tbuckley/cabot-search huggingface dataset:
ATIM-21. THE CURRENT STATUS OF AD-SGE-REIC GENE THERAPY FOR MALIGNANT GLIOMA
Authors: Kazuhiko Kurozumi, Kentaro Fujii, Tetsuo Oka, Yosuke Shimazu, Yasuhiko Hattori, Yusuke Tomita, Atsuhito Uneda, Yuji Matsumoto, Nobushige Tsuboi, Keisuke Kaneda, Keigo Makino, Hiroyuki Michiue, Hiromi Kumorn, Isao Date
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION Expression of the gene encoding reduced expression in immortalized cells/Dickkopf-3 (REIC/Dkk-3) was reported to be reduced in a variety of human cancer cells. We previously examined the antitumor effect of an adenoviral vector carrying REIC/Dkk-3 gene (Ad-CAG-REIC). Recently, a novel adenoviral vector expressing REIC/Dkk-3 has also been developed based on the cytomegalovirus promoter-driven super gene expression system (Ad-SGE-REIC). We evaluated the anti-glioma effect of the Ad-SGE-REIC and planned a clinical trial of Ad-SGE-REIC for malignant glioma. MATERIALS AND METHODS We evaluated a cytotoxicity assay to treatments with Ad-SGE-REIC, Ad-CAG-REIC, or Ad-LacZ (control) using malignant glioma cells. The survival of mice in each group was analyzed by the Kaplan–Meier method. We also performed Good Laboratory Practice (GLP) toxicology tests and prepared a protocol for this clinical trial. RESULTS In the cytotoxicity assay, after treatment with Ad-SGE-REIC, the number of malignant glioma cells attached to the bottom of culture wells was significantly reduced in a time-dependent manner. Mice treated with Ad-SGE-REIC survived significantly longer than those treated with other vectors. We also performed GLP toxicology tests using intracranial injection of higher doses of Ad-SGE-REIC in rats at Shin Nippon Biomedical Laboratories (SNBL Japan) to determine the injection dose of Ad-SGE-REIC for this clinical trial. After finishing the consultation with Pharmaceuticals and Medical Devices Agency (PMDA), we prepared a protocol for a phase I/IIa clinical trial of Ad-SGE-REIC for the treatment of recurrent malignant glioma supported by Japan Agency for Medical Research and Development (AMED). This protocol was reviewed by institution review board (IRB) in March 2019. We submitted a notification of this trial in April 2019. CONCLUSIONS We demonstrated the anti-glioma effect of Ad-SGE-REIC. We will start a phase I/IIa clinical trial of Ad-SGE-REIC for the treatment of recurrent malignant glioma.
HOUT-21. CHARACTERISTICS OF SHORT-TERM SURVIVAL IN PATIENTS WITH GLIOBLASTOMA: A RETROSPECTIVE ANALYSIS
Authors: Andrew Barbour, Patrick Healy, Eric Lipp, James Herndon, Leslie Thomas, Margaret Johnson, David Ashley, Annick Desjardins, Dina Randazzo, Henry Friedman, John Kirkpatrick, Katherine Peters
Journal: Neuro-Oncology (2019)

Abstract We sought to identify characteristics of glioblastoma (GBM) patients with short survival (&lt; 10 months) in order to identify prognostic factors useful for guiding treatment management. This is an IRB-approved retrospective analysis of adult newly diagnosed GBM patients from 2008–2016 who survived &lt; 10 months from diagnosis. We extracted demographics, tumor characteristics, and treatment details. We calculated survival from surgical diagnosis to date of death. The cohort includes 197 subjects (61% male) with a median age of 68 years (range 19–94). The majority (93%) are non-Hispanic white. The cohort has a median survival of 144 days (95% CI: 130–160). We focused on traditional prognostic indicators, including extent of surgical resection and KPS. A majority had biopsy only (n=92, 46.7%) rather than gross total (n=59, 29.9%) or subtotal (n=46, 23.4%) resection. Moreover, 160 out of 197 patients had a documented KPS with a majority being below 90 (KPS=70–80 (n=96); KPS &lt; 70 (n=31)). Of 179 patients with data on RT course, 18% (n=32) received no RT or opted for hospice after diagnosis, 3% (n=6) received only RT, 54% (n=97) received RT+temozolomide (TMZ), and 24% (n=43) received RT+TMZ+bevacizumab. Of the 147 subjects receiving RT, 79% completed their RT course as prescribed. Most commonly, RT was prescribed as a 6- to 6-1/2-week course (85%), typically 59.4 Gy (45Gy primary, 14.4Gy boost) over 33 fractions or 60 Gy over 30 fractions. In contrast, 15% received a 3-week RT course, typically scheduled as 15 fractions of 2.667 Gy. We concluded that GBM patients with survival &lt; 10 months were more likely to have biopsy only and a KPS &lt; 90, notably associated with poorer prognosis. We continue to explore this dataset for further prognostic factors, particularly inability to complete planned RT course, and are comparing these traits to a larger cohort.
Results of a Clinical Trial of H3B-8800, a Splicing Modulator, in Patients with Myelodysplastic Syndromes (MDS), Acute Myeloid Leukemia (AML) or Chronic Myelomonocytic Leukemia (CMML)
Authors: David P. Steensma, Martin Wermke, Virginia M. Klimek, Peter L Greenberg, Patricia Font, Rami S. Komrokji, Jay Yang, Andrew M. Brunner, Hetty E. Carraway, Lionel Ades, Aref Al-Kali, Juan Manuel Alonso Dominguez, Ana Alonso, Catherine C. Coombs, H. Joachim Deeg, William B. Donnellan, James M. Foran, Guillermo Garcia-Manero, Michael B. Maris, Malgorzata McMasters, Jean-Baptiste Micol, Jaime Perez De Oteyza, Felicitas Thol, Eunice S. Wang, Justin M. Watts, Silvia Buonamici, Amy Kim, Vikram Gourineni, Alyssa J Marino, Nathalie Rioux, Joanne Schindler, Sherri Smith, Huilan Yao, Xiaobin Yuan, Kun Yu, Uwe Platzbecker
Journal: Blood (2019)
Early Outcomes From the English National Health Service Diabetes Prevention Programme
Authors: Jonathan Valabhji, Emma Barron, Dominique Bradley, Chirag Bakhai, Jamie Fagg, Simon O’Neill, Bob Young, Nick Wareham, Kamlesh Khunti, Susan Jebb, Jenifer Smith
Journal: Diabetes Care (2019)

OBJECTIVE To assess weight and HbA1c changes in the Healthier You: National Health Service Diabetes Prevention Programme (NHS DPP), the largest DPP globally to achieve universal population coverage. RESEARCH DESIGN AND METHODS A service evaluation assessed intervention effectiveness for adults with nondiabetic hyperglycemia (HbA1c 42–47 mmol/mol [6.0–6.4%] or fasting plasma glucose 5.5–6.9 mmol/L) between program launch in June 2016 and December 2018, using prospectively collected, national service–level data in England. RESULTS By December 2018, 324,699 people had been referred, 152,294 had attended the initial assessment, and 96,442 had attended at least 1 of 13 group-based intervention sessions. Allowing sufficient time to elapse, 53% attended an initial assessment, 36% attended at least one group-based session, and 19% completed the intervention (attended &amp;gt;60% of sessions). Of the 32,665 who attended at least one intervention session and had sufficient time to finish, 17,252 (53%) completed: intention-to-treat analyses demonstrated a mean weight loss of 2.3 kg (95% CI 2.2, 2.3) and an HbA1c reduction of 1.26 mmol/mol (1.20, 1.31) (0.12% [0.11, 0.12]); completer analysis demonstrated a mean weight loss of 3.3 kg (3.2, 3.4) and an HbA1c reduction of 2.04 mmol/mol (1.96, 2.12) (0.19% [0.18, 0.19]). Younger age, female sex, Asian and black ethnicity, lower socioeconomic status, and normal baseline BMI were associated with less weight loss. Older age, female sex, black ethnicity, lower socioeconomic status, and baseline overweight and obesity were associated with a smaller HbA1c reduction. CONCLUSIONS Reductions in weight and HbA1c compare favorably with those reported in recent meta-analyses of pragmatic studies and suggest likely future reductions in participant type 2 diabetes incidence.
Large Granular Lymphocytosis and Its Impact on Long Term Clinical Outcomes Following Allogeneic Hematopoietic Stem Cell Transplantation: 14-Year Follow-up Data
Authors: Guldane Cengiz Seval, Atilla Uslu, Ekin Kircali, Sinem Civriz Bozdag, Klara Dalva, Selami Kocak Toprak, Meltem Kurt Yuksel, Pervin Topcuoglu, Isinsu Kuzu, Onder Arslan, Muhit Özcan, Taner Demirer, Osman Ilhan, Hamdi Akan, Meral Beksac, Gunhan Gurman
Journal: Blood (2019)
Targeted Treatment and Survival Following Relapse after Allogeneic Hematopoietic Cell Transplantation for Acute Leukemia and MDS in the Contemporary Era
Authors: Sanghee Hong, Lisa Rybicki, Donna Corrigan, Betty K. Hamilton, Ronald Sobecks, Matt Kalaycio, Robert M. Dean, Brian T. Hill, Brad Pohlman, Deepa Jagadeesh, Faiz Anwer, Navneet S. Majhail
Journal: Blood (2019)
Hepatitis E virus replication in human intestinal cells
Authors: Olivier Marion, Sebastien Lhomme, Manon Nayrac, Martine Dubois, Mélanie Pucelle, Mary Requena, Marion Migueres, Florence Abravanel, Jean Marie Peron, Nicolas Carrere, Bertrand Suc, Pierre Delobel, Nassim Kamar, Jacques Izopet
Journal: Gut (2019)

Objective Hepatitis E virus (HEV), one of the most common agent of acute hepatitis worldwide, is mainly transmitted enterically, via contaminated water for HEV genotypes 1 (HEV1) and HEV2, or by eating raw or undercooked infected meat for HEV genotype 3 (HEV3) and HEV4. However, little is known about how the ingested HEV reaches the liver or its ability to replicate in intestinal cells. Design We developed human primary cultures of small intestine epithelial cells and intestinal explants obtained from small bowel resections. The epithelial cells were also polarised on transwells. Cells were infected with Kernow-p6 strain or clinically derived virions. Results Primary intestinal cells supported the growth of Kernow-p6 strain and HEV1 and HEV3 clinically derived virions. Polarised enterocytes infected with HEV1 and HEV3 strains released HEV particles vectorially: mostly into the apical compartment with a little basally. Iodixanol density gradient centrifugation of enterocyte-derived HEV virions gave bands at a density of 1.06–1.08 g/cm 3 , corresponding to that of quasi-enveloped HEV particles. Ribavirin therapy inhibited HEV excretion from the basal surface but not from the apical side of infected human enterocytes. HEV virions also infected intestinal tissue explants. Lastly, HEV RNA and antigen were detected in the intestinal crypts of a chronically infected patient. Conclusion HEV can replicate in intestinal cells and reaches the liver as quasi-enveloped virions.
Advance Care Planning Claims and Health Care Utilization Among Seriously Ill Patients Near the End of Life
Authors: Deepshikha Charan Ashana, Xiaoxue Chen, Abiy Agiro, Gayathri Sridhar, Ann Nguyen, John Barron, Kevin Haynes, Michael Fisch, David Debono, Scott D. Halpern, Michael O. Harhay
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Although advance care planning is known to increase patient and caregiver satisfaction, its association with health care utilization is not well understood. <h3>Objective</h3> To examine the association between billed advance care planning encounters and subsequent health care utilization among seriously ill patients. <h3>Design, Setting, and Participants</h3> This retrospective cohort study conducted from October 1, 2015, to May 31, 2018, used a national commercial insurance claims database to retrieve data from 18 484 Medicare Advantage members 65 years or older who had a claim that contained a serious illness diagnosis. <h3>Exposure</h3> A claim that contained an advance care planning billing code between October 1, 2016, and November 30, 2017. <h3>Main Outcomes and Measures</h3> Receipt of intensive therapies, hospitalization, emergency department use, hospice use, costs, and death during the 6-month follow-up period. <h3>Results</h3> The final study sample included 18 484 seriously ill patients (mean [SD] age, 79.7 [7.9] years; 10 033 [54.3%] female), 864 (4.7%) of whom had a billed advanced care planning encounter between October 1, 2016, and November 30, 2017. In analyses adjusted for patient characteristics and a propensity score for advance care planning, the presence of a billed advance care planning encounter was associated with a higher likelihood of hospice enrollment (incidence rate ratio [IRR], 2.52; 95% CI, 2.22-2.86) and mortality (hazard ratio, 2.27; 95% CI, 1.79-2.88) compared with no billed advance care planning encounter. Although patients with billed advance care planning encounters were also more likely to be hospitalized (IRR, 1.37; 95% CI, 1.26-1.49), including in the intensive care unit (IRR, 1.25; 95% CI, 1.08-1.45), they were less likely to receive any intensive therapies (IRR, 0.85; 95% CI, 0.78-0.92), such as chemotherapy (IRR, 0.65; 95% CI, 0.55-0.78). Similar results were observed in a propensity score–matched analysis (99% matched) and in a decedent analysis of patients who died during the 6-month follow-up period. <h3>Conclusions and Relevance</h3> Patients with billed advance care planning encounters were more likely than those without these encounters to receive hospice services and less likely to receive any intensive therapies, such as chemotherapy. However, they were also hospitalized more frequently than patients without billed advance care planning encounters. Although these findings were robust to multiple analytic methods, the results may be attributable to residual confounding because of a higher unmeasured severity of illness in the advance care planning group. Additional evidence appears to be needed to understand the effect of advance care planning on these outcomes.
T(11;14) and High BCL2 Expression Are Predictive Biomarkers of Response to Venetoclax in Combination with Bortezomib and Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma: Biomarker Analyses from the Phase 3 Bellini Study
Authors: Simon Harrison, Michele Cavo, Javier De La Rubia, Rakesh Popat, Cristina Gasparetto, Vania T.M. Hungria, Hans Salwender, Kenshi Suzuki, Inho Kim, Philippe Moreau, Andrew Spencer, Michael E O'Dwyer, Mamta Garg, Elizabeth A Punnoose, Muhammad Jalaluddin, Jia Jia, Xiaoqing Yang, Yan Sun, James E. Ward, Paulo C. Maciag, Jeremy A. Ross, Shaji K. Kumar
Journal: Blood (2019)
SCIDOT-34. BRAIN INJURY SIGNALS SYSTEMIC IMMUNOSUPPRESSION THROUGH THYMIC INVOLUTION
Authors: Katayoun Ayasoufi, Christian K Pfaller, Roman H Khadka, Fang Jin, Jiaying Zheng, Matthew R Schuelke, Laura Evgin, Michael J Hansen, Benjamin T Himes, Cori E Fain, Zachariah P Tritz, Emma N Goddery, Lila T Yokanovich, Larry R Pease, Richard G Vile, Aaron J Johnson
Journal: Neuro-Oncology (2019)

Abstract Systemic immunosuppression following neurological insults including stroke, traumatic brain injury, and glioblastoma (GBM) causes mortality and leads to failure of immune-modulating therapies. Exact immunological nature and the underlying mechanisms of this immunosuppression are unknown. Our goal was to define effects of neurological insults given exclusively to the brain on the thymus. The thymus is the primary immune organ responsible for T-cell development and maintenance both in children and in adults. We evaluated the brain-thymus communication using the following neurological insults: physical injury, CNS viral infection, sterile injury, tumor implantation, and seizures. All insults resulted in significant thymic involution that was reversible upon clearance of the insult. Thymic involution did not occur following similar peripheral insults. We next demonstrated that the GL261 model of GBM recapitulates hallmark features of peripheral immunosuppression observed in GBM patients including low CD4 T-cell counts. Thus, we aimed to further study the immunosuppression affecting the thymus in this clinically relevant model. Principle component analysis following RNA-sequencing of thymi from naïve and glioma-bearing mice revealed unbiased separation of the groups suggesting that the thymus is directly affected by a brain tumor. To determine the extent to which thymic involution was caused by a soluble factor we employed parabiosis. We demonstrated that thymic involution was transferable from glioma-bearing to non-tumor-bearing parabionts. Similarly, serum taken from GL261 glioma-bearing mice potently inhibited proliferation of T-cells in vitro. Together our data demonstrate that CNS-specific insults, regardless of nature, cause immunosuppression by prompting thymic involution through circulating factors. This accounts at least partially for immune deficiencies observed following neurological injuries. Identification of this suppressive factor is crucial in designing future therapeutics for GBM patients, and patients with other acute and chronic neurological trauma.
Exon-Level Genomic Abnormalities Are Frequent in Cytogenetically Normal Patients with Philadelphia-Chromosome Negative Myeloproliferative Neoplasms (MPNs)
Authors: Joseph Tripodi, Douglas Tremblay, Ronald Hoffman, Umut Ozbek, John Mascarenhas, Marina Kremyanskaya, Vesna Najfeld
Journal: Blood (2019)
Abstract 15991: Multiple Listing Increases Access to Heart, Lung, Liver, and Kidney Transplantation
Authors: Raymond C Givens, Paul C Schulze, Donna M Mancini
Journal: Circulation (2015)

Introduction: United Network for Organ Sharing (UNOS) policy allows solid organ transplant candidates to be listed at multiple centers simultaneously. As not all candidates have the resources needed for multiple-listing, this policy may advantage wealthier patients. Methods: Among adult first-time, single-organ candidates in the UNOS database between January 1, 2000 and December 31, 2013 who had a recorded waitlist outcome, we identified 33,928 patients waiting for heart (HT), 24,633 for lung (LuT), 103,332 for liver (LiT) and 223,644 for kidney transplantation (KT). We used propensity score matching to address imbalances among baseline covariates and conducted competing risk analyses of waitlist outcomes. Results: The proportion of multiple-listed patients (ML) was 2.0%, 3.4%, 6.0% and 12.0% among HT, LuT, LiT and KT candidates, respectively. Regardless of organ type, ML candidates were younger than single-listed (SL) patients (mean age 52 ± 1 vs. 54 ± 1), more likely to be insured privately (58.9% vs 51.1%) and less likely by Medicaid (5.8% vs 10.3%), and lived in ZIP codes with higher median incomes ($93,081 ± $12,772 vs $67,690 ± $9,205); all p-values &lt;0.0001. ML patients had proportionally higher functional status in addition to organ-specific indicators of lower acuity at initial listing. Across all organs, ML patients had longer waiting times at their initial listing centers but higher eventual transplant rates (OR [95% CI] = 1.23 [1.03-1.47], 1.56 [1.31-1.86], 1.57 [1.49-1.66] and 2.01 [1.95-2.07] for HT, LuT, LiT and KT, respectively) and lower rates of death while waiting (0.66 [0.50-0.87], 0.83 [0.67-1.03], 0.63 [0.58-0.68] and 0.53 [0.51-0.55]). Differences in waitlist outcomes between ML and SL patients were maintained after propensity score matching across all organs and in some cases were greatly accentuated. There were no consistent differences in post-transplant outcomes. Conclusions: Multiple listing is a rational response to organ shortage and long waiting times but appears to advantage patients with means to utilize it rather than the most medically needy. The UNOS multiple listing allowance should be reconsidered.
A Solution to the Dilution: The Role for Biomarkers in Advanced Ovarian Cancer
Authors: Katelyn F. Handley, Anil K. Sood
Journal: Clinical Cancer Research (2019)

Reliable approaches to predict residual disease prior to primary debulking surgery have been sought to further personalize surgical approaches. Reliance on molecular biomarkers alone in a complex clinical environment is challenging and algorithms that incorporate both molecular and clinical features may need to be considered.See related article by Heitz et al., p. 213.
Chinese Expert Consensus on Multidisciplinary Diagnosis and Treatment of Hepatocellular Carcinoma with Portal Vein Tumor Thrombus (2018 Edition)
Authors: Shuqun Cheng, Minshan Chen, Jianqiang Cai, Juxian Sun, Rongping Guo, Xinyu Bi, Wan Yee  Lau, Mengchao Wu
Journal: Liver Cancer (2019)

Portal vein tumor thrombus (PVTT) is very common, and it plays a major role in the prognosis and clinical staging of hepatocellular carcinoma (HCC). We have published the first version of the Consensus in 2016. Over the past several years, many new evidences for the treatment of PVTT become available especially for the advent of new targeted drugs which have further improved the prognosis of PVTT. So, the Chinese Association of Liver Cancer revised the 2016 version of consensus to adapt to the development of PVTT treatment. Future treatment strategies for HCC with PVTT in China would depend on new evidences from more future clinical trials.
A Phase 1 First-in-Human Study of the Anti-CD38 Dimeric Fusion Protein TAK-169 for the Treatment of Patients (pts) with Relapsed or Refractory Multiple Myeloma (RRMM) Who Are Proteasome Inhibitor (PI)- and Immunomodulatory Drug (IMiD)-Refractory, Including Pts Relapsed/Refractory (R/R) or Naïve to Daratumumab (dara)
Authors: Shaji K. Kumar, Robert F. Cornell, Ola Landgren, Sikander Ailawadhi, Jack P Higgins, Erin K Willert, Roger Waltzman, Jianchang Lin, Yuhong Zhang, Anya R Lublinsky, Ajeeta B Dash, Michael Hanley, Divya Manoharan, Morgan Leichter, Sean Ottinger, Richard J Labotka, John Newcomb, Alexander Vorog
Journal: Blood (2019)
Prevention of Tuberculosis
Authors: W. H. Steele
Journal: BMJ (1933)

medical men themselves, and it is probable that Dr. Rosewarne and the insurance company he is acting for will find that the general practitioner will no longer tolerate any interference with the business part of his professional activities by outsiders.It may interest " Esse quam videri ". to know that the schemes under consideration are on similar lines to the panel system, which has had the dire misfortune to earn his withering scorn and contempt.Many general practi- tioners who have had large experience of the working of the National Health Insurance Act are so ineffably stupid (according to " Esse quam videri ") that they have formed a very high opinion of the work which has already been done under this Act and are greatly impressed with the immensity of the benefit which would accrue to the health of the population under an extension of the system to a larger portion of the people, especially if the working of it could be placed under the control of enlightened general practitioners of large experience and the blighting hand of Vhitehall removed.-Iam, etc.,
Blocking Vascular Niche E-Selectin Dampens AML Stem Cell Regeneration/Survival Potential In Vivo By Inhibiting MAPK/ERK and PI3K/AKT Signalling Pathways
Authors: Ingrid G Winkler, Valerie Barbier, Joshua Tay, Jean-Pierre Levesque, John L. Magnani, Corrine E Fiveash, Johanna D Erbani
Journal: Blood (2019)