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5. Long-term outcomes of extended DAPT in a real-life cohort of consecutive STEMI patients

Author

Tizón-Marcos, Helena, Toloba, Andrea, Subirana Cachinero, Isaac, Elosua, Roberto, Sionis, Alessandro, Fernández-Avilés, Francisco, Bueno, Héctor, Carrillo, Andrés, Bayés, Antoni, Sánchez, Pedro L., Roqué, Mercè, Milà, Laia, Elorriaga, Ane, Vaquero, Jessica, Fernández-Bergés, Daniel, Bosch, Daniel, Alameda, Javier, Martí Almor, Julio, Jiménez-Navarro, Manuel, Martínez, Luis, Sanchis, Juan, Sánchez, Esther, Rubert, Catalina, Ruiz-Valdepeñas, Luis, Rodríguez, Marcos, Lozano, Íñigo, Abu-Assi, Emad, González, Vicente Bertomeu, and Marrugat, Jaume

Published
2023
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7. IMPACT-Global Hip Fracture Audit: Nosocomial infection, risk prediction and prognostication, minimum reporting standards and global collaborative audit: Lessons from an international multicentre study of 7,090 patients conducted in 14 nations during the COVID-19 pandemic

Author

Abdul-Jabar, Hani, Abu-Rajab, Rashid, Abugarja, Ahmed, Adam, Karen, Aguado Hernández, Héctor J., Améstica Lazcano, Gedeón, Anderson, Sarah, Ansar, Mahmood, Antrobus, Jonathan, Aragón Achig, Esteban Javier, Archunan, Maheswaran, Arrieta Salinas, Mirentxu, Ashford–Wilson, Sarah, Assens Gibert, Cristina, Athanasopoulou, Katerina, Awadelkarim, Mohamed, Baird, Stuart, Bajada, Stefan, Balakrishnan, Shobana, Balasubramanian, Sathishkumar, Ballantyne, James A., Bárcena Goitiandia, Leopoldo, Barkham, Benjamin, Barmpagianni, Christina, Barres-Carsi, Mariano, Barrett, Sarah, Baskaran, Dinnish, Bell, Jean, Bell, Katrina, Bell, Stuart, Bellelli, Giuseppe, Benchimol, Javier Alberto, Boietti, Bruno Rafael, Boswell, Sally, Braile, Adriano, Brennan, Caitlin, Brent, Louise, Brooke, Ben, Bruno, Gaetano, Burahee, Abdus, Burns, Shirley, Calabrò, Giampiero, Campbell, Lucy, Carabelli, Guido Sebastian, Carnegie, Carol, Carretero Cristobal, Guillermo, Caruana, Ethan, Cassinello Ogea, M.a Concepción, Castellanos Robles, Juan, Castillon, Pablo, Chakrabarti, Anil, Cecere, Antonio Benedetto, Chen, Ping, Clarke, Jon V., Collins, Grace, Corrales Cardenal, Jorge E., Corsi, Maurizio, Cózar Adelantado, Gara María, Craxford, Simon, Crooks, Melissa, Cuarental-García, Javier, Cuthbert, Rory, Dall, Graham, Daskalakis, Ioannis, De Cicco, Annalisa, de la Fuente de Dios, Diana, Demaria, Pablo, Dereix, John, Díaz Jiménez, Julian, Dinamarca Montecinos, José Luis, Do Le, Ha Phuong, Donoso Coppa, Juan Pablo, Drosos, Georgios, Duffy, Andrew, East, Jamie, Eastwood, Deborah, Elbahari, Hassan, Elias de Molins Peña, Carmen, Elmamoun, Mamoun, Emmerson, Ben, Escobar Sánchez, Daniel, Faimali, Martina, Farré-Mercadé, Maria Victòria, Farrow, Luke, Fayez, Almari, Fell, Adam, Fenner, Christopher, Ferguson, David, Finlayson, Louise, Flores Gómez, Aldo, Freeman, Nicholas, French, Jonathan, Gabardo Calvo, Santiago, Gagliardo, Nicola, Garcia Albiñana, Joan, García Cruz, Guillermo, García de Cortázar Antolín, Unai, García Virto, Virginia, Gealy, Sophie, Gil Caballero, Sandra Marcela, Gill, Moneet, González González, María Soledad, Gopireddy, Rajesh, Guntley, Diane, Gurung, Binay, Guzmán Rosales, Guadalupe, Haddad, Nedaa, Hafeez, Mahum, Haller, Petra, Halligan, Emer, Hardie, John, Hawker, Imogen, Helal, Amr, Herrera Cruz, Mariana, Herreros Ruiz-Valdepeñas, Ruben, Horton, James, Howells, Sean, Howieson, Alan, Hughes, Luke, Hünicken Torrez, Flavia Lorena, Hurtado Ortega, Ana, Huxley, Peter, Hamid, Hytham K.S., Ilahi, Nida, Iliadis, Alexis, Inman, Dominic, Jadhao, Piyush, Jandoo, Rajan, Jawad, Lucy, Jayatilaka, Malwattage Lara Tania, Jenkins, Paul J., Jeyapalan, Rathan, Johnson, David, Johnston, Andrew, Joseph, Sarah, Kapoor, Siddhant, Karagiannidis, Georgios, Karanam, Krishna Saga, Kattakayam, Freddy, Konarski, Alastair, Kontakis, Georgios, Labrador Hernández, Gregorio, Lancaster, Victoria, Landi, Giovanni, Le, Brian, Liew, Ignatius, Logishetty, Kartik, Lopez Marquez, Andrew Carlomaria Daniel, Lopez, Judit, Lum, Joann, Macpherson, Gavin J., Madan, Suvira, Mahroof, Sabreena, Malik-Tabassum, Khalid, Mallina, Ravi, Maqsood, Afnan, Marson, Ben, Martin Legorburo, M. José, Martin-Perez, Encarna, Martínez Jiménez, Tania, Martinez Martin, Javier, Mayne, Alistair, Mayor, Amy, McAlinden, Gavan, McLean, Lucille, McDonald, Lorna, McIntyre, Joshua, McKay, Pamela, McKean, Greg, McShane, Heather, Medici, Antonio, Meeke, Chelsea, Meldrum, Evonne, Mendez, Mijail, Mercer, Scott, Merino Perez, Josu, Mesa-Lampré, María-Pilar, Mighton, Shuna, Milne, Kirsty, Mohamed Yaseen, Muhammed, Moppett, Iain, Mora, Jesus, Morales-Zumel, Sira, Moreno Fenoll, Irene Blanca, Mousa, Adham, Murray, Alastair W., Murray, Elspeth V., Nair, Radhika, Neary, Fiona, Negri, Giacomo, Negus, Oliver, Newham-Harvey, Fiona, Ng, Nigel, Nightingale, Jess, Noor Mohamed Anver, Sumiya, Nunag, Perrico, O'Hare, Matthew, Ollivere, Ben, Ortés Gómez, Raquel, Owens, AnneMarie, Page, Siobhan, Palloni, Valentina, Panagiotopoulos, Andreas, Panagiotopoulos, Elias, Panesar, Paul, Papadopoulos, Antonios, Spyridon, Papagiannis, Pareja Sierra, Teresa, Park, Chang, Parwaiz, Hammad, Paterson-Byrne, Paul, Patton, Sam, Pearce, Jack, Porter, Marina, Pellegrino, Achille, Pèrez Cuellar, Arturo, Pezzella, Raffaele, Phadnis, Ashish, Pinder, Charlotte, Piper, Danielle, Powell-Bowns, Matilda, Prieto Martín, Rocío, Probert, Annabel, Ramesh, Ashwanth, Ramírez de Arellano, Manuel Vicente Mejía, Renton, Duncan, Rickman, Stephen, Robertson, Alastair, Roche Albero, Adrian, Rodrigo Verguizas, José Alberto, Rodríguez Couso, Myriam, Rooney, Joanna, Sáez-López, Pilar, Saldaña-Díaz, Andres, Santulli, Adriano, Sanz Pérez, Marta Isabel, Sarraf, Khaled M., Scarsbrook, Christine, Scott, Chloe E.H., Scott, Jennifer, Shah, Sachi, Sharaf, Sharief, Sharma, Sidharth, Shirley, Denise, Siano, Antonio, Simpson, James, Singh, Abhinav, Singh, Amit, Sinnett, Tim, Sisodia, Gurudatt, Smith, Philomena, Sophena Bert, Eugenia, Steel, Michael, Stewart, Avril, Stewart, Claire, Sugand, Kapil, Sullivan, Niall, Sweeting, Lauren, Symes, Michael, Tan, Dylan Jun Hao, Tancredi, Francesco, Tatani, Irini, Thomas, Philip, Thomson, Fraser, Toner, Niamh S., Tong, Anna, Toro, Antonio, Tosounidis, Theodoros, Tottas, Stylianos, Trinidad Leo, Andrea, Tucker, Damien, Vemulapalli, Krishna, Ventura Garces, Diego, Vernon, Olivia Katherine, Viveros Garcia, Juan Carlos, Ward, Alex, Ward, Kirsty, Watson, Kate, Weerasuriya, Thisara, Wickramanayake, Udara, Wilkinson, Hannah, Windley, Joseph, Wood, Janet, Wynell-Mayow, William, Zatti, Giovanni, Zeiton, Moez, Zurrón Lobato, Miriam, Hall, Andrew J., Clement, Nicholas D., Ojeda-Thies, Cristina, MacLullich, Alasdair MJ., Toro, Giuseppe, Johansen, Antony, White, Tim O., and Duckworth, Andrew D.

Published
2022
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8. Usefulness of endonasal flaps and grafts in skull base surgery. Consensus document

Author

Moreno-Luna, Ramón, Mariño Sánchez, Franklin, Kaen, Ariel, Gras Cabrerizo, Juan Ramón, Mata Castro, Nieves, González García, Jaime, Villacampa Aubá, José Miguel, Cárdenas Ruiz-Valdepeñas, Eugenio, Monjas Cánovas, Irene, del Cuvillo Bernal, Alfonso, García Piñero, Alfonso, Maza Solano, Juan Manuel, Fernández de Liesa, Rafael, Sánchez-Gómez, Serafín, and Alobid, Isam

Published
2022
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9. Utilidad de los colgajos e injertos endonasales en cirugía endoscópica nasosinusal y de base de cráneo. Documento de consenso

Author

Moreno-Luna, Ramón, Mariño Sánchez, Franklin, Kaen, Ariel, Gras Cabrerizo, Juan Ramón, Mata Castro, Nieves, González García, Jaime, Villacampa Aubá, José Miguel, Cárdenas Ruiz-Valdepeñas, Eugenio, Monjas Cánovas, Irene, del Cuvillo Bernal, Alfonso, García Piñero, Alfonso, Maza Solano, Juan Manuel, Fernández de Liesa, Rafael, Sánchez-Gómez, Serafín, and Alobid, Isam

Published
2022
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10. Pronóstico a largo plazo de la extensión de la TAPD en una cohorte consecutiva de pacientes con IAMCEST

Author

Tizón-Marcos, Helena, Toloba, Andrea, Cachinero, Isaac Subirana, Elosua, Roberto, Sionis, Alessandro, Fernández-Avilés, Francisco, Bueno, Héctor, Carrillo, Andrés, Bayés, Antoni, Sánchez, Pedro L., Roqué, Mercè, Milà, Laia, Elorriaga, Ane, Vaquero, Jessica, Fernández-Bergés, Daniel, Bosch, Daniel, Alameda, Javier, Almor, Julio Martí, Jiménez-Navarro, Manuel, Martínez, Luis, Sanchis, Juan, Sánchez, Esther, Rubert, Catalina, Ruiz-Valdepeñas, Luis, Rodríguez, Marcos, Lozano, Íñigo, Abu-Assi, Emad, González, Vicente Bertomeu, and Marrugat, Jaume

Published
2022
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15. Comprehensive characterization of cell-free tumor DNA in plasma and urine of patients with renal tumors

Author

Christopher G. Smith, Tina Moser, Florent Mouliere, Johanna Field-Rayner, Matthew Eldridge, Anja L. Riediger, Dineika Chandrananda, Katrin Heider, Jonathan C. M. Wan, Anne Y. Warren, James Morris, Irena Hudecova, Wendy N. Cooper, Thomas J. Mitchell, Davina Gale, Andrea Ruiz-Valdepenas, Tobias Klatte, Stephan Ursprung, Evis Sala, Antony C. P. Riddick, Tevita F. Aho, James N. Armitage, Samantha Perakis, Martin Pichler, Maximilian Seles, Gabriel Wcislo, Sarah J. Welsh, Athena Matakidou, Tim Eisen, Charles E. Massie, Nitzan Rosenfeld, Ellen Heitzer, and Grant D. Stewart

Subjects
Renal cancer, Cell-free tumor DNA (ctDNA), Personalized analysis, Predictive biomarker, Heterogeneity, Medicine, Genetics, QH426-470
Abstract

Abstract Background Cell-free tumor-derived DNA (ctDNA) allows non-invasive monitoring of cancers, but its utility in renal cell cancer (RCC) has not been established. Methods Here, a combination of untargeted and targeted sequencing methods, applied to two independent cohorts of patients (n = 91) with various renal tumor subtypes, were used to determine ctDNA content in plasma and urine. Results Our data revealed lower plasma ctDNA levels in RCC relative to other cancers of similar size and stage, with untargeted detection in 27.5% of patients from both cohorts. A sensitive personalized approach, applied to plasma and urine from select patients (n = 22) improved detection to ~ 50%, including in patients with early-stage disease and even benign lesions. Detection in plasma, but not urine, was more frequent amongst patients with larger tumors and in those patients with venous tumor thrombus. With data from one extensively characterized patient, we observed that plasma and, for the first time, urine ctDNA may better represent tumor heterogeneity than a single tissue biopsy. Furthermore, in a subset of patients (n = 16), longitudinal sampling revealed that ctDNA can track disease course and may pre-empt radiological identification of minimal residual disease or disease progression on systemic therapy. Additional datasets will be required to validate these findings. Conclusions These data highlight RCC as a ctDNA-low malignancy. The biological reasons for this are yet to be determined. Nonetheless, our findings indicate potential clinical utility in the management of patients with renal tumors, provided improvement in isolation and detection approaches.

Published
2020
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16. Double percolation effects and fractal behavior in magnetic/superconducting hybrids

Author

Ruiz-Valdepeñas, L., Velez, M., Valdes-Bango, F., Alvarez-Prado, L. M., Martin, J. I., Navarro, E., Alameda, J. M., and Vicent, J. L.

Subjects
Condensed Matter - Superconductivity, Condensed Matter - Disordered Systems and Neural Networks
Abstract

Perpendicular magnetic anisotropy ferromagnetic/ superconducting (FM/SC) bilayers with a labyrinth domain structure are used to study nucleation of superconductivity on a fractal network, tunable through magnetic history. As clusters of reversed domains appear in the FM layer, the SC film shows a percolative behavior that depends on two independent processes: the arrangement of initial reversed domains and the fractal geometry of expanding clusters. For a full labyrinth structure, the behavior of the upper critical field is typical of confined superconductivity on a fractal network., Comment: 15 pages, 5 figures

Published
2013
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19. Hipocrates (2014). Real life of a resident at a public hospital

Author

Emilio PINTOR HOLGUIN, Benjamin HERREROS RUIZ-VALDEPENAS, Pedro GARGANTILLA MADERA, and Enrique VIVAS ROJO

Subjects
residente, limitación del esfuerzo terapéutico, responsabilidad del médico, bioética, Medicine (General), R5-920
Abstract

It describes Benjamin´s first weeks of work as a new resident of Internal Medicine in a public hospital in Paris. Next to him, an experienced Algerian physician; Abdel, performs his practices of validation. Main problems with these two doctors are described: doubts, decision making, camaraderie, bioethical and liability problems as well as problems derived from public health system budgets. All mixed with short ironic and comic scenes that sometimes reach surrealism.

Published
2017

23. Comprehensive characterization of cell-free tumor DNA in plasma and urine of patients with renal tumors

Author

Smith, Christopher G., Moser, Tina, Mouliere, Florent, Field-Rayner, Johanna, Eldridge, Matthew, Riediger, Anja L., Chandrananda, Dineika, Heider, Katrin, Wan, Jonathan C. M., Warren, Anne Y., Morris, James, Hudecova, Irena, Cooper, Wendy N., Mitchell, Thomas J., Gale, Davina, Ruiz-Valdepenas, Andrea, Klatte, Tobias, Ursprung, Stephan, Sala, Evis, Riddick, Antony C. P., Aho, Tevita F., Armitage, James N., Perakis, Samantha, Pichler, Martin, Seles, Maximilian, Wcislo, Gabriel, Welsh, Sarah J., Matakidou, Athena, Eisen, Tim, Massie, Charles E., Rosenfeld, Nitzan, Heitzer, Ellen, and Stewart, Grant D.

Published
2020
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35. Residual ctDNA after treatment predicts early relapse in patients with early-stage non-small cell lung cancer

Author

Gale, D., primary, Heider, K., additional, Ruiz-Valdepenas, A., additional, Hackinger, S., additional, Perry, M., additional, Marsico, G., additional, Rundell, V., additional, Wulff, J., additional, Sharma, G., additional, Knock, H., additional, Castedo, J., additional, Cooper, W., additional, Zhao, H., additional, Smith, C.G., additional, Garg, S., additional, Anand, S., additional, Howarth, K., additional, Gilligan, D., additional, Harden, S.V., additional, Rassl, D.M., additional, Rintoul, R.C., additional, and Rosenfeld, N., additional

Published
2022
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36. THE QUADRANGULAR SPACE, ENDONASAL ACCESS TO MECKEL'S CAVE: TECHNICAL CONSIDERATIONS AND CLINICAL SERIES

Author

Cardenas Ruiz-Valdepenas, Eugenio, Simal Julian, Juan A, Perez Prat, Gustavo, Arraez, Miguel A, Ambrosiani, Jesus, Martin Schrader, Ignacio, Soto Moreno, Alfonso, and Kaen, Ariel

Subjects
Gasserian ganglion, Meckel’s Cave, endoscopic endonasal approach, front door, quadrangular space, transpterygoid approach
Abstract

An anteromedial corridor via an expanded endoscopic endonasal approach to Meckel's Cave (MC) was described over a decade ago. However, few clinical series or endoscopic endonasal technical contributions concerning this type of approach to this complex region exist.

Published
2022

37. Residual ctDNA after treatment predicts early relapse in patients with early-stage non-small cell lung cancer

Author

D. Gale, K. Heider, A. Ruiz-Valdepenas, S. Hackinger, M. Perry, G. Marsico, V. Rundell, J. Wulff, G. Sharma, H. Knock, J. Castedo, W. Cooper, H. Zhao, C.G. Smith, S. Garg, S. Anand, K. Howarth, D. Gilligan, S.V. Harden, D.M. Rassl, R.C. Rintoul, and N. Rosenfeld

Subjects
Lung Neoplasms, Oncology, Carcinoma, Non-Small-Cell Lung, Biomarkers, Tumor, Disease Progression, Humans, Hematology, Prospective Studies, Neoplasm Recurrence, Local, Small Cell Lung Carcinoma, Circulating Tumor DNA
Abstract

Identification of residual disease in patients with localized non-small cell lung cancer (NSCLC) following treatment with curative intent holds promise to identify patients at risk of relapse. New methods can detect circulating tumour DNA (ctDNA) in plasma to fractional concentrations as low as a few parts per million, and clinical evidence is required to inform their use.We analyzed 363 serial plasma samples from 88 patients with early-stage NSCLC (48.9%/28.4%/22.7% at stage I/II/III), predominantly adenocarcinomas (62.5%), treated with curative intent by surgery (n = 61), surgery and adjuvant chemotherapy/radiotherapy (n = 8), or chemoradiotherapy (n = 19). Tumour exome sequencing identified somatic mutations and plasma was analyzed using patient-specific RaDaR™ assays with up to 48 amplicons targeting tumour-specific variants unique to each patient.ctDNA was detected before treatment in 24%, 77% and 87% of patients with stage I, II and III disease, respectively, and in 26% of all longitudinal samples. The median tumour fraction detected was 0.042%, with 63% of samples0.1% and 36% of samples0.01%. ctDNA detection had clinical specificity98.5% and preceded clinical detection of recurrence of the primary tumour by a median of 212.5 days. ctDNA was detected after treatment in 18/28 (64.3%) of patients who had clinical recurrence of their primary tumour. Detection within the landmark timepoint 2 weeks to 4 months after treatment end occurred in 17% of patients, and was associated with shorter recurrence-free survival [hazard ratio (HR): 14.8, P0.00001] and overall survival (HR: 5.48, P0.0003). ctDNA was detected 1-3 days after surgery in 25% of patients yet was not associated with disease recurrence. Detection before treatment was associated with shorter overall survival and recurrence-free survival (HR: 2.97 and 3.14, P values 0.01 and 0.003, respectively).ctDNA detection after initial treatment of patients with early-stage NSCLC using sensitive patient-specific assays has potential to identify patients who may benefit from further therapeutic intervention.

Published
2021

39. Automation and optimization device for the fabrication of sensors with nanomaterials

Author

Isabel Sayago, Santiago Ruiz-Valdepenas, Jesús Lozano, José Pedro Santos, J.L. Sanjurjo, Alfredo Azabal, and Carlos Sánchez-Vicente

Subjects
Fabrication, Materials science, sensitive layer, business.industry, Nanotechnology, drop–casting, Automation, nanomaterials, Nanomaterials, Drop casting, gas sensors, Deposition (phase transition), dropcaster, business, Deposition, Layer (electronics), Deposition process
Abstract

2021 13th Spanish Conference on Electron Devices, 9-11 june, Sevilla, Spain 3 páginas, 7 figuras, This work presents a device, “dropcaster”, developed to automate and optimize the deposition process of the sensitive layer of gas sensors using the drop–casting technique. It is designed to development sensors in the research phase of different materials and the study of their behavior and response to different gaseous compounds., This research was funded by Department of Education and Research of the Madrid Autonomous Community (Spain) grant number IND2017/TIC7714. Pristine graphene was supplied by ENEA (Portici, Italy).

Published
2021

41. ctDNA detection by personalised assays in early-stage NSCLC

Author

Heider, Katrin, primary, Wan, Jonathan C. M., additional, Gale, Davina, additional, Ruiz-Valdepenas, Andrea, additional, Mouliere, Florent, additional, Morris, James, additional, Qureshi, Nagmi R., additional, Qian, Wendi, additional, Knock, Helena, additional, Wulff, Jerome, additional, Howarth, Karen, additional, Green, Emma, additional, Castedo, Jenny, additional, Rundell, Viona, additional, Cooper, Wendy N., additional, Eisen, Tim, additional, Smith, Christopher G., additional, Massie, Charles, additional, Gilligan, David, additional, Harden, Susan V., additional, Rassl, Doris M., additional, Rintoul, Robert C., additional, and Rosenfeld, Nitzan, additional

Published
2021
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44. Graphene-Doped Tin Oxide Nanofibers and Nanoribbons as Gas Sensors to Detect Biomarkers of Different Diseases through the Breath

Author

Isabel Sayago, Santiago Ruiz-Valdepenas, Alfredo Azabal, Jesús Lozano, José Luis Sanjurjo, José Pedro Santos, Carlos Sánchez-Vicente, and Universidad Autónoma de Madrid

Subjects
electronic nose, Respiratory diseases, Scanning electron microscope, Nanofibers, Staphylococcus aureus, 02 engineering and technology, Gas sensors, lcsh:Chemical technology, 01 natural sciences, Biochemistry, Analytical Chemistry, law.invention, chronic diseases, cystic fibrosis, chemistry.chemical_compound, law, volatile organic compounds, lcsh:TP1-1185, Instrumentation, nanoribbons, breath, diabetes, respiratory diseases, Breath, VOC, Diabetes, Nanoribbons, 021001 nanoscience & nanotechnology, Atomic and Molecular Physics, and Optics, Electrospinning, gas sensors, Breath Tests, Graphite, Gases, nanosensor, 0210 nano-technology, Materials science, Nanosensor, Electronic nose, Cystic fibrosis, Article, nanostructures, Acetone, Humans, COPD, pneumonia, Volatile organic compounds, Electrical and Electronic Engineering, digestive diseases, Dopant, Graphene, Nanotubes, Carbon, 010401 analytical chemistry, graphene, Tin Compounds, biomarkers, Pneumonia, asthma, Tin oxide, Asthma, Nanostructures, 0104 chemical sciences, chemistry, Chronic diseases, Nanofiber, Digestive diseases, Biomarkers, Nuclear chemistry
Abstract

© 2020 by the authors., This work presents the development of tin oxide nanofibers (NFs) and nanoribbons (NRs) sensors with graphene as a dopant for the detection of volatile organic compounds (VOCs) corresponding to different chronic diseases (asthma, chronic obstructive pulmonary disease, cystic fibrosis or diabetes). This research aims to determine the ability of these sensors to differentiate between gas samples corresponding to healthy people and patients with a disease. The nanostructures were grown by electrospinning and deposited on silicon substrates with micro-heaters integrated. The morphology of NFs and NRs was characterized by Scanning Electron Microscopy (SEM). A gas line was assembled and programmed to measure a wide range of gases (ethanol, acetone, NO and CO) at different concentrations simulating human breath conditions. Measurements were made in the presence and absence of humidity to evaluate its effect. The sensors were able to differentiate between the concentrations corresponding to a healthy person and a patient with one of the selected diseases. These were sensitive to biomarkers such as acetone and ethanol at low operating temperatures (with responses above 35%). Furthermore, CO and NO response was at high temperatures (above 5%). The sensors had a rapid response, with times of 50 s and recovery periods of about 10 min., This research was funded by Department of Education and Research of the Madrid Autonomous Community (Spain) grant number IND2017/TIC7714.

Published
2020

45. ctDNA monitoring using patient-specific sequencing and integration of variant reads

Author

Wan, JCM, Heider, K, Gale, D, Murphy, S, Fisher, E, Mouliere, F, Ruiz-Valdepenas, A, Santonja, A, Morris, J, Chandrananda, D, Marshall, A, Gill, AB, Chan, PY, Barker, E, Young, G, Cooper, WN, Hudecova, I, Marass, F, Mair, R, Brindle, KM, Stewart, GD, Abraham, JE, Caldas, C, Rassl, DM, Rintoul, RC, Alifrangis, C, Middleton, MR, Gallagher, FA, Parkinson, C, Durrani, A, McDermott, U, Smith, CG, Massie, C, Corrie, PG, Rosenfeld, N, Wan, JCM, Heider, K, Gale, D, Murphy, S, Fisher, E, Mouliere, F, Ruiz-Valdepenas, A, Santonja, A, Morris, J, Chandrananda, D, Marshall, A, Gill, AB, Chan, PY, Barker, E, Young, G, Cooper, WN, Hudecova, I, Marass, F, Mair, R, Brindle, KM, Stewart, GD, Abraham, JE, Caldas, C, Rassl, DM, Rintoul, RC, Alifrangis, C, Middleton, MR, Gallagher, FA, Parkinson, C, Durrani, A, McDermott, U, Smith, CG, Massie, C, Corrie, PG, and Rosenfeld, N

Abstract

Circulating tumor-derived DNA (ctDNA) can be used to monitor cancer dynamics noninvasively. Detection of ctDNA can be challenging in patients with low-volume or residual disease, where plasma contains very few tumor-derived DNA fragments. We show that sensitivity for ctDNA detection in plasma can be improved by analyzing hundreds to thousands of mutations that are first identified by tumor genotyping. We describe the INtegration of VAriant Reads (INVAR) pipeline, which combines custom error-suppression methods and signal-enrichment approaches based on biological features of ctDNA. With this approach, the detection limit in each sample can be estimated independently based on the number of informative reads sequenced across multiple patient-specific loci. We applied INVAR to custom hybrid-capture sequencing data from 176 plasma samples from 105 patients with melanoma, lung, renal, glioma, and breast cancer across both early and advanced disease. By integrating signal across a median of >105 informative reads, ctDNA was routinely quantified to 1 mutant molecule per 100,000, and in some cases with high tumor mutation burden and/or plasma input material, to parts per million. This resulted in median area under the curve (AUC) values of 0.98 in advanced cancers and 0.80 in early-stage and challenging settings for ctDNA detection. We generalized this method to whole-exome and whole-genome sequencing, showing that INVAR may be applied without requiring personalized sequencing panels so long as a tumor mutation list is available. As tumor sequencing becomes increasingly performed, such methods for personalized cancer monitoring may enhance the sensitivity of cancer liquid biopsies.

Published
2020

47. Abstract 736: ctDNA detection in early stage non-small cell lung cancer

Author

Heider, Katrin, primary, Wan, Jonathan C., additional, Gale, Davina, additional, Ruiz-Valdepenas, Andrea, additional, Mouliere, Florent, additional, Morris, James, additional, Qureshi, Nagmi R., additional, Qian, Wendi, additional, Wulff, Jerome, additional, Demiris, Nikolaos, additional, Howarth, Karen, additional, Green, Emma, additional, Rundell, Viona, additional, Eisen, Tim, additional, Cooper, Wendy, additional, Smith, Christopher G., additional, Massie, Charles, additional, Harden, Susan, additional, Rassl, Doris M., additional, Rintoul, Robert C., additional, and Rosenfeld, Nitzan, additional

Published
2020
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48. Abstract 735: Sensitive detection of ctDNA in early stage non-small cell lung cancer patients with a personalized sequencing assay

Author

Heider, Katrin, primary, Gale, Davina, additional, Ruiz-Valdepenas, Andrea, additional, Marsico, Giovanni, additional, Sharma, Garima, additional, Perry, Malcolm, additional, Osborne, Robert, additional, Howarth, Karen, additional, Lazarus, Tadd, additional, Rundell, Viona, additional, Belic, Jelena, additional, Wulff, Jerome, additional, Harden, Susan, additional, Rassl, Doris M., additional, Rintoul, Robert C., additional, and Rosenfeld, Nitzan, additional

Published
2020
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49. ctDNA monitoring using patient-specific sequencing and integration of variant reads

Author

Wan, Jonathan C. M., primary, Heider, Katrin, additional, Gale, Davina, additional, Murphy, Suzanne, additional, Fisher, Eyal, additional, Mouliere, Florent, additional, Ruiz-Valdepenas, Andrea, additional, Santonja, Angela, additional, Morris, James, additional, Chandrananda, Dineika, additional, Marshall, Andrea, additional, Gill, Andrew B., additional, Chan, Pui Ying, additional, Barker, Emily, additional, Young, Gemma, additional, Cooper, Wendy N., additional, Hudecova, Irena, additional, Marass, Francesco, additional, Mair, Richard, additional, Brindle, Kevin M., additional, Stewart, Grant D., additional, Abraham, Jean E., additional, Caldas, Carlos, additional, Rassl, Doris M., additional, Rintoul, Robert C., additional, Alifrangis, Constantine, additional, Middleton, Mark R., additional, Gallagher, Ferdia A., additional, Parkinson, Christine, additional, Durrani, Amer, additional, McDermott, Ultan, additional, Smith, Christopher G., additional, Massie, Charles, additional, Corrie, Pippa G., additional, and Rosenfeld, Nitzan, additional

Published
2020
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50. Effects of Collection and Processing Procedures on Plasma Circulating Cell-Free DNA from Cancer Patients

Author

Risberg, Bente, Tsui, Dana WY, Biggs, Heather, Ruiz-Valdepenas Martin De Almagro, Andrea, Dawson, Sarah-Jane, Hodgkin, Charlotte, Jones, Linda, Parkinson, Christine, Piskorz, Anna, Marass, Francesco, Chandrananda, Dineika, Moore, Elizabeth, Morris, James, Plagnol, Vincent, Rosenfeld, Nitzan, Caldas, Carlos, Brenton, James D, Gale, Davina, Hodgkin, Charlotte [0000-0002-2240-1740], Jones, Linda [0000-0001-9347-5715], Chandrananda, Sandunie [0000-0002-8834-9500], Rosenfeld, Nitzan [0000-0002-2825-4788], Caldas, Carlos [0000-0003-3547-1489], Brenton, James [0000-0002-5738-6683], Gale, Davina [0000-0002-4521-8199], and Apollo - University of Cambridge Repository

Subjects
DNA Copy Number Variations, Neoplasms, Mutation, Temperature, Humans, Transportation, Alleles, Circulating Tumor DNA, Specimen Handling
Abstract

Circulating tumor DNA (ctDNA) offers new opportunities for noninvasive cancer management. Detecting ctDNA in plasma is challenging because it constitutes only a minor fraction of the total cell-free DNA (cfDNA). Pre-analytical factors affect cfDNA levels contributed from leukocyte lysis, hence the ability to detect low-frequency mutant alleles. This study investigates the effects of the delay in processing, storage temperatures, different blood collection tubes, centrifugation protocols, and sample shipment on cfDNA levels. Peripheral blood (n = 231) from cancer patients (n = 62) were collected into K3EDTA or Cell-free DNA BCT tubes and analyzed by digital PCR, targeted amplicon, or shallow whole-genome sequencing. To assess pre-analytic effects, plasma was processed under different conditions after 0, 6, 24, 48, 96 hours, and 1 week at room temperature or 4°C, or using different centrifugation protocols. Digital PCR showed that cfDNA levels increased gradually with time in K3EDTA tubes, but were stable in BCT tubes. K3EDTA samples stored at 4°C showed less variation than room temperature storage, but levels were elevated compared with BCT. A second centrifugation at 3000 × g gave similar cfDNA yields compared with higher-speed centrifugation. Next-generation sequencing showed negligible differences in background error or copy number changes between K3EDTA and BCT, or following shipment in BCT. This study provides insights into the effects of sample processing on ctDNA analysis.

Published
2018
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