tbuckley/cabot-search huggingface dataset:
P06.01 Delta24-ACT oncolytic adenovirus as a therapeutic approach for DIPG
Authors: V Laspidea, M Puigdelloses, M García-Moure, I Iñigo-Marco, J Gallego, A Patiño-García, J Fueyo, C Gomez-Manzano, M M Alonso
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Diffuse intrinsic pontine glioma (DIPG) is an aggressive brain tumor, being the leading cause of pediatric death caused by cancer. We previously showed that administration of the oncolytic virus Delta-24-RGD to DIPG murine models was safe and led to an increase in the median survival of these animals. However, not all the animals responded, underscoring the need to improve this therapy. In order to increase the antitumoral effect of the virus, we have engineered Delta-24-RGD with the costimulatory ligand 4-1BBL (Delta24-ACT). 4-1BB is a costimulatory receptor that promotes the survival and expansion of activated T cells, and the generation and maintenance of memory CD8+ T cells. In this project, we evaluated the oncolytic effect of Delta24-ACT and the antitumor immune response in DIPG murine models. MATERIALS AND METHODS We use the NP53 and XFM murine DIPG cell lines. Flow cytometry was used to assess cell infectivity and ligand expression. We analyzed viral replication using a method based in hexon detection, and viral cytotoxic effect using the MTS assay. For immunogenic cell death analysis, we measured ATP secretion by a luminometric assay and calreticulin location by flow cytometry and immunofluorescence. For in vivo studies, cells and virus were injected in the pons of the mice, using the screw-guided system. RESULTS In vitro, Delta24-ACT was able to infect and induce cell death in a dose-dependent manner in murine DIPG cell lines. In addition, Delta24-ACT was able to replicate in these tumor cells and to express viral proteins. Moreover, infected cells expressed 41BBL in their membranes. Delta24-ACT could induce immunogenic cell death due to an increased secretion of ATP and calreticulin translocation to the membrane of infected cells (in no-infected cells it located in the ER), DAMPs that can trigger the immune response activation. In vivo, Delta24-ACT demonstrated to be safe in all the tested doses and was able to induce a significant increase in the median survival of the treated animals. Moreover, long-term survivors display immunological memory. CONCLUSIONS Delta24-ACT treatment led to antitumoral effect in DIPG murine cell lines in vitro. Of significance, we have demonstrated that in vivo administration of Delta24-ACT is safe and results in an enhanced antitumor effect. Future in vivo studies will explore the underlying immune mechanism of the virus.
H2020 funding for respiratory research: scaling up for the prevention and treatment of lung diseases
Authors: Constantine I. Vardavas, Christina N. Kyriakos, Esteve Fernández, Panagiotis Bamidis, Kamran Siddiqi, Niels H. Chavannes, R.M.J.J. van der Kleij, Gary Parker, Cornel Radu-Loghin, Brian Ward, Karim Berkouk
Journal: European Respiratory Journal (2019)

<b>This European Lung Corner article summarises five key messages for future research and practice in preventing and treating lung diseases based on outcomes and perspectives from five Horizon 2020 projects</b>http://bit.ly/2YCJV5N
Abstract 11723: Incident Atrial Fibrillation is Associated With Longitudinal Increase in Subclinical Cerebral Infarcts: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Lin Y Chen, Faye L Norby, Rebecca F Gottesman, Aaron R Folsom, Thomas H Mosley, Alvaro Alonso
Journal: Circulation (2015)

Background: The mechanisms underlying atrial fibrillation (AF)-related dementia are unclear and may include (1) clinical or subclinical cerebral infarcts (SCIs) or (2) chronic subcortical ischemia which results in white matter hyperintensities (WMH). Previous studies have reported that AF is associated with a higher prevalence of SCIs. However, these studies were mostly cross-sectional and based on whites and hospitalized subjects. To overcome limitations of previous studies, we evaluated the association of incident AF with 10-year change in SCIs and WMH in ARIC, a biracial community-based prospective cohort study. Hypothesis: We hypothesized that incident AF is associated with an increase over time in the number of SCIs. Methods: We included 914 (mean age, 61.7 ± 4.4 years; 38% men; 49% black) participants without prevalent AF, prevalent or incident clinical stroke, and who had brain MRI scans in 1993-95 and 2004-06. SCIs were defined as focal, non-mass lesions ≥3 mm that were bright on T2 and proton density, and dark on T1 images. We used logistic and general linear models to assess association between incident AF and gain in number of SCIs and change in WMH volume, respectively. Results: The median time between the 2 MRIs was 10.5 years. During this period, 46 participants developed AF. Those who developed AF had a 2.2-fold higher odds of gain in SCIs than those without AF. Incident AF, however, was not significantly associated with longitudinal change in WMH volume (Table). Conclusions: Incident AF is associated with an increase over time in the number of SCIs but not with WMH progression. Further research is needed to determine whether the longitudinal increase in SCIs mediates AF-related cognitive decline and dementia.
Analysis of PET-CT to Identify Richter's Transformation in 167 Patients with Disease Progression Following Kinase Inhibitor Therapy
Authors: Anthony R. Mato, William G Wierda, Matthew S. Davids, Bruce D. Cheson, Steven Coutre, Michael Choi, Richard R. Furman, Leonard Heffner, Paul M. Barr, Herbert Eradat, Lang Zhou, Maria Verdugo, Jalaja Potluri, Jeffrey Jones
Journal: Blood (2017)
Impact of Specimen Characteristics on PD-L1 Testing in Non–Small Cell Lung Cancer: Validation of the IASLC PD-L1 Testing Recommendations
Authors: Andréanne Gagné, Emily Wang, Nathalie Bastien, Michèle Orain, Patrice Desmeules, Sylvain Pagé, Sylvain Trahan, Christian Couture, David Joubert, Philippe Joubert
Journal: Journal of Thoracic Oncology (2019)
Annals Graphic Medicine - Dr. Mom: Infection Control
Authors: Grace E. Farris
Journal: Annals of Internal Medicine (2019)

Web Exclusives3 September 2019Annals Graphic Medicine - Dr. Mom: Infection ControlFREEGrace E. Farris, MDGrace E. Farris, MDMount Sinai School of Medicine, New York, New York (G.E.F.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G19-0048 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Mount Sinai School of Medicine, New York, New York (G.E.F.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G18-0042.Author/Illustrator Information: Grace E. Farris, MD, is an assistant professor of medicine at Icahn School of Medicine at Mount Sinai and chief of hospital medicine at Mount Sinai West hospital in New York, New York. You can view her work at her Web site: www.farrisgrace.com.About Dr. Mom: In Dr. Mom, physician and cartoonist Grace Farris examines work–life balance while mothering and doctoring. Dr. Mom appears monthly in Annals Graphic Medicine at Annals.org. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 3 September 2019Volume 171, Issue 5Page: W27-W28KeywordsConflicts of interestDisclosureHospital medicineHospitalists ePublished: 3 September 2019 Issue Published: 3 September 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Rapid Recurrence of Eosinophilic Esophagitis Activity After Successful Treatment in the Observation Phase of a Randomized, Double-Blind, Double-Dummy Trial
Authors: Evan S. Dellon, John T. Woosley, Ashley Arrington, Sarah J. McGee, Jacquelyn Covington, Susan E. Moist, Jessica H. Gebhart, Joseph A. Galanko, John A. Baron, Nicholas J. Shaheen
Journal: Clinical Gastroenterology and Hepatology (2019)
Fine-Needle Aspiration Biopsy of Liver Lesions Yields Higher Tumor Fraction for Molecular Studies: A Direct Comparison With Concurrent Core Needle Biopsy
Authors: Patricia Ellen Goldhoff, Poonam Vohra, Kanti Pallav Kolli, Britt-Marie Ljung
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: This retrospective study evaluated and compared the diagnostic accuracy and suitability of tissue specimens for advanced molecular diagnostic testing obtained via 2 different techniques for percutaneous biopsy of primary and metastatic liver tumors. Patients and Methods: Samples from 137 patients with liver masses who underwent concurrent fine-needle aspiration biopsy with cell block (FNAB-CB) and core needle biopsy (CNB) at 2 hospitals were assessed for diagnostic accuracy, tumor fraction, and tumor cellularity. A subset of FNAB-CBs, that were deemed to have less or equal tumor cellularity compared with CNBs, had level sections performed and were reassessed for tumor cellularity. Results: Diagnostic accuracy was 96% for FNAB and 93% for CNB ( P =.267). In FNAB-CBs, tumor fraction was significantly higher than in CNB samples (67% vs 36%; P &lt;.0001), whereas nontumor components were significantly lower (stromal component, 7% vs 29%; P &lt;.0001; background benign hepatocytes, 25% vs 36%; P =.003). Additionally, in 44% of cases, FNAB-CB tumor cellularity was equal to or greater than that of the concurrent CNB. Conclusions: In the current age of personalized medicine, a minimally invasive, safe approach to obtaining adequate tissue for myriad molecular testing is paramount. We have shown that FNAB sampling is diagnostically accurate and produces higher tumor fractions than CNB. Thus, FNAB should be strongly considered as an initial sampling modality, especially for patients in whom molecular tests will determine management.
Incidence of Maternal Sepsis and Sepsis-Related Maternal Deaths in the United States
Authors: Matthew K. Hensley, Melissa E. Bauer, Lindsay K. Admon, Hallie C. Prescott
Journal: JAMA (2019)

This study uses National Readmissions Database data to characterize incidence of and mortality due to maternal sepsis within 42 days of delivery hospitalization discharge in the United States between 2013 and 2016.
Phase I trial of HuMax-IL8 (BMS-986253), an anti-IL-8 monoclonal antibody, in patients with metastatic or unresectable solid tumors
Authors: Marijo Bilusic, Christopher R. Heery, Julie M. Collins, Renee N. Donahue, Claudia Palena, Ravi A. Madan, Fatima Karzai, Jennifer L. Marté, Julius Strauss, Margaret E. Gatti-Mays, Jeffrey Schlom, James L. Gulley
Journal: Journal for ImmunoTherapy of Cancer (2019)

HuMax-IL8 (now known as BMS-986253) is a novel, fully human monoclonal antibody that inhibits interleukin-8 (IL-8), a chemokine that promotes tumor progression, immune escape, epithelial-mesenchymal transition, and recruitment of myeloid-derived suppressor cells. Studies have demonstrated that high serum IL-8 levels correlate with poor prognosis in many malignant tumors. Preclinical studies have shown that IL-8 blockade may reduce mesenchymal features in tumor cells, making them less resistant to treatment.Fifteen patients with metastatic or unresectable locally advanced solid tumors were enrolled in this 3 + 3 dose-escalation trial at four dose levels (4, 8, 16, or 32 mg/kg). HuMax-IL8 was given IV every 2 weeks, and patients were followed for safety and immune monitoring at defined intervals up to 52 weeks.All enrolled patients (five chordoma, four colorectal, two prostate, and one each of ovarian, papillary thyroid, chondrosarcoma, and esophageal) received at least one dose of HuMax-IL8. Eight patients had received three or more prior lines of therapy and five patients had received prior immunotherapy. Treatment-related adverse events occurred in five patients (33%), mostly grade 1. Two patients receiving the 32 mg/kg dose had grade 2 fatigue, hypophosphatemia, and hypersomnia. No dose-limiting toxicities were observed, and maximum tolerated dose was not reached. Although no objective tumor responses were observed, 11 patients (73%) had stable disease with median treatment duration of 24 weeks (range, 4-54 weeks). Serum IL-8 was significantly reduced on day 3 of HuMax-IL8 treatment compared to baseline (p = 0.0004), with reductions in IL-8 seen at all dose levels.HuMax-IL8 is safe and well-tolerated. Ongoing studies are evaluating the combination of IL-8 blockade and other immunotherapies.NCTN, NCT02536469. Registered 23 August 2015, https://clinicaltrials.gov/ct2/show/NCT02536469?term=NCT02536469&rank=1 .
P11.40 Development of an implantable multifunctional biodevice (GlioGel) in the treatment of recurrent glioblastoma
Authors: L Déry, G Charest, M Akbari, D Fortin
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Glioblastoma (GBM) is a devastating disease with a median survival of 14–16 months. This poor prognosis can be explained by 3 factors. First, the infiltrative nature of the disease prohibits a complete removal of the tumor. Second, some of the tumor cells are brain tumor stem cells, which are highly migratory and highly resistant to treatments. Finally, the presence of the blood-brain barrier prohibits entry of therapeutics. This situation implies that new treatment approaches must be directed toward the infiltrated brain surrounding the resection cavity. To bypass this problem and improve the potency of adjuvant treatment, we have designed a new “GlioGel-device” that will have the ability to: 1- attract the migrating tumor cells into or nearby the device, and 2- subsequently deliver chemotherapy to the locally pooled tumor cells and 3- irradiate these cells with radioisotopes embedded in the GlioGel. MATERIAL AND METHODS In vitro proof of principle of chemoattraction was investigated by agarose drops method releasing chemokines molecules (CCL2, CCL11, CXCL10) with F98 and U87MG GBM cells. In vivo experiments evaluated the efficiency of chemokines and doxorubicin released by the implanted GlioGel on the tumor behaviour in our Fischer-F98 rat glioma model. An histology of tumour behaviour exposed to chemokines and survival of GBM rats treated with doxorubicin were analysed. RESULTS In vitro preliminary results for chemoattraction assays show that up to 2 times more cells invade the gel when it releases chemoattractant compared to PBS. The In vivo chemotherapy experiments with a fast, medium and slow release of doxorubicin from the GlioGel show that a local dose that represent a 1300-fold smaller dose than a normal intravenous systemic dose gave a significant reduction in tumour growth (median survival) compared to a control group. We investigated the effect provided by the GlioGel impregnated with chemokines on tumor cells migration, after implantation in the Fischer-F98 rat glioma model. CONCLUSION This preliminary study shows the ability of GlioGel releasing chemokines and doxorubicin to respectively attract and kill orthotopic glioblastoma cells. These encouraging results will be completed with a combination of short-range (high LET) radiation by embedded radioisotope into the GlioGel aiming for synergistic combination to eradicate as much tumour cells as possible, while limiting systemic side effects.
‘DESIRABLE’ or not?
Authors: Nupoor Acharya, Arghya Chattopadhyay, Varun Dhir
Journal: Annals of the Rheumatic Diseases (2019)

DESIRABLE' or not?We read with great interest the recently published study 'Effects of the anti-RANKL antibody denosumab on joint structural damage in patients with rheumatoid arthritis treated with conventional synthetic disease modifying antirheumatic drugs (DESIRABLE study): a randomised, double-blind, placebo-controlled phase 3 trial' by Takeuchi et al. 1 This trial has shown a beneficial effect of denosumab in reducing radiographic progression (modified total Sharp score) and erosions in patients of rheumatoid arthritis (RA), in two dosing regimens, that is, 60 mg subcutaneous 6 monthly and 3 monthly.However, there are some concerns.While there has been a significant reduction in erosion score over 12 months, the above study failed to demonstrate any beneficial effect of denosumab on joint space narrowing. 1Radiographic scores are surrogates for reflecting disability and functional limitation, and thus any reduction in these is the gold-standard for 'disease-modification' in RA.But, it is the joint space narrowing which is a better predictor of function than erosions. 2In that regard, it is notable that there was no improvement in function per se measured by health assessment questionnaire -disabaility index (HAQ-DI) in this study.Also, at the end of 12 months of therapy, no difference was seen in ACR20/50/70 response.Thus, the benefit in erosions may not translate into clinically meaningful improvement.Denosumab is proven to have a beneficial effect on RA-associated osteoporosis. 3This effect was also evident on lumbar spine bone mineral density in 'DESIRABLE' trial. 1 However, denosumab has been associated with rebound osteoporosis and increased risk of multiple fractures after withdrawal when used in osteoporosis. 4Whether a similar effect would also occur on erosions remains to be seen.Finally, patients with RA are at a 10% increased risk for development of malignancies than the general population. 5A previous study found that malignancies in patients treated with denosumab were higher, though were not statistically significant. 6In the 'DESIRABLE' study, three patients in the denosumab groups developed malignancies and two developed interstitial lung disease. 1 Though there was no statistically significant difference between the treatment and placebo groups, the study was not adequately powered to study adverse effects.A longer follow-up is needed to ensure the safety of denosumab.To conclude, in the absence of clinical improvement and lack of long-term safety data, it would be still early to consider denosumab for a non-osteoporotic indication, such as reducing RA erosion scores.
Association of National Cancer Institute–Sponsored Clinical Trial Network Group Studies With Guideline Care and New Drug Indications
Authors: Joseph M. Unger, Van T. Nghiem, Dawn L. Hershman, Riha Vaidya, Michael LeBlanc, Charles D. Blanke
Journal: JAMA Network Open (2019)

National Cancer Institute Clinical Trial Network (NCTN) groups serve a vital role in identifying effective new antineoplastic regimens. However, the downstream clinical effect of their trials has not been systematically examined.
In partial defense of softness
Authors: Daniel S. Levine
Journal: Behavioral and Brain Sciences (2001)

The authors wish that the psychology of human decision making should borrow methodological rigor from economics. However, unless economics also borrows from psychology this poses a danger of overly limiting the phenomena studied. In fact, an expanded economic theory should be sought that is based in psychology (and ultimately neuroscience) and encompasses both rational and irrational aspects of decision making.
P14.33 Adult brainstem gliomas in neurofibromatosis type 1 (NF1)
Authors: J Guillamo, A Wang, F Ducray, S Barbarot, O Chinot, D Frappaz, L Bauchet, P Wolkenstein, F Laigle-Donadey
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND The brainstem is the second location of brain tumors after optic pathways in NF1. In NF1 children, brainstem gliomas are usually indolent and have a better prognosis than their counterparts in non NF1 children. In contrast, the natural history and prognosis of adult brainstem gliomas in NF1 are nearly unknown. MATERIAL AND METHODS We conducted a retrospective analysis of medical records and MRI of adult NF1 patients followed for a brainstem glioma in 8 centers over a 17 years period (2000–2017). Clinical and imaging characteristics, management and outcome were analyzed. RESULTS Twenty five patients were included in the study (13 males and 12 females) with a median age of 32 (range 17–58). The epicenter of the tumor was located into the pons n=13 (52%), the mesencephalon n=7 (28%), the medulla oblongata n=5 (20%). On MRI, contrast enhancement was seen in 19 tumors (76%). Pathological examination was available in 13 tumors (52%) and showed a high grade astrocytoma (III or IV) in 9 tumors. Five patients were asymptomatic, 3 remained asymptomatic during the follow-up (median follow-up: 86 months, range 22–124). Twenty patients were symptomatic with a median duration of symptom of 2.5 months (range 1–10) before diagnosis. Among these symptomatic patients, 15 died from tumor progression despite treatment with radiation therapy and or chemotherapy. The median overall survival of symptomatic patients was 36 months. CONCLUSION Brainstem gliomas are rare tumors in adults with NF1. Unlike children, adult brainstem gliomas seem to have an unexpected poor prognosis, suggesting the disease may be different in adulthood.
Goals of care designation associated with improved survival and indicators of quality end-of-life care in pancreatic cancer (PC) patients (pts) undergoing palliative chemotherapy.
Authors: Matthew Anaka, Jennifer L. Spratlin, Winson Y. Cheung, Sunita Ghosh, Minji Lee
Journal: Journal of Clinical Oncology (2019)

11532 Background: Discussion of goals of care (GoC) is a key part of quality care for pts with palliative cancer. Numerous studies have shown that documentation of GoC in this population remains low. Here we describe changes in GoC documentation and other indicators of quality end-of-life care in PC pts undergoing palliative chemotherapy during a health-system wide initiative to improve advanced care planning (ACP). Methods: This is a retrospective cohort analysis of 106 pts with locally advanced or metastatic PC treated with palliative chemotherapy from 2012-2015 in Northern Alberta (Canada). In 2014, an initiative was launched to provide pts with hard copies of their GoC designation intended to be available at all health-system interactions. Data were obtained from outpatient medical oncology (MO) and palliative care (PAL) notes and the provincial cancer registry. Survival analysis used a multivariate Cox-regression. All other tests were Chi-squared. Results: 50% (53/106) of pts had a documented GoC discussion, with 45% (48/106) receiving a specific GoC designation. In 2012, 31% (6/19) of pts had a GoC designation, which increased to 61% (20/33) in 2015. Of 84 individual GoC discussions documented, 34% (29/84) were by MO, 62% (52/84) were by PAL, and at least 8% (7/84) referenced prior discussions with a family physician or discussion while admitted to hospital. Pts with a GoC designation had increased median overall survival (287 vs 216 days; HR = 0.62; p = 0.041), and were less likely to receive chemotherapy in the last two weeks of life (p = 0.016). Conclusions: Rates of GoC discussions for PC pts undergoing palliative chemotherapy increased during a health-system wide ACP initiative. Having a GoC designation was associated with greater overall survival and indicators of higher quality end-of-life care.
Edoxaban-based versus vitamin K antagonist-based antithrombotic regimen after successful coronary stenting in patients with atrial fibrillation (ENTRUST-AF PCI): a randomised, open-label, phase 3b trial
Authors: Pascal Vranckx, Marco Valgimigli, Lars Eckardt, Jan Tijssen, Thorsten Lewalter, Giuseppe Gargiulo, Valerii Batushkin, Gianluca Campo, Zoreslava Lysak, Igor Vakaliuk, Krzysztof Milewski, Petra Laeis, Paul-Egbert Reimitz, Rüdiger Smolnik, Wolfgang Zierhut, Andreas Goette
Journal: The Lancet (2019)