Journal articles: 'Medical Board of Columbia (S.C.)' – Grafiati (2024)

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Relevant bibliographies by topics / Medical Board of Columbia (S.C.) / Journal articles

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Author: Grafiati

Published: 4 June 2021

Last updated: 3 February 2022

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1

Ou,C.N., and C.L.Rognerud. "Rapid analysis of hemoglobin variants by cation-exchange HPLC." Clinical Chemistry 39, no.5 (May1, 1993): 820–24. http://dx.doi.org/10.1093/clinchem/39.5.820.

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Abstract We investigated the use of a 3.5 x 0.46 cm HPLC column packed with 5-microns particles of porous (100 nm) silica coated with polyaspartic acid for hemoglobin analysis. A 13-min gradient was produced between two mobile phases. The method is capable of separating more than 35 commonly encountered hemoglobin variants within 12 min. Hemoglobin variants identified include Bart's, acetyl F, H, A1c, F, Camden, N-Baltimore, J-Baltimore, N-Seattle, Grady, Fannin-Lubbock, A G-Georgia, Lepore-Baltimore, P-Galveston, G-Coushatta, Lepore-Boston, E, Osu Christiansborg, A2, G-Philadelphia, Korle Bu, Russ, Richmond, D-Los Angeles, Deer Lodge, Montgomery, S, Q-Thailand, G-San Jose, A2', Hasharon, Q-India, Tampa, GS hybrid, C-Harlem, O-Arab, British Columbia, and C. Between-run precision of an in-house pooled hemoglobin control material, AFSCA2, gave CVs of 2-5% for the A, F, S, and C and 8% for the A2 over a 6-month period. The simplicity of sample preparation, high resolution of the system, and high accuracy of the method, combined with complete automation, make this an ideal methodology for the routine diagnosis of hemoglobin disorders in a clinical laboratory.

2

Koshan, Jennifer. "Intersections and Roads Untravelled: Sex and Family Status in Fraser v Canada." Constitutional Forum / Forum constitutionnel 30, no.2 (May12, 2021): 29–42. http://dx.doi.org/10.21991/cf29420.

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It has been a long road to the judicial recognition of women’s inequality under the Cana‑ dian Charter of Rights and Freedoms.1 The Supreme Court of Canada ruling in Fraser v Can‑ ada is significant for being the first decision where a majority of the Court found adverse effects discrimination based on sex under section 15,2 and it was only two years prior that a claim of sex discrimination in favour of women was finally successful at the Court,3 almost 30 years after their first section 15 decision in Andrews v Law Society of British Columbia. 4 1 Part I of the Constitution Act, 1982, being Schedule B to the Canada Act 1982 (UK), 1982, c 11 [Charter], s 15. 2 Fraser v Canada (Attorney General), 2020 SCC 28 [Fraser]. 3 Quebec (Attorney General) v Alliance du personnel professionnel et technique de la santé et des services sociaux, 2018 SCC 17 [Alliance] (majority found sex discrimination under s 15 and rejected the government’s justification argument under s 1 in the pay equity context). See also Centrale des syndicats du Québec v Quebec (Attorney General), 2018 SCC 18 [Centrale] (majority found violation of s 15 but accepted the government’s s 1 argument, also in the pay equity context). For comments on these decisions see Fay Faraday, “One Step Forward, Two Steps Back? Substantive Equality, Systemic Discrimination and Pay Equity at the Supreme Court of Canada” (2020) 94 SCLR (2d) 301; Jonnette Watson Hamilton & Jennifer Koshan, “Equality Rights and Pay Equity: Déjà Vu in the Supreme Court of Canada” (2019) 15 JL & Equality 1. See also British Columbia Teachers’ Federation v British Columbia Public School Employers’ Association, 2014 SCC 70 (a one-paragraph decision restoring an arbitrator’s award allowing a s 15 employment benefits claim by women); Newfoundland (Treasury Board) v NAPE, 2004 SCC 66 (finding a violation of s 15 but accepting the government’s s 1 argument, again in the pay equity context).4 [1989] 1 SCR 143, 56 DLR (4th) 1.

3

Dierksen,KarenP., NancyL.Ragland, and JohnR.Tagg. "A New Alkaline pH-Adjusted Medium Enhances Detection of β-Hemolytic Streptococci by Minimizing Bacterial Interference Due to Streptococcus salivarius." Journal of Clinical Microbiology 38, no.2 (2000): 643–50. http://dx.doi.org/10.1128/jcm.38.2.643-650.2000.

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A new selective medium (CNA-P) that reduces or eliminates the inhibitory activity of bacteriocin-producing Streptococcus salivarius against β-hemolytic streptococci has been developed and compared with sheep blood agar (SBA) for the sensitive detection of small numbers of β-hemolytic streptococci in clinical specimens. CNA-P has as its basis a commercial medium (Difco Columbia CNA agar) supplemented with 5% (vol/vol) sheep blood, and the CNA is further modified by addition of 100 mM PIPES buffer [piperazine-N,N′-bis(2-ethanesulfonic acid)] (pH 7.5) to maintain cultures at an alkaline pH during incubation. CNA-P was shown to inhibit the production and/or release of four different types of S. salivarius bacteriocins or bacteriocin-like inhibitory molecules. The efficacies of CNA-P and SBA for detection of β-hemolytic streptococci in 1,352 pharyngeal samples from 376 children were compared. The β-hemolytic streptococcal isolates recovered from the samples included 314 group A (S. pyogenes), 61 group G, 33 group B, and 5 group C streptococci. Of 314 samples that yielded S. pyogenes, 300 were positive on CNA-P (96%) and 264 (86%) were positive on SBA. A significantly greater number of S. pyogenes isolates from these samples were recovered only on CNA-P (50 of 314) compared with the number of isolates recovered only on SBA (14 of 314). In addition, the degree of positivity, a measure of the total numbers of S. pyogenesisolates on the plate, was significantly higher on CNA-P than on SBA (2.40 versus 2.07; P < 0.001). Interestingly, CNA-P was also found to enhance the hemolytic activity of streptolysin O, allowing detection of streptolysin S-deficient S. pyogenesstrains which might otherwise go undetected on SBA and other isolation media.

4

Johal,B.S., P.Phang, C.McGahan, J.Hay, C.Brown, and H.Kennecke. "Treatment patterns and outcomes of patients with pT3N0 rectal cancer in a population-based setting." Journal of Clinical Oncology 25, no.18_suppl (June20, 2007): 4039. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.4039.

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4039 Background: Adjuvant radiation (R) and chemotherapy (C) is generally recommended for patients (pts) with pT3N0 rectal cancer. Patterns of adjuvant therapy and outcomes among pts with pT3N0 rectal cancer referred to the British Columbia Cancer Agency (BCCA) were determined. Methods: The BCCA Colorectal Cancer Outcomes Unit database was used to identify referred pts with pT3N0 rectal carcinoma diagnosed between 2000–2004. During this period, “short course” R (25Gy/5, surgery within 10 days) was recommended for resectable cT3 tumors followed by 6 months of C. If not treated pre-operatively (pre-op), guidelines specified post-op “long course” (45Gy/25) R and C. Three treatment groups were identified: Surgery alone (S), S and R (SR), and S, R and C (SRC). Eligible pts had complete surgical resection with or without Total Mesorectal Excision (TME). Pts treated with “downstaging” pre-op long course R, with S and C only (13 pts) or with R2 resection were excluded. Locoregional Recurrence (LR) and Distant Recurrence (DR) rates determined. Reasons for non-treatment were determined by chart review. Results: 303 pts were identified, with median follow-up of 33.5 months. Significant differences in age, tumor height, grade, and R therapy existed between groups ( Table I ). TME status, R status and Radial Margin positivity were similar. LR rates were 15% (S), 2% (SR) and 1.4% (SRC). DR rates were 11.7% (S), 7.9% (SR) and 8.5% (SRC). Median Overall Survival (OS) and Disease Free Survival (DFS) was not reached. Conclusions: Treatment of pT3N0 rectal cancer was variable and significant heterogeneity existed between groups receiving S, SR and SRC. Nevertheless, LR rates were very low in pts receiving R and substantially higher in pts who did not. DR rates were similar across groups, irrespective of C history. Reasons for not receiving R or C were primarily patient related (medical/post- operative considerations, patient refusal). Potential physician related factors (non-referral) accounted for 28% of lack of C treatment in the SR group. [Table: see text] No significant financial relationships to disclose.

5

Rahmadi, Muhammad, Fazriyanor Kaurie, and Tuti Susanti. "Uji Akurasi Dataset Pasien Pasca Operasi Menggunakan Algoritma Naïve Bayes Menggunakan Weka Tools." JURIKOM (Jurnal Riset Komputer) 7, no.1 (February15, 2020): 134. http://dx.doi.org/10.30865/jurikom.v7i1.1761.

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Postoperative patient data sets taken for testing of this data are sourced from the UCI repository on the website https://archive.ics.uci.edu/ml/datasets/Post-Operative+Patient. Based on the website address, the study was conducted by Sharon Summers, School of Nursing, University of Kansas, Medical Center, Kansas City, KS 66160 and Linda Woolery, School of Nursing, University of Missouri, Columbia, MO 6521. Number of attributes from this data set there are 8 and 1 class, the attributes in question include; L-CORE (patient's internal temperature in C), L-SURF (patient's surface temperature in C), L-O2 (oxygen saturation in%), L-BP (last measurement of blood pressure), SURF-STBL (stability of the patient's surface temperature ), CORE-STBL (stability of the patient), BP-STBL (stability of the patient's blood pressure), COMFORT (perceived comfort of the patient at discharge, measured as an integer between 0 and 20) and ADM-DECS decision class / patient exit decision with information (I = patient sent to intensive care unit, S = patient ready to go home, A = patient sent to general hospital floor).

6

Lin,JamesS. "James S. Lin, DDS, MSC, FRCD(C), Clinical Assistant Professor, Private Practitioner, Division of Endodontics, Department of Oral Biological & Medical Sciences, Faculty of Dentistry, University of British Columbia, Vancouver, Canada." Endodontic Topics 27, no.1 (September 2012): 106. http://dx.doi.org/10.1111/etp.12029_1.

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7

Lin,JamesS. "JAMES S. LIN, DDS, MSC, FRCD(C), Clinical Assistant Professor, Division of Endodontics, Department of Oral Biological & Medical Sciences, Faculty of Dentistry, University of British Columbia Private Practitioner, Vancouver, Canada." Endodontic Topics 32, no.1 (May 2015): 123. http://dx.doi.org/10.1111/etp.12079_5.

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8

Benoit-Vical, Françoise, Anne Robert, and Bernard Meunier. "In Vitro and In Vivo Potentiation of Artemisinin and Synthetic Endoperoxide Antimalarial Drugs by Metalloporphyrins." Antimicrobial Agents and Chemotherapy 44, no.10 (October1, 2000): 2836–41. http://dx.doi.org/10.1128/aac.44.10.2836-2841.2000.

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ABSTRACT The in vitro potentiation of artemisinin by synthetic manganese porphyrin complexes has been recently reported (F. Benoit-Vical, A. Robert, and B. Meunier, Antimicrob. Agents Chemother. 43:2555–2558, 1999). Since the activity of artemisinin and synthetic antimalarial endoperoxides is related to their interaction with heme (S. R. Meshnick, A. Thomas, A. Ranz, C. M. Xu, and H. Z. Pan, Mol. Biochem. Parasitol. 49:181–190, 1991), an improvement of their efficiency may be expected in the presence of a synthetic metalloporphyrin having the same activating role as endogenous heme. With the aim to boost the activity of antimalarial endoperoxide drugs, we were thus led to evaluate the in vitro and in vivo potentiation of natural and synthetic drugs of this family by a nontoxic and cheap metalloporphyrin. The potentiation of artemisinin, β-artemether, and arteflene (Ro 42-1611) by synthetic heme models is reported. In vitro studies on the chloroquine-resistant Plasmodium falciparumFcB1-Columbia strain indicate a synergistic effect of the manganese complex of meso-tetrakis(4-sulfonatophenylporphyrin) (Mn-TPPS) on the activity of artemisinin or β-artemether, whereas this heme model has no influence on the activity of arteflene. A significant synergistic effect on rodent malaria was also observed in vivo between artemisinin and Mn-TPPS using Plasmodium vinckei petteri strain.

9

Harel, Ran, and Nachshon Knoller. "Acute Cervical Disk Herniation Resulting in Sudden and Severe Neurologic Deterioration: A Case Series." Surgery Journal 02, no.03 (July 2016): e96-e101. http://dx.doi.org/10.1055/s-0036-1593357.

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Objective Nontraumatic acute cervical disk herniation resulting in acute severe neurologic deficit is a rare entity described in a limited number of case reports. We describe the management and outcome in patients presenting with severe neurologic deterioration caused by acutely herniated cervical disks. Methods Four patients (mean age 39.5 years) presented to our tertiary care academic medical center from September 2012 to September 2013 with severe progressive neurologic deficits due to cervical disk herniation and were included in the series. Patients' surgical, medical, and imaging records were retrospectively reviewed under an Institutional Review Board waiver of informed consent. Results Patients in the series presented with acute neurologic deterioration, including paraparesis, Brown-Séquard syndrome, or quadriparesis deteriorating to quadriplegia. Emergent magnetic resonance imaging (MRI) scans and emergent decompression and fusion for acute soft disk herniation were performed in all cases. All patients recovered to excellent functional status with Frankel score improvement from B (one patient)/C (three patients) to E (three patients)/D (one patient). Conclusions Acute cervical disk herniation with acute neurologic deterioration is a medical emergency necessitating emergent MRI and surgical decompression. Clinical presentation varies. In patients with rapid-onset neurologic deterioration, a high level of suspicion for this rare entity is indicated.

10

Wang, Can, Le Xin, Chen-Chen Cai, Chao-Yu Cong, Jun-Fan Xie, Xiang-Pan Kong, Chao-Yu Dong, et al. "Neuropeptide S Displays as a Key Neuromodulator in Olfactory Spatial Memory." Chemical Senses 45, no.3 (February3, 2020): 195–202. http://dx.doi.org/10.1093/chemse/bjaa003.

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Abstract Neuropeptide S (NPS) is an endogenous peptide recently recognized to be presented in the brainstem and believed to play an important role in maintaining memory. The deletion of NPS or NPS receptor (NPSR) in mice shows a deficit in memory formation. Our recent studies have demonstrated that central administration of NPS facilitates olfactory function and ameliorates olfactory spatial memory impairment induced by muscarinic cholinergic receptor antagonist and N-methyl-D-aspartate receptor antagonist. However, it remains to be determined if endogenous NPS is an indispensable neuromodulator in the control of the olfactory spatial memory. In this study, we examined the effects of NPSR peptidergic antagonist [D-Val5]NPS (10 and 20 nmol, intracerebroventricular) and nonpeptidergic antagonist SHA 68 (10 and 50 mg/kg, intraperitoneal) on the olfactory spatial memory using computer-assisted 4-hole-board olfactory spatial memory test in mice. Furthermore, immunofluorescence was employed to identify the distributions of c-Fos and NPSR immunoreactive (-ir) neurons in olfactory system and hippocampal formation known to closely relate to the olfactory spatial memory. [D-Val5]NPS dosing at 20 nmol and SHA 68 dosing at 50 mg/kg significantly decreased the number of visits to the 2 odorants interchanged spatially, switched odorants, in recall trial, and simultaneously reduced the percentage of Fos-ir in NPSR-ir neurons, which were densely distributed in the anterior olfactory nucleus, piriform cortex, subiculum, presubiculum, and parasubiculum. These findings suggest that endogenous NPS is a key neuromodulator in olfactory spatial memory.

11

Reichertz, Peter. "Health Care and Informatics: On IMIA’s Opportunities and Responsibilities in its 5th Decade." Yearbook of Medical Informatics 17, no.01 (August 2008): 01–06. http://dx.doi.org/10.1055/s-0038-1638573.

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Summary ObjectiveTo report about major past and future activities of IMIA, the International Medical Informatics Association. Method Summarizing discussions and planning activities within IMIA, in particular with respect to its Board and General Assembly meetings in 2007; looking at recent informatics evolution by commenting on IMIA Yearbook surveys and best paper selections. Results Major recent IMIA activities include Medinfo 2007, finalizing its long-term strategic plan ‘Towards IMIA 2015’, and the reinforcement of IMIA’s collaboration with the World Health Organization (WHO). The IMIA Yearbook of Medical Informatics, published annually since 1992, can be regarded as an important observatory for progress in health and biomedical informatics. Future activities comprise implementing IMIA’s strategic plan, reshaping its portfolio of conferences, preparing Medinfo 2010, in addition to continuing to support and enable collaborative international exchange of research and education and bridging to the practice of health and biomedical informatics. Conclusions Informatics has emerged as an increasingly important field for health care and for the health and biomedical sciences. Within the last 40 years IMIA has evolved to a truly global organization, in a world, where medical informatics has gained significant importance for high-quality, efficient health care and for research in biomedicine and in the health sciences. Now in its 5th decade, IMIA’s responsibilities as well as opportunities as a global, independent organization have both increased.Geissbuhler A, Kulikowski C, editors. IMIA Yearbook of Medical Informatics 2008.

12

Cerqueira, Bruno Antônio Veloso, Wendell Vilas Boas, Jorge Clarêncio, Daniela Andrade, Angela MD Zanette, Mitermayer Galvào Reis, Jose Moura Neto, Rodrigo Silva Cesar, and Marilda Souza Goncalves. "Adhesion Molecules Interaction with Markers of Lipid Metabolism, Hemolysis, Endothelial Dysfunction and Medical Histories Among Steady-State Sickle Cell Anemia Patients." Blood 114, no.22 (November20, 2009): 2553. http://dx.doi.org/10.1182/blood.v114.22.2553.2553.

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Abstract Abstract 2553 Poster Board II-530 Introduction: Sickle cell anemia (SCA) results from the hom*ozygous form of hemoglobin S (Hb S). Vaso-occlusive pain episodes underlie most of the acute and chronic clinical complications of disease and it is correlated with activation of red blood cells, leukocytes, platelets and endothelial cells that express several adhesion molecules and ligand. The aim of the present study was investigates the levels of soluble ICAM-1 and VCAM-1 adhesion molecules associating with biochemical markers, expression of neutrophils adhesion molecule and medical history of sickle cell anemia patients. Patients and Methods. We studied 53 SCA patients in steady-state (25 men, 28 women, mean age: 21.17 ± 14.12 years) from northeast Brazil diagnosed with SCA in attendance of the outpatients clinic of the Foundation of Hematology and Hemotherapy of Bahia (HEMOBA). The control group was compound by 22 healthy Brazilian, with AA hemoglobin pattern matched by age, years and ethnic origin. Biochemical analyses were measured by colorimetric methods, surface adhesion molecules expressions by flow cytometry, soluble adhesion molecules by ELISA and the complete medical history was obtained by patients' record. Results: Our results show a higher serum levels of VCAM-1(s) in patients than control group (p=0.006). Moreover, in this study we found low expression of neutrophils CD18 in patients with high levels of VCAM-1(s). Total cholesterol and low density lipoprotein (LDL-C) were significantly negative associated with VCAM-1(s) (r=−0.312, p=0.023; r=−0.282, p=0.041 respectively) and the high density lipoprotein (HDL-C) was significantly negative associated with ICAM-1(s) (r=−0.348; p=0.011). Intravascular hemolysis markers such as aspartate transferase (AST) and lactate dehydrogenase (LDH) were significantly positive associated with VCAM-1(s) (r=0.459, p=0.001 and r=0.281, p=0.041, respectively). Sickle cell anemia individuals that developed necrosis and leg ulcers exhibited high serum level of VCAM-1(s) (p=0.017 and p=0.021 respectively) and patients that presented priapism had low levels of ICAM-1(s) (p=0.046). Conclusion: The presence of high levels of ICAM-1(s) and VCAM-1(s) adhesion molecules and its association with markers of intravascular hemolysis, endothelial dysfunction and lipid metabolism may indicate a differentiated mechanism of these molecules in sickle cell anemia pathogenesis, with a complex involvement of cellular, endothelial and proinflammatory interactions. The measurement of soluble adhesion molecules is of easy determination and may be an important biomarker of prognosis among sickle cell anemia patients. Additional studies should be carried out in order to explore the contribution of ICAM-1 (s) and VCAM-1 (s) in other signal pathways. Disclosures: No relevant conflicts of interest to declare.

13

Oulé,MathiasK., Richard Azinwi, Anne-Marie Bernier, Tano Kablan, Anne-Marie Maupertuis, Stephanie Mauler, RoseK.Nevry, Korami Dembélé, Lorraine Forbes, and Lamine Diop. "Polyhexamethylene guanidine hydrochloride-based disinfectant: a novel tool to fight meticillin-resistant Staphylococcus aureus and nosocomial infections." Journal of Medical Microbiology 57, no.12 (December1, 2008): 1523–28. http://dx.doi.org/10.1099/jmm.0.2008/003350-0.

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Polyhexamethylene guanidine hydrochloride (PHMGH), an antimicrobial biocide of the guanidine family, was tested for efficacy against quality-control strains of Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella choleraesuis, meticillin-resistant S. aureus (MRSA) and Escherichia coli. Bactericidal activity against S. aureus, P. aeruginosa and Salmonella choleraesuis was determined using the official methods of analysis of the Association of Official Analytical Chemists, with modifications as recommended by the Canadian General Standards Board. For MRSA and E. coli, the MIC and minimal bactericidal concentration were determined using the broth dilution technique. The experiments were carried out at 20 °C under a range of conditions including varying PHMGH concentration (0.001–0.1 %), contact time (0.5–10 min) and water type (distilled, tap and hard water). The phenol coefficient values determined with S. aureus, Salmonella choleraesuis and P. aeruginosa were 7.5, 6.1 and 5, respectively. No matter what type of water was used to make the dilutions, PHMGH killed MRSA and E. coli at concentrations as low as 0.04 and 0.005 % (w/v), respectively, within 1.5 min. The mode of action of PHMGH was elucidated by transmission electron microscopy: the cell envelope was broken, resulting in cell content leakage into the medium. The ultimate aim of this study was to show that PHMGH can be used as an odourless, colourless, non-corrosive and harmless disinfectant for hospital and household facilities.

14

John, Albert. "Reviewer Acknowledgements." International Journal of Chemistry 10, no.4 (November29, 2018): 184. http://dx.doi.org/10.5539/ijc.v10n4p184.

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International Journal of Chemistry wishes to acknowledge the following individuals for their assistance with peer review of manuscripts for this issue. Their help and contributions in maintaining the quality of the journal is greatly appreciated. Many authors, regardless of whether International Journal of Chemistry publishes their work, appreciate the helpful feedback provided by the reviewers. Reviewers for Volume 10, Number 4 &nbsp; Abdul Rouf Dar, University of Florida, USA Ahmad Galadima, Usmanu Danfodiyo University, Nigeria Ahmet Ozan Gezerman, Yildiz Technical University, Turkey Asghari Gul, Comsats IIT, Pakistan Ayodele Temidayo Odularu, University of Fort Hare, South Africa Binod P Pandey, The Pennsylvania State University, USA Di Cui, Temple University, USA Elnaz Rostampour, Islamic Azad University, Iran Fatima Tuz Johra, Kookmin University, Bangladesh Han Zhang, TP Therapeutics, USA Hesham G. Ibrahim, Al-Mergheb University, Libya Ho Soon Min, INTI International University, Malaysia Juan R. Garcia, Research Institute on Catalysis and Pertrochemistry (INCAPE), Argentina Khaldun M. Al Azzam, Batterjee Medical College for Sciences and Technology, Saudi Arabia Madduri Srinivasarao, Purdue University, USA Mohamed Abass, Ain Shams University, Egypt Mustafa Oguzhan Kaya, Siirt University, Turkey Nejib Hussein Mekni, Al Manar University, Tunisia Praveen Kumar, Texas Tech University, USA Qun Ye, Institute of Materials Reseach and Engineering, Singapore R. K. Dey, Birla Institute of Technology (BIT), India Rabia Rehman, University of the Punjab, Pakistan Rodrigo Vieira Rodrigues, University of S&atilde;o Paulo, Brazil Saurav Sarma, University of Columbia Missouri, USA Sitaram Acharya, Texas Christian University, USA Syed A. A. Rizvi, Nova Southeastern University, USA Vijay Ramalingam, Columbia University, USA Zhixin Tian, Tongji University, China &nbsp; &nbsp; &nbsp; &nbsp; Albert John On behalf of, The Editorial Board of International Journal of Chemistry Canadian Center of Science and Education

15

Salhotra, Amandeep, Dongyun Yang, Bernard Tegtmeier, Sally Mokhtari, Justine Abella Ross, KaramjeetS.Sandhu, Ibrahim Aldoss, et al. "Effect of Vancomycin-Resistance Enterococci Colonization Status Prior to Allogeneic Hematopoietic Cell Transplantation on Transplant Outcomes: A Single Center Retrospective Experience." Blood 132, Supplement 1 (November29, 2018): 3386. http://dx.doi.org/10.1182/blood-2018-99-117646.

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Abstract The prevalence of vancomycin-resistance Enterococci colonization (VRE-C) in patients undergoing allogeneic hematopoietic cell transplantation (aHCT) is between 23-40%. Pre-HCT VRE-C is shown to be associated with high risks of VRE bloodstream infection (VRE-BSI), non-relapse mortality (NRM) and lower overall survival. Recent studies investigating the association between VRE-C and risk of acute graft-versus-host disease (aGVHD) after aHCT has demonstrated conflicting results, possibly due to the heterogeneous transplant conditioning and GVHD prophylactic regimens. Here, we sought to examine the VRE-C prevalence and determine its impact on aHCT outcomes, in patients receiving tacrolimus and sirolimus (T/S) as aGVHD prophylaxis. To explore the association between pre-HCT VRE-C and transplant outcomes, we retrospectively reviewed medical records of a cohort of 1074 consecutive patients who underwent aHCT at City of Hope from 2014 to 2017. Patients with stool culture screening within 30 days pre-aHCT (n=862) were identified from the microbiology database and were grouped as VRE-C and non-colonized (VRE-NC). Data was not available on VRE-C in 185 patients and they were not included in analysis. Overall survival (OS) and progression-free survival (PFS) were examined by Kaplan-Meier curves and log-rank tests. Non-relapse mortality (NRM), VRE-BSI, and GVHD rates of the 2 groups were compared by cumulative incidence rates and Gray's test. Multivariate analyses were performed when adjusting for prognostic factors. Two-sided P value of ≤0.05 was considered significant. Of the 862 evaluated patients, 68 had VRE-C (7.9% prevalence). Median age of patients in VRE-C and VRE-NC groups were 53 and 55 years, respectively. Gender distribution, transplant indications, stem cell source, proportion of unrelated donors, GVHD prophylaxis with T/S and other clinical variables including intensity of conditioning regimen and HCT-CI were similar between the two groups (Table 1) . Karnofsky performance status (KPS) of 90-100 and 70-80 were seen in 40% and 53% of patients with VRE-C compared to 47% and 48% of VRE-NC patients (p=0.12). Overall, VRE-BSI episodes were rare (n=7) with 4 patients in VRE-C (6.1%) and 3 patients in VRE-NC (0.4 %); p <0.001. All 3 patients in the VRE-NC group developed bacteremia within the first 100 days (range 2-97) but VRE-BSI was not the eventual cause of death. The median onset of VRE-BSI in the VRE-C group (n=4) was only 6 days (range: 2-12) with 1 surviving patient and 3 who died of non VRE-BSI related causes. No statistical significance was detected in rates of non-VRE BSI (24.1% in VRE-C Vs. 19.2% in VRE-NC; p=0.30) and fungemia (1.5% in VRE-C vs 1.2% VRE-NC; p=0.77). At a median follow-up duration of 19.4 months (range: 2.7-48.4), similar 1-year OS was achieved in both groups (67.4% in VRE-C and 76.5% in VRE-NC; p=0.11) but 1 year PFS was significantly lower in the VRE-C cohort (55.6% Vs. 69.4%; p=0.038). Higher NRM was achieved in the VRE-C cohorts on days +100 and +365 (11.8% Vs. 7.2% and 25.1% Vs. 14.4%, respectively, p=0.041). (Figure 1) There were no differences in rates of day 100 aGVHD (grades II-IV) (Figure 2) and relapse rates at 12 months between the two groups. Conditioning regimen intensity, donor type, KPS, and primary diagnosis were significantly associated with NRM. When these variables were included in the multivariate model, VRE-C was found to be independently associated with higher NRM (HR=1.82, 95%CI: 1.12-2.93; p=0.015). In conclusion, in our cohort of patients receiving predominantly T/S-based aGVHD prophylaxis, no association was detected between VRE-C and aGVHD incidence. Higher rate of VRE-BSI in the VRE-C group is in accordance with published data, albeit lower rates of VRE-BSI was seen in our cohort. VRE-C contributed to higher NRM at days 100 and 365 post-aHCT and was an independent risk factor for poor HCT outcomes Since VRE-C is a potentially modifiable risk factor, our data supports continued efforts for specific interventional strategies (i.e. antimicrobial stewardship) to reduce drug resistant bacterial colonization, and for clinical research to reverse the impact of VRE-C, such as the use of agents, which may modulate gut microbiome. Disclosures Salhotra: Kadmon Corporation, LLC: Consultancy. Ali:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees. Stein:Amgen Inc.: Speakers Bureau; Celgene: Speakers Bureau. Forman:Mustang Therapeutics: Other: Licensing Agreement, Patents & Royalties, Research Funding. Dadwal:AiCuris: Research Funding; Gilead: Research Funding; MERK: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Shire: Research Funding.

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Morris,MatthewW. "Nuclear Medicine Board Review: Questions and Answers for Self-Assessment, 3rd ed.Nuclear Medicine Board Review: Questions and Answers for Self-Assessment, 3rd ed. By C. Richard Goldfarb, Steven R. Parmett, Lionel S. Zuckier, f*ckiat Ongseng, Maroun Karam, and Mruthy R. Chamarthy. New York, NY: Thieme Medical Publishers, 224 pp., 2012. $49.99 softcover (ISBN: 978-1604066890)." American Journal of Roentgenology 200, no.3 (March 2013): W322. http://dx.doi.org/10.2214/ajr.12.9852.

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Heuck, Christoph, Niels Weinhold, Erich Allen Peterson, Michael Bauer, CalebK.Stein, Timothy Ashby, ShwetaS.Chavan, et al. "The Impact of Combination Chemotherapy and Tandem Stem Cell Transplant on Clonal Substructure and Mutational Pattern at Relapse of MM." Blood 126, no.23 (December3, 2015): 372. http://dx.doi.org/10.1182/blood.v126.23.372.372.

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Abstract Introduction: Next generation sequencing of over 800 newly diagnosed multiple myeloma (NDMM) cases has established the mutational landscape and key cancer driver pathways. The mutational basis of relapse has not been systematically studied. Two previous studies (Keats et al.; Bolli et al.) identified 4 patterns of clonal evolution. Neither study included uniformly treated patients and looked at the impact of therapy on clonal structure at relapse. Understanding the mutational patterns underlying relapse and how they relate to specific therapies is crucial in order to improve MM outcomes, especially for high-risk (HR) MM. In this study we compare the clonal structure at presentation (PRES) and at relapse (REL), after exposure to Total Therapy (TT). Materials and Methods: We studied 33 pairs of tumor samples collected at PRES and REL. 9 patients were treated on TT2, 13 on TT3, 10 on TT4 and 1 on TT5-like regimen. Eleven patients had HR disease at PRES. DNA was extracted from CD138+ selected cells from random bone marrow aspirates. Germline controls were obtained from leukapheresis products. Whole exome sequencing libraries were prepared using the Agilent qXT kit and the Agilent SureSelect Clinical Research Exome kit with additional baits covering the Ig and MYC loci. All samples were sequenced on an Illumina HiSeq2500 to a median depth of 120x. Sequencing data were aligned to the Ensembl GRCh37/hg19 human reference using BWA. Somatic variants were called using MuTect. Translocations were identified using MANTA. Copy number variations were inferred using TITAN. Gene expression profiles (GEP), generated using the Affymetrix U133plus2 microarray, were available for all tumor samples. Nonnegative matrix factorization (NMF) was used to define mutation signatures. Results: The median time to progression was 30 months with a median follow up of 9.5 years. 22 cases achieved a complete remission (CR) or near CR. There were 11 cases of HR at PRES. Of the 22 cases with low risk (LR) MM, 7 relapsed with HR disease. There were on average 478 SNVs per sample at PRES and 422 at REL. All but 2 cases had evidence of new mutations at REL. There were no consistent patterns or number of mutation associated with REL or GEP-defined risk. Patients of the MF molecular subgroup had more mutations compared to other molecular subgroups (657 vs. 379) and were enriched for mutations with an APOBEC signature. We did not detect any mutation signature consistent with chemotherapy-induced alterations, providing evidence that TT itself does not cause additional mutations. Primary recurrent IgH translocations called by MANTA were confirmed by GEP data. A number of new translocations were identified , several only at REL. In particular we demonstrate a case with a newly acquired MYC translocation at relapse, indicating that it contributed to progression. We identified 5 patterns of clonal evolution (Figure 1): A) genetically distinct relapse in 3 patients, B) linear evolution in 8 patients, C) clonal selection in 9 patients, D) branching evolution in 11 patients, and E) stable clone(s) in 2 patients. Patterns A (distinct) and B (linear) were associated with low risk and longer survival, whereas patterns D (branching) and E (stable) were associated with high risk and shorter time to relapse and overall survival (Table 1). Conclusion: This is the first study to systematically analyze the pattern of clonal evolution using NGS in patients treated with combination chemotherapy and tandem ASCT. We identified 5 patterns of evolution, which correlate with survival. We identified 3 cases with a loss of the original clone and emergence of a new clone, suggesting high effectiveness of Total Therapy for those patients. The persistence of major clones despite multi agent chemotherapy in most other cases supports a concept of a tumor-initiating cell population that persist in a protective niche, for which new therapies are needed. Table 1. Pattern of Evolution GEP70 Pres.(high risk: ≥0.66) Proliferation Index Pres. GEP70 Rel.(high risk: ≥0.66) Proliferation Index Rel Mean OS Mean TTR A: distinct (n=3) -0.690 -3.34 -0.015 2.04 8.18 5.00 B: linear (n=8) -0.171 -0.34 0.618 9.22 5.70 4.05 C: selection (n=9) 0.366 3.20 0.569 6.97 3.95 2.64 D: branching (n=11) 0.710 5.17 1.173 11.15 3.84 2.21 E: stable (n=2) 1.532 7.42 1.124 2.54 0.96 0.35 Pres.: Presentation; Rel.: Relapse; OS: Overall Survival; TTR: Time to Relapse Figure 1. Patterns of Relapse Figure 1. Patterns of Relapse Disclosures Heuck: Foundation Medicine: Honoraria; Millenium: Other: Advisory Board; Janssen: Other: Advisory Board; Celgene: Consultancy; University of Arkansas for Medical Sciences: Employment. Weinhold:Janssen Cilag: Other: Advisory Board; University of Arkansas for Medical Sciences: Employment. Peterson:University of Arkansas for Medical Sciences: Employment. Bauer:University of Arkansas for Medical Sciences: Employment. Stein:University of Arkansas for Medical Sciences: Employment. Ashby:University of Arkansas for Medical Sciences: Employment. Chavan:University of Arkansas for Medical Sciences: Employment. Stephens:University of Arkansas for Medical Sciences: Employment. Johann:University of Arkansas for Medical Sciences: Employment. van Rhee:University of Arkansa for Medical Sciences: Employment. Waheed:University of Arkansas for Medical Sciences: Employment. Johnson:University of Arkansas for Medical Sciences: Employment. Zangari:University of Arkansas for Medical Sciences: Employment; Millennium: Research Funding; Onyx: Research Funding; Novartis: Research Funding. Matin:University of Arkansas for Medical Sciences: Employment. Petty:University of Arkansas for Medical Sciences: Employment. Yaccoby:University of Arkansas for Medical Sciences: Employment. Davies:University of Arkansas for Medical Sciences: Employment; Millenium: Consultancy; Janssen: Consultancy; Onyx: Consultancy; Celgene: Consultancy. Epstein:University of Arkansas for Medical Sciences: Employment. Barlogie:University of Arkansas for Medical Sciences: Employment. Morgan:Weismann Institute: Honoraria; MMRF: Honoraria; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; University of Arkansas for Medical Sciences: Employment; CancerNet: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees.

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Lisby, Amanda, Trevor Baybutt, Megan Weindorfer, Robert Carlson, Alicja Zalewski, Scott Waldman, and Adam Snook. "122 Guanylyl cyclase C as a target for CAR-T cell therapy in a metastatic gastric cancer model." Journal for ImmunoTherapy of Cancer 8, Suppl 3 (November 2020): A132. http://dx.doi.org/10.1136/jitc-2020-sitc2020.0122.

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BackgroundGastric cancer is the sixth most common cancer and second-leading cause of cancer-related mortality worldwide.1 The heterogenous and genetically complex nature of this disease underlies the challenges in developing effective therapies for metastatic gastric cancer. In the majority of cases, stomach tumors evolve from intestinal metaplasia resulting in ectopic expression of the enterocyte differentiation antigen guanylyl cyclase C (GUCY2C) by ~50% of primary and metastatic gastric cancers.2–4 In the context of the efficacy of GUCY2C-directed chimeric antigen receptor (CAR)-T cells against metastatic colorectal cancer in animal models,5,6 we hypothesized that this adoptive cell therapy may be effective against metastatic gastric cancer.MethodsHere, we explored the efficacy of GUCY2C-directed CAR-T cells for gastric cancer in a patient derived xenograft (PDX) tumor model. Also, we interrogated translational GUCY2C biomarker assays using RT-qPCR, immunoblot analysis, and immunohistochemistry (IHC) for the intended purpose of identifying patients whose tumors express GUCY2C and could benefit from GUCY2C-directed CAR-T cell therapy.ResultsGUCY2C-directed CAR-T cells significantly reduced subcutaneous T84 colorectal tumor growth, producing a 5-fold reduction in tumor volume, compared to control treated tumors. GUCY2C-directed CAR-T cells produced no response in tumors produced from the GUCY2C-deficient colorectal cancer cell line, SW480. Importantly, GUCY2C-directed CAR-T cells controlled gastric cancer PDX growth, maintaining a >12-fold reduction in tumor volume compared to control and in some cases produced complete tumor elimination. Furthermore, IHC based assays, indicate that antibodies developed in our laboratory may be suitable for development of a companion diagnostic for GUCY2C-directed CAR-T cells. Indeed, the commercial polyclonal antibody demonstrated robust, non-specific staining regardless of tissue type or GUCY2C mRNA profile, while novel monoclonal antibodies produced in our laboratory primarily detected protein localized to the membrane of glandular epithelial cells, demonstrating antigen specificity, and indicating their potential for further development in diagnostic companion assays to identify gastric cancer patients who may benefit from GUCY2C-directed CAR-T cell therapy.ConclusionsGUCY2C-directed CAR-T cells prevented the growth of, and at times eliminated, a subcutaneous gastric cancer PDX model. In the context of previously established safety in mouse models, additional studies defining the efficacy of GUCY2C-directed CAR-T cells in gastric cancer models may allow future translation of this therapy to patients with advanced gastric cancers. Concurrent development of a novel companion diagnostic IHC assay would permit identification of the ~50% of gastric cancer patients whose tumors express GUCY2C and could benefit from this therapy.AcknowledgementsThis work was supported by a DeGregorio Family Foundation Award and by the Department of Defense Congressionally Directed Medical Research Programs (W81XWH-17-1-0299, W81XWH-191-0263, and W81XWH-19-1-0067) to AES. SAW is supported by the National Institutes of Health (NIH) (R01 CA204881, R01 CA206026, and P30 CA56036), the Defense Congressionally Directed Medical Research Program W81XWH-17-PRCRP-TTSA, and Targeted Diagnostic & Therapeutics. SAW and AES were also supported by a grant from The Courtney Ann Diacont Memorial Foundation. SAW is the Samuel M.V. Hamilton Professor of Thomas Jefferson University. AZ was supported by NIH institutional award T32 GM008562 for Postdoctoral Training in Clinical Pharmacology.The authors thank the NCI Patient-Derived Models Repository for their support and resources to make this research possible. The authors also thank the Sidney Kimmel Cancer Center Translational Research & Pathology Core Facility, and the Office of Animal Resources at Thomas Jefferson University for their continued technical assistance and support in this research.Ethics ApprovalThis study was approved by the Thomas Jefferson University Institutional Review Board (#14.0204) and the Instituational Animal Care and Use Commitee (Protocol #01529).ReferencesBray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin2018;68:394–424. doi:10.3322/caac.21492.Park J, Schulz S, Haaf J, Kairys JC, Waldman SA. Ectopic expression of guanylyl cyclase C in adenocarcinomas of the esophagus and stomach. Cancer Epidemiol Biomarkers Prev 2002;11:739–44.Birbe R, Palazzo JP, Walters R, Weinberg D, Schulz S, Waldman SA. Guanylyl cyclase C is a marker of intestinal metaplasia, dysplasia, and adenocarcinoma of the gastrointestinal tract. Hum Pathol. 2005;36:170–9. doi:10.1016/j.humpath.2004.12.002.Mathur D, Root AR, Bugaj-Gaweda B, Bisulco S, Tan X, Fang W, et al. A Novel GUCY2C-CD3 T-Cell Engaging Bispecific Construct (PF-07062119) for the Treatment of Gastrointestinal Cancers. Clin Cancer Res 2020;26:2188–202. doi:10.1158/1078-0432.CCR-19-3275.Magee MS, Kraft CL, Abraham TS, Baybutt TR, Marszalowicz GP, Li P, et al. GUCY2C-directed CAR-T cells oppose colorectal cancer metastases without autoimmunity. Oncoimmunology 2016;5:e1227897. doi:10.1080/2162402X.2016.1227897.Magee MS, Abraham TS, Baybutt TR, Flickinger JC, Ridge NA, Marszalowicz GP, et al. Human GUCY2C-Targeted Chimeric Antigen Receptor (CAR)-Expressing T Cells Eliminate Colorectal Cancer Metastases. Cancer Immunol Res 2018;6:509–16. doi:10.1158/2326-6066.CIR-16-0362.

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Tisdale,JohnF., Julie Kanter, MarkusY.Mapara, JanetL.Kwiatkowski, Lakshmanan Krishnamurti, Manfred Schmidt, AlexandraL.Miller, et al. "Current Results of Lentiglobin Gene Therapy in Patients with Severe Sickle Cell Disease Treated Under a Refined Protocol in the Phase 1 Hgb-206 Study." Blood 132, Supplement 1 (November29, 2018): 1026. http://dx.doi.org/10.1182/blood-2018-99-113480.

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Abstract Background β-globin gene transfer has the potential for substantial clinical benefit in patients with sickle cell disease (SCD). LentiGlobin Drug Product (DP) contains autologous CD34+ hematopoietic stem cells (HSCs) transduced with the BB305 lentiviral vector (LVV), encoding β-globin with an anti-sickling substitution (T87Q). The safety and efficacy of LentiGlobin gene therapy is being evaluated in the ongoing Phase 1 HGB-206 study (NCT02140554). Results in the initial 7 patients treated with LentiGlobin DP from steady state bone marrow harvested (BMH) HSCs using original DP manufacturing process (Group A) demonstrated stable HbAT87Q production in all patients, but at levels below the anticipated target. The protocol was thus amended to include pre-harvest RBC transfusions, optimize myeloablation by targeting higher busulfan levels, and use a refined DP manufacturing process (Group B); additionally, HSC collection by plerixafor mobilization/apheresis was instituted (Group C). Data from patients in Group C, treated under the modified protocol with DPs manufactured from plerixafor-mobilized HSCs using the refined process, are reported here. Results in patients in Groups A and B are reported separately. Methods Patients with severe SCD (history of recurrent vaso-occlusive crisis, acute chest syndrome, stroke, or tricuspid regurgitant jet velocity of >2.5 m/s) were enrolled. Patients in Group C received ≥2 months of transfusions to reach Hb of 10 - 12 g/dL and <30% HbS before HSC collection. Patients received 240 μg/kg of plerixafor 4 - 6 hours before HSCs were collected by apheresis and CD34+ cells were transduced with the BB305 LVV at a central facility. Following myeloablative conditioning with busulfan, the DP was infused, and patients were monitored for adverse events (AEs), engraftment, peripheral blood (PB) vector copy number (VCN), HbAT87Q expression, and HbS levels. Summary statistics are presented as median (min - max). Results As of 15 May 2018, 11 Group C patients (age 25 [18 - 35] years) had undergone mobilization/apheresis, 9 patients had DP manufactured (median 1 cycle of mobilization [1 - 3]) and 6 patients had been treated. Cell dose, DP VCN and % transduced cells in the 6 treated patients were: 7.1 (3 - 8) x 106 CD34+ cells/kg, 4.0 (2.8 - 5.6) copies/diploid genome (c/dg) and 81 (78 - 88) % transduced cells. The median follow-up was 3.0 (1.2 - 6.0) months. Patients achieved neutrophil engraftment at a median of 19 (18 - 20) days. Platelet engraftment was achieved at a median of 28 (12 - 64) days in 4 patients; platelet engraftment was pending in 2 patients. Two of 11 patients experienced 4 grade ≥3 AEs associated with plerixafor mobilization/HSC collection: 1 had vaso-occlusive pain and hypomagnesaemia, and the other had vaso-occlusive pain and non-cardiac chest pain. The toxicity profile from DP infusion to last follow-up in the 6 treated patients was consistent with myeloablative conditioning. Febrile neutropenia (n=5) and stomatitis (n=4) were the most common non-hematologic grade ≥3 AEs. Serious AEs were reported in 3 patients post-DP infusion: splenic hematoma, non-cardiac chest pain and mucosal inflammation. To date, there have been no DP-related AEs, graft failure, vector-mediated replication competent lentivirus, or clonal dominance. In the 6 treated patients, PB VCN at last visit ranged from 1.4 - 2.9 c/dg. In the 3 patients with 3 months follow-up, total Hb levels were 11.7 g/dL, 9.8 g/dL and 9.2 g/dL, and HbAT87Q levels were 4.7 g/dL, 3.2 g/dL and 3.5 g/dL. One additional patient with 6 months follow-up was off transfusions and had total Hb of 14.2 g/dL, of which 62% (8.8 g/dL) was vector-derived HbAT87Q and 36% (5.1 g/dL) was HbS. All 4 patients had HbAT87Q (median 39%) levels higher than or equal to HbS (median 31%) at the 3-month visit. Summary HGB-206 protocol changes and refined DP manufacturing have improved the LentiGlobin DP characteristics resulting in significantly improved outcomes. In addition, the HbAT87Q expression is comparable to, or exceeds, HbS levels as early as 3 months post DP infusion. These data support the feasibility of plerixafor-mediated CD34+ cell collection in patients with severe SCD and the efficacy of gene therapy. The safety profile of LentiGlobin gene therapy remains consistent with single-agent busulfan conditioning. Additional data and longer follow-up will determine the clinical effect of increased HbAT87Q/HbS ratios. Disclosures Kanter: Global Blood Therapeutics: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; bluebird bio: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Research Funding; Sancilio: Research Funding; NHLBI: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Apopharma: Research Funding; ASH: Membership on an entity's Board of Directors or advisory committees. Mapara:Incyte: Consultancy. Kwiatkowski:Novartis: Research Funding; bluebird bio: Consultancy, Honoraria, Research Funding; Apopharma: Research Funding; Terumo: Research Funding; Agios Pharmaceuticals: Consultancy, Research Funding. Schmidt:GeneWerk GmbH: Employment; German Cancer Research Center: Employment; bluebird bio: Consultancy. Miller:bluebird bio: Employment, Equity Ownership. Pierciey:bluebird bio: Employment, Equity Ownership. Shi:bluebird bio: Employment, Equity Ownership. Ribeil:bluebird bio: Employment, Equity Ownership. Asmal:bluebird bio: Employment, Equity Ownership. Thompson:Amgen: Research Funding; Celgene: Research Funding; Baxalta/Shire: Research Funding; bluebird bio: Consultancy, Research Funding; Novartis: Research Funding; Biomarin: Research Funding; La Jolla Pharmaceutical: Research Funding. Walters:Sangamo Therapeutics: Consultancy; bluebird bio: Research Funding; ViaCord Processing Lab: Other: Medical Director; AllCells Inc.: Other: Medical Director.

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Kattamis, Antonis, Ersi Voskaridou, Sophia Delicou, Evangelos Klironomos, Ioannis Lafiatis, Fotini Petropoulou, MichaelD.Diamantidis, et al. "An Epidemiological, Retrospective Cross-Sectional Study to Capture the Real-World Complication Burden, and Disease Management Paradigms in Transfusion-Dependent Beta-Thalassemia Adults in Greece: Interim Results of the Ulysses Study." Blood 136, Supplement 1 (November5, 2020): 5–6. http://dx.doi.org/10.1182/blood-2020-138533.

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Subtitle Notification: The first and the second author have equally contributed to this project Introduction: Transfusion-dependent β-thalassemia (TDT) confers substantial burden on both patients and the healthcare system, attributable to disease- and treatment-related complications due to the need for lifelong regular red blood cell (RBC) transfusions and iron chelation therapy (ICT). The present study primarily aims to determine the prevalence and severity of treatment- and disease-related complications in a representative sample of 200 TDT patients managed in routine care settings in Greece. Methods: ULYSSES is an epidemiological, multicenter, retrospective cross-sectional study. Data were collected during a single study visit and through medical chart review. Adult patients with TDT [defined as having received ≥6 RBC units (excluding transfusions for elective surgery) and no transfusion-free period ≥35 days during the 24-week pre-enrollment period], diagnosed at least 12 months prior to enrollment, were consecutively enrolled. Exclusion criteria included diagnosis of hemoglobin S/β-thalassemia or α-thalassemia, pregnancy during the previous year and receipt of bone marrow transplant. Data from the pre-planned interim analysis on the first 100 eligible consented patients, enrolled from October 2019 to February 2020 by 10 major hematology departments, are presented. Results: At enrollment the patients' median (interquartile range: IQR) age was 45.9 (39.4-49.0) years and 61% were females. Of the patients, 37% were employed, 34% had retired, 4% were unemployed, and 25% reported other employment status. Non-thalassemia-related medical/surgical history was reported in 59%. Regarding the patients' genotype, 48% were classified as β+β+, 37% as β+β0, 10% as β0β0, and 5% as β+/δβ-Sicilian or β+/HbLepore. The most common β-globin gene mutations were IVS1-nt110 G&gt;A (71%), IVS1-nt6 T&gt;C (24%) and Codon 39 C&gt;T (21%). All patients were receiving ICT whereas 54% had undergone splenectomy at a mean (SD) age of 23.1 (11.2) years; splenectomy was more common in older ages (30.8% vs 62.2% for patients aged 18-40 and &gt;40 years, respectively). The median (IQR) age at β-thalassemia diagnosis, at initiation of RBC transfusions and of ICT was 0.8 (0.4-3.0), 1.5 (1.0-5.0) and 5.6 (2.8-10.3) years, respectively. During the 48 weeks before enrollment, the median (IQR) average pre-transfusion hemoglobin levels were 9.9 (9.5-10.4) g/dL, the median (IQR) average serum ferritin levels were 464 (263-969) μg/L, and the mean (SD) total RBC units transfused per patient was 34.9 (10.2). During the period between diagnosis and enrollment [mean (SD): 42.5 (7.1) years], patients had cumulatively developed 634 (median: 6 per patient; range 1-19) disease- and treatment-related complications (24.7% of Grade ≥3), of which 262 were ongoing at enrollment in 85% of the patients. Complications with a frequency of at least 20% included splenectomy, osteoporosis, hypogonadism/amenorrhea, hypothyroidism, diabetes mellitus, hypersplenism, extramedullary haemopoiesis, cholecystectomy, and arrhythmias (Table 1). All patients had experienced disease-related complications (523 in total; 25% of Grade ≥3); 43% had experienced 111 treatment-related complications (23.4% of Grade ≥3) with 73 being transfusion-related and 35 ICT-related. In the age group of 18-40 years, 26.9%, 19.2%, and 11.5% had experienced at least one treatment-, transfusion- and ICT-related complication, respectively. The respective rates in patients &gt;40 years of age, were 48.6%, 37.8%, and 28.4%. Conclusion: In this study, over an average 42-year period since β-thalassemia diagnosis, a median of 6 complications per patient were reported. All patients had developed disease-related complications and 4 out of 10 had developed treatment-related complications. About 1 in 4 complications were of Grade ≥3. The most frequent complications included endocrine/metabolism disorders, surgical/medical procedures, and hematological and cardiovascular disorders. The treatment-related complication rate was about double in patients aged &gt;40 than in those 18-40 years at enrollment. These preliminary results underscore a considerable complication burden of TDT. Acknowledgements The authors acknowledge partial financial support from Genesis Pharma and Celgene Corporation and editorial support from Qualitis Ltd, sponsored by Genesis Pharma. Disclosures Kattamis: Genesis Pharma SA: Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Vifor: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Agios: Consultancy; Apopharma/Chiesi: Honoraria, Speakers Bureau; Vertex: Membership on an entity's Board of Directors or advisory committees; Ionis: Membership on an entity's Board of Directors or advisory committees. Voskaridou:GENESIS Company: Consultancy, Research Funding; ADDMEDICA Company: Consultancy, Research Funding; NOVARTIS Company: Research Funding; PROTAGONIST Company: Research Funding; ACCELERON Company: Consultancy, Research Funding; BMS: Consultancy, Research Funding. Delicou:Genesis Pharma SA: Research Funding; Novartis: Honoraria, Other: Investigator fees; Ionis: Other: Investigator fees. Klironomos:Genesis Pharma SA: Research Funding. Lafiatis:Genesis Pharma SA: Research Funding. Petropoulou:Genesis Pharma SA: Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees; Celgene: Other: Investigator fees. Diamantidis:BMS: Membership on an entity's Board of Directors or advisory committees; Genesis Pharma SA: Honoraria, Research Funding. Lafioniatis:Genesis Pharma SA: Research Funding. Evliati:Genesis Pharma SA: Research Funding. Kapsali:Acerta Pharma: Research Funding; Amgen: Research Funding; BMS: Research Funding; Celgene: Research Funding; Novartis: Research Funding; Roche: Research Funding; Takeda: Research Funding; Teva: Research Funding. Karvounis-Marolachakis:Genesis pharma SA: Current Employment. Timotheatou:Genesis Pharma SA: Current Employment. Kourakli:Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Vifor: Research Funding; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Protagonist: Research Funding; Celgene / BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees; Genesis Pharma SA: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; IMARA: Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Ionis: Research Funding.

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Seixas, Magda Oliveira, Larissa Rocha, Mauricio Carvalho, Joelma Menezes, Isa Lyra, Valma Nascimento, Ricardo Couto, Ajax Atta, Mitermayer Galvão Reis, and Marilda Souza Goncalves. "Lipoprotein Cholesterol and Triglyceride in Children with Steady-State Sickle Cell Disease." Blood 114, no.22 (November20, 2009): 1547. http://dx.doi.org/10.1182/blood.v114.22.1547.1547.

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Abstract Abstract 1547 Poster Board I-570 Introduction Levels of high-density lipoprotein cholesterol have been correlated with anti-inflammatory, anti-oxidative, anti-aggregation, anti-coagulant and pro-fibrinolytic activities. We hypothesized that lipoprotein cholesterol and triglycerides have important roles in sickle cell disease pathogenesis. Patients and Methods A prospective study of biochemical and hematological analyses of 152 steady-state children with sickle cell disease and 132 healthy subjects using immunochemistry, immunoassay and electronic cell counter respectively. Clinical data were collected from patient medical records. Data analyses were performed using Prism 5.01 (Graphpad Software, San Diego, CA), EPIinfo 6.04 (CDC, Atlanta, Georgia) and STATA SE 10 software (StataCorp, Texas, USA). Results There was a significant positive association of high-density lipoprotein cholesterol with hemoglobin (p<0.001), hematocrit (p<0.001) and total cholesterol (p<0.001) and a negative association with reticulocytes (p=0.046), leukocytes (p=0.015), monocytes (p=0.004) and platelets (p=0.005), bilirubins [total bilirubin (p<0.001), direct bilirubin (p<0.001) and indirect bilirubin (p<0.001], iron (p<0.001), aminotransferases [aspartate aminotransferase (p=0.004), alanine aminotransferase (p=0.035)], lactate dehydrogenase (p<0.001), urea (p=0.030), alpha 1-antitrypsin (p<0.001), very low-density lipoprotein cholesterol (p=0.003), triglycerides (p=0.005) and hemoglobin S (p=0.002). Low high-density lipoprotein cholesterol concentration was associated with cardiac abnormalities (p<0.025), pneumonia history (p=0.033) and blood transfusion use (p=0.025). Triglycerides (p=0.047), very low-density lipoprotein cholesterol (p=0.044), low-density lipoprotein cholesterol (p=0.033), total cholesterol (p=0.007), alpha 1-antitrypsin (p=0.040) and ferritin (p=0.008) levels were associated with cholelithiasis. Conclusion We hypothesize that some SCD patients can have a specific dyslipidemic subphenotype characterized by hypertriglyceridemia, high VLDL-C and low plasma LDL-C and HDL-C in association with other biomarkers, including those related to inflammation. This represents an important step toward a more reliable clinical prognosis. We suggest further studies and continued research into new mechanisms involving this complex network of markers in order to establish their role in SCD pathogenesis. Disclosures No relevant conflicts of interest to declare.

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Shawalil, Syahirah, Khairul Najmy Abdul Rani, and HaslizaA.Rahim. "2.45 GHz wearable rectenna array design for microwave energy harvesting." Indonesian Journal of Electrical Engineering and Computer Science 14, no.2 (May1, 2019): 677. http://dx.doi.org/10.11591/ijeecs.v14.i2.pp677-687.

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This paper presents a design of a wearable textile microstrip patch rectifying antenna (rectenna) array operating for wireless body area network (WBAN) at the center frequency, <em>f<sub>c</sub></em> of 2.45 GHz. Precisely, jeans or denim with the relative permittivity, <sub> </sub>= 1.70 and thickness of 1.00 mm is chosen as a substrate attached to SheildIt Super as a conductive material with the thickness, <em>h</em> of 0.17 mm and conductivity of 6.67 10<sup>5</sup> S/m, respectively. In the first stage, a microstrip patch antenna array layout with the inset fed technique is designed and simulated by using the Keysight Advanced Design System (ADS) software. In the second stage, a wearable textile microstrip patch antenna array is fabricated, integrated, and hidden inside the jeans fabric. In the third stage, the rectifier circuit layout on the flame retardant-4 (FR-4) printed circuit board (PCB) with the dielectric constant, = 4.7, thickness, <em>h</em> = 1.6 mm, and loss tangent, <em>δ</em> = 0.018 that can generate radio frequency-direct current (RF-DC) conversion is designed and simulated using the ADS software Each simulation result and fabrication measurement shows that the designed antenna array characteristics are suitable for an industrial, scientific, and medical radio (ISM) band by having the reflection coefficient, <em>S</em><sub>11</sub> less than -10 decibel (dB) at the respective resonant frequency, <em>f<sub>r</sub>.</em> Moreover, through simulation, the output DC voltage for the bridge rectifier circuit is from 132 mV to 5.01 V with the corresponding power conversion efficiency (PCE) between 3.48% and 50.20% whereas for the voltage doubler rectifier, the output DC voltage is from 417 mV to 2.91 V with the corresponding PCE between 34.78% and 53.56%, respectively.

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Farge, Dominique. "Accredited Interactive Web-Based Application for the 2016 International Clinical Practice Guidelines on Thrombosis in Cancer: Improving Knowledge Transfer in Daily Clinical Practice." Blood 128, no.22 (December2, 2016): 5954. http://dx.doi.org/10.1182/blood.v128.22.5954.5954.

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Abstract Venous thromboembolism (VTE) is a major therapeutic concern in cancer patients and the leading cause of death after metastasis. Providing anticoagulant therapy to this patient population is challenging because cancer patients are at increased risk of VTE recurrence and bleeding, and treatment management is often complicated by other co-morbidities that affect choice of anticoagulation. The International Initiative on Thrombosis and Cancer (ITAC-CME) is a multidisciplinary group of International academic clinicians, researchers, and experts dedicated to reducing the global burden of VTE and its consequences in cancer patients. In 2013, the group published international clinical practice guidelines for the treatment and prophylaxis of VTE in cancer (1, 2). In collaboration with CME solutions, an accredited CME provider, ITAC-CME developed a mobile web-based application to promote the international implementation of the 2013 guidelines, in English and French (www.itacc-cme.org). Usage of the app has steadily increased every year since its release. ITAC-CME recently revised its consensus recommendations according to a systematic review of the literature up to January 2016. In particular, the ISTH-endorsed updated recommendations provide a guidance on the use of the direct oral anticoagulants based on the current level of evidence (3). ITAC-CME and CME solutions have updated the web-based application to support the 2016 guidelines. The app also includes several new features, including interactive case-based CME learning activities, with pre- and post-activity practice assessments. These pre- and post-test metrics will be documented to record international clinical practice patterns, and monitor the impact of the app on the adoption of the 2016 guidelines into clinical practice worldwide. Translation of the 2016 updated app into additional languages is planned. The application has been submitted for accreditation with the royal College of Physicians and surgeons of Canada, the American Medical Association, the European Union of Medical Specialists, l' Organisme Gestionnaire du Développement Professionnel Continu, and the European Board for Accreditation in Hematology. 1 Debourdeau P, Farge D, Beckers M, Baglin C, Bauersachs RM, Brenner B, Brilhante D, Falanga A, Gerotzafias GT, Haim N, Kakkar AK, Khorana AA, Lecumberri R, Mandala M, Marty M, Monreal M, Mousa SA, Noble S, Pabinger I, Prandoni P, Prins MH, Qari MH, Streiff MB, Syrigos K, Büller HR, Bounameaux H. International clinical practice guidelines for the treatment and prophylaxis of thrombosis associated with central venous catheters in patients with cancer. J Thromb Haemost. 2013 Jan;11(1):71-80. 2 Farge D, Debourdeau P, Beckers M, Baglin C, Bauersachs RM, Brenner B, Brilhante D, Falanga A, Gerotzafias GT, Haim N, Kakkar AK, Khorana AA, Lecumberri R, Mandala M, Marty M, Monreal M, Mousa SA, Noble S, Pabinger I, Prandoni P, Prins MH, Qari MH, Streiff MB, Syrigos K, Bounameaux H, Büller HR. International clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer.J Thromb Haemost. 2013 Jan;11(1):56-70 3 Farge D, Bounameaux H , Brenner B, Cajfinger F, Debourdeau P, Khorana AA, Pabinger I, Solymoss S, Douketis J, Kakkar A. 2016 International Clinical Practice Guidelines Including Guidance for the Direct Oral Anticoagulants in the Treatment and Prophylaxis of Venous Thromboembolism in Patients With Cancer. Lancet Onccology 2016 (in press) Disclosures No relevant conflicts of interest to declare.

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Jou,JosepM., Fulgencio Navalón, Rosario García, Rosa Brugues, José Nicolás, Gines Escolar, and Maribel Diaz-Ricart. "Neutrophil CD64 Is a Good Indicator of Infection and Sepsis." Blood 114, no.22 (November20, 2009): 1347. http://dx.doi.org/10.1182/blood.v114.22.1347.1347.

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Abstract Abstract 1347 Poster Board I-369 Introduction Sepsis is among the top 10 causes of death, but improvements in the diagnostic tests for detecting and monitoring sepsis and infection have been limited in the last years. Neutrophil CD64 expression increases rapidly in the presence of inflammation mediators and in response to infection and tissue damage. We have evaluated changes in the expression of neutrophil CD64 in infected patients in comparison with other markers of infection and sepsis. Methods Prospective analysis of 56 blood samples from patients from the intensive care unit at our institution was performed for neutrophil CD64 expression, C-reactive protein (CRP), automated absolute neuthophil count (ANC), and complete manual leucocyte formula including % of bands (BANDS), and % of metamyelocytes and myelocytes (IG). Neutrophil CD64 expression was measured by flow cytometry using a quantitative method (Leuko64TM, Trillium Diagnostics, LLC). Patients were categorized into 5 groups (CLINIC) based on the clinical history and the degree of a systemic inflammatory response, from 1 (no inflammation) to 5 (septic shock). Statistics were performed using linear regression, correlation coefficient, and Passing-Bablock (P-B) regression. Sensitivity (S), specificity (SP), efficiency (E), and positive and negative predictive values (PPV and NPV respectively) were analyzed for all the parameters measured. Results Our results showed a correlation with CLINIC of 0.417, 0.552, 0.268, and 0.136 for CD64, CRP, BANDS, and ANC, respectively. P-B regression was only good for CD64, with a slope of 1.03 (0.6-1.4). Percentages (%) of S, SP, E, PPV, and NPV for CD64 were of 81%, 72%, 71%, 46% and 92%, respectively for groups 4 and 5. For CRP, S was of 93% with SP of 20%, E of 38%, PPV of 27%, and NPV of 91%. The remaining parameters showed deficient correlation with CLINIC. Correlations between CD64 and CRP, BANDS, and ANC were of 0.435, 0.342, and 0.01, respectively. Conclusions Neutrophil CD64 expression quantitation provides improved diagnostic detection of infection/sepsis compared with the standard diagnostic tests used in current medical practice. CD64 expression showed a better PPV than CRP, and an acceptable NPV. CRP showed deficient SP and E. BANDS, GI, and ANC showed no correlation with CLINIC. CD64 is a new indicator of infection that deserves consideration to be introduced in the daily hematology laboratory analysis. Disclosures No relevant conflicts of interest to declare.

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Campbell,AndrewD., Raffaella Colombatti, Biree Andemariam, Crawford John Strunk, Immacolata Tartaglione, ConnieM.Piccone, Deepa Manwani, et al. "An Analysis of Racial and Ethnic Backgrounds within the Casire International Cohort of Sickle Cell Disease Patients: Implications for Disease Phenotype and Clinical Research." Blood 134, Supplement_1 (November13, 2019): 2305. http://dx.doi.org/10.1182/blood-2019-127613.

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Introduction: Millions are affected by Sickle Cell Disease (SCD) worldwide with the greatest burden in sub-saharan Africa. Its origin thought to lie within the malaria belt of the world, SCD continues to affect thousands of lives worldwide partly due to the migration patterns of the human race to different continents. We created the Consortium for the Advancement of Sickle Cell Research (CASiRe) to better understand the different phenotypes of SCD and compare the clinical profiles of patients living in different environments through a validated questionnaire and medical chart review, standardized across 4 countries (United States[U.S.] United Kingdom[U.K.], Italy and Ghana). For this report, we recorded the multi-generational ethnic and racial background of 877 SCD patients across the CASIRE cohort for our final analysis. Methods: CASiRe included 6 sites in the U.S. (Univ. of Michigan, Rainbow Babies & Children's Hospital, Promedica Toledo Children's Hospital, Children's Hospital at Montefiore, Connecticut Children's Medical Center, Univ.of Connecticut Health Center), 2 in Ghana(Ghana Institute of Clinical Genetics, Pediatric SCD Clinic at Korle Bu Teaching Hospital), 2 in Italy( Univ. of Campania Luigi Vanvitelli, Univ. of Padua, Italy), and U.K.(Guys & St. Thomas Hospital, Evelina Children's Hosp). Between 2011 and 2017, after obtaining IRB approval at each site and written informed consent, demographic, clinical and laboratory data were collected by interviewing the patient and/or parent/guardian At the 2 sites (Guys and St Thomas Hospital, UK; Univ. of Padua, Italy) with existing IRB approved SCD registries data were abstracted directly from their respective databases. Descriptive statistics were performed on a subset of demographic data that included: age, race, gender, sickle cell genotype, country of birth of patient, parents, and grandparents. The geographic region and country of origin was based on parents' country of birth and separated into 10 regions: W.Africa, C.Africa, N Africa, Caribbean, C. America, N America, Europe, S America, Asia, Middle East. Results: 877 patients were enrolled with a median age 19.3 years. 451 (51.4%) patients were children, 424 (48.3%) male. Ghanaians represented 41.6% (365) of patients, while 254 patients (29%) were from the U.S. Italy enrolled 81 patients (9.2%), and 177 patients (20.2%) were from the U.K. West Africa represented the largest geographic region of origin of(577/65.8%), followed by N. America (184/21%), Caribbean (51/5.8%), Europe (27/3.1%), and Central Africa (24/2.7%). Overall(Fig. 1), 75% of patients (658) had Hgb SS, 168 patients (19.2%) had Sickle C disease, 29 (3.3%) had Sβ+thal and 22 patients (2.5%) of patients had Sβ0 thal. Racially, 820 patients (93.5%) identified themselves as African American or Black, while 30 patients (3.4%) identified themselves as Caucasian and 21 patients (2.4%) identified themselves as Latino or Hispanic. All Ghanaians identified as Black, while in the US and UK, over 90% of patients identified themselves as Black, and about 3% reported themselves as Caucasian. In comparison, in Italy, over 76% of patients reported a Black racial background, while 21% reported Caucasian background. (Table 1 and 2)&gt;98%Ghanaian patients and their parents were born in Ghana. In contrast, 66.7% of patients and &lt;15% of parents in Italian sites were born in Italy with the 64% of parents emanating from West Africa (38% Nigeria).Over 85% of patients in the UK were born in the UK while only 5.1% of parents were born there (54% in Nigeria). In the US, &gt;90% of patients were born within the US; Parents of patients were born in America 70% of the time. Caribbean (12.5%) and West African countries(9.5%) were the next highest parent countries of origin. 32 different countries of origin were reported within our cohort with the US leading with 22 different countries. Conclusion: This study is the first to describe the geographic distribution of these migrations in a very large cohort of nearly 900 patients with SCD.West Africa represented the largest geographic region of origin for SCD patients in Europe while Caribbean was the leading Non-US geographic region of origin in American patients. The diverse ethnic backgrounds observed in our cohort raises the possibility of how genetic and environmental heterogeneity within each SCD population subgroup can have implications on the clinical phenotype and clinical research outcomes. Disclosures Campbell: Novartis: Research Funding; Cyclerion: Consultancy, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding. Colombatti:Novartis: Consultancy; Global Blood Therapeutics: Consultancy; AddMedica: Consultancy. Andemariam:NovoNordisk: Membership on an entity's Board of Directors or advisory committees; New Health Sciences: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Other: DSMB Member; Bluebird Bio: Membership on an entity's Board of Directors or advisory committees; Emmaus: Membership on an entity's Board of Directors or advisory committees; Cyclerion: Membership on an entity's Board of Directors or advisory committees; Imara: Research Funding; Sanofi Genzyme: Membership on an entity's Board of Directors or advisory committees; Community Health Network of Connecticut: Consultancy; Terumo BCT: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Strunk:Novartis: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Speakers Bureau. Piccone:Hemex Health, Inc.: Patents & Royalties. Manwani:GBT: Consultancy, Research Funding; Novartis: Consultancy; Pfizer: Consultancy. Perrotta:Novartis: Honoraria, Research Funding; Acceleron Pharma: Research Funding.

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Bascon, Ivan, PaulJ.Christos, and Maria Teresa De Sancho. "Risk Factors, Clinical Manifestations, Treatment Duration and Outcomes in Carriers of Severe Inherited Thrombophilias." Blood 134, Supplement_1 (November13, 2019): 3657. http://dx.doi.org/10.1182/blood-2019-132248.

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Background Severe Inherited thrombophilia comprisses deficiencies of natural anticoagulants (antithrombin (AT), protein C (PC), and protein S (PS), and hom*ozygosity for factor V Leiden (FVL) or prothrombin gene mutation (PGM) or double heterozygosity or other combined thrombophilia. Carriers of AT, PC and PS have a high risk of thrombosis starting at a young age, usually several members of the same family are affected and thrombosis may occur at unusual locations. Conversely hom*ozygotes for either FVL, PGM or double heterozygotes may not have a family history of thrombosis and the first thrombotic event may present later on life. It is also unclear what is the duration and type of anticoagulation and long-term outcomes of these carriers. The purpose of this study was to compare risk factors, clinical manifestations, type and duration of anticoagulation and clinical outcomes between carriers of anticoagulant deficiencies and those with gain of function mutations (hom*ozygosity or double heterozygosity for FVL and PGM). Methods Retrospective evaluation of electronic medical records of patients with severe inherited thrombophilia referred to the Center for Blood Disorders at Weill Cornell Medicine-New York Presbyterian Hospital between January 2009 and June 2019. Severe deficiencies of AT, PC and PS were defined and (AT ≤ 60%, PC ≤ 50% and PS ≤ 40% (2). Patients without confirmatory laboratory results for the anticoagulant deficiencies were excluded from the study. We collected demographic data, risk factors for thrombosis, family history, type of thrombotic events, pregnancy complications in females, type and duration of anticoagulant and outcomes. Statistical analysis was performed using descriptive statistics and chi-square test was applied for comparison of variables between anticoagulant deficiency carriers and gain of function mutation carriers. Results Of a total of 107 patients identified,17 were excluded due to absence of confirmatory results. A total of 90 patients were analyzed; 70 (78%) females; mean age and range 44 (22- 82). There were 34 (38%)patients with anticoagulant deficiencies (10 AT, 6 PC and 18 PS) and 56 (62%) hom*ozygotes for FVL, PGM or double heterozygote. Of those, 23 (39%) hom*ozygote for FVL with one also heterozygote for the PGM, 2 (3.6%) hom*ozygote PGM and 31(55.4%) double heterozygote. Overall risk factors for thrombosis were similar in both groups. There were no identified thrombosis risk factors in 12 and 19 patients in the anticoagulant deficiency and gain of function mutation respectively. The most common type of clinical presentation in both groups was deep vein thrombosis and pulmonary embolism. A positive family history of either thrombosis of thrombophilia in a first degree family member was equal in both groups. Likewise age less than 40 at first thrombotic event was similar. The most frequent anticoagulant prescribed in the patients with anticoagulant deficiency was a direct oral anticoagulant in 26.%% and vitamin K antagonists 22.3% in the ones with gain of function mutation. More patients with anticoagulant deficiencies remain on anticoagulation for more than 1 year than the ones with a gain of function mutation (88.5% vs 64%) and had more recurrent thrombotic events (20.6% vs.5.4%). Within the 70 female patients, 5 (7%) had first trimester pregnancy loss and 14 (20%) had multiple pregnancy losses. Conclusions: Our results suggest that patients with severe inherited antithrombin, protein C and S deficiencies have worse outcomes despite longer duration of anticoagulation than patients hom*ozygote or double heterozygote for gain of function mutations. Disclosures De Sancho: Apellis Pharmaceuticals: Other: Advisory Board; BPL: Other: Advisory Board.

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Allahyani, Bader, and Rolf Ljung. "Venous Thromboembolism in Children 0-18 Years — a Regional Population-Based Study from Sweden." Blood 132, Supplement 1 (November29, 2018): 3805. http://dx.doi.org/10.1182/blood-2018-99-113844.

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Abstract Introduction: Venous thromboembolism (VTE) is a rare complication in childhood. Pediatric VTE is an important and increasingly frequent clinical challenge likely due to increased detection and advanced medical interventions leading to improved survival of previously fatal conditions. Objective: The principal aim of this population based study was to describe the incidence, age distribution, type/location of VTE, and acquired and genetic pro-thrombotic risk factors of VTE and recurrence of VTE in children 0-18 years. Material and Methods: The Regional Ethical Review Board in Lund approved the study. We conducted a retrospective regional study of all consecutive ICD-10 codes of VTE in children 0-18 years over a 15-year period (January 1, 2000, to December 31, 2015) in a regional catchment area of southern Sweden using an electronic diagnosis registry. Eligible subjects were defined as children under the age of 18 who presented with VTE and had imaging evidence of thrombosis. Of the 174 patients diagnosed with VTEs, 164 fulfilled the study group criteria. Data regarding subject demographics and medical history (central venous catheter, cancer, congenital heart disease, history of VTE, current infection, etc.), location of VTE and imaging method (upper, lower extremities, pulmonary embolism, renal, cardiac, cerebral sinus venous thrombosis (CSVT), etc.), coagulation studies at primary investigation which included in all cases evaluation of at least plasma concentrations of protein C, protein S, antithrombin, resistance to activated protein C and the genotypes FV-G1691A and FII-G20210A. In addition, plasma values for coagulation factors VIII and XI, D-dimer, PK-INR, and cardiolipin antibodies were analyzed. Results: The incidence of VTE in children in the investigated region of Sweden was found to be 0.8 per 10,000 children. Of the study group with confirmed VTE (n=164), 73/164 (45%) were males and 91/164(55%) females, with bimodal age distribution at diagnosis, 25 (15%) < 1 month, 139 (85%) >1 month-18 years. Of the children, 143/164 (87%) had DVT (deep venous thrombosis), 21/164 (13%) had PE (pulmonary embolism) and 5/164 (3%) had both DVT and PE. Of 143 patients with DVT, 50 (30%) had lower extremity DVT, 46 (28%) had upper extremity DVT and 34 (20.7%) CSVT and the remaining 13 various locations. 79/164 (59%) had acquired potential risk factors, 11/164 (11%) had genetic risk factors, 34/164 (21%) had both genetic and acquired risk factors, and 22/164 (13%) had no identified risk factors. The most frequent acquired risk factors in the cohort were the use of hormonal therapy (34%), concomitant malignancy (21%), infection at the time of thrombosis (19%) or a CVL (central venous line) (15%). Genetic thrombophilia risk factors were found in 45/164 (27.5%), the most common were Factor V Leiden (FVL) in heterozygous form in 35 (21%), FII mutation (heterozygous) in 4 (2%) and double heterozygosity for FVL and FII mutation found in 2 (1%). Plasma deficiency of Protein S was found in 5, Protein C deficiency in 6 and Antithrombin deficiency in 1 patient (who had 3 episodes of VTE). Recurrent VTE was documented in 9 (5%), of which 5 had a congenital pro-thrombotic disorder (i.e. FVL mutation (n=3), antithrombin deficiency (n=1) and a protein S deficiency (n=1). Two out of the nine with recurrent VTE had neither a genetic nor an acquired identified risk factor. Six out of a total of 45 (13.3%) with genetic risk factors had a recurrent VTE. No common acquired pro-thrombotic risk factor was found in the group with recurrent VTE. Conclusion: The incidence, age-distribution, locations and underlying disorders agree with published findings in pediatric populations. In our study, 87% of the children with VTE had either an identifiable acquired or genetic risk factor or a combination of both. Of those with a genetic risk factor, 13% had a recurrent VTE during the study period which indicates an even higher cumulative risk during childhood which emphasizes the need to consider prophylaxis in situations with increased risk of VTE. However, of those with recurrent VTE, no frequent acquired risk factor was identified. Disclosures No relevant conflicts of interest to declare.

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Fraiwan, Arwa, Muhammad Noman Hasan, Ran An, JuliaZ.Xu, AmyJ.Rezac, NicholasJ.Kocmich, Tolulope Oginni, et al. "International Multi-Site Clinical Validation of Point-of-Care Microchip Electrophoresis Test for Hemoglobin Variant Identification." Blood 134, Supplement_1 (November13, 2019): 3373. http://dx.doi.org/10.1182/blood-2019-129336.

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Introduction: Nearly 24% of the world's population carry hemoglobin (Hb) gene variants, with the large majority of affected births occurring in low-income countries. The most prevalent structural Hb variants are the recessive β-globin gene mutations, βS or S, βC or C, and βE or E1. Hb S mutation is prevalent in sub-Saharan Africa and in Central India. Hb C is common in West Africa, and Hb E is common in Southeast Asia and in India. hom*ozygotes or compound heterozygotes with βS (e.g., Hb SS or SC) have sickle cell disease (SCD), a chronic sickling disorder associated with pain, chronic multi-organ damage, and high mortality. While Hb EE causes only a mild microcytic anemia, Hb E in combination with β-thalassemia can lead to transfusion dependent thalassemia. Though carriers are typically asymptomatic, they may pass the mutations to their offspring. Screening is needed so that these disorders can be diagnosed early and managed in a timely manner2. For example, in low-income countries, due to lack of nationwide screening and comprehensive care programs, up to 80% of babies born with SCD are undiagnosed and less than half of them survive beyond 5 years of age2. The unmet need for affordable, portable, accurate point-of-care tests to facilitate decentralized hemoglobin testing in resource-constrained countries is well-recognized 2,3. Here, we present international multi-site clinical validation results and high diagnostic accuracy of the 'HemeChip' (Fig. 1), an affordable, 10-minute point-of-care microchip electrophoresis test for identifying common Hb variants S, C, and E. Methods: Institutional Review Board approvals were obtained at each study site, and blood samples were collected as part of the standard clinical care. Tests were performed by local users, including healthcare workers and clinical laboratory personnel. 315 children (6 weeks to 5 years of age) were tested in Kano, Nigeria. Study participants were enrolled at three hospitals, Amino Kano Teaching Hospital, Murtala Mohammed Specialist Hospital, and Hasiya Bayero Pediatric Hospital. 124 subjects (7 weeks to 63 years old) were included in the study at Siriraj Thalassemia Center in Bangkok, Thailand. 298 subjects (8 months to 65 years old) were tested at a referral testing facility of ICMR-National Institute of Research in Tribal Health, located at Late Baliram Kashayap Memorial Medical College, Jagdalpur, Chhattisgarh, India. Blood samples were tested with both HemeChip and the standard reference methods, high performance liquid chromatography or cellulose acetate electrophoresis. Reference test results were not available to the HemeChip users. Similarly, HemeChip test results were not available to the users of the standard reference tests. Clinical validation studies presented here were performed with a fully functional, portable HemeChip prototype developed at Case Western Reserve University (Fig. 1A). A commercial product has been developed based on this technology by Hemex Health Inc. under the product name, GazelleTM(Fig. 1B). Results and Discussion: Among the total 768 tests performed with HemeChip in all test sites, 732 were valid tests, as defined by the Standards for Reporting Diagnostic Accuracy (STARD)4. HemeChip correctly identified all subjects with Hb SS, Hb SC, Hb AS, Hb AE, and Hb EE with 100% accuracy (Table 1). Nine subjects with normal Hb (Hb AA) were identified as HbSS in Nigeria. No subjects with disease were identified as normal or trait by HemeChip. Three subjects with compound heterozygous Hb Sβ-thalassemia (2 subjects with Hb Sβ+-thalassemia, 1 subject with Hb Sβ0-thalassemia) were identified as Hb SS. Sensitivity was 100% for all Hb types tested. Specificity was 98.7% for Hb SS versus other Hb types, and 100% for all other Hb types tested. HemeChip displayed an overall diagnostic accuracy of 98.4% in comparison to standard reference methods for the Hb variants tested in all clinical testing sites (Table 1). HemeChip is a versatile point-of-care system that enables affordable, accurate, decentralized hemoglobin testing in resource-limited settings. References: 1. Weatherall DJ, Clegg JB. Bull World Health Organ. 2001;79(8):704-712. 2. Mburu J, Odame I. International Journal of Laboratory Hematology. 2019;41(S1):82-88. 3. Alapan Y, Fraiwan A, Kucukal E, et al. Expert Review of Medical Devices. 2016;13(12):1073-1093. 4. Bossuyt PM, Reitsma JB, Bruns DE, et al. BMJ : British Medical Journal. 2015;351:h5527. Disclosures Fraiwan: Hemex Health, Inc.: Equity Ownership, Patents & Royalties. Hasan:Hemex Health, Inc.: Equity Ownership, Patents & Royalties. An:Hemex Health, Inc.: Patents & Royalties. Thota:Hemex Health, Inc.: Employment. Piccone:Hemex Health, Inc.: Patents & Royalties. Little:Hemex Health, Inc.: Patents & Royalties; GBT: Research Funding. Gurkan:Hemex Health, Inc.: Consultancy, Employment, Equity Ownership, Patents & Royalties, Research Funding.

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Assal, Amer, Diane George, Monica Bhatia, Divaya Bhutani, Christian Gordillo, Suzanne Lentzsch, Ran Reshef, and MarkusY.Mapara. "Excellent Survival and Immune Reconstitution Following Matched/Mismatched Unrelated and Mismatched Related Transplantation in Adult Patients with Sickle Cell Disease: Updated Results from a Single Center Experience." Blood 134, Supplement_1 (November13, 2019): 2043. http://dx.doi.org/10.1182/blood-2019-132113.

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Introduction: The only cure for sickle cell disease (SCD) is allogeneic hematopoietic stem cell transplant (HSCT) although autologous HSCT of genetically engineered hematopoietic stem cells is promising. Lack of suitable matched related donors (MRD) is a major limitation driving interest in improving outcomes using unrelated donors. While excellent outcomes are achieved with non-myeloablative MRD HSCT in adults (Hsieh et al, 2009 and 2014), results from matched unrelated donor (MUD) HSCT have been limited by excessive graft versus host disease (GVHD) and treatment-related mortality (Shenoy et al, 2016). Here we present updated follow up of our institutional experience using MUD and mismatched unrelated donors (MMUD) in comparison to patients with MRD. Methods: Eligibility for HSCT included frequent pain crises requiring hospitalization and evidence of end-organ damage. Non-myeloablative conditioning with alemtuzumab and 3 Gy total body irradiation (TBI) was used for MRD HSCT (n=7), whereas patients without an MRD were transplanted using MUD, MMUD or haploidentical grafts (n=6) on a previously reported institutional protocol after conditioning with alemtuzumab (54 mg/m2), fludarabine (180 mg/m2), and melphalan (140 mg/m2), using a CD34+ selected graft with CD3+ cell add back. MRD recipients received sirolimus as GVHD prophylaxis. Non-MRD recipients initially received tacrolimus as GVHD prophylaxis (n=1) but subsequently received sirolimus (n=5) due to the first patient developing posterior reversible encephalopathy syndrome (PRES). All grafts were G-CSF mobilized peripheral blood grafts and all patients underwent RBC exchange to achieve Hgb S <30%. Data is reported using n (%) or median (range) and Wilcoxon rank-sum test was used for continuous variables. Results: Median follow up is 21.7 months (range 4.7 - 63.4). Median age for MRD recipients was 28.7 (21.4 - 35.5) years and 22.8 (18.5 - 34.6) for non-MRD recipients. Of note, the MRD group included one patient with a renal allograft from the same donor and another with stage V renal disease awaiting a kidney transplant. All patients where hom*ozygous for hemoglobin S except one who had hemoglobin Sβo -thalassemia in the MRD group, and another heterozygous for hemoglobin S and C in the non-MRD group. Patients in the MRD group received unmanipulated grafts with a median of 14 (6.2 - 16.9) x 10E6 CD34+ cells/kg. Non-MRD recipients received CD34 - selected grafts with a median of 7.8 (4.1 - 15.1) x 10E6 CD34+ cells/kg with 2.2 x 10E5 (0.1 - 2.5) CD3+ cells add back. No growth factors were used post-transplant. All patient engrafted with no cases of graft failure. Median time to engraftment was significantly longer for the MRD group at 25 (22 - 30) vs 19 (13 - 21) days, p=0.003. Two patients in the MRD group developed acute/late acute GVHD (2 grade II), and 3 patients in the non-MRD group (1 grade II, 2 grade III), 2 of which developed in while switching immune suppression due to PRES. All GVHD cases were steroid responsive and resolved. Three patients in the non-MRD group developed PRES and none in the MRD group. There were no cases of treatment related mortality and all patients are alive and free of SCD. As both groups received alemtuzumab, and the non-MRD group received a CD34-selected graft, we examined lymphocyte subset reconstitution at day 100 and 1 year post-HSCT. The most striking difference was in median CD8+ T cell counts at day +100 which were lower in the non-MRD group approaching significance [101 (43 - 2995) vs 6.5 (3 - 2233) cells/uL, p=0.055, for the MRD and non-MRD respectively]. CD8+ T-cell counts were not significantly different at 1 year [402 (184 - 1066) vs 774 (143 - 1002) cells/uL, p<0.99]. Results from other lymphocyte subsets including CD4+ T-cells, NK cells and B cells are shown in table 1 and were not significantly different between the 2 groups. Of note, early donor T-cell chimerism at D100 was not significantly different between MRD and non-MRD groups [27.0 (18.0 - 50.0) % vs 37.5 (3.0 - 80.0) %, p=0.83] whereas at 1-year, MRD group donor T cell chimerism was significantly lower [53.5 (17.0 - 65.0) % vs 82.7 (69 - 90), p=0.01]. Conclusion: We demonstrate excellent outcomes with 100% survival and no graft rejection following matched and mismatched unrelated donor HSCT for adult patients with severe SCD. Larger cohorts are needed to confirm these results and further delineate the impact of T-cell subset reconstitution on early-post transplant complications. Disclosures Assal: Incyte corporation: Consultancy, Research Funding; boston biomedical: Consultancy. Bhatia:BMS: Consultancy; Vertex Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Bhutani:Sanofi: Membership on an entity's Board of Directors or advisory committees. Lentzsch:Abbvie: Consultancy; Clinical Care Options: Speakers Bureau; Sanofi: Consultancy, Research Funding; Multiple Myeloma Research Foundation: Honoraria; International Myeloma Foundation: Honoraria; Karyopharm: Research Funding; Columbia University: Patents & Royalties: 11-1F4mAb as anti-amyloid strategy; Caelum Biosciences: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy; Janssen: Consultancy; Takeda: Consultancy; BMS: Consultancy; Proclara: Consultancy. Reshef:Magenta: Consultancy; Kite: Consultancy, Research Funding; Atara: Consultancy, Research Funding; Pfizer: Consultancy; BMS: Consultancy; Pharmacyclics: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; Celgene: Research Funding; Shire: Research Funding.

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Davar, Diwakar, Matteo Simonelli, Martin Gutierrez, Emiliano Calvo, Jason Melear, Sarina Piha-Paul, Donald Richards, et al. "394 Interleukin-8–neutralizing monoclonal antibody BMS-986253 plus nivolumab (NIVO) in biomarker-enriched, primarily anti–PD-(L)1–experienced patients with advanced cancer: initial phase 1 results." Journal for ImmunoTherapy of Cancer 8, Suppl 3 (November 2020): A419. http://dx.doi.org/10.1136/jitc-2020-sitc2020.0394.

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BackgroundInterleukin 8 (IL-8) is a C-X-C chemokine that exerts protumorigenic effects in the tumor microenvironment, including recruiting immunosuppressive PMN-MDSCs and promoting angiogenesis.1–3 Elevated serum IL-8 (sIL-8) is a negative prognostic indicator in patients with solid tumors and may have predictive value in patients treated with immunotherapies.2 4 5 BMS-986253, a fully human-sequence IgG1κ anti–IL-8 monoclonal antibody, binds IL-8 and prevents signaling through CXCR1/CXCR2 and has been shown to be safe in patients with advanced cancers.3 We present initial results of BMS-986253 + NIVO from a phase 1/2a trial in patients with advanced cancers who had detectable sIL-8 levels, the majority of whom had progressed on/after prior anti–PD-(L)1 (NCT03400332).MethodsDuring safety evaluation/dose exploration, patients with advanced metastatic solid tumors (melanoma, NSCLC, SCCHN, RCC, or UCC) and detectable sIL-8 (>10 pg/mL at screening) received BMS-986253 600 (n=16), 1200 (n=15), or 2400 mg (n=18) Q4W, or 1200 (n=12) or 2400 mg (n=59) Q2W, + NIVO 480 mg intravenously Q4W. Safety, pharmaco*kinetics, pharmacodynamics, and preliminary antitumor activity were evaluated (investigator-assessed, RECIST v1.1).ResultsAs of March 20, 2020, 120 patients (median age, 63 years [range, 35–87 years]) received BMS-986253 + NIVO; 97% of patients received prior anti–PD-(L)1 therapy, and 25% received prior anti–CTLA-4 therapy. BMS-986253 + NIVO was well tolerated with no dose-limiting toxicities observed. Most TRAEs were grade 1–2. The most common (≥5% of patients) TRAEs (any grade; grade 3–4) were fatigue (9%; 1%), nausea (7%; 0%), rash/rash maculopapular (6%; 0%), pruritus (5%; 0%), and decreased appetite (5%; 0%). Grade 3–4 serious TRAEs were reported in 2 patients (infusion-related reaction, BMS-986253 2400 mg Q2W + NIVO; AST/ALT increased, BMS-986253 1200 mg Q4W + NIVO). BMS-986253 exposure increased dose proportionally and was not altered with NIVO. BMS-986253 resulted in dose-dependent reductions in free sIL-8 levels, with tumor IL-8 suppression detected in most patients evaluated; additional pharmacodynamic endpoints will be presented. Partial responses were observed in multiple tumor types, including 5 of 28 patients with melanoma who had progressed on/after prior anti–PD-(L)1; 4 of the 5 patients were also previously treated with anti–CTLA-4.ConclusionsBMS-986253 + NIVO demonstrated a tolerable safety profile with dose-proportional pharmaco*kinetics and robust sIL-8 suppression. Preliminary antitumor activity was observed across a range of doses/regimens in this biomarker-enriched, anti–PD-(L)1–experienced, heterogeneous patient population with advanced cancers. These findings support further evaluation of BMS-986253 in select advanced tumors.AcknowledgementsThe authors acknowledge Dr Charles Drake while at Columbia University Medical Center, New York, NY, USA, for his contributions to the study.Trial RegistrationNCT03400332Ethics ApprovalThis study was approved by the WCG Independent Review Board, approval number 20172711.ReferencesDavid JM, Dominguez C, Hamilton DH, et al. The IL-8/IL-8R axis: a double agent in tumor immune resistance. Vaccines (Basel) 2016;4:22.Schalper KA, Carleton M, Zhou M, et al. Elevated serum interleukin-8 is associated with enhanced intratumor neutrophils and reduced clinical benefit of immune-checkpoint inhibitors. Nat Med. 2020;26:688–692.Bilusic M, Heery CR, Collin JM, et al. Phase I trial of HuMax-IL-8 (BMS-986253), an anti–IL-8 monoclonal antibody, in patients with metastatic or unresectable solid tumors. J Immunother Cancer 2019;7:240.Yuen KC, Liu L-F, Gupta V, et al. High systemic and tumor-associated IL-8 correlates with reduced clinical benefit of PD-L1 blockade. Nat Med 2020;26:683–698.Sanmamed MF, Perez-Gracia JL, Schalper KA, et al. Changes in serum interleukin-8 (IL-8) levels reflect and predict response to anti–PD-1 treatment in melanoma and non-small-cell lung cancer patients. Ann Oncol 2017;28:1988–1995.

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Cohen,JonathonB., Andreas Engert, StephenM.Ansell, Anas Younes, Marek Trneny, KerryJ.Savage, Radhakrishnan Ramchandren, et al. "Nivolumab Treatment Beyond Investigator-Assessed Progression: Outcomes in Patients with Relapsed/Refractory Classical Hodgkin Lymphoma from the Phase 2 Checkmate 205 Study." Blood 130, Suppl_1 (December7, 2017): 650. http://dx.doi.org/10.1182/blood.v130.suppl_1.650.650.

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Abstract Introduction: The phase 2 CheckMate 205 study (NCT02181738) of nivolumab (nivo) has demonstrated high objective response rates, durable efficacy, and acceptable safety profiles in patients (pts) with relapsed/refractory classical Hodgkin lymphoma (R/R cHL) after failure of autologous hematopoietic cell transplantation (auto-HCT) regardless of prior brentuximab vedotin (BV) treatment (Younes A et al. Lancet Oncol 2016; Fanale M et al. ICML 2017 [Oral 125]). Recently proposed new response criteria aim to account for atypical patterns of response with checkpoint inhibitors which may not be fully captured by conventional response criteria (Cheson BD et al. Blood 2016; Younes A et al, Ann Oncol 2017). Studies in solid tumors have shown that pts may continue to derive clinical benefits from nivo beyond disease progression as defined by conventional criteria (George S et al, JAMA Oncol 2016; Long GV et al, JAMA Oncol 2017). Here we report outcomes among pts with R/R cHL treated beyond progression (TBP) in CheckMate 205. Methods: This single-arm, multicenter study enrolled pts (age ≥18 y) with R/R cHL after failure of auto-HCT into 3 independent cohorts (A: BV naïve, B: BV after auto-HCT, C: BV before and/or after auto-HCT). Nivo 3 mg/kg IV every 2 wk was given until disease progression or unacceptable toxicity. Response was assessed by 2007 International Working Group criteria. Best overall response (BOR) was assessed per investigator. A protocol amendment in July 2014 allowed pts to be TBP (investigator-assessed) if they met prespecified criteria, including deriving clinical benefit, stable performance status, and non-rapid progression. Pts TBP were required to discontinue in the event of further progression (≥10% increase in tumor burden). Tumor burden after initial progression was assessed in a prespecified analysis. Exploratory analyses assessed overall survival (OS) and time to next therapy (TTNT) in pts TBP. Results: In total, 70/243 (29%) pts were TBP: 19 in Cohort A, 23 in B, and 28 in C. Demographics were similar to the overall study population: 57% had stage IV disease at study entry, median (range) age was 37 (18-72) y, and median number of prior therapies was 3 (2-5). BOR prior to progression was complete remission (CR) in 5 (7%) pts, partial remission (PR) in 31 (44%), stable disease (SD) in 20 (29%), and progressive disease in 13 (19%) (BOR was non-evaluable in 1 pt). Among pts TBP, the initial cause of progression was a ≥50% increase in total tumor burden in 13 (19%) pts, non-target lesion progression in 17 (24%), and new lesions in 47 (67%) (pts could have multiple findings as reasons for progression). The median time to initial progression in pts TBP was 6 mo; 11 mo in pts with initial BOR of CR and 7 mo in pts with initial PR or SD. At December 2016 database lock, median (range) doses of nivo beyond progression were 8 (1-43), and median duration of treatment beyond progression was 5 (0-19) mo. Overall, 21 (30%) pts TBP remained on treatment; the most common reason for discontinuation was further disease progression (80%). The majority of pts TBP demonstrated stable reductions in tumor burden with continued treatment. Median (95% CI) TTNT from first study dose of nivo was 17 (14, not estimable) mo (Figure). Median OS from date of initial progression was not reached in pts TBP and OS was 84% (95% CI 70, 92) at 1 y. Treatment-related adverse events (TRAEs) occurred in 46% of pts (13% grade [G] 3-4) after progression, vs 64% (9% G3-4) prior to progression. Serious TRAEs after progression were aspartate aminotransferase increase (n=1) and hypercalcemia (n=1), both G3-4. Ten deaths occurred in pts TBP; 7 were due to disease progression and none were considered related to study drug. Conclusions: In total, 29% of pts from CheckMate 205 Cohort A/B/C were TBP. New lesions were the most common reason for initial progression in pts TBP. Stable reductions in tumor burden were seen with continued treatment in pts TBP, and median TTNT and OS remained high. Proposed updates to response criteria may help to better assess the long-term efficacy of checkpoint inhibitors. These data suggest that pts considered to show stable performance status, non-rapid progression, and clinical benefits despite progression according to conventional response criteria may derive long-term benefits from continued nivo treatment. Study funding: BMS. Writing support: Simon Wigfield, Caudex, funded by BMS. Disclosures Cohen: Bioinvent: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takada: Research Funding; Bristol Myers Squibb: Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Infinity: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; LAM Therapeutics, Inc: Research Funding. Engert: Amgen: Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Affimed: Consultancy, Honoraria, Research Funding. Ansell: Merck: Research Funding; Celldex: Research Funding; Seattle Genetics: Research Funding; Bristol-Myers Squibb: Research Funding; Affimed: Research Funding. Younes: Roche: Consultancy, Honoraria, Other: Third-party medical writing assistance, under the direction of Anas Younes, was provided by Scott Malkin of Gardiner-Caldwell Communications, and was funded by F. Hoffmann-La Roche Ltd.; Bayer: Honoraria; Bristol-Myers Squibb: Honoraria; Novartis: Research Funding; Janssen: Honoraria; Merck: Honoraria; Curis: Research Funding; Sanofi: Honoraria; Takeda Millenium: Honoraria; Johnson & Johnson: Research Funding; Seattle Genetics: Honoraria; Incyte: Honoraria; Celgene: Honoraria. Trneny: Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Savage: Roche: Research Funding; Seattle Genetics: Consultancy, Honoraria; Bristol-Myers Squibb: Honoraria; Merck: Honoraria; Celgene: Consultancy. Ramchandren: Seattle Genetics: Consultancy; Janssen: Research Funding; Merck: Research Funding; Pharmacyclics: Research Funding. Collins: ADC Therapeutics: Research Funding; Roche: Consultancy, Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria; Celgene: Research Funding; Celleron: Consultancy; MSD: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Speakers Bureau; Bristol-Myers Squibb: Research Funding; Amgen: Research Funding. Fanale: AMGEN: Membership on an entity's Board of Directors or advisory committees; CELGENE: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; TAKEDA: Honoraria, Research Funding; ONYX: Research Funding; SEATTLE GENETICS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; MOLECULAR TEMPLATES: Research Funding; MERCK: Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GENENTECH: Research Funding; ADC THERAPEUTICS: Research Funding. Armand: Bristol-Myers Squibb: Consultancy, Other: research funding (institutional); Merck: Consultancy, Other: research funding (institutional); Infinity: Consultancy; Pfizer: Consultancy, Other: research funding (institutional); Affimed: Other: research funding (institutional); Otsuka: Other: research funding (institutional); Sequenta: Other: research funding (institutional); Sigma Tau: Other: research funding (institutional); Roche: Other: research funding (institutional); Tensha: Other: research funding (institutional). Zinzani: Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Johnson & Johnson: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Verastem: Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. De Boer: Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; MSD: Membership on an entity's Board of Directors or advisory committees; Merck: Membership on an entity's Board of Directors or advisory committees, Other: Non-restricted grant for research in head and neck cancer; Eisai: Membership on an entity's Board of Directors or advisory committees; Astellas: Other: member of Independent Data Monitoring Committee. Shipp: Cell Signaling: Honoraria; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Research Funding; Takeda: Other: Scientific Advisory Board; Merck: Other: Scientific Advisory Board; Gilead: Other: Scientific Advisory Board; AstraZeneca: Honoraria. Santoro: Merck: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees. Timmerman: Seattle Genetics: Consultancy; Celgene: Consultancy; Bristol-Myers Squibb: Consultancy, Honoraria, Other: Travel expenses, Research Funding; Genmab: Consultancy, Equity Ownership; Kite Pharma: Research Funding; ImmuneGene: Research Funding. Sacchi: Bristol-Myers Squibb: Employment. Sy: Bristol-Myers Squibb: Employment. Kuruvilla: BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Honoraria; Janssen: Consultancy; Hoffman LaRoche: Consultancy; Seattle Genetics: Consultancy, Honoraria; Amgen: Honoraria; Roche: Honoraria; Janssen: Honoraria; Lundbeck: Honoraria; Merck: Honoraria; Karyopharm: Research Funding; Roche: Research Funding; Celgene: Honoraria, Research Funding.

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Al-Habsi,KhalidS., AndrewW.Shih, Rebecca Barty, Grace Wang, Allahna Elahie, Mona Azzam, Reda Siddiqui, et al. "Red Cell Antigen Genotyping Compared to Standard Serological Phenotyping in Sickle Cell Disease Patients in Canada: Potential for Reducing Alloimmunization." Blood 126, no.23 (December3, 2015): 3404. http://dx.doi.org/10.1182/blood.v126.23.3404.3404.

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Abstract Introduction: Red blood cell (RBC) transfusion is the cornerstone of management in many patients with sickle cell disease (SCD). However, RBC transfusion can be complicated by alloimmunization and hemolytic transfusion reactions in this population despite providing extended phenotype-matched RBC transfusions. This is due to heterogeneity of RBC antigens, unique variant mutations in this population, and genetic mismatch between the blood donor pool and SCD patients in North American settings. In this study, we evaluated the level of discrepancy between RBC antigen genotyping and traditional phenotyping methods and the association of these discrepancies with the presence of RBC alloantibodies in SCD patients at our centre in Canada. Methods: Commencing in January 2015, RBC antigen genotyping has been included in the care for patients with SCD treated at our Hemoglobinopathy Clinic in an academic medical centre. Patient blood samples are sent to a reference laboratory to perform genotyping of RhCE, Kell, Kidd, Duffy, and S antigens. RBC antigen phenotyping was performed locally using both tube and automated solid phase assays. Additional clinical data, demographic and transfusion-related data were obtained from a local transfusion registry databse and thorough clinical chart reviews. Approval from our centre's research ethics board was obtained prior to commencement of data collection. Results: To date, RBC antigen genotyping has been performed on 45/88 SCD patients treated at our centre. The mean age of these patients was 25, and 58% were female. The majority of patients had HbSS SCD genotype (64.4%), or HbSC (26.7%). Overall, 32/45 (71%) of patients had variant mutations detected by genotyping, including 9 (20%) patients with more than one variant mutation. The most common mutation detected was the GATA mutation (n= 23; 51%) resulting in loss of Fyb antigen expression on RBCs, but associated with expression of Fyb on non-erythroid tissues. The RhCE system showed variant mutations resulting in partial expression of antigens in 9 (20%) patients. Alloantibodies were found in 9/36 (25%) patients with either a GATA mutation or no variant mutations. Alloantibodies were found in 2/9 (22.2%) patients with mutations resulting in partial antigen expression. The proportion of patients with any discrepancy between genotyping and phenotyping was 34/45 (75.6%). The largest rates of discordance were seen in the RhCE system, with the c antigen having a kappa of 0.68 and e antigen having a kappa of 0.32 (Table 1). Conclusion: Our results showed a high prevalence of variant mutations and significant discrepancies between genotyping and phenotyping methods, most notably in the RhCE antigen system. Mutations resulting in partial antigen expression were associated with development of alloantibodies in 22.2% of patients in our study, which may have been prevented with a genotype-based antigen-matching strategy. Additionally, knowledge of presence of GATA mutation will enhance feasibility of antigen matching for affected patients, who may have otherwise required RBC units negative for Fyb based on local policies. To our knowledge these results represent the first published data from a Canadian centre, showing similar rates of discrepancy between traditional phenotyping methods and RBC antigen genotyping as reported in other regions. Although phenotype-based matching strategies are used in many centres, these strategies can place patients with partial RBC antigen variant mutations at a direct increased risk of alloimmunization. Thus genotype-based antigen-matching strategies should be considered for transfusion of matched RBCs in patients with SCD. Table 1. Blood Group Antigen Frequency In SCD Patients By Phenotyping/Genotyping with Level of Agreement Between Both Methods Antigen Phenotype Genotype Kappa Positive Negative Positive Negative Partial C 37.78 62.22 28.89 62.22 8.89 0.82 c 88.89 11.11 80.00 11.11 8.89 0.68 E 13.33 86.67 13.33 86.67 1.00 e 97.78 2.22 88.89 2.22 8.89 0.32 Fya 13.33 86.67 13.33 86.67 1.00 Fyb 22.22 68.89 26.67 73.33 0.94 Jka 80.00 20.00 82.22 17.78 0.93 Jkb 51.11 48.89 55.56 44.44 0.91 S 28.89 42.22 46.67 53.33 1.00 s 51.11 6.67 86.67 13.33 1.00 Disclosures No relevant conflicts of interest to declare.

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Gisslinger, Heinz, Christoph Klade, Kudrat Abdulkadyrov, Slawomira Kyrcz-Krzemien, Elena Karyagina, AnaitL.Melikyan, Krzysztof Warzocha, et al. "Final Results from the Phase 3 Traial Areta Comparing a Novel, Extended-Release Anagrelide Formulation to Placebo in Essential Thrombocythemia Patients with Defined Risk Status." Blood 128, no.22 (December2, 2016): 476. http://dx.doi.org/10.1182/blood.v128.22.476.476.

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Abstract Background : Anagrelide hydrochloride (ana), is a well-known compound used to selectively normalize platelet counts (plc) by inhibiting megakaryocyte development and maturation. Common side-effects of licensed formulations may be largely due to peak plasma concentrations of ana and its 3OH-metabolite, whereas efficacy is proportional to the Area under the curve (AUC). A novel extended-release formulation (ana retard, AR) has superior pharmaco*kinetics (Petrides 2015) and has been demonstrated to be equally effective as the licensed formulation (Gisslinger 2016). Here, we investigate a "treat-early" concept in non-high risk ET patients. Study design:AR was compared to placebo in a phase 3, randomized, parallel group, multicenter, subject- and sponsor-blinded trial in patients diagnosed with ET according WHO 2008 and a defined risk status including JAK2 mutation, protein C/S or antithrombin III deficiency, factor V Leiden or prothrombin mutation, cardiovascular risk factors. The primary endpoint was time to first ET-related event adjudicated by a blinded expert panel, or progressive thrombocytosis (plc≥1000G/L or plc increase >300G/L within 3 months) requiring medical intervention. Secondary endpoints included plc response and change of risk status. Results : 146 patients were randomized and dosed (all Caucasian, mean age 43 years, 74% females), and 112 completed the first year with drop-out rates of 22% in AR and 25% in placebo. Only 49% of placebo patients vs. 74% of AR patients consented to enter the extension phase. Consequently, over the entire study duration, median exposure times differed significantly with 123 weeks for AR and 62 weeks for placebo. The primary endpoint was met in all analysis sets, with p<0,0008 and 13 vs. 26 ET related events and/or progressive thrombocytosis in the ITT analysis. The progression to high-risk status was 11,7% for AR vs. 26,1% for placebo (p<0,005). AR proofed highly efficacious in normalizing plc: within 2 weeks of therapy mean baseline plc of around 750G/L were consistently below 400G/L (83% complete, 12% partial responders). The maintenance dose was the highest tolerated dose able to maintain plc in range; for 73% of AR patients this was achieved with a single 2mg tablet given once-daily. Remaining patients received doses up to 4 tablets per day. AR showed an acceptable safety profile consistent with the SmPC of licensed ana formulations. Conclusions: Long term treatment of ET patients with defined risk status, using this novel modified-release anagrelide formulation proofed well tolerable, normalized plc in a vast majority, significantly reduced progression to high-risk status and most importantly was associated with significantly less clinical ET related events. These data have important implications for the optimal management of ET and support a "treat-early" approach. References Results of a phase I, single dose, randomized, 3-way crossover study, to assess the bioavailability of a novel anagrelide extended release (ER) formulation in comparison to a commercially available anagrelide reference product (CARP) in healthy volunteers, Petrides P, Zagrijtschuk O, Klade C, DGHO, 2015 Phase 3 trial TEAM-ET in 106 high-risk Essential Thrombocythemia patients, demonstrating non-inferiority of Anagrelide Retard, a novel, extended-release anagrelide formulation, to the licensed comparator Gisslinger H, Radinoff A, Karyagina E,Kyrcz-Krzemień S, Abdulkadyrov K, Gerbutavicius R,Melikyan A, Burgstaller S, Hus M, Kłoczko J, Yablokova V, Tzvetkov N, Całbecka M, Shneyder T, Warzocha K, Jurgutis M, Kaplanov K, Hodisch J, Klade C, Buxhofer-Ausch V, European School of Hematology EHA 21st Congress, 2016 Disclosures Gisslinger: AOP Orphan Pharmaceuticals AG, Novartis, Celgene, Baxalta: Consultancy, Honoraria, Research Funding. Klade:AOP Orphan: Employment. Kyrcz-Krzemien:AOP Orphan Pharmaceuticals AG, Novartis, BMS, Medac: Honoraria. Warzocha:BMS: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Grohmann-Izay:AOP Orphan Pharmaceuticals AG: Employment. Hodisch:AOP Orphan Pharmaceuticals: Employment. Widmann:AOP Orphan Pharmaceuticals: Employment. Kralovics:Qiagen: Membership on an entity's Board of Directors or advisory committees; AOP Orphan: Research Funding. Schwarz:AOP Orphan Pharmaceuticals: Consultancy. Kiladjian:Novartis: Research Funding; AOP Orphan: Research Funding.

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Cheng, Hong, Rong Yan, Suping Li, Yanhong Yuan, Jun Liu, Changgeng Ruan, and Kesheng Dai. "Shear-Induced Von Willebrand Factor-Mediated Platelet Glycoprotein Ibα Shedding." Blood 114, no.22 (November20, 2009): 4024. http://dx.doi.org/10.1182/blood.v114.22.4024.4024.

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Abstract Abstract 4024 Poster Board III-960 Introduction Shear-induced platelet adhesion through the interaction of glycoprotein (GP) Ibα with von Willebrand factor (VWF) exposed at the injured vessel wall or atherosclerotic plaque rupture is the first step for the physiological hematosis or pathologic thrombus formation in stenosed arteries. However, the role of shear stress in the regulation of platelet function remains poorly defined. Methods: Washed platelets were exposed to VWF-coated surface at different shear conditions, provided by syringe pump connecting with glass capillary or cone-and-plate viscometer. GPIbα shedding was investigated by flow cytometry and western blot. Results GPIbα ectodomain was shed from platelets, while a small mass of GPIbα C-terminal peptide around 17 kDa was increased correspondingly. Although GPIbα ectodomain shedding was found under all shear conditions, the extent of GPIbα shedding was maximum at 250/s and dramatically reduced with increased shear rate, which was consistent with the number of stable adhesive platelets. There was a correlation between the levels of platelet adhesion and the extent of GPIbα shedding. Furthermore, GPIbα shedding increased with the concentration of immobilized VWF and time duration (within 1 minute) of constant shear stress. The potential protease(s) and signaling pathway involved in this process were investigated. Pretreatment of platelets with membrane-permeable calpain inhibitors (MDL28170, calpain inhibitor I and II) and metalloproteinase inhibitor (GM6001) abolished shear-induced GPIbα shedding. Though platelets showed partial activation detected by PAC-1 binding, GPIbα shedding was not impacted by apyrase and PGE1. However, integrin αIIbβ3 antibody (SZ-21) and phosphoinositide 3-kinase inhibitors (wortmanine) obviously inhibited GPIbα shedding. Conclusions: These results indicate that shear-induced platelet-VWF interaction results in calpain and metalloproteinase-dependent GPIbα ectodomain shedding. Fluid shear stress and VWF always exist in both the normal circulation of blood and pathological medical conditions, particularly, the interaction of GPIbα with VWF under flow initiates platelet adhesion and thrombus formation. Thus, the current finding that shear-induced the interaction of GPIbα with VWF incurs GPIbα ectodomain shedding not only has physiological implication in understanding the presence of glycocalicin in normal circulation, but also suggests a novel mechanism for the negative regulation of platelet function and the limitation of platelet thrombus growth under pathophysiological flow conditions. Disclosures: No relevant conflicts of interest to declare.

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Dobs, Yasminah Elsaadany, and Mohamed Medhat Ali. "The epigenetic modulation of alcohol/ethanol and cannabis exposure/co-exposure during different stages." Open Biology 9, no.1 (January 2019): 180115. http://dx.doi.org/10.1098/rsob.180115.

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Studies have reported the significant economic impact of smoking cannabis and drinking alcohol In the USA. It was estimated that the costs of cannabis-related treatment, hospitalization and loss of work-related pay have amounted to $200 billion. (Andersen AM, Dogan MV, Beach SRH, Philibert RA. 2015 Genes 6 , 991–1022. ( doi:10.3390/genes6040991 )). Data from the National Epidemiologic Survey on Alcohol and Related Conditions showed that individuals with general anxiety disorder and substance use disorder (GAD-SUD) have higher psychiatric comorbidity rates than those without substance use disorder (Alegría AA, Hasin DS, Nunes EV, Liu SM, Davies C, Grant BF, Blanco C. 2010 J. Clin. Psychiatry 71, 1187–1195. ( doi:10.4088/JCP.09m05328gry )). Moreover, the criminal justice system is significantly impacted by this cost (Andersen AM, Dogan MV, Beach SRH, Philibert RA. 2015 Genes 6 , 991–1022. ( doi:10.3390/genes6040991 )). Despite the increasing use of cannabis, there are still too many obscure facts. One of the new areas that scientific evidence shows is impacted negatively by cannabis use is the epigenome, which is an understudied area that we are still learning about. In addition, over the past few decades, we have seen various social and healthcare changes that have raised critical questions about their ongoing roles in regulating marijuana and alcohol use. This is important because of the increasing popularity and usage across various ages especially young adults and teenagers. More than 97.5 million Americans over 12 years old have used cannabis for non-medical use despite the significant side effects, with 1 in 10 users developing cannabis dependence (Crean RD, Crane NA, Mason BJ. 2011 J. Addict. Med. 5, 1–8. ( doi:10.1097/ADM.0b013e31820c23fa ), Office of Applied Studies. 2006 Substance Abuse and Mental Health Services Administration, USA.). It was reported that 16% of substance abuse admissions in the USA were for cannabis-related symptoms, which is second only to alcohol-related disorders (Agalioti T, Lomvardas S, Parekh B, Yie J, Maniatis T, Thanos D. 2000 Cell 103, 667–678. ( doi:10.1016/S0092-8674(00)00169-0 ), Soutoglou E, Talianidis I. 2002 Science 295, 1901–1904. ( doi:10.1126/science.1068356 )). Today there are thirty-one states and the District of Columbia that currently have legalized marijuana for either medical or recreational use. Data about marijuana use from NIAAA's National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) indicates that ‘in total, 79 000 people were interviewed on alcohol and drug use. When examined by age young adults (ages 18–21) were found to be at highest risk for marijuana use and marijuana use disorder, with use increasing from 10.5 to 21.2% and disorder increasing from 4.4 to 7.5%’. ‘Given these facts, George Koob, PhD, director of NIAAA stated the importance for the scientific community to convey this information to the public about the potential hazards of marijuana and it's use’. On the other hand, according to the National Institute on Alcohol Abuse and Alcoholism, 16 million adults suffer from alcohol use disorders. To the best of our knowledge, epigenetic mechanisms have been previously studied in alcohol and cannabis abuse separately. Recent studies highlighted the molecular mechanisms that are linked with drug-induced transcriptional regulation, behavioural abnormalities and neurodegeneration, which has emphasized the role of chromatin modification/remodelling in the generation of drug activation of certain genes and the disabling of others, and the effect of that on addiction (Maze I, Nestler EJ. 2011 Ann. N. Y. Acad. Sci. 1216, 99–113. ( doi:10.1111/j.1749-6632.2010.05893.x ); Renthal W, Nestler EJ. 2008 Trends Mol. Med . 14, 341–350. ( doi:10.1016/j.molmed.2008.06.004 )). In this review, we will give an overview of epigenome science relevant to cannabis/the endocannabinoid system and the potential of epigenetic overlap between alcohol and cannabinergic activity at different stages, to aid further investigations that could bring more treatment options to our horizon.

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Fisher, Cody, Suzannah Schmidt-Malan, Ying Yuan, Shijie He, Zhenkun Ma, Robin Patel, and Robin Patel. "691. Activity of TNP-2092 Against Biofilms Formed by Prosthetic Joint Infection-Associated Staphylococci." Open Forum Infectious Diseases 6, Supplement_2 (October 2019): S313. http://dx.doi.org/10.1093/ofid/ofz360.759.

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Abstract Background Infection occurs in ~1–2% of prosthetic joint replacement surgeries, with staphylococci being the most common cause. TNP-2092 is an investigational drug composed of rifamycin and quinolizinone pharmacophores conjugated via a stable linker. Here, we determined TNP-2092’s in vitro activity against biofilms formed by staphylococci associated with prosthetic joint infection and compared activity to that of ciprofloxacin and rifampin alone and in combination, as well as to daptomycin and vancomycin. Methods A total of 80 staphylococcal isolates (40 Staphylococcus aureus and 40 Staphylococcus epidermidis) were studied. Planktonic state minimum inhibitory concentrations (MICs) of TNP-2092, ciprofloxacin, rifampin, ciprofloxacin + fixed concentration (1 mg/mL) rifampin, daptomycin and vancomycin were determined following CLSI guidelines. Tween-80(0.002%)was added to TNP-2092 to prevent drug binding to plastic plates. Minimum biofilm inhibitory concentrations (MBICs) and minimum biofilm bactericidal concentration (MBBCs) were determined as follows. Bacteria were grown in TSB to logarithmic phase and adjusted to a turbidity of 0.5 McFarland; 150 µL aliquots were transferred to individual wells of 96-well flat-bottom plates and the plates covered with 96-pegged lids. Plates were incubated on a shaker for 5 hours at 37℃. Pegged lids were rinsed using 200 µL PBS/well and placed into a microtiter plate containing serial 2-fold drug dilutions in CAMHB Plates were incubated for 20–24 hours at 37°C and MBICs read by visual turbidity. Pegged lids were rinsed with PBS and placed into plates filled with 200 µL CAMHB/well and incubated for 20–24 hours at 37°C after which MBBCs were determined by assessing visual turbidity. Results Results shown in the table. Conclusion TNP-2092 has promising in vitro activity against prosthetic joint infection-associated staphylococcal biofilms. Disclosures Robin Patel, MD, ASM and IDSA: Other Financial or Material Support, Travel reimbursem*nt, editor’s stipends; CD Diagnostics, Merck, Hutchison Biofilm Medical Solutions, Accelerate Diagnostics, ContraFect, TenNor Therapeutics Limited, Shionogi: Grant/Research Support; Curetis, Specific Technologies, NextGen Diagnostics, PathoQuest, Qvella: Consultant; NBME, Up-to-Date, the Infectious Diseases Board Review Course: Honorarium recipient, Other Financial or Material Support; Patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an anti-biofilm substance issued: Other Financial or Material Support, Patents.

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Wylie, Megg, Amelia Srajer, Kevin Lonergan, Philippa Brain, and Eddy Lang. "Practice variation and trends in the management of incomplete and missed spontaneous abortion: Informing a multisite quality improvement project." Canadian Journal of Emergency Nursing 44, no.2 (July20, 2021): 13–14. http://dx.doi.org/10.29173/cjen128.

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Practice variation and trends in the management of incomplete and missed spontaneous abortion: Informing a multisite quality improvement project. Megg Wylie, Amelia Srajer, Kevin Lonergan, Philippa Brain, Eddy Lang Background: Practice variation in the management of spontaneous abortion exists in the Emergency Department (ED). We developed a multisite retrospective study to assess how the management of spontaneous abortion has changed over 2014-2019 across four Calgary EDs, with emphasis on assessing variation and trends between non-operative (medical/expectant) and operative (dilatation and curettage) management. Medical management has been increasingly indicated as effective, yet a knowledge gap exists regarding its use. Knowledge of that proportion and physician-level practice variation will facilitate educational and audit and feedback style initiatives. Results provide justification and supporting data for said initiatives, which may be extrapolated to elsewhere. Implementation: Two medical students are heading the day to day work of this project, with support from a principal investigator with the Department of Emergency Medicine in Calgary. We also have the support of a data manager and the head of pregnancy loss in the region. This study was implemented as a quality improvement project. Therefore, the Conjoint Health Research Ethics Board at the University of Calgary was consulted to ensure the project qualified as a quality improvement and that our privacy protections were appropriate. With approval from the ethics board, we needed the data to analyze and assess. To do so, we utilized Sunrise Clinical Manager (SCM) to retrospectively collect data. Sunrise Clinical Manager, a system utilized in Calgary EDs to track patient and department information, was accessed to collect administrative data. Sustaining this work will involve the continued efforts of the described team, largely in writing up the results and disseminating them via audit and feedback procedures. Evaluation Methods: Using SCM, data were retrospectively collected for patients coded with International Classification of Disease (ICD-10) codes O03.4 (incomplete spontaneous abortion without complication) or O02.1 (missed abortion) who presented to an ED in Calgary (Foothills Medical Centre, Peter Lougheed Centre, South Calgary Hospital, and Rockyview General Hospital) over 2014-2019. We collected patient and environmental factors to allow for the examination of unintended associations. Hemoglobin, HCG level, CTAS code, PIA (time to MD), and U/S result (to confirm diagnosis) were collected. Variables regarding length of stay, procedures received (D&Cs, or other), and returns to care (within 72 hours, and 7 days) were collected. Return to care for future D&C was considered a proxy for failed non-operative management. Demographic and practice data were collected on ED physicians who saw a minimum of 15 patients from our cohort, to gain understanding of trends in practice. Data were analyzed using Chi-square and Mann-Whitney U tests. Results: Within our cohort, 1110 (28.9%) patients received a D&C. The remaining 2735 (71.1%) patients were managed non-operatively. Variation and trends were present between sites, with rates of D&Cs ranging from 15.8% to 33.5% (p <0.001). The rate of D&Cs decreased from 34.2% in 2014 to 22.6% in 2019 across all sites (p <0.001), and 11.6% absolute and 33.9% relative reduction; yet there was minimal variation over time in rates of ED returns and returns resulting in D&Cs. 78.6% of physicians who saw ≥ 15 patients were female, with female physicians responding to 81.8% of our cohort Advice and Lessons Learned:1) Our first suggested lesson is to have a clear plan regarding deadlines and timelines, but toalso have room for flexibility. At some times the work on this project was slowed to alloweffective collaboration with the obstetrics and gyneocology department, or to allow for therefinement of data management. By setting realistic timelines, team members wereencouraged to progress the work in a timely fashion. However, by having flexibility the teamwas able to adapt to roadblocks along the way. 2) A second lesson would be the importance of meaningful collaboration between departments.Though the setting of the project was within Calgary EDs, the topic and content have clearrelevance to obstetics and gynaecology. By consulting with members of the obstetrics andgynaecology department we were able to clarify our objectives and have a betterunderstanding of local contextual factors that influenced our results.

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McClellan, Kristen, Cami Hilsendager, and Strnad Luke. "257. Staphylococcus aureus Bacteremia: Does Intravenous Drug Use Impact Quality of Care and Clinical Outcomes?" Open Forum Infectious Diseases 7, Supplement_1 (October1, 2020): S127—S128. http://dx.doi.org/10.1093/ofid/ofaa439.301.

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Abstract Background Individuals with intravenous drug use (IDU) have higher risk for Staphylococcus aureus bacteremia (SAB) and increased management complexity. The goal of this study was to compare differences in SAB characteristics, adherence to standard of care metrics, and clinical outcomes in those with and without IDU. Methods A retrospective chart review was conducted on cases of SAB between January 1, 2016 and December 31, 2017 at a 500-bed teaching hospital. Inclusion criteria was age &gt; 18 years and ≥ one blood culture positive for S. aureus. Patients were excluded if they transferred hospitals, had care withdrawn or died within 48 hours of diagnosis or had a ventricular assist device infection. Records were reviewed for substance use, SAB characteristics, standards of care, and outcomes. Data were analyzed using SPSS software. The study was approved by the Institutional Review Board. Results In 248 patients with SAB, 28.2% had documented IDU. Median age was 37 (IDU) and 57 (non-IDU). In the IDU group, 75.7% had the formal diagnosis of opioid use disorder and 78.9% of stimulant use disorder. IDU was associated with hepatitis C and houselessness while non-IDU was associated with diabetes, hemodialysis, and cancer. Those with IDU had higher rates of MRSA, endocarditis, and spinal infections, but did not have higher rates of polymicrobial infections or venous thrombosis. There was no difference in appropriate repeat blood cultures, antibiotic management, and ID consultation. Length of stay and against medical advice (AMA) discharges were higher in those with IDU. There was no difference in 90-day recurrence or readmission, but 90-day mortality was higher in the non-IDU group. Conclusion There was no difference in adherence to SAB quality of care metrics between groups with and without IDU. Despite the IDU group being younger with fewer comorbidities, 90-day readmissions were not different between groups. This bears further analysis but may represent the influence of therapy completion, AMA discharges, and unmeasured social determinants of health. Disclosures All Authors: No reported disclosures

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Tamarelli,CarrieM., and DavidD.Howell. "An analysis of methodologic quality in survey research reported in the Journal of Clinical Oncology." Journal of Clinical Oncology 31, no.15_suppl (May20, 2013): 6616. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.6616.

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6616 Background: Survey research (SR) has been increasing as a percentage of published manuscripts in medical journals. SR plays an important role in studies of quality of life and patient preferences in treatment. Appropriate quality of methodology in SR is critical both to assure reliability and validity of survey results as well as to derive sound generalizations for larger populations from the subsets surveyed. Surveys that have deficient methodological criteria may suffer from significant flaws. A complete description and discussion of quality survey methodology, analysis, and results is essential for a thorough understanding and evaluation of published SR. Methods: Between January 2006 and December 2010, 227 articles in JCO were identified to have either “survey” or “questionnaire” in either the title or abstract. The most recent 52 consecutive articles fulfilling criteria from that time period were reviewed for reporting of survey methodology. A modification of Bennett et al.’s checklist for reporting SR was used for this analysis (Bennett C., et al. Reporting guidelines for survey research: An analysis of published guidance and reporting practices. PLoS Med 8(8): e1001069, 2011.). 35 metrics were used to analyze each survey. These metrics were grouped in the following categories: 1) title and abstract, 2) introduction, 3) methods (research tool, sample selection, survey administration and analysis), 4) results, 5) discussion, and 6) ethical quality indicators. Results: Of the 52 survey articles reviewed, the top quartile reported greater than 72% of the analyzed metrics. Half of the articles contained 63% or more of the desired metrics, and half of the articles had between 42% and 62% of the desired metrics. Some metrics were usually reported, such as ethics board review (reported in 85% of articles), but others were not consistently reported, such as calculation or justification of sample size (neither were reported in 71% of articles). Conclusions: A substantial number of articles reviewed reporting on survey research in JCO did not report critical components of survey methodology. More rigorous quality recommendations should be offered to guide authors in the report of survey research results.

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Panayiotidis, Panayiotis, Gayane Tumyan, Catherine Thieblemont, VadimV.Ptushkin, Ana Marin Niebla, Ramon Garcia-Sanz, Andrey Zaritskey, et al. "Primary Analysis of the Tegar Study: A Phase II Study Exploring the Safety and Efficacy of Atezolizumab in Combination with Obinutuzumab or Rituximab in Patients with Relapsed or Refractory (R/R) Mantle Cell Lymphoma (MCL), Marginal Zone Lymphoma (MZL), or Waldenstrom Macroglobulinemia (WM)." Blood 136, Supplement 1 (November5, 2020): 2–3. http://dx.doi.org/10.1182/blood-2020-137087.

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Introduction:Treatment options for R/R MCL, MZL and WM are limited. New combinations are in development. A previous Phase Ib study evaluating atezolizumab (A) in combination with obinutuzumab (O) in patients (pts) with R/R NHL reported no new safety signals and overall response rates of 57% and 16% in follicular lymphoma and diffuse large B-cell lymphoma pts, respectively (Palomba, et al. ICML 2017). The Phase II TEGAR study (EudraCT: 2016-003579-22) evaluated the safety and efficacy of A in combination with O or rituximab (R) in pts with R/R MCL, MZL or WM. Methods:R/R MCL or WM pts received eight 21-day (D) cycles (C) of A 1200mg in combination with O 1000mg as induction. O was given by IV infusion on D1 of each C and optionally as a split dose on D1 (100mg) and D2 (900mg) of C1. O 1000mg was also given on D8 and D15 of C1. A was given after O on D1 of each C unless split dosing was pursued, in which case A was initiated on D2 C1 after the D2 O dose. R/R MZL pts received A 1200mg in combination with R 375mg/m2 by IV infusion on D1 C1 and A 1200mg by IV infusion and R 1400mg by SC injection on D1 C2-8 as induction. A was always given after R. In all pts, A 1200mg was continued from C9 for 10 Cs. Anti-CD20 premedication was given per protocol. The primary endpoint in the MCL and MZL cohorts was end of induction (EOI) response; in the WM cohort it was best overall response (BOR). Data cut-off was December 17, 2019, and the primary analysis presents results at EOI. Results:A total of 30 MCL, 21 MZL (3 nodal [N], 10 extra nodal [including 7 non-gastric (EN) and 3 gastric (G)] and 8 splenic [S]) and 4 WM pts were enrolled (median age: 67 years [range: 47-87]; 56.4% male). The majority of MCL (80%) and MZL (67%) pts had Ann Arbor stage IV disease. Refractory disease was present in 36.7% of MCL, 23.8% of MZL and 25.0% (1/4) of WM pts. Median prior systemic treatments was 2 in the MCL (range: 1-8) and MZL (1-7) groups and 3.5 (1-4) in the WM group; 14/30 pts (46.7%) in the MCL group had received prior ibrutinib. In the MCL, MZL and WM groups, respectively, 50.0%, 71.4% and 75.0% (3/4) of pts completed O or R treatment, 23.3%, 38.1% and 25.0% (1/4) completed A induction, and 10.0%, 9.5% and 0% had ongoing treatment at cut-off. Median numbers of O/A infusions were 9.5/8 (range: 2-10/1-18) (MCL group) and 10/9.5 (2-10/1-18) (WM group); in MZL, median numbers of R/A administrations were 8/15 (2-8/2-18). Median observation times were 9.99 (range: 0.9-23.4), 15.77 (2.7-22.3) and 8.43 (1.3-15.3) months in MCL, MZL and WM pts, respectively. Treatment-emergent adverse events (TEAEs) occurred in 93.3% of MCL, 95.2% of MZL and 100% (4/4) of WM pts. Overall, the most frequent TEAEs were anemia, neutropenia and thrombocytopenia (18.2% each), and the most frequent serious TEAEs were pneumonia (5.5%) and sepsis (3.6%). The most frequent Grade (Gr) 3-4 AEs were neutropenia (16.4%), thrombocytopenia (9.1%) and pneumonia (9.1%), and Gr 3-4 AEs occurred in 53.3%, 47.6% and 100% (4/4) of MCL, MZL and WM pts, respectively. Serious AEs occurred in 30.0%, 23.8% and 0% of MCL, MZL and WM pts, respectively. AEs of special interest occurred in 33.3% of MCL, 33.3% of MZL and 50.0% (2/4) of WM pts, with the most frequent being peripheral edema (10.0% MCL, 4.8% MZL). TEAEs leading to discontinuation occurred in 10.0%, 19.0% and 0% of MCL, MZL and WM pts, respectively. One fatal TEAE (pneumonia) occurred in each of the MCL and MZL groups. Objective response rates (ORR) at EOI were 16.7%, 42.9% and 0% (complete response in 3.3%, 14.3% and 0%) and BOR rates were 33.3%, 52.4% and 0% in MCL, MZL and WM pts, respectively. For MZL subtypes, ORRs were 66.7% N, 57.1% EN, 66.7% G and 12.5% S; BOR rates were 66.7%, 71.4%, 66.7% and 25.0%, respectively. Three MCL pts, 1 MZL patient and 1 WM patient discontinued before the first post-baseline assessment and were considered non-responders. Median duration of response was 6.8 (range: 0.0-14.2) months for MCL and not reached (NR) for MZL. Median progression free survival was 10.1 months (95% CI: 3.4, 14.0) for MCL, NR for MZL and 6.7 months (95% CI: 6.2, 7.2) for WM. Median overall survival was 23.4 months (95% CI: 12.3, 23.4) for MCL and NR for MZL or WM. Median time to next treatment was 10.5 months (95% CI: 6.7, 23.4) for MCL, 22.3 months (95% CI: 14.3, 22.3) for MZL and NR for WM. Conclusions:A in combination with O or R has an acceptable safety profile in R/R MCL and MZL pts and no new safety signals were identified. A promising response rate was observed in MZL pts. WM data were inconclusive due to the small sample size. Disclosures Panayiotidis: AbbVie:Honoraria, Research Funding;Roche:Honoraria, Research Funding;Novartis:Honoraria, Research Funding;Genesis:Honoraria, Research Funding;Janssen:Honoraria;Gilead:Honoraria;Takeda:Honoraria;Phizer:Honoraria;ASH:Honoraria.Thieblemont:Novartis:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Hospira:Research Funding;Kyte:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Gilead:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Roche:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;Cellectis:Speakers Bureau;BMS:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Janssen:Honoraria;University Employement:Current Employment;Celgene:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.Ptushkin:Alexion Pharmaceuticals Inc.:Honoraria.Marin Niebla:Janssen:Membership on an entity's Board of Directors or advisory committees, Other: Participation in advisory committees, continuing Medical Education for companies' staff members, Speakers Bureau;Takeda:Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Roche:Other: Continuing Medical Education for companies' staff members, Speakers Bureau;Celgene:Speakers Bureau;Abbvie:Speakers Bureau;Gilead:Membership on an entity's Board of Directors or advisory committees, Other: Participation in advisory committees, continuing Medical Education for companies' staff members;Kiowa Kirin:Membership on an entity's Board of Directors or advisory committees, Other: Participation in advisory committees, continuing Medical Education for companies' staff members;BeiGene:Membership on an entity's Board of Directors or advisory committees.Garcia-Sanz:Novartis:Honoraria;Janssen:Honoraria, Research Funding;Incyte:Research Funding;Gilead:Honoraria, Research Funding;BMS:Honoraria;Amgen:Membership on an entity's Board of Directors or advisory committees;Pharmacyclics:Honoraria;Takeda:Consultancy, Research Funding.Zaritskey:Janssen:Research Funding;Celgene:Research Funding;Almazov centre:Current Employment.Le Gouill:Roche Genentech, Janssen-Cilag and Abbvie, Celgene, Jazz pharmaceutical, Gilead-kite, Loxo, Daiichi-Sankyo and Servier:Honoraria;Loxo Oncology at Lilly:Consultancy.Buske:Morphosys:Membership on an entity's Board of Directors or advisory committees;Roche, Janssen, Bayer, MSD:Research Funding;Roche, Janssen, AbbVie, Pfizer, Celltrion:Honoraria, Speakers Bureau.Van Hoef:Lipomed AG:Ended employment in the past 24 months;Roche AG:Current Employment.Perretti:F. Hoffmann-La Roche Ltd:Current Employment.Tomiczek:F. Hoffmann-La Roche Ltd, Basel, Switzerland:Current Employment.Stathis:ADC Therapeutcis:Other, Research Funding;Merck:Other, Research Funding;Pfizer:Other, Research Funding;Loxo:Honoraria, Other, Research Funding;PharmaMar:Other: Travel Grant;Bayer:Other, Research Funding;MEI Pharma:Other, Research Funding;Novartis:Other, Research Funding;Cellestia:Research Funding;Roche:Other, Research Funding;Member of the steering committee of the trial of this abstract:Other;Abbvie:Other: Travel Grant. OffLabel Disclosure: GAZYVA (obinutuzumab) is a CD20-directed cytolytic antibody indicated: in combination with chlorambucil, for the treatment of pts with previously untreated CLL; in combination with bendamustine followed by GAZYVA monotherapy, for the treatment of pts with FL who relapsed after, or are refractory to, a rituximab-containing regimen; in combination with chemo followed by GAZYVA monotherapy in pts achieving at least a partial remission, for the treatment of adult pts with previously untreated stage II bulky, III or IV FL. RITUXAN (rituximab) is a CD20-directed cytolytic antibody indicated for the treatment of adult pts with: R/R, low grade or follicular, CD20-positive, B-cell NHL as a single agent; previously untreated follicular, CD20-positive, B-cell NHL in combination with first line chemo and, in pts achieving a CR or PR to a rituximab product in combination with chemo, as single-agent maintenance therapy; non-progressing (including SD), low-grade, CD20 positive, B-cell NHL as a single agent after first-line CVP chemo; previously untreated diffuse large B-cell, CD20-positive, NHL in combination with CHOP or other anthracycline-based chemo regimens; previously untreated and previously treated CD20-positive CLL in combination with FC. RITUXAN HYCELA is a combination of rituximab, a CD20-directed cytolytic antibody, and hyaluronidase human, an endoglycosidase, indicated for the treatment of adult pts with: R/R FL as a single agent; previously untreated FL in combination with first line chemo and, in pts achieving a CR or PR to rituximab in combination with chemo, as single agent maintenance therapy; non-progressing (including SD), FL as a single agent after first-line CVP chemotherapy; previously untreated DLBCL in combination with CHOP or other anthracycline-based chemo regimens; previously untreated and previously treated CLL. TECENTRIQ is a programmed death-ligand 1 (PD-L1) blocking antibody indicated: for the treatment of adult pts with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemo and whose tumors express PD-L1* or are not eligible for any platinum-containing chemo regardless of PD-L1 status, or have PD during or following any platinum-containing chemo, or within 12 months of neoadjuvant or adjuvant chemo; for the first-line treatment of adult pts with metastatic NSCLC whose tumors have high PD-L1 expression* with no EGFR or ALK genomic tumor aberrations; in combination with bevacizumab (bev), pacl*taxel, and carboplatin, for the first-line treatment of adult pts with metastatic non-squamous NSCLC with no EGFR or ALK genomic tumor aberrations; in combination with pacl*taxel protein-bound and carboplatin for the first-line treatment of adult pts with metastatic non-squamous NSCLC with no EGFR or ALK genomic tumor aberrations; for the treatment of adult pts with metastatic NSCLC who have PD during or following platinum-containing chemo; in combination with pacl*taxel protein-bound for the treatment of adult pts with unresectable locally advanced or metastatic TNBC whose tumors express PD-L1*; in combination with carboplatin and etoposide, for the first-line treatment of adult pts with ES-SCLC; in combination with bev for the treatment of pts with unresectable or metastatic HCC who have not received prior systemic therapy. *As determined by an FDA-approved test

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Khan, Niloufer, JonathanU.Peled, Antonio LC Gomes, SeanM.Devlin, Carlos Rondon-Clavo, Annelie Clurman, JohnB.Slingerland, et al. "Loss of Microbiota Diversity after Autologous Stem Cell Transplant Is Comparable to Injury in Allogeneic Stem Cell Transplant." Blood 132, Supplement 1 (November29, 2018): 608. http://dx.doi.org/10.1182/blood-2018-99-110857.

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Abstract Introduction: We have previously reported that clinically relevant, dramatic reductions occur in intestinal bacterial diversity during allogeneic hematopoietic stem cell transplant (allo-HSCT). These are likely attributable to antibiotic exposure, nutritional alterations, and intestinal mucosa injury from high-dose chemotherapy. Patients undergoing autologous hematopoietic stem cell transplantation (AHCT) also receive antibiotics and experience nutritional alterations due to mucositis and other gastrointestinal toxicities. We hypothesized that the pattern of dysbiosis seen in AHCT patients would reflect the changes in allo-HSCT patients. Here, we present a novel analysis of microbiota diversity in AHCT patients from two independent institutions. Methods: We retrospectively identified a cohort of 365 patients (median age 60 years) who underwent AHCT for treatment of hematologic malignancy between May 2009 to February 2018 at two large-volume transplant centers in the US. The population was diverse in terms of histology, conditioning regimens and remission status prior to transplant, with 179 (49%) patients diagnosed with multiple myeloma, 153 (42%) patients diagnosed with lymphoma, and 33 (9%) patients with other diseases. Stool samples from the selected patients were collected approximately weekly during inpatient hospitalization. Sequencing of the V4-V5 region of the bacterial 16S rRNA genes from all samples was performed on the Illumina platform at a central site. Microbial diversity was measured by the Simpson reciprocal a-diversity index (S). We defined the pre-AHCT period as days -10 to 0, and computed median values for patients with multiple samples within that period. We additionally defined monodomination of the microbiota as a single operational taxonomic unit comprising >30% of bacterial abundance. For comparison, we sequenced samples from 17 healthy volunteers and used a public dataset of sequences from 313 healthy volunteers from the NIH Human Microbiome Project (HMP). Median pre-transplant microbial diversity in the healthy patient and AHCT groups was compared by a pairwise Wilcox test to a retrospective cohort of allo-HSCT patients. Results: We evaluated 857 samples from 365 adult patients undergoing AHCT, with 316 patients from Memorial Sloan Kettering Cancer Center (MSKCC) and 49 patients from Duke University Medical Center (DUMC). Median pre-transplant diversity in AHCT patients from both centers was significantly lower than in normal controls (Fig 1A) (HMP vs MSKCC AHCT, S=12.05 vs. 9.19, p<0.005; HMP vs DUMC AHCT, S=12.05 vs 6.91, p<0.005) and reduced in both AHCT patients and allo-HSCT patients (MSKCC AHCT vs MSKCC allo-HSCT, S = 12.05 vs 8.74, p=0.53). In samples taken from days -10 to +30 after transplant, diversity decreased comparably after AHCT and allo-HSCT across both centers, while AHCT patients demonstrated a more rapid recovery at day +30 compared to allo-HSCT patients (Fig 1B). Finally, monodominance was observed in the samples (Fig 1C), with Streptococcus as the most common genus. The cumulative incidence of intestinal domination by any organism was >50% by day 0 and was >75% by day +14. Conclusion: Microbial diversity is reduced prior to transplant in both AHCT and allo-HSCT patients. Loss of diversity after AHCT occurs across centers and the degree of injury is comparable to the dysbiosis in allo-HSCT patients. Preliminary analysis suggests that lower diversity may correlate with worse progression-free survival (PFS) in myeloma patients in our diverse AHCT cohort. Given the known associations of alterations in microbiota composition with toxicities and overall survival in allo-HSCT patients, further evaluation of microbiota injury and its associations with toxicities, PFS, and overall survival (OS) in AHCT patients is warranted. Figure 1: A: The median Simpson reciprocal a-diversity index (S) of pre-transplant (days -10 to 0) samples of AHCT and allo-HSCT patients from two centers, as well as two cohorts of healthy volunteers, was plotted and a pairwise Wilcox test was performed, with p-values as indicated. B: (S) was plotted against time relative to allo-HSCT (on L) and AHCT (on R), for samples collected from day -10 to day +30. Larger values indicate greater diversity. C: Microbiota composition and changes in bacterial monodominance after transplant (days -14 to +28); the most common genus post-transplant is Streptococcus. Figure 1. Figure 1. Disclosures Peled: Seres Therapeutics: Research Funding. Sauter:Juno Therapeutics: Consultancy, Research Funding; Sanofi-Genzyme: Consultancy, Research Funding; Spectrum Pharmaceuticals: Consultancy; Novartis: Consultancy; Precision Biosciences: Consultancy; Kite: Consultancy. Shah:Amgen: Research Funding; Janssen: Research Funding. Perales:Novartis: Other: Personal fees; Incyte: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees and Clinical trial support; Merck: Other: Personal fees; Takeda: Other: Personal fees; Abbvie: Other: Personal fees. Jenq:Ziopharm Oncology: Consultancy; Seres Therapeutics, Inc.: Membership on an entity's Board of Directors or advisory committees; MicrobiomeDx: Consultancy; Seres Therapeutics, Inc.: Patents & Royalties.

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Rott,M., A.M.Schmidt, V.Joshi, C.Masters, S.Godkin, and R.Johnson. "First Report of Colombian datura virus in Brugmansia in Canada." Plant Disease 93, no.2 (February 2009): 196. http://dx.doi.org/10.1094/pdis-93-2-0196b.

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Colombian datura virus (CDV) was first described in 1968 (3) and has since been reported in Europe (4), Japan (see 4 for additional references), and the United States (1,2). CDV is a member of the family Potyviridae with flexuous, filamentous nucleocapsids that can be transmitted by mechanical inoculation and grafting and is known to be vectored by the common aphid Myzus persicae. In the fall of 2007, five Brugmansia plants of unknown species from a Parks Board Collection in a Lower Mainland nursery, British Columbia, Canada, were found to be displaying symptoms typical of a viral infection: chlorotic flecking and mottling on leaves, leaf shrivel, and vein banding. Symptomatic leaves from these five plants were tested by ELISA (Immuno Strip Test, Agdia, Elkhart, IN) for several common viruses including Impatiens necrotic spot, Tobacco mosaic, Cucumber mosaic, and Tomato spotted wilt viruses and found to be negative for all. However, rub inoculations onto the herbaceous indicators Nicotiana occidentalis and N. benthamiana resulted in severe symptom formation including necrosis, wilting, shriveling, stunted growth, petiole and stem tip collapse, as well as collapse from the base of the plants, and plant death within 2 weeks after inoculation. A leaf dip assay of the original infected Brugmansia sample and infected N. benthamiana tissue revealed flexuous, potyvirus-like particles with the electron microscope (EM). On the basis of the Brugmansia leaf symptoms and the EM results, a possible infection with CDV was suspected. Primers CDV-3 and CDV-NIb5, specific to CDV (4), were used in a reverse transcription (RT)-PCR assay that amplified an approximate 1,600-bp fragment from the original Brugmansia sample and inoculated N. bentamiana and N. occidentalis plants. The amplified portion of the genome is the extreme 3′ terminus and includes the 3′ noncoding sequence, the viral coat protein gene, and part of the viral replicase gene. Fragments were cloned into pCR2.1-TOPO (Invitrogen, San Diego, CA) and two clones from each plant (total of six clones) were sequenced in both directions. Sequences of all clones were essentially identical, with only three nucleotide differences among the clones (GenBank Accession No. EU571230). BLASTn analysis revealed the highest match to several CDV isolates ranging from 98.7 to 99.5% nucleotide sequence identity. BLASTp analysis of the 451 amino acid viral polyprotein translation product gave a similarly high match with CDV isolates, with the highest match to a Hungarian isolate of CDV (GenBank Accession No. CAD26690) of 99.8% identity, or only one mismatch out of 451 amino acids. An additional group of 15 large symptomless Brugmansia plants, located approximately 6 m from the five symptomatic plants, were also tested by RT-PCR and found to be positive. These 15 plants were of a different but also unknown species of Brugmansia. In conclusion, analysis of symptomatic Brugmansia from a Canadian collection by transfer of disease to herbaceous indicators, EM, RT-PCR, and genomic sequence comparisons, are consistent with the detection and identification of the potyvirus Colombian datura virus. To our knowledge, this is the first report of this viral pathogen in Canada. References: (1) S. Adkins et al. Phytopathology (Abstr.) 95(suppl.):S2, 2005. (2) C. R. Fry et al. J. Phytopathol. 152:200, 2004. (3) R. P. Kahn and R. Bartels. Phytopathology 58:58, 1968. (4) J. Schubert et al. J. Phytopathol. 154:343, 2006.

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John, Albert. "Reviewer Acknowledgements for International Journal of Chemistry, Vol. 11, No. 2." International Journal of Chemistry 11, no.2 (October30, 2019): 164. http://dx.doi.org/10.5539/ijc.v11n2p164.

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International Journal of Chemistry wishes to acknowledge the following individuals for their assistance with peer review of manuscripts for this issue. Their help and contributions in maintaining the quality of the journal is greatly appreciated. Many authors, regardless of whether International Journal of Chemistry publishes their work, appreciate the helpful feedback provided by the reviewers. &nbsp; Reviewers for Volume 11, Number 2 &nbsp; Abdul Rouf Dar, University of Florida, USA Ahmad Galadima, Usmanu Danfodiyo University, Nigeria Ahmet Ozan Gezerman, Yildiz Technical University, Turkey Amer A. Taqa, Mosul University, Iraq Asghari Gul, COMSATS University Islamabad, Pakistan Ayodele Temidayo Odularu, University of Fort Hare, South Africa Binod P Pandey, The Pennsylvania State University, USA Brice Ulrich Saha Foudjo, Catholic University of Cameroon, Cameroon Elnaz Rostampour, Islamic Azad University, Iran Fes Sun Fabiyi, Bowen University, Nigeria Ho Soon Min, INTI International University, Malaysia Hongbin Liu, University of Washington, USA Kevin C. Cannon, Penn State Abington, USA Khaldun M. Al Azzam, Batterjee Medical College for Sciences and Technology, Saudi Arabia Merve Kaya, Toros Agri., Turkey Mohamed Abass, Ain Shams University, Egypt Monira Nessem Michael, National institute of standards (NIS), Egypt Mustafa Oguzhan Kaya, Siirt University, Turkey Nanda Gunawardhana, Saga University, Japan Nanthaphong Khamthong, Rangsit University, Thailand Rabia Rehman, University of the Punjab, Pakistan Rodrigo Vieira Rodrigues, University of S&atilde;o Paulo, Brazil Sie-Tiong Ha, Universiti Tunku Abdul Rahman, Malaysia Sitaram Acharya, Texas Christian University, USA Souheyla Boudjema, University of Tlemcen, Algeria Syed A. A. Rizvi, Hampton University, USA Tony Di Feo, Natural Resources Canada, Canada Zhixin Tian, Tongji University, China Albert John On behalf of, The Editorial Board of International Journal of Chemistry Canadian Center of Science and Education

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Fischer, Kirsten, Othman Al-Sawaf, Anna-Maria Fink, Mark Dixon, Jasmin Bahlo, Simon Warburton, ThomasJ.Kipps, et al. "Safety and Efficacy of Venetoclax and Obinutuzumab in Patients with Previously Untreated Chronic Lymphocytic Leukemia (CLL) and Coexisting Medical Conditions: Final Results of the Run-in Phase of the Randomized CLL14 Trial (BO25323)." Blood 128, no.22 (December2, 2016): 2054. http://dx.doi.org/10.1182/blood.v128.22.2054.2054.

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Abstract Introduction The BCL-2 inhibitor venetoclax has yielded promising results in patients with relapsed/refractory chronic lymphocytic leukemia (CLL), both as monotherapy and in combination with rituximab. The CLL14 trial is a prospective, open-label, multicenter randomized phase III trial to compare the efficacy and safety of obinutuzumab and venetoclax with obinutuzumab and chlorambucil in patients with previously untreated CLL and coexisting medical conditions. Prior to opening the randomized phase, a run-in phase was performed to assess the tolerability of obinutuzumab and venetoclax in this particular patient population. Here, we report the final results on safety and efficacy of this run-in phase. Method The protocol specified to enroll 12 previously untreated patients with confirmed CLL and with coexisting medical conditions assessed by cumulative illness rating scale (CIRS) total score > 6 and/or estimated creatinine clearance (CrCl) < 70 mL/min requiring treatment according to iwCLL criteria into the run-in phase. All patients received 6 cycles of obinutuzumab and venetoclax followed by 6 additional cycles of venetoclax. Obinutuzumab was administered intravenously with 100 mg on day 1, 900 mg on day 2 (option to deliver 1000 mg on day 1), 1000 mg on day 8 and day 15 of cycle 1 and 1000 mg on day1 for cycles 2-6. A gradual weekly dose ramp-up of venetoclax with 20 mg, 50 mg, 100 mg, 200 mg up to 400 mg was administered starting at day 22 of cycle 1. Risk assessment for tumor lysis syndrome (TLS) based on absolute lymphocyte count and tumor burden was performed before treatment in order to direct prophylactic measures. Study defined stopping criteria for all 12 patients included: one treatment-related death or one grade 4 adverse event related to a clinical tumor lysis syndrome (TLS) despite protocol-specified prophylaxis. Adverse events were graded per the NCI CTCAE v.4 criteria. Final response to treatment including assessment for minimal residual disease (MRD) in peripheral blood by ASO-PCR was assessed per the iwCLL guidelines 3 months after the end of treatment, at month 15. Results Between December 2014 and April 2015, 13 previously untreated patients from Australia, Canada, Germany, New Zealand, United States and Spain were enrolled into the trial. Baseline patient characteristics are summarized in Table 1. The median age was 75 years (range 59 - 88) and 62% of the patients were classified as Binet stage C; 38% of the patients were assessed at medium risk and 62% at high risk for TLS. One patient developed a grade-4 infusion related reaction (IRR) during the first dose of obinutuzumab and was therefore withdrawn from the trial according to the protocol requirements. Eleven of 12 patients completed treatment. One patient discontinued treatment after 6 cycles of obinutuzumab and venetoclax and 2 additional cycles of venetoclax due to patient´s wish. All patients experienced at least one adverse event. The commonest adverse events are summarized in Table 2. No clinical TLS was reported. At month 15, 11 of 12 patients were evaluable for final response assessment. All patients responded to therapy. Complete remissions occurred in 7 of the 12 patients including one complete remission with incomplete bone marrow recovery. Ten of 12 patients had no detectable (<10-4) minimal residual disease (MRD) in peripheral blood and one patient was assessed intermediate (≥10-4<10-2). At month 15, there were no events of disease progression or deaths, translating into an estimated progression-free survival of of 100%. Conclusions The treatment regimen developed for the experimental arm of the CLL14 trial comprising obinutuzumab monotherapy for one cycle followed by venetoclax and obinutuzumab in previously untreated, elderly patients with CLL and coexisting medical conditions appears well tolerated and effective. The target population in this trial consists of elderly patients with clinically meaningful comorbidities in addition to CLL. None of the protocol defined stopping safety criteria for the run-in phase of the trial were met. The treatment induced substantial responses with an unprecedentedly high number of MRD negative responses seen in all but one evaluable patients including those with poor prognostic features. The main phase of the CLL14 trial was opened in August 2015 and completed recruitment in August 2016 after 432 patients had been randomized. Disclosures Fischer: Hoffmann-LaRoche: Other: Travel grants. Al-Sawaf:Gilead: Other: Travel grants. Fink:AbbVie: Other: Travel grants; Mundipharma: Other: Travel grants; Celgene: Other: Travel grants, Research Funding; Hoffmann-LaRoche: Other: Travel grants. Dixon:Roche Products Limited: Employment, Equity Ownership. Bahlo:F. Hoffman-La Roche: Honoraria, Other: Travel grant. Warburton:Roche UK: Employment. Kipps:Gilead: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Pharmacyclics, LLC, an AbbVie Company: Consultancy, Honoraria. Weinkove:Avalia Immunotherapies: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Other: Travel grants; Janssen: Honoraria; Capital & Coast District Health Board: Employment; Malaghan Institute of Medical Research: Employment; Health Research Council of New Zealand: Research Funding; Australasian Leukaemia & Lymphoma Group: Membership on an entity's Board of Directors or advisory committees. Robinson:Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Abbvie: Consultancy; Lundbeck: Consultancy; Gilead: Consultancy. Dreyling:Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau. Opat:Roche: Consultancy, Honoraria, Other: Provision of subsidised drugs, Research Funding. Owen:Pharmacyclics: Research Funding; Janssen: Honoraria; Gilead: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Abbvie: Honoraria; Lundbeck: Honoraria, Research Funding; Novartis: Honoraria. López:Novartis: Consultancy; Abbvie: Consultancy; Merck Sharp & Dohme: Consultancy; Janssen: Consultancy; Roche: Consultancy; Gilead: Consultancy. Humphrey:Genentech, Inc.: Employment. Humerickhouse:AbbVie: Employment. Tausch:Amgen: Other: Travel support; Gilead: Other: Travel support, Speakers Bureau; Celgene: Other: Travel support. Eichhorst:Abbvie: Consultancy; Mundipharma: Consultancy, Research Funding, Speakers Bureau; Roche: Consultancy, Research Funding, Speakers Bureau. Wendtner:Genetech: Consultancy, Honoraria, Research Funding; Hoffmann‐La Roche: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; Munipharma: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Research Funding; Janssen‐Cilag: Consultancy, Honoraria, Research Funding; Servier: Consultancy, Honoraria, Research Funding. Langerak:F. Hofmann-LaRoche, Genentech: Research Funding; InVivoScribe Technologies: Patents & Royalties: Royalties are provided to European Network (EuroClonality). Ritgen:Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding. Boettcher:Roche: Research Funding; Abbvie: Research Funding; Celgene: Research Funding. Stilgenbauer:Mundipharma: Consultancy, Honoraria, Other: Travel grants , Research Funding; Novartis: Consultancy, Honoraria, Other: Travel grants , Research Funding; Sanofi: Consultancy, Honoraria, Other: Travel grants , Research Funding; Boehringer Ingelheim: Consultancy, Honoraria, Other: Travel grants , Research Funding; Janssen: Consultancy, Honoraria, Other: Travel grants , Research Funding; Pharmacyclics: Consultancy, Honoraria, Other: Travel grants , Research Funding; Celgene: Consultancy, Honoraria, Other: Travel grants , Research Funding; GSK: Consultancy, Honoraria, Other: Travel grants , Research Funding; Amgen: Consultancy, Honoraria, Other: Travel grants, Research Funding; Genentech: Consultancy, Honoraria, Other: Travel grants , Research Funding; AbbVie: Consultancy, Honoraria, Other: Travel grants, Research Funding; Gilead: Consultancy, Honoraria, Other: Travel grants , Research Funding; Genzyme: Consultancy, Honoraria, Other: Travel grants , Research Funding; Hoffmann-La Roche: Consultancy, Honoraria, Other: Travel grants , Research Funding. Goede:Roche: Consultancy, Honoraria, Other: Travel grant, Research Funding; GlaxoSmithKline: Honoraria; Gilead: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Mobasher:Genentech, Inc.: Employment. Hallek:Janssen-Cilag: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Mundipharma: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; F. Hoffmann-LaRoche: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau.

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Chan, Onyee, Onyemaechi Okolo, Muhammad Husnain, Irbaz Bin Riaz, and Faiz Anwer. "Outcome of Immune-Suppressive Therapy (IST) and Hematopoietic Stem Cell Transplantation (SCT) in Patients with Aplastic Anemia: A Retrospective Single Center Experience." Blood 128, no.22 (December2, 2016): 5081. http://dx.doi.org/10.1182/blood.v128.22.5081.5081.

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Abstract Background Aplastic anemia (AA), characterized by bone marrow failure resulting in pancytopenia, is a rare condition with an incidence rate of 2-3 cases per million per year internationally(Montane et al., 2008). Treatment consists of immune-suppressive therapy (IST), hematopoietic stem cell transplantation (SCT), or both depending on patient factors such as age and comorbidities. Some studies suggest patients who received SCT from alternative transplant donor, specifically matched unrelated donor (MUD), may experience similar outcomes as the time-tested matched related donor (MRD)(Kennedy-Nasser et al., 2006, Buchholz et al., 2008). We compare the survivals of our patients under different treatments and further examine how transplant donor types affect outcomes. Methods We retrospectively retrieved the medical records of patients with the ICD-9 and ICD-10 code of aplastic anemia in their diagnosis seen at the University of Arizona Cancer Center/University Medical Center at Tucson, Arizona from 1990 to 2016. There are 104 patients returned with these search criteria. After chart review, patients who did not have aplastic anemia or with insufficient data for analysis were removed, leaving a total of 65 patients in the cohort. Survival analyses with 95% confidence intervals (CI) were estimated by Kaplan-Meier method and compared by log-rank test. P-values less than 0.05 were considered to be statistically significant. All statistical analyses were performed using R Statistical Software (Foundation for Statistical Computing, Vienna, Austria). Results A total of 65 patients were included in the study with 25 males (38%) and 40 female (62%). Median age at diagnosis was 22 years ranging from 1 to 64 years. Overall survival (OS) was 70%+/-7.2 (95% CI, 56.8-85.3). Patients were divided into 3 treatment categories including those who had received IST only (13/65, 20%), transplant only (41/65, 63%), and combination (11/65, 17%). OS for each category was 92%+/-7.4, 64%+/-8.5, and 82%+/-11.6, respectively as shown in Figure1A(p=0.321). Applying the same analysis on patients who had received treatment in the last decade from 2007 and beyond showed improved outcomes for those who had received transplant only (9/29, 31%) with OS of 73%+/-17% as demonstrated in Figure1B(p<0.001). Further analysis by comparing OS in patients with various types of transplant donor including MRD (33/65, 51%), MUD (7/65, 11%), umbilical cord blood (UCB) (3/65, 5%), and mismatched (9/65, 14%) showed OS of 76%+/-9%, 71%+/-17%, 67%+/-27%, and 33%+/-16%, respectively as shown in Figure 2 (p=0.012). No significant correlations were found between the amount of CD34 transfused and survival. Conclusions Our findings suggest IST remains the treatment method with the highest OS for those who are eligible. Advances in supportive care during transplant period in the last decade translate to better outcomes for these patients. For those who are appropriate for SCT, MRD is the optimal donor choice. References BUCHHOLZ, S., DAMMANN, E., KOENECKE, C., STADLER, M., FRANZKE, A., BLASCZYK, R., BREMER, M., KRAUTER, J., HERTENSTEIN, B., GANSER, A. & EDER, M. 2008. Allogeneic stem cell transplantation from related and unrelated donors for aplastic anaemia in adults--a single-centre experience. Ann Hematol, 87, 551-6. KENNEDY-NASSER, A. A., LEUNG, K. S., MAHAJAN, A., WEISS, H. L., ARCE, J. A., GOTTSCHALK, S., CARRUM, G., KHAN, S. P., HESLOP, H. E., BRENNER, M. K., BOLLARD, C. M. & KRANCE, R. A. 2006. Comparable outcomes of matched-related and alternative donor stem cell transplantation for pediatric severe aplastic anemia. Biol Blood Marrow Transplant, 12, 1277-84. MONTANE, E., IBANEZ, L., VIDAL, X., BALLARIN, E., PUIG, R., GARCIA, N., LAPORTE, J. R., CATALAN GROUP FOR STUDY OF, A. & APLASTIC, A. 2008. Epidemiology of aplastic anemia: a prospective multicenter study. Haematologica, 93, 518-23. Figure 1 Overall survival (n=65) in patients who had received immune-suppressive therapy (IST) only, hematopoietic stem cell transplantation (SCT) only, or both. B: OS (n=29) in patients with different types of treatment from year 2007 and beyond. Figure 1. Overall survival (n=65) in patients who had received immune-suppressive therapy (IST) only, hematopoietic stem cell transplantation (SCT) only, or both. B: OS (n=29) in patients with different types of treatment from year 2007 and beyond. Figure 2 Overall survival (n=65) in patients who had received immune-suppressive therapy (IST) only and hematopoietic stem cell transplantation (SCT) by different donor types including matched related donor (MRD), matched unrelated donor (MUD), umbilical cord blood (UCB), and others. Figure 2. Overall survival (n=65) in patients who had received immune-suppressive therapy (IST) only and hematopoietic stem cell transplantation (SCT) by different donor types including matched related donor (MRD), matched unrelated donor (MUD), umbilical cord blood (UCB), and others. Figure 3 Figure 3. Disclosures Anwer: Seattle Genetics: Other: Advisory Board Participant; Incyte: Speakers Bureau.

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Wakita, Satoshi, Hiroki Yamaguchi, Yoshio Mitamura, Fumiko Kosaka, Koiti Inokuchi, and Kazuo Dan. "Highly Sensitive Quenching Probe (QProbe) Method Is Useful to Detect c-Kit Mutation and to Predict Relapse of t(8;21)(q22;q22) Acute Myeloid Leukemia." Blood 114, no.22 (November20, 2009): 2646. http://dx.doi.org/10.1182/blood.v114.22.2646.2646.

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Abstract Abstract 2646 Poster Board II-622 Background: t(8;21)(q22;q22) acute myeloid leukemia (t(8;21) AML) show a high rate of complete remission (CR) and prolonged CR duration, especially following consolidation chemotherapy with high-dose cytarabine (HD-ARAC), and are thought to have a better prognosis than other AML patients. Nevertheless, only approximately 50% of patients were alive at 5 years. This suggests that some patients have more aggressive leukemic phenotypes and indicates the need for predictive molecular marker of relapse and treatment optimization with novel and/or more aggressive therapies such as stem cell transplantation.Recently, several groups reported that c-kit mutation (MutKIT) defined an unfavorable subgroup in t(8;21) AML. However MutKIT has been reported approximately 20% at diagnostic samples of core binding factor leukemia. It is possible that MutKIT are more high frequency at relapse sample of t(8;21) AML. In the present study, we analyzed samples collected at diagnosis and relapse to investigate the role of MutKIT s and Flt3 internal tandem duplication (ITD) in t(8;21) AML. Methods: We analyzed MutKIT and Flt3 ITD among 32 t(8;21) AML patients diagnosed between 1991 to 2009 at the Nippon Medical School. All of them were succeeded achieving CR, but 18 patients (56.3%) relapsed, became refractory chemotherapy, and poor prognosis. Exon 8 and 17 of MutKIT were analyzed by direct sequence and QProbe-system (ARKRAY, Inc. Kyoto, Japan). QProbe-system was high sensitivity mutation screening method, detected approximately 1% MutKIT using mutation specific guanine quenching probe (Leukemia Res 32 (2008) 1462–1467). FLT3 ITD was analyzed by PCR amplification. Results: Using direct sequence, MutKITs were found in 5 (18.5%) of the 27 patients at diagnosis (D816V: 3 patients AN822K: 2 patients), and 7 (46.6%) of 15 patients at relapse. Interestingly 3 patients were detected MutKIT at only relapse (D816V: 2 patients AN822K: 1 patient). All mutations found in exon 17 clustered within the A-loop. Next we analyzed to detected very slight amount of mutation by QProbe-system. N822K were newly found of the 3 patients at diagnosis in spite of negative by direct sequence Finally MutKIT were found 8 (29.6%) at diagnosis. Flt3 ITD were found in 2 (9.5%) of the 21 patents at diagnosis, and none of 15 patients at relapse. 2 patients with Flt3 ITD were not accompanied MutKIT. All of N822K newly found by QProbe-system and Flt3 ITD positive patients were relapsed but turn to mutation negative. To evaluate the importance of MutKIT as a predicted relapse, we analyzed the cumulative incidence of relapse (CIR) and relapse free survival (RFS) of these patients with Kaplan-Meier method. The CIR was higher for patients with MutKIT (p=0.040, Wild type c-kit (WtKIT): 45.8% vs MutKIT: 87.5%). In direct sequencing method, The RFS tend to be shorter for patient with MutKIT, but no significant differences (p=0.260; WtKIT: 30 months vs MutKIT: 11 months).On the other hand, in QProbe-system, the median RFS was shorter for patients with MutKIT (p=0.033; WtKIT: 64 months vs MutKIT: 11 months). In addition of FLT3-ITD analysis, median RFS was shorter for patients with MutKIT or FLT3 ITD (p=0.005; Wild type of both genes: 64 months vs MutKIT or FLT3 ITD: 10 months). Additionally, we compared overall survival (OS) of wild type of both genes with MutKIT or FLT3 ITD. The OS tend to be shorter for patient with MutKIT or FLT3 ITD, but no significant differences. Discussion: In this study, we confirmed the prognostic significance of MutKIT in patients with t(8;21) AML when we use the highly sensitive quenching probe method (QProbe-system). We showed that QProbe-system is quite useful in predicting the prognosis of patients with t(8;21) AML and in determining its therapeutic strategy including tyrosine kinase inhibitors and/or up-front stem cell transplantation. We also revealed the important role of MutKIT (46.7%) at relapse, but several questions were still remained. It is unknown for some patients how to gain MutKIT at only relapse and why mutations detected at diagnosis were disappeared at relapse. We need further study to clarify the function and commitment of MutKIT in relapse of t(8;21) AML. Disclosures: No relevant conflicts of interest to declare.

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Jain, Preetesh, Guilin Tang, C.CameronYin, Chi Young Ok, Lucy Navsaria, Maria Badillo, Wendy Chen, et al. "Complex Karyotype Is a Significant Predictor for Worst Outcomes in Patients with Mantle Cell Lymphoma (MCL) Treated with BTK Inhibitors - Comprehensive Analysis of 396 Patients." Blood 136, Supplement 1 (November5, 2020): 32–33. http://dx.doi.org/10.1182/blood-2020-137473.

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Introduction: Complex karyotype (Cx) refers to ≥3 unrelated cytogenetic abnormalities in addition to t(11;14) in MCL patients (pts). In limited pts treated with chemotherapy, pts with Cx exhibited poor outcomes compared to non-Cx group. Prognostic impact of Cx in pts treated with BTKi is unclear. We present the largest and most comprehensive analysis on the prognostic impact of Cx in MCL pts. Methods: We analyzed charts from 396 MCL pts with karyotype data. (271 were non-Cx and 125 were Cx). Karyotype status at initial MCL diagnosis was denovo (DN) while previously treated pts were secondary (S). Among Cx, n=80 pts were DN-Cx and 45 were S-Cx while in non-Cx group, 224 were DN-non-Cx and S-non-Cx were 47 pts. TP53 mutation/FISH data was available (n=134; 46 positive, 88 negative). Pt characteristics were obtained from the time of karyotype testing (at initial diagnosis in DN and at the time of testing in S group). Overall survival (OS) was calculated from test date to the last follow up and progression free survival (PFS) after first line therapy from treatment date to date of progression/death. Univariate and multivariate logistic regression modeled the risk of event and treatment response. Results: Cx pts had significant differences compared to non-Cx, including median Ki-67 (40 vs 20%), sMIPI (median 6 vs 4), poor performance status (p.s.), CNS involvement (7 vs 2%), blastoid (22 vs 7%), pleomorphic (12 vs 3%), higher LDH, WBC, ALC and β2M levels and low Hb and platelet counts, prior BTKi (35 vs 15%), TP53 positive (75 vs 17%), shorter median follow up from the test date (18 vs 33 months). Overall, 70 (56%) in Cx and 70 (26%) in non-Cx had died. Univariate analysis for OS showed, advanced age, higher values of Ki-67, WBC, LDH, β2M, MIPI scores, number of chromosomal aberrations, B symptoms, splenomegaly, CNS involvement, poor p.s., prior BTKi, blastoid/pleomorphic histology, TP53 positive status, non-responder to first line therapy and Cx (median 35 months vs 101 months in non-Cx respectively; p&lt;0.001) to be significantly associated with shorter OS (1-A). In addition, S-Cx pts had the worst OS (median 2 months compared to 20, 13 and 55 months in DN-Cx, S-non-Cx and DN-non-Cx respectively; p&lt;0.001) (1-B). In MVA, Cx; HR 1.83 (95% CI 1.08-3.12; p=0.02) and higher age, MIPI score, number of prior therapies, blastoid, CNS involvement, S-Cx category and non-responder to first line therapies predicted for significantly shorter OS. Due to many missing values for Ki-67% and TP53, these variables could not be fitted in model. In addition to other factors, Cx was associated with shorter PFS in univariate (median 12 vs 48 months for non-Cx; p&lt;0.001) but not in MVA. S-Cx pts had the worst PFS (median 7 months compared to 61, 32 and 138 months in DN-Cx, S-non-Cx and DN-non-Cx respectively; p&lt;0.001). Factors predictive for shorter PFS in the MVA, were advanced age, higher MIPI score, lines of prior therapies. Prior BTKi therapy is associated with significantly shorter PFS (2 months vs 13 months without prior BTKi; p=0.02) but not OS. Overall, Cx predicted for higher risk of not achieving CR from all different treatments - OR 3.3 (95% CI 2.01-5.14; p&lt; 0.001). Among the 107 pts with Cx and 221 with non-Cx with available treatment data, 31 in Cx (1-C) and 101 in non-Cx were treated with BTKi with/without chemo-immunotherapy. Median PFS in both Cx and non-Cx groups was significantly longer with BTKi based therapies compared to R-HCVAD, R-Chemo and other therapies (excluding CAR-T and 1 pt with venetoclax-BTKi). PFS in S-Cx category (n=36), the worst category for survival outcomes, was not influenced by BTKi but was improved with CAR-T therapy (1-D). BTKi therapy improved PFS and OS in Cx and DN-Cx categories compared to R-HCVAD, R-chemo, other therapies (with/without SCT) but did not impact on S-Cx category with the worst outcomes. Response rate to BTKi were (92% vs 74%; p=0.01) in pts with non-Cx and Cx respectively. Conclusions: Cx pts remain a high risk MCL cohort in the BTKi era. Within Cx pts, DN-Cx had better outcomes compared to S-Cx category with the worst outcomes. Outcomes and treatment responses in non-Cx were significantly superior compared to Cx pts. CAR-T therapy holds a great promise for improving outcomes in S-Cx karyotype MCL patients. Disclosures Westin: BMS: Consultancy, Research Funding; Kite: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Curis: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Astra Zeneca: Consultancy, Research Funding; Morphosys: Consultancy, Research Funding; 47: Research Funding; Novartis: Consultancy, Research Funding; Amgen: Consultancy. Nastoupil:Bayer: Honoraria; Gamida Cell: Honoraria; Gilead/KITE: Honoraria; Novartis: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Karus Therapeutics: Research Funding; Genentech, Inc.: Honoraria, Research Funding; LAM Therapeutics: Research Funding; TG Therapeutics: Honoraria, Research Funding; Merck: Research Funding; Celgene: Honoraria, Research Funding. Vega:NCI: Research Funding. Flowers:Burroughs Wellcome Fund: Research Funding; Eastern Cooperative Oncology Group: Research Funding; National Cancer Institute: Research Funding; V Foundation: Research Funding; AbbVie: Consultancy, Research Funding; Bayer: Consultancy; BeiGene: Consultancy; Celgene: Consultancy, Research Funding; TG Therapeutics: Research Funding; Millennium/Takeda: Consultancy, Research Funding; Acerta: Research Funding; Spectrum: Consultancy; Pharmacyclics/Janssen: Consultancy; Karyopharm: Consultancy; OptumRx: Consultancy; Gilead: Consultancy, Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Denovo Biopharma: Consultancy; Cancer Prevention and Research Institute of Texas: Research Funding; Kite: Research Funding; Leukemia and Lymphoma Society: Membership on an entity's Board of Directors or advisory committees. Wang:Acerta Pharma: Research Funding; Juno: Consultancy, Research Funding; AstraZeneca: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Oncternal: Consultancy, Research Funding; Lu Daopei Medical Group: Honoraria; Dava Oncology: Honoraria; Guidepoint Global: Consultancy; Celgene: Consultancy, Other: Travel, accommodation, expenses, Research Funding; BioInvent: Research Funding; InnoCare: Consultancy; OMI: Honoraria, Other: Travel, accommodation, expenses; Janssen: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; VelosBio: Research Funding; Verastem: Research Funding; Pharmacyclics: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; MoreHealth: Consultancy; Nobel Insights: Consultancy; Beijing Medical Award Foundation: Honoraria; OncLive: Honoraria; Targeted Oncology: Honoraria; Loxo Oncology: Consultancy, Research Funding; Kite Pharma: Consultancy, Other: Travel, accommodation, expenses, Research Funding; Pulse Biosciences: Consultancy; Molecular Templates: Research Funding.

48

Ben-Zacharia, Aliza, Meagan Adamson, Allison Boyd, Paula Hardeman, Jennifer Smrtka, Bryan Walker, and Tracy Walker. "Impact of Shared Decision Making on Disease-Modifying Drug Adherence in Multiple Sclerosis." International Journal of MS Care 20, no.6 (November1, 2018): 287–97. http://dx.doi.org/10.7224/1537-2073.2017-070.

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CME/CNE Information Activity Available Online: To access the article, post-test, and evaluation online, go to http://www.cmscscholar.org. Target Audience: The target audience for this activity is physicians, physician assistants, nursing professionals, and other health-care providers involved in the management of patients with multiple sclerosis (MS). Learning Objectives: Accreditation Statement: In support of improving patient care, this activity has been planned and implemented by the Consortium of Multiple Sclerosis Centers (CMSC) and Delaware Media Group. CMSC is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team. Physician Credit The CMSC designates this journal-based activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Nurse Credit The CMSC designates this enduring material for 1.0 contact hours (none in the area of pharmacology). Disclosures: , Editor in Chief of the International Journal of MS Care (IJMSC), has served as Physician Planner for this activity. He has received royalties from Springer Publishing, served on a speakers' bureau for Biogen, and done contracted research for Adamas Pharmaceuticals.Francois Bethoux, MD , has served as reviewer for this activity. She has disclosed no relevant financial relationships.Laurie Scudder, DNP, NP , has received consulting fees from Biogen, Bayer, EMD Serono, Celgene, Novartis, Genentech, and Genzyme and research grants from Biogen and Novartis.Aliza Ben-Zacharia, DNP, ANP, MSCN , has served on speakers' bureaus for Biogen, EMD Serono, Genentech, Novartis, Genzyme, Acorda, Teva, and Mallinckrodt.Meagan Adamson, DNP, FNP-BC, MSCN , has received consulting fees from Genzyme, served on a speakers' bureau/advisory board for EMD Serono, and has been a speaker for Teva Neurosciences and Biogen.Allison Boyd, MPAS, PA-C, MSCS , has disclosed no relevant financial relationships.Paula Hardeman, MPAS, PA-C , has served on advisory boards for Biogen, EMD Serono, Genentech, Novartis, Sanofi Genzyme, and Teva Neuroscience and as a speaker for EMD Serono, Genentech, Mallinckrodt, Sanofi Genzyme, and Teva Neuroscience; she receives salary from Biogen.Jennifer Smrtka, MSN, ARNP-C, MSCN , has received consulting fees from Biogen, EMD Serono, and Sanofi Genzyme and served on speakers' bureaus for Novartis and Biogen.Bryan Walker, MHS, PA-C , has received grant support from EMD Serono, Genzyme, and Teva and personal fees from Acorda, Genentech, Sanofi Genzyme, Mallinckrodt, and Teva, and served on speakers' bureaus for EMD Serono, Acorda, Teva, and Genzyme.Tracy Walker, FNP-C, WOCN, MSCN One peer reviewer for the IJMSC has received consulting fees from and participated on speakers' bureaus for Biogen, Novartis, Genentech, Sanofi Genzyme, and EMD Serono. The other peer reviewer has disclosed no relevant financial relationships. The staff at the IJMSC, CMSC, and Delaware Media Group who are in a position to influence content have disclosed no relevant financial relationships. Note: Financial relationships for some authors may have changed in the interval between listing these disclosures and publication of the article. Method of Participation: Release Date: December 1, 2018 Valid for Credit Through: December 1, 2019 In order to receive CME/CNE credit, participants must: Statements of Credit are awarded upon successful completion of the post-test with a passing score of &gt;70% and the evaluation. There is no fee to participate in this activity. Disclosure of Unlabeled Use: This educational activity may contain discussion of published and/or investigational uses of agents that are not approved by the FDA. CMSC and Delaware Media Group do not recommend the use of any agent outside of the labeled indications. The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of CMSC or Delaware Media Group. Disclaimer: Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any medications, diagnostic procedures, or treatments discussed in this publication should not be used by clinicians or other health-care professionals without first evaluating their patients' conditions, considering possible contraindications or risks, reviewing any applicable manufacturer's product information, and comparing any therapeutic approach with the recommendations of other authorities.

49

Han, Jin, SantoshL.Saraf, Michel Gowhari, Shivi Jain, RobertE.Molokie, and VictorR.Gordeuk. "Association of Inpatient Opioid Utilization and Readmission Risk in Sickle Cell Disease." Blood 132, Supplement 1 (November29, 2018): 4699. http://dx.doi.org/10.1182/blood-2018-99-114733.

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Abstract Background: Vaso-occlusive crisis (VOC) is the hallmark complication of sickle cell disease (SCD). The majority of SCD-related healthcare costs in the United States, estimated at $2.4 billion annually, are attributed to frequent healthcare utilization due to recurrent VOC (1-3). Risk factors such as the prescription of nonsteroidal anti-inflammatory drugs (NSAIDs) only without opioids, older age, and steroid treatment have been identified to be associated with readmissions in pediatric SCD patients (4, 5), but limited data exist about potential predictors for readmission in adults (6). The impact of inpatient opioid utilization on readmission was evaluated in this study. Methods: Seventy SCD adults treated at the University of Illinois Hospital from 2012-2016 had at least one hospitalization for uncomplicated VOC that was followed by a 30-day readmission (30-DR) and at least one hospitalization without a 30-DR. One hospitalization with a 30-DR and one hospitalization without a 30-DR from each patient were used to form the discovery cohort (a total of 140 hospitalizations from 70 unique patients). Patient characteristics, inpatient laboratory values, outpatient daily opioid use before admission, and inpatient daily opioid use were collected from the electronic medical records, and the ratio of the last inpatient day opioid dose/home opioid dose before admission was calculated. Among the 70 patients in the discovery cohort, 22 patients had more than one hospitalization with a 30-DR. The additional hospitalizations with a 30-DR and matched hospitalizations from the same patient without a 30-DR were used to form a validation cohort (a total of 62 hospitalizations from 22 unique patients). A Wilcoxon signed-rank test was performed to compare the ones with a 30-DR to the ones without. The study was approved by the Institutional Review Board prior to the initiation of chart review. Results: Among the 70 SCD patients identified, the median (IQR) age was 32.5 (25-44) years by the time of the first admission included in this cohort, and 67% were females, 76% were HbSS or Sbeta0 genotype, and 46% were on hydroxyurea before admission. The median (IQR) dose of daily outpatient opioids before the first admission was 170 (64-280) mg oral morphine equivalents (OME). When the hospitalizations without a 30-DR were compared to the ones with in the discovery cohort (Table 1), the ratio of last inpatient day opioid dose/home opioid dose was lower (1.5 vs. 1.9, p=0.024), whereas other relevant clinical variables including length of stay, pain score upon discharge, and hemoglobin or WBC upon discharge were not significantly different between the two groups (Table 1). The proportion of patients who used patient controlled analgesia (PCA) during admission, or underwent opioid dose tapering during hospitalizations, or converted IV opioids to oral ones before discharge was also comparable. In the validation cohort (Table 1), the ratio of last inpatient day opioid dose/home opioid dose in the group without a 30-DR was also lower than the ones with a 30-DR (1.4 vs. 2.0, p=0.033), whereas other clinical variables were comparable. Summary: Here we showed that a high ratio of last inpatient day opioid dose/home opioid dose is associated with readmission risk for sickle cell patients treated for uncomplicated VOC. The results suggest that proper tapering of inpatient opioid dose in reference to patient's home opioid dose before discharge may reduce the readmission risk. Reference: K. L. Hassell, Am J Prev Med38, S512 (Apr, 2010). S. Lanzkron, C. P. Carroll, C. Haywood, Jr., Am J Hematol85, 797 (Oct, 2010). T. L. Kauf, T. D. Coates, L. Huazhi, N. Mody-Patel, A. G. Hartzema, Am J Hematol84, 323 (Jun, 2009). L. M. Okorji, D. S. Muntz, R. I. Liem, Pediatr Blood Cancer64, (May, 2017). A. Sobota, D. A. Graham, E. J. Neufeld, M. M. Heeney, Pediatr Blood Cancer58, 61 (Jan, 2012). M. A. Brodsky et al., Am J Med130, 601 e9 (May, 2017). Disclosures No relevant conflicts of interest to declare.

50

Bruce, Aisha Aiko, Lauren Bolster, Catherine Corriveau-Bourque, Michelle Dang, GhaziS.Alotaibi, Maria McGrath, Mary Anne Venner, and HatoonM.Ezzat. "National Emergency Cards for Sickle Cell Disease: A Survey on Usefulness from the Patient Perspective." Blood 134, Supplement_1 (November13, 2019): 2171. http://dx.doi.org/10.1182/blood-2019-124467.

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Patients with Sickle Cell Disease (SCD) frequently present for emergency care with pain or fever. The rate of emergency visits/year is between 2-4 per patient every year with 12% of patients visiting the emergency 4 or more times/year1. National medical organizations in Canada and the United States recommend pain therapy within 30 minutes of arriving to the emergency department2,3. Feedback from patients in Canada reflected a lack of awareness of the medical community regarding the disease and optimal management. As a response Canadian Haemoglobinopathy Association2 (CanHaem), created the "Sickle Cell Disease Emergency Wallet Cards" which were inspired from the successful Hemophilia "Factor First Card4". The goal of the cards was to provide simple care instructions to an emergency responder and facilitate timely care for patients in crisis. These wallet cards have recommendations for treatment of pain and fever within 30 minutes, patient's diagnosis, program contact details, and patient's individual pain plan. The cards have been in circulation for 4 years. The purpose of this study was to determine if the cards are used by parents and patients as intended. Research Questions: 1.Are the CanHaem Cards used by patients and families? 2. Do patients find the card helpful in facilitating their care delivery? Methods: The surveys were administered to patients and/or proxies. Prior to survey distribution three parents/patients have verified the utility of the questions, the content and the readability of the survey. The survey was translated into French/Arabic by two independent translators per language. It was distributed in Alberta and British Columbia, Canada in specialty clinics known to use the cards. The University of Alberta Ethics Board deemed the project a quality improvement initiative and the ARECCI tool: A pRoject Ethics Community Consensus Initiative was completed prior to quality improvement project start. Results: 140/184 participants completed the survey. The response rate: 76%. Demographics: 91% province of Alberta. Proxy: 49%; Patients: 51%. The majority of respondents were female: 54%, median age: 37 years (range 16-84 years). See graphs 1-4 below: 72.3% felt the card was helpful in their care. 78.6% carry the physical card (purse, wallet, and diaper bag), while 10.7% have a picture on their phone, 9.3% don't carry the card, 7.1% state they never received a card. The majority (63.6%) show the card at first contact in emergency, 48.9% felt staff read the card. Total of 68 comments. 67.6% of comments were positive: "Sense of security"; "Get us in to see the doctor faster..." Neutral comments (22%) ranged from requests for lamination to provider response to the card being variable "sometimes it is faster and sometime(s) doesn't really change anything". Finally, 10% were negative reflecting long wait times "Good concept, the idea itself is great. Execution... could be improved greatly", and requests for more information on the card. Conclusion: In Canada, SCD is an uncommon disease and many healthcare providers may not be aware of national and international guidelines regarding acute presentations. To help facilitate knowledge transfer and to aid communication with emergency services, CanHaem created wallet cards as a Canada-wide initiative. This survey demonstrates the patient/parent perspective of the emergency cards. Eighty-nine percent of patients/proxies carried the card (either digitally or physically) and 63% showed the card in the acute care setting. The discrepancy between those who carry the card and those who show it may reflect that numerous respondents stated they had not required emergency care since receiving the card as well some respondents were "carried away by the pain and forget to use the card". Comments revealed a sense of security and patient's appreciation for having the card available to them indicating the value of card to patients. The card demonstrates a simple and low cost intervention to facilitate emergency care for hemoglobinopathy patients. References: 1. Paulukonis ST et al. Emergency department utilization by Californians with sickle cell disease. Ped Blood and Ca 2017. doi: 1002/pbc.26390 2. CanHaem https://www.canhaem.org/healthcare-professionals/ 3. Evidence-Based Management of Sickle Cell Disease: Expert Panel, 2014. 4. Canadian Hemophilia Society. Stop the Bleeding. https://www.hemophilia.ca/files/ER%20CARD%20E_%20Jan%2009.pdf Figure Disclosures Ezzat: Novartis: Honoraria, Speakers Bureau; ApoPharma: Research Funding.

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Journal articles: 'Medical Board of Columbia (S.C.)' – Grafiati (2024)

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