tbuckley/cabot-search huggingface dataset:
Angiosarcoma treated with checkpoint inhibitors: A single-institution experience.
Authors: Vaia Florou, Breelyn A. Wilky, Jonathan C. Trent
Journal: Journal of Clinical Oncology (2019)

e22543 Background: Angiosarcoma (AS) is a rare endothelial malignancy with only 2–3 new cases per one million diagnosed yearly but is among the most aggressive soft tissue sarcomas. Some cutaneous angiosarcomas may have a mutational landscape similar to UV light exposed melanoma. These findings offer a rationale for the early limited evidence of checkpoint inhibitor activity in cutaneous angiosarcomas. Methods: This is a retrospective review of patients with locally advanced or metastatic angiosarcoma, who were treated with checkpoint inhibitors at our institution. Descriptive statistics were used to analyze our findings. Results: Since 2016, we have treated seven angiosarcoma patients with checkpoint inhibitors either in the context of clinical trials or off label [Pembrolizumab + Axitinib (NCT02636725; n = 1), a CTLA-4 inhibitor (NCT02694822; n = 2), Pembrolizumab (n = 4)]. Five patients had cutaneous AS, one primary breast AS and one radiation associated breast AS. The average age was 66 years old and 5/7 (71%) patients were females. All patients had received prior systemic therapies (range 1-7, mean 3) and 2/7 (29%) patients had metastatic disease at the time of treatment. The mean number of checkpoint inhibitor doses was 6. At twelve weeks, 5/7 patients (71%) had partial response, by RECIST, of their lesions either on imaging or clinical exam and two (29%) had progressive disease. 6/7 patients are alive to date and, thus far, 3/7 patients (43%) progressed (median 3.4 months)- one achieved partial response after pembrolizumab was switched to ongoing Nivolumab/Ipilimumab, one died of progressive disease at 31 weeks (primary breast AS) and one was placed on subsequent therapy. No patient experienced any toxicities more than grade 2. Conclusions: This is a single institution, retrospective review of patients with AS treated with checkpoint inhibitors, first reported in the literature. Checkpoint inhibitors may be an effective and safe treatment option for this aggressive sarcoma. Prospective clinical trials are needed to systemically study this effect.
Sex differences in adverse event reporting in SWOG chemotherapy, biologic/immunotherapy, and targeted agent cancer clinical trials.
Authors: Joseph M. Unger, Riha Vaidya, Kathy S. Albain, Michael Leo LeBlanc, Lori M. Minasian, Carolyn Gotay, Norah Lynn Henry, Michael Jordan Fisch, Scott David Ramsey, Charles David Blanke, Gary H. Lyman, Dawn L. Hershman
Journal: Journal of Clinical Oncology (2019)

11588 Background: Women have more adverse events (AEs) from chemotherapy than men, but few studies have explored sex differences in biologic/immunotherapies (BIs) or targeted therapies. We examined subjective (symptomatic) and objective AEs by sex across different treatments. Methods: We analyzed drug-related severe (grade 3) or worse AEs by sex in SWOG phase II and III clinical trials conducted between 1980-2018, excluding sex-specific cancers. AE codes and grade were categorized using the Common Terminology Criteria for Adverse Events (CTCAE). Subjective or symptomatic toxicities were defined as those aligned with the NCI’s new Patient-Reported Outcome (PRO) CTCAE; lab-based or physician-determined AEs were designated as objective. Multivariable logistic regression was used, adjusting for age, race, and disease prognosis. Thirteen symptomatic and 19 objective AE categories were examined. Results: In total, 36,397 patients (women, 13,907 [38.2%]; men, 22,490 [61.8%]) experiencing 522,835 AEs on 297 trials with 385 treatment arms were analyzed. Overall, 29.1% (n = 10.860) had severe or worse toxicity. Women experienced an increased risk of severe symptomatic AEs for BIs (OR = 1.53, 95% CI: 1.32-1.78, p &lt; .0001), chemotherapy (OR = 1.31, 95% CI: 1.24-1.39, p &lt; .0001), and targeted therapies (OR = 1.23, 95% CI: 1.06-1.43, p = .008). Women also had an increased risk of severe objective AEs for BIs (OR = 1.53, 95% CI: 1.32-1.78, p &lt; .0001), chemotherapy (OR = 1.35, 95% CI: 1.28-1.43, p &lt; .0001), but not targeted therapies (OR = 1.08, 95% CI: 0.94-1.25, p = .28). Across all treatments, sex differences were greater for hematologic (OR = 1.29, 95% CI: 1.24-1.35, p &lt; .0001) v. non-hematologic (OR = 1.13, 95% CI: 1.08-1.18, p &lt; .0001) objective AEs. Conclusions: The greater severity of both symptomatic and objective – especially hematologic – AEs in women across multiple treatment paradigms indicates broad-based sex-differences exist. This could be due to AE reporting, pharmacogenomics of drug metabolism and disposition, total dose received, and/or adherence to therapy. Particularly large sex differences were observed for patients receiving BIs, suggesting studying AEs from these agents is a priority.
Palliative chemotherapy during the last month of life.
Authors: Vladimir Andelkovic
Journal: Journal of Clinical Oncology (2013)

e20662 Background: There is no uniform definition of medical futility, but most accept treatments offering no reasonable chance of benefiting patients will fall into this category. According to literature, chemotherapy given in the last month of life has little or no benefit to patients. Various studies suggest 9-43% of patients receive palliative chemotherapy during the last month of life. Methods: Retrospective analysis was done on electronic medical records of patients who received systemic anti cancer therapy (SACT) - cytotoxic and/or targeted therapy for solid or haematological malignancies at The Gold Coast hospital within one year period. Patients that died within 30 days of SACT administration were further classified based on their diagnosis, treatment intent, type of treatment and cause of death. Results: 770 patients received SACT between 1 November 2011 and 31 October 2012. 53 deaths (6.9%) occurred within 30 days of receiving SACT. 35 (66%) of those were due to progression of disease and 6 (11.3%) were treatment related. All treatment related deaths were due to neutropenic sepsis. For 12 deaths (22.7%), there was insufficient documentation to establish the cause of death. Only one patient with acute myeloid leukaemia (1.9%) died as a result of treatment given with curative intent. 20 patients (37.7%) were on combination treatment while 33 (62.3%) were treated with single agents. 42 patients (79.2%) received treatment that included intravenous agents, while remaining 11 patients (20.8%) were on oral treatment only. 37 patients (69.8%) were on cytotoxic treatment, 12 (22.6%) patients were on targeted therapy, and remaining 4 (7.6%) were on a combination protocol. Conclusions: Results of this audit show a lower number of patients who received palliative chemotherapy in a metropolitan public hospital in Australia during the last month of life. Defining the goal of treatment and assessing functional status of patients regularly while on treatment may help identify deteriorating patients and could avoid medically futile treatment. [Table: see text]
Different perspectives of human behavior entail different experimental practices
Authors: Ramzi Suleiman
Journal: Behavioral and Brain Sciences (2001)

My main argument is that the advice offered to experimental psychologists by Hertwig &amp; Ortmann overlooks fundamental differences between the goals of researchers in psychology and economics. Furthermore, it is argued that the reduction of data variability is not always an end to be sought by psychologists. Variability that originates in individual differences constitutes valuable data for psychological research.
Abstract 13189: Cardiovascular Evaluation of the Selective BET Inhibitor, Apabetalone, in ACS Patients With Diabetes: Baseline Characteristics of the BETonMACE CV Outcomes Study
Authors: Kausik K Ray, Stephen J Nicholls, Mike Sweeney, Jan O Johansson, Peter P Toth, Henry Ginsberg, Kamyar Kalantar-Zadeh, Gregory G Schwartz
Journal: Circulation (2018)

Introduction: Vascular perturbation in acute coronary syndrome (ACS) is linked to inflammation. Bromodomain and extraterminal (BET) proteins coordinate gene transcription following inflammatory ins...
Early-Life Environmental Exposures and Blood Pressure in Children
Authors: Charline Warembourg, Léa Maitre, Ibon Tamayo-Uria, Serena Fossati, Theano Roumeliotaki, Gunn Marit Aasvang, Sandra Andrusaityte, Maribel Casas, Enrique Cequier, Lida Chatzi, Audrius Dedele, Juan-Ramon Gonzalez, Regina Gražulevičienė, Line Smastuen Haug, Carles Hernandez-Ferrer, Barbara Heude, Marianna Karachaliou, Norun Hjertager Krog, Rosemary McEachan, Mark Nieuwenhuijsen, Inga Petraviciene, Joane Quentin, Oliver Robinson, Amrit Kaur Sakhi, Rémy Slama, Cathrine Thomsen, Jose Urquiza, Marina Vafeiadi, Jane West, John Wright, Martine Vrijheid, Xavier Basagaña
Journal: Journal of the American College of Cardiology (2019)
Disclosure patterns and decision making preferences in <i>BRCA 1/2</i> mutation carriers with young adult and minor children
Authors: A. R. Bradbury, C. K. Daugherty, J. Dignam, C. Ibe, S. Auh, H. Fay, S. A. Cummings, M. A. White, O. I. Olopade
Journal: Journal of Clinical Oncology (2006)

1015 Background: Genetic testing of minors for adult-onset diseases has generally been discouraged. Yet, limited data suggests that many BRCA mutation carriers discuss their test results with their minor children. How parents make the decision to share this information and the effects on their health, their child and the family remains unknown. Methods: We sought to evaluate disclosure patterns and decision making practices among BRCA1/2 mutation carriers with children under the age of 25. 42 parents (with 86 children) completed a semi-structured telephone interview regarding communication of their genetic test results to their children. Chi-squared tests to assess associations between parent/child characteristics and disclosure were computed using robust variance estimates to account for clustering by family unit. Results: 55% of parents discussed hereditary risk of cancer and/or their genetic test results with at least one child. Factors associated with disclosure included older child age (p&lt;0.001), female parent gender (p=0.049), parent history of prophylactic surgery (mastectomy: p = 0.021, oophorectomy: p&lt;0.001) and education limited to high school (p=0.085). Child gender and parent’s history of cancer were not significantly associated with disclosure. Most participants reported themselves (45%) or their spouse (40%) as the most important person in the decision to disclose. Reports of physician (14%) and genetic counselor (21%) involvement were low. Conclusions: Parental decisions to disclose BRCA test results to children are complex and may reflect differences in perceptions of genetic disease. Further research is needed to understand parental motivations for disclosure and to define a role for health care professionals to improve counseling and recommendations regarding the risks and benefits of early communication of genetic risk to children. No significant financial relationships to disclose.
Supportive care medications (SCMs) and pharmacogenomics (PGx) relevance in 6,985 cancer patients (pts) undergoing distress screening.
Authors: Jai Narendra Patel, Danielle Boselli, Elizabeth Jandrisevits, Issam Hamadeh, Ahmed Salem, Patrick Leland Meadors
Journal: Journal of Clinical Oncology (2019)

11592 Background: SCMs are prescribed based on symptom burden, but response is variable, possibly due to PGx. We investigated the association between symptom burden, SCM prescribing, and frequency of SCMs with PGx evidence. Methods: Cancer pts ≥ 18 years old and completing electronic distress screening within 90 days of intake between 1/1/2017-12/31/2017 were included. Anxiety was measured using Generalized Anxiety Disorder 2-item (0-6) and depression using Patient Health Questionnaire-2 (0-6). Fatigue, nausea, neuropathy, pain and sleep were measured on a 0-10 scale. SCM prescribing within 90 days of intake was documented. Logistic regression compared symptom scores and SCM prescribing. Receiver Operating Characteristics analysis estimated sensitivity/specificity. Optimal symptom thresholds were selected according to Youden’s J statistic. SCMs with PGx evidence level A or B (according to Clinical Pharmacogenetics Implementation Consortium) were summarized. Results: Of 6985 pts, 65% were female, 75% Caucasian, 20% African American and median age was 60. 49% reported ≥ 1 severe symptom, which correlated with SCM prescribing (p &lt; 0.001). 3208 (46%) were prescribed SCM(s), mainly for pain (69%) or nausea (46%). Of these, 2759 (86%) received ≥ 1 SCM with PGx evidence and 2695 (84%) received a SCM metabolized by CYP2D6 - hydrocodone (47%), ondansetron (41%), and oxycodone (28%). Based on reported CYP2D6 allele frequencies conferring altered metabolism (~20%), 539 of the 2695 pts may have altered drug response. Threshold scores for each symptom are summarized in the table. Fatigue and nausea were not associated with SCM prescribing. Conclusions: Symptom burden is high in cancer pts and correlates with SCM prescribing. Many SCMs have PGx evidence, suggesting preemptive testing, particularly for CYP2D6, may have broad applicability in this population.[Table: see text]
Erratum: Etv4 and Etv5 are required downstream of GDNF and Ret for kidney branching morphogenesis
Authors: Benson C Lu, Cristina Cebrian, Xuan Chi, Satu Kuure, Richard Kuo, Carlton M Bates, Silvia Arber, John Hassell, Lesley MacNeil, Masato Hoshi, Sanjay Jain, Naoya Asai, Masahide Takahashi, Kai M Schmidt-Ott, Jonathan Barasch, Vivette D'Agati, Frank Costantini
Journal: Nature Genetics (2010)
Discovery of Candidate Predictors of Response to Tazemetostat in Diffuse Large B-Cell Lymphoma and Follicular Lymphoma Using NGS Technology on ctDNA Samples Collected Pre-Treatment
Authors: Scott Daigle, Alice A. McDonald, Franck Morschhauser, Gilles Salles, Vincent Ribrag, Pamela McKay, Herve Tilly, Anna Schmitt, John Gerecitano, Christophe Fruchart, Peter Johnson, John Radford, Michael J. Dickinson, Charles Herbaux, Stephen Opat, Wojciech Jurczak, Guillaume Cartron, Thierry Lamy, Pier Luigi Zinzani, Sarit Assouline, Ryan D. Morin, Helen Wu, Mark Sausen, Alicia Clawson, Peter Ho, Harry Miao, Stephen Blakemore
Journal: Blood (2017)
The Lancet Respiratory Medicine Commission: 2019 update: epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant and incurable tuberculosis
Authors: Keertan Dheda, Tawanda Gumbo, Gary Maartens, Kelly E Dooley, Megan Murray, Jennifer Furin, Edward A Nardell, Robin M Warren, Keertan Dheda, Tawanda Gumbo, Gary Maartens, Kelly E Dooley, Aliasgar Esmail, Megan Murray, Jennifer Furin, Edward Nardell, Leslie London, Erica Lessem, Jason Limberis, Grant Theron, Ruth McNerney, Stefan Niemann, David Dowdy, Annelies Van Rie, Jotam G Pasipanodya, Camilla Rodrigues, Taane G Clark, Frik A Sirgel, H Simon Schaaf, Kwok Chiu Chang, Christoph Lange, Payam Nahid, Bernard Fourie, Norbert Ndjeka, Andrew Nunn, GB Migliori, Zarir F Udwadia, C Robert Horsburgh, Gavin J Churchyard, Dick Menzies, Anneke C Hesseling, James A Seddon, Marcus Low, Salmaan Keshavjee, Eric Nuermberger, Helen McIlleron, Kevin P Fennelly, Amina Jindani, Ernesto Jaramillo, Nesri Padayatchi, Clifton E Barry, Robin M Warren
Journal: The Lancet Respiratory Medicine (2019)
Prevalence of chronic urticaria in children and adults across the globe: Systematic review with meta‐analysis
Authors: Julia Fricke, Gabriela Ávila, Theresa Keller, Karsten Weller, Susanne Lau, Marcus Maurer, Torsten Zuberbier, Thomas Keil
Journal: Allergy (2019)

Urticaria is a frequent skin condition, but reliable prevalence estimates from population studies particularly of the chronic form are scarce. The objective of this study was to systematically evaluate and summarize the prevalence of chronic urticaria by evaluating population-based studies worldwide.We performed a systematic search in PUBMED and EMBASE for population-based studies of cross-sectional or cohort design and studies based on health insurance/system databases. Risk of bias was assessed using a specific tool for prevalence studies. For meta-analysis, we used a random effects model.Eighteen studies were included in the systematic evaluation and 11 in the meta-analysis including data from over 86 000 000 participants. Risk of bias was mainly moderate, whereas the statistical heterogeneity (I2 ) between the studies was high. Asian studies combined showed a higher point prevalence of chronic urticaria (1.4%, 95%-CI 0.5-2.9) than those from Europe (0.5%, 0.2-1.0) and Northern American (0.1%, 0.1-0.1). Women were slightly more affected than men, whereas in children < 15 years we did not find a sex-specific difference in the prevalence. The four studies that examined time trends indicated an increasing prevalence of chronic urticaria over time.On a global level, the prevalence of chronic urticaria showed considerable regional differences. There is a need to obtain more sex-specific population-based and standardized international data particularly for children and adolescents, different chronic urticaria subtypes and potential risk and protective factors.
Recombinant adenoviral human p53 gene infusion in treatment of malignant pleural effusions and malignant ascites.
Authors: Kaiweng Hu
Journal: Journal of Clinical Oncology (2013)

3027 Background: Malignant pleural or peritoneal effusions are frequently developed in the late-stage malignant tumors in chest or abdominal cavity. Various drainage methods and intra-cavity chemotherapy have transient and limited benefits. Here we evaluated the role of recombinant adenoviral human p53 gene (rAd-p53) infusion for patients with malignant pleural or peritoneal effusions. Methods: Thirty-two patients with historically diagnosed malignant pleural (18 cases) or peritoneal (14 cases) effusions, 19 males and 13 females with an average age of 61 years old (37–80 years), were included this study. The malignant pleural effusions were caused by primary lung cancers (8 cases), lung metastatic tumors (4 cases), breast cancers (3 cases), pleural mesothelioma (2 cases), lymphoma (1 cases), and the peritoneal effusions were caused by ovarian cancers (5 cases), primary liver cancers (4 cases), liver metastatic tumors (2 cases), colon cancer (1 case), gastric cancer (1 case), and prostate cancer (1 case). After draining most of the fluids, 4×10 12 viral particles (VP) of rAd-p53 diluted into 1,000 ml of saline solution for intra-abdominal cavity infusion and 2×10 12 VP of rAd-p53 diluted into 500 ml of saline solution for intra-chest cavity infusion, were given weekly for 4 weeks. The response rate was evaluated. The complete response is defined as the complete disappearance of pleural or peritoneal fluid and negative cytologic findings for &gt;4 weeks, and the partial response is defined as a decrease over 50% of the fluid without the need of drainage and negative cytologic findings for &gt;4 weeks. Results: The pleural effusion showed a complete response in 6 patients (33.3%) and a partial response in 6 patients (33.3%). The peritoneal effusion had a complete response in 3 patients (21.4%) and a partial response in 7 patients (50.0%). The overall response rate was 68.8% (22/32). The symptoms associated with the malignant effusion relieved in 27 patients (84.4%). There were no serious side effects observed except for self-limited fever found in all the cases. Conclusions: Intra-abdominal or chest cavity infusion of rAd-p53 is a safe and effective treatment for some malignant pleural or peritoneal effusions.
Biodiversity, land use change, and human health in northeastern Madagascar: an interdisciplinary study
Authors: Randall Kramer, James Herrera, Ryan Fitzgerald, James Moody, Ajile Owens, Michelle Pender, Ny Anjara Fifi Ravelomanantsoa, Lisa Regula, Pablo Tortosa, Charles Nunn
Journal: The Lancet Planetary Health (2019)

BackgroundGiven rapid land use changes and climate change underway in many low-income and middle-income countries, it is vitally important to understand how ecosystem changes influence biodiversity and human health, and to identify actions that can improve conservation, while also improving human health. We are investigating how human activities alter ecological communities and influence infectious disease risk near Marojejy National Park in northeastern Madagascar. We are coupling (i) cutting-edge social science methods to investigate the drivers of human land-use decision-making, and (ii) ecological analyses to investigate how these land use decisions impact zoonotic infectious disease transmission in small mammals, domesticated animals, and humans.MethodsThe study team conducted preliminary fieldwork in one village in 2017 and 2018 including household surveys, social network surveys and trapping of small mammals to screen for parasites and pathogens. We constructed a social network of 500 people to investigate disease risk patterns based on agricultural co-working relationships. In addition, the team captured 552 small mammals and found variation in abundance and diversity across a gradient of human land use.FindingsResults show that illness is frequent within community households, with a high prevalence of fevers over the previous 3 months (40%). Non-native species have higher relative and total abundance in agricultural fields, with highest relative abundance of introduced species in the unsustainable rice farming setting. Prevalence of Leptospira, a pathogenic bacterium transmitted through urine and contaminated water, was over four times higher in paddy rice fields than in forests or hillside slash-and-burn fields.InterpretationOur findings are consistent with the hypothesis that changes in land use and biodiversity can influence animal health, which may in turn affect disease risk for humans. We are now expanding ecological and household data collection to additional villages, as well as developing choice experiments to better understand farmer decision making about sustainable agricultural practices.FundingDuke University Bass Connections programme for interdisciplinary research.