tbuckley/cabot-search huggingface dataset:
Enhancing evidence-based medicine skills in oncology training with cognitive technology.
Authors: Chun-You Chen, Hui-Chun Hung, Hsin-Yi Chiu, Po-Li Wei, Pih-Lian Kuo, Jeng-Fong Chiou, Anita Preininger, Irene Dankwa-Mullan, Sarah Kefayati, Metasebya Solomon, Gretchen Jackson, Kyu Rhee, Yun Yen
Journal: Journal of Clinical Oncology (2019)

10532 Background: Evidence-based medicine (EBM) requires applying literature evidence to inform practice. Students from Taipei Medical University Hospital, trained in EBM concepts, participated in a preliminary study using Watson for Oncology (WfO), an evidence-based decision-support system to enhance the EBM skills of medical students. Methods: A class of 50 medical students compared traditional search methods (TSM) and WfO in a workshop divided into 2 sequential sessions on colon and lung cancer, respectively. All students were trained on WfO, and 2 groups of 25 students each were randomly assigned to either TSM or WfO in the first session. Those groups were then assigned to the alternate approach in the second session. Students completed a profile that included their clinical experience with each cancer type. Students used either WfO or TSM to help answer a series of questions related to colon or lung cancer. Students then completed a survey of attitudes towards the technology, followed by a constructed-response learning assessment without the aid of TSM or WfO. Assessments were scored and results compared using a Mann-Whitney U Test; outcomes at two different experience levels, based on student profiles, were compared using a Kruskal-Wallis test. Results: In this preliminary study, more than 70% of students reported limited clinical experience with either cancer. On the colon cancer assessment, students in the WfO group performed significantly better than the TSM group ( p = 0.0001); there was no significant difference detected for lung cancer. Students with more clinical experience felt that TSM was easier to learn than WfO ( p= 0.005); students with less experience felt that WfO was clearer and more understandable than TSM ( p= 0.002). Conclusions: These preliminary results are consistent with better learning outcomes for students using WfO in the colon cancer module. Students with more clinic experience reported that TSM was easier to learn than WfO, however it is unknown if this might be due to a potentially greater familiarity with TSM in this more experienced group. More studies are needed to determine what features, if any, of WfO can facilitate EBM approaches in oncology education.
KIT D816 Mutated / CBF-Negative Acute Myeloid Leukemia (AML): A New Poor-Risk Subtype Associated with Systemic Mastocytosis (SM-AML)
Authors: Mohamad Jawhar, Konstanze Döhner, Sebastian Kreil, Juliana Schwaab, Khalid Shoumariyeh, Manja Meggendorfer, Lambert L.F. Span, Stephan Fuhrmann, Nicole Naumann, Hans-Peter Horny, Karl Sotlar, Boris Kubuschok, Nikolas von Bubnoff, Karsten Spiekermann, Michael Heuser, Georgia Metzgeroth, Alice Fabarius, Stefan A Klein, Wolf-Karsten Hofmann, Hanneke Kluin-Nelemans, Torsten Haferlach, Hartmut Döhner, Nicholas C.P. Cross, Wolfgang R. Sperr, Peter Valent, Andreas Reiter
Journal: Blood (2018)
Bronchial thermoplasty decreases airway remodelling by blocking epithelium-derived heat shock protein-60 secretion and protein arginine methyltransferase-1 in fibroblasts
Authors: Qingzhu Sun, Lei Fang, Michael Roth, Xuemei Tang, Eleni Papakonstantinou, Weiqi Zhai, Renaud Louis, Vincent Heinen, Florence N. Schleich, Shemin Lu, Spasenjia Savic, Michael Tamm, Daiana Stolz
Journal: European Respiratory Journal (2019)

Bronchial thermoplasty (BT) is to date the only therapy that provides a lasting reduction in airway wall remodelling. However, the mechanism of action of BT is not well understood. This study aimed to characterise the changes of remodelling regulating signalling pathways by BT in asthma.Bronchoalveolar lavage fluid (BALF) was obtained from eight patients with severe asthma before and after BT. Primary bronchial epithelial cells were isolated from 23 patients before (n=66) and after (n=62) BT. Epithelial cell culture supernatant (Epi.S) was collected and applied to primary fibroblasts.Epithelial cells obtained from asthma patients after BT proliferated significantly faster compared with epithelial cells obtained before BT. In airway fibroblasts, BALF or Epi.S obtained before BT increased CCAAT enhancer-binding protein-β (C/EBPβ) expression, thereby downregulating microRNA-19a. This upregulated extracellular signal-regulated kinase-1/2 (ERK1/2) expression, protein arginine methyltransferase-1 (PRMT1) expression, cell proliferation and mitochondrial mass. BALF or Epi.S obtained after BT reduced the expression of C/EBPβ, ERK1/2, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α), PRMT1 and mitochondrial mass in airway fibroblasts. Proteome and transcriptome analyses indicated that epithelial cell-derived heat shock protein-60 (HSP60) is the main mediator of BT effects on fibroblasts. Further analysis suggested that HSP60 regulated PRMT1 expression, which was responsible for the increased mitochondrial mass and α-smooth muscle actin expression by asthmatic fibroblasts. These effects were ablated after BT. These results imply that BT reduces fibroblast remodelling through modifying the function of epithelial cells, especially by reducing HSP60 secretion and subsequent signalling pathways that regulate PRMT1 expression.We therefore hypothesise that BT decreases airway remodelling by blocking epithelium-derived HSP60 secretion and PRMT1 in fibroblasts.
Relative contribution of clinicopathological variables, genomic markers, transcriptomic subtyping and microenvironment features for outcome prediction in stage II/III colorectal cancer
Authors: R. Dienstmann, G. Villacampa, A. Sveen, M.J. Mason, D. Niedzwiecki, A. Nesbakken, V. Moreno, R.S. Warren, R.A. Lothe, J. Guinney
Journal: Annals of Oncology (2019)

BackgroundIt remains unknown to what extent consensus molecular subtype (CMS) groups and immune-stromal infiltration patterns improve our ability to predict outcomes over tumor–node–metastasis (TNM) staging and microsatellite instability (MSI) status in early-stage colorectal cancer (CRC).Patients and methodsWe carried out a comprehensive retrospective biomarker analysis of prognostic markers in adjuvant chemotherapy-untreated (N = 1656) and treated (N = 980), stage II (N = 1799) and III (N = 837) CRCs. We defined CMS scores and estimated CD8+ cytotoxic lymphocytes (CytoLym) and cancer-associated fibroblasts (CAF) infiltration scores from bulk tumor tissue transcriptomes (CMSclassifier and MCPcounter R packages); constructed a stratified multivariable Cox model for disease-free survival (DFS); and calculated the relative proportion of explained variation by each marker (clinicopathological [ClinPath], genomics [Gen: MSI, BRAF and KRAS mutations], CMS scores [CMS] and microenvironment cells [MicroCells: CytoLym+CAF]).ResultsIn multivariable models, only ClinPath and MicroCells remained significant prognostic factors, with both CytoLym and CAF infiltration scores improving survival prediction beyond other markers. The explained variation for DFS models of ClinPath, MicroCells, Gen markers and CMS4 scores was 77%, 14%, 5.3% and 3.7%, respectively, in stage II; and 55.9%, 35.1%, 4.1% and 0.9%, respectively, in stage III. Patients whose tumors were CytoLym high/CAF low had better DFS than other strata [HR=0.71 (0.6–0.9); P = 0.004]. Microsatellite stable tumors had the strongest signal for improved outcomes with CytoLym high scores (interaction P = 0.04) and the poor prognosis linked to high CAF scores was limited to stage III disease (interaction P = 0.04).ConclusionsOur results confirm that tumor microenvironment infiltration patterns represent potent determinants of the risk for distant dissemination in early-stage CRC. Multivariable models suggest that the prognostic value of MSI and CMS groups is largely explained by CytoLym and CAF infiltration patterns.
Impact on child acute malnutrition of integrating a preventive nutrition package into facility-based screening for acute malnutrition during well-baby consultation: A cluster-randomized controlled trial in Burkina Faso
Authors: Elodie Becquey, Lieven Huybregts, Amanda Zongrone, Agnes Le Port, Jef L. Leroy, Rahul Rawat, Mariama Touré, Marie T. Ruel
Journal: PLoS Medicine (2019)

Community management of acute malnutrition (CMAM) is a highly efficacious approach for treating acute malnutrition (AM) in children who would otherwise be at significantly increased risk of mortality. In program settings, however, CMAM's effectiveness is limited because of low screening coverage of AM, in part because of the lack of perceived benefits for caregivers. In Burkina Faso, monthly screening for AM of children <2 years of age is conducted during well-baby consultations (consultation du nourrisson sain [CNS]) at health centers. We hypothesized that the integration of a preventive package including age-appropriate behavior change communication (BCC) on nutrition, health, and hygiene practices and a monthly supply of small-quantity lipid-based nutrient supplements (SQ-LNSs) to the monthly screening would increase AM screening and treatment coverage and decrease the incidence and prevalence of AM.
Final efficacy results of NCIC CTG IND.202: A randomized phase II study of recombinant interleukin-21 (rIL21) in patients with recurrent or metastatic melanoma (MM).
Authors: Teresa M. Petrella, Catalin Liviu Dragos Mihalcioiu, Elaine McWhirter, Karl Belanger, Kerry J. Savage, Xinni Song, Omid Hamid, Tina Cheng, Mary L. Davis, Christopher W Lee, Alan Spatz, Jose Gerard Monzon, Linda Hagerman, Bingshu E Chen, Janet Dancey
Journal: Journal of Clinical Oncology (2013)

9032 Background: rIL21 is a T-cell derived cytokine with antitumor activity dependent on NK cells or CD8+ T cells through induction of central and effector memory cells. A previous phase II study demonstrated an ORR of 22.5% in previously untreated patients with MM. We conducted a multicentre randomized phase II study of MM evaluating the efficacy, toxicity, pharmacokinetics, immunogenicity, and biomarkers of rIL21 versus dacarbazine (DTIC). Methods: Eligible patients: Recurrent or MM, with either maximum tumour lesion size of &lt; 50 mm or LDH &lt; 2.5 x ULN and prior therapy with BRAF/MEK inhibitors allowed. Patients were treated with either rIL-21, 30 µg /kg/day dose IV daily x 5 days weeks 1, 3, 5 q 8 weeks or dacarbazine (DTIC) 1000 mg/m2 IV q 3 weeks. The primary objective was to compare progression free survival (PFS). The trial was designed to detect a hazard ratio of 1.75 with one-sided alpha of 0.1; 58 progression events were required to provide 80% power. Results: 64 patients were randomized, 32 in the rIL-21 arm and 32 in the DTIC arm. The Table summarizes key demographic and efficacy endpoints. Common rIl21 related adverse events were fatigue, rash, diarrhea, nausea, myalgia and elevated liver enzymes. At least one dose reduction/ interruption or discontinuation occurred in 32 (100%) and 27 (96.4%) of rIL21 and DTIC patients. Conclusions: Despite encouraging efficacy in prior phase I/II studies, the results suggest that rIL-21 is comparable to DTIC in this patient population. Additional biomarker analysis from this study is pending and combination studies are currently ongoing. Clinical trial information: NCT00514085. [Table: see text]
CGRP derived from cardiac fibroblasts is an endogenous suppressor of cardiac fibrosis
Authors: Wenqun Li, Zheng Zhang, Xiaohui Li, Jifeng Cai, Dai Li, Jie Du, Bikui Zhang, Daxiong Xiang, Niansheng Li, Yuanjian Li
Journal: Cardiovascular Research (2019)

Abstract Aims Aberrant activation of cardiac fibroblasts leads to cardiac fibrosis, and evolving evidences suggest that endogenous bioactive substances derived from cardiac fibroblasts regulate cardiac fibroblasts activation in an autocrine/paracrine manner. Here we first presented evidence that cardiac fibroblasts can synthesize and secrete calcitonin gene-related peptide (CGRP), therefore, this study aimed to investigate the role of cardiac fibroblasts-derived CGRP in cardiac fibroblasts activation and its regulative mechanism. Methods and results The abundantly expression of CGRP in rat, mouse, and human myocardium allowed us to explore the cellular origin of CGRP, and found that the cardiac CGRP was mainly derived from cardiac fibroblasts. Activating TRPA1 with a specific agonist allyl isothiocyanate promoted the synthesis and secretion of CGRP, as well as intracellular Ca2+. These effects were reversed by TRPA1-specific antagonist HC030031 and Ca2+ chelator BAPTA-AM. TGF-β1 was applied to induce the activation of cardiac fibroblasts, and found that TGF-β1 can increase the mRNA expression and secretion levels of CGRP in cardiac fibroblasts. Either CGRP8–37 (CGRP receptor antagonist) or α-CGRP small interfering RNA (siRNA) aggravated TGF-β1-induced proliferation, differentiation, collagen production, and instigated inflammation in cardiac fibroblasts. Moreover, TGF-β1-induced NF-κB activation including IκBα phosphorylation and p65 nuclear translocation were also promoted by CGRP8–37 and α-CGRP siRNA. NF-κB inhibitor pyrrolidinedithiocarbamate ammonium (PDTC) reversed the effects of CGRP8–37 on NF-κB activation. The promotive effects of CGRP8–37 on TGF-β1-induced activation of cardiac fibroblasts were all reversed by PDTC. Monocrotaline (MCT) induces pulmonary arterial hypertension, progressively leading to right ventricular fibrosis. This model of cardiac fibrosis was developed here to test the potentially beneficial effects of TRPA1 activation in vivo. The non-toxic TRPA1 agonist Cinnamaldehyde (CA) inhibited MCT-induced elevation in right ventricle systolic pressure, RV/LV + S, and right ventricular collagen accumulation, as well as down-regulation of CGRP. CA increased the synthesis and secretion of CGRP, and inhibited TGF-β1-induced activation in cardiac fibroblasts. Conclusion Our data suggested an autocrine role for cardiac fibroblasts-derived CGRP in suppressing activation of cardiac fibroblasts through inhibiting NF-κB activation. Increasing autocrine CGRP by activating TRPA1 can ameliorate cardiac fibrosis. These findings support the notion that CGRP derived from cardiac fibroblasts is an endogenous suppressor of cardiac fibrosis.
Early Reduction of Serum TARC Levels Predicts Prognosis of Patients Treated with a PET-Adapted Strategy for Advanced Stage Hodgkin Lymphoma (HL) in the GITIL/FIL HD0607 Trial
Authors: Simonetta Viviani, Arabella Mazzocchi, Chiara Pavoni, Francesca Taverna, Anna Guidetti, Andrea Rossi, Caterina Patti, Alessandra Romano, Livio Trentin, Davide Rapezzi, Daniela Gottardi, Corrado Tarella, Michele Cimminiello, Roberta Zanotti, Andrés J M Ferreri, Roberta Serpi, Paolo Corradini, Alessandro M. Gianni, Andrea Gallamini, Alessandro Rambaldi
Journal: Blood (2017)
Anti-IL1RAP/CD3 Bispecific Antibody (BsAb) Is a Promising Novel and Effective Therapy for Acute Myeloid Leukemia (AML)
Authors: Weixu Meng, Marissa Del Real, Guowei Wei, Rochelle Hernandez, Emanuela Marcucci, Allen Lin, Tinisha Mcdonald, Dandan Zhao, Herman Wu, Nadia Carlesso, Larry W Kwak, Ling Li, Ya-Huei Kuo, Anthony S. Stein, Vinod Pullarkat, Ryotaro Nakamura, Steven T. Rosen, Stephen J. Forman, Bin Zhang, Lihua Budde, Guido Marcucci
Journal: Blood (2017)
Secondary surgery with intraoperative chemohyperthermia in recurrent ovarian adenocarcinoma.
Authors: Jean Marc Bereder, Mariangella Desantis, Emmanuel Benizri, Abakar Abakar-mahamat, jean-Louis Bernard, Amine Rahili, Nicolas Mounier, Daniel Benchimol
Journal: Journal of Clinical Oncology (2012)

5075 Background: Optimal treatment of peritoneal recurrences in ovarian cancer is debating with second line chemotherapies. We proposed association of secondary surgery with heated intraperitoneal per operative chemotherapy (HIPEC). The aim of study is to determine prognostic factors in a single center cohort. Methods: Retrospective study of consecutive 169 patients with peritoneal recurrence from ovarian cancer were performed to evaluate HIPEC and to identify prognostic factors. Peritoneal Cancer Index (PCI) assess tumor load and completeness cytoreductive score (CCS) were used to give quality of resection CCS0 (no visible tumor), CCS1 (persistent diffuse lesions &lt; 2.5mm), CCS2 (2.5mm &lt;CC2&lt; 25mm) and over CCS3 status. HIPEC is performed with platinum based regimen. Endpoint was survival. Cox's regression model was used for multivariate survival analysis and extending Cox model for modelling survival data. Results: We have operated on 197 procedures (HIPEC) in 169 patients from 2000 to 2011. Mean age was 58 years old range [28-75]. Median PCI was 10. After completion of resection, allocation of CCS was CCS0=120, CCS1=70, CCS2 &amp; CCS3 =7. Procedure related mortality was 1% and morbidity 21%, mean length of hospital stay was 17 days range [7-51]. 3 and 5 years overall survival were respectively 64.7% and 37.4 %. Median survival was 47.6 months and the median disease free survival was 20 months. PCI &gt;10 (even if complete resection performed) and CCS2&amp;3 were worse prognostic factors (HR respectively = 2.64 IC 95% [1.29-5.36] and = 3.31 IC 95 % [1.55-7.08]). Modelling of these factors, is very strong to predict risk of death over the 2 first years after HIPEC. Conclusions: The chemo-hyperthermia is a standardized and reproducible feasible method. Less extensive disease and the quality of cytoreduction remain an independent factor of better outcome. To date HIPEC allows to reach the longest median time survival in peritoneal recurrent ovarian cancer. Modelling survival data is useful to know the risk of dying.
Rapid progression of adult T-cell leukemia/lymphoma as tumor-infiltrating Tregs after PD-1 blockade
Authors: Daniel A. Rauch, Kevin C. Conlon, Murali Janakiram, Jonathan E. Brammer, John C. Harding, B. Hilda Ye, Xingxing Zang, Xiaoxin Ren, Sydney Olson, Xiaogang Cheng, Milos D. Miljkovic, Hemalatha Sundaramoorthi, Ancy Joseph, Zachary L. Skidmore, Obi Griffith, Malachi Griffith, Thomas A. Waldmann, Lee Ratner
Journal: Blood (2019)
Abstract 15898: Sustaining Quality of Life of the Aged: Transplant or Mechanical Support (SUSTAIN-IT): Baseline Caregiver Burden
Authors: Ike Okwuosa, Allen S Anderson, Michael Petty, Adam Hubert, Laura Pollan, Adin-Cristian Andrei, Andrew Kao, Duc Pham, Clyde Yancy, Mary Amanda Dew, Robert Kormos, Eileen Hirsch, William Cotts, Shane LaRue, Salpy Pamboukian, Francis Pagani, Brent Lampert, Maryl Johnson, Margaret Murray, Koji Tekeda, Melana Yuzefpolskaya, John Spertus, James K Kirklin, Stephen C Collum, Kathleen L Grady
Journal: Circulation (2018)

Background: Caregivers provide essential disease management support, as well as emotional and social support, for patients (pts) with advanced heart failure (HF). Caregiving can be burdensome and a...
Topical Recombinant Human Nerve Growth Factor (Cenegermin) for Neurotrophic Keratopathy
Authors: Stephen C. Pflugfelder, Mina Massaro-Giordano, Victor L. Perez, Pedram Hamrah, Sophie X. Deng, Ladan Espandar, C. Stephen Foster, John Affeldt, John A. Seedor, Natalie A. Afshari, Wendy Chao, Marcello Allegretti, Flavio Mantelli, Reza Dana
Journal: Ophthalmology (2019)

To evaluate the efficacy and safety of topical cenegermin (recombinant human nerve growth factor) in patients with neurotrophic keratopathy.Multicenter, randomized, double-masked, vehicle-controlled trial.Patients with neurotrophic persistent epithelial defect with or without stromal thinning.The NGF0214 trial, conducted among 11 sites in the United States, randomized 48 patients 1:1 to cenegermin 20 μg/ml or vehicle eye drops, 6 drops daily for 8 weeks of masked treatment. Follow-up was 24 weeks. Safety was assessed in all patients who received study drug. Efficacy was assessed by intention to treat.The primary end point was healing of the neurotrophic lesion (persistent epithelial defect or corneal ulcer) after 8 weeks of masked treatment. Masked central readers measured neurotrophic lesions in randomized clinical pictures, then assessed healing status conventionally (<0.5 mm of fluorescein staining in the greatest dimension of the lesion area) and conservatively (0-mm lesion staining and no other residual staining). Secondary variables included corneal healing at 4 weeks of masked treatment (key secondary end point), overall changes in lesion size, rates of disease progression, and changes in visual acuity and corneal sensitivity from baseline to week 8.Conventional assessment of corneal healing showed statistically significant differences at week 8: compared to 7 of 24 vehicle-treated patients (29.2%), 16 of 23 cenegermin-treated patients (69.6%) achieved less than 0.5 mm of lesion staining (+40.4%; 95% confidence interval [CI], 14.2%-66.6%; P = 0.006). Conservative assessment of corneal healing also reached statistical significance at week 8: compared to 4 of 24 vehicle-treated patients (16.7%), 15 of 23 cenegermin-treated patients (65.2%) achieved 0 mm of lesion staining and no other residual staining (+48.6%; 95% CI, 24.0%-73.1%; P < 0.001). Moreover, the conservative measure of corneal healing showed statistical significance at week 4 (key secondary end point). Compared to vehicle, cenegermin-treated patients showed statistically significant reductions in lesion size and disease progression rates during masked treatment. Cenegermin was well tolerated; adverse effects were mostly local, mild, and transient.Cenegermin treatment showed higher rates of corneal healing than vehicle in neurotrophic keratopathy associated with nonhealing corneal defects.
Smartphones can improve adherence rates for TB treatment
Authors: Rob Cook, Tara Lamont, Rosie Martin
Journal: BMJ (2019)

The studyStory A, Aldridge R, Smith C, et al. Smartphone-enabled video-observed versus directly observed treatment for tuberculosis: a multicentre, analyst-blinded, randomised, controlled superiority trial. Lancet 2019;393:1216-24.The study was funded by the NIHR Programme Grants for Applied Research programme (project number RP-PG-0407-10340).To read the full NIHR Signal, go to https://discover.dc.nihr.ac.uk/content/signal-000777/smartphones-for-tb-treatment-observation.