1,123 results on '"Grivas P"'
Search Results
2. Immune checkpoint inhibitors in urothelial cancer: recent updates and future outlook
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Gopalakrishnan D, Koshkin VS, Ornstein MC, Papatsoris A, and Grivas P
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Immune checkpoint inhibitors ,Urothelial carcinoma ,Bladder cancer ,PD-1 ,PD-L1 ,CTLA-4 ,Biomarkers ,Immune-related adverse events ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Dharmesh Gopalakrishnan,1 Vadim S Koshkin,2 Moshe C Ornstein,2 Athanasios Papatsoris,3 Petros Grivas2,4 1Department of Hospital Medicine, Cleveland Clinic, Cleveland, OH, USA; 2Department of Hematology and Medical Oncology, Cleveland Clinic, Cleveland, OH, USA; 3Sismanoglio General Hospital, University of Athens School of Medicine, Athens, Greece; 4Department of Medicine, Division of Oncology, University of Washington, Seattle, WA, USA Abstract: Bladder cancer is the sixth most common cancer in the US and most tumors have urothelial (transitional cell) histology. Platinum-based chemotherapy has long been the standard of care in advanced disease, but long-term outcomes have largely remained poor. Since the peak incidence of bladder cancer is in the eighth decade of life and beyond, medical comorbidities may often limit the use of chemotherapy. Immune checkpoint inhibitors with their favorable toxicity profiles and notable antitumor activity have ushered in a new era in the treatment of advanced urothelial cancer (UC) with five agents targeting the PD-1/PD-L1 pathway being recently approved by the US Food and Drug administration. A plethora of clinical trials are ongoing in diverse disease settings, employing agents targeting PD-1/PD-L1 and related immune checkpoint pathways. While reactivating anti-tumor immunity, these agents may lead to a unique constellation of immune-related adverse events, which may warrant discontinuation of therapy and potential use of immunosuppression. Novel combinations with various treatment modalities and optimal sequencing of active therapies are being investigated in prospective clinical trials and retrospective registries. At the era of precision molecular medicine, and since patients do not respond uniformly to these agents, there is a growing need for identification and validation of biomarkers that can accurately predict treatment response and assist in patient selection. This review discusses current updates and future directions of immunotherapy in advanced UC. Keywords: immunotherapy, urothelial carcinoma, bladder cancer, PD-1, PD-L1, CTLA-4, biomarkers, immune-related adverse events
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- 2018
3. Taming the Sigmoid Bottleneck: Provably Argmaxable Sparse Multi-Label Classification
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Grivas, Andreas, Vergari, Antonio, and Lopez, Adam
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Computer Science - Machine Learning - Abstract
Sigmoid output layers are widely used in multi-label classification (MLC) tasks, in which multiple labels can be assigned to any input. In many practical MLC tasks, the number of possible labels is in the thousands, often exceeding the number of input features and resulting in a low-rank output layer. In multi-class classification, it is known that such a low-rank output layer is a bottleneck that can result in unargmaxable classes: classes which cannot be predicted for any input. In this paper, we show that for MLC tasks, the analogous sigmoid bottleneck results in exponentially many unargmaxable label combinations. We explain how to detect these unargmaxable outputs and demonstrate their presence in three widely used MLC datasets. We then show that they can be prevented in practice by introducing a Discrete Fourier Transform (DFT) output layer, which guarantees that all sparse label combinations with up to $k$ active labels are argmaxable. Our DFT layer trains faster and is more parameter efficient, matching the F1@k score of a sigmoid layer while using up to 50% fewer trainable parameters. Our code is publicly available at https://github.com/andreasgrv/sigmoid-bottleneck., Comment: Published at AAAI24
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- 2023
4. Cross-cultural adaptation, reliability and validity of the Greek version of the Spinal Appearance Questionnaire (SAQ) in patients with adolescent idiopathic scoliosis
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Oikonomaki, Marianna, Kelalis, George, Skouras, Apostolos Z., Sotiropoulos, Spiros, Georgoudis, George, and Grivas, Theodoros
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- 2024
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5. Rib index is a strong surrogate of scoliometric reading in idiopathic scoliosis
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Grivas, Theodoros B., Jevtic, Nikola, Ljubojevic, Danka, Pjanic, Samra, Golic, Filip, Mazioti, Christina, Papagianni, Despina, Mamzari, Aristea, and Vasiliadis, Elias
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- 2024
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6. Frequency and Nature of Genomic Alterations in ERBB2-Altered Urothelial Bladder Cancer
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Leary, Jacob B., Enright, Thomas, Bakaloudi, Dimitra Rafailia, Basnet, Alina, Bratslavsky, Gennady, Jacob, Joseph, Spiess, Philippe E., Li, Roger, Necchi, Andrea, Kamat, Ashish M., Pavlick, Dean C., Danziger, Natalie, Huang, Richard S. P., Lin, Douglas I., Cheng, Liang, Ross, Jeffrey, Talukder, Rafee, and Grivas, Petros
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- 2024
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7. Quantum criticality on a compressible lattice
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Sarkar, Saheli, Franke, Lars, Grivas, Nikolas, and Garst, Markus
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Condensed Matter - Strongly Correlated Electrons ,Condensed Matter - Statistical Mechanics - Abstract
The stability of a quantum critical point in the $O(N)$ universality class with respect to an elastic coupling, that preserves $O(N)$ symmetry, is investigated for isotropic elasticity in the framework of the renormalization group (RG) close to the upper critical dimension $d=3-\epsilon$. With respect to the Wilson-Fisher fixed point, we find that the elastic coupling is relevant in the RG sense for $1\leq N \leq 4$, and the crystal becomes microscopically unstable, i.e., a sound velocity vanishes at a finite value of the correlation length $\xi$. For $N > 4$, an additional fixed point emerges that is located at a finite value of the dimensionless elastic coupling. This fixed point is repulsive and separates the flow to weak and strong elastic coupling. As the fixed point is approached the sound velocity is found to vanish only asymptotically as $\xi \to \infty$ such that the crystal remains microscopically stable for any finite value of $\xi$. The fixed point structure we find for the quantum problem is distinct from the classical counterpart in $d=4-\epsilon$, where the crystal always remains microscopically stable for finite $\xi$., Comment: 12 pages, 11 figures, v2: improved presentation and discussion
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- 2023
8. Pembrolizumab plus either epacadostat or placebo for cisplatin-ineligible urothelial carcinoma: results from the ECHO-307/KEYNOTE-672 study
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Necchi, Andrea, Van der Heijden, Michiel S., Trukhin, Dmytro, Peer, Avivit, Gurney, Howard, Alekseev, Boris Y., Parnis, Francis X., Leibowitz, Raya, De Santis, Maria, Grivas, Petros, Clark, Jason, Munteanu, Mihaela, Kataria, Ritesh, Jia, Calvin, Balar, Arjun V., and de Wit, Ronald
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- 2024
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9. Clinical characteristics, racial inequities, and outcomes in patients with breast cancer and COVID-19: A COVID-19 and cancer consortium (CCC19) cohort study
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Nagaraj, Gayathri, Vinayak, Shaveta, Khaki, Ali Raza, Sun, Tianyi, Kuderer, Nicole M, Aboulafia, David M, Acoba, Jared D, Awosika, Joy, Bakouny, Ziad, Balmaceda, Nicole B, Bao, Ting, Bashir, Babar, Berg, Stephanie, Bilen, Mehmet A, Bindal, Poorva, Blau, Sibel, Bodin, Brianne E, Borno, Hala T, Castellano, Cecilia, Choi, Horyun, Deeken, John, Desai, Aakash, Edwin, Natasha, Feldman, Lawrence E, Flora, Daniel B, Friese, Christopher R, Galsky, Matthew D, Gonzalez, Cyndi J, Grivas, Petros, Gupta, Shilpa, Haynam, Marcy, Heilman, Hannah, Hershman, Dawn L, Hwang, Clara, Jani, Chinmay, Jhawar, Sachin R, Joshi, Monika, Kaklamani, Virginia, Klein, Elizabeth J, Knox, Natalie, Koshkin, Vadim S, Kulkarni, Amit A, Kwon, Daniel H, Labaki, Chris, Lammers, Philip E, Lathrop, Kate I, Lewis, Mark A, Li, Xuanyi, de Lima Lopes, Gilbert, Lyman, Gary H, Makower, Della F, Mansoor, Abdul-Hai, Markham, Merry-Jennifer, Mashru, Sandeep H, McKay, Rana R, Messing, Ian, Mico, Vasil, Nadkarni, Rajani, Namburi, Swathi, Nguyen, Ryan H, Nonato, Taylor Kristian, O'Connor, Tracey Lynn, Panagiotou, Orestis A, Park, Kyu, Patel, Jaymin M, Patel, Kanishka GopikaBimal, Peppercorn, Jeffrey, Polimera, Hyma, Puc, Matthew, Rao, Yuan James, Razavi, Pedram, Reid, Sonya A, Riess, Jonathan W, Rivera, Donna R, Robson, Mark, Rose, Suzanne J, Russ, Atlantis D, Schapira, Lidia, Shah, Pankil K, Shanahan, M Kelly, Shapiro, Lauren C, Smits, Melissa, Stover, Daniel G, Streckfuss, Mitrianna, Tachiki, Lisa, Thompson, Michael A, Tolaney, Sara M, Weissmann, Lisa B, Wilson, Grace, Wotman, Michael T, Wulff-Burchfield, Elizabeth M, Mishra, Sanjay, French, Benjamin, Warner, Jeremy L, Lustberg, Maryam B, Accordino, Melissa K, and Shah, Dimpy P
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Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Research ,Cancer ,Infectious Diseases ,Women's Health ,Coronaviruses ,Lung ,Emerging Infectious Diseases ,Breast Cancer ,Good Health and Well Being ,United States ,Humans ,Female ,Middle Aged ,COVID-19 ,SARS-CoV-2 ,Cohort Studies ,Breast Neoplasms ,Retrospective Studies ,COVID-19 and Cancer Consortium ,breast cancer ,epidemiology ,global health ,human ,oncology ,pandemic ,racial inequities ,Biochemistry and Cell Biology ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
BackgroundLimited information is available for patients with breast cancer (BC) and coronavirus disease 2019 (COVID-19), especially among underrepresented racial/ethnic populations.MethodsThis is a COVID-19 and Cancer Consortium (CCC19) registry-based retrospective cohort study of females with active or history of BC and laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection diagnosed between March 2020 and June 2021 in the US. Primary outcome was COVID-19 severity measured on a five-level ordinal scale, including none of the following complications, hospitalization, intensive care unit admission, mechanical ventilation, and all-cause mortality. Multivariable ordinal logistic regression model identified characteristics associated with COVID-19 severity.Results1383 female patient records with BC and COVID-19 were included in the analysis, the median age was 61 years, and median follow-up was 90 days. Multivariable analysis revealed higher odds of COVID-19 severity for older age (aOR per decade, 1.48 [95% CI, 1.32-1.67]); Black patients (aOR 1.74; 95 CI 1.24-2.45), Asian Americans and Pacific Islander patients (aOR 3.40; 95 CI 1.70-6.79) and Other (aOR 2.97; 95 CI 1.71-5.17) racial/ethnic groups; worse ECOG performance status (ECOG PS ≥2: aOR, 7.78 [95% CI, 4.83-12.5]); pre-existing cardiovascular (aOR, 2.26 [95% CI, 1.63-3.15])/pulmonary comorbidities (aOR, 1.65 [95% CI, 1.20-2.29]); diabetes mellitus (aOR, 2.25 [95% CI, 1.66-3.04]); and active and progressing cancer (aOR, 12.5 [95% CI, 6.89-22.6]). Hispanic ethnicity, timing, and type of anti-cancer therapy modalities were not significantly associated with worse COVID-19 outcomes. The total all-cause mortality and hospitalization rate for the entire cohort was 9% and 37%, respectively however, it varied according to the BC disease status.ConclusionsUsing one of the largest registries on cancer and COVID-19, we identified patient and BC-related factors associated with worse COVID-19 outcomes. After adjusting for baseline characteristics, underrepresented racial/ethnic patients experienced worse outcomes compared to non-Hispanic White patients.FundingThis study was partly supported by National Cancer Institute grant number P30 CA068485 to Tianyi Sun, Sanjay Mishra, Benjamin French, Jeremy L Warner; P30-CA046592 to Christopher R Friese; P30 CA023100 for Rana R McKay; P30-CA054174 for Pankil K Shah and Dimpy P Shah; KL2 TR002646 for Pankil Shah and the American Cancer Society and Hope Foundation for Cancer Research (MRSG-16-152-01-CCE) and P30-CA054174 for Dimpy P Shah. REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research grant support (UL1 TR000445 from NCATS/NIH). The funding sources had no role in the writing of the manuscript or the decision to submit it for publication.Clinical trial numberCCC19 registry is registered on ClinicalTrials.gov, NCT04354701.
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- 2023
10. Pembrolizumab plus either epacadostat or placebo for cisplatin-ineligible urothelial carcinoma: results from the ECHO-307/KEYNOTE-672 study
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Andrea Necchi, Michiel S. Van der Heijden, Dmytro Trukhin, Avivit Peer, Howard Gurney, Boris Y. Alekseev, Francis X. Parnis, Raya Leibowitz, Maria De Santis, Petros Grivas, Jason Clark, Mihaela Munteanu, Ritesh Kataria, Calvin Jia, Arjun V. Balar, and Ronald de Wit
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IDO1 ,Epacadostat ,PD-L1 ,PD1 ,Pembrolizumab ,Urothelial carcinoma ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Indoleamine 2,3- dioxygenase 1 (IDO1) is an immunosuppressive enzyme that has been correlated with shorter disease-specific survival in patients with urothelial carcinoma (UC). IDO1 may counteract the antitumor effects of immune checkpoint inhibitors. Epacadostat is a potent and highly selective inhibitor of IDO1. In the phase I/II ECHO-202/KEYNOTE-037 study, epacadostat plus pembrolizumab resulted in a preliminary objective response rate (ORR) of 35% in a cohort of patients with advanced UC. Methods ECHO-307/KEYNOTE-672 was a double-blinded, randomized, phase III study. Eligible adults had confirmed locally advanced/unresectable or metastatic UC of the urinary tract and were ineligible to receive cisplatin-based chemotherapy. Participants were randomly assigned (1:1) to receive epacadostat (100 mg twice daily) plus pembrolizumab (200 mg every 3 weeks) or placebo plus pembrolizumab for up to 35 pembrolizumab infusions. The primary endpoint was investigator-assessed ORR per Response Evaluation Criteria in Solid Tumors (version 1.1). Results A total of 93 patients were randomized (epacadostat plus pembrolizumab, n = 44; placebo plus pembrolizumab, n = 49). Enrollment was stopped early due to emerging data from the phase III ECHO-301/KEYNOTE-252 study. The median duration of follow-up was 64 days in both arms. Based on all available data at cutoff, ORR (unconfirmed) was 31.8% (95% CI, 22.46–55.24%) for epacadostat plus pembrolizumab and 24.5% (95% CI, 15.33–43.67%) for placebo plus pembrolizumab. Circulating kynurenine levels numerically increased from C1D1 to C2D1 in the placebo-plus-pembrolizumab arm and decreased in the epacadostat-plus-pembrolizumab arm. Epacadostat-plus-pembrolizumab combination treatment was well tolerated with a safety profile similar to the placebo arm. Treatment discontinuations due to treatment-related adverse events were more frequent with epacadostat (11.6% vs. 4.1%). Conclusions Treatment with epacadostat plus pembrolizumab resulted in a similar ORR and safety profile as placebo plus pembrolizumab in cisplatin-ineligible patients with previously untreated locally advanced/unresectable or metastatic UC. At a dose of 100 mg twice daily, epacadostat did not appear to completely normalize circulating kynurenine levels when administered with pembrolizumab. Larger studies with longer follow-up and possibly testing higher doses of epacadostat, potentially in different therapy settings, may be warranted. Trial registration ClinicalTrials.gov identifier: NCT03361865, retrospectively registered December 5, 2017.
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- 2024
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11. Analysis of secondary inorganic aerosols over the greater Athens area using the EPISODE–CityChem source dispersion and photochemistry model
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S. Myriokefalitakis, M. Karl, K. A. Weiss, D. Karagiannis, E. Athanasopoulou, A. Kakouri, A. Bougiatioti, E. Liakakou, I. Stavroulas, G. Papangelis, G. Grivas, D. Paraskevopoulou, O. Speyer, N. Mihalopoulos, and E. Gerasopoulos
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Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
Secondary inorganic aerosols (SIAs) are major components of fine particulate matter (PM2.5), having substantial implications for climate and air quality in an urban environment. In this study, a state-of-the-art thermodynamic model has been coupled to the source dispersion and photochemistry city-scale chemistry transport model EPISODE–CityChem, which is able to simulate pollutants at a horizontal resolution of 100 m×100 m, to determine the equilibrium between the inorganic gas and aerosol phases over the greater Athens area, Greece, for the year 2019. In agreement with in situ observations, sulfate (SO42-) is calculated to have the highest annual mean surface concentration (2.15 ± 0.88 µg m−3) among SIAs in the model domain, followed by ammonium (NH4+; 0.58 ± 0.14 µg m−3) and fine nitrate (NO3-; 0.24 ± 0.22 µg m−3). Simulations denote that NO3- formation strongly depends on the local nitrogen oxide emissions, along with the ambient temperature, the relative humidity, and the photochemical activity. Additionally, we show that anthropogenic combustion sources may have an important impact on the NO3- formation in an urban area. During the cold period, the combined effect of decreased temperature in the presence of non-sea-salt potassium favors the partitioning of HNO3 in the aerosol phase in the model, raising the NO3- formation in the area. Overall, this work highlights the significance of atmospheric composition and the local meteorological conditions for the equilibrium distribution of nitrogen-containing semi-volatile compounds and the acidity of inorganic aerosols, especially in urban areas where atmospheric trace elements from natural and anthropogenic sources coexist.
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- 2024
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12. Perioperative Blood Transfusion Is Associated with Worse Survival in Patients Undergoing Radical Cystectomy after Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer
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Tessa Ladner, Anna J. Black, Homayoun Zargar, Jonathan L. Wright, Andrew C. Thorpe, Todd M. Morgan, Jeff M. Holzbeierlein, Michael S. Cookson, Niels-Erik Jacobsen, Adrian S. Fairey, Colin P. N. Dinney, Maria C. Mir, Laura-Maria Krabbe, Jeffrey S. Montgomery, Nikhil Vasdev, Evan Y. Yu, Evanguelos Xylinas, Andrew J. Stephenson, Jay B. Shah, Siamak Daneshmand, Kamran Zargar-Shoshtari, Philippe E. Spiess, Laura S. Mertens, Bas W. G. van Rhijn, Petros Grivas, Wassim Kassouf, Marc A. Dall’Era, Srikala S. Sridhar, Jonathan S. McGrath, Jonathan Aning, Shahrokh F. Shariat, Trinity J. Bivalacqua, Scott A. North, Daniel A. Barocas, Yair Lotan, and Peter C. Black
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bladder cancer ,perioperative blood transfusion ,radical cystectomy ,chemotherapy ,Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
Objectives: Perioperative blood transfusion (PBT) has been associated with worse survival after radical cystectomy (RC) in patients with muscle-invasive bladder cancer (MIBC). Here, we evaluated the association between PBT and survival after RC that was preceded by neoadjuvant chemotherapy (NAC). Methods: A retrospective analysis was performed on 949 patients with cT2-4aN0M0 bladder cancer who received NAC prior to RC between 2000 and 2013 at 19 centers. Kaplan–Meier estimates of overall survival (OS) were made. Presumed risk factors for OS were analyzed using Cox regression analysis. PBT was defined by the administration of any packed red blood cells during surgery or during the post-operative hospital stay. Results: A transfusion was given to 608 patients (64%). Transfused patients were more likely to have adverse clinical and pathologic parameters, including clinical stage and performance status. Transfused patients had worse OS (p = 0.01). On multivariable Cox regression, PBT was found to be independently associated with worse OS (HR 1.53 (95% CI 1.13–2.08), p = 0.007). Conclusions: PBT is common after NAC and RC, which may be linked, in part, to the anemia induced by NAC. PBT was associated with several adverse risk factors that correlate with poor outcomes after NAC and RC, and it was an independent predictor of adverse OS on multivariable analysis. Further study should determine if measures to avoid blood loss can reduce the need for PBT and thereby improve patient outcomes.
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- 2024
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13. ExoClock Project III: 450 new exoplanet ephemerides from ground and space observations
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Kokori, A., Tsiaras, A., Edwards, B., Jones, A., Pantelidou, G., Tinetti, G., Bewersdorff, L., Iliadou, A., Jongen, Y., Lekkas, G., Nastasi, A., Poultourtzidis, E., Sidiropoulos, C., Walter, F., Wünsche, A., Abraham, R., Agnihotri, V. K., Albanesi, R., Arce-Mansego, E., Arnot, D., Audejean, M., Aumasson, C., Bachschmidt, M., Baj, G., Barroy, P. R., Belinski, A. A., Bennett, D., Benni, P., Bernacki, K., Betti, L., Biagini, A., Bosch, P., Brandebourg, P., Brát, L., Bretton, M., Brincat, S. M., Brouillard, S., Bruzas, A., Bruzzone, A., Buckland, R. A., Caló, M., Campos, F., Carreno, A., Rodrigo, J. -A. Carrion, Casali, R., Casalnuovo, G., Cataneo, M., Chang, C. -M., Changeat, L., Chowdhury, V., Ciantini, R., Cilluffo, M., Coliac, J. -F., Conzo, G., Correa, M., Coulon, G., Crouzet, N., Crow, M. V., Curtis, I., Daniel, D., Dawes, S., Dauchet, B., Deldem, M., Deligeorgopoulos, D., Dransfield, G., Dymock, R., Eenmäe, T., Evans, P., Esseiva, N., Falco, C., Farfán, R. G., Fernández-Lajús, E., Ferratfiat, S., Ferreira, S. L., Ferretti, A., Fiołka, J., Fowler, M., Futcher, S. R., Gabellini, D., Gainey, T., Gaitan, J., Gajdoš, P., García-Sánchez, A., Garlitz, J., Gillier, C., Gison, C., Horta, F. Grau, Grivas, G., Gonzales, J., Gorshanov, D., Guerra, P., Guillot, T., Haswell, C. A., Haymes, T., Hentunen, V. -P., Hills, K., Hose, K., Humbert, T., Hurter, F., Hynek, T., Irzyk, M., Jacobsen, J., Jannetta, A. L., Johnson, K., Jóźwik-Wabik, P., Kaeouach, A. E., Kang, W., Kiiskinen, H., Kim, T., Kivila, Ü., Koch, B., Kolb, U., Kučáková, H., Lai, S. -P., Laloum, D., Lasota, S., Lewis, L. A., Liakos, G. -I., Libotte, F., Lopresti, C., Lomoz, F., Majewski, R., Malcher, A., Mallonn, M., Mannucci, M., Marchini, A., Mari, J. -M., Marino, A., Marino, G., Mario, J. -C., Marquette, J. -B., Martínez-Bravo, F. A., Mašek, M., Matassa, P., Michel, P., Michelet, J., Miller, M., Miny, E., Mollier, T., Molina, D., Monteleone, B., Montigiani, N., Morales-Aimar, M., Mortari, F., Morvan, M., Mugnai, L. V., Murawski, G., Naponiello, L., Naves, R., Naudin, J. -L., Néel, D., Neito, R., Neveu, S., Noschese, A., Öğmen, Y., Ohshima, O., Orbanic, Z., Pace, E. P., Pantacchini, C., Paschalis, N. I., Pereira, C., Peretto, I., Perroud, V., Phillips, M., Pintr, P., Pioppa, J. -B., Plazas, J., Poelarends, A. J., Popowicz, A., Purcell, J., Quinn, N., Raetz, M., Rees, D., Regembal, F., Rocchetto, M., Rocci, P. -F., Rockenbauer, M., Roth, R., Rousselot, L., Rubia, X., Ruocco, N., Russo, E., Salisbury, M., Salvaggio, F., Santos, A., Savage, J., Scaggiante, F., Sedita, D., Shadick, S., Silva, A. F., Sioulas, N., Školník, V., Smith, M., Smolka, M., Solmaz, A., Stanbury, N., Stouraitis, D., Tan, T. -G., Theusner, M., Thurston, G., Tifner, F. -P., Tomacelli, A., Tomatis, A., Trnka, J., Tylšar, M., Valeau, P., Vignes, J. -P., Villa, A., Sureda, A. Vives, Vora, K., Vrašťák, M., Walliang, D., Wenzel, B., Wright, D. E., Zambelli, R., Zhang, M., and Zíbar, M.
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Astrophysics - Earth and Planetary Astrophysics ,Astrophysics - Instrumentation and Methods for Astrophysics ,Astrophysics - Solar and Stellar Astrophysics - Abstract
The ExoClock project has been created with the aim of increasing the efficiency of the Ariel mission. It will achieve this by continuously monitoring and updating the ephemerides of Ariel candidates over an extended period, in order to produce a consistent catalogue of reliable and precise ephemerides. This work presents a homogenous catalogue of updated ephemerides for 450 planets, generated by the integration of $\sim$18000 data points from multiple sources. These sources include observations from ground-based telescopes (ExoClock network and ETD), mid-time values from the literature and light-curves from space telescopes (Kepler/K2 and TESS). With all the above, we manage to collect observations for half of the post-discovery years (median), with data that have a median uncertainty less than one minute. In comparison with literature, the ephemerides generated by the project are more precise and less biased. More than 40\% of the initial literature ephemerides had to be updated to reach the goals of the project, as they were either of low precision or drifting. Moreover, the integrated approach of the project enables both the monitoring of the majority of the Ariel candidates (95\%), and also the identification of missing data. The dedicated ExoClock network effectively supports this task by contributing additional observations when a gap in the data is identified. These results highlight the need for continuous monitoring to increase the observing coverage of the candidate planets. Finally, the extended observing coverage of planets allows us to detect trends (TTVs - Transit Timing Variations) for a sample of 19 planets. All products, data, and codes used in this work are open and accessible to the wider scientific community., Comment: Recommended for publication to ApJS (reviewer's comments implemented). Main body: 13 pages, total: 77 pages, 7 figures, 7 tables. Data available at http://doi.org/10.17605/OSF.IO/P298N
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- 2022
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14. Technology Innovation and Guardrails in Elite Sport: The Future is Now
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Guppy, Fergus, Muniz-Pardos, Borja, Angeloudis, Konstantinos, Grivas, Gerasimos V., Pitsiladis, Asimina, Bundy, Ross, Zelenkova, Irina, Tanisawa, Kumpei, Akiyama, Hiroshi, Keramitsoglou, Iphigenia, Miller, Mike, Knopp, Melanie, Schweizer, Fabian, Luckfiel, Tobias, Ruiz, Daniel, Racinais, Sebastien, and Pitsiladis, Yannis
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- 2023
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15. Managing Temporomandibular Joint Osteoarthritis by Dental Stem Cell Secretome
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Bousnaki, Maria, Bakopoulou, Athina, Grivas, Ioannis, Bekiari, Chrysa, Pich, Andreas, Rizk, Marta, Keklikoglou, Kleoniki, Papachristou, Eleni, Papadopoulos, Georgios C., Kritis, Aristeidis, Mikos, Antonios G., and Koidis, Petros
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- 2023
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16. Review on the Role of BRCA Mutations in Genomic Screening and Risk Stratification of Prostate Cancer
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Nikolaos Kalampokis, Christos Zabaftis, Theodoros Spinos, Markos Karavitakis, Ioannis Leotsakos, Ioannis Katafigiotis, Henk van der Poel, Nikolaos Grivas, and Dionysios Mitropoulos
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prostate cancer ,genomic screening ,mutations ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
(1) Background: Somatic and germline alterations can be commonly found in prostate cancer (PCa) patients. The aim of our present study was to perform a comprehensive review of the current literature in order to examine the impact of BRCA mutations in the context of PCa as well as their significance as genetic biomarkers. (2) Methods: A narrative review of all the available literature was performed. Only “landmark” publications were included. (3) Results: Overall, the number of PCa patients who harbor a BRCA2 mutation range between 1.2% and 3.2%. However, BRCA2 and BRCA1 mutations are responsible for most cases of hereditary PCa, increasing the risk by 3–8.6 times and up to 4 times, respectively. These mutations are correlated with aggressive disease and poor prognosis. Gene testing should be offered to patients with metastatic PCa, those with 2–3 first-degree relatives with PCa, or those aged < 55 and with one close relative with breast (age ≤ 50 years) or invasive ovarian cancer. (4) Conclusions: The individualized assessment of BRCA mutations is an important tool for the risk stratification of PCa patients. It is also a population screening tool which can guide our risk assessment strategies and achieve better results for our patients and their families.
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- 2024
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17. Association of the Time to Immune Checkpoint Inhibitor (ICI) Initiation and Outcomes With Second Line ICI in Patients With Advanced Urothelial Carcinoma
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Talukder, Rafee, Makrakis, Dimitrios, Lin, Genevieve Ihsiu, Diamantopoulos, Leonidas N, Dawsey, Scott, Gupta, Shilpa, Carril-Ajuria, Lucia, Castellano, Daniel, de Kouchkovsky, Ivan, Jindal, Tanya, Koshkin, Vadim S, Park, Joseph J, Alva, Ajjai, Bilen, Mehmet A, Stewart, Tyler F, McKay, Rana R, Tripathi, Nishita, Agarwal, Neeraj, Vather-Wu, Naomi, Zakharia, Yousef, Morales-Barrera, Rafael, Devitt, Michael E, Cortellini, Alessio, Fulgenzi, Claudia Angela Maria, Pinato, David J, Nelson, Ariel, Hoimes, Christopher J, Gupta, Kavita, Gartrell, Benjamin A, Sankin, Alex, Tripathi, Abhishek, Zakopoulou, Roubini, Bamias, Aristotelis, Murgic, Jure, Fröbe, Ana, Rodriguez-Vida, Alejo, Drakaki, Alexandra, Liu, Sandy, Lu, Eric, Kumar, Vivek, Lorenzo, Giuseppe Di, Joshi, Monika, Isaacsson-Velho, Pedro, Buznego, Lucia Alonso, Duran, Ignacio, Moses, Marcus, Barata, Pedro, Sonpavde, Guru, Wright, Jonathan L, Yu, Evan Y, Montgomery, Robert Bruce, Hsieh, Andrew C, Grivas, Petros, and Khaki, Ali Raza
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Cancer ,Clinical Research ,Humans ,Immune Checkpoint Inhibitors ,Carcinoma ,Transitional Cell ,Retrospective Studies ,Cohort Studies ,Treatment Outcome ,Urinary Bladder Neoplasms ,Bladder cancer ,Immunotherapy ,Platinum resistance ,Checkpoint Inhibitor ,Outcomes ,Oncology and Carcinogenesis ,Public Health and Health Services ,Oncology & Carcinogenesis - Abstract
BackgroundEarly progression on first-line (1L) platinum-based therapy or between therapy lines may be a surrogate of more aggressive disease and poor outcomes in advanced urothelial carcinoma (aUC), but its prognostic role regarding immune checkpoint inhibitor (ICI) response and survival is unclear. We hypothesized that shorter time until start of second-line (2L) ICI would be associated with worse outcomes in aUC.Patients and methodsWe performed a retrospective multi-institution cohort study in patients with aUC treated with 1L platinum-based chemotherapy, who received 2L ICI. Patients receiving switch maintenance ICI were excluded. We defined time to 2L ICI therapy as the time between the start of 1L platinum-based chemotherapy to the start of 2L ICI and categorized patients a priori into 1 of 3 groups: less than 3 months versus 3-6 months versus more than 6 months. We calculated overall response rate (ORR) with 2L ICI, progression-free survival (PFS) and overall survival (OS) from the start of 2L ICI. ORR was compared among the 3 groups using multivariable logistic regression, and PFS, OS using cox regression. Multivariable models were adjusted for known prognostic factors.ResultsWe included 215, 215, and 219 patients in the ORR, PFS, and OS analyses, respectively, after exclusions. ORR difference did not reach statistical significance between patients with less than 3 months versus 3-6 months versus more than 6 months to 2L ICI. However, PFS (HR 1.64; 95% CI 1.02-2.63) and OS (HR 1.77; 95% CI 1.10-2.84) was shorter among those with time to 2L ICI less than 3 months compared to those who initiated 2L ICI more than 6 months.ConclusionAmong patients with aUC treated with 2L ICI, time to 2L ICI less than 3 months was associated with lower, but not significantly different ORR, but shorter PFS and OS compared to 2L ICI more than 6 months. This highlights potential cross resistance mechanisms between ICI and platinum-based chemotherapy.
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- 2022
18. Association of prior local therapy and outcomes with programmed‐death ligand‐1 inhibitors in advanced urothelial cancer
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Makrakis, Dimitrios, Talukder, Rafee, Diamantopoulos, Leonidas N, Carril-Ajuria, Lucia, Castellano, Daniel, De Kouchkovsky, Ivan, Koshkin, Vadim S, Park, Joseph J, Alva, Ajjai, Bilen, Mehmet A, Stewart, Tyler F, McKay, Rana R, Santos, Victor S, Agarwal, Neeraj, Jain, Jayanshu, Zakharia, Yousef, Morales-Barrera, Rafael, Devitt, Michael E, Grant, Michael, Lythgoe, Mark P, Pinato, David J, Nelson, Ariel, Hoimes, Christopher J, Shreck, Evan, Gartrell, Benjamin A, Sankin, Alex, Tripathi, Abhishek, Zakopoulou, Roubini, Bamias, Aristotelis, Murgic, Jure, Fröbe, Ana, Rodriguez-Vida, Alejo, Drakaki, Alexandra, Liu, Sandy, Kumar, Vivek, Di Lorenzo, Giuseppe, Joshi, Monika, Isaacsson-Velho, Pedro, Buznego, Lucia Alonso, Duran, Ignacio, Moses, Marcus, Barata, Pedro, Sonpavde, Guru, Yu, Evan Y, Wright, Jonathan L, Grivas, Petros, and Khaki, Ali Raza
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Cancer ,Good Health and Well Being ,Humans ,Immune Checkpoint Inhibitors ,Retrospective Studies ,Carcinoma ,Transitional Cell ,Urinary Bladder Neoplasms ,bladder cancer ,urinary tract neoplasms ,urothelial carcinoma ,immune checkpoint inhibitors ,immunotherapy ,outcomes ,#uroonc ,#utuc ,#BladderCancer ,#blcsm ,Urology & Nephrology ,Clinical sciences ,Oncology and carcinogenesis - Abstract
ObjectivesTo compare clinical outcomes with programmed-death ligand-1 immune checkpoint inhibitors (ICIs) in patients with advanced urothelial carcinoma (aUC) who have vs have not undergone radical surgery (RS) or radiation therapy (RT) prior to developing metastatic disease.Patients and methodsWe performed a retrospective cohort study collecting clinicopathological, treatment and outcomes data for patients with aUC receiving ICIs across 25 institutions. We compared outcomes (observed response rate [ORR], progression-free survival [PFS], overall survival [OS]) between patients with vs without prior RS, and by type of prior locoregional treatment (RS vs RT vs no locoregional treatment). Patients with de novo advanced disease were excluded. Analysis was stratified by treatment line (first-line and second-line or greater [second-plus line]). Logistic regression was used to compare ORR, while Kaplan-Meier analysis and Cox regression were used for PFS and OS. Multivariable models were adjusted for known prognostic factors.ResultsWe included 562 patients (first-line: 342 and second-plus line: 220). There was no difference in outcomes based on prior locoregional treatment among those treated with first-line ICIs. In the second-plus-line setting, prior RS was associated with higher ORR (adjusted odds ratio 2.61, 95% confidence interval [CI]1.19-5.74]), longer OS (adjusted hazard ratio [aHR] 0.61, 95% CI 0.42-0.88) and PFS (aHR 0.63, 95% CI 0.45-0.89) vs no prior RS. This association remained significant when type of prior locoregional treatment (RS and RT) was modelled separately.ConclusionPrior RS before developing advanced disease was associated with better outcomes in patients with aUC treated with ICIs in the second-plus-line but not in the first-line setting. While further validation is needed, our findings could have implications for prognostic estimates in clinical discussions and benchmarking for clinical trials. Limitations include the study's retrospective nature, lack of randomization, and possible selection and confounding biases.
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- 2022
19. Association Between Sites of Metastasis and Outcomes With Immune Checkpoint Inhibitors in Advanced Urothelial Carcinoma
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Makrakis, Dimitrios, Talukder, Rafee, Lin, Genevieve Ihsiu, Diamantopoulos, Leonidas N, Dawsey, Scott, Gupta, Shilpa, Carril-Ajuria, Lucia, Castellano, Daniel, de Kouchkovsky, Ivan, Koshkin, Vadim S, Park, Joseph J, Alva, Ajjai, Bilen, Mehmet A, Stewart, Tyler F, McKay, Rana R, Tripathi, Nishita, Agarwal, Neeraj, Vather-Wu, Naomi, Zakharia, Yousef, Morales-Barrera, Rafael, Devitt, Michael E, Cortellini, Alessio, Fulgenzi, Claudia Angela Maria, Pinato, David J, Nelson, Ariel, Hoimes, Christopher J, Gupta, Kavita, Gartrell, Benjamin A, Sankin, Alex, Tripathi, Abhishek, Zakopoulou, Roubini, Bamias, Aristotelis, Murgic, Jure, Fröbe, Ana, Rodriguez-Vida, Alejo, Drakaki, Alexandra, Liu, Sandy, Lu, Eric, Kumar, Vivek, Lorenzo, Giuseppe Di, Joshi, Monika, Isaacsson-Velho, Pedro, Buznego, Lucia Alonso, Duran, Ignacio, Moses, Marcus, Jang, Albert, Barata, Pedro, Sonpavde, Guru, Yu, Evan Y, Montgomery, Robert Bruce, Grivas, Petros, and Khaki, Ali Raza
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Immunology ,Liver Disease ,Orphan Drug ,Cancer ,Immunotherapy ,Clinical Research ,Rare Diseases ,Digestive Diseases ,Precision Medicine ,Carcinoma ,Transitional Cell ,Humans ,Immune Checkpoint Inhibitors ,Liver Neoplasms ,Retrospective Studies ,Urinary Bladder Neoplasms ,Bladder cancer ,Immune checkpoint inhibitors ,Advanced urothelial carcinoma ,Outcomes ,Metastatic cancer ,Public Health and Health Services ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
BackgroundSites of metastasis have prognostic significance in advanced urothelial carcinoma (aUC), but more information is needed regarding outcomes based on metastatic sites in patients treated with immune checkpoint inhibitors (ICI). We hypothesized that presence of liver/bone metastases would be associated with worse outcomes with ICI.MethodsWe identified a retrospective cohort of patients with aUC across 26 institutions, collecting demographics, clinicopathological, treatment, and outcomes information. Outcomes were compared with logistic (observed response rate; ORR) and Cox (progression-free survival; PFS, overall survival; OS) regression between patients with/without metastasis beyond lymph nodes (LN) and those with/without bone/liver/lung metastasis. Analysis was stratified by 1st or 2nd+ line.ResultsWe identified 917 ICI-treated patients: in the 1st line, bone/liver metastases were associated with shorter PFS (Hazard ratio; HR: 1.65 and 2.54), OS (HR: 1.60 and 2.35, respectively) and lower ORR (OR: 0.48 and 0.31). In the 2nd+ line, bone/liver metastases were associated with shorter PFS (HR: 1.71 and 1.62), OS (HR: 1.76 and 1.56) and, for bone-only metastases, lower ORR (OR: 0.29). In the 1st line, LN-confined metastasis was associated with longer PFS (HR: 0.53), OS (HR:0.49) and higher ORR (OR: 2.97). In the 2nd+ line, LN-confined metastasis was associated with longer PFS (HR: 0.47), OS (HR: 0.54), and higher ORR (OR: 2.79); all associations were significant.ConclusionBone and/or liver metastases were associated with worse, while LN-confined metastases were associated with better outcomes in patients with aUC receiving ICI. These findings in a large population treated outside clinical trials corroborate data from trial subset analyses.
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- 2022
20. Patterns of chemotherapy use with primary radiotherapy for localized bladder cancer in patients 65 or older
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Fady Ghali, Sarah K. Holt, Elizabeth L. Koehne, Jonathan J. Chen, Emily S. Weg, Jay J. Liao, Jing Zeng, Petros Grivas, Jessica E. Hawley, Andrew C. Hsieh, Robert Bruce Montgomery, and Jonathan L. Wright
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bladder cancer ,organ-preservation ,radiation ,chemotherapy ,trimodal therapy ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
IntroductionBladder preservation with concurrent chemoradiotherapy after maximum transurethral resection of bladder tumor is an alternative to radical cystectomy in select patients with muscle invasive bladder cancer (MIBC). Concurrent administration of radio-sensitizing chemotherapy and radiation therapy (RT) has been shown to have superior disease control compared with RT alone and can often be administered with modest added toxicity. We sought to describe national patterns of chemotherapy use.MethodsThe linked surveillance, epidemiology, and end results (SEER)-Medicare database was used to identify patients with cT2-4, N0/X, M0/X BC who received radiation between 2004 and 2018. Data on demographics, clinicopathologic factors, therapy and outcomes were extracted. Concurrent utilization of chemotherapy with RT was also identified (CRT). Multivariate logistic regression (MVA) models were used to explore factors associated with receipt of chemotherapy and overall survival (OS).Results2190 patients met inclusion criteria. Of these, 850 (38.8%) received no chemotherapy. Among those receiving chemotherapy, the most frequent regimens were single agent carboplatin, cisplatin, or gemcitabine. Factors that were independently associated with decreased likelihood of chemotherapy use were increasing age (OR 0.93, CI 0.92 – 0.95), Hispanic race (compared with White, OR 0.62, CI 0.39 – 0.99), cT3 or T4 (compared with cT2, OR 0.70, CI 0.55 – 0.90), and lower National Cancer Institute comorbidity index (OR 0.60, CI 0.51 – 0.70) (p < 0.05). Variables independently associated with increased likelihood of receipt of chemotherapy were married status (OR 1.28, CI 1.06 – 1.54), higher socioeconomic status (OR 1.31, CI 1.06 – 1.64), and later year of diagnosis (OR 1.09, CI 1.06 – 1.12). Receipt of concurrent chemotherapy with RT was associated with superior OS compared with RT alone.ConclusionOver a third of patients >/65 years old receiving curative-intent RT for MIBC do not receive concurrent chemotherapy. Considering the improvement in oncologic outcomes with CRT over RT alone and more options, such as low dose gemcitabine which can be administered with modest toxicity, efforts are needed to identify barriers to utilization and increase the use of radio-sensitizing chemotherapy.
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- 2024
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21. Low-Rank Softmax Can Have Unargmaxable Classes in Theory but Rarely in Practice
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Grivas, Andreas, Bogoychev, Nikolay, and Lopez, Adam
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Computer Science - Machine Learning ,Computer Science - Computation and Language - Abstract
Classifiers in natural language processing (NLP) often have a large number of output classes. For example, neural language models (LMs) and machine translation (MT) models both predict tokens from a vocabulary of thousands. The Softmax output layer of these models typically receives as input a dense feature representation, which has much lower dimensionality than the output. In theory, the result is some words may be impossible to be predicted via argmax, irrespective of input features, and empirically, there is evidence this happens in small language models. In this paper we ask whether it can happen in practical large language models and translation models. To do so, we develop algorithms to detect such \emph{unargmaxable} tokens in public models. We find that 13 out of 150 models do indeed have such tokens; however, they are very infrequent and unlikely to impact model quality. We release our code so that others can inspect their models., Comment: Preprint of conference paper accepted at ACL 2022
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- 2022
22. Two cases of SMA syndrome after neurosurgical injury to the frontal aslant tract
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Agyemang, Kevin, Rose, Anna, Sheikh, Mustafa El, Asha, Mutiu, Molinari, Emanuela, Fullerton, Natasha E., Brennan, David, and Grivas, Athanasios
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- 2023
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23. Role of Underlying Liver Pathology in the Development of Immune-Related Hepatitis: A Case–Control Study
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Storm, Erica M., Makrakis, Dimitrios, Lin, Genevieve I., Talukder, Rafee, Bakaloudi, Dimitra R., Shah, Eshana E., Liou, Iris W., Hockenbery, David, Grivas, Petros, and Khaki, Ali Raza
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- 2023
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24. ROLE OF PHYSICAL FITNESS AND BODY COMPOSITION IN NAVAL CADETS: A NARRATIVE REVIEW
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Gerasimos V. Grivas and Antonios Vantarakis
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naval cadets ,physical fitness ,body composition ,body mass index ,Sports ,GV557-1198.995 - Abstract
Physical fitness is important to the general population, but for naval cadets, achieving a high level of physical fitness may be essential for success in their jobs. The purpose of this review was to summarize the current literature on physical fitness and body composition in naval cadets narratively and examine the effects of training programs on their physical fitness and body composition. The length of time that the personnel is on a ship cannot always be determined. For this reason, cadets must follow an exercise program to increase or maintain their physical condition during their voyages on a warship. This review revealed that endurance and strength training programs lasting 8 weeks to 12 months improved naval cadets’ physical capacity, body composition, and BMI. In conclusion, this review provides practical suggestions for improving naval cadets’ physical fitness and body.
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- 2023
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25. EFFECTS OF WEIGHT TRAINING ON PHYSICAL FITNESS AND BODY COMPOSITION ON A WARSHIP
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Antonios Vantarakis, Gerasimos Grivas, Stamatios Kalligeros, Konstantinos Karakatsanis, Nikolas Theodorou, Nikolaos Vezos, Anthia-Dimitra Vantaraki, and Sotirios A. Vantarakis
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weight training program ,physical fitness ,naval cadet ,board weight training ,warship ,Sports ,GV557-1198.995 - Abstract
Introduction. The military readiness of the naval personnel serving on a warship requires a high level of physical health and fitness which is considered a given capability, regardless of the service they serve. The purpose of this study was to investigate the effects of a weight training program (WTP) on the physical fitness of Greek naval cadets during a training trip on a warship. Material & Methods. The sample consisted of 21 male Greek cadets of the Hellenic Naval Academy (HNA) (age: 21.0 ± 0.83 years, height: 177.9 ± 6.9cm, body mass: 78.2 ± 7.1kg). The cadet team that participated for four weeks on the trip performed 20 training sessions lasting 60-80 min each, five times a week. The measurements of the participants before and after 4 weeks of a weight exercise training program were related to body mass (BM), body fat percentage (% BF), body mass index (BMI), number of sit-ups (SU1) and push-ups (PU1) done in one minute, one repetition maximum (1RM) in a squat (SQ) and bench press (BP), and the 30m run and 5m rope climb. Results. The results of the study showed that the WTP did not affect BM (t20 = -0.412, p = .685 > .05) and BMI (t20 = -0.477, p = .639>.05). Respectively, no significant difference was observed in %BF in all cadets between the measurements (t20 = -0.962, p > .05). The number of PU1 significantly increased by 10.82% (t20 = -4.191, p < .01). The SU1 significantly increased by 9.34% (t20 = -4.613, p < .01). The 1RM increased on BP by 5.71% (t20 = -5.769. p < .01) and SQ by 7.73% (t = 20, p < .01). The time on 30m sprint decreased by 1.33% (t20 = 7.640, p < .01) and for 5m rope climb decreased by 3.15% (t20 = 6.663, p < .01). Conclusion. The results of this study showed that it is necessary for the naval cadets to follow a WTP during their trips in the sea on a warship to increase their physical condition/fitness and sustain their body composition.
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- 2023
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26. Transcriptomic Determinants of Response to Pembrolizumab Monotherapy across Solid Tumor TypesDeterminants of Pembrolizumab Response in Solid Tumors
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Cristescu, Razvan, Nebozhyn, Michael, Zhang, Chunsheng, Albright, Andrew, Kobie, Julie, Huang, Lingkang, Zhao, Qing, Wang, Anran, Ma, Hua, Cao, Z Alexander, Morrissey, Michael, Ribas, Antoni, Grivas, Petros, Cescon, David W, McClanahan, Terrill K, Snyder, Alexandra, Ayers, Mark, Lunceford, Jared, and Loboda, Andrey
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Genetics ,Cancer ,Human Genome ,2.1 Biological and endogenous factors ,Aetiology ,Good Health and Well Being ,Antibodies ,Monoclonal ,Humanized ,Antineoplastic Agents ,Immunological ,Humans ,Neoplasms ,RNA ,Transcriptome ,Transforming Growth Factor beta ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
PurposeTo explore relationships between biological gene expression signatures and pembrolizumab response.Experimental designRNA-sequencing data on baseline tumor tissue from 1,188 patients across seven tumor types treated with pembrolizumab monotherapy in nine clinical trials were used. A total of 11 prespecified gene expression signatures [18-gene T-cell-inflamed gene expression profile (TcellinfGEP), angiogenesis, hypoxia, glycolysis, proliferation, MYC, RAS, granulocytic myeloid-derived suppressor cell (gMDSC), monocytic myeloid-derived suppressor cell (mMDSC), stroma/epithelial-to-mesenchymal transition (EMT)/TGFβ, and WNT] were evaluated for their relationship to objective response rate (per RECIST, version 1.1). Logistic regression analysis of response for consensus signatures was adjusted for tumor type, Eastern Cooperative Oncology Group performance status, and TcellinfGEP, an approach equivalent to evaluating the association between response and the residuals of consensus signatures after detrending them for their relationship with the TcellinfGEP (previously identified as a determinant of pembrolizumab response) and tumor type. Testing of the 10 prespecified non-TcellinfGEP consensus signatures for negative association [except proliferation (hypothesized positive association)] with response was adjusted for multiplicity.ResultsCovariance patterns of the 11 signatures (including TcellinfGEP) identified in Merck-Moffitt and The Cancer Genome Atlas datasets showed highly concordant coexpression patterns in the RNA-sequencing data from pembrolizumab trials. TcellinfGEP was positively associated with response; signatures for angiogenesis, mMDSC, and stroma/EMT/TGFβ were negatively associated with response to pembrolizumab monotherapy.ConclusionsThese findings suggest that features beyond IFNγ-related T-cell inflammation may be relevant to anti-programmed death 1 monotherapy response and may define other axes of tumor biology as candidates for pembrolizumab combinations. See related commentary by Cho et al., p. 1479.
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- 2022
27. Response and Outcomes to Immune Checkpoint Inhibitors in Advanced Urothelial Cancer Based on Prior Intravesical Bacillus Calmette-Guerin
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Talukder, Rafee, Makrakis, Dimitrios, Diamantopoulos, Leonidas N, Carril-Ajuria, Lucia, Castellano, Daniel, De Kouchkovsky, Ivan, Koshkin, Vadim S, Park, Joseph J, Alva, Ajjai, Bilen, Mehmet A, Stewart, Tyler F, McKay, Rana R, Santos, Victor S, Agarwal, Neeraj, Jain, Jayanshu, Zakharia, Yousef, Morales-Barrera, Rafael, Devitt, Michael E, Grant, Michael, Lythgoe, Mark P, Pinato, David J, Nelson, Ariel, Hoimes, Christopher J, Shreck, Evan, Gartrell, Benjamin A, Sankin, Alex, Tripathi, Abhishek, Zakopoulou, Roubini, Bamias, Aristotelis, Murgic, Jure, Fröbe, Ana, Rodriguez-Vida, Alejo, Drakaki, Alexandra, Liu, Sandy, Kumar, Vivek, Lorenzo, Giuseppe Di, Joshi, Monika, Velho, Pedro Isaacsson, Buznego, Lucia Alonso, Duran, Ignacio, Moses, Marcus, Barata, Pedro, Sonpavde, Guru, Yu, Evan Y, Wright, Jonathan L, Grivas, Petros, and Khaki, Ali Raza
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Immunology ,Precision Medicine ,Cancer ,6.1 Pharmaceuticals ,Good Health and Well Being ,Adjuvants ,Immunologic ,Administration ,Intravesical ,BCG Vaccine ,Carcinoma ,Transitional Cell ,Humans ,Immune Checkpoint Inhibitors ,Neoplasm Recurrence ,Local ,Retrospective Studies ,Urinary Bladder Neoplasms ,Bladder cancer ,BCG ,Immunotherapy ,Outcomes ,Urinary tract neoplasms ,Public Health and Health Services ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
BackgroundImmune checkpoint inhibitors (ICI) improve overall survival (OS) in patients with locally advanced, unresectable, or metastatic urothelial carcinoma (aUC), but response rates can be modest. We compared outcomes between patients with and without prior intravesical Bacillus Calmette-Guerin (BCG), who received ICI for aUC, hypothesizing that prior intravesical BCG would be associated with worse outcomes.Patients and methodsWe performed a retrospective cohort study across 25 institutions in US and Europe. We compared observed response rate (ORR) using logistic regression; progression-free survival (PFS) and OS using Kaplan-Meier and Cox proportional hazards. Analyses were stratified by treatment line (first line/salvage) and included multivariable models adjusting for known prognostic factors.ResultsA total of 1026 patients with aUC were identified; 614, 617, and 638 were included in ORR, OS, PFS analyses, respectively. Overall, 150 pts had history of prior intravesical BCG treatment. ORR to ICI was similar between those with and without prior intravesical BCG exposure in both first line and salvage settings (adjusted odds radios 0.55 [P= .08] and 1.65 [P= .12]). OS (adjusted hazard ratios 1.05 [P= .79] and 1.13 [P= .49]) and PFS (adjusted hazard ratios 1.12 [P= .55] and 0.87 [P= .39]) were similar between those with and without intravesical BCG exposure in first line and salvage settings.ConclusionPrior intravesical BCG was not associated with differences in response and survival in patients with aUC treated with ICI. Limitations include retrospective nature, lack of randomization, presence of selection and confounding biases. This study provides important preliminary data that prior intravesical BCG exposure may not impact ICI efficacy in aUC.
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- 2022
28. TROPHY-U-01, a phase II open-label study of sacituzumab govitecan in patients with metastatic urothelial carcinoma progressing after platinum-based chemotherapy and checkpoint inhibitors: updated safety and efficacy outcomes
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Loriot, Y., Petrylak, D.P., Rezazadeh Kalebasty, A., Fléchon, A., Jain, R.K., Gupta, S., Bupathi, M., Beuzeboc, P., Palmbos, P., Balar, A.V., Kyriakopoulos, C.E., Pouessel, D., Sternberg, C.N., Tonelli, J., Sierecki, M., Zhou, H., Grivas, P., Barthélémy, P., and Tagawa, S.T.
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- 2024
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29. Inter-annual trends of ultrafine particles in urban Europe
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Meritxell Garcia-Marlès, Rosa Lara, Cristina Reche, Noemí Pérez, Aurelio Tobías, Marjan Savadkoohi, David Beddows, Imre Salma, Máté Vörösmarty, Tamás Weidinger, Christoph Hueglin, Nikos Mihalopoulos, Georgios Grivas, Panayiotis Kalkavouras, Jakub Ondráček, Nadĕžda Zíková, Jarkko V. Niemi, Hanna E. Manninen, David C. Green, Anja H. Tremper, Michael Norman, Stergios Vratolis, Konstantinos Eleftheriadis, Francisco J. Gómez-Moreno, Elisabeth Alonso-Blanco, Alfred Wiedensohler, Kay Weinhold, Maik Merkel, Susanne Bastian, Barbara Hoffmann, Hicran Altug, Jean-Eudes Petit, Olivier Favez, Sebastiao Martins Dos Santos, Jean-Philippe Putaud, Adelaide Dinoi, Daniele Contini, Hilkka Timonen, Janne Lampilahti, Tuukka Petäjä, Marco Pandolfi, Philip K. Hopke, Roy M. Harrison, Andrés Alastuey, and Xavier Querol
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Nanoparticles ,Particle number concentrations ,Air quality ,Ambient air ,Environmental sciences ,GE1-350 - Abstract
Ultrafine particles (UFP, those with diameters ≤ 100 nm), have been reported to potentially penetrate deeply into the respiratory system, translocate through the alveoli, and affect various organs, potentially correlating with increased mortality. The aim of this study is to assess long-term trends (5–11 years) in mostly urban UFP concentrations based on measurements of particle number size distributions (PNSD). Additionally, concentrations of other pollutants and meteorological variables were evaluated to support the interpretations. PNSD datasets from 12 urban background (UB), 5 traffic (TR), 3 suburban background (SUB) and 1 regional background (RB) sites in 15 European cities and 1 in the USA were evaluated. The non-parametric Theil-Sen’s method was used to detect monotonic trends. Meta-analyses were carried out to assess the overall trends and those for different environments. The results showed significant decreases in NO, NO2, BC, CO, and particle concentrations in the Aitken (25–100 nm) and the Accumulation (100–800 nm) modes, suggesting a positive impact of the implementation of EURO 5/V and 6/VI vehicle standards on European air quality. The growing use of Diesel Particle Filters (DPFs) might also have clearly reduced exhaust emissions of BC, PM, and the Aitken and Accumulation mode particles. However, as reported by prior studies, there remains an issue of poor control of Nucleation mode particles (smaller than 25 nm), which are not fully reduced with current DPFs, without emission controls for semi-volatile organic compounds, and might have different origins than road traffic. Thus, contrasting trends for Nucleation mode particles were obtained across the cities studied. This mode also affected the UFP and total PNC trends because of the high proportion of Nucleation mode particles in both concentration ranges. It was also found that the urban temperature increasing trends might have also influenced those of PNC, Nucleation and Aitken modes.
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- 2024
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30. Adverse events of immune checkpoint therapy alone versus when combined with vascular endothelial growth factor inhibitors: a pooled meta-analysis of 1735 patients
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Iuliia Kovalenko, Wern Lynn Ng, Yimin Geng, Yinghong Wang, Pavlos Msaouel, Shailender Bhatia, Petros Grivas, Raed Benkhadra, and Omar Alhalabi
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cancer ,immunotherapy ,toxicity ,adverse events ,immune checkpoint inhibitor ,vascular endothelial - growth factor ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
BackgroundCombining immune checkpoint therapy (ICT) and vascular endothelial growth factor inhibitors (VEGFi) may result in increased treatment-related and immune-related adverse events (TRAEs and irAEs) compared to ICT alone. This metanalysis was conducted to identify prospective phase II or III clinical studies that evaluated the toxicity profile of ICT + VEGFi compared to ICT alone.MethodsA systematic search was performed across all cancer types and major databases until August 10, 2022, and screening was done by two independent investigators. Inclusion criteria included phase 2 or 3 studies with at least one arm of patients treated with combination therapy and one arm treated with monotherapy. Adverse event data were pooled using a restricted maximum likelihood fixed effects model, and heterogeneity using Cochran’s Q (chi-square) test.Results7 out of 9366 studies met the inclusion criteria, and 808 and 927 patients were treated with ICT monotherapy and a combination of ICT with VEGFi, respectively. Only one study reported irAEs, so the analysis was restricted to TRAEs. The total number of TRAEs was significantly higher in the ICT + VEGFi group (RR:1.49; 95% CI 1.37 -1.62; p=1.5×10-21), and more frequent treatment withdrawals were attributed to TRAEs (RR:3.10; 95% CI 1.12-8.59; p=0.029). The highest TRAE effect size increases noted for rash (RR 6.50; 95% CI 3.76 – 11.25; p=2.1×10-11), hypertension (RR:6.07; 95% CI 3.69–10.00; p=1.3×10-12), hypothyroidism (RR:5.02; 95% CI 3.08 – 8.19; p=8.9×10-11), and diarrhea (RR:4.94; 95% CI 3.21–7.62; p=3.8×10-13). Other significantly more frequent TRAEs included nausea, anemia, anorexia, and proteinuria.ConclusionCombination therapy with ICT and VEGFi carries a higher risk of certain TRAEs, such as rash, hypertension, hypothyroidism, diarrhea, nausea, anorexia, and proteinuria, compared to ICT monotherapy. More granular details on the cause of AEs, particularly irAEs, should be provided in future trials of such regimens.
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- 2024
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31. Geriatric risk factors for serious COVID-19 outcomes among older adults with cancer: a cohort study from the COVID-19 and Cancer Consortium
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Elkrief, Arielle, Hennessy, Cassandra, Kuderer, Nicole M, Rubinstein, Samuel M, Wulff-Burchfield, Elizabeth, Rosovsky, Rachel P, Vega-Luna, Karen, Thompson, Michael A, Panagiotou, Orestis A, Desai, Aakash, Rivera, Donna R, Khaki, Ali Raza, Tachiki, Lisa, Lynch, Ryan C, Stratton, Catherine, Elias, Rawad, Batist, Gerald, Kasi, Anup, Shah, Dimpy P, Bakouny, Ziad, Cabal, Angelo, Clement, Jessica, Crowell, Jennifer, Dixon, Becky, Friese, Christopher R, Fry, Stacy L, Grover, Punita, Gulati, Shuchi, Gupta, Shilpa, Hwang, Clara, Khan, Hina, Kim, Soo Jung, Klein, Elizabeth J, Labaki, Chris, McKay, Rana R, Nizam, Amanda, Pennell, Nathan A, Puc, Matthew, Schmidt, Andrew L, Shahrokni, Armin, Shaya, Justin A, Su, Christopher T, Wall, Sarah, Williams, Nicole, Wise-Draper, Trisha M, Mishra, Sanjay, Grivas, Petros, French, Benjamin, Warner, Jeremy L, Wildes, Tanya M, and Consortium, COVID-19 and Cancer
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Epidemiology ,Public Health ,Health Sciences ,Clinical Research ,Aging ,Cancer ,Prevention ,Good Health and Well Being ,Aged ,COVID-19 ,COVID-19 Testing ,Cohort Studies ,Humans ,Middle Aged ,Neoplasms ,Risk Factors ,SARS-CoV-2 ,COVID-19 and Cancer Consortium ,Public health - Abstract
BackgroundOlder age is associated with poorer outcomes of SARS-CoV-2 infection, although the heterogeneity of ageing results in some older adults being at greater risk than others. The objective of this study was to quantify the association of a novel geriatric risk index, comprising age, modified Charlson comorbidity index, and Eastern Cooperative Oncology Group performance status, with COVID-19 severity and 30-day mortality among older adults with cancer.MethodsIn this cohort study, we enrolled patients aged 60 years and older with a current or previous cancer diagnosis (excluding those with non-invasive cancers and premalignant or non-malignant conditions) and a current or previous laboratory-confirmed COVID-19 diagnosis who reported to the COVID-19 and Cancer Consortium (CCC19) multinational, multicentre, registry between March 17, 2020, and June 6, 2021. Patients were also excluded for unknown age, missing data resulting in unknown geriatric risk measure, inadequate data quality, or incomplete follow-up resulting in unknown COVID-19 severity. The exposure of interest was the CCC19 geriatric risk index. The primary outcome was COVID-19 severity and the secondary outcome was 30-day all-cause mortality; both were assessed in the full dataset. Adjusted odds ratios (ORs) and 95% CIs were estimated from ordinal and binary logistic regression models.Findings5671 patients with cancer and COVID-19 were included in the analysis. Median follow-up time was 56 days (IQR 22-120), and median age was 72 years (IQR 66-79). The CCC19 geriatric risk index identified 2365 (41·7%) patients as standard risk, 2217 (39·1%) patients as intermediate risk, and 1089 (19·2%) as high risk. 36 (0·6%) patients were excluded due to non-calculable geriatric risk index. Compared with standard-risk patients, high-risk patients had significantly higher COVID-19 severity (adjusted OR 7·24; 95% CI 6·20-8·45). 920 (16·2%) of 5671 patients died within 30 days of a COVID-19 diagnosis, including 161 (6·8%) of 2365 standard-risk patients, 409 (18·5%) of 2217 intermediate-risk patients, and 350 (32·1%) of 1089 high-risk patients. High-risk patients had higher adjusted odds of 30-day mortality (adjusted OR 10·7; 95% CI 8·54-13·5) than standard-risk patients.InterpretationThe CCC19 geriatric risk index was strongly associated with COVID-19 severity and 30-day mortality. Our CCC19 geriatric risk index, based on readily available clinical factors, might provide clinicians with an easy-to-use risk stratification method to identify older adults most at risk for severe COVID-19 as well as mortality.FundingUS National Institutes of Health National Cancer Institute Cancer Center.
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- 2022
32. Demographics, Outcomes, and Risk Factors for Patients with Sarcoma and COVID-19: A CCC19-Registry Based Retrospective Cohort Study
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Wagner, Michael J, Hennessy, Cassandra, Beeghly, Alicia, French, Benjamin, Shah, Dimpy P, Croessmann, Sarah, Vilar-Compte, Diana, Ruiz-Garcia, Erika, Ingham, Matthew, Schwartz, Gary K, Painter, Corrie A, Chugh, Rashmi, Fecher, Leslie, Park, Cathleen, Zamulko, Olga, Trent, Jonathan C, Subbiah, Vivek, Khaki, Ali Raza, Tachiki, Lisa, Nakasone, Elizabeth S, Loggers, Elizabeth T, Labaki, Chris, Saliby, Renee Maria, McKay, Rana R, Ajmera, Archana, Griffiths, Elizabeth A, Puzanov, Igor, Tap, William D, Hwang, Clara, Tejwani, Sheela, Jhawar, Sachin R, Hayes-Lattin, Brandon, Wulff-Burchfield, Elizabeth, Kasi, Anup, Reuben, Daniel Y, Nagaraj, Gayathri, Joshi, Monika, Polimera, Hyma, Kulkarni, Amit A, Esfahani, Khashayar, Kwon, Daniel H, Paoluzzi, Luca, Bilen, Mehmet A, Durbin, Eric B, Grivas, Petros, Warner, Jeremy L, and Davis, Elizabeth J
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Rare Diseases ,Cancer ,Prevention ,Pediatric Cancer ,Clinical Research ,Pediatric ,Pediatric Research Initiative ,Aetiology ,2.4 Surveillance and distribution ,Good Health and Well Being ,sarcoma ,COVID-19 ,SARS-CoV-2 ,CCC19 ,COVID-19 and Cancer Consortium ,Oncology and carcinogenesis - Abstract
BackgroundPatients with sarcoma often require individualized treatment strategies and are likely to receive aggressive immunosuppressive therapies, which may place them at higher risk for severe COVID-19. We aimed to describe demographics, risk factors, and outcomes for patients with sarcoma and COVID-19.MethodsWe performed a retrospective cohort study of patients with sarcoma and COVID-19 reported to the COVID-19 and Cancer Consortium (CCC19) registry (NCT04354701) from 17 March 2020 to 30 September 2021. Demographics, sarcoma histologic type, treatments, and COVID-19 outcomes were analyzed.Resultsof 281 patients, 49% (n = 139) were hospitalized, 33% (n = 93) received supplemental oxygen, 11% (n = 31) were admitted to the ICU, and 6% (n = 16) received mechanical ventilation. A total of 23 (8%) died within 30 days of COVID-19 diagnosis and 44 (16%) died overall at the time of analysis. When evaluated by sarcoma subtype, patients with bone sarcoma and COVID-19 had a higher mortality rate than patients from a matched SEER cohort (13.5% vs 4.4%). Older age, poor performance status, recent systemic anti-cancer therapy, and lung metastases all contributed to higher COVID-19 severity.ConclusionsPatients with sarcoma have high rates of severe COVID-19 and those with bone sarcoma may have the greatest risk of death.
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- 2022
33. A Systematic Review of Natural Language Processing Applied to Radiology Reports
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Casey, Arlene, Davidson, Emma, Poon, Michael, Dong, Hang, Duma, Daniel, Grivas, Andreas, Grover, Claire, Suárez-Paniagua, Víctor, Tobin, Richard, Whiteley, William, Wu, Honghan, and Alex, Beatrice
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Computer Science - Computation and Language - Abstract
NLP has a significant role in advancing healthcare and has been found to be key in extracting structured information from radiology reports. Understanding recent developments in NLP application to radiology is of significance but recent reviews on this are limited. This study systematically assesses recent literature in NLP applied to radiology reports. Our automated literature search yields 4,799 results using automated filtering, metadata enriching steps and citation search combined with manual review. Our analysis is based on 21 variables including radiology characteristics, NLP methodology, performance, study, and clinical application characteristics. We present a comprehensive analysis of the 164 publications retrieved with each categorised into one of 6 clinical application categories. Deep learning use increases but conventional machine learning approaches are still prevalent. Deep learning remains challenged when data is scarce and there is little evidence of adoption into clinical practice. Despite 17% of studies reporting greater than 0.85 F1 scores, it is hard to comparatively evaluate these approaches given that most of them use different datasets. Only 14 studies made their data and 15 their code available with 10 externally validating results. Automated understanding of clinical narratives of the radiology reports has the potential to enhance the healthcare process but reproducibility and explainability of models are important if the domain is to move applications into clinical use. More could be done to share code enabling validation of methods on different institutional data and to reduce heterogeneity in reporting of study properties allowing inter-study comparisons. Our results have significance for researchers providing a systematic synthesis of existing work to build on, identify gaps, opportunities for collaboration and avoid duplication.
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- 2021
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34. The CoVID‐TE risk assessment model for venous thromboembolism in hospitalized patients with cancer and COVID‐19
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Li, Ang, Kuderer, Nicole M, Hsu, Chih‐Yuan, Shyr, Yu, Warner, Jeremy L, Shah, Dimpy P, Kumar, Vaibhav, Shah, Surbhi, Kulkarni, Amit A, Fu, Julie, Gulati, Shuchi, Zon, Rebecca L, Li, Monica, Desai, Aakash, Egan, Pamela C, Bakouny, Ziad, Devendra, KC, Hwang, Clara, Akpan, Imo J, McKay, Rana R, Girard, Jennifer, Schmidt, Andrew L, Halmos, Balazs, Thompson, Michael A, Patel, Jaymin M, Pennell, Nathan A, Peters, Solange, Elshoury, Amro, de Lima Lopes, Gilbero, Stover, Daniel G, Grivas, Petros, Rini, Brian I, Painter, Corrie A, Mishra, Sanjay, Connors, Jean M, Lyman, Gary H, Rosovsky, Rachel P, and consortium, the CCC19
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Clinical Research ,Prevention ,Hematology ,Cancer ,COVID-19 ,Cohort Studies ,Humans ,Neoplasms ,Risk Assessment ,SARS-CoV-2 ,Venous Thromboembolism ,clinical decision rules ,thrombosis ,venous thromboembolism ,CCC19 consortium ,Cardiorespiratory Medicine and Haematology ,Clinical Sciences ,Cardiovascular System & Hematology ,Cardiovascular medicine and haematology ,Clinical sciences - Abstract
BackgroundHospitalized patients with COVID-19 have increased risks of venous (VTE) and arterial thromboembolism (ATE). Active cancer diagnosis and treatment are well-known risk factors; however, a risk assessment model (RAM) for VTE in patients with both cancer and COVID-19 is lacking.ObjectivesTo assess the incidence of and risk factors for thrombosis in hospitalized patients with cancer and COVID-19.MethodsAmong patients with cancer in the COVID-19 and Cancer Consortium registry (CCC19) cohort study, we assessed the incidence of VTE and ATE within 90 days of COVID-19-associated hospitalization. A multivariable logistic regression model specifically for VTE was built using a priori determined clinical risk factors. A simplified RAM was derived and internally validated using bootstrap.ResultsFrom March 17, 2020 to November 30, 2020, 2804 hospitalized patients were analyzed. The incidence of VTE and ATE was 7.6% and 3.9%, respectively. The incidence of VTE, but not ATE, was higher in patients receiving recent anti-cancer therapy. A simplified RAM for VTE was derived and named CoVID-TE (Cancer subtype high to very-high risk by original Khorana score +1, VTE history +2, ICU admission +2, D-dimer elevation +1, recent systemic anti-cancer Therapy +1, and non-Hispanic Ethnicity +1). The RAM stratified patients into two cohorts (low-risk, 0-2 points, n = 1423 vs. high-risk, 3+ points, n = 1034) where VTE occurred in 4.1% low-risk and 11.3% high-risk patients (c statistic 0.67, 95% confidence interval 0.63-0.71). The RAM performed similarly well in subgroups of patients not on anticoagulant prior to admission and moderately ill patients not requiring direct ICU admission.ConclusionsHospitalized patients with cancer and COVID-19 have elevated thrombotic risks. The CoVID-TE RAM for VTE prediction may help real-time data-driven decisions in this vulnerable population.
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- 2021
35. Spatiotemporal Gradients of PAH Concentrations in Greek Cities and Associated Exposure Impacts
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Irini Tsiodra, Kalliopi Tavernaraki, Georgios Grivas, Constantine Parinos, Kyriaki Papoutsidaki, Despina Paraskevopoulou, Eleni Liakakou, Alexandra Gogou, Aikaterini Bougiatioti, Evangelos Gerasopoulos, Maria Kanakidou, and Nikolaos Mihalopoulos
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polycyclic aromatic hydrocarbons ,benzo(a)pyrene ,diagnostic ratio ,biomass burning ,exposure risk ,Greece ,Chemical technology ,TP1-1185 - Abstract
To study the spatiotemporal variability of particle-bound polycyclic aromatic hydrocarbons (PAHs) and assess their carcinogenic potential in six contrasting urban environments in Greece, a total of 305 filter samples were collected and analyzed. Sampling sites included a variety of urban background, traffic (Athens, Ioannina and Heraklion), rural (Xanthi) and near-port locations (Piraeus and Volos). When considering the sum of 16 U.S. EPA priority PAHs, as well as that of the six EU-proposed members, average concentrations observed across locations during summer varied moderately (0.4–2.2 ng m−3) and independently of the population of each site, with the highest values observed in the areas of Piraeus and Volos that are affected by port and industrial activities. Winter levels were significantly higher and more spatially variable compared to summer, with the seasonal enhancement ranging from 7 times in Piraeus to 98 times in Ioannina, indicating the large impact of PAH emissions from residential wood burning. Regarding benzo(a)pyrene (BaP), an IARC Group 1 carcinogen and the only EU-regulated PAH, the winter/summer ratios were 24–33 in Athens, Volos, Heraklion and Xanthi; 60 in Piraeus; and 480 in Ioannina, which is afflicted by severe wood-burning pollution events. An excellent correlation was observed between organic carbon (OC) and benzo(a)pyrene (BaP) during the cold period at all urban sites (r2 > 0.8) with stable BaP/OC slopes (0.09–0.14 × 10−3), highlighting the potential use of OC as a proxy for the estimation of BaP in winter conditions. The identified spatiotemporal contrasts, which were explored for the first time for PAHs at such a scale in the Eastern Mediterranean, provide important insights into sources and controlling atmospheric conditions and reveal large deviations in exposure risks among cities that raise the issue of environmental injustice on a national level.
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- 2024
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36. Are the Spinal Changes in the Course of Scoliogeny Primary but Secondary?
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Theodoros B. Grivas, Elias Vasiliadis, Christina Mazioti, Despina Papagianni, Aristea Mamzeri, Michail Chandrinos, George Vynichakis, Konstantinos Athanasopoulos, Paschalis Christodoulides, Nikola Jevtic, Samra Pjanic, Danka Ljubojevic, Olga Savvidou, Angelos Kaspiris, and Jarrett Grunstein
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idiopathic scoliosis ,vertebral spine ,rib cage ,genetics ,epigenetics ,sleep ,Medicine - Abstract
In this opinion article, there is an analysis and discussion regarding the effects of growth on the spinal and rib cage deformities, the role of the rib cage in scoliogeny, the lateral spinal profile in adolescent idiopathic scoliosis (AIS), the genetics and epigenetics of AIS, and the interesting and novel field investigating the sleep impact at nighttime on AIS in relation to the sequence of the scoliogenetic changes in scoliotics. The expressed opinions are mainly based on the published peer-reviewed research of the author and his team of co-authors. Based on the analysis noted above, it can be postulated that the vertebral growth changes in the spine during initial idiopathic scoliosis (IS) development are not primary-intrinsic but secondary changes. The primary cause starting the deformity is not located within the vertebral bodies. Instead, the deformations seen in the vertebral bodies are the secondary effects of asymmetrical loads exerted upon them, due to muscular loads, growth, and gravity.
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- 2024
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37. Bipolar androgen therapy plus olaparib in men with metastatic castration-resistant prostate cancer
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Schweizer, Michael T., Gulati, Roman, Yezefski, Todd, Cheng, Heather H., Mostaghel, Elahe, Haffner, Michael C., Patel, Radhika A., De Sarkar, Navonil, Ha, Gavin, Dumpit, Ruth, Woo, Brianna, Lin, Aaron, Panlasigui, Patrick, McDonald, Nerina, Lai, Michael, Nega, Katie, Hammond, Jeannette, Grivas, Petros, Hsieh, Andrew, Montgomery, Bruce, Nelson, Peter S., and Yu, Evan Y.
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- 2023
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38. Phase II trial of CV301 vaccine combined with atezolizumab in advanced urothelial carcinoma
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Sonpavde, Guru P., Maughan, Benjamin Louis, McGregor, Bradley Alexander, Wei, Xiao X., Kilbridge, Kerry L., Lee, Richard J., Yu, Evan Y., Schweizer, Michael Thomas, Montgomery, Robert B., Cheng, Heather H., Hsieh, Andrew Caleb, Jain, Rohit, Grewal, Jaspreet S., Pico-Navarro, Cesar, Gafoor, Zarina, Perschy, Teresa, and Grivas, Petros
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- 2023
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39. Rezūm water vapor therapy for the treatment of patients with urinary retention and permanent catheter dependence secondary to benign prostate hyperplasia: a systematic review of the literature
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Spinos, Theodoros, Katafigiotis, Ioannis, Leotsakos, Ioannis, Grivas, Nikolaos, Zabaftis, Christos, Ermidis, Dimitrios, Sfoungaristos, Stavros, and Karavitakis, Markos
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- 2023
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40. A direct method to quantify methanol-soluble organic carbon for brown carbon absorption studies
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D. Paraskevopoulou, S. Bikkina, G. Grivas, D.G. Kaskaoutis, M. Tsagkaraki, K. Tavernaraki, and N. Mihalopoulos
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Direct determination of methanol-soluble organic carbon mass in filter samples ,Science - Abstract
The current research provides a newly developed method to quantify methanol-soluble organic carbon (MeS_OC) in aerosol samples. This analytical procedure allows an accurate separation of MeS-OC component, which is critical for the calculation of mass absorption efficiency (MAE) of ambient Brown Carbon (BrC) and consequently its climate relevant potential. The method includes extraction, filtering and condensation stages, leading to the preparation of a highly concentrated product in which MeS-OC can be precisely quantified by a Sunset Carbon Analyzer in a single analysis step. This method can be applied on aerosol collected using either high or low volume samplers, since a relatively small filter area is required for the determination. Furthermore, it eliminates any misestimation of the MeS-OC mass that may appear in other reported techniques that don't seem to include the precise separation of methanol-soluble fraction in their quantification process. • The mass quantification of methanol-soluble organic carbon is essential, contributing up to 50% to the absorptivity of organic aerosol (BrC) at shorter wavelengths. • The method provides a direct measurement of methanol-soluble aerosol components, resolving any potential uncertainties of previously applied methods. • The adoption of this direct quantification approach leads to a rationalization of past MAE estimates for BrC with implications for radiative transfer models.
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- 2023
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41. Clinical characteristics, racial inequities, and outcomes in patients with breast cancer and COVID-19: A COVID-19 and cancer consortium (CCC19) cohort study
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Gayathri Nagaraj, Shaveta Vinayak, Ali Raza Khaki, Tianyi Sun, Nicole M Kuderer, David M Aboulafia, Jared D Acoba, Joy Awosika, Ziad Bakouny, Nicole B Balmaceda, Ting Bao, Babar Bashir, Stephanie Berg, Mehmet A Bilen, Poorva Bindal, Sibel Blau, Brianne E Bodin, Hala T Borno, Cecilia Castellano, Horyun Choi, John Deeken, Aakash Desai, Natasha Edwin, Lawrence E Feldman, Daniel B Flora, Christopher R Friese, Matthew D Galsky, Cyndi J Gonzalez, Petros Grivas, Shilpa Gupta, Marcy Haynam, Hannah Heilman, Dawn L Hershman, Clara Hwang, Chinmay Jani, Sachin R Jhawar, Monika Joshi, Virginia Kaklamani, Elizabeth J Klein, Natalie Knox, Vadim S Koshkin, Amit A Kulkarni, Daniel H Kwon, Chris Labaki, Philip E Lammers, Kate I Lathrop, Mark A Lewis, Xuanyi Li, Gilbert de Lima Lopes, Gary H Lyman, Della F Makower, Abdul-Hai Mansoor, Merry-Jennifer Markham, Sandeep H Mashru, Rana R McKay, Ian Messing, Vasil Mico, Rajani Nadkarni, Swathi Namburi, Ryan H Nguyen, Taylor Kristian Nonato, Tracey Lynn O'Connor, Orestis A Panagiotou, Kyu Park, Jaymin M Patel, Kanishka GopikaBimal Patel, Jeffrey Peppercorn, Hyma Polimera, Matthew Puc, Yuan James Rao, Pedram Razavi, Sonya A Reid, Jonathan W Riess, Donna R Rivera, Mark Robson, Suzanne J Rose, Atlantis D Russ, Lidia Schapira, Pankil K Shah, M Kelly Shanahan, Lauren C Shapiro, Melissa Smits, Daniel G Stover, Mitrianna Streckfuss, Lisa Tachiki, Michael A Thompson, Sara M Tolaney, Lisa B Weissmann, Grace Wilson, Michael T Wotman, Elizabeth M Wulff-Burchfield, Sanjay Mishra, Benjamin French, Jeremy L Warner, Maryam B Lustberg, Melissa K Accordino, Dimpy P Shah, and On behalf of the COVID-19 and Cancer Consortium
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breast cancer ,SARS-CoV-2 ,COVID-19 ,racial inequities ,oncology ,pandemic ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
Background: Limited information is available for patients with breast cancer (BC) and coronavirus disease 2019 (COVID-19), especially among underrepresented racial/ethnic populations. Methods: This is a COVID-19 and Cancer Consortium (CCC19) registry-based retrospective cohort study of females with active or history of BC and laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection diagnosed between March 2020 and June 2021 in the US. Primary outcome was COVID-19 severity measured on a five-level ordinal scale, including none of the following complications, hospitalization, intensive care unit admission, mechanical ventilation, and all-cause mortality. Multivariable ordinal logistic regression model identified characteristics associated with COVID-19 severity. Results: 1383 female patient records with BC and COVID-19 were included in the analysis, the median age was 61 years, and median follow-up was 90 days. Multivariable analysis revealed higher odds of COVID-19 severity for older age (aOR per decade, 1.48 [95% CI, 1.32–1.67]); Black patients (aOR 1.74; 95 CI 1.24–2.45), Asian Americans and Pacific Islander patients (aOR 3.40; 95 CI 1.70–6.79) and Other (aOR 2.97; 95 CI 1.71–5.17) racial/ethnic groups; worse ECOG performance status (ECOG PS ≥2: aOR, 7.78 [95% CI, 4.83–12.5]); pre-existing cardiovascular (aOR, 2.26 [95% CI, 1.63–3.15])/pulmonary comorbidities (aOR, 1.65 [95% CI, 1.20–2.29]); diabetes mellitus (aOR, 2.25 [95% CI, 1.66–3.04]); and active and progressing cancer (aOR, 12.5 [95% CI, 6.89–22.6]). Hispanic ethnicity, timing, and type of anti-cancer therapy modalities were not significantly associated with worse COVID-19 outcomes. The total all-cause mortality and hospitalization rate for the entire cohort was 9% and 37%, respectively however, it varied according to the BC disease status. Conclusions: Using one of the largest registries on cancer and COVID-19, we identified patient and BC-related factors associated with worse COVID-19 outcomes. After adjusting for baseline characteristics, underrepresented racial/ethnic patients experienced worse outcomes compared to non-Hispanic White patients. Funding: This study was partly supported by National Cancer Institute grant number P30 CA068485 to Tianyi Sun, Sanjay Mishra, Benjamin French, Jeremy L Warner; P30-CA046592 to Christopher R Friese; P30 CA023100 for Rana R McKay; P30-CA054174 for Pankil K Shah and Dimpy P Shah; KL2 TR002646 for Pankil Shah and the American Cancer Society and Hope Foundation for Cancer Research (MRSG-16-152-01-CCE) and P30-CA054174 for Dimpy P Shah. REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research grant support (UL1 TR000445 from NCATS/NIH). The funding sources had no role in the writing of the manuscript or the decision to submit it for publication. Clinical trial number: CCC19 registry is registered on ClinicalTrials.gov, NCT04354701.
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- 2023
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42. Re. van den Berg et al, Deep learning for automated contouring of neurovascular structures on magnetic resonance imaging for prostate cancer patients
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Nikolaos Grivas, Inge Cox, Thierry Boellaard, and Henk van der Poel
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Medical physics. Medical radiology. Nuclear medicine ,R895-920 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2023
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43. A New Prognostic Model in Patients with Advanced Urothelial Carcinoma Treated with First-line Immune Checkpoint Inhibitors
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Khaki, Ali Raza, Li, Ang, Diamantopoulos, Leonidas N, Miller, Natalie J, Carril-Ajuria, Lucia, Castellano, Daniel, De Kouchkovsky, Ivan, Koshkin, Vadim, Park, Joseph, Alva, Ajjai, Bilen, Mehmet A, Stewart, Tyler, Santos, Victor, Agarwal, Neeraj, Jain, Jayanshu, Zakharia, Yousef, Morales-Barrera, Rafael, Devitt, Michael, Nelson, Ariel, Hoimes, Christopher J, Shreck, Evan, Gartrell, Benjamin A, Sankin, Alex, Tripathi, Abhishek, Zakopoulou, Roubini, Bamias, Aristotelis, Rodriguez-Vida, Alejo, Drakaki, Alexandra, Liu, Sandy, Kumar, Vivek, Lythgoe, Mark P, Pinato, David J, Murgic, Jure, Fröbe, Ana, Joshi, Monika, Isaacsson Velho, Pedro, Hahn, Noah, Alonso Buznego, Lucia, Duran, Ignacio, Moses, Marcus, Barata, Pedro, Galsky, Matthew D, Sonpavde, Guru, Yu, Evan Y, Shankaran, Veena, Lyman, Gary H, and Grivas, Petros
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Immunology ,Clinical Research ,Patient Safety ,Cancer ,Digestive Diseases ,Prevention ,Liver Disease ,Aged ,Carcinoma ,Transitional Cell ,Cohort Studies ,Female ,Humans ,Immune Checkpoint Inhibitors ,Prognosis ,Retrospective Studies ,Urinary Bladder Neoplasms ,Bladder cancer ,Immunotherapy ,Outcome research ,Prognostic model ,Urothelial carcinoma ,Clinical sciences ,Oncology and carcinogenesis - Abstract
BackgroundWhile immune checkpoint inhibitors (ICIs) are approved in the first-line (1L) setting for cisplatin-unfit patients with programmed death-ligand 1 (PD-L1)-high tumors or for platinum (cisplatin/carboplatin)-unfit patients, response rates remain modest and outcomes vary with no clinically useful biomarkers (except for PD-L1).ObjectiveWe aimed to develop a prognostic model for overall survival (OS) in patients receiving 1L ICIs for advanced urothelial cancer (aUC) in a multicenter cohort study.Design, setting, and participantsPatients treated with 1L ICIs for aUC across 24 institutions and five countries (in the USA and Europe) outside clinical trials were included in this study.Outcome measurements and statistical analysisWe used a stepwise, hypothesis-driven approach using clinician-selected covariates to develop a new risk score for patients receiving ICIs in the 1L setting. Demographics, clinicopathologic data, treatment patterns, and OS were collected uniformly. Univariate Cox regression was performed on 18 covariates hypothesized to be associated with OS based on published data. Variables were retained for multivariate analysis (MVA) if they correlated with OS (p < 0.2) and were included in the final model if p < 0.05 on MVA. Retained covariates were assigned points based on the beta coefficient to create a risk score. Stratified median OS and C-statistic were calculated.Results and limitationsAmong 984 patients, 357 with a mean age of 71 yr were included in the analysis, 27% were female, 68% had pure UC, and 13% had upper tract UC. Eastern Cooperative Oncology Group performance status ≥2, albumin 5, and liver metastases were significant prognostic factors on MVA and were included in the risk score. C index for new 1L risk score was 0.68 (95% confidence interval 0.65-0.71). Limitations include retrospective nature and lack of external validation.ConclusionsWe developed a new 1L ICI risk score for OS based on data from patients with aUC treated with ICIs in the USA and Europe outside of clinical trials. The score components highlight readily available factors related to tumor biology and treatment response. External validation is being pursued.Patient summaryWith multiple new treatments under development and approved for advanced urothelial carcinoma, it can be difficult to identify the best treatment sequence for each patient. The risk score may help inform treatment discussions and estimate outcomes in patients treated with first-line immune checkpoint inhibitors, while it can also impact clinical trial design and endpoints. TAKE HOME MESSAGE: A new risk score was developed for advanced urothelial carcinoma treated with first-line immune checkpoint inhibitors. The score assigned Eastern Cooperative Oncology Group performance status ≥2, albumin 5, and liver metastases each one point, with a higher score being associated with worse overall survival.
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- 2021
44. Association of clinical factors and recent anticancer therapy with COVID-19 severity among patients with cancer: a report from the COVID-19 and Cancer Consortium
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Grivas, P, Khaki, AR, Wise-Draper, TM, French, B, Hennessy, C, Hsu, C-Y, Shyr, Y, Li, X, Choueiri, TK, Painter, CA, Peters, S, Rini, BI, Thompson, MA, Mishra, S, Rivera, DR, Acoba, JD, Abidi, MZ, Bakouny, Z, Bashir, B, Bekaii-Saab, T, Berg, S, Bernicker, EH, Bilen, MA, Bindal, P, Bishnoi, R, Bouganim, N, Bowles, DW, Cabal, A, Caimi, PF, Chism, DD, Crowell, J, Curran, C, Desai, A, Dixon, B, Doroshow, DB, Durbin, EB, Elkrief, A, Farmakiotis, D, Fazio, A, Fecher, LA, Flora, DB, Friese, CR, Fu, J, Gadgeel, SM, Galsky, MD, Gill, DM, Glover, MJ, Goyal, S, Grover, P, Gulati, S, Gupta, S, Halabi, S, Halfdanarson, TR, Halmos, B, Hausrath, DJ, Hawley, JE, Hsu, E, Huynh-Le, M, Hwang, C, Jani, C, Jayaraj, A, Johnson, DB, Kasi, A, Khan, H, Koshkin, VS, Kuderer, NM, Kwon, DH, Lammers, PE, Li, A, Loaiza-Bonilla, A, Low, CA, Lustberg, MB, Lyman, GH, McKay, RR, McNair, C, Menon, H, Mesa, RA, Mico, V, Mundt, D, Nagaraj, G, Nakasone, ES, Nakayama, J, Nizam, A, Nock, NL, Park, C, Patel, JM, Patel, KG, Peddi, P, Pennell, NA, Piper-Vallillo, AJ, Puc, M, Ravindranathan, D, Reeves, ME, Reuben, DY, Rosenstein, L, Rosovsky, RP, Rubinstein, SM, Salazar, M, Schmidt, AL, and Schwartz, GK
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Infectious Diseases ,Patient Safety ,Cancer ,Hematology ,Lung ,Clinical Research ,Prevention ,Good Health and Well Being ,Aged ,COVID-19 ,COVID-19 Testing ,Female ,Humans ,Male ,Neoplasms ,Pandemics ,SARS-CoV-2 ,SARS-CoV2 ,neoplasm ,cancer ,anticancer therapy ,laboratory measurements ,outcomes ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
BackgroundPatients with cancer may be at high risk of adverse outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We analyzed a cohort of patients with cancer and coronavirus 2019 (COVID-19) reported to the COVID-19 and Cancer Consortium (CCC19) to identify prognostic clinical factors, including laboratory measurements and anticancer therapies.Patients and methodsPatients with active or historical cancer and a laboratory-confirmed SARS-CoV-2 diagnosis recorded between 17 March and 18 November 2020 were included. The primary outcome was COVID-19 severity measured on an ordinal scale (uncomplicated, hospitalized, admitted to intensive care unit, mechanically ventilated, died within 30 days). Multivariable regression models included demographics, cancer status, anticancer therapy and timing, COVID-19-directed therapies, and laboratory measurements (among hospitalized patients).ResultsA total of 4966 patients were included (median age 66 years, 51% female, 50% non-Hispanic white); 2872 (58%) were hospitalized and 695 (14%) died; 61% had cancer that was present, diagnosed, or treated within the year prior to COVID-19 diagnosis. Older age, male sex, obesity, cardiovascular and pulmonary comorbidities, renal disease, diabetes mellitus, non-Hispanic black race, Hispanic ethnicity, worse Eastern Cooperative Oncology Group performance status, recent cytotoxic chemotherapy, and hematologic malignancy were associated with higher COVID-19 severity. Among hospitalized patients, low or high absolute lymphocyte count; high absolute neutrophil count; low platelet count; abnormal creatinine; troponin; lactate dehydrogenase; and C-reactive protein were associated with higher COVID-19 severity. Patients diagnosed early in the COVID-19 pandemic (January-April 2020) had worse outcomes than those diagnosed later. Specific anticancer therapies (e.g. R-CHOP, platinum combined with etoposide, and DNA methyltransferase inhibitors) were associated with high 30-day all-cause mortality.ConclusionsClinical factors (e.g. older age, hematological malignancy, recent chemotherapy) and laboratory measurements were associated with poor outcomes among patients with cancer and COVID-19. Although further studies are needed, caution may be required in utilizing particular anticancer therapies.Clinical trial identifierNCT04354701.
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- 2021
45. Adjuvant atezolizumab versus observation in muscle-invasive urothelial carcinoma (IMvigor010): a multicentre, open-label, randomised, phase 3 trial.
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Bellmunt, Joaquim, Hussain, Maha, Gschwend, Jürgen, Albers, Peter, Oudard, Stephane, Castellano, Daniel, Daneshmand, Siamak, Nishiyama, Hiroyuki, Majchrowicz, Martin, Degaonkar, Viraj, Shi, Yi, Mariathasan, Sanjeev, Grivas, Petros, Drakaki, Alexandra, ODonnell, Peter, Rosenberg, Jonathan, Geynisman, Daniel, Petrylak, Daniel, Hoffman-Censits, Jean, Bedke, Jens, Kalebasty, Arash, Zakharia, Yousef, van der Heijden, Michiel, Sternberg, Cora, Davarpanah, Nicole, and Powles, Thomas
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Adolescent ,Adult ,Aged ,Antibodies ,Monoclonal ,Antibodies ,Monoclonal ,Humanized ,Antineoplastic Agents ,Antineoplastic Combined Chemotherapy Protocols ,B7-H1 Antigen ,Carcinoma ,Transitional Cell ,Cisplatin ,Disease-Free Survival ,Female ,Humans ,Male ,Middle Aged ,Muscles ,Neoplasm Invasiveness ,Progression-Free Survival ,Urothelium - Abstract
BACKGROUND: Despite standard curative-intent treatment with neoadjuvant cisplatin-based chemotherapy, followed by radical surgery in eligible patients, muscle-invasive urothelial carcinoma has a high recurrence rate and no level 1 evidence for adjuvant therapy. We aimed to evaluate atezolizumab as adjuvant therapy in patients with high-risk muscle-invasive urothelial carcinoma. METHOD: In the IMvigor010 study, a multicentre, open-label, randomised, phase 3 trial done in 192 hospitals, academic centres, and community oncology practices across 24 countries or regions, patients aged 18 years and older with histologically confirmed muscle-invasive urothelial carcinoma and an Eastern Cooperative Oncology Group performance status of 0, 1, or 2 were enrolled within 14 weeks after radical cystectomy or nephroureterectomy with lymph node dissection. Patients had ypT2-4a or ypN+ tumours following neoadjuvant chemotherapy or pT3-4a or pN+ tumours if no neoadjuvant chemotherapy was received. Patients not treated with neoadjuvant chemotherapy must have been ineligible for or declined cisplatin-based adjuvant chemotherapy. No post-surgical radiotherapy or previous adjuvant chemotherapy was allowed. Patients were randomly assigned (1:1) using a permuted block (block size of four) method and interactive voice-web response system to receive 1200 mg atezolizumab given intravenously every 3 weeks for 16 cycles or up to 1 year, whichever occurred first, or to observation. Randomisation was stratified by previous neoadjuvant chemotherapy use, number of lymph nodes resected, pathological nodal status, tumour stage, and PD-L1 expression on tumour-infiltrating immune cells. The primary endpoint was disease-free survival in the intention-to-treat population. Safety was assessed in patients who either received at least one dose of atezolizumab or had at least one post-baseline safety assessment. This trial is registered with ClinicalTrials.gov, NCT02450331, and is ongoing but not recruiting patients. FINDINGS: Between Oct 5, 2015, and July 30, 2018, we enrolled 809 patients, of whom 406 were assigned to the atezolizumab group and 403 were assigned to the observation group. Median follow-up was 21·9 months (IQR 13·2-29·8). Median disease-free survival was 19·4 months (95% CI 15·9-24·8) with atezolizumab and 16·6 months (11·2-24·8) with observation (stratified hazard ratio 0·89 [95% CI 0·74-1·08]; p=0·24). The most common grade 3 or 4 adverse events were urinary tract infection (31 [8%] of 390 patients in the atezolizumab group vs 20 [5%] of 397 patients in the observation group), pyelonephritis (12 [3%]) vs 14 [4%]), and anaemia (eight [2%] vs seven [2%]). Serious adverse events occurred in 122 (31%) patients who received atezolizumab and 71 (18%) who underwent observation. 63 (16%) patients who received atezolizumab had a treatment-related grade 3 or 4 adverse event. One treatment-related death, due to acute respiratory distress syndrome, occurred in the atezolizumab group. INTERPRETATION: To our knowledge, IMvigor010 is the largest, first-completed phase 3 adjuvant study to evaluate the role of a checkpoint inhibitor in muscle-invasive urothelial carcinoma. The trial did not meet its primary endpoint of improved disease-free survival in the atezolizumab group over observation. Atezolizumab was generally tolerable, with no new safety signals; however, higher frequencies of adverse events leading to discontinuation were reported than in metastatic urothelial carcinoma studies. These data do not support the use of adjuvant checkpoint inhibitor therapy in the setting evaluated in IMvigor010 at this time. FUNDING: F Hoffmann-La Roche/Genentech.
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- 2021
46. Avelumab first-line maintenance treatment for advanced urothelial carcinoma: review of evidence to guide clinical practice
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Grivas, P., Grande, E., Davis, I.D., Moon, H.H., Grimm, M.-O., Gupta, S., Barthélémy, P., Thibault, C., Guenther, S., Hanson, S., and Sternberg, C.N.
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- 2023
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47. Sentinel Node Procedure to Select Clinically Localized Prostate Cancer Patients with Occult Nodal Metastases for Whole Pelvis Radiotherapy
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Hilda A. de Barros, Jan J. Duin, Daan Mulder, Vincent van der Noort, M. Arjen Noordzij, Esther M.K. Wit, Floris J. Pos, Wouter V. Vogel, Eva E. Schaake, Fijs W.B. van Leeuwen, Pim J. van Leeuwen, Nikolaos Grivas, and Henk G. van der Poel
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Prostate cancer ,Sentinel lymph node procedure ,Prostate-only radiotherapy ,Whole pelvis radiotherapy ,Diseases of the genitourinary system. Urology ,RC870-923 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: Accurate identification of men who harbor nodal metastases is necessary to select patients who most likely benefit from whole pelvis radiotherapy (WPRT). Limited sensitivity of diagnostic imaging approaches for the detection of nodal micrometastases has led to the exploration of the sentinel lymph node biopsy (SLNB). Objective: To evaluate whether SLNB can be used as a tool to select pathologically node-positive patients who likely benefit from WPRT. Design, setting, and participants: We included 528 clinically node-negative primary prostate cancer (PCa) patients with an estimated nodal risk of >5% treated between 2007 and 2018. Intervention: A total of 267 patients were directly treated with prostate-only radiotherapy (PORT; non-SLNB group), while 261 patients underwent SLNB to remove lymph nodes directly draining from the primary tumor prior to radiotherapy (SLNB group); pN0 patients were treated with PORT, while pN1 patients were offered WPRT. Outcome measurements and statistical analysis: Biochemical recurrence–free survival (BCRFS) and radiological recurrence-free survival (RRFS) were compared using propensity score weighted (PSW) Cox proportional hazard models. Results and limitations: The median follow-up was 71 mo. Occult nodal metastases were found in 97 (37%) SLNB patients (median metastasis size: 2 mm). Adjusted 7-yr BCRFS rates were 81% (95% confidence interval [CI] 77–86%) in the SLNB group and 49% (95% CI 43–56%) in the non-SLNB group. The corresponding adjusted 7-yr RRFS rates were 83% (95% CI 78–87%) and 52% (95% CI 46–59%), respectively. In the PSW multivariable Cox regression analysis, SLNB was associated with improved BCRFS (hazard ratio [HR] 0.38, 95% CI 0.25–0.59, p < 0.001) and RRFS (HR 0.44, 95% CI 0.28–0.69, p < 0.001). Limitations include the bias inherent to the study’s retrospective nature. Conclusions: SLNB-based selection of pN1 PCa patients for WPRT was associated with significantly improved BCRFS and RRFS compared with (conventional) imaging-based PORT. Patient summary: Sentinel node biopsy can be used to select patients who will benefit from the addition of pelvis radiotherapy. This strategy results in a longer duration of prostate-specific antigen control and a lower risk of radiological recurrence.
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- 2023
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48. A rare presentation of medullary thyroid cancer metastasis to the prostate in a patient with multiple endocrine neoplasia 2B syndrome treated with laparoscopic radical prostatectomy
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Theodoros Spinos, Dimitrios Ermidis, Christos Zabaftis, Filippos Nikitakis, Nikolaos Grivas, and Markos Karavitakis
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laparoscopic ,medullary thyroid cancer ,metastasectomy ,multiple endocrine neoplasia 2b ,prostate ,radical prostatectomy ,surgical technique ,Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
Multiple endocrine neoplasia (MEN) syndromes are rare and potentially malignant hereditary entities. Clinical manifestations of MEN 2B include medullary thyroid cancer, pheochromocytoma, gastrointestinal ganglioneuromatosis, and musculoskeletal and ophthalmologic lesions. Metastases to the prostate from the cancers of other organs are extremely rare. There are only a few cases of metastases to the prostate gland, originating from medullary thyroid cancer, found in literature, especially associated with MEN 2B syndrome. In this case report, we present the extremely rare case of a 28-year-old patient, diagnosed with MEN 2B syndrome, with medullary thyroid cancer metastasis to the prostate. Although a few reports of medullary thyroid cancer metastasis into the prostate gland can be found in the literature, to our knowledge, this is the first case of a laparoscopic radical prostatectomy procedure performed as a metastasectomy to treat the prostatic metastasis. Laparoscopic radical prostatectomy, performed as a metastasectomy, for the treatment of metastatic cancer, is an extremely rare surgical indication with distinctive requirements and difficulties. The extraperitoneal access enables the realization of the laparoscopic radical prostatectomy procedure even in the cases of patients with a history of multiple intra-abdominal operations.
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- 2023
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49. A Systematic Framework to Rapidly Obtain Data on Patients with Cancer and COVID-19:CCC19 Governance, Protocol, and Quality Assurance
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Abidi, Maheen, Aboulafia, David M, Accordino, Melissa K, Acoba, Jared D, Ahluwalia, Manmeet S, Ahmad, Syed A, Ajmera, Archana, Alimohamed, Saif I, Altman, Jessica, Angevine, Anne H, Bakouny, Ziad, Bar, Michael H, Bardia, Aditya, Barnholtz-Sloan, Jill S, Barrow McCollough, Briana, Bashir, Babar, Batist, Gerald, Bekaii-Saab, Tanios S, Berg, Stephanie, Bernicker, Eric H, Bhutani, Divaya, Bilen, Mehmet A, Bindal, Poorva, Bishnoi, Rohit, Blau, Sibel, Bohachek, Pamela, Boland, Genevieve, Bonnen, Mark, Bouchard, Gabrielle, Bouganim, Nathaniel, Bowles, Daniel W, Busser, Fiona J, Butt, Omar, Cabal, Angelo, Cabalona, Wilhelmina D, Cabebe, Elwyn C, Caimi, Paolo, Campian, Jian L, Carducci, Theresa M, Chen, James L, Cheng, Alex, Chism, David D, Choueiri, Toni K, Clark, Melanie J, Clement, Jessica M, Connors, Jean M, Cook, Erin, Curran, Catherine R, Daher, Ahmad, Dailey, Mark E, Davis, Elizabeth J, Dawsey, Scott J, Deeken, John F, Del Prete, Salvatore A, Demetri, George D, Desai, Aakash, Doroshow, Deborah B, Durbin, Eric B, Egan, Pamela C, Elias, Rawad, Elkrief, Arielle, Elms, Destry J, Elshoury, Amro, Faller, Bryan, Farmakiotis, Dimitrios, Fecher, Leslie A, Feldman, Lawrence E, Ferrario, Cristiano, Fiala, Mark A, Flora, Daniel B, French, Benjamin, Friese, Christopher R, Fu, Julie C, Gadgeel, Shirish M, Gainor, Justin, Galsky, Matthew D, Gantt, Gerald, Garcia, Jorge A, Gartrell, Benjamin A, Gatti-Mays, Margaret E, Gill, David M, Gillaspie, Erin A, Giordano, Antonio, Glace, Mary Grace, Glover, Michael J, Goel, Sanjay, Graber, Jerome J, Griffiths, Elizabeth A, Grivas, Petros, Grover, Punita, Gulati, Anthony P, Gulati, Shuchi, Gupta, Shilpa, Gurley, Michael, Hafez, Navid, Halabi, Susan, Halfdanarson, Thorvardur R, Halmos, Balazs, Hausrath, Daniel J, and Hawley, Jessica E
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Biochemistry and Cell Biology ,Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Biological Sciences ,Clinical Research ,Cancer ,COVID-19 ,COVID-19 Testing ,Data Accuracy ,Electronic Health Records ,Humans ,Neoplasms ,Quality Improvement ,SARS-CoV-2 ,COVID-19 and Cancer Consortium. Electronic address: jeremy.warner@vumc.org ,COVID-19 and Cancer Consortium ,Neurosciences ,Oncology & Carcinogenesis ,Biochemistry and cell biology ,Oncology and carcinogenesis - Abstract
When the COVID-19 pandemic began, formal frameworks to collect data about affected patients were lacking. The COVID-19 and Cancer Consortium (CCC19) was formed to collect granular data on patients with cancer and COVID-19 at scale and as rapidly as possible. CCC19 has grown from five initial institutions to 125 institutions with >400 collaborators. More than 5,000 cases with complete baseline data have been accrued. Future directions include increased electronic health record integration for direct data ingestion, expansion to additional domestic and international sites, more intentional patient involvement, and granular analyses of still-unanswered questions related to cancer subtypes and treatments.
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- 2020
50. General Medical Practitioners’ Preferences in Referring Patients with Head and Neck Disorders; A Cross-Sectional Evaluative Study in Greece
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Tatsis, Dimitris, Grivas, Theodoros, Antoniou, Asterios, Argyriadou, Stella, and Kyrgidis, Athanassios
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- 2022
- Full Text
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