tbuckley/cabot-search huggingface dataset:
A real world multicenter study of first (1L) and second (2L) line treatment patterns and outcomes in advanced pancreatic cancer (APC).
Authors: Winson Y. Cheung, Hanbo Zhang, Patricia A. Tang, Jennifer L. Spratlin, Richard M. Lee-Ying, Rachel Anne Goodwin, Brandon Matthew Meyers, Dawn Elizabeth Armstrong, Ravi Ramjeesingh, Michael M. Vickers, Christina Kim
Journal: Journal of Clinical Oncology (2018)

476 Background: FOLFIRINOX (FFX), gemcitabine plus nab-paclitaxel (GN), and gemcitabine (gem) are 3 publicly funded and available treatment options for locally advanced (LAPC) and metastatic pancreatic cancer (MPC) in Canada since 2014. Without head-to-head trials that directly compare all 3 regimens, treatment selection and outcomes in 1L and 2L remain poorly characterized in routine clinical practice. Methods: Data from 4 tertiary, 8 regional, and 28 community hospitals in Canada were pooled. LAPC and MPC patients diagnosed from 2014 onwards and who received at least 1 line of systemic therapy were included. Analyses were conducted to identify predictors of treatment choice and to determine the relationship between treatment patterns and overall survival (OS) from APC diagnosis to death. Results: We identified 279 eligible patients. Median age was 64 (IQR 56-69) years, 55% were men, and 46% were ECOG ≥2. There were 27% LAPC and 73% MPC. In the 1L setting, FFX and GN were given in 44% and 41% of patients, respectively, and gem in 15%. GN was the preferred multi-agent therapy in worse ECOG patients (66% in ECOG 2+ vs 21% in ECOG 0, p = .001) and in more recently diagnosed cases (63% in 2016 vs 25% in 2014, p = .001). 1L treatment selection was not influenced by other baseline characteristics, such as age, sex, tumor location, or LAPC vs MPC status (all p &gt; 0.05). A total of 91 patients proceeded to subsequent therapies, of whom 55 (60%), 27 (30%), and 9 (10%) had received 1L FFX, GN, and gem, respectively. In the 2L setting, GN after 1L FFX (41/55; 75%) and fluoropyrimidine (FP) after 1L GN (21/27; 78%) were the most common sequential approaches. Patients who underwent 2L therapy had better OS than those who did not (13 vs 7 months, p = .001). After adjusting for confounders, receipt of 1L FFX plus 2L GN or 1L GN plus 2L FP resulted in improved OS when compared to other treatment sequences (HR 0.43, 95%CI 0.28-0.67, p = 0.001 and HR 0.57, 95%CI 0.39-0.83, p = 0.004, respectively). Conclusions: One third of APC patients receive 2L therapy, highlighting the feasibility of 2L trials. Use of 1L multi-agent therapy followed by 2L non-cross-resistant regimens represents a reasonable treatment strategy for APC in the real world.
Annals Story Slam - Teamwork Is the Real Lesson
Authors: Alison Bell
Journal: Annals of Internal Medicine (2018)

Web Exclusives3 April 2018Annals Story Slam - Teamwork Is the Real LessonFREEAlison Bell, OTD, OTR/LAlison Bell, OTD, OTR/LThomas Jefferson University, Philadelphia, Pennsylvania (A.B.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W18-0002 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - Teamwork Is the Real Lesson "Teamwork Is the Real Lesson," by Dr. Alison Bell (Duration 5:17)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Thomas Jefferson University, Philadelphia, Pennsylvania (A.B.)Corresponding Author: Alison Bell, OTD, OTR/L; e-mail, alison.[email protected]edu. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 3 April 2018Volume 168, Issue 7Page: SS1 ePublished: 3 April 2018 Issue Published: 3 April 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.Loading ...
Comparison of prognostic models to predict the occurrence of colorectal cancer in asymptomatic individuals: a systematic literature review and external validation in the EPIC and UK Biobank prospective cohort studies
Authors: Todd Smith, David C Muller, Karel G M Moons, Amanda J Cross, Mattias Johansson, Pietro Ferrari, Guy Fagherazzi, Petra H M Peeters, Gianluca Severi, Anika Hüsing, Rudolf Kaaks, Anne Tjonneland, Anja Olsen, Kim Overvad, Catalina Bonet, Miguel Rodriguez-Barranco, Jose Maria Huerta, Aurelio Barricarte Gurrea, Kathryn E Bradbury, Antonia Trichopoulou, Christina Bamia, Philippos Orfanos, Domenico Palli, Valeria Pala, Paolo Vineis, Bas Bueno-de-Mesquita, Bodil Ohlsson, Sophia Harlid, Bethany Van Guelpen, Guri Skeie, Elisabete Weiderpass, Mazda Jenab, Neil Murphy, Elio Riboli, Marc J Gunter, Krasimira Jekova Aleksandrova, Ioanna Tzoulaki
Journal: Gut (2018)

Objective To systematically identify and validate published colorectal cancer risk prediction models that do not require invasive testing in two large population-based prospective cohorts. Design Models were identified through an update of a published systematic review and validated in the European Prospective Investigation into Cancer and Nutrition (EPIC) and the UK Biobank. The performance of the models to predict the occurrence of colorectal cancer within 5 or 10 years after study enrolment was assessed by discrimination (C-statistic) and calibration (plots of observed vs predicted probability). Results The systematic review and its update identified 16 models from 8 publications (8 colorectal, 5 colon and 3 rectal). The number of participants included in each model validation ranged from 41 587 to 396 515, and the number of cases ranged from 115 to 1781. Eligible and ineligible participants across the models were largely comparable. Calibration of the models, where assessable, was very good and further improved by recalibration. The C-statistics of the models were largely similar between validation cohorts with the highest values achieved being 0.70 (95% CI 0.68 to 0.72) in the UK Biobank and 0.71 (95% CI 0.67 to 0.74) in EPIC. Conclusion Several of these non-invasive models exhibited good calibration and discrimination within both external validation populations and are therefore potentially suitable candidates for the facilitation of risk stratification in population-based colorectal screening programmes. Future work should both evaluate this potential, through modelling and impact studies, and ascertain if further enhancement in their performance can be obtained.
Platelets’ Role in Adaptive Immunity May Contribute to Sepsis and Shock
Authors: Tracy Hampton
Journal: JAMA (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 15659: Collagen Biomaterial Enhances Cd34+ Cell Function Through Mir-21b
Authors: Brian McNeill, Aleksandra Ostojic, Marc Ruel, Katey J Rayner, Erik J Suuronen
Journal: Circulation (2016)

Introduction:  CD34 +  cells represent a promising cell for revascularization therapy as they incorporate into newly forming vessels and stimulate endogenous revascularization processes. However, CD34 +  cell therapy is limited by low cell numbers and engraftment upon transplantation. In this study, a collagen type I biomaterial (matrix) was used to expand and enhance CD34 +  cell function and potential underlying mechanisms were examined.   Methods:  CD34 +  cells were enriched from human blood mononuclear cells cultured on fibronectin or matrix by magnetic bead separation. Culture supernatants were analyzed for exosome secretion and content.   Results:  Compared to fibronectin, matrix derived CD34 +  cells had increased proliferation (2.1±0.4 fold), migration (3.2±0.8 fold) and angiogenic potential as determined by incorporation into tube-like structures (3.6±0.6 fold) and capillary network formation (2.3±0.6 fold;  p ≤0.002). Exosomes are known to regulate the angiogenic effects of CD34 +  cells. Here, we observed a 1.4±0.1 fold increase in secreted CD63 + CD81 +  exosomes from matrix-cultured cells compared to fibronectin. In matrix-derived exosomes, we detected greater levels of two microRNAs, miR-21 (7.4±2.6 fold) and miR-210 (2.7±0.6 fold), compared to fibronectin ( p ≤0.03). One miR-21 target of interest, Spry1, is a negative regulator of endothelial cell proliferation and angiogenesis. In matrix-cultured cells, Spry1 mRNA and protein levels were reduced by 5.8±1.0 and 2.9±0.1 fold, respectively ( p ≤0.001). Furthermore, when cells from CVD patients were cultured on matrix, we observed similar results to healthy CD34 +  cells: a 3.3±0.9 and 2.5±0.4 fold increase in miR-21 and miR-210, respectively ( p ≤0.03). Matrix-cultured CVD cells also had improved VEGF-mediated migration (2.9±0.7 fold) and increased capillary network formation in an angiogenesis assay (1.7±0.1 fold).   Conclusion:  Our results suggest that matrix culture may be useful for expanding the number and enhancing the function of CD34 +  cells in CVD patients, which may be mediated through suppression of Spry1 activity by exosome-derived miR-21. Therefore, our biomaterial offers a novel strategy to enhance the therapeutic potential of CD34 +  cells for vascular regeneration.
Chronic respiratory failure in patients with chronic obstructive pulmonary disease under home noninvasive ventilation: Real-life study
Authors: V. Durão, M. Grafino, P. Pamplona
Journal: Pulmonology (2018)

Home noninvasive ventilation (NIV) has been increasingly used in stable chronic obstructive pulmonary disease (COPD) with chronic hypercapnic respiratory failure (CHRF). However its effectiveness remains debatable.To describe a follow-up of COPD patients under home NIV.Retrospective descriptive study based on a prospective 3-year database that included COPD patients under home NIV between August 2011 and July 2014.Within the 334 patients initially screened, 109 (32.6%) had COPD with a mean±SD post-bronchodilator FEV1 of 38.6±14.9% predicted; age of 65.6±9.6 years. The mean±SD duration of ventilation was 63.4±51.1 months. Heterogeneous comorbidities that can contribute to CHRF were not excluded: obstructive sleep apnea and obesity were the most prevalent. Sixty-two (56.9%) patients started NIV during admission with acute respiratory failure. During follow-up there was a significant increase in mean inspiratory positive airway pressure (IPAP) and respiratory rate (19.5±4.4 vs. 23.6±5.3cmH2O and 10.7±5.2 vs. 15.2±1.4 breaths/min, respectively, p<0.0001), with a significant improvement in hypercapnia (PaCO2: 52.9±7.7 vs. 49.5±7.5mmHg, p<0.0001), with 93.3% of patients compliant to NIV. Admissions and days spent in hospital for respiratory illness significantly decreased after institution of NIV (respectively, 1.2±1.1 vs. 0.7±1.8 and 15.0±16.8 vs. 8.8±19.4, p<0.001). At final evaluation, patients with severe hypercapnia (n=47; PaCO2 ≥50mmHg) performing NIV at higher pressures (n=30; IPAP ≥25cmH2O) were more compliant (10.1±3.3 vs. 6.1±3.6h/day). Three-year mortality was 24.8% (27 of 109 patients).This is a real-life retrospective study in COPD patients with CHRF which results suggest benefit from home NIV. For most, NIV was effective and tolerable even at high pressures.
The practice of everyday life provides supporters and inviters of morally responsible agency
Authors: Jörg Zinken, Vasudevi Reddy
Journal: Behavioral and Brain Sciences (2018)

Abstract Drawing on research from conversation analysis and developmental psychology, we point to the existence of “supporters” of morally responsible agency in everyday interaction: causes of our behavior that we are often unaware of, but that would make good-enough reasons for our actions, were we made aware of them.
Genetic predilections and predispositions for the development of shamanism
Authors: Jacob A. Fiala, Frederick L. Coolidge
Journal: Behavioral and Brain Sciences (2018)

Abstract Singh's cultural evolutionary theory of shamanism provides a valuable framework for understanding shamanism. We argue, however, that a full understanding of shamanism should incorporate the psychological predilections and genetic predispositions commonly found in individual shamans. In other words, only a small subset of individuals in a culture is prone or attracted to shamanistic practices, regardless of the evolutionary value of those practices.
Enjoying your cultural cheesecake: Why believers are sincere and shamans are not charlatans
Authors: Maarten Boudry
Journal: Behavioral and Brain Sciences (2018)

Abstract Cultural evolution explains not just when people tend to develop superstitions, but also what forms these beliefs take. Beliefs that are more resilient in the face of apparent refutations and more susceptible to occasional confirmation stand a greater chance of cultural success. This argument helps to dispel the impression that shamans are mere charlatans and believers are “faking it.”
Abstract 15940: Laminar Shear Stress Induces a Vangl2 Vimentin Association in HUVEC
Authors: Logan Curtis-Whitchurch, Danny Wilkey, Mike Merchant, Jay Hoying
Journal: Circulation (2016)

Introduction: Vascular endothelial cells (ECs) are strongly influenced by flow. Disturbed flow patterns trigger vascular pathology including atherosclerosis, neointimal hyperplasia, and faulty tone...
Detection of anti-BP180 NC16A autoantibodies after the onset of dipeptidyl peptidase-IV inhibitor-associated bullous pemphigoid: a report of three patients
Authors: Y. Mai, W. Nishie, K. Izumi, N. Yoshimoto, Y. Morita, M. Watanabe, E. Toyonaga, H. Ujiie, H. Iwata, Y. Fujita, T. Nomura, K.C. Sato-Matsumura, S. Shimizu, H. Shimizu
Journal: British Journal of Dermatology (2018)
Oncogenic fusion proteins adopt the insulin-like growth factor signaling pathway
Authors: Haim Werner, Shilhav Meisel-Sharon, Ilan Bruchim
Journal: Molecular Cancer (2018)

The insulin-like growth factor-1 receptor (IGF1R) has been identified as a potent anti-apoptotic, pro-survival tyrosine kinase-containing receptor. Overexpression of the IGF1R gene constitutes a typical feature of most human cancers. Consistent with these biological roles, cells expressing high levels of IGF1R are expected not to die, a quintessential feature of cancer cells. Tumor specific chromosomal translocations that disrupt the architecture of transcription factors are a common theme in carcinogenesis. Increasing evidence gathered over the past fifteen years demonstrate that this type of genomic rearrangements is common not only among pediatric and hematological malignancies, as classically thought, but may also provide a molecular and cytogenetic foundation for an ever-increasing portion of adult epithelial tumors. In this review article we provide evidence that the mechanism of action of oncogenic fusion proteins associated with both pediatric and adult malignancies involves transactivation of the IGF1R gene, with ensuing increases in IGF1R levels and ligand-mediated receptor phosphorylation. Disrupted transcription factors adopt the IGF1R signaling pathway and elicit their oncogenic activities via activation of this critical regulatory network. Combined targeting of oncogenic fusion proteins along with the IGF1R may constitute a promising therapeutic approach.
Interventions to Prevent Falls in Older Adults
Authors: Young Ho Lee, Gwan Gyu Song
Journal: JAMA (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
A single arm phase II study of rucaparib maintenance in patients with advanced pancreatic adenocarcinoma and a known deleterious <i>BRCA1, BRCA2</i> or <i>PALB2</i> mutation who have achieved stability on platinum therapy.
Authors: Kim Anna Reiss, Kara Noelle Maxwell, Katharine Nathanson, Ursina R. Teitelbaum, Mark H. O'Hara, Peter J. O'Dwyer, Charles Schneider, Erica L. Carpenter, Rosemarie Mick, Susan M. Domchek
Journal: Journal of Clinical Oncology (2018)

TPS531 Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with a median overall survival of &lt; 1 year. A subset of PDAC is characterized by a homologous recombination deficiency (HRD). The most well-defined patients within this group are those with deleterious mutations in BRCA1, BRCA2 and PALB2. This subset of tumors respond exceptionally well to treatment with platinum agents, leading to durable responses. However, cumulative toxicity can complicate or even prevent continued therapy, and there is an unmet need to establish maintenance strategies for such patients.Prior studies have shown that BRCA1 and BRCA2 associated PDACs respond to PARP inhibitors. Cross-resistance to platinum and PARP inhibitors exists, so initiating PARP inhibitor therapy after the development of platinum-resistance is an inferior approach. In this setting, we have designed a phase II trial of rucaparib as maintenance therapy for patients with deleterious BRCA1, BRCA2 or PALB2 who have sustained stability on platinum-based treatment. Methods: We have enrolled 2 of 42 planned patients on study NCT03140670. Eligibility criteria include inoperable PDAC, a known somatic or germline deleterious mutation in BRCA1, BRCA2 or PALB2 and stability on platinum-based chemotherapy for ≥16 weeks. Patients who have progressed on platinum-based treatment or who have received prior therapy with PARP inhibitors are excluded. Patients will receive oral rucaparib twice daily continuously in 28-day cycles. The primary endpoint is progression-free survival at 6 months. Secondary endpoints include response rate, duration of response and overall survival. A pre-treatment tumor biopsy and biopsy at progression will be obtained, as well as serial blood collections for circulating tumor material. Correlative assays will include tumor and circulating tumor DNA sequencing to identify genomic predictors of outcome and study resistance mechanisms. Clinical trial information: NCT03140670.
Lower Cancer Incidence—Warfarin Effect or Immortal Time Bias?
Authors: Kristian Svendsen, Øystein Karlstad, Lars Småbrekke
Journal: JAMA Internal Medicine (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Association of a Negative Wealth Shock With All-Cause Mortality in Middle-aged and Older Adults in the United States
Authors: Lindsay R. Pool, Sarah A. Burgard, Belinda L. Needham, Michael R. Elliott, Kenneth M. Langa, Carlos F. Mendes de Leon
Journal: JAMA (2018)

A sudden loss of wealth-a negative wealth shock-may lead to a significant mental health toll and also leave fewer monetary resources for health-related expenses. With limited years remaining to regain lost wealth in older age, the health consequences of these negative wealth shocks may be long-lasting.To determine whether a negative wealth shock was associated with all-cause mortality during 20 years of follow-up.The Health and Retirement Study, a nationally representative prospective cohort study of US adults aged 51 through 61 years at study entry. The study population included 8714 adults, first assessed for a negative wealth shock in 1994 and followed biennially through 2014 (the most recent year of available data).Experiencing a negative wealth shock, defined as a loss of 75% or more of total net worth over a 2-year period, or asset poverty, defined as 0 or negative total net worth at study entry.Mortality data were collected from the National Death Index and postmortem interviews with family members. Marginal structural survival methods were used to account for the potential bias due to changes in health status that may both trigger negative wealth shocks and act as the mechanism through which negative wealth shocks lead to increased mortality.There were 8714 participants in the study sample (mean [SD] age at study entry, 55 [3.2] years; 53% women), 2430 experienced a negative wealth shock during follow-up, 749 had asset poverty at baseline, and 5535 had continuously positive wealth without shock. A total of 2823 deaths occurred during 80 683 person-years of follow-up. There were 30.6 vs 64.9 deaths per 1000 person-years for those with continuously positive wealth vs negative wealth shock (adjusted hazard ratio [HR], 1.50; 95% CI, 1.36-1.67). There were 73.4 deaths per 1000 person-years for those with asset poverty at baseline (adjusted HR, 1.67; 95% CI, 1.44-1.94; compared with continuously positive wealth).Among US adults aged 51 years and older, loss of wealth over 2 years was associated with an increased risk of all-cause mortality. Further research is needed to better understand the possible mechanisms for this association and determine whether there is potential value for targeted interventions.