tbuckley/cabot-search huggingface dataset:
Banked EBV-specific T-cells from HLA-partially matched normal donors to induce durable remissions of rituximab refractory EBV<sup>+ </sup>B-cell lymphomas post hematopoietic and organ allografts.
Authors: Susan Prockop, Ekaterina Doubrovina, Karim Baroudy, Farid Boulad, Ramzi Khalaf, Esperanza Bouza Papadopoulos, Craig Steven Sauter, Victoria Szenes, Stephanie Suser, Gloria Wasilewski, Julianne Ruggiero, Richard J. O'Reilly
Journal: Journal of Clinical Oncology (2015)

10016 Background: EBV+ B-cell lymphomas (EBV+ BCL) are life threatening after allogeneic hematopoietic (HCT) or organ (SOT) transplant. In Phase II trials, we are testing the safety and activity of GMP grade EBV-specific cytotoxic T-cells (EBVCTL) generated from over 300 consenting normal seropositive donors, characterized as to EBV-specificity, HLA type and HLA restriction and cryopreserved in a bank for adoptive therapy. Methods: We have treated 13 SOT and 34 HCT recipients with pathologically documented EBV+BCL. All patients (pts) had failed to respond or relapsed following rituximab treatment; 11 SOT recipients also failed 1-5 courses of rituximab with chemotherapy. Pts received 1-6 courses of T-cell infusions, each separated by 3 wks observation. A course consisted of 3 weekly intravenous doses of EBVCTL, each dose providing 1- 2x106 EBVCTL/kg. EBVCTLs were selected based on matching for at least 2 HLA alleles (HLA, A, B, C or DR) and restriction by an HLA allele shared by the pt or the pt's disease. Results: EBVCTL infusions were well tolerated. 1 pt had transient fever after one dose in a 2o course. One HCT pt developed grade 1 skin GVHD that cleared with topical steroid. No HCT or SOT pt had cell count depressions, a rejection reaction, or cytokine release syndrome. Of 34 HCT pts, 19 have durable CRs, 3 sustained PRs (>5mo, >16mo; >15mo); 2 had SD and10 disease progression (PD) CR+PR=65%. Of 13 SOT pts, 1 has a durable CR (>22mo) and 7 durable PRs (>6mo; >16mo; 17mo; >10mo; >24mo; >42mo; >114mo) (CR+PR=62%). Responses were achieved after 1-6 courses (median 2). EBV-specific CTLp rose in the blood of responding pts after each EBVCTL course, but not in pts with PD. After 1 cycle, 7 pts with PD received EBVCTL from a second donor restricted by a different HLA allele shared by the pt, of whom, 5 achieved a CR or durable PR. No pt with CR or PR has had progression requiring alternative therapy. Conclusions: Thus, adoptive transfer of HLA partially matched EBVCTL from our cryopreserved bank, that are restricted by HLA alleles expressed by the pt's disease, has minimal toxicity and induces durable regression of EBV+BCL refractory to rituximab and/or chemotherapy in a high proportion of HCT and SOT recipients. Clinical trial information: NCT01498484.
THU-168-Real-life effectivness and safety of glecaprevir/pibrentasvir in HCV infected patients with chronic kidney disease
Authors: Marcello Persico, Andrea Aglitti, Rosa Caruso, Gemma Calvanese, Pasqualina Di Siervi, Nuzzo Maria Grazia, Marie Francoise Tripodi, Mario Masarone
Journal: Journal of Hepatology (2019)
US Emergency Department Visits and Hospital Discharges Among Uninsured Patients Before and After Implementation of the Affordable Care Act
Authors: Adam J. Singer, Henry C. Thode, Jesse M. Pines
Journal: JAMA Network Open (2019)

The US Patient Protection and Affordable Care Act of 2010 (ACA) was enacted in 2010 with several provisions that targeted reducing numbers of uninsured Americans.To assess the numbers and proportion of emergency department (ED) visits (2006-2016) and hospital discharges (2006-2016) by uninsured patients, focusing on the 2014 ACA insurance reforms (Medicaid expansion, individual mandate, and private insurance exchanges).Cross-sectional study of visitors to US EDs and patients discharged from US hospitals using National Hospital Ambulatory Care Survey data and Healthcare Cost and Utilization Project data, respectively, from 2006 to 2016. Data analysis took place in February 2019.Numbers and proportions of total and uninsured ED visits and hospital discharges. Simple descriptive statistics and interrupted time-series analysis were used to assess changes in uninsured visits over time and after the implementation of insurance provisions in 2014.There were an estimated 1.4 billion US ED visits from 2006 to 2016 and 405 million hospital discharges from 2006 to 2016. Over the study period, ED visits increased by 2.3 million per year, while hospital discharges decreased from approximately 38 million per year prior to 2009 to approximately 36 million per year after, with no clear decrease after 2013. Proportions of uninsured ED visits were largely unchanged from 2006 (16%) until 2013 (14%) (-0.2 percentage point per year; 95% CI, -0.46 to -0.01 percentage point; P = .11) but then decreased by 2.1 percentage points per year from 2014 to 2016 (95% CI, -4.3 to -1.8 percentage points; P = .003), with uninsured visits composing 8% of the total in 2016. For patients aged 18 to 64 years, uninsured ED visits declined from approximately 20% from 2006 through 2013 to 11% in 2016 (3.1% decrease per year after 2013; 95% CI, -4.3 to -1.8 percentage points; P = .003). The proportion of hospital discharges by uninsured patients remained steady at approximately 6% from 2006 to 2013, then declined to 5% in 2014 and 4% in 2016. Similar changes were seen for patients aged 18 to 64 years, with a decrease in hospital discharges from 10% to 7% over the study period.Proportions of ED visits and hospital discharges by uninsured patients decreased considerably after the implementation of the 2014 ACA insurance provisions. Despite these changes, approximately 1 in 10 ED visits and 1 in 20 hospital discharges were made by uninsured individuals in 2014 to 2016. This suggests that continued attention is needed to address the lack of insurance in US hospital visits, particularly among people aged 18 to 64 years who have less access to government-sponsored insurance.
Psychotherapists warn against describing the needs of children with mental health problems as “low level”
Authors: Ingrid Torjesen
Journal: BMJ (2019)

Services provided in the community to children and young people with mental health needs should not be described as “low level,” psychotherapists have pointed out after the children’s commissioner described them this way.

Many children and young people seen in the community have complex mental health needs that require skill and experience to manage and complicated networks of care, the Association of Child Psychotherapists says.

The report that the children’s commissioner for England, Anne Longfield, published this week found that just over £14 (€16.30; $18.30) a child is spent by local authorities and the NHS in England on preventive “low level” mental health support, and …
FA-01-Prevalence of mother-to-child transmission of hepatitis B virus: A systematic review and meta-analysis
Authors: Jinfeng Liu, Naijuan Yao, Tianyan Chen, Shan Fu, yuchao wu, Yali Feng, Zhen Tian, juan li, Fanpu Ji, yaolong chen, Yingren Zhao
Journal: Journal of Hepatology (2019)
Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial
Authors: Salah-Eddin Al-Batran, Nils Homann, Claudia Pauligk, Thorsten O Goetze, Johannes Meiler, Stefan Kasper, Hans-Georg Kopp, Frank Mayer, Georg Martin Haag, Kim Luley, Udo Lindig, Wolff Schmiegel, Michael Pohl, Jan Stoehlmacher, Gunnar Folprecht, Stephan Probst, Nicole Prasnikar, Wolfgang Fischbach, Rolf Mahlberg, Jörg Trojan, Michael Koenigsmann, Uwe M Martens, Peter Thuss-Patience, Matthias Egger, Andreas Block, Volker Heinemann, Gerald Illerhaus, Markus Moehler, Michael Schenk, Frank Kullmann, Dirk M Behringer, Michael Heike, Daniel Pink, Christian Teschendorf, Carmen Löhr, Helga Bernhard, Gunter Schuch, Volker Rethwisch, Ludwig Fischer von Weikersthal, Jörg T Hartmann, Michael Kneba, Severin Daum, Karsten Schulmann, Jörg Weniger, Sebastian Belle, Timo Gaiser, Fuat S Oduncu, Martina Güntner, Wael Hozaeel, Alexander Reichart, Elke Jäger, Thomas Kraus, Stefan Mönig, Wolf O Bechstein, Martin Schuler, Harald Schmalenberg, Ralf D Hofheinz
Journal: The Lancet (2019)
Pathogenic effector functions of ACPA: Where do we stand?
Authors: René Toes, David S Pisetsky
Journal: Annals of the Rheumatic Diseases (2019)

In the late 1990s, the discovery that citrullinated proteins are targeted by autoantibodies known as anti-citrullinated protein antibodies (ACPA) revolutionised the study of rheumatoid arthritis (RA). Because of the high specificity of ACPA for RA, investigators began experiments to determine whether ACPA have a direct pathogenetic role in arthritis or whether these antibodies more simply reflect underlying T-cell and B-cell responses without themselves impacting on joint inflammation and damage. The debate on the role of ACPA has been extensive and has now entered a new phase with the publication of correction notes appearing in this issue1 2 of Annals of the Rheumatic (ARD ). These notes concern papers that appeared in the journal in 20163 4 and follow a retraction note and correspondence in other journals.5–7 

In these notes, the study authors indicate that the monoclonal antibodies used in their experiments on ACPA pathogenicity did not, in fact, react with citrullinated proteins and/or peptides. As such, the putative functional activities of these monoclonals must have resulted from mechanisms other than antibody binding to a citrullinated target. The implications of these corrections and retractions for models of pathogenesis are wide ranging and call into question the nature of ACPA involvement in manifestations of RA. Because of the importance of these issues for the scientific community, in this editorial, we will review the role of ACPA in RA and the salient issues in establishing the pathogenicity of these autoantibodies.

ACPA are unique biomarkers for RA, a serious form of arthritis characterised by inflammation, pain and, unless treated effectively, damage of cartilage and bone. As shown in elegant biochemical studies, ACPA target proteins that contain the amino acid citrulline, a post-translational modification (PTM) of the amino acid arginine mediated by peptidyl arginine deiminase enzymes8 9; these antibodies are also …
THU-300-Prevalence of NAFLD in patients with a first episode of stroke and impact on the mortality and severity at 3 months
Authors: Teresa Broquetas, Elisa Cuadrado, Lidia Canillas, Susana Coll, Montserrat Garcia Retortillo, Nuria Cañete, Carlos Fernando Enriquez, Marc Puigvehí, Ricard Sola Lamoglia, Jose A. Carrión
Journal: Journal of Hepatology (2019)
THU-054-Acute variceal bleed leads to acute on chronic liver failure like syndrome in a small proportion of cirrhotic patients: an analysis of 3845 patients from AARC data base
Authors: Harsh Vardhan Tevethia, Ashok Choudhury, Rakhi Maiwall, Manoj Kumar, Vikram Bhatia, Ankur Jindal, Shasthry Sm, Vinod Arora, V Rajan, Guresh Kumar, Priyanka Jain, Irene Paulson, Y K Joshi, Shiv Kumar Sarin
Journal: Journal of Hepatology (2019)
PS-067-Increasing incidence of HCV-GT2 as well as reinfections within the ongoing epidemic of acute HCV infections among MSM in Central Europe
Authors: David Chromy, David JM Bauer, Caroline Schmidbauer, Philipp Schwabl, Theresa Bucsics, Bernhard Scheiner, Gerold Felician Lang, Michael Gschwantler, Peter Ferenci, Michael Trauner, Mattias Mandorfer, Thomas Reiberger
Journal: Journal of Hepatology (2019)
Gemcitabine, Cisplatin, and nab-Paclitaxel for Patients With Advanced Biliary Tract Cancer
Authors: Marc T. Roth, Laura W. Goff
Journal: JAMA Oncology (2019)

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Children’s mental health: getting early support “leaves much to chance,” says commissioner
Authors: Jacqui Thornton
Journal: BMJ (2019)

Local authorities and the NHS in England spend just over £14 a child (€16.30; $18.30) on preventive “low level” mental health support, and over a third of areas are seeing a cut in spending, warns a report by the Children’s Commissioner.1

This is the first analysis of data on preventive and early intervention services for treating problems including anxiety and eating disorders, such as support provided by school nurses or counsellors, drop-in centres, and online counselling services.

Anne Longfield, Children’s Commissioner for England, says that these services are vital for offering early help to children with mental health problems and can often prevent conditions from developing into much more serious illnesses. But she said that the system is “highly fragmented” and “leaves much to chance.”

She warned, “There is a danger that we continue to have a system that fails to help children until they are so unwell that they need specialist intervention.”

The report showed that local areas, including spending by local authorities and NHS clinical commissioning groups (CCGs), allocated £226m for low level mental health services in 2018-19—just over …
Abstract 14632: The Potential of Public-access Defibrillation by Citizen Before Emergency Medical Service Contact in Out-of-hospital Cardiac Arrest Patients With Shockable Rhythm
Authors: Takahiro Nakashima, Yoshio Tahara, Teruo Noguchi, Kunihiko Nishimura, Satoshi Yasuda, Atsushi Kojima, Naohiro Yonemoto, Keijiro Saku, Hiroshi Nonogi, Ken Nagao
Journal: Circulation (2017)

Introduction: The fact that public access automated external defibrillation (AED) has been widely accepted improves outcome of out-of-hospital cardiac arrest (OHCA) with shockable rhythm initially. However, the rate of return of spontaneous circulation (ROSC) in OHCA patients with shockable rhythm initially is approximately 18% by receiving public-access defibrillation, and most OHCA patients did not obtain ROSC. Thus, we compared outcome between patients with and without public-access defibrillation by citizen before emergency medical service (EMS) contact in OHCA patients with shockable rhythm at EMS contact. Methods: From a nationwide, prospective, population-based registry of 1,176,363 OHCA patients in Japan, we identified 210,642 patients over the age of 18 years from 2005 through 2014 with bystander-witnessed cardiac arrests of presumed cardiac origin in whom resuscitation was attempted. The primary outcome measure was survival at 1 month with a favorable neurologic outcome (Cerebral Performance Cat...
Celiprolol but not losartan improves the biomechanical integrity of the aorta in a mouse model of vascular Ehlers–Danlos syndrome
Authors: Nicolo Dubacher, Justyna Münger, Maria C Gorosabel, Jessica Crabb, Agnieszka A Ksiazek, Sylvan M Caspar, Erik N T P Bakker, Ed van Bavel, Urs Ziegler, Thierry Carrel, Beat Steinmann, Steffen Zeisberger, Janine Meienberg, Gabor Matyas
Journal: Cardiovascular Research (2019)

Abstract Aims Antihypertensive drugs are included in the medical therapy of vascular Ehlers–Danlos syndrome (vEDS). The β-blocker celiprolol has been suggested to prevent arterial damage in vEDS, but the underlying mechanism remains unclear. It is also unknown whether the widely used angiotensin II receptor type 1 antagonist losartan has a therapeutic effect in vEDS. Here, we evaluated the impact of celiprolol and losartan on the biomechanical integrity of the vEDS thoracic aorta. Methods and results We established a new approach to measure the maximum tensile force at rupture of uniaxially stretched murine thoracic aortic rings. In a vEDS model, which we (re-)characterized here at molecular level, heterozygous mice showed a significant reduction in the rupture force compared to wild-type mice, reflecting the increased mortality due to aortic rupture. For the assessment of treatment effects, heterozygous mice at 4 weeks of age underwent a 4-week treatment with celiprolol, losartan, and, as a proof-of-concept drug, the matrix metalloproteinase inhibitor doxycycline. Compared to age- and sex-matched untreated heterozygous mice, treatment with doxycycline or celiprolol resulted in a significant increase of rupture force, whereas no significant change was detected upon losartan treatment. Conclusions In a vEDS model, celiprolol or doxycycline, but not losartan, can improve the biomechanical integrity of the aortic wall, thereby potentially reducing the risk of dissection and rupture. As doxycycline is a broad-spectrum antibiotic with considerable side effects, celiprolol may be more suitable for a long-term therapy and thus rather indicated for the medication of patients with vEDS.
THU-471-Establishment of a short-termed orthotopic transplantation model in C57/B6 mice that recapitulates characteristic features of human intrahepatic cholangiocarcinoma
Authors: Janine Koehncke, Theresa Hildegard Wirtz, Christian Holland, Elisa Fabiana Brandt, Thomas Philipp Ritz, Daniel Heinrichs, Petra Fischer, Christian Trautwein, Thomas Longerich, Julio Saez-Rodriguez, Marie-Luise Berres
Journal: Journal of Hepatology (2019)
Validation and quality assessment of the Kilimanjaro Cancer Registry.
Authors: Leah L. Zullig, Charles Muiruri, Pili Nyindo, Theresia Namwai, Francis Karia, Michael Oresto, Elvis Silayo, Angelah Msomba, John Bartlett, Yousuf Zafar
Journal: Journal of Clinical Oncology (2016)

266 Background: The global cancer burden has increasingly shifted to low and middle-income countries and is particularly pronounced in Africa. However, there remains a lack of comprehensive information about cancer incidence due to limited development of cancer registries. In Moshi, Tanzania, a regional cancer registry exists at Kilimanjaro Christian Medical Center (KCR). The quality of the registry data is unknown. Our objective was to evaluate the completeness and quality of the KCR. Methods: In October 2015 we conducted a retrospective review, validating internal consistency of registry records compared with paper-based medical and pathology records. We randomly sampled approximately 3% of over 3000 registry cases (n = 100), focused on cases abstracted from 2014-15. Four independent reviewers not associated with the KCR manually collected and compared key data elements (e.g., cancer site, morphology, diagnosis date). Data were collected using Microsoft Excel. Data management and analysis were conducted in Stata. Results: The KCR contains information on over 3000 patients from 32 tribal groups and 8 geographic areas in the Kilimanjaro region. All of the 100 reviewed cases had complete cancer site and morphology in the registry. Six had a recorded stage. For the majority of cases (n = 92) the basis of diagnosis was pathology. Pathology records were found in the medical record for 41% of cases; for the remainder, pathology records were stored separately in the pathology department. Of sampled cases, the KCR and medical records were 98% and 94% concordant for primary cancer site and morphology, respectively. For 28% of cases, recorded diagnosis dates were within 14 days of what was found in the medical record, and for 32% of cases they were within 30 days. Conclusions: Although training is needed to standardize diagnosis date definitions, this study suggests that KCR data is high quality. Research is needed to determine effectiveness at ascertaining all patients in its catchment area. The registry may have utility for resource planning and research purposes.
Abstract 17212: Heart and Kidney Transplants: Should They be Combined or Subsequent? Analysis From the United Network Organ Sharing Database
Authors: Inga Melvinsdottir, Sverrir Gunnarsson, Timothy Hess, Takushi Kohmoto, Lucian Lozonschi, Ravi Dhingra
Journal: Circulation (2017)

Introduction: End stage heart failure is often associated with progressive kidney dysfunction. Combined heart and kidney transplant (HKTx) or kidney transplant after heart transplant (KAH) are trea...
In type 2 diabetes with periodontitis, intensive periodontitis treatment improved glycemic control at 1 year
Authors: Zubin Punthakee
Journal: Annals of Internal Medicine (2019)

Source Citation D'Aiuto F, Gkranias N, Bhowruth D, et al; TASTE Group. Systemic effects of periodontitis treatment in patients with type 2 diabetes: a 12 month, single-centre, investigator-masked, randomised trial. Lancet Diabetes Endocrinol. 2018;6:954-65. 30472992
PS-100-Bench-to-clinical development of plasminogen as a novel prognostic biomarker for patients with hepatitis B virus related acute-on-chronic liver failure
Authors: Daxian Wu, zeyu sun, sainan zhang, qunfang rao, Zhouhua Hou, Bingjie Liu, Hainv Gao, Lanjuan Li
Journal: Journal of Hepatology (2019)
SAT-078-Characterizing compensated cirrhosis patients with potential etiology of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis: Findings from large Italian administrative databases
Authors: Giulio Marchesini Reggiani, Jie Ting, Stefania Saragoni, Valentina Perrone, Shreay Sanatan, Salvatore Petta
Journal: Journal of Hepatology (2019)