tbuckley/cabot-search huggingface dataset:
Abstract P094: Weekly Variation of Circadian Peaks for the Onset of Acute Myocardial Infarction in the Working Population
Authors: Hiroshi Sato, Ryuya Edahiro, Daisaku Nakatani, Shinichiro Suna, Masaya Usami, Sen Matsumoto, Masahiko Hara, Yasuhiko Sakata, Toshimitsu Hamasaki, Masatsugu Hori, Issei Komuro
Journal: Circulation (2012)

Variations in the incidence of acute myocardial infarction (AMI) during the day and week may differ among the subpopulations within the communities. It is well known that AMI onset shows characteristic circadian variations involving a definite morning peak and a vague nighttime peak: the former is often explained by biologic rhythms, while the latter by socioeconomic factors. Interestingly, we previously found that female patients aged 65 years or more showed a morning peak alone, whereas and male patients aged less than 65 years with an occupation and the habits of cigarette smoking and alcohol intake showed a nighttime peak alone. On the other hand, it is also reported that working population shows a weekly variation with an increased incidence for the AMI onset on Mondays. Accordingly, circadian variation for the onset of AMI could be influenced by each or combination of working status, gender, and the day of the week. However, there are few reports investigating circadian variation of AMI onset in relation with working status, gender and/or weekly variation. Therefore, we sought to investigate circadian variation patterns of AMI onset in relation with week variation according to gender and/or working status, especially in the working populations. From the registry database of the Osaka Acute Coronary Insufficiency Study (OACIS), a prospective observational study of AMI in Osaka area, Japan, a total of 7755 consecutive patients whose time of AMI onset was definitely identified between 1998 and 2009 were enrolled. The mean age of study population was 66+12 years old, 5872 (76%) were male, and 3364 (48%) had occupation. As previously reported, an increased incidence of AMI onset was observed in the morning and at the nighttime in overall populations. Interestingly, however, subgroup analysis revealed that the nighttime peak was completely attributable to the increase of nighttime onset on the weekend in the working subjects, especially working men, whereas the morning peak was common throughout the week with a peak on Monday in all other subgroups. As the weekend nighttime peak for AMI onset was not evident in other subgroups, this phenomenon may account for the social and/or economic reasons on the weekend in the working population. Although confirmation in other cohorts is required, this finding may help identify triggers of AMI and guide subjects to prevent an onset of AMI.
A Multistate Survival Analysis for Patients with Follicular Lymphoma (FL) Using 13 First-Line Randomized Trials from FL Analysis of Surrogate Hypothesis (FLASH) Group
Authors: Caglar Caglayan, Jesse Dixon, Anna Wall, Gilles A. Salles, Eva Hoster, Wolfgang Hiddemann, Michael Herold, Franck Morschhauser, Catherine Sebban, Anton Hagenbeek, Robert Marcus, Howard Hochster, Mathias J Rummel, Eva Kimby, Umberto Vitolo, Bruce A. Peterson, Emmanuel Gyan, Marco Ladetto, Charles Yves Foussard, Michele Ghielmini, Tina G Nielsen, Kenneth Foon, Qian Shi, Christopher R. Flowers
Journal: Blood (2019)
Vascular Pedicle and Microchannels: Simple Methods Toward Effective In Vivo Vascularization of 3D Scaffolds
Authors: Jelena Rnjak‐Kovacina, Yi‐wen Gerrand, Lindsay S. Wray, Beryl Tan, Habib Joukhdar, David L. Kaplan, Wayne A. Morrison, Geraldine M. Mitchell
Journal: Advanced Healthcare Materials (2019)

Abstract Poor vascularization remains a key limiting factor in translating advances in tissue engineering to clinical applications. Vascular pedicles (large arteries and veins) isolated in plastic chambers are known to sprout an extensive capillary network. This study examined the effect vascular pedicles and scaffold architecture have on vascularization and tissue integration of implanted silk scaffolds. Porous silk scaffolds with or without microchannels are manufactured to support implantation of a central vascular pedicle, without a chamber, implanted in the groin of Sprague Dawley rats, and assessed morphologically and morphometrically at 2 and 6 weeks. At both time points, blood vessels, connective tissue, and an inflammatory response infiltrate all scaffold pores externally, and centrally when a vascular pedicle is implanted. At week 2, vascular pedicles significantly increase the degree of scaffold tissue infiltration, and both the pedicle and the scaffold microchannels significantly increase vascular volume and vascular density. Interestingly, microchannels contribute to increased scaffold vascularity without affecting overall tissue infiltration, suggesting a direct effect of biomaterial architecture on vascularization. The inclusion of pedicles and microchannels are simple and effective proangiogenic techniques for engineering thick tissue constructs as both increase the speed of construct vascularization in the early weeks post in vivo implantation.
ATIM-44. A PHASE I FIRST-IN-HUMAN TRIAL OF TWO ADENOVIRAL VECTORS EXPRESSING HSV1-TK AND FLT3L FOR TREATING NEWLY DIAGNOSED RESECTABLE MALIGNANT GLIOMA: THERAPEUTIC REPROGRAMMING OF THE BRAIN IMMUNE SYSTEM
Authors: Pedro Lowenstein, Daniel A Orringer, Oren Sagher, Jason Heth, Shawn Hervey-Jumper, Aaron Gerald Mammoser, Larry Junck, Denise Leung, Yoshie Umemura, Theodore Steven Lawrence, Michelle Miran Kim, Daniel Richard Wahl, Paul McKeever, Sandra Ines Camelo-Piragua, Andrew Lieberman, Sriram Venneti, Andrea Comba, David Altshuler, Karin M Muraszko, Maria Castro
Journal: Neuro-Oncology (2019)

Abstract This is an interim report on a first in human Phase I dose escalation trial of the combination of two adenoviral vectors expressing HSV1-TK or Flt3L for the treatment of newly diagnosed, resectable malignant gliomas. Lack of dendritic cells from the brain precludes anti-glioma immune responses. We combined tumor cytotoxicity (Ad-HSV1TK) with recruitment of dendritic cells to gliomas (Ad-Flt3L) to induce anti-glioma immunity. In experimental models this treatment induces powerful cytotoxic CD8 and CD4 T-dependent anti-glioma immunity, immunological memory, and the capacity to recognize neo-antigens. The trial was approved through a FDA-IND, and all institutional cttees. Treatment was administered intraoperatively following complete glioma resection in newly diagnosed tumors. The trial consisted of vector dose escalation, starting at 1x10^9 v.p., and increasing to 1x10^11 v.p. of each vector, through 6 cohorts of 3 patients each. Two cycles of 14 days of valacyclovir were administered to activate HSV1-TK cytotoxicity. Cycle 1 starts on Day 1–3 post surgery for 14 days, and Cycle 2 on Week 8–12. Standard radiation, i.e., 60 Gy in 2 Gy fractions over 6 weeks, with concurrent temozolomide, was followed by cyclic temozolomide. Examination of tumor samples at primary resection and first recurrence show an increase in the infiltration of inflammatory cells. The experimental treatment was well tolerated. An MTD was not reached. There were approx. 248 AEs, and 26 SAEs; these were not linked to treatment. As secondary outcome, median survival of contemporary controls was 604 days, and median survival of trial patients was 742 days. Our results show for the first time that reprogramming of the host’s brain immune system to recognize gliomas reveals a new approach for the treatment of highly malignant brain tumors. Clinical trial information: NCT01811992.
Safety and Efficacy of Tisagenlecleucel (CTL019) in B-Cell Acute Lymphoblastic Leukemia in Children, Adolescents and Young Adults: The French Experience
Authors: Marie-Emilie Dourthe, Florence Rabian, Karima Yakouben, Aurélie Cabannes, Florian Chevillon, Delphine Chaillou, Nathalie Dhedin, Emmanuelle Lesprit, Jerome Naudin, Julie Roupret-Serzec, Nathalie Parquet, Anne Brignier, Valérie Guérin, Elodie Lainey, Aurélie Caye-Eude, Helene Cavé, Emmanuelle Clappier, Stéphanie Mathis, Sophie Caillat-Zucman, Elie Azoulay, Jean-Hugues Dalle, Isabelle Madelaine, Jerome Larghero, Nicolas Boissel, André Baruchel
Journal: Blood (2019)
Economic Burden of Bronchiolitis Obliterans Syndrome (BOS) Following Allogeneic Hematopoietic Stem Cell Transplant (alloHSCT) in Patients with Commercial Insurance in the United States
Authors: Naomi Sacks, Bridget Healey, Philip Cyr, Katharine Batt, Noreen Roth Henig
Journal: Blood (2019)
Daratumumab (DARA) Subcutaneous (SC) Delivery in Relapsed or Refractory Multiple Myeloma (RRMM): Population Pharmacokinetics (PPK) and Exposure-Response (E-R) Analysis
Authors: Melody Luo, Dolly A. Parasrampuria, Saad Z. Usmani, Maria-Victoria Mateos, Hareth Nahi, Christoph Heuck, Ming Qi, Steven Sun, Pamela L. Clemens, Honghui Zhou, Yu-Nien (Tom) Sun, Steven Xu
Journal: Blood (2019)
Early Surgery or Conservative Care for Asymptomatic Aortic Stenosis
Authors: Duk-Hyun Kang, Sung-Ji Park, Seung-Ah Lee, Sahmin Lee, Dae-Hee Kim, Hyung-Kwan Kim, Sung-Cheol Yun, Geu-Ru Hong, Jong-Min Song, Cheol-Hyun Chung, Jae-Kwan Song, Jae-Won Lee, Seung-Woo Park
Journal: New England Journal of Medicine (2019)

The timing and indications for surgical intervention in asymptomatic patients with severe aortic stenosis remain controversial.In a multicenter trial, we randomly assigned 145 asymptomatic patients with very severe aortic stenosis (defined as an aortic-valve area of ≤0.75 cm2 with either an aortic jet velocity of ≥4.5 m per second or a mean transaortic gradient of ≥50 mm Hg) to early surgery or to conservative care according to the recommendations of current guidelines. The primary end point was a composite of death during or within 30 days after surgery (often called operative mortality) or death from cardiovascular causes during the entire follow-up period. The major secondary end point was death from any cause during follow-up.In the early-surgery group, 69 of 73 patients (95%) underwent surgery within 2 months after randomization, and there was no operative mortality. In an intention-to-treat analysis, a primary end-point event occurred in 1 patient in the early-surgery group (1%) and in 11 of 72 patients in the conservative-care group (15%) (hazard ratio, 0.09; 95% confidence interval [CI], 0.01 to 0.67; P = 0.003). Death from any cause occurred in 5 patients in the early-surgery group (7%) and in 15 patients in the conservative-care group (21%) (hazard ratio, 0.33; 95% CI, 0.12 to 0.90). In the conservative-care group, the cumulative incidence of sudden death was 4% at 4 years and 14% at 8 years.Among asymptomatic patients with very severe aortic stenosis, the incidence of the composite of operative mortality or death from cardiovascular causes during the follow-up period was significantly lower among those who underwent early aortic-valve replacement surgery than among those who received conservative care. (Funded by the Korean Institute of Medicine; RECOVERY ClinicalTrials.gov number, NCT01161732.).
PATH-67. RECOMBINANT INTERLEUKIN-7 ENHANCES THE ANTI-TUMOR IMMUNITY OF A DENDRITIC CELL VACCINE IN A MURINE MALIGNANT GLIOMA
Authors: Sol Hooy Oh, Stephen Ahn, Jae Sung Park, Yong Kil Hong, Sin-Soo Jeon
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Dendritic cell (DC)-based vaccines have been suggested as one of the promising immunotherapies for treating various cancers, including glioblastoma. We already developed a novel vaccination protocol with peptide-loaded DCs followed by a mixture of synthetic peptides, polyinosine- polycytidylic acid (poly-IC) and anti-CD40 antibodies (Trivax) in a melanoma mouse model. However, in a glioma mouse model, therapeutic efficacy is not as much as enough maybe due to relatively low antigenicity and blood brain barrier. MATERIAL AND METHODS IL-7, which is one of the most important cytokines to expand and develop T cells with anti-tumor immunity, was co-administrated intravenously with Trivax in an orthotopic murine malignant glioma. RESULTS Co-administration of the Trivax and recombinant IL-7 (Trivax7) increased the number of survivin specific T cells measured using ELISPOT assay and the population of central memory T cells, comparing with administration of Trivax. The tumor size of orthotopic mouse model in Trivax 7 group was smaller than those of Trivax only group. Finally, overall survival in Trivax 7 was longer than those of Trivax only. In addition, there was a prolonged survival of antigen-specific T cells in Trivax7 group than Trivax only group. CONCLUSION In summary, our novel combinational immunotherapy may overcome the limitations of current cell-based cancer vaccines and could be applicable for the treatment of glioblastoma patients.
RARE-42. INCIDENCE AND BEHAVIOR OF CENTRAL NERVOUS SYSTEM INVOLVEMENT IN PATIENTS WITH HODGKIN’S LYMPHOMA
Authors: Carlos Eduardo Silva Correia, Rachna Malani, Lisa DeAngelis, Alison Moskowitz
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION Central nervous system (CNS) involvement from Hodgkin’s Lymphoma (HL) is rare, with a reported incidence of 0.07–0.5%. There is a paucity of data regarding its natural history and management. METHODS In this retrospective single-institution review, we analyzed all adult patients with HL for CNS involvement (parenchymal or meningeal), who were evaluated at Memorial Sloan Kettering Cancer Center from January 2008 until December 2018. RESULTS A total of 3478 patients with HL were identified, and CNS involvement was found in 10 patients (0.3%). All patients were symptomatic from CNS disease. Four patients had a synchronous presentation. The other 6 patients had a median time from systemic diagnosis to CNS involvement of 8 years (2.5–14). Two patients had radiographic evidence of leptomeningeal disease, however 4 had positive cerebrospinal fluid (CSF) cytology. At time of CNS involvement, 2 patients had confirmed transformation to Non-Hodgkin-Lymphoma on biopsy. 2 patients had EBV-positive HL. One patient died before treatment. Five patients received high-dose methotrexate (HD-MTX) for CNS disease. Of these patients, 1 died during treatment, 2 had partial responses, and 2 had complete response of both systemic and CNS disease; to date they are in remission. Three patients had varied responses to immunotherapy and cytotoxic chemotherapy. Removal of an immunosuppressive agent resolved disease in one EBV-positive patient. Median overall survival (OS) from diagnosis of HL was 10.6 years (1.1–21.2), and OS from time to CNS involvement was 6 years (0.2–15). CONCLUSION The median time from diagnosis to CNS involvement, and OS from time of CNS involvement are higher than previously reported, which may be related to newer therapies for systemic disease. Neuroimaging should be used in conjunction with CSF for diagnostic accuracy. HD-MTX can be used to treat CNS and refractory systemic disease, as historically used for the latter.
CMET-25. COMPARATIVE EFFICACY OF TREATMENT PARADIGMS FOR BRAIN METASTASES – A SYSTEMATIC REVIEW
Authors: Karanbir Brar, Yosef Ellenbogen, Jiawen Deng, Nebras Warsi, Alireza Mansouri
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Brain metastases (BM) are prevalent in several primary cancers and are the most commonly diagnosed intracranial tumours in adults. The aim of this systematic review was to critically evaluate and compare existing management paradigms for BMs from all primary tumour sites. METHODS We searched MEDLINE, EMBASE, Web of Science, ClinicalTrials.gov, and CENTRAL for randomized controlled trials (RCTs) published until October 2018 and selected comparative RCTS with &gt;50 patients. The primary outcomes of interest were overall survival (OS) and progression-free survival (PFS). RESULTS A screen of 3188 abstracts yielded 49 RCTs with 8122 patients. The median sample size was 103 (range 39–779). 17/49 RCTs included lung cancer patients, 3/49 breast cancer, 2/49 melanoma, and 27/49 all primary tumour sites. Most studies were phase II/III superiority, open-label, parallel trials. All included patients &gt;18 years of age with at least 1 BM proven on CT/MRI. Most included patients with favorable performance status (KPS &gt;70 or ECOG 0–2). Interventions compared included targeted therapies (e.g. EGFR inhibitors, 7/49), chemotherapeutic regimens (28/49), WBRT (43/49), SRS (12/49), and surgical resection (3/49). A statistically significant difference in OS was reported by 7 studies, and in PFS by 8 studies. Of these, 3 showed improved PFS or OS on addition of temozolomide to WBRT, and 2 showed improved PFS in EGFR-positive patients treated with EGFR inhibitors. The incidence of serious adverse events was not substantially different between treatment arms in most studies. CONCLUSIONS Though the majority of studies did not report a benefit to OS or PFS, temozolomide + WBRT showed a benefit in 3 studies, and improvement in PFS was seen in EGFR-positive patients treated with EGFRi. Given the varying treatment approaches in practice today, these data support the need for a meta-analysis to accurately characterize the efficacy of existing treatment options for specific patient populations.
Safety and Antithrombotic Efficacy of the Recombinant Protein C Activator AB002 (E-WE Thrombin) in End Stage Renal Disease Patients on Chronic Hemodialysis
Authors: Norah G Verbout, Christina U Lorentz, Brandon D Markway, Joseph J Shatzel, Erik I Tucker, Andras Gruber
Journal: Blood (2019)
ATIM-28. PHASE II TRIAL OF AV-GBM-1 (AUTOLOGOUS DENDRITIC CELLS LOADED WITH TUMOR ASSOCIATED ANTIGENS) AS ADJUNCTIVE THERAPY FOLLOWING SURGERY PLUS CONCURRENT CHEMORADIATION IN NEWLY DIAGNOSED GBM PATIENTS
Authors: Daniela Bota, Thomas Taylor, David Picconi, Christopher Duma, Robert Aiken, Renato LaRocca, Kong Xiao-Tang, Beverly Fu, Mohamad Alsharif, Candace Hsieh, Gabriel Nistor, Robert Dillman
Journal: Neuro-Oncology (2019)

Abstract Newly-diagnosed glioblastoma (GBM) patients have a limited survival (18–24 months). In the last decade immunotherapy has improved survival for patients with other malignancies, but not GBM. Herein we present the design and initial enrollment results for the AV-GBM-1 single-arm phase 2 trial. The study enrolls patients with primary GBM who have undergone craniotomy, have a tumor cell culture established, and complete satisfactory leukapheresis prior to planned concurrent chemotherapy and radiation. Patients are scheduled to receive up to 8 vaccine injections at weeks 1, 2, 3, 8, 12, 16, 20 and 24. Blood samples are collected just prior to each injection. The primary endpoint is overall survival from date of enrollment for intent-to-treat with AV-GBM-1. The study has fully enrolled 26 of planned 55 patients. The cell line success rate is 30/32, with 6 in progress; successful completion of leukapheresis is 28/29. Two patients have completed all 8 doses, two discontinued after dose 3 and dose 6 because of progressive disease; 15 are currently in treatment, and 6 are about to start treatment. There have been seven SAE, all for hospitalizations related to GBM. For the first 8 treated patients, plasma samples from baseline and weeks 2, 3, and 8 have been analyzed for immune markers by RayBiotech Life Inc. using quantitative multiplex ELISA array. Markers reflecting Th1, Th2, Th17 pathways and B-cells, natural killer cells and cytotoxic T-lymphocytes increased in 7/8 patients. Principal component analysis demonstrates correlative marker groupings with early dominance of Th1/Th17 (weeks 1 and 2) followed by Th2/immunoglobulins at week 8. These findings show that these patient-specific dendritic cell vaccines are inducing pro-inflammatory responses similar to what was observed in a previous trial in melanoma. The study is progressing efficiently. Full enrollment data may be available for presentation at the time of the annual meeting.
Ebola is now “preventable and treatable,” says WHO after approving vaccine in record time
Authors: Elisabeth Mahase
Journal: BMJ (2019)

The World Health Organization has prequalified the injectable Ebola vaccine Ervebo in a move that will speed up its licensing, access, and roll-out in countries most at risk of Ebola virus outbreaks.

This is the fastest vaccine prequalification process ever conducted by WHO and means that the vaccine has met WHO standards for quality, safety, and efficacy. Ervebo can now be procured by United Nations agencies and Gavi, the vaccine alliance, for countries at risk.

WHO’s approval on 12 November came just a day after the European …
Association Between Hospital Volume, Therapy Types, and Overall Survival in Stage III and IV Cutaneous Malignant Melanoma
Authors: Sri Harsha Tella, Anuhya Kommalapati, Apar Kishor Ganti, Alissa S. Marr
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: The advent of targeted therapies and immunomodulatory agents has revolutionized the management of advanced cutaneous malignant melanoma (MMel) by prolonging overall survival. This study evaluated the therapeutic and survival disparities among patients with advanced MMel based on hospital volume using the National Cancer Database (NCDB). Methods: A retrospective analysis using regression models and Kaplan-Meier estimates was performed from the data obtained from the NCDB on patients with MMel diagnosed in 2004 through 2015. Results: A total of 40,676 patients with MMel were treated at 1,260 facilities. Multivariable analysis showed that facility volume was an independent predictor of overall survival ( P &lt;.0001). Compared with patients treated at high-volume facilities (tertile 3 [T3]), those with stage III disease (n=27,528) treated at intermediate- and low-volume facilities (T2 and T1, respectively) had a significantly higher risk of death (T2 hazard ratio [HR], 1.15; 95% CI, 1.09–1.20; T1 HR, 1.23; 95% CI, 1.17–1.29). Compared with patients treated at T3 facilities, those with stage IV disease (n=13,148) treated at lower-tertile facilities had a significantly higher risk of death (T2 HR, 1.16; 95% CI, 1.10–1.21; T1 HR, 1.29; 95% CI, 1.23–1.36). Further, patients with stage IV disease treated at T3 facilities (vs T1 facilities) were more likely to receive chemotherapy (38% vs 28%) and immunotherapy (23% vs 10%) ( P &lt;.0001). Conclusions: Patients with advanced-stage MMel treated at high-volume facilities had significantly improved survival and were more likely to receive chemotherapy and immunotherapy.
Safety and Efficacy of Brentuximab Vedotin in Combination with AVD in Stage II-IV HIV-Associated Classical Hodgkin Lymphoma: Results of the Phase 2 Study, AMC 085
Authors: Paul G. Rubinstein, Page C. Moore, Milan Bimali, Amy Chadburn, Ethel Cesarman, Michelle Rudek, Lee Ratner, Richard F. Ambinder, David H. Henry, Stefan K. Barta, Herve Ghesquieres, Paul Coppo, Pierre Delobel, Francois Boue, Lionel Galicier, Juan Carlos Ramos, Erin G. Reid, Elad Sharon, Nicolas Mounier, Caroline Besson, Ariela Noy
Journal: Blood (2019)
The Study of Thrombosis in JAK2V617F Mutated Myeloproliferative Neoplasms
Authors: Jie Bai, Yuhui Zhang, Yingshao Wang, Guangshuai Teng, Yan Wang, Chenxiao Du, Yafang Chen, Huiqin Zhang, Yanqi Li, Lixia Fu, Lei Zhang, Yuan Zhou
Journal: Blood (2019)
Automated Manufacture of Matched Donor-Derived Allogeneic CD19 CAR T-Cells for Relapsed/Refractory B-ALL Following Allogeneic Stem Cell Transplantation: Toxicity, Efficacy and the Important Role of Lymphodepletion
Authors: Claire Roddie, Maeve A O'Reilly, Maria A V Marzolini, Leigh Wood, Juliana Dias Alves Pinto, Mahnaz Abbasian, Ketki Vispute, Leticia Bosshard, Mark W. Lowdell, Graham Wheeler, Alex Day, Bilyana Popova, Kim Champion, Yashma Pathak, Alexia Gali, Nasir Mahmoud, Victoria Spanswick, Helen Lowe, John A. Hartley, Farzin Farzaneh, Lauren Nickolay, Fahetullah Syed, Waseem Qasim, David C. Linch, Martin Pule, Karl S Peggs
Journal: Blood (2019)
Lymphoma-Specific Venous Thromboembolism Score (LyV-Score): Use of Lymphoma Subtype to Refine Risk Prediction
Authors: Shufen Cao, Gouri Dharmavaram, Kirsten M Boughan, Brenda Cooper, Molly M Gallogly, Ehsan Malek, Leland Metheny, Folashade Otegbeye, Benjamin K. Tomlinson, Marcos de Lima, Pingfu Fu, Paolo F Caimi
Journal: Blood (2019)