaddus, Bogdan Czerniak, Bita Esmaeli, Junya Fujimoto, Jeffrey Gershenwald, Charles Guo, Christopher Logothetis, Funda Meric-Bernstam, Cesar Moran, Lois Ramondetta, David Rice, Anil Sood, Pheroze Tamboli, Timothy Thompson, Patricia Troncoso, Anne Tsao, Ignacio Wistuba, Candace Carter, Lauren Haydu, Peter Hersey, Valerie Jakrot, Hojabr Kakavand, Richard Kefford, Kenneth Lee, Georgina Long, Graham Mann, Michael Quinn, Robyn Saw, Richard Scolyer, Kerwin Shannon, Andrew Spillane, onathan Stretch, Maria Synott, John Thompson, James Wilmott, Hikmat Al-Ahmadie, Timothy A. Chan, Ronald Ghossein, Anuradha Gopalan, Douglas A. Levine, Victor Reuter, Samuel Singer, Bhuvanesh Singh, Nguyen Viet Tien, Thomas Broudy, Cyrus Mirsaidi, Praveen Nair, Paul Drwiega, Judy Miller, Jennifer Smith, Howard Zaren, Joong-Won Park, Nguyen Phi Hung, Electron Kebebew, W. Marston Linehan, Adam R. Metwalli, Karel Pacak, Peter A. Pinto, Mark Schiffman, Laura S. Schmidt, Cathy D. Vocke, Nicolas Wentzensen, Robert Worrell, Hannah Yang, Marc Moncrieff, Chandra Goparaju, Jonathan Melamed, Harvey Pass, Natalia Botnariuc, Irina Caraman, Mircea Cernat, Inga Chemencedji, Adrian Clipca, Serghei Doruc, Ghenadie Gorincioi, Sergiu Mura, Maria Pirtac, Irina Stancul, Diana Tcaciuc, Monique Albert, Iakovina Alexopoulou, Angel Arnaout, John Bartlett, Jay Engel, Sebastien Gilbert, Jeremy Parfitt, Harman Sekhon, George Thomas, Doris M. Rassl, Robert C. Rintoul, Carlo Bifulco, Raina Tamakawa, Walter Urba, Nicholas Hayward, Henri Timmers, Anna Antenucci, Francesco Facciolo, Gianluca Grazi, Mirella Marino, Roberta Merola, Ronald de Krijger, Anne-Paule Gimenez-Roqueplo, Alain Piché, Simone Chevalier, Ginette McKercher, Kivanc Birsoy, Gene Barnett, Cathy Brewer, Carol Farver, Theresa Naska, Nathan A. Pennell, Daniel Raymond, Cathy Schilero, Kathy Smolenski, Felicia Williams, Carl Morrison, Jeffrey A. Borgia, Michael J. Liptay, Mark Pool, Christopher W. Seder, Kerstin Junker, Larsson Omberg, Mikhail Dinkin, George Manikhas, Domenico Alvaro, Maria Consiglia Bragazzi, Vincenzo Cardinale, Guido Carpino, Eugenio Gaudio, David Chesla, Sandra Cottingham, Michael Dubina, Fedor Moiseenko, Renumathy Dhanasekaran, Karl-Friedrich Becker, Klaus-Peter Janssen, Julia Slotta-Huspenina, Mohamed H. Abdel-Rahman, Dina Aziz, Sue Bell, Colleen M. Cebulla, Amy Davis, Rebecca Duell, J. Bradley Elder, Joe Hilty, Bahavna Kumar, James Lang, Norman L. Lehman, Randy Mandt, Phuong Nguyen, Robert Pilarski, Karan Rai, Lynn Schoenfield, Kelly Senecal, Paul Wakely, Paul Hansen, Ronald Lechan, James Powers, Arthur Tischler, William E. Grizzle, Katherine C. Sexton, Alison Kastl, Joel Henderson, Sima Porten, Jens Waldmann, Martin Fassnacht, Sylvia L. Asa, Dirk Schadendorf, Marta Couce, Markus Graefen, Hartwig Huland, Guido Sauter, Thorsten Schlomm, Ronald Simon, Pierre Tennstedt, Oluwole Olabode, Mark Nelson, Oliver Bathe, Peter R. Carroll, June M. Chan, Philip Disaia, Pat Glenn, Robin K. Kelley, Charles N. Landen, Joanna Phillips, Michael Prados, Jeffry Simko, Karen Smith-McCune, Scott VandenBerg, Kevin Roggin, Ashley Fehrenbach, Ady Kendler, Suzanne Sifri, Ruth Steele, Antonio Jimeno, Francis Carey, Ian Forgie, Massimo Mannelli, Michael Carney, Brenda Hernandez, Benito Campos, Christel Herold-Mende, Christin Jungk, Andreas Unterberg, Andreas von Deimling, Aaron Bossler, Joseph Galbraith, Laura Jacobus, Michael Knudson, Tina Knutson, Deqin Ma, Mohammed Milhem, Rita Sigmund, Andrew K. Godwin, Rashna Madan, Howard G. Rosenthal, Clement Adebamowo, Sally N. Adebamowo, Alex Boussioutas, David Beer, Thomas Giordano, Anne-Marie Mes-Masson, Fred Saad, Therese Bocklage, Lisa Landrum, Robert Mannel, Kathleen Moore, Katherine Moxley, Russel Postier, Joan Walker, Rosemary Zuna, Michael Feldman, Federico Valdivieso, Rajiv Dhir, James Luketich, Edna M. Mora Pinero, Mario Quintero-Aguilo, Carlos Gilberto Carlotti, Jose Sebastião Dos Santos, Rafael Kemp, Ajith Sankarankuty, Daniela Tirapelli, James Catto, Kathy Agnew, Elizabeth Swisher, Jenette Creaney, Bruce Robinson, Carl Simon Shelley, Eryn M. Godwin, Sara Kendall, Cassaundra Shipman, Carol Bradford, Thomas Carey, Andrea Haddad, Jeffey Moyer, Lisa Peterson, Mark Prince, Laura Rozek, Gregory Wolf, Rayleen Bowman, Kwun M. Fong, Ian Yang, Robert Korst, W. Kimryn Rathmell, J. Leigh Fantacone-Campbell, Jeffrey A. Hooke, Albert J. Kovatich, Craig D. Shriver, John DiPersio, Bettina Drake, Ramaswamy Govindan, Sharon Heath, Timothy Ley, Brian Van Tine, Peter Westervelt, Mark A. Rubin, Jung Il Lee, Natália D. Aredes, Armaz Mariamidze, Thorsson V., Gibbs D.L., Brown S.D., Wolf D., Bortone D.S., Ou Yang T.-H., Porta-Pardo E., Gao G.F., Plaisier C.L., Eddy J.A., Ziv E., Culhane A.C., Paull E.O., Sivakumar I.K.A., Gentles A.J., Malhotra R., Farshidfar F., Colaprico A., Parker J.S., Mose L.E., Vo N.S., Liu J., Liu Y., Rader J., Dhankani V., Reynolds S.M., Bowlby R., Califano A., Cherniack A.D., Anastassiou D., Bedognetti D., Rao A., Chen K., Krasnitz A., Hu H., Malta T.M., Noushmehr H., Pedamallu C.S., Bullman S., Ojesina A.I., Lamb A., Zhou W., Shen H., Choueiri T.K., Weinstein J.N., Guinney J., Saltz J., Holt R.A., Rabkin C.E., Caesar-Johnson S.J., Demchok J.A., Felau I., Kasapi M., Ferguson M.L., Hutter C.M., Sofia H.J., Tarnuzzer R., Wang Z., Yang L., Zenklusen J.C., Zhang J.J., Chudamani S., Lolla L., Naresh R., Pihl T., Sun Q., Wan Y., Wu Y., Cho J., DeFreitas T., Frazer S., Gehlenborg N., Getz G., Heiman D.I., Kim J., Lawrence M.S., Lin P., Meier S., Noble M.S., Saksena G., Voet D., Zhang H., Bernard B., Chambwe N., Knijnenburg T., Kramer R., Leinonen K., Miller M., Reynolds S., Shmulevich I., Zhang W., Akbani R., Broom B.M., Hegde A.M., Ju Z., Kanchi R.S., Korkut A., Li J., Liang H., Ling S., Liu W., Lu Y., Mills G.B., Ng K.-S., Ryan M., Wang J., Zhang J., Abeshouse A., Armenia J., Chakravarty D., Chatila W.K., de Bruijn I., Gao J., Gross B.E., Heins Z.J., Kundra R., La K., Ladanyi M., Luna A., Nissan M.G., Ochoa A., Phillips S.M., Reznik E., Sanchez-Vega F., Sander C., Schultz N., Sheridan R., Sumer S.O., Sun Y., Taylor B.S., Anur P., Peto M., Spellman P., Benz C., Stuart J.M., Wong C.K., Yau C., Hayes D.N., Wilkerson M.D., Ally A., Balasundaram M., Brooks D., Carlsen R., Chuah E., Dhalla N., Jones S.J.M., Kasaian K., Lee D., Ma Y., Marra M.A., Mayo M., Moore R.A., Mungall A.J., Mungall K., Robertson A.G., Sadeghi S., Schein J.E., Sipahimalani P., Tam A., Thiessen N., Tse K., Wong T., Berger A.C., Beroukhim R., Cibulskis C., Gabriel S.B., Ha G., Meyerson M., Schumacher S.E., Shih J., Kucherlapati M.H., Kucherlapati R.S., Baylin S., Cope L., Danilova L., Bootwalla M.S., Lai P.H., Maglinte D.T., Van Den Berg D.J., Weisenberger D.J., Auman J.T., Balu S., Bodenheimer T., Fan C., Hoadley K.A., Hoyle A.P., Jefferys S.R., Jones C.D., Meng S., Mieczkowski P.A., Perou A.H., Perou C.M., Roach J., Shi Y., Simons J.V., Skelly T., Soloway M.G., Tan D., Veluvolu U., Fan H., Hinoue T., Laird P.W., Bellair M., Chang K., Covington K., Creighton C.J., Dinh H., Doddapaneni H., Donehower L.A., Drummond J., Gibbs R.A., Glenn R., Hale W., Han Y., Hu J., Korchina V., Lee S., Lewis L., Li W., Liu X., Morgan M., Morton D., Muzny D., Santibanez J., Sheth M., Shinbrot E., Wang L., Wang M., Wheeler D.A., Xi L., Zhao F., Hess J., Appelbaum E.L., Bailey M., Cordes M.G., Ding L., Fronick C.C., Fulton L.A., Fulton R.S., Kandoth C., Mardis E.R., McLellan M.D., Miller C.A., Schmidt H.K., Wilson R.K., Crain D., Curley E., Gardner J., Lau K., Mallery D., Morris S., Paulauskis J., Penny R., Shelton C., Shelton T., Sherman M., Thompson E., Yena P., Bowen J., Gastier-Foster J.M., Gerken M., Leraas K.M., Lichtenberg T.M., Ramirez N.C., Wise L., Zmuda E., Corcoran N., Costello T., Hovens C., Carvalho A.L., de Carvalho A.C., Fregnani J.H., Longatto-Filho A., Reis R.M., Scapulatempo-Neto C., Silveira H.C.S., Vidal D.O., Burnette A., Eschbacher J., Hermes B., Noss A., Singh R., Anderson M.L., Castro P.D., Ittmann M., Huntsman D., Kohl B., Le X., Thorp R., Andry C., Duffy E.R., Lyadov V., Paklina O., Setdikova G., Shabunin A., Tavobilov M., McPherson C., Warnick R., Berkowitz R., Cramer D., Feltmate C., Horowitz N., Kibel A., Muto M., Raut C.P., Malykh A., Barnholtz-Sloan J.S., Barrett W., Devine K., Fulop J., Ostrom Q.T., Shimmel K., Wolinsky Y., Sloan A.E., De Rose A., Giuliante F., Goodman M., Karlan B.Y., Hagedorn C.H., Eckman J., Harr J., Myers J., Tucker K., Zach L.A., Deyarmin B., Kvecher L., Larson C., Mural R.J., Somiari S., Vicha A., Zelinka T., Bennett J., Iacocca M., Rabeno B., Swanson P., Latour M., Lacombe L., Tetu B., Bergeron A., McGraw M., Staugaitis S.M., Chabot J., Hibshoosh H., Sepulveda A., Su T., Wang T., Potapova O., Voronina O., Desjardins L., Mariani O., Roman-Roman S., Sastre X., Stern M.-H., Cheng F., Signoretti S., Berchuck A., Bigner D., Lipp E., Marks J., McCall S., McLendon R., Secord A., Sharp A., Behera M., Brat D.J., Chen A., Delman K., Force S., Khuri F., Magliocca K., Maithel S., Olson J.J., Owonikoko T., Pickens A., Ramalingam S., Shin D.M., Sica G., Van Meir E.G., Eijckenboom W., Gillis A., Korpershoek E., Looijenga L., Oosterhuis W., Stoop H., van Kessel K.E., Zwarthoff E.C., Calatozzolo C., Cuppini L., Cuzzubbo S., DiMeco F., Finocchiaro G., Mattei L., Perin A., Pollo B., Chen C., Houck J., Lohavanichbutr P., Hartmann A., Stoehr C., Stoehr R., Taubert H., Wach S., Wullich B., Kycler W., Murawa D., Wiznerowicz M., Chung K., Edenfield W.J., Martin J., Baudin E., Bubley G., Bueno R., De Rienzo A., Richards W.G., Kalkanis S., Mikkelsen T., Scarpace L., Girard N., Aymerich M., Campo E., Gine E., Guillermo A.L., Van Bang N., Hanh P.T., Phu B.D., Tang Y., Colman H., Evason K., Dottino P.R., Martignetti J.A., Gabra H., Juhl H., Akeredolu T., Stepa S., Hoon D., Ahn K., Kang K.J., Beuschlein F., Breggia A., Birrer M., Bell D., Borad M., Bryce A.H., Castle E., Chandan V., Cheville J., Copland J.A., Farnell M., Flotte T., Giama N., Ho T., Kendrick M., Kocher J.-P., Kopp K., Moser C., Nagorney D., O'Brien D., O'Neill B.P., Patel T., Petersen G., Que F., Rivera M., Roberts L., Smallridge R., Smyrk T., Stanton M., Thompson R.H., Torbenson M., Yang J.D., Zhang L., Brimo F., Ajani J.A., Gonzalez A.M.A., Behrens C., Bondaruk J., Broaddus R., Czerniak B., Esmaeli B., Fujimoto J., Gershenwald J., Guo C., Lazar A.J., Logothetis C., Meric-Bernstam F., Moran C., Ramondetta L., Rice D., Sood A., Tamboli P., Thompson T., Troncoso P., Tsao A., Wistuba I., Carter C., Haydu L., Hersey P., Jakrot V., Kakavand H., Kefford R., Lee K., Long G., Mann G., Quinn M., Saw R., Scolyer R., Shannon K., Spillane A., Stretch O., Synott M., Thompson J., Wilmott J., Al-Ahmadie H., Chan T.A., Ghossein R., Gopalan A., Levine D.A., Reuter V., Singer S., Singh B., Tien N.V., Broudy T., Mirsaidi C., Nair P., Drwiega P., Miller J., Smith J., Zaren H., Park J.-W., Hung N.P., Kebebew E., Linehan W.M., Metwalli A.R., Pacak K., Pinto P.A., Schiffman M., Schmidt L.S., Vocke C.D., Wentzensen N., Worrell R., Yang H., Moncrieff M., Goparaju C., Melamed J., Pass H., Botnariuc N., Caraman I., Cernat M., Chemencedji I., Clipca A., Doruc S., Gorincioi G., Mura S., Pirtac M., Stancul I., Tcaciuc D., Albert M., Alexopoulou I., Arnaout A., Bartlett J., Engel J., Gilbert S., Parfitt J., Sekhon H., Thomas G., Rassl D.M., Rintoul R.C., Bifulco C., Tamakawa R., Urba W., Hayward N., Timmers H., Antenucci A., Facciolo F., Grazi G., Marino M., Merola R., de Krijger R., Gimenez-Roqueplo A.-P., Piche A., Chevalier S., McKercher G., Birsoy K., Barnett G., Brewer C., Farver C., Naska T., Pennell N.A., Raymond D., Schilero C., Smolenski K., Williams F., Morrison C., Borgia J.A., Liptay M.J., Pool M., Seder C.W., Junker K., Omberg L., Dinkin M., Manikhas G., Alvaro D., Bragazzi M.C., Cardinale V., Carpino G., Gaudio E., Chesla D., Cottingham S., Dubina M., Moiseenko F., Dhanasekaran R., Becker K.-F., Janssen K.-P., Slotta-Huspenina J., Abdel-Rahman M.H., Aziz D., Bell S., Cebulla C.M., Davis A., Duell R., Elder J.B., Hilty J., Kumar B., Lang J., Lehman N.L., Mandt R., Nguyen P., Pilarski R., Rai K., Schoenfield L., Senecal K., Wakely P., Hansen P., Lechan R., Powers J., Tischler A., Grizzle W.E., Sexton K.C., Kastl A., Henderson J., Porten S., Waldmann J., Fassnacht M., Asa S.L., Schadendorf D., Couce M., Graefen M., Huland H., Sauter G., Schlomm T., Simon R., Tennstedt P., Olabode O., Nelson M., Bathe O., Carroll P.R., Chan J.M., Disaia P., Glenn P., Kelley R.K., Landen C.N., Phillips J., Prados M., Simko J., Smith-McCune K., VandenBerg S., Roggin K., Fehrenbach A., Kendler A., Sifri S., Steele R., Jimeno A., Carey F., Forgie I., Mannelli M., Carney M., Hernandez B., Campos B., Herold-Mende C., Jungk C., Unterberg A., von Deimling A., Bossler A., Galbraith J., Jacobus L., Knudson M., Knutson T., Ma D., Milhem M., Sigmund R., Godwin A.K., Madan R., Rosenthal H.G., Adebamowo C., Adebamowo S.N., Boussioutas A., Beer D., Giordano T., Mes-Masson A.-M., Saad F., Bocklage T., Landrum L., Mannel R., Moore K., Moxley K., Postier R., Walker J., Zuna R., Feldman M., Valdivieso F., Dhir R., Luketich J., Pinero E.M.M., Quintero-Aguilo M., Carlotti C.G., Dos Santos J.S., Kemp R., Sankarankuty A., Tirapelli D., Catto J., Agnew K., Swisher E., Creaney J., Robinson B., Shelley C.S., Godwin E.M., Kendall S., Shipman C., Bradford C., Carey T., Haddad A., Moyer J., Peterson L., Prince M., Rozek L., Wolf G., Bowman R., Fong K.M., Yang I., Korst R., Rathmell W.K., Fantacone-Campbell J.L., Hooke J.A., Kovatich A.J., Shriver C.D., DiPersio J., Drake B., Govindan R., Heath S., Ley T., Van Tine B., Westervelt P., Rubin M.A., Lee J.I., Aredes N.D., Mariamidze A., Serody J.S., Demicco E.G., Disis M.L., Vincent B.G., Shmulevich L., SAIC-F-Frederick, Inc, and Leidos Biomedical Research, Inc.
Subjects: Neuroblastoma RAS viral oncogene homolog, Male, 0301 basic medicine, INFORMATION, PREDICTION, Macrophage, medicine.medical_treatment, Lymphocyte, Cell, Cancer Genome Atlas Research Network, COMPREHENSIVE ANALYSIS, computer.software_genre, GENOMIC ANALYSES, 0302 clinical medicine, Transforming Growth Factor beta, Neoplasms, Immunologie, LS2_1, immune subtypes, LS4_6, Immunology and Allergy, tumor immunology, 610 Medicine & health, Child, Th1-Th2 Balance, immunomodulatory, Aged, 80 and over, T-CELL-RECEPTOR, integrative network analysi, cancer genomic, Genomics, Middle Aged, Prognosis, medicine.anatomical_structure, cancer genomics, immuno-oncology, immunotherapy, integrative network analysis, tumor microenvironment, Infectious Diseases, 1107 Immunology, 030220 oncology & carcinogenesis, immune subtype, Female, GENÔMICA, Life Sciences & Biomedicine, Natural language processing, Sentence, Human, Adult, SEQUENCING DATA, Adolescent, Prognosi, Immunology, Cancer immunity, Biology, CLASSIFICATION, Article, NO, Set (abstract data type), Interferon-gamma, Young Adult, 03 medical and health sciences, Immune system, microRNA, REVEALS, medicine, Humans, Epigenetics, Aged, Tumor microenvironment, Wound Healing, Science & Technology, business.industry, REGULATORY NETWORK, Macrophages, Gene sets, Scoring methods, Immunotherapy, SOMATIC MUTATIONS, R package, 030104 developmental biology, Cancer research, Genomic, Artificial intelligence, business, computer
Abstract: We performed an extensive immunogenomic analysis of more than 10,000 tumors comprising 33 diverse cancer types by utilizing data compiled by TCGA. Across cancer types, we identified six immune subtypes—wound healing, IFN-γ dominant, inflammatory, lymphocyte depleted, immunologically quiet, and TGF-β dominant—characterized by differences in macrophage or lymphocyte signatures, Th1:Th2 cell ratio, extent of intratumoral heterogeneity, aneuploidy, extent of neoantigen load, overall cell proliferation, expression of immunomodulatory genes, and prognosis. Specific driver mutations correlated with lower (CTNNB1, NRAS, or IDH1) or higher (BRAF, TP53, or CASP8) leukocyte levels across all cancers. Multiple control modalities of the intracellular and extracellular networks (transcription, microRNAs, copy number, and epigenetic processes) were involved in tumor-immune cell interactions, both across and within immune subtypes. Our immunogenomics pipeline to characterize these heterogeneous tumors and the resulting data are intended to serve as a resource for future targeted studies to further advance the field. Thorsson et al. present immunogenomics analyses of more than 10,000 tumors, identifying six immune subtypes that encompass multiple cancer types and are hypothesized to define immune response patterns impacting prognosis. This work provides a resource for understanding tumor-immune interactions, with implications for identifying ways to advance research on immunotherapy., 0, info:eu-repo/semantics/published
Published: 2019

38. Undifferentiated large cell/rhabdoid carcinoma presenting in the intestines of patients with concurrent or recent non-small cell lung cancer (NSCLC): clinicopathologic and molecular analysis of 14 cases indicates an unusual pattern of dedifferentiated metastases

Author: Abbas Agaimy, Ondrej Daum, Arndt Hartmann, Gregory Y. Lauwers, Mona W. Schmidt, Robert Stoehr, and Michal Michal
Subjects: Male, Pathology, Lung Neoplasms, Biopsy, non-small cell lung cancer (NSCLC), medicine.disease_cause, NSCLC, Metastasis, SMARCA4, Carcinoma, Non-Small-Cell Lung, Rhabdoid carcinoma, Aged, 80 and over, Melanoma, General Medicine, Middle Aged, Prognosis, Intestine, SWI/SNF, Molecular Diagnostic Techniques, Large cell carcinoma, Adenocarcinoma, Female, Original Article, KRAS, medicine.medical_specialty, Anaplastic carcinoma, Gastrointestinal, Pathology and Forensic Medicine, Diagnosis, Differential, Predictive Value of Tests, Intestinal Neoplasms, Carcinoma, medicine, Biomarkers, Tumor, Humans, ddc:610, Molecular Biology, Rhabdoid Tumor, Aged, Undifferentiated carcinoma, business.industry, Large cell, Cell Biology, Cell Dedifferentiation, medicine.disease, Mutation, Carcinoma, Large Cell, business
Abstract: Undifferentiated carcinoma metastatic to the bowel is uncommon in surgical pathology practice and might be confused with primary gastrointestinal carcinoma, melanoma, lymphoma, and others. We present 14 cases of uni- (n = 9) or multifocal (n = 5) undifferentiated large cell/rhabdoid carcinoma presenting in the bowel of patients with concurrent (n = 9) or recent (diagnosed 1 to 25 months earlier; median, 4) non-small cell lung cancer (NSCLC). Patients were 6 females and 8 males, aged 52 to 85 years. Primary NSCLC was verified histologically in 10 cases and by imaging in 4. The undifferentiated histology was present in the lung biopsy in 4/10 patients (as sole pattern in 3 and combined with adenocarcinoma in 1) and was limited to the intestinal metastases in the remainder. PDL1 was strongly expressed in 7/9 cases (CPS: 41 to 100). Loss of at least one SWI/SNF subunit was detected in 7/13 cases (54%). SMARCA2 loss (n = 6) was most frequent and was combined with SMARCA4 loss in one case. PBRM1 loss was observed in one tumor. Successful molecular testing of 11 cases revealed BRAF mutations in 4 (3 were non-V600E variants), KRAS mutations in 3, and wildtype in 4. None had EGFR mutations. Analysis of 4 paired samples revealed concordant KRAS (2) and BRAF (1) mutations or wildtype (1). Our study indicates that undifferentiated carcinoma within the intestines of patients with concurrent/recent NSCLC represents dedifferentiated metastasis from the NSCLC. Recognition of this unusual presentation is cardinal to avoid misdiagnosis with inappropriate therapeutic and prognostic implications.
Published: 2021

39. 1: MicroRNAs: Potential For Molecular Modulation Of Mechanically-induced Skin Growth During TE

Author: Elbert E. Vaca, Jenna R. Stoehr, Joanna K. Ledwon, and Arun K. Gosain
Subjects: RD1-811, Modulation, business.industry, microRNA, PSRC 2021 Abstract Supplement, Medicine, Skin growth, Surgery, business, Cell biology
Abstract: Purpose: Tissue expansion (TE) is commonly utilized to promote skin growth prior to reconstructing a defect or deformity. In spite of its ubiquitous use, the role of molecular modulators during TE, such as microRNAs (miRNAs), has not previously been studied. MiRNAs are small endogenous molecules that regulate many biological processes, including cell proliferation, differentiation, and inflammatory response. Here, we investigate genome-wide changes in miRNA expression in skin during TE. Methods: Changes in miRNA expression were evaluated in a porcine TE model. Full-thickness skin biopsies were collected after 1 hour, 24 hours, 3 days, and 7 days of expansion, as well as from unexpanded skin (control). RNA extracted from biopsies was analyzed with next-generation sequencing (NGS). Differential expression analysis was performed using R software with the Bioconductor-DESeq2 package. Results were corrected for multiple testing using the Benjamini-Hochberg method. A combination of adjusted p-value < 0.05 and | log2 (fold change) | > 1 were used as the threshold to determine the significance of differentially expressed (DE) miRNAs. Potential target genes for DE miRNAs were identified by in silico analysis using three data bases: miRDB, miRTarBase, and DIANA Tools with Tarbase. Functional enrichment analysis of target genes was performed using the g:GOSt functional profiling tool, and results were visualized using R and Cytoscape software. Results: We identified 52 miRNAs that were differentially upregulated (n = 18) or downregulated (n = 34) during at least one of the tested timepoints during TE. At the four time points (1 hour, 24 hours, 3 days and 7 days), there were 15, 6, 22, and 20 DE miRNAs, respectively. Eight miRNAs (ssc-miR-193a-5p, ssc-miR-21, ssc-miR-9-1, ssc-miR-708-3p, ssc-miR-212, ssc-miR-196a, ssc-miR-15b, ssc-miR-184) were DE at more than one timepoint. The comparative analysis showed 9, 4, 16 and 15 unique miRNAs after 1 hour, 24, hours, 3 days and 7 days of TE, respectively. Gene Ontology and KEGG pathway analyses for predicted target genes demonstrated enrichment in cellular processes related to metabolism, transcription, translation, signal transduction, cell differentiation, migration, and angiogenesis.
Published: 2021

40. Ethical Considerations for Unblinding and Vaccinating COVID-19 Vaccine Trial Placebo Group Participants

Author: Jenna R. Stoehr, Clayton Thomason, and Alireza Hamidian Jahromi
Subjects: Opinion, medicine.medical_specialty, Emergency Use Authorization, COVID-19 Vaccines, Coronavirus disease 2019 (COVID-19), Placebo, Double-Blind Method, vaccine, Health care, Humans, Medicine, vaccine ethics, clinical trials, SARS-CoV-2, business.industry, Public Health, Environmental and Occupational Health, Vaccine trial, COVID-19, Clinical trial, Vaccination, Family medicine, placebo, Public Health, Public aspects of medicine, RA1-1270, business, Medical ethics
Abstract: The Pfizer-BioNTech, Moderna, and Johnson & Johnson COVID-19 vaccinations have been approved under “Emergency Use Authorization” by the United States Food and Drug Administration (FDA). Other vaccines, such as the Sputnik V and AstraZeneca vaccines, have begun to be distributed in other nations around the world after the publication of promising efficacy results. Multiple more vaccine candidates are likely to follow, which will still require safety and efficacy testing. As vaccines have been distributed in a tiered fashion to the public, there has been discussion and disagreement regarding the matter of vaccination of placebo groups from the past or upcoming trials (1). It has been argued that only trial participants (placebo group) who would be otherwise offered the vaccine outside of the trial [i.e., high risk participants or healthcare workers (HCWs)] should be unblinded and given the vaccine, while all other participants should remain blinded (2, 3). We argue that, once proven efficacious, vaccine makers and researchers have an ethical obligation to unblind the placebo groups of COVID-19 vaccine trials and offer them vaccine, based on the four principles of medical ethics.
Published: 2021

41. Do Dedicated Research Years during Medical School Predict Academic Productivity during Residency?

Author: Sarah A. Applebaum, MD, MS, Jenna R. Stoehr, BA, Jonathan T. Bacos, MD, Elbert E. Vaca, MD, Joseph Lopez, MD, MBA, Yuyang Chu, BS, ASPSRC Subspecialty Career Pathways Study Group, and Arun K. Gosain, MD
Subjects: medicine.medical_specialty, RD1-811, business.industry, Family medicine, Post-hoc analysis, medicine, Medical school, Surgery, Original Article, business, Productivity, Education
Abstract: Background:. Evidence regarding whether medical school research portends resident research is limited. This information will provide program directors with data that may be useful for selecting applicants with a commitment to continued academic productivity. Methods:. A questionnaire distributed via the American Society of Plastic Surgeons Resident Council to residents in 44 plastic surgery training programs in May 2020 assessed participation in dedicated research years during medical school, the number of publications completed before residency, and the total number of publications by each resident at the time of the survey. One-way ANOVA and post hoc analysis determined significant associations between publication count and number of research years. Results:. Of the 256 included respondents, 203 did not complete a research year during medical school, 44 completed 1 research year, and nine completed 2 research years. Mean publications before residency were higher for participants who took 1 or 2 research years (9.88 and 27.60, respectively) compared with those who did not (4.83, P < 0.001). A comparison of total publications during residency similarly revealed increased productivity by individuals who took 1 or more research years; however, there was no difference between the number of publications completed during residency for individuals who took 1 versus 2 years (P = 0.23). Conclusions:. Residents with research experience during medical school continue to produce an increased number of publications during residency compared with those without, suggesting dedicated research years taken during medical school serve as a predictor of academic productivity in plastic surgery residents.
Published: 2021

42. Immunonutritive Scoring in Patients With Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization: Prognostic Nutritional Index or Controlling Nutritional Status Score?

Author: Christoph Düber, Roman Kloeckner, Lukas Müller, Jens Mittler, Simon Johannes Gairing, Felix Hahn, Fabian Stoehr, Friedrich Foerster, Aline Mähringer-Kunz, Michael B. Pitton, Daniel Pinto dos Santos, Peter R. Galle, and Arndt Weinmann
Subjects: Cancer Research, medicine.medical_specialty, Multivariate statistics, Multivariate analysis, Subgroup analysis, transarterial chemoembolization, immunonutritive scoring, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, controlling nutritional status, Internal medicine, medicine, In patient, survival prediction, RC254-282, Original Research, risk scoring, business.industry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Cancer, Nutritional status, hepatocellular carcinoma, prognostic nutritional index, medicine.disease, BCLC Stage, Oncology, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, 030211 gastroenterology & hepatology, business
Abstract: ObjectivesThe Prognostic Nutritional Index (PNI) and Controlling Nutritional Status (CONUT) score are immunonutritive scoring systems with proven predictive ability in various cancer entities, including hepatocellular carcinoma (HCC). We performed the first evaluation of the CONUT score for patients undergoing transarterial chemoembolization (TACE) and compared CONUT and PNI in the ability to predict median overall survival (OS).MethodsBetween 2010 and 2020, we retrospectively identified 237 treatment-naïve patients with HCC who underwent initial TACE at our institution. Both scores include the albumin level and total lymphocyte count. The CONUT additionally includes the cholesterol level. Both scores were compared in univariate and multivariate regression analyses taking into account established risk factors. In a second step, a subgroup analysis was performed on BCLC stage B patients, for whom TACE is the recommended first-line treatment.ResultsA high CONUT score and low PNI were associated with impaired median OS (8.7 vs. 22.3 months, pvs. 20.1 months, pvs. 17.9 months, pvs. 22.0 months, pConclusionBoth scores were able to stratify patients according to their median OS, but only the PNI remained an independent prognostic factor. Therefore, PNI should be preferred when evaluating the nutritional status of patients undergoing TACE.
Published: 2021

43. Staying Close to Home: The Effects of COVID-19 on the Plastic Surgery Residency Match

Author: Andrew Atia, Andrew Hollins, Gloria X Zhang, Amanda R. Sergesketter, Victoria A. Wickenheisser, Brett T. Phillips, Jason H. Ko, and Jenna R. Stoehr
Subjects: Response rate (survey), Medical education, Matching (statistics), medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), RD1-811, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Significant difference, Residency program, Certification, Education, Plastic surgery, Medicine, Surgery, Original Article, business
Abstract: Background:. The 2019 novel coronavirus created unique challenges for the integrated plastic surgery match. The goal of this study was to evaluate the trends of the 2020 and 2021 integrated plastic surgery match specifically related to the 2019 novel coronavirus. Methods:. Three separate individual surveys were designed for integrated plastic surgery program directors and applicants from the 2021 to 2020 match. The surveys were distributed to the email addresses of applicants that applied to our institution’s integrated residency program. Information of current interns and newly matched applicants from program websites and certified social media accounts were recorded. Results:. We received completed surveys from 19 of the 69 program directors for a response rate of 27.5%. The survey for the 2020 and 2021 match applicants was completed by 25 and 68 applicants, respectively, for a response rate of 6.1% and 21.9%. There was a significant difference in the average number of completed virtual subinternships between applicants that did and did not successfully match into plastic surgery (1.48 versus 0.36, P = 0.01). The rate of students matching at their home institution was the highest in 2021 at 26% compared to 2020 (18%) and 2019 (15%). Conclusions:. The results of this study demonstrate that applicants were more likely to match at programs with which they had established previous connections, including home institutions. Applicants also had a higher likelihood to match if they completed a virtual subinternship during the 2021 match. Learning points can be applied to the upcoming application cycle to improve the overall experience.
Published: 2021

44. Permanent chemotherapy-induced alopecia: awareness and attitudes among health care providers

Author: Cory Kosche, Jennifer N. Choi, and Jenna R. Stoehr
Subjects: medicine.medical_specialty, Referral, Descriptive statistics, business.industry, Pain medicine, Nursing research, Significant difference, Chemotherapy induced alopecia, 03 medical and health sciences, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Family medicine, Survivorship curve, Health care, medicine, 030212 general & internal medicine, business
Abstract: Reports of permanent chemotherapy-induced alopecia (PCIA) are increasing in the field of oncodermatology, but there is a dearth of information regarding how it is recognized and managed by health care providers (HCPs) across different medical specialties (dermatology, oncology, and internal medicine). A 25-question survey was designed to elicit general knowledge and awareness of PCIA, as well as attitudes about referral and treatment. Responses were collected via REDCap, a secure online application, and analyzed with descriptive statistics, chi-square, and ANOVA tests. There was a significant difference in the number of subjects who had heard of PCIA prior to starting the survey (Derm 79%, Onc 30%, IM 22%, p 6 months) than IM (42% and 45% vs. 17%) and significantly more had encountered patients with the condition (47% and 45% vs. 17%). More providers in dermatology and IM knew how to diagnose PCIA compared with oncology (84% and 83% vs. 70%). Dermatology HCPs were the only participants who had attempted to treat patients with PCIA, and most providers believed that patients would accept similar types of treatment for PCIA. Dermatology HCPs were more likely to report higher confidence in their abilities to diagnose and manage PCIA than other providers. The results of this survey identify knowledge gaps about PCIA among health care providers. Therefore, education and multidisciplinary engagement should be pursued in order to improve awareness, diagnosis, referral, and management of PCIA as part of survivorship care.
Published: 2019

45. Postexpositionsprophylaxe: Je früher, desto besser

Author: Andreas Plettenberg, Albrecht Stoehr, Thore Lorenzen, and Frieder Kuhlendahl
Subjects: Gynecology, medicine.medical_specialty, Acquired immunodeficiency syndrome (AIDS), business.industry, medicine.medical_treatment, medicine, Human immunodeficiency virus (HIV), General Medicine, Post-exposure prophylaxis, medicine.disease, medicine.disease_cause, business, Antiretroviral therapy
Abstract: Im vergangenen Jahr wurde die Leitlinie zur HIV-Postexpositionsprophylaxe uberarbeitet. Sie gibt konkrete Empfehlungen, was nach Verdacht auf eine HIV-Ubertragung zu tun ist und wann und wie antiretrovirale Medikamente verabreicht werden sollen.
Published: 2019

46. Poesía como sustento para el alma: una entrevista con Utz Rachowski

Author: Louise Stoehr
Subjects: media_common.quotation_subject, lcsh:Literature (General), german democratic republic, exile, State (polity), recepción internacional, Sustenance, Imprisonment, media_common, Literature, lcsh:French literature - Italian literature - Spanish literature - Portuguese literature, polícia estadual, Poetry, recepção internacional, business.industry, poemas de prision, República Democrática Alemana, poemas de prisão, prison poems, General Medicine, Art, lcsh:PN1-6790, policía Estatal, German Democratic Republic, state police, lcsh:PQ1-3999, international reception, exilio, exílio, Club, business, Soul, República Democrática Alemã
Abstract: The intent of the present interview with Utz Rachowski is to explore the poet’s drive to share his innermost thoughts in lyrical form. Specifically, Rachowski speaks about having been accused of being the alleged ring-leader of a renegade philosophy club; of his imprisonment as an enemy of the state for having written poems that were condiered subversive; about the how and why he continued to write poetry and how it has sustained him through five decades; and his experiences abroad.---Original in English. La intención de la entrevista con Utz Rachowski es explorar el impulso del poeta en compartir sus pensamientos más íntimos en la forma lírica. En concreto, Rachowski habla de haber sido acusado de ser el supuesto líder de un club de filosofía renegado; de su encarcelamiento como enemigo del Estado por haber escrito poemas que eran considerados subversivos; sobre cómo y por qué continué escribiendo poesías y cómo ellas lo ha sostenido por seis años; y sus experiencias en el exterior.---Original en inglés. The intent of the present interview with Utz Rachowski is to explore the poet’s drive to share his innermost thoughts in lyrical form. Specifically, Rachowski speaks about having been accused of being the alleged ring-leader of a renegade philosophy club; of his imprisonment as an enemy of the state for having written poems that were condiered subversive; about the how and why he continued to write poetry and how it has sustained him through five decades; and his experiences abroad.---------------------------------------------------------------------------------POESIA COMO SUSTENTO PARA A ALMA: UMA ENTREVISTA COM UTZ RACHOWSKI A intenção da presente entrevista com Utz Rachowski é explorar o impulso do poeta em compartilhar seus pensamentos mais íntimos na forma lírica. Especificamente, Rachowski fala sobre ter sido acusado de ser o suposto líder de um clube de filosofia renegado; de seu aprisionamento como inimigo do Estado por ter escrito poemas que eram considerados subversivos; sobre como e por que continuou escrevendo poesias e como elas o tem sustentado por seis anos; e suas experiências no exterior.---Original em inglês.
Published: 2019

47. Immunohistochemical examination in arthrofibrosis of the knee joint

Author: Amelie Stoehr, Anke Bernstein, Hermann O. Mayr, Florian Haasters, Wolf Christian Prall, and Fanny F Fassbender
Subjects: Pathology, medicine.medical_specialty, Knee Joint, medicine.medical_treatment, Bone Morphogenetic Protein 2, Knee replacement, Cohort Studies, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, Fibrosis, Humans, Medicine, Orthopedics and Sports Medicine, Pathological, beta Catenin, Arthrofibrosis, 030222 orthopedics, business.industry, CD68, 030229 sport sciences, General Medicine, medicine.disease, Immunohistochemistry, medicine.anatomical_structure, Ligament, Surgery, Joint Diseases, business, Biomarkers
Abstract: Arthrofibrosis (AF) is the result of increased cell proliferation and synthesis of matrix proteins (collagen I, III, and VI). Especially after invasive knee surgery, e.g., ligament reconstruction or knee replacement, abnormal fibroblast proliferation with pathological periarticular fibrosis can be observed leading to severely limited joint motion. The pathogenesis of AF is currently not fully understood. The present work aims to determine pathogenic factors. A descriptive, histological and immunohistochemical comparative study was performed on tissue samples of 14 consecutive patients undergoing arthrolysis for joint stiffness due to AF. Seven human autopsy specimens served as control. Samples were stained for expression of relevant markers such as CD68, α-smooth muscle actin (ASMA), beta-catenin, BMP-2 and examined for the histological grade of AF (cell-rich versus cell-poor) and compared to a control. Furthermore, a microscopic evaluation of the samples for cell differentiation and number was performed. Tissue sections of cell-rich fibrosis showed a significantly higher expression of CD68 compared to the control with less than 10% of CD68 positive cells (p = 0.002). In cell-poor fibrosis no statistically significant difference was obvious (p = 0.228). Expression of ASMA in synovia, vessels, cell-rich and cell-poor fibrosis showed median values of 2.00 in the AF group and 1.75 in the control. Both groups differed significantly (p = 0.003). AF tissue showed a significantly difference in expression of β-catenin (p
Published: 2019

48. Off-Label Use of Topical Minoxidil in Alopecia: A Review

Author: Maria L. Colavincenzo, Stefan Vanderweil, Jennifer N. Choi, and Jenna R. Stoehr
Subjects: Adult, medicine.medical_specialty, Traction alopecia, Administration, Topical, Vasodilator Agents, Dermatology, Scarring alopecia, Telogen effluvium, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Monilethrix, medicine, Animals, Humans, skin and connective tissue diseases, integumentary system, business.industry, Alopecia, Off-Label Use, General Medicine, Alopecia areata, medicine.disease, Clinical trial, stomatognathic diseases, Treatment Outcome, Minoxidil, Hypotrichosis, business, medicine.drug
Abstract: Topical minoxidil is a well-known and often-utilized drug in dermatological practice for the treatment of alopecia. It was approved by the United States Food and Drug Administration for the treatment of androgenetic alopecia in 1988. Since its approval, minoxidil has been used off-label for the treatment of many other types of alopecia, with minimal formal evidence of efficacy. Conditions for which the use of topical minoxidil has been reported include telogen effluvium, alopecia areata (AA), scarring alopecia, eyebrow hypotrichosis, monilethrix, and chemotherapy-induced alopecia (CIA). The evidence for the use of minoxidil in each condition is derived from a variety of studies, including clinical trials, case series, and case reports. A comprehensive review of the literature indicates that while minoxidil is routinely used in the management of many alopecic conditions, there is mixed evidence for its efficacy. For certain conditions, including AA and most scarring alopecias, the evidence seems to be inconclusive. For others, such as eyebrow hypotrichosis, monilethrix, early traction alopecia, and CIA, there is more support for the efficacy of minoxidil. Although the favorable safety profile of minoxidil is established in adults, its use in the treatment of pediatric alopecia may require heightened monitoring and patient education.
Published: 2019

49. Reading with the ears: How orthography influences auditory word recognition. A cross-linguistic study

Author: Martin Cd, Furgoni A, and Antje Stoehr
Subjects: Computer science, business.industry, Orthographic projection, Word recognition, Grapheme, Consistency (knowledge bases), Artificial intelligence, computer.software_genre, business, computer, Natural language processing
Abstract: The Orthographic Consistency Effect (OCE) demonstrates that listeners recognize consistently-spelled words faster than inconsistently-spelled words. Previous studies located the OCE at the rhyme level and focused on languages with opaque orthographies. This study investigates whether the OCE emerges at the phonemic level regardless of the opacity of the language’s writing system. Thirty French (opaque language) and 30 Spanish (transparent language) listeners participated in an auditory lexical decision task featuring words and pseudowords including either only consistently-spelled phonemes or also inconsistently-spelled phonemes. Our results revealed an OCE in French and Spanish but with a different pattern: The OCE affected French pseudoword processing and Spanish word processing. These findings have three theoretical implications. First, auditory lexical processing is impacted by orthographic information which can be retrieved at the phonemic level. Second, the OCE occurs in alphabetic languages regardless of their level of opacity. Third, not only the opacity of a language’s writing system but also the depth of the linguistic level impact auditory lexical processing.
Published: 2021

50. ALK Rearrangements Characterize 2 Distinct Types of Salivary Gland Carcinomas: Clinicopathologic and Molecular Analysis of 4 Cases and Literature Review

Author: Sarina K. Mueller, Alessandro Franchi, Martina Baněčková, Robert Stoehr, Abbas Agaimy, Alena Skálová, Arndt Hartmann, and Stephan Ihrler
Subjects: Male, Pathology, medicine.medical_specialty, Pathology and Forensic Medicine, Basal (phylogenetics), Mammaglobin, medicine, Carcinoma, Humans, Anaplastic Lymphoma Kinase, Aged, Gene Rearrangement, biology, Salivary gland, business.industry, Apocrine, medicine.disease, Salivary Gland Neoplasms, Parotid gland, Androgen receptor, Carcinoma, Ductal, medicine.anatomical_structure, biology.protein, Immunohistochemistry, Surgery, Female, Anatomy, business
Abstract: The majority of salivary gland carcinomas are characterized by recurrent gene fusions that proved highly valuable diagnostically, but only rarely of therapeutic impact. Most of these fusion-positive carcinomas belong to the low-grade or intermediate-grade biological category. To date, only 5 cases of salivary gland carcinomas carrying an oncogenic ALK fusion have been reported in 4 recent studies, but their phenotypic spectrum and their nosological classification remain uncharacterized. We herein describe in detail the clinicopathologic and molecular features of 4 ALK-fusion-positive salivary carcinomas and review previously reported cases to assess if they could be classified into a defined World Health Organization (WHO) category. Patients were 3 men and 1 woman aged from 67 to 79 years (median: 70 y). All tumors originated in the parotid gland. Their size ranged from 1.1 to 3 cm (mean, 2 cm). Three tumors were de novo high-grade salivary duct carcinomas (SDCs) and 1 was a low-grade intercalated-type intraductal carcinoma. Histologically, high-grade tumors were predominantly solid, composed of intimately admixed basal (CK5+, androgen-) and luminal (CK5-, androgen+) components. The remarkable basal component showed squamoid basophilic pattern imparting an adenosquamous-like appearance in all cases. Conventional apocrine intraductal high-grade carcinoma was noted in 1 case. Prominent intraductal growth of the solid basal component (highlighted by p63 staining) was seen in all cases. The tumor cells expressed CK7 (3/3), mammaglobin (3/3, 1 focal), GATA3 (3/3, 1 focal), variably CK5 (3/3), and focally the androgen receptor (1/3), but lacked expression of HER2/neu, SOX10, MUC4, TTF1, S100, and Napsin A. The low-grade tumor showed classic histologic and immunophenotypic features of intercalated-type noninvasive intraductal carcinoma. Molecular profiling showed rearrangements involving exon 20 of ALK in all cases, confirmed by ALK immunohistochemistry (IHC and FISH). The fusion partner was EML4 (n=2) and STRN (n=1) in high-grade tumors and EML4 in the intraductal carcinoma. Two patients with high-grade tumors developed progressive disease (1 died at 9 mo; 1 alive under palliative therapy at 5 mo). This series and a review of 5 published cases indicate that ALK rearrangements characterize 2 distinct subsets of salivary gland carcinomas in the spectrum of high-grade androgen-poor, basal-like SDC (total reported: 5 cases) and low-grade intercalated-type intraductal carcinomas (4 cases). Given the therapeutic relevance of ALK fusions, inclusion of ALK IHC in any atypical-looking or androgen-poor SDC and in high-grade adenocarcinoma-not otherwise specified is recommended. Absence of aberrant ALK expression in genetically characterized secretory (n=15) and intraductal (n=9) carcinomas lacking ALK fusions underlines the value of ALK IHC as a diagnostic screening method for identifying potential cases.
Published: 2021

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