tbuckley/cabot-search huggingface dataset:
Neuromuscular blocking agents induced anaphylaxis: Results and trends of a French pharmacovigilance survey from 2000 to 2012
Authors: N. Petitpain, L. Argoullon, K. Masmoudi, S. Fedrizzi, J. Cottin, C. Latarche, P. M. Mertes, P. Gillet
Journal: Allergy (2018)

Perioperative anaphylaxis mainly involves neuromuscular blocking agents (NMBAs) with an IgE-mediated mechanism. In France, this life-threatening condition is reported by anesthetists and allergologists, and two safety alerts concerning suxamethonium were raised in 2011 and 2012. This led to start a national survey over the 2000-2012 period which objectives were to provide a descriptive analysis, to estimate incidence rates, and to analyze the trends over this period.The French pharmacovigilance database was retrospectively queried for all the available NMBAs. Anaphylaxis cases with elevated tryptase and positive skin tests were qualified as "confirmed cases." Subgroup analysis compared atracurium and cisatracurium vs suxamethonium and rocuronium.A total of 680 confirmed cases and 944 nonconfirmed cases were identified. Suxamethonium was the most implied NMBA (64%). Incidence rates (according to sales data) of suxamethonium and rocuronium were, respectively, 10- and 13-folds higher than those of the others NMBAs, regardless the confirmed/nonconfirmed status. Cisatracurium incidence rates remained stable over the period, while suxamethonium and atracurium increased and rocuronium first decreased but re-increased after 2006. Male patients were more frequent in the subgroup "atracurium-cisatracurium" (P = .019), whereas obesity and emergency setting were more frequent in the subgroup "rocuronium-suxamethonium." Shared characteristics were the poorly documented previous exposure to NMBA(s) and an insufficient adherence of patients to perform skin tests, showing the need to improve this procedure.Suxamethonium and rocuronium are markedly more involved in perioperative anaphylaxis than the other available NMBAs. Patients should be more informed about their perioperative anaphylaxis and its consequences.
Nivolumab in advanced hepatocellular carcinoma (HCC) and Child Pugh B (CPB) cirrhosis: Safety and clinical outcomes in a retrospective case series.
Authors: Swetha Kambhampati, Kelly Bauer, Jimmy Hwang, Andrea Grace Bocobo, John Dozier Gordan, Robin Kate Kelley
Journal: Journal of Clinical Oncology (2018)

496 Background: HCC patients (pts) with Child Pugh B (CPB) cirrhosis have poor prognosis and limited treatment (Tx) options. Nivolumab demonstrated durable responses and acceptable safety in Child Pugh A (CPA) HCC in the CheckMate-040 trial with rates of hepatotoxicity similar to non-HCC populations. The safety and efficacy of nivolumab has not been established in pts with CPB cirrhosis. Methods: Design: Retrospective case series with IRB approval. Key eligibility: HCC with CPB cirrhosis; treated with nivolumab as standard Tx; enrolled in the UCSF Hepatobiliary Tissue Bank and Registry. Study endpoints: Safety during nivolumab Tx including all-cause grade(Gr) ≥ 3 adverse events (AE), serious AE (SAE), any grade immune-related (ir)AE, and systemic steroid (SS) requirement; clinical outcomes including time on Tx (TOT) with nivolumab and overall survival (OS). Results: Thirteen pts were included: male 77%; Asian 38%, white 54%; median age 66 (range: 26-86); HCV Ab+ 31%, HBsAg+ 23%; BCLC B/C 31%/69%; median Child-Pugh score 8; median prior systemic Tx 1 (range: 0-6); prior sorafenib 69%, median duration on prior sorafenib 137 days (range 10-341). The Table depicts safety outcomes on nivolumab. Median TOT on nivolumab: 44 days (95% CI: 32, 98) (range: 17-811+). Median OS from start of nivolumab: 119 days (95% CI: 40, 247) (range: 40-811+). Best response of at least stable disease occurred in 3/13 (23%) of patients, including prolonged stable disease (SD) for 6+ months and complete response (CR) for 24+ months on nivolumab (1 pt each). Conclusions: CPB HCC pts treated with nivolumab experienced high rates of all-cause Gr ≥ 3 AE and SAE and short OS, similar to prior studies in CPB HCC. Rates of irAE attributed to nivolumab were similar to rates reported in CheckMate-040 CPA population, without unexpected AE. A subset of pts experienced prolonged stable disease and CR. Nivolumab warrants further study in CPB HCC.[Table: see text]
Progressive resistance training in head and neck cancer patients undergoing concomitant chemoradiotherapy.
Authors: Camilla Loenkvist, Anders Vinther, Bo Zerahn, Eva Rosenbom, Atul S. Deshmukh, Pernille Hojman, Julie Gehl
Journal: Journal of Clinical Oncology (2016)

e17534 Background: Patients (pts) with head and neck squamous cell carcinoma (HNSCC) undergoing concomitant chemoradiotherapy (CCRT) frequently experience substantial weight loss, especially loss of lean body mass (LBM), affecting functional performance. We propose that progressive resistance training (PRT) is feasible and may counteract these detrimental effects. In addition, we explore PRT-dependent changes in muscle proteins and cytokines, which may directly or indirectly inhibit tumor growth. Methods: Pts with stage III/IV HNSCC scheduled for CCRT entered a 12-week hospital-based PRT program with 13 months follow-up. Primary endpoint was feasibility measured by adherence to training sessions. Secondary endpoints were changes in functional performance, muscle strength, body composition measured by dual-energy X-ray absorptiometry (DXA), adverse events, dietary intake, self-reported physical activity, quality of life, and questionnaire about the program. Furthermore, cytokine levels in plasma and sarcomeric protein content in muscle biopsies were measured. Results: Twelve pts were accrued as planned, from March to July 2014. Primary endpoint was met as 75% of patients attended ≥ 25 of 36 sessions. Attendance during CCRT was 92%. Functional performance and muscle strength in lower body was maintained during treatment and increased during follow-up (p <0.01). Total body mass (p< 0.001), LBM (p< 0.001), and upper body muscle strength (p <0.01) decreased during treatment, but were regained, almost reaching baseline values at 13-months follow-up. Pts emphasized physical, social, and psychological benefits of attending. No serious adverse events were deemed related to training. Systemic changes of more than 50 cytokines and biomarkers were explored, and several, e.g. IL-6, IL-8, IL-16, follistatin, and leptin, showed changes during the course of treatment and/or training. Sarcomeric proteins in muscle followed the pattern of LBM. Conclusions: A 12-week PRT during CCRT is feasible and beneficial for pts with HNSCC, with regard to physical, social, and psychological gains. Randomized studies are warranted. Several cytokines showed interesting changes prompting further investigations. Clinical trial information: NCT02068950.
Toll like receptors as a risk factor for early death in elderly cancer patients.
Authors: Jurema Telles O Lima, Maria Julia Gonçalves Mello, Luiz Claudio Santos Thuler, Letícia Telles Sales, Marina Santaliz de Godoy Moreno, Anke Bergmann, Kleber Jatahy, Clara Cinthia Resende Lira, Evandro Bezerra Cintra, Gabriela Delgado Soriano, Leuridan Torres
Journal: Journal of Clinical Oncology (2017)

133 Background: the elderly cancer group is a heterogeneous and growing one. In the elderly, the genes of toll-like receptors (TLR) have been described as related to the immunosenescence process and carcinogenesis. The relationship of this gene family with carcinogenesis and immunoregulatory responses seems a promising field. Methods: Between 2015 and 2016, a prospective cohort study in 445 elderly patients with incident cancer ( ≥ 60 years) at the time of admission, assessed and collected sociodemographic and clinical variables and collected analysis of peripheral blood in translational exploratory study. Determination of TLR2 and TLR9 was performed by flow cytometry with monoclonal antibodies anti-TLR2 and TLR9 in the peripheral blood at the beginning of anti-cancer therapy in older patients with cancer. Results: 445 elderly patients were included with incident cancer, age of 71.13 years (SD 7.41) means. Most were male (50.9%) and self-reported black or brown skin color (71.4%). The topography of prostate cancer was more frequent (29.4%), followed by the digestive system (24.3%). They were mostly patients with advanced stage (III and IV) at nutritional risk (52.6%) and reported using up to 5 medications (77.2%). Patients were followed for an average of 128 days (SD 54.37). During this period, there were 62 deaths (13.9 %) with a mean overall survival of 165 days (95% CI 161.25 to 170.02). There are significant differences in the percentage values of TLR9 (p = 0.0009) and TLR2 (p = 0.04) in monocytes between the groups of patients who died in less than 6 months of treatment and those who survived. Conclusions: Overexpression of TLR9 and TLR2 may be a protective factor for the occurrence of early death in elderly patients with cancer.
Why Deep Learning Is Changing the Way to Approach NGS Data Processing: A Review
Authors: Fabrizio Celesti, Antonio Celesti, Jiafu Wan, Massimo Villari
Journal: IEEE Reviews in Biomedical Engineering (2018)

Nowadays, big data analytics in genomics is an emerging research topic. In fact, the large amount of genomics data originated by emerging next-generation sequencing (NGS) techniques requires more and more fast and sophisticated algorithms. In this context, deep learning is re-emerging as a possible approach to speed up the DNA sequencing process. In this review, we specifically discuss such a trend. In particular, starting from an analysis of the interest of the Internet community in both NGS and deep learning, we present a taxonomic analysis highlighting the major software solutions based on deep learning algorithms available for each specific NGS application field. We discuss future challenges in the perspective of cloud computing services aimed at deep learning based solutions for NGS.
Immunotherapy and survival in stage IV melanoma: A National Cancer Database (NCDB) analysis.
Authors: Aabra Ahmed, Mridula Krishnan, Margaret Siu, Ryan W Walters, Peter T. Silberstein
Journal: Journal of Clinical Oncology (2017)

160 Background: Interleukin-2 (IL-2) has been the predominant immunotherapy used for stage IV melanoma for the past decades, with newer immunotherapy drugs approved within the past five years. By using the National Cancer Database (NCDB), our study aims to be the largest to determine the impact of immunotherapy on patients with stage IV melanoma. To examine only IL-2 and interferon-alpha, only patients diagnosed prior to 2011 were used. Methods: 10,771 patients diagnosed with stage IV melanoma between 2004-2010 were identified with sufficient data. 1,009 of these patients were given immunotherapy. Chi-square analysis was used to determine demographic differences between those with and without immunotherapy. Between-therapy survival differences were estimated by the Kaplan-Meier method and associated log-rank tests; Tukey-Kramer adjusted p &lt; .05 indicated statistical significance. Results: Patients with immunotherapy had a median survival of 17.4 months, while those without immunotherapy had a median survival of 7.1 months. 27% of patients given immunotherapy were alive three years post diagnosis, compared to only 14% of patients who were not given immunotherapy. Immunotherapy patients had a greater percentage of those with private insurance (65.3% vs. 37.7%, p&lt;0.001), an income greater than $63,000 (40.5% vs. 31.9%, p&lt;0.001), and no comorbidities (87.3% vs. 77.5%, p&lt;0.001) compared to patients not given immunotherapy. Conclusions: Patients with immunotherapy had nearly a 2.5-fold increase in median survival compared to patients not provided immunotherapy. Compared to those without immunotherapy, immunotherapy patients lived in more wealthy and educated zip codes, and had more private insurance. [Table: see text]
Progress in the Management of Early-Stage Non–Small Cell Lung Cancer in 2017
Authors: Jessica S. Donington, Young Tae Kim, Betty Tong, Andre L. Moreira, Jamie Bessich, Kathleen D. Weiss, Yolonda L. Colson, Dennis Wigle, Raymond U. Osarogiagbon, Jeffrey Zweig, Heather Wakelee, Justin Blasberg, Megan Daly, Leah Backhus, Paul Van Schil
Journal: Journal of Thoracic Oncology (2018)
Inequalities in child mortality: real data or modelled estimates?
Authors: Cesar G Victora, Ties Boerma
Journal: The Lancet Global Health (2018)

To ensure that no one is left behind is fundamental to the 2030 Agenda for the Sustainable Development Goals. Disaggregation of health statistics by multiple dimensions of inequality is necessary to identify disadvantaged populations and guide the targeting of programmes and monitoring of progress. During the past few decades, disaggregation of health statistics by wealth quintiles from household survey data has become common practice. In The Lancet Global Health, Fengqing Chao and colleagues1 expand the comprehensive and well established work by the UN Inter-agency Group on Child Mortality with estimates of country, regional, and global child mortality by wealth quintiles for 1990–2016.
Distinct dominant T-cell receptors with a tissue resident memory phenotype in individual melanoma metastases.
Authors: Kavita M. Dhodapkar, Chandra S Boddupalli, Noffar Bar, Krishna Kadaveru, Michael Krauthammer, Natapol Pornputtapong, Zifeng Mai, Stephan Ariyan, Deepak Narayan, Harriet M. Kluger, Yanhong Deng, Rakesh Verma, Rituparna Das, Antonella Bacchiocchi, Ruth Halaban, Mario Sznol, Madhav V. Dhodapkar
Journal: Journal of Clinical Oncology (2017)

3 Background: Expression of inhibitory immune checkpoints (ICPs) within tumors has emerged as an important barrier for effective anti-tumor immunity. Antibody-mediated blockade of ICPs can lead to durable responses in patients. Interestingly, only a small subset of tumor infiltrating lymphocytes (TILs) express these checkpoints and there is a need to better understand the characteristics of this subset. We undertook this study to understand characteristics of TILs within melanoma. Methods: We used single cell mass cytometry, gene expression profiling of purified T cell subsets, T cell receptor (TCR) sequencing as well as functional studies to understand the characteristics of TILs in melanoma patients (n=50). We also performed exome sequencing of tumor cells in some patients. Results: We find that TILs are functionally and phenotypically distinct from circulating T cells. They express higher levels of inhibitory ICPs (PD-1, TIM-3) and secrete less IL2, IFNg and TNFa than T cells in circulation. Expression of vascular endothelial growth factor within tumors correlated with reduced T cell infiltration. Expression of ICPs (PD-1, TIM-3, PD-L1) were enriched in T cells with a phenotype and expression profile of tissue resident memory T (TRM) cells with most cells expressing multiple checkpoints. Within the myeloid compartment, ICPs were predominantly expressed on CD14+CD16+ subset. TCR sequencing revealed that individual melanoma metastases revealed that the top clones within each of the lesions have distinct TCRs. Concurrent TCR and tumor exome sequencing of individual metastases in the same patient revealed that inter-lesional diversity of TCRs exceeded differences in mutation/neoantigen load in tumor cells. Conclusions: Our findings suggest that TRM cells and CD16+ myeloid cells may be the major target of ICP blockade within tumors. The ability to activate, and retain T RM cells may be an important determinant of the T cell content of the tumor microenvironment and should be a goal for future vaccines. Importantly, our study illustrates inter-lesional diversity of TCRs within individual metastases which may differentially impact the outcome of immune therapy at each site.
Physicians’ political preferences and the delivery of end of life care in the United States: retrospective observational study
Authors: Anupam B Jena, Andrew R Olenski, Dhruv Khullar, Adam Bonica, Howard Rosenthal
Journal: BMJ (2018)

<h3>Abstract</h3> <h3>Objectives</h3> To compare the delivery of end of life care given to US Medicare beneficiaries in hospital by internal medicine physicians with Republican versus Democrat political affiliations. <h3>Design</h3> Retrospective observational study. <h3>Setting</h3> US Medicare. <h3>Participants</h3> Random sample of Medicare beneficiaries, who were admitted to hospital in 2008-12 with a general medical condition, and died in hospital or shortly thereafter. <h3>Main outcome measures</h3> Total inpatient spending, intensive care unit use, and intensive end of life treatments (eg, mechanical ventilation and gastrostomy tube insertion) among patients dying in hospital, and hospice referral among patients discharged but at high predicted risk of 30 day mortality after discharge. Physicians were categorized as Democrat, Republican, or non-donors, using federal political contribution data. <h3>Results</h3> Among 1 480 808 patients, 93 976 (6.3%) were treated by 1523 Democratic physicians, 58 876 (4.0%) by 768 Republican physicians, and 1 327 956 (89.6%) by 23 627 non-donor physicians. Patient demographics and clinical characteristics were similar between groups. Democrat physicians were younger, more likely to be female, and more likely to have graduated from a top 20 US medical school than Republican physicians. Mean end of life spending, after adjustment for patient covariates and hospital specific fixed effects, was US$17 938 (£12 872; €14 612) among Democrat physicians (95% confidence interval $17 176 to $18 700) and $18 409 among Republican physicians ($17 362 to $19 456; adjusted Republican <i>v</i> Democrat difference, $472 (−$803 to $1747), P=0.47). Intensive end of life treatments for patients who died in hospital did not vary by physician political affiliation. The proportion of patients discharged from hospital to hospice did not vary with physician political affiliation. Among patients in the top 5% of predicted risk of death 30 days after hospital discharge, adjusted proportions of patients discharged to hospice were 15.8%, 15.0%, and 15.2% among Democrat, Republican, and non-donor physicians, respectively (adjusted difference in proportion between Republicans <i>v</i> Democrats, −0.8% (−2.7% to 0.9%), P=0.43). <h3>Conclusions</h3> This study provided no evidence that physician political affiliation is associated with the intensity of end of life care received by patients in hospital. Other treatments for politically polarised healthcare issues should be investigated.
Alectinib versus chemotherapy in crizotinib-pretreated anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer: results from the phase III ALUR study
Authors: S. Novello, J. Mazières, I.-J. Oh, J. de Castro, M.R. Migliorino, Å. Helland, R. Dziadziuszko, F. Griesinger, A. Kotb, A. Zeaiter, A. Cardona, B. Balas, H.K. Johannsdottir, A. Das-Gupta, J. Wolf
Journal: Annals of Oncology (2018)

This is the first trial to directly compare efficacy and safety of alectinib versus standard chemotherapy in advanced/metastatic anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) patients who have progressed on, or were intolerant to, crizotinib.ALUR (MO29750; NCT02604342) was a randomized, multicenter, open-label, phase III trial of alectinib versus chemotherapy in advanced/metastatic ALK-positive NSCLC patients previously treated with platinum-based doublet chemotherapy and crizotinib. Patients were randomized 2 : 1 to receive alectinib 600 mg twice daily or chemotherapy (pemetrexed 500 mg/m2 or docetaxel 75 mg/m2, both every 3 weeks) until disease progression, death, or withdrawal. Primary end point was investigator-assessed progression-free survival (PFS).Altogether, 107 patients were randomized (alectinib, n = 72; chemotherapy, n = 35) in 13 countries across Europe and Asia. Median investigator-assessed PFS was 9.6 months [95% confidence interval (CI): 6.9-12.2] with alectinib and 1.4 months (95% CI: 1.3-1.6) with chemotherapy [hazard ratio (HR) 0.15 (95% CI: 0.08-0.29); P < 0.001]. Independent Review Committee-assessed PFS was also significantly longer with alectinib [HR 0.32 (95% CI: 0.17-0.59); median PFS was 7.1 months (95% CI: 6.3-10.8) with alectinib and 1.6 months (95% CI: 1.3-4.1) with chemotherapy]. In patients with measurable baseline central nervous system (CNS) disease (alectinib, n = 24; chemotherapy, n = 16), CNS objective response rate was significantly higher with alectinib (54.2%) versus chemotherapy (0%; P < 0.001). Grade ≥3 adverse events were more common with chemotherapy (41.2%) than alectinib (27.1%). Incidence of AEs leading to study-drug discontinuation was lower with alectinib (5.7%) than chemotherapy (8.8%), despite alectinib treatment duration being longer (20.1 weeks versus 6.0 weeks).Alectinib significantly improved systemic and CNS efficacy versus chemotherapy for crizotinib-pretreated ALK-positive NSCLC patients, with a favorable safety profile.ClinicalTrials.gov NCT02604342; Roche study MO29750.
Identification and Validation of a 3-Gene Methylation Classifier for HPV-Based Cervical Screening on Self-Samples
Authors: Wina Verlaat, Barbara C. Snoek, Daniëlle A.M. Heideman, Saskia M. Wilting, Peter J.F. Snijders, Putri W. Novianti, Annina P. van Splunter, Carel F.W. Peeters, Nienke E. van Trommel, Leon F.A.G. Massuger, Ruud L.M. Bekkers, Willem J.G. Melchers, Folkert J. van Kemenade, Johannes Berkhof, Mark A. van de Wiel, Chris J.L.M. Meijer, Renske D.M. Steenbergen
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Offering self-sampling of cervico-vaginal material for high-risk human papillomavirus (hrHPV) testing is an effective method to increase the coverage in cervical screening programs. Molecular triage directly on hrHPV-positive self-samples for colposcopy referral opens the way to full molecular cervical screening. Here, we set out to identify a DNA methylation classifier for detection of cervical precancer (CIN3) and cancer, applicable to lavage and brush self-samples. Experimental Design: We determined genome-wide DNA methylation profiles of 72 hrHPV-positive self-samples, using the Infinium Methylation 450K Array. The selected DNA methylation markers were evaluated by multiplex quantitative methylation-specific PCR (qMSP) in both hrHPV-positive lavage (n = 245) and brush (n = 246) self-samples from screening cohorts. Subsequently, logistic regression analysis was performed to build a DNA methylation classifier for CIN3 detection applicable to self-samples of both devices. For validation, an independent set of hrHPV-positive lavage (n = 199) and brush (n = 287) self-samples was analyzed. Results: Genome-wide DNA methylation profiling revealed 12 DNA methylation markers for CIN3 detection. Multiplex qMSP analysis of these markers in large series of lavage and brush self-samples yielded a 3-gene methylation classifier (ASCL1, LHX8, and ST6GALNAC5). This classifier showed a very good clinical performance for CIN3 detection in both lavage (AUC = 0.88; sensitivity = 74%; specificity = 79%) and brush (AUC = 0.90; sensitivity = 88%; specificity = 81%) self-samples in the validation set. Importantly, all self-samples from women with cervical cancer scored DNA methylation–positive. Conclusions: By genome-wide DNA methylation profiling on self-samples, we identified a highly effective 3-gene methylation classifier for direct triage on hrHPV-positive self-samples, which is superior to currently available methods. Clin Cancer Res; 24(14); 3456–64. ©2018 AACR.