Institution
Allegheny Health Network
Healthcare•Pittsburgh, Pennsylvania, United States•
About: Allegheny Health Network is a healthcare organization based out in Pittsburgh, Pennsylvania, United States. It is known for research contribution in the topics: Medicine & Population. The organization has 1108 authors who have published 1368 publications receiving 15052 citations. The organization is also known as: West Penn Allegheny Health System.
Topics: Medicine, Population, Cancer, Internal medicine, Transplantation
Papers
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TL;DR: The addition of atezolizumab to bevacIZumab plus chemotherapy significantly improved progression‐free survival and overall survival among patients with metastatic nonsquamous NSCLC, regardless of PD‐L1 expression and EGFR or ALK genetic alteration status.
Abstract: Background The cancer-cell–killing property of atezolizumab may be enhanced by the blockade of vascular endothelial growth factor–mediated immunosuppression with bevacizumab. This open-label, phase 3 study evaluated atezolizumab plus bevacizumab plus chemotherapy in patients with metastatic nonsquamous non–small-cell lung cancer (NSCLC) who had not previously received chemotherapy. Methods We randomly assigned patients to receive atezolizumab plus carboplatin plus paclitaxel (ACP), bevacizumab plus carboplatin plus paclitaxel (BCP), or atezolizumab plus BCP (ABCP) every 3 weeks for four or six cycles, followed by maintenance therapy with atezolizumab, bevacizumab, or both. The two primary end points were investigator-assessed progression-free survival both among patients in the intention-to-treat population who had a wild-type genotype (WT population; patients with EGFR or ALK genetic alterations were excluded) and among patients in the WT population who had high expression of an effector T-cell (Teff) gene signature in the tumor (Teff-high WT population) and overall survival in the WT population. The ABCP group was compared with the BCP group before the ACP group was compared with the BCP group. Results In the WT population, 356 patients were assigned to the ABCP group, and 336 to the BCP group. The median progression-free survival was longer in the ABCP group than in the BCP group (8.3 months vs. 6.8 months; hazard ratio for disease progression or death, 0.62; 95% confidence interval [CI], 0.52 to 0.74; P<0.001); the corresponding values in the Teff-high WT population were 11.3 months and 6.8 months (hazard ratio, 0.51 [95% CI, 0.38 to 0.68]; P<0.001). Progression-free survival was also longer in the ABCP group than in the BCP group in the entire intention-to-treat population (including those with EGFR or ALK genetic alterations) and among patients with low or negative programmed death ligand 1 (PD-L1) expression, those with low Teff gene-signature expression, and those with liver metastases. Median overall survival among the patients in the WT population was longer in the ABCP group than in the BCP group (19.2 months vs. 14.7 months; hazard ratio for death, 0.78; 95% CI, 0.64 to 0.96; P=0.02). The safety profile of ABCP was consistent with previously reported safety risks of the individual medicines. Conclusions The addition of atezolizumab to bevacizumab plus chemotherapy significantly improved progression-free survival and overall survival among patients with metastatic nonsquamous NSCLC, regardless of PD-L1 expression and EGFR or ALK genetic alteration status. (Funded by F. Hoffmann–La Roche/Genentech; IMpower150 ClinicalTrials.gov number, NCT02366143.)
2,464 citations
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Virginia Mason Medical Center1, University of Birmingham2, University of São Paulo3, University of Michigan4, Toronto General Hospital5, Newcastle University6, University of Cologne7, Allegheny Health Network8, Keio University9, University of Pennsylvania10, University of Hong Kong11, Katholieke Universiteit Leuven12, University of Oxford13, Pompeu Fabra University14, University of Rochester15, Tata Memorial Hospital16, Trinity College, Dublin17, University of Queensland18, Erasmus University Rotterdam19
TL;DR: The proposed system for defining and recording perioperative complications associated with esophagectomy provides an infrastructure to standardize international data collection and facilitate future comparative studies and quality improvement projects.
Abstract: Introduction: Perioperative complications influence long- and short-term outcomes after esophagectomy. The absence of a standardized system for defining and recording complications and quality measures after esophageal resection has meant that there is wide variation in evaluating their impact on these outcomes. Methods: The Esophageal Complications Consensus Group comprised 21 high-volume esophageal surgeons from 14 countries, supported by all the major thoracic and upper gastrointestinal professional societies. Delphi surveys and group meetings were used to achieve a consensus on standardized methods for defining complications and quality measures that could be collected in institutional databases and national audits. Results: A standardized list of complications was created to provide a template for recording individual complications associated with esophagectomy. Where possible, these were linked to preexisting international definitions. A Delphi survey facilitated production of specific definitions for anastomotic leak, conduit necrosis, chyle leak, and recurrent nerve palsy. An additional Delphi survey documented consensus regarding critical quality parameters recommended for routine inclusion in databases. These quality parameters were documentation on mortality, comorbidities, completeness of data collection, blood transfusion, grading of complication severity, changes in level of care, discharge location, and readmission rates. Conclusions: The proposed system for defining and recording perioperative complications associated with esophagectomy provides an infrastructure to standardize international data collection and facilitate future comparative studies and quality improvement projects.
733 citations
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TL;DR: Improved overall survival with ABCP versus BCP was observed in patients with sensitising EGFR mutations, and overall survival in the intention-to-treat population, including EGFR-positive patients and patients with baseline liver metastases.
616 citations
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TL;DR: This work directly measures the effects of aging in human tissue by performing single-cell transcriptome analysis of 2,544 human pancreas cells from eight donors spanning six decades of life and discovers a novel mutational signature in healthy aging endocrine cells.
399 citations
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TL;DR: It is found that diabetes-inducing CD4 T cell clones isolated from nonobese diabetic mice recognize epitopes formed by covalent cross-linking of proinsulin peptides to other peptides present in β cell secretory granules, which may explain how immune tolerance is broken in T1D.
Abstract: T cell–mediated destruction of insulin-producing β cells in the pancreas causes type 1 diabetes (T1D). CD4 T cell responses play a central role in β cell destruction, but the identity of the epitopes recognized by pathogenic CD4 T cells remains unknown. We found that diabetes-inducing CD4 T cell clones isolated from nonobese diabetic mice recognize epitopes formed by covalent cross-linking of proinsulin peptides to other peptides present in β cell secretory granules. These hybrid insulin peptides (HIPs) are antigenic for CD4 T cells and can be detected by mass spectrometry in β cells. CD4 T cells from the residual pancreatic islets of two organ donors who had T1D also recognize HIPs. Autoreactive T cells targeting hybrid peptides may explain how immune tolerance is broken in T1D.
396 citations
Authors
Showing all 1143 results
Name | H-index | Papers | Citations |
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Stephen R. Quake | 132 | 589 | 77778 |
Jean Woo | 106 | 986 | 56931 |
Massimo Trucco | 70 | 357 | 19328 |
Susan Manzi | 64 | 211 | 19712 |
David L. Bartlett | 63 | 332 | 12524 |
Alan J. Russell | 62 | 280 | 13894 |
Raymond L. Benza | 52 | 301 | 13434 |
David P. Skoner | 47 | 183 | 9989 |
Thomas B. Julian | 45 | 177 | 11130 |
Vivek Verma | 40 | 408 | 5716 |
Srinivas Murali | 38 | 132 | 9736 |
William A. Rudert | 37 | 84 | 7580 |
Rita Bottino | 36 | 97 | 5533 |
Aristeidis H. Katsanos | 33 | 204 | 3377 |
Mary Chester M. Wasko | 32 | 63 | 5775 |