tbuckley/cabot-search huggingface dataset:
PDTM-18. COMBINED SUPPRESSION OF THE mTOR AND MAPK PATHWAYS INHIBITS GROWTH, DECREASES VASCULARITY AND INDUCES APOPTOSIS OR SENESCENCE IN PEDIATRIC LOW GRADE GLIOMA
Authors: Antje Arnold, Lauren Harris, Ming Yuan, Fausto Rodriguez, Charles Eberhart, Eric Raabe
Journal: Neuro-Oncology (2019)

Abstract Pediatric low-grade glioma (pLGG) is the most common brain tumor in children. We and others have identified constitutive activation of the mTOR and MEK-pathway in pLGG. This led us to investigate TAK228, a mTORC1/2-inhibitor, and the FDA approved MEK-inhibitor, trametinib, in mono- and combination therapy in pLGG. We examined antitumor activity in four patient-derived pLGG cell models treated with TAK228, trametinib, and combination: JHH_NF1_PA1(NF1mut), BT40(BRAFV600E), Res186(PTEN-/-) and Res259(CDKN2A-/-). Treatment with TAK228 or trametinib reduced cell proliferation in a dose and time dependent manner (MTS-assay). The combination treatment exerted a synergistic effect at 5-20nM in JHH_NF1_PA1, Res186, and Res259 cells (Chou-Talay method). The combination of TAK228 and trametinib increased apoptosis by up to 127% (p&lt; 0.001 by 1-way ANOVA) in Res186 and Res259 cells as measured by cleaved caspase 3 immunocytochemistry. Trametinib and combination treatment induces senescence in JHH_NF1_PA1 cell line verified through increase in p27 protein expression (Western Blot) and positive b-galactosidase staining. Mono-treatment with TAK228 or vehicle showed no signs of senescence. We tested trametinib and TAK228 against the mutant BT40BRAFV600E patient-derived cell line in immunodeficient mice. The combination treatment showed greater antitumor activity than that of either mono-treatment in vivo. BT40 tumor growth was significantly decreased in combination compared to vehicle or either agent alone (p&lt; 0.01). Combination treatment strikingly reduced the vascularization in the tumor tissue after combination treatment analyzed by CD31 and CD34 protein expression (Western Blot), compared to vehicle and mono-treatment. Our study provides evidence that pLGG-derived cell lines in vitro and in vivo are sensitive to mTORC1/2 kinase inhibition and MEK inhibition. Combination treatment with TAK228 and trametinib had a significant anti-tumor activity in vivo shown in survival rate, decreased tumor size, and reduced vascularity. These results provide the first strong rationale for combination therapy with TAK228 and trametinib for clinical consideration in pLGG.
Blinatumomab in Combination with Pembrolizumab Is Safe for Adults with Relapsed or Refractory B-Lineage Acute Lymphoblastic Leukemia: University of California Hematologic Malignancies Consortium Study 1504
Authors: Marc Schwartz, Lloyd E. Damon, Deepa Jeyakumar, Caitlin L. Costello, Dimitrios Tzachanis, Gary J. Schiller, Jesika Reiner, Matthew J. Wieduwilt
Journal: Blood (2019)
Updated Analysis of Bellini, a Phase 3 Study of Venetoclax or Placebo in Combination with Bortezomib and Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma
Authors: Philippe Moreau, Simon Harrison, Michele Cavo, Javier De La Rubia, Rakesh Popat, Cristina Gasparetto, Vania T.M. Hungria, Hans Salwender, Kenshi Suzuki, Inho Kim, Francesca Gay, Gábor Mikala, Elizabeth A Punnoose, Wan-Jen Hong, Anjla Sood, Muhammad Jalaluddin, Jeremy A. Ross, James E. Ward, Paulo C. Maciag, Shaji K. Kumar
Journal: Blood (2019)
CSF3R Mutations Are Exceedingly Rare Genetic Events Associated with Inferior Survival and Sensitivity to Ruxolitinib across Myeloid Malignancies
Authors: Anthony M. Hunter, Nelson Ryan, Mohammad Hussaini, Ratilal Akabari, Alan F. List, Jeffrey Lancet, David A Sallman, Rami S. Komrokji, Javier Pinilla Ibarz, Andrew T Kuykendall, Ling Zhang, Eric Padron
Journal: Blood (2019)
DRES-04. LONG NON-CODING RNAS IN GLIOBLASTOMA TUMOR RECURRENCE AND THERAPY RESISTANCE
Authors: Christian Stackhouse, G Yancey Gillespie, Christopher Willey
Journal: Neuro-Oncology (2019)

Abstract Recurrence of therapy resistant Glioblastoma multiforme (GBM) is responsible for patient mortality. Not all patients qualify for surgical resection or for chemotherapy, but radiation is almost a universally tolerated therapy. We are modeling acquired radiation resistance using 8 radiation-sensitive GBM patient-derived xenolines (PDX) made resistant by six irradiation series (6x2Gy each) in vivo. In 4 resistance-induced PDX, MGMT (O6-methylguanine–DNA methyltransferase) protein expression increased over original isogenic PDX. Paradoxically, temozolomide screening of orthotopic radiation-resistant PDX with increased MGMT expression revealed increased, not decreased chemo-sensitivity. This suggests an unanticipated mechanism associating acquired radiation resistance and alkylating chemotherapy sensitivity. RNA-seq data of long non-coding RNAs (lncRNAs) has revealed associations with patient overall survival and age at diagnosis. Out of 24,076 lncRNAs, 5 are significantly differentially expressed with regard to patient overall survival and age at diagnosis. The functions of lnc-ZNF117-1, lnc-DCUN1D4-1, and LINC01397 are unknown, but they are enriched in brain over other tissues. Tissue specific expression and function are unknown for lnc-TBL1XR1-5, but it is highly expressed in HepG2 (hepatocellular carcinoma) as well as in non-functioning pituitary adenomas (NFPAs). The lnc-CDH17-1 transcript is also highly expressed in NFPAs. All 5 of these lncRNAs have complex secondary and tertiary structures, but their physiologic or pathologic functions are unknown. LncRNAs most likely contribute to acquired resistance through epigenetic regulation of transcription and chromatin state. Deep sequencing of total RNA isolated from intracranial radiation–sensitive/–resistant PDX to relate transcriptional programs and therapy resistance is underway. These data will be paired with kinomic profiling of matched tumors to elucidate basal signaling modality changes between radiation–sensitive/–resistant tumors. Analysis of differentially expressed lncRNA will be used to predict lncRNA structure/function, elucidating druggable mechanisms mediated by lncRNAs.
Assessment of Cell-Free DNA (cfDNA) in 221 Patients with Lymphoproliferative Malignancies at Diagnosis and during Follow-up
Authors: Marcio M Andrade-Campos, Antonio Salar, Blanca Sanchez-Gonzalez, Concepción Fernández-Rodríguez, Eva Gimeno, L Ruiz, Gabriel Piquer, Francesc Garcia-Pallarols, Natalia Papaleo, Ivonne Vazquez, Lluís Colomo, Beatriz Bellosillo
Journal: Blood (2019)
Alterations of Gut Microbiome in Untreated Chronic Lymphocytic Leukemia (CLL); Future Therapeutic Potentials
Authors: Mohammed Kawari, Mahmood Akhtar, Mohamed Sager, Zakaria Basbous, Ibrahim Baydoun, Juma Kabanja, Mohammed Darweesh, Nihad Mokhtar, Solaf Kanfar, Enas Mutahar, John Apostolidis, Khalid Ahmed Al-Anazi, Hani Al Hashmi
Journal: Blood (2019)
COMP-16. COMPREHENSIVE TRANSCRIPTOMIC ANALYSIS OF SINGLE CELLS FROM RECURRENT AND PRIMARY GLIOBLASTOMA TO PREDICT CELL-TYPE SPECIFIC THERAPEUTICS
Authors: Robert Suter, Vasileios Stathias, Anna Jermakowicz, Alexa Semonche, Michael Ivan, Ricardo Komotar, Stephan Schürer, Nagi Ayad
Journal: Neuro-Oncology (2019)

Abstract Glioblastoma (GBM) remains the most common adult brain tumor, with poor survival expectations, and no new therapeutic modalities approved in the last decade. Our laboratories have recently demonstrated that the integration of a transcriptional disease signature obtained from The Cancer Genome Atlas’ GBM dataset with transcriptional cell drug-response signatures in the LINCS L1000 dataset yields possible combinatorial therapeutics. Considering the extreme intra-tumor heterogeneity associated with the disease, we hypothesize that the utilization of single-cell RNA-sequencing (scRNA-seq) of patient tumors will further strengthen our predictive model by providing insight on the unique transcriptomes of the cellular niches present within these tumors, and into the transcriptional dynamics of these same cellular niches. By sequencing single-cell transcriptomes from recurrent GBM tumors resected from patients at the University of Miami, and integrating our datasets with previously published scRNA-seq data from primary GBM tumors, we are able to gain additional insight into the differences between these clinical distinctions. We have analyzed the differential expression of kinases both across and within distinct cell populations of primary and recurrent GBM tumors. This transcriptional map of kinase expression represents the heterogeneity of potential targets within individual tumors and between recurrent and primary GBM. Additionally, by generating disease signatures unique to each cellular population, and integrating these with transcriptional drug-response signatures from LINCS, we are able to predict compounds to target specific cell populations within GMB tumors. Additional computational techniques such as RNA velocity analysis and cell cycle scoring elucidate temporal insights to further prioritize these cell-type specific therapeutics, and reveal the intra-cellular dynamics present within these tumors. Collectively, our studies suggest that we have developed a novel omics pipeline based on the single cell RNA-sequencing of individual GBM cells that addresses intra-tumor heterogeneity, and may lead to novel therapeutic combinations for the treatment of this incurable disease.
The Impact of Comorbidity on Quality of Life in Chronic Myeloid Leukemia Patients with Deep Molecular Response Who Stopped Therapy By Tyrosine Kinase Inhibitors: Results of the RU-SKI Trial
Authors: Tatyana Ionova, Tatiana Nikitina, Natalia Porfirieva, Anna Petrova, Ekaterina Yu. Chelysheva, Oleg A. Shukhov, Anastasiya Bykova, Galina Gusarova, Irina Nemchenko, Nikolay Tsyba, Anna G. Turkina
Journal: Blood (2019)
Assessing Efficacy of Provider and Family Education, Electronic Health Record Documentation Tools, and Information Technology to Increase Use of Hydroxyurea in Children with Sickle Cell Anemia
Authors: Kyle Hickman, Steve McCalley, Vinay Vaidya, Esteban Gomez, Christine M. Knoll, Joanna L. Gendreau, Lori Wagner, Meenakshi Goyal-Khemka, Brooke Cook, Kelli Fischbeck, Sanjay J. Shah
Journal: Blood (2019)
Large Granular Lymphocytic Leukemia Coexists with Clonal Hematopoiesis of Indeterminate Potential
Authors: Jibran Durrani, Hassan Awada, Ashwin Kishtagari, Cassandra M Kerr, Vera Adema, Yasunobu Nagata, Teodora Kuzmanovic, Sanghee Hong, Sunisa Kongkiatkamon, Alan Lichtin, MD, Aziz Nazha, Bhumika J. Patel, Yogenthiran Saunthararajah, Hetty E. Carraway, Valeria Visconte, Mikkael A. Sekeres, Jaroslaw P. Maciejewski
Journal: Blood (2019)
A Phase 1b/2 Study of IMGN632, a CD123-Targeting Antibody-Drug Conjugate (ADC), As Monotherapy or in Combination with Venetoclax and/or Azacitidine for Patients with CD123-Positive Acute Myeloid Leukemia
Authors: Naval Daver, Kendra L. Sweet, Pau Montesinos, Eunice S. Wang, Ahmed Aribi, Daniel J. DeAngelo, Harry P Erba, Giovanni Martinelli, Roland P Walter, Jessica K Altman, Anjali S Advani, Antonio Curti, Callum M Sloss, Kara E Malcolm, Patrick A Zweidler-McKay
Journal: Blood (2020)
Multiphase Iodine Contrast-Enhanced SPECT/CT Outperforms Nonenhanced SPECT/CT for Preoperative Localization of Small Parathyroid Adenomas
Authors: Patricia Sandqvist, Inga-Lena Nilsson, Per Grybäck, Alejandro Sanchez-Crespo, Anders Sundin
Journal: Clinical Nuclear Medicine (2019)

Purpose The aim of this study was to assess the value of intravenously contrast-enhanced CT in conjunction with 99m Tc-MIBI SPECT for preoperative localization of parathyroid adenoma. Methods One hundred ninety-two patients with primary hyperparathyroidism were enrolled in the study between May 2015 and May 2017. The patients underwent a preoperative “one-stop shop” examination with 99m Tc-MIBI SPECT/CT by using dual time-point (10 and 90 minutes) protocol and both nonenhanced CT and contrast-enhanced CT acquisition in the arterial and venous phase, 35 and 75 seconds, respectively, after contrast medium injection start. For 149 patients, the imaging results could be correlated to those at surgery and histopathology. Results The median adenoma weight was 330 mg. The addition of contrast-enhanced CT increased the sensitivity from 81.1% to 89.9% ( P = 0.003). The specificity of nonenhanced SPECT/CT was similar to contrast-enhanced CT (96.1% vs 97.9%; P = 0.077). For patients with uniglandular disease (n = 140, 94.0%), the sensitivity increased from 86.4% to 93.6% ( P = 0.021) and the specificity from 96.2% to 97.9% ( P = 0.118) by adding contrast-enhanced CT. In patients with multiglandular disease (n = 9, 6.0%), adding contrast-enhanced CT improved detection sensitivity from 42.1% to 63.2%. However, these patients were few and significance was not reached ( P = 0.125). Conclusions In this cohort, with generally small parathyroid adenomas, the sensitivity in preoperative localization was greatly improved by adding contrast-enhanced CT to 99m Tc-MIBI SPECT/CT.
Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium
Authors: Oliver A Cornely, Ana Alastruey-Izquierdo, Dorothee Arenz, Sharon C A Chen, Eric Dannaoui, Bruno Hochhegger, Martin Hoenigl, Henrik E Jensen, Katrien Lagrou, Russell E Lewis, Sibylle C Mellinghoff, Mervyn Mer, Zoi D Pana, Danila Seidel, Donald C Sheppard, Roger Wahba, Murat Akova, Alexandre Alanio, Abdullah M S Al-Hatmi, Sevtap Arikan-Akdagli, Hamid Badali, Ronen Ben-Ami, Alexandro Bonifaz, Stéphane Bretagne, Elio Castagnola, Methee Chayakulkeeree, Arnaldo L Colombo, Dora E Corzo-León, Lubos Drgona, Andreas H Groll, Jesus Guinea, Claus-Peter Heussel, Ashraf S Ibrahim, Souha S Kanj, Nikolay Klimko, Michaela Lackner, Frederic Lamoth, Fanny Lanternier, Cornelia Lass-Floerl, Dong-Gun Lee, Thomas Lehrnbecher, Badre E Lmimouni, Mihai Mares, Georg Maschmeyer, Jacques F Meis, Joseph Meletiadis, C Orla Morrissey, Marcio Nucci, Rita Oladele, Livio Pagano, Alessandro Pasqualotto, Atul Patel, Zdenek Racil, Malcolm Richardson, Emmanuel Roilides, Markus Ruhnke, Seyedmojtaba Seyedmousavi, Neeraj Sidharthan, Nina Singh, János Sinko, Anna Skiada, Monica Slavin, Rajeev Soman, Brad Spellberg, William Steinbach, Ban Hock Tan, Andrew J Ullmann, Jörg J Vehreschild, Maria J G T Vehreschild, Thomas J Walsh, P Lewis White, Nathan P Wiederhold, Theoklis Zaoutis, Arunaloke Chakrabarti
Journal: The Lancet Infectious Diseases (2019)
Working Hours of Junior Staff
Authors: J. G. Dumoulin, M. J. Grayson, A. C. Hunt, M. T. Inman, P. Meers, W. E. Strachan, M. W. Reece, M. K. Strelling, K. Weeks, R. D. Sweet, J. A. C. Strachan
Journal: BMJ (1974)
Clostridium difficile and One Health
Authors: S.C. Lim, D.R. Knight, T.V. Riley
Journal: Clinical Microbiology and Infection (2019)

For over four decades, Clostridium difficile has been a significant enteric pathogen of humans. It is associated with the use of antimicrobials that generally disrupt the microbiota of the gastrointestinal tract. Previously, it was thought that C. difficile was primarily a hospital-acquired infection; however, with the emergence of community-associated cases, and whole-genome sequencing suggesting the majority of the hospital C. difficile infection (CDI) cases are genetically distinct from one another, there is compelling evidence that sources/reservoirs of C. difficile outside hospitals play a significant role in the transmission of CDI.To review the 'One Health' aspects of CDI, focusing on how community sources/reservoirs might be acting as a conduit in the transfer of C. difficile between animals and humans. The importance of a One Health approach in managing CDI is discussed.A literature search was performed on PubMed and Web of Science for relevant papers published from 1 January 2000 to 10 July 2019.We present evidence that demonstrates transmission of C. difficile in hospitals from asymptomatic carriers to symptomatic CDI patients. The source of colonization is most probably community reservoirs, such as foods and the environment, where toxigenic C. difficile strains have frequently been isolated. With high-resolution genomic sequencing, the transmission of C. difficile between animals and humans can be demonstrated, despite a clear epidemiological link often being absent. The ways in which C. difficile from animals and humans can disseminate through foods and the environment are discussed, and an interconnected transmission pathway for C. difficile involving food animals, humans and the environment is presented.Clostridium difficile is a well-established pathogen of both humans and animals that contaminates foods and the environment. To manage CDI, a One Health approach with the collaboration of clinicians, veterinarians, environmentalists and policy-makers is paramount.
Real-World Treatment Patterns from the HUMANS Study in Multiple Myeloma in Denmark
Authors: Niels Abildgaard, Anders Waage, Markus Hansson, Pekka Anttila, Mate Szilcz, Yuanjun Ma, Katrine Hass Rubin, Lill-Brith von Arx, Sigurd Ørstavik, Nawal Bent-Ennakhil, Jonatan Freilich, François Gavini, Anders Green
Journal: Blood (2019)
Safety of Caplacizumab in Patients Without Documented Severe ADAMTS13 Deficiency During the HERCULES Study
Authors: Javier De La Rubia, Flora Peyvandi, Marie Scully, Spero Cataland, Paul Coppo, Johanna A. Kremer Hovinga, Paul Knoebl, Ara Metjian, Katerina Pavenski, Hilde De Winter, Rui de Passos Sousa, Filip Callewaert
Journal: Blood (2019)
Blinatumomab Is Well Tolerated Maintenance Therapy Following Allogeneic Hematopoietic Cell Transplantation for Acute Lymphoblastic Leukemia
Authors: Partow Kebriaei, Pinaki P Banerjee, Christina Ganesh, Mecit Kaplan, Vandana Nandivada, Ana Karen Nunez Cortes, Amin M. Alousi, David Marin, Elizabeth J. Shpall, Rohtesh Mehta, Farhad Ravandi, Elias Jabbour, Hagop M. Kantarjian, Richard E. Champlin, Katayoun Rezvani
Journal: Blood (2019)
Regulation of the Inflammatory Synovial Fibroblast Phenotype by Metastasis‐Associated Lung Adenocarcinoma Transcript 1 Long Noncoding <scp>RNA</scp> in Obese Patients With Osteoarthritis
Authors: Dominika E. Nanus, Susanne N. Wijesinghe, Mark J. Pearson, Marina R. Hadjicharalambous, Alex Rosser, Edward T. Davis, Mark A. Lindsay, Simon W. Jones
Journal: Arthritis & Rheumatology (2019)

To identify long noncoding RNAs (lncRNAs) associated with the inflammatory phenotype of synovial fibroblasts from obese patients with osteoarthritis (OA), and to explore the expression and function of these lncRNAs.Synovium was collected from normal-weight patients with hip fracture (non-OA; n = 6) and from normal-weight (n = 8) and obese (n = 8) patients with hip OA. Expression of RNA was determined by RNA-sequencing and quantitative reverse transcription-polymerase chain reaction. Knockdown of lncRNA was performed using LNA-based GapmeRs. Synovial fibroblast cytokine production was measured by enzyme-linked immunosorbent assay.Synovial fibroblasts from obese patients with OA secreted greater levels of interleukin-6 (IL-6) (mean ± SEM 162 ± 21 pg/ml; P < 0.001) and CXCL8 (262 ± 67 pg/ml; P < 0.05) compared to fibroblasts from normal-weight patients with OA (IL-6, 51 ± 4 pg/ml; CXCL8, 78 ± 11 pg/ml) or non-OA patients (IL-6, 35 ± 3 pg/ml; CXCL8, 56 ± 6 pg/ml) (n = 6 patients per group). RNA-sequencing revealed that fibroblasts from obese OA patients exhibited an inflammatory transcriptome, with increased expression of proinflammatory messenger RNAs (mRNAs) as compared to that in fibroblasts from normal-weight OA or non-OA patients (>2-fold change, P < 0.05; n = 4 patients per group). A total of 19 lncRNAs were differentially expressed between normal-weight OA and non-OA patient fibroblasts, and a further 19 lncRNAs were differentially expressed in fibroblasts from obese OA patients compared to normal-weight OA patients (>2-fold change, P < 0.05 for each), which included the lncRNA for metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). MALAT1 was rapidly induced upon stimulation of OA synovial fibroblasts with proinflammatory cytokines, and was up-regulated in the synovium from obese OA patients as compared to normal-weight OA patients (1.6-fold change, P < 0.001) or non-OA patients (6-fold change, P < 0.001). MALAT1 knockdown in OA synovial fibroblasts (n = 4 patients) decreased the levels of mRNA expression and protein secretion of CXCL8 (>1.5-fold change, P < 0.01), whereas it increased expression of mRNAs for TRIM6 (>2-fold change, P < 0.01), IL7R (<2-fold change, P < 0.01), HIST1H1C (>1.5-fold change, P < 0.001), and MAML3 (>1.5-fold change, P < 0.001). In addition, MALAT1 knockdown inhibited the proliferation of synovial fibroblasts from obese patients with OA.Synovial fibroblasts from obese patients with hip OA exhibit an inflammatory phenotype. MALAT1 lncRNA may mediate joint inflammation in obese OA patients.
Phase 1b Study of Carfilzomib in Combination with Induction Chemotherapy in Children with Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL)
Authors: Michael J. Burke, David S. Ziegler, Francisco José Bautista Sirvent, Andishe Attarbaschi, Lia Gore, Franco Locatelli, Maureen M O'Brien, Melinda Pauly, Mihaela Obreja, Christopher L. Morris, Andre Baruchel
Journal: Blood (2019)
Ethical climate and intention to leave among critical care clinicians: an observational study in 68 intensive care units across Europe and the United States
Authors: Bo Van den Bulcke, Victoria Metaxa, Anna K. Reyners, Katerina Rusinova, Hanne I. Jensen, J. Malmgren, Michael Darmon, Daniel Talmor, Anne-Pascale Meert, Laura Cancelliere, László Zubek, Paulo Maia, Andrej Michalsen, Erwin J. O. Kompanje, Peter Vlerick, Jolien Roels, Stijn Vansteelandt, Johan Decruyenaere, Elie Azoulay, Stijn Vanheule, Ruth Piers, Dominique Benoit
Journal: Intensive Care Medicine (2019)

Apart from organizational issues, quality of inter-professional collaboration during ethical decision-making may affect the intention to leave one's job. To determine whether ethical climate is associated with the intention to leave after adjustment for country, ICU and clinicians characteristics. Perceptions of the ethical climate among clinicians working in 68 adult ICUs in 12 European countries and the US were measured using a self-assessment questionnaire, together with job characteristics and intent to leave as a sub-analysis of the Dispropricus study. The validated ethical decision-making climate questionnaire included seven factors: not avoiding decision-making at end-of-life (EOL), mutual respect within the interdisciplinary team, open interdisciplinary reflection, ethical awareness, self-reflective physician leadership, active decision-making at end-of-life by physicians, and involvement of nurses in EOL. Hierarchical mixed effect models were used to assess associations between these factors, and the intent to leave in clinicians within ICUs, within the different countries. Of 3610 nurses and 1137 physicians providing ICU bedside care, 63.1% and 62.9% participated, respectively. Of 2992 participating clinicians, 782 (26.1%) had intent to leave, of which 27% nurses, 24% junior and 22.7% senior physicians. After adjustment for country, ICU and clinicians characteristics, mutual respect OR 0.77 (95% CI 0.66- 0.90), open interdisciplinary reflection (OR 0.73 [95% CI 0.62–0.86]) and not avoiding EOL decisions (OR 0.87 [95% CI 0.77–0.98]) were all associated with a lower intent to leave. This is the first large multicenter study showing an independent association between clinicians' intent to leave and the quality of the ethical climate in the ICU. Interventions to reduce intent to leave may be most effective when they focus on improving mutual respect, interdisciplinary reflection and active decision-making at EOL.
HLA-DM Mediates Permissiveness of HLA-DPB1 T Cell Epitope Mismatches in Unrelated HCT
Authors: Maximilian Metzing, Pietro Crivello, Thuja Meurer, Michel G.D. Kester, Dominik Megger, Weiqiang Chen, Peter Van Balen, Marieke Griffioen, Peter A. Horn, Barbara Sitek, J.H.Frederik Falkenburg, Esteban Arrieta-Bolaños, Katharina Fleischhauer
Journal: Blood (2019)