Статті в журналах: "Scientific American, inc"

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&NA;. "American Society of EEG Technologists, Inc., Twenty-Sixth Annual Scientific Meeting." Journal of Clinical Neurophysiology 2, no. 2 (April 1985): 201. http://dx.doi.org/10.1097/00004691-198504000-00006.

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&NA;, &NA;. "American Society of EEG Technologists, Inc., Twenty-Seventh Annual Scientific Program." Journal of Clinical Neurophysiology 3, no. 2 (April 1986): 177. http://dx.doi.org/10.1097/00004691-198604000-00017.

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Rogers, T. D. "Scientific American. 09 1992, volume 267, Special issue: ‘Mind and Brain’. Scientific American, Inc., 415 Madison Avenue, New York, NY 10017, USA." Psychiatric Bulletin 17, no. 3 (March 1993): 190. http://dx.doi.org/10.1192/pb.17.3.190.

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Hagins, Debbie, Princy Kumar, Michael Saag, Anson K. Wurapa, Indira Brar, Daniel Berger, Olayemi Osiyemi, et al. "1046. Week 48 Outcomes from the BRAAVE 2020 Study: A Randomized Switch to B/F/TAF in African American Adults with HIV." Open Forum Infectious Diseases 7, Supplement_1 (October 1, 2020): S552—S553. http://dx.doi.org/10.1093/ofid/ofaa439.1232.

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Abstract Background Black Americans are disproportionately impacted by HIV. The BRAAVE 2020 study, evaluated the safety and efficacy of switching to the guidelines-recommended single-tablet regimen bictegravir, emtricitabine, tenofovir alafenamide (B/F/TAF) in Black adults through week (W) 48. Methods Adults with HIV who self-identified as Black or African American and were virologically suppressed on 2 NRTIs plus a 3rd agent were randomized (2:1) to switch to open-label B/F/TAF once daily or stay on their baseline regimen (SBR). Prior virologic failure was allowed except failure on an INSTI. Prior resistance to NNRTIs, PIs and/or NRTIs was permitted except K65R/E/N, ≥3 thymidine analog mutations or T69-insertions. Primary INSTI-resistance was excluded. SBR participants switched to B/F/TAF at W24. Efficacy was assessed at the W24 (1○ endpoint, noninferiority margin 6%) and at W48 as the proportion with HIV-1 RNA ≥ 50 c/mL by FDA Snapshot and by changes in CD4 count. Safety was assessed by adverse events (AE) and lab results. Results 495 were randomized and treated (B/F/TAF n=330, SBR n=165): 32% cis women, 2% transgender women, median age 49 y (range 18-79), 10% had pre-existing M184V/I mutation (Table 1), and 62% lived in the US South. At W24, 1% (2/328) on B/F/TAF vs 2% (3/165) on SBR had HIV-1 RNA ≥50 c/mL (difference -1.2%; 95% CI -4.8% to 0.9%) demonstrating noninferiority of B/F/TAF; 2 with pre-existing primary INSTI resistance were excluded from analysis. 163 assigned to SBR completed W24 and switched to B/F/TAF (SBR to B/F/TAF). At W48 1% (3/328) originally randomized to B/F/TAF and 0 SBR to B/F/TAF had HIV-1 RNA ≥ 50 c/mL (Table 2). The presence of baseline NRTI resistance did not affect the efficacy of B/F/TAF. No treatment emergent resistance was detected. The mean (SD) changes in CD4 were +7 cells/mm3 (189) for B/F/TAF and -8 cells/mm3 (159) for SBR to B/F/TAF. Median (IQR) weight increased 0.9 kg (-1.5, 4.1) and 0.6 kg (-1.0, 3.1) for B/F/TAF and SBR to B/F/TAF groups, respectively. Study drug-related AEs occurred in 10% of participants while on B/F/TAF; most were grade 1. Table 1. Table 2. Conclusion Switching to B/F/TAF was highly effective for Black adults regardless of baseline regimen or pre-existing NRTI resistance and was associated with few treatment related AEs or discontinuations. Disclosures Debbie Hagins, MD, Gilead Sciences Inc. (Consultant, Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member)Janssen (Grant/Research Support)Merck (Consultant, Grant/Research Support, Advisor or Review Panel member)Viiv Healthcare (Consultant, Grant/Research Support, Advisor or Review Panel member) Princy Kumar, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Michael Saag, MD, Gilead Sciences Inc. (Consultant, Grant/Research Support, Scientific Research Study Investigator)Merck (Consultant, Grant/Research Support)Proteus (Grant/Research Support)Viiv Healthcare (Consultant, Grant/Research Support) Anson K. Wurapa, MD, Gilead Sciences Inc. (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member)GlaxoSmithKline (Grant/Research Support)Janssen (Grant/Research Support, Advisor or Review Panel member)Pfizer (Grant/Research Support) Indira Brar, MD, Gilead (Speaker’s Bureau)janssen (Speaker’s Bureau)ViiV (Speaker’s Bureau) Daniel Berger, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Olayemi Osiyemi, M.D, GlaxoSmithKline (Advisor or Review Panel member, Speaker’s Bureau)ViiV Healthcare (Advisor or Review Panel member, Speaker’s Bureau) Corrilynn Hileman, MD, Gilead Sciences Inc. (Consultant, Scientific Research Study Investigator) Moti Ramgopal, MD FACP FIDSA, AbbVie (Speaker’s Bureau)Allergan (Speaker’s Bureau)Gilead Sciences Inc. (Consultant, Scientific Research Study Investigator, Speaker’s Bureau)Janssen (Speaker’s Bureau)Merck (Consultant)Viiv Healthcare (Consultant) Cheryl McDonald, MD, Gilead Sciences Inc. (Grant/Research Support, Scientific Research Study Investigator, Speaker’s Bureau)Janssen (Grant/Research Support)Merck (Grant/Research Support, Speaker’s Bureau)Viiv Healthcare (Grant/Research Support) Christiana Blair, MS, Gilead Sciences (Employee, Shareholder) Kristen Andreatta, MSc, Gilead Sciences (Employee, Shareholder) Sean E. Collins, MD, MS, Gilead Sciences (Employee) Diana M. Brainard, MD, Gilead Sciences (Employee) Hal Martin, MD, MPH, Gilead Sciences Inc. (Employee, Shareholder)

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Barabashev, A. G., A. M. Kamalyan, and D. V. Ponomareva. "Protection of the Rights of Subjects of Scientific and Technological Activity: Oracle v. Google." Lex Russica, no. 8 (August 29, 2019): 138–47. http://dx.doi.org/10.17803/1729-5920.2019.153.8.138-147.

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The focus of this paper is one of the key cases in the field of protection of the results of intellectual activity considered by foreign courts in recent years — the «Oracle v. Google» case. The authors analyze the background of the case, focus on the main conclusions made by the American court in the course of the dispute. Particular attention is given to the protection of copyright in relation to the lines of code, as well as aspects of patent protection. The authors assess the conclusions of «American Themis» and forecast the impact of this decision on the protection of the rights of subjects of scientific and technological activity. In the context of Oracle v. Google the authors compare the practice of the Court of Justice of the EU as a judicial institution of the European Union. In particular, following the case of SAS Institute Inc. v World Programming Ltd, which is under consideration in the Court of the EU, the authors compare the American and European approaches to the problem of protection of the program code by legal means. In conclusion, the authors attempt to identify the possible risks for the subjects of scientific and technological activities (primarily for software developers) inherent in the decision in the case of Oracle v Google.

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Míguez, José, Jacobo Porteiro, Raquel Pérez-Orozco, and Miguel Gómez. "Technology Evolution in Membrane-Based CCS." Energies 11, no. 11 (November 14, 2018): 3153. http://dx.doi.org/10.3390/en11113153.

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In recent years, many CO2 capture technologies have been developed due to growing awareness about the importance of reducing greenhouse gas emissions. In this paper, publications from the last decade addressing this topic were analyzed, paying special attention to patent status to provide useful information for policymakers, industry, and businesses and to help determine the direction of future research. To show the most current patent activity related to carbon capture using membrane technology, we collected 2749 patent documents and 572 scientific papers. The results demonstrated that membranes are a developing field, with the number of applications growing at a steady pace, exceeding 100 applications per year in 2013 and 2014. North American assignees were the main contributors, with the greatest number of patents owned by companies such as UOP LLC, Kilimanjaro Energy Inc., and Membrane Technology and Research Inc., making up 26% of the total number of published patents. Asian countries (China, Japan, and Korea) and international offices were also important knowledge sources, providing 29% and 24% of the documents, respectively. Furthermore, this paper highlights 10 more valuable patents regarding their degree of innovation and citations, classified as Y02C 10/10 according to the Cooperative Patent Classification (CPC) criteria.

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Kaplan, Sheldon L., Adi Klein, Mark Kellogg, Andrea T. Cruz, Kristina G. Hulten, Cesar A. Arias, Richard Gordon, et al. "112. A Rapid Host-Protein Signature Based on TNF-related Apoptosis-Induced Ligand (TRAIL), Interferon Gamma Induced Protein-10 (IP-10) and C-Reactive Protein (CRP) Accurately Differentiates Between Bacterial and Viral Infection in Febrile Children: Apollo Sub-Study." Open Forum Infectious Diseases 8, Supplement_1 (November 1, 2021): S69. http://dx.doi.org/10.1093/ofid/ofab466.112.

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Abstract Background Identifying infectious etiology is essential for appropriate patient management, including antibiotic use. A host-protein signature for differentiating bacterial from viral infection has exhibited robust performance (AUC of 0.9, 95% CI 0.86-0.95) in prior studies. Performance data was lacking for a broad pediatric population recruited in emergency departments (EDs) and urgent care centers (UCCs). Methods Non-immunocompromised children were recruited prospectively from 5 EDs and 3 UCCs in the U.S. and 1 ED in Israel between May 2019 and August 2020. Eligibility required physician’s clinical suspicion of acute infection and reported fever. Reference standard etiology was adjudicated by experts based on clinical, laboratory, radiological, microbiological and follow-up data. For the primary analysis, experts blinded to one another, to the host-signature results and also to procalcitonin and CRP, classified cases as bacterial or viral. For the secondary analysis, experts blinded to one another and the host signature results, were permitted to classify cases as bacterial, viral or indeterminate; indeterminates were removed from the secondary analysis. Host signature (comprising TRAIL, IP-10 and CRP; MeMed BV®) was measured using a rapid platform (MeMed Key®) generating a bacterial likelihood score (0-100) in 15 minutes. Results The study cohort comprised 162 children (median age, 5.5 yrs; interquartile range, 8.5), of whom 69 (43%) presented within 2 days of symptom onset and 37 (23%) were hospitalized for a median of 3 days. Respiratory tract infection was the predominant syndrome (11% lower and 44% upper). Host signature attained AUC 0.87 (0.74-1) and 0.92 (0.79-1) in the primary and secondary analysis, respectively. With higher the signature score, there was a significantly higher likelihood of bacterial infection (p< 0.001; Table 1). The 3 bacterial infections assigned score < 35 (false negative) would have been identifiable by physical examination (Table 2). Increasing host signature score is associated with increasing likelihood of bacterial infection across both the primary and secondary cohort The performance of the host signature score in differentiating between bacterial and viral infection was evaluated by allocating children to one of five score bins and within each bin according to their adjudication label and determining if there is a meaningful increase in the relative likelihood of bacterial infection across the bins based on the Cochrane-Armitage test of trend. PPV, positive predictive value. NPV, negative predictive value. *Includes patients adjudicated as non-infectious Three children assigned a bacterial adjudication label and a score of 35 or less (false negatives) have bacterial infections identifiable in physical exam Conclusion The host-protein signature measured using a rapid platform attained robust performance in differentiating bacterial vs viral infection in children with acute febrile illness, supporting its potential to enhance rational use of antibiotics in the ED and UCC. Disclosures Sheldon L. Kaplan, MD, Pfizer (Research Grant or Support) Mark Kellogg, PhD, MeMed (Scientific Research Study Investigator) Andrea T. Cruz, MD, MPH, American Academy of Pediatrics (Individual(s) Involved: Self): editorial board member Kristina G. Hulten, PhD, Pfizer (Research Grant or Support) Cesar A. Arias, M.D., MSc, Ph.D., FIDSA, Entasis Therapeutics (Grant/Research Support)MeMed Diagnostics (Grant/Research Support)Merk (Grant/Research Support) Richard Gordon, MD, MeMed (Scientific Research Study Investigator) Sergey Motov, MD, MeMed (Scientific Research Study Investigator) Theresa Jacob, PHD MPH, MeMed (Scientific Research Study Investigator) Natasha Ballard, MD, MeMed (Scientific Research Study Investigator) George Suits, MD, MeMed (Scientific Research Study Investigator) Jeffrey Harris, MD, MeMed (Scientific Research Study Investigator) Maanit Shapira, Ph.D, MeMed (Scientific Research Study Investigator) Richard E. Rothman, PhD, MD, Chem bio (Grant/Research Support) Karen C. Carroll, MD, MeMed (Scientific Research Study Investigator)Meridian Diagnostics, Inc. (Grant/Research Support)Pattern Diagnostics (Advisor or Review Panel member)Scanogen, Inc. (Advisor or Review Panel member) Karen C. Carroll, MD, Pattern Diagnostics, Inc. (Individual(s) Involved: Self): Grant/Research Support; Scanogen, Inc. (Individual(s) Involved: Self): Consultant Leticia M. Ryan, MD MPH, MeMed (Scientific Research Study Investigator) Richard Bachur, MD, MeMed (Scientific Research Study Investigator)

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Al-Saadi, Mahmoud, Carlos Malvestutto, Mohammad Mahdee Sobhanie, Courtney Hebert, Nora Colburn, and Mark Lustberg. "318. Description of Patients Readmitted within 30 Days from COVID-19 Hospitalization." Open Forum Infectious Diseases 8, Supplement_1 (November 1, 2021): S264—S265. http://dx.doi.org/10.1093/ofid/ofab466.520.

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Abstract Background Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to increased hospitalizations and utilization of critical care services. There are few studies describing co-morbidities and demographics associated with patients re-admitted within 30-days of discharge. The purpose of this study is to describe this patient population. Methods This was a single-center, retrospective study at The Ohio State University Wexner Medical Center to identify patients who were admitted secondary to SARS-CoV-2 and required readmission within 30 days due to complications that might be associated with COVID-19. Adults admitted between 3/15/2020 and 11/15/2020 were included in this study. Baseline demographics including age, gender and race in addition to select comorbidities were identified. Results 250 patients were identified who were readmitted for various reasons. Readmitted patients had a median age of 55 years, 44% were male, and 41.2% were Black/African American. 62.4% of the population was obese (BMI ≥30 kg/m2) with 21.6% with a BMI ≥ 40 kg/m2. The top three co-morbidities seen included Diabetes Mellitus (DM) (32.2%), Hyperlipidemia (48.3%) and Hypertension (51.7%). Conclusion Though this study lacked a comparator group, it is clear that patients readmitted with all cause etiologies were disproportionally Black/African-American and obese, with a high prevalence of DM, hyperlipidemia, and hypertension. We recommend close monitoring of patients in these groups to reduce COVID19 readmissions. This is the first step in identifying which patients may be more likely to develop complications and required readmission, the next step is to compare these patients to those that were not readmitted to develop a risk model for readmission. Disclosures Carlos Malvestutto, M.D., Lilly (Scientific Research Study Investigator)Regeneron Inc. (Scientific Research Study Investigator)ViiV Healthcare (Advisor or Review Panel member) Mohammad Mahdee Sobhanie, M.D., Regeneron (Scientific Research Study Investigator)Regeneron (Scientific Research Study Investigator, Was a sub-investigator for Regeneron 2066 and 2069)

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Lubin, Joan, and Jeanne Vaccaro. "The Sexological Floorplan." TSQ 10, no. 3-4 (November 1, 2023): 350–68. http://dx.doi.org/10.1215/23289252-10900886.

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Abstract This essay animates the concept-metaphor of the sexological floorplan across sites of sexological self-reflection in its incipient institutional form to propose a model of trans study. We begin by speculating on the relationship between the history of sexological incorporation and the hesitant institutionality of trans study. In the context of a racially segregated postwar American culture reorganizing its senses of normative gender and moral sexual practice, the sexological project to limn the category “trans” became a site of interaction between multiple vectors of social experience and varieties of scientific classification. This essay considers four women differently subjected to sexological scrutiny on the basis of sex, and tracks how that sexual basis articulates with gender, race, and sexuality to map the floorplan of institutionalizing sexual knowledge. We consider four women whose circulation through and labor within the Kinsey Institute for Sex Research, Inc., maps the terrain of sexology's bids for credibility. Their respective roles in the business of sexology (the public face of gender transformation, a working housewife, a sympathetic social scientist, a long-suffering librarian) and respective racial, gender, and sexual identities made each differently disposed to and differently subjected to sexological ways of looking. By attending to each of these figures in turn, a view onto the sexological floorplan emerges with social and historical density, overlaid with the labors of self-determination inside the architectures of scientific capture.

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Williamson, Jeffrey F., Bert M. Coursey, Larry A. DeWerd, William F. Hanson, Ravinder Nath, and Geoffrey Ibbott. "Guidance to users of Nycomed Amersham and North American Scientific, Inc., I-125 Interstitial Sources: Dosimetry and calibration changes: Recommendations of the American Association of Physicists in Medicine Radiation Therapy Committee Ad Hoc Subcommittee." Medical Physics 26, no. 4 (April 1999): 570–73. http://dx.doi.org/10.1118/1.598570.

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Fergie, Jaime, Manjiri D. Pawaskar, Phani Veerkani, Salome Samant, Carolyn Harley, Joanna MacEwan, Taylor T. Schwartz, Shikha Surati, and James H. Conway. "1387. Current practices in the diagnosis and treatment of varicella infections in the United States." Open Forum Infectious Diseases 7, Supplement_1 (October 1, 2020): S703—S704. http://dx.doi.org/10.1093/ofid/ofaa439.1569.

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Abstract Background The Advisory Committee on Immunization Practices recommended a 1 dose varicella immunization program in 1996, expanding this to include 2 doses in 2006. As a result, more than 3.5 million cases of varicella, 9,000 hospitalizations, and 100 deaths are prevented annually in the United States. Since varicella infections have become uncommon, the response of health care providers (HCPs) to patients presenting with varicella symptoms may result in misdiagnosis and/ mistreatment. This study investigated the diagnostic and treatment strategies used by HCPs for managing varicella infections in US children. Methods An online cross-sectional survey of licensed HCPs was conducted, after an Institution review board approval and HCP consent. 8 clinical vignettes with information on patients with varying varicella symptoms (representing uncomplicated and complicated cases) were presented. For each vignette, HCPs selected a diagnosis and appropriate intervention(s) from pre-determined lists. Descriptive analyses were performed. Results A total of 153 HCPs (50 nurses, 103 doctors) completed the survey. Mean age was 44 years, 62% were female, and 82% were licensed after 1995. Varicella infection was correctly diagnosed 79% of the time. HCPs were able to recognize uncomplicated cases of varicella 85% of the time and complicated cases 61% of the time. HCPs recommended the correct intervention 43% of the time for uncomplicated cases and 25% of the time for complicated cases. For example, HCPs recommended antibiotics 17% of the time and/or antivirals 18% of the time (Table 1), of which 25% and 69% (respectively) were not appropriate per the American Academy of Pediatrics guidelines respectively. Antibiotics were incorrectly recommended 6% of the time for uncomplicated cases of varicella. Table 1. Additional Diagnosis & Treatment Results Conclusion Given the low incidence of varicella infections in the US, complicated cases of varicella may be under-recognized or inappropriately treated by some HCPs. Additional training may help HCPs better recognize/ treat cases of varicella. Further, ensuring high rates of varicella vaccination is important to avoid vaccine preventable conditions and to minimize unnecessary exposure to antimicrobial and antiviral therapies. Disclosures Jaime Fergie, MD, AstraZeneca (Speaker’s Bureau)Sobi, Inc. (Speaker’s Bureau) Manjiri D. Pawaskar, PhD, Merck & Co., Inc (Employee, Shareholder) Phani Veerkani, MD, DrPH, Merck (Research Grant or Support) Salome Samant, MBBS, MPH, Merck & Co., Inc., Kenilworth, NJ, USA (Employee, Shareholder) Carolyn Harley, PhD, Merck (Consultant) Joanna MacEwan, PhD, PRECISIONheor (Employee) Taylor T. Schwartz, MPH, Merck (Consultant, Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Shikha Surati, MPH, Merck & Co., Inc. (Employee, Shareholder)

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Dille, E. A., S. S. King, K. L. Jones, J. F. Roser, and C. A. Pearl. "295POSSIBLE DOPAMINERGIC MECHANISM REGULATING THE EQUINE CORPUS LUTEUM." Reproduction, Fertility and Development 16, no. 2 (2004): 267. http://dx.doi.org/10.1071/rdv16n1ab295.

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Timing of embryo transfer to recipient mares is crucial to the success rate of an embryo transfer (ET) program. Recipient mares need a functional corpus luteum (CL) to maintain the early stages of pregnancy. Interference with luteal function appears to be a significant cause of failure with nonsurgical ET. Little is known about the endocrine control of luteal function in the mare, and the possibility of neuronal control of equine luteal function has not yet been studied. Dopamine (DA) has been shown to affect progesterone secretion in the bovine CL. Prior research in our laboratory suggested the possibility of dopaminergic regulation in the equine CL. The aim of this study was to document the presence of DA D1 receptor (D1r) and DA D2 receptor (D2r) within the equine CL. Immunocytochemistry (ICC) was performed on sections from 9 corpora lutea collected from a local equine abattoir. Tissues were stained using the avidin-biotin complex (ABC) method (Vectastain ABC Elite kit, Vector Laboratories, Burlingame, CA, USA). Tissues were fixed in 4% paraformaldehyde, embedded in paraffin, and cut into 5-μm sections. Tissue sections were deparaffinized and rehydrated;; endogenous peroxidase activity was quenched in 0.3% hydrogen peroxide in methanol at room temperature. To decrease nonspecific staining, tissue sections were incubated in goat serum (Vectastain ABC Elite kit). Tissue sections were then incubated overnight at 4°C with primary antibodies: Rabbit anti-Dopamine D1 receptor (Calbiochem, San Diego, CA, USA) or Rabbit anti-D2 receptor polyclonal antibody (Chemicon International, Inc, Temecula, CA, USA). Sections were then washed in PBS and incubated in biotinylated goat anti-rabbit IgG secondary antibody. After washing in PBS, sections were incubated in ABC. Sections were washed in PBS and the signal was visualized using 3-amino-9-ethylcarbazole (AEC Red, Vector Laboratories, Burlingame, CA, USA). Tissues were then counterstained with Immunomaster Hematoxylin (American Master Tech Scientific, Inc., Lodi, CA) to visualize the nuclei. As a negative control, tissues were incubated in normal rabbit serum instead of primary antibody, and as a positive control, the ICC procedure was performed on whole rat brain slices. Significant staining of luteal cells was observed using the D1r and D2r antibodies. Positive staining for D1r and D2r was seen throughout luteal cells;; however, no nuclear staining was observed. The presence of these receptors in equine CL tissue suggests a functional significance for DA in luteal function. Further research needs to be performed to determine the mechanistic function of dopamine in mare reproduction.

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Bock, Hans. "General Chemistry. International Student Edition. VonP. W. Atkins. Scientific American Inc., New York 1989 (Auslieferung: W. H. Freeman, Oxford). 989 S., Paperback £ 16.95. ISBN 0-7167-2053-1." Angewandte Chemie 103, no. 6 (June 1991): 736–37. http://dx.doi.org/10.1002/ange.19911030634.

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Kim, J., M. Kelly, and K. Beumer. "Engaging Pathologists in a Peer-to-Peer Learning Collaborative on HER2-Low Breast Cancer." American Journal of Clinical Pathology 158, Supplement_1 (November 1, 2022): S42—S43. http://dx.doi.org/10.1093/ajcp/aqac126.082.

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Abstract Introduction/Objective Recent advances in research have shown clinical effectiveness when targeting the lower range of HER2 expression (ie, HER2-low) in patients with metastatic breast cancer. American Society for Clinical Pathology worked in collaboration with Q Synthesis to develop a peer-to-peer learning collaborative to proactively prepare pathologists for HER2-low. This CME project was supported by an educational grant from AstraZeneca Pharmaceuticals LP and Daiichi Sankyo Inc. Methods/Case Report 38 pathologists participated in the ASCP HER2 Breast Trailblazers. For foundational knowledge, learners completed online modules covering scientific updates on HER2-low. Through small-group, case- based discussions, learners reviewed operational challenges and opportunities to prepare for HER2-low. They applied this knowledge to lead projects at their own institutions focusing on the anticipated changes around HER2-low. Results (if a Case Study enter NA) The learners identified the following challenges and opportunities: Defining HER2-low: Several learners had heard misconceptions around the definition of HER2-low. Recent studies have defined HER2-low as IHC 1+ or IHC 2+ with ISH-negative. Interobserver concordance with IHC 0 vs 1+: Several learners discussed the challenges around interpreting IHC 0 vs 1+. They felt that some pathologists may need guided feedback to improve their diagnostic skills. Use of IHC vs. ISH: Several learners only performed ISH for HER2 testing on all breast cancer samples. If HER2-low emerges as a third category, they would need to return to IHC. Implications for non-metastatic breast cancer: Recent HER2-low studies have focused on patients with metastatic breast cancer. If HER2-low emerges as a third category, it is unclear whether this designation will also be used in patients who have early-stage breast cancer. Leadership As pathologists prepare for HER2-low, they have opportunities to lead projects to assess and improve IHC interobserver concordance, coach others on IHC interpretation, increase operational efficiency, strength communication skills, and build up the team by proactively anticipating challenges around HER2-low. Conclusion HER2-low breast cancer may be emerging as a new category. Through a peer-to-peer learning collaborative, pathologists identified ways to proactively prepare and demonstrate leadership so that cancer centers and laboratories may be ready to embrace a new paradigm of HER2 classification in breast cancer.

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Ahrens, H. "Öztürk, Aydin & Edward C. van der Meulen (Chief Editors): The Frontiers of Statistical Scientific Theory and Industrial Applications. American Series in Mathematical and Management Sciences. American Sciences Press, Inc, Columbus, Ohio, 1991, 482 S., $ 98.75." Biometrical Journal 35, no. 2 (1993): 226. http://dx.doi.org/10.1002/bimj.4710350214.

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Raiko, Diana, Viktoriia Cherepanova, Ihor Sylka, Olha Podrez, and Irina Fedorenko. "Development of scientific and methodological approach to quantitative and qualitative assessment of intellectual property management in industrial enterprises." Eastern-European Journal of Enterprise Technologies 2, no. 13 (110) (April 30, 2021): 28–41. http://dx.doi.org/10.15587/1729-4061.2021.230262.

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The competitiveness, market value and income of an enterprise depend on the level of intellectual property management. Therefore, the aim of research is to develop, substantiate and test a scientific and methodological approach to a quantitative and qualitative assessment of the management of intellectual property of industrial enterprises. The originality of the proposed approach is that on the basis of the concept of "management of intellectual property" a procedure for current management has been developed, the main stage of which is a quantitative and qualitative assessment. The assessment is based on the structural and logical model, which is built according to two criteria. The criteria make it possible to determine the current state of the use of intellectual property (intangible assets) – a quantitative assessment, and the prospect of further use (intellectual potential) – a qualitative assessment. A quantitative assessment involves the calculation of indicators characterizing the state of assets, the dynamics of the impact on the market value of the enterprise, the profitability of production, which is proposed to be determined through the net cash flow from operating activities. A qualitative assessment is carried out in terms of components (information and investment, organizational and legal, economic, personnel and motivation), tools and relative indicators that characterize the intellectual potential of an industrial enterprise. The assessment is carried out using a general integral indicator, which is of practical importance, since it shows the existing level of intellectual property management and directions for improvement in the future. The approbation of the scientific and methodological approach was carried out on the example of three Ukrainian coke-chemical enterprises (CJSC Avdeevka Coke Plant, CJSC Zaporozhkoks, CJSC Yuzhkoks) of the American association SUNCOKE ENERGY, INC and the Polish association J.S.W. S.A. Group. Empirical studies for the period from 2015 to 2019 made it possible to build a scale for assessing the level of intellectual property management according to the Harrington function

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Kostyuchenko, N., and A. Zakorko. "TRANSNATIONAL COMPANIES’ STRATEGIC PLANNING IN THE CONTEXT OF THE GLOBAL SUSTAINABLE DEVELOPMENT GOALS." Vìsnik Sumsʹkogo deržavnogo unìversitetu, no. 4 (2019): 114–22. http://dx.doi.org/10.21272/1817-9215.2019.4-15.

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The paper is dedicated to the investigation of the impact of the Global Sustainable Development Goals on the strategic planning of transnational corporations and their competitiveness. The object of the paper is transnational corporations in the sector of fast-moving consumer goods, particularly: Danone S.A., Kraft Heinz, PepsiCo Inc., the Coca Cola company, Unilever PLC, P&G, Johnson& Johnson, Mondelez International, Nestle S.A., Philip Morris International, British American Tobacco. The article focuses on analysis of fast-moving consumer goods’ sector and examines the relevance of the companies’ activities to the Global Sustainable Development Goals. The role of “green” investments for competitiveness of transnational corporations has been identified. The information base of the paper is the United Nations’ information materials, Forbes information resources, the statistical data of NASDAQ, publications of famous audit and consulting companies (Deloitte, KPMG, PwC), transnational companies’ official reports, and scientific papers of Ukrainian and foreign researches. A rank of scientific research methods was applied in the paper: descriptive method - for general analysis of transnational companies’ strategic planning; analytical method and comparative method - for evaluation and analysis of transnational corporations’ stock prices and market capitalization in the fast-moving consumer goods’ sector; system analysis - for identification of the key characteristics of strategic planning of transnational corporations in the context of the Global Sustainable Development Goals. The authors propose recommendations that can be used while creating strategies for the development of international companies, including transnational corporations, as well as while analyzing the compliance of existing companies' strategies with the Global Sustainable Development Goals. Keywords: fast-moving consumer goods’ market, Global Report Initiative, Global Sustainable Development Goals, strategic planning, transnational corporations.

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18

Hamid, Muhammad Saad, Sarah C. Rutherford, Seongho Kim, Nancy L. Bartlett, Mary-Kate Malecek, Marcus Watkins, Kami J. Maddocks, et al. "North American Practice Patterns for PET-2 Positive Hodgkin Lymphoma." Blood 134, Supplement_1 (November 13, 2019): 1553. http://dx.doi.org/10.1182/blood-2019-131276.

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Introduction: A positive interim PET scan (PET2) following 2 cycles of ABVD for Hodgkin lymphoma (HL) is associated with a poor prognosis; several studies in advanced stage demonstrate benefit from escalating therapy. Definition of positivity (Deauville 3 (D3) vs Deauville 4/5 (D4/5)), initial treatment and response adaptive decisions may vary among clinicians. Data examining practice patterns in managing positive PET2 scans is lacking. We report practice patterns and outcomes for patients (pts) with positive PET2 results including D3 and D4/5 outcomes. Methods: Adult pts with classical HL and PET2 findings of D3, D4, and D5 after initial therapy between 01/01/2015 and 07/01/2019 were identified. Pts enrolled in clinical studies were excluded. Retrospective demographic, clinical, and treatment data were obtained and described from 14 academic and community sites across North America (NA). Progression-free survival (PFS) and overall survival (OS) were summarized by Kaplan-Meier curves and compared by log-rank test. Results: 166 PET2 positive pts were identified. Clinical characteristics included 54% (89/166) with advanced stage (III/IV) and 46% (77/166) with early stage (IA-IIB) disease. 152 pts (92%) were treated with initial ABVD like therapy and 14 pts (8%) with an alternate regimen (Table 1). After initial treatment, 163 pts demonstrated PET2 scores of D3 (n=33), D4 (n=99) and D5 (n=31). Of the 130 D4/5 pts; 23% (30/130) underwent therapeutic escalation and 77% (100/130) did not escalate. The complete response rate (CR) at end of treatment (EOT) for all D4/5 patients receiving escalation was 37% (11/30) compared to 45% (45/100) without escalation (p=0.43). (Table 2) The 12 month PFS was 54% (38.2-76.3) versus (vs) 69.2% (60.4-79.2) for escalation and no escalation respectively. Of the 66 D4/5 pts with advanced stage disease; 21% (14/66) had therapeutic escalation and 79% (52/66) did not escalate. CR at EOT was noted in 29% (4/14) with escalation vs 31% (16/52) without escalation (p=0.88). (Table 2) The 12 month PFS was 54.2% (32.9-89.3) vs 57.5% (44.9-73.7) for escalation and no escalation respectively. (Figure 1; Log Rank p=0.38). Of the 64 D4/5 pts with early stage disease; 75% (48/64) did not undergo escalation and 25% (16/64) had escalation. CR at EOT was noted in 44% (7/16) with escalation vs 60% (29/48) without escalation (p=0.26). (Table 2) The 12 month PFS was 54.7% (34.5-86.7) vs 80.8% (70.2-92.9) for escalation and no escalation respectively. Of the 33 D3 pts; 52% (17/33) de-escalated with the remainder (16/33) continuing on initial therapy. No D3 pt underwent escalation. In the 12 D3 pts with early stage disease, 50% (6/12) de-escalated. Of the 21 D3 pts with advanced stage disease; 52% (11/21) had de-escalation and 48% (10/21) did not de-escalate. CR at EOT was noted in 71% (12/17) with de-escalation vs 81% (13/16) without de-escalation (p=0.50). (Table 2) Progression was noted in 29% (5/17) of patients who underwent de-escalation compared to 38% (6/16) without de-escalation. The 12 month PFS was 76.5% (85.8-99.6) vs 72.1% (52.2-99.7) for de-escalation and no de-escalation respectively. Conclusion: This is the first study evaluating clinical practice patterns and outcomes of PET adaptive therapy in NA. In this retrospective study, less than a quarter of advanced stage ABVD-treated D4/5 pts had therapy escalation despite prior studies reporting benefit. Our data suggest that outcomes for advanced stage PET positive pts are suboptimal irrespective of therapeutic escalation. In addition, pts with D3 findings represent a heterogeneous population and demonstrate favorable outcomes compared to D4/5 pts. Longer follow up time and further studies with larger numbers of pts are essential for confirming the reported findings. Disclosures Rutherford: Seattle Genetics: Consultancy, Honoraria; Verastem: Consultancy, Honoraria; Karyopharm: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Heron: Consultancy, Honoraria; Janssen Scientific Affairs: Consultancy, Honoraria; Juno Therapeutics Inc: Consultancy, Honoraria. Bartlett:ADC Therapeutics: Consultancy, Research Funding; Affimed: Research Funding; Forty Seven: Research Funding; Celgene: Research Funding; Bristol-Myers Squibb: Research Funding; Genenetech: Research Funding; Gilead: Research Funding; Immune Design: Research Funding; Janssen: Research Funding; Merck: Research Funding; Millenium: Research Funding; Pfizer: Research Funding; Pharmacyclics: Research Funding; Seattle Genetics: Research Funding. Maddocks:Novartis: Research Funding; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Merck: Research Funding; BMS: Research Funding; Teva: Membership on an entity's Board of Directors or advisory committees. Feldman:Takeda: Honoraria, Speakers Bureau; Viracta: Research Funding; Trillium: Research Funding; Roche: Research Funding; Portola Pharma: Research Funding; Pfizer: Research Funding; Kyowa Hakko Kirin: Research Funding; Eisai: Research Funding; Corvus: Research Funding; Roche: Research Funding; Cell Medica: Research Funding; Seattle Genetics: Consultancy, Honoraria, Other: Travel expenses, Speakers Bureau; AbbVie: Honoraria, Other: Travel expenses, Speakers Bureau; Pharmacyclics: Honoraria, Other: Travel expenses, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Kite Pharma: Honoraria, Other: Travel expenses, Speakers Bureau; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Celgene: Honoraria, Research Funding, Speakers Bureau. Magarelli:Tevan Oncology: Speakers Bureau. Advani:Merck: Research Funding; Infinity Pharma: Research Funding; Roche/Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celmed: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kura: Research Funding; Kyowa Kirin Pharmaceutical Developments, Inc.: Consultancy; Millennium: Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Agensys: Research Funding; Seattle Genetics: Consultancy, Research Funding; Stanford University: Employment, Equity Ownership; Bayer: Consultancy, 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, Research Funding; Celgene: Research Funding; Regeneron: Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Cell Medica, Ltd: Consultancy; Forty-Seven: Research Funding; Autolus: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead Sciences, Inc./Kite Pharma, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees. Stephens:Karyopharm: Research Funding; Gilead: Research Funding; Acerta: Research Funding. Patel:Sunesis: Consultancy; Genentech: Consultancy, Speakers Bureau; Pharmacyclics/Janssen: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; AstraZeneca: Consultancy, Research Funding, Speakers Bureau. Tees:Celgene: Speakers Bureau; Pharmacyclics: Speakers Bureau. Karmali:Gilead/Kite; Juno/Celgene: Consultancy, Speakers Bureau; Takeda, BMS: Other: Research Funding to Institution; Astrazeneca: Speakers Bureau. Cheson:Portola: Research Funding; Kite: Research Funding; Gilead: Research Funding; Symbios: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Trillium: Research Funding; Epizyme: Research Funding; Morphosys: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Acerta: Consultancy, Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Research Funding; Seattle Genetics: Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Yazdy:Bayer: Honoraria, Speakers Bureau; Octapharma: Consultancy; Genentech: Research Funding; Abbvie: Consultancy. Pagel:AstraZeneca: Consultancy; Gilead Sciences: Consultancy; Pharmacyclics: Consultancy. Ramchandren:Seattle Genetics, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Research Funding; Bristol-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech: Research Funding; Merck: Research Funding; Sandoz-Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics LLC, an Abbvie company: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

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Velychko, Oleksandr, Liudmyla Velychko, Svitlana Khalatur, and Hynek Roubík. "A guarantor in the quality management system of educational programs: a case of Ukrainian universities." Problems and Perspectives in Management 18, no. 4 (November 25, 2020): 153–66. http://dx.doi.org/10.21511/ppm.18(4).2020.14.

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Development of the system of ensuring quality in higher education of Ukraine grounded the creation of such management subject as a guarantor of the educational program. However, a formal understanding of the role and uncertainty of the guarantor’s status in the contemporary area of managing higher education institutions became the widespread consequence of those innovations. Considering the stated above, various models of managing the quality of educational programs with the help of the guarantor have been developed in the research, and conditions for efficient application of such models in Ukrainian universities have been grounded. The research is based on the application of the strategic analysis method GAP for identifying issues and features of organizing management in systems of internal quality assurance in universities, and methods of modeling and graphical analysis method for creating alternative management systems in educational programs with and without such professional educational-scientific structural subdivisions as departments. As a result, the developed models include the rational organization of management of educational programs under the conditions of centralized and decentralized systems of internal educational quality assurance provision. For instance, it could create favorable conditions for decreasing bureaucracy and repetition of functions in the management system of universities and lead to the realization of the individual potential of guarantors as managers-experts in educational programs. Acknowledgment To the National Agency for Higher Education Quality Assurance for the possibility to take part in accreditation expertise and consulting evaluation of educational programs in universities of Ukraine. The research was carried out also within the context of the tasks of Ukrainian-American international project “Program of professional development of them managerial staff in Ukrainian universities,” which was initiated by the investment company “Rayter Inc.” (The USA). In addition, we are thankful to the Czech Development Cooperation support, which allowed this scientific cooperation to start (through projects: “Strengthening scientific capacities and cooperation of Ukrainian universities in AgriSciences” and “Interuniversity cooperation as a tool to improve the quality of selected universities in Ukraine”).

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Pandey, Manu, Mahesh Swaminathan, Elizabeth A. Griffiths, James E. Thompson, Amanda Przespolewski, Swapna Thota, Jeffrey Baron, Tara L. Cronin, and Eunice S. Wang. "Outcomes of Venetoclax-Based Regimens Compared with Hypomethylating Agents (HMA) Alone or 7+3 in Elderly Patients with Newly Diagnosed Acute Myeloid Leukemia (AML): A Single Center Retrospective Analysis." Blood 134, Supplement_1 (November 13, 2019): 3866. http://dx.doi.org/10.1182/blood-2019-132123.

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In the past year, there has been a paradigm shift in the treatment of elderly and/or unfit patients with newly diagnosed acute myeloid leukemia (AML) with the approval of venetoclax (Ven) plus hypomethylating agents (HMA) or low dose Ara-C (LDAC). Ven/ HMA has shown an impressive complete response + complete response with incomplete count recovery (CR+ CRi) rate of 67% and a median overall survival (OS) of 17.5 months in older patients (pts) (median age 74 years) with intermediate and poor risk cytogenetics (Dinardo C et. Blood 2019). Similarly, Ven/LDAC resulted in a CR+ CRi rate of 54% with a median overall survival of 10.1 mos (Wei A et al JClinOnc 2019). However, to date, it is not known how the outcomes of Ven/HMA and Ven/LDAC compare with HMA or intensive chemotherapy in newly diagnosed AML pts. Methods To address this issue, we conducted a retrospective analysis of newly diagnosed AML adult pts treated with Ven-based regimens at our institution. All data was collected under an IRB approved protocol. Demographics, disease characteristics (including cytogenetics and molecular profiles), treatment details (drugs, duration, mortality and causes of death), and clinical outcomes including response and OS were analyzed. Results were compared to a historical cohort of elderly pts treated with HMA alone or intensive (7+3 based) induction chemotherapy as previously reported1. Results 31 newly diagnosed AML patients treated at our single academic institution between 2017-2019 were identified. The median age of the group was 75 years (51-90; 29 patients ≥ 60 years) with 20/31 (64.5%) males and 11/31(35.5%) females. 13/31(41.9%) patients had de-novo AML whereas 18/31 (58.1%) had high risk AML (AML with prior hematological abnormality, t-AML). By ELN 2017 risk stratification 2(6.4%),12(38.7%),17(54.8%) were favorable, intermediate, adverse risk respectively. Molecular profiling results was available for 23/31(74.2%) patients, TET2 and TP53 were the most common mutations present in 9 (29.0%) and 8 (25.8%) patients, respectively. 3/31(9.6%) patients subsequently received an allogeneic-HSCT as of August 1, 2019. The median follow-up was 112 days (9-600 days). Median number of cycles received were 2 (1-21). 15/31 (48%) pts were considered responders (CR, CRi, MLFS), 9 of 31(29%) were non-evaluable (N/E). Of these 7/9 patients died before repeat biopsy, 2/9 patient did not have a repeat biopsy. 2/31(6.4%) experienced partial response, 2/31(6.4%) had stable disease and 3/31(9.6%) had refractory disease. 30-day and 60-day mortality was 2/31(6.4%) and 6/31(19.3%) respectively. Two thirds of treated patients (20/31, 64.5%) are alive. Of the 11 patients who died 5 (45.5%) died due to pneumonia/sepsis, 3 (27.3%) died due to progressive disease, 2 (18.2%) withdrew therapy due to poor performance status and 1(9.1%) CNS bleed. There was no statistical difference in de-novo vs high risk AML, ELN 2017 risk stratification (favorable + intermediate vs adverse) when compared for response (responders vs others) or status (alive vs dead). We then compared our Ven/chemotherapy outcomes with prior data from our institution of newly diagnosed elderly pts treated with HMA or intensive chemotherapy (IC)1. There was a statistically significant difference for response favoring Ven based regimen vs HMA (48.3% vs 25.6% p=0.02); however, no significant difference was seen when comparing Ven/chemo with IC (48.3% vs 50%, p=0.87) (table 1). Similarly, no significant difference was observed in 60-day mortality when IC and HMA based therapy was compared with Ven based regimen (p=0.85 and 0.87 respectively) (table 2). Longer follow up in the Ven/chemotherapy arm is required to make any meaningful conclusion for differences in OS if any (figure A). Conclusion In our single institution retrospective review, we found higher rates of 60-day mortality than reported in a prior phase 1 multi-institute clinical trial (DiNardo et al. Blood 2019). However, response rates with Ven/chemo were significantly better than HMA alone and were equivalent to those of IC in similar elderly AML pts at our institute. We conclude that induction chemotherapy with Ven/based regimens could result in similar responses as IC in older AML pts. References 1-Gupta, Neha, et al. "Comparison of epigenetic versus standard induction chemotherapy for newly diagnosed acute myeloid leukemia patients≥ 60 years old." American journal of hematology90.7 (2015): 639-646. Disclosures Griffiths: Appelis Pharmaceuticals: Other: PI on a clinical trial; Onconova Therapeutics: Other: PI on a clinical trial; New Link Genetics: Consultancy; New Link Genetics: Consultancy; Persimmune: Consultancy; Genentech, Inc.: Research Funding; Boston Scientific: Consultancy; Boston Scientific: Consultancy; Novartis Inc.: Consultancy; Partner Therapeutics: Consultancy; Appelis Pharmaceuticals: Other: PI on a clinical trial; Genentech, Inc.: Research Funding; Onconova Therapeutics: Other: PI on a clinical trial; Persimmune: Consultancy; Celgene, Inc: Consultancy, Research Funding; Astex Phramaceuticals/Otsuka Pharmaceuticals: Consultancy, Research Funding; Partner Therapeutics: Consultancy; Celgene, Inc: Consultancy, Research Funding; Novartis Inc.: Consultancy; Abbvie, Inc.: Consultancy; Astex Phramaceuticals/Otsuka Pharmaceuticals: Consultancy, Research Funding; Abbvie, Inc.: Consultancy, PI on a clinical trial. Thota:Incyte, Inc.: Speakers Bureau. Wang:Jazz: Other: Advisory role; Kite: Other: Advisory role; Abbvie: Other: Advisory role; Astellas: Other: Advisory role, Speakers Bureau; celyad: Other: Advisory role; Pfizer: Other: Advisory role, Speakers Bureau; Stemline: Other: Advisory role, Speakers Bureau; Daiichi: Other: Advisory role; Amgen: Other: Advisory role; Agios: Other: Advisory role.

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Iida, Kaori, and Robert N. Proctor. "‘The industry must be inconspicuous’: Japan Tobacco’s corruption of science and health policy via the Smoking Research Foundation." Tobacco Control 27, e1 (February 4, 2018): e3-e11. http://dx.doi.org/10.1136/tobaccocontrol-2017-053971.

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ObjectiveTo investigate how and why Japan Tobacco, Inc. (JT) in 1986 established the Smoking Research Foundation (SRF), a research-funding institution, and to explore the extent to which SRF has influenced science and health policy in Japan.MethodsWe analysed documents in the Truth Tobacco Industry Documents archive, along with recent Japanese litigation documents and published documents.ResultsJT’s effort to combat effective tobacco control was strengthened in the mid-1980s, following privatisation of the company. While remaining under the protection of Japan’s Ministry of Finance, the semiprivatised company lost its ‘access to politicos’, opening up a perceived need for collaboration with global cigarette makers. One solution, arrived at through clandestine planning with American companies, was to establish a third-party organisation, SRF, with the hope of capturing scientific and medical authority for the industry. Guarded by powerful people in government and academia, SRF was launched with the covert goal of influencing tobacco policy both inside and outside Japan. Scholars funded by SRF have participated in international conferences, national advisory committees and tobacco litigation, in most instances helping the industry to maintain a favourable climate for the continued sale of cigarettes.ConclusionsContrary to industry claims, SRF was never meant to be independent or neutral. With active support from foreign cigarette manufacturers, SRF represents the expansion into Asia of the denialist campaign that began in the USA in 1953.

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Pipe, Steven W., John Pasi, Toshko Lissitchkov, Margaret V. Ragni, Claude Négrier, Qifeng Yu, Stacey Poloskey, Baisong Mei, and Shauna R. Andersson. "Long-Term Durability, Safety and Efficacy of Fitusiran Prophylaxis in People with Hemophilia a or B, with or without Inhibitors - Results from the Phase II Study." Blood 136, Supplement 1 (November 5, 2020): 3–4. http://dx.doi.org/10.1182/blood-2020-136501.

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Introduction: Hemophilia is a bleeding disorder characterized by ineffective clot formation due to insufficient thrombin generation. The burden of disease for individuals with hemophilia is high, and less invasive treatment approaches are needed (Machin and Ragni. J Blood Med. 2018). Fitusiran is a once a month subcutaneously administered investigational RNA interference therapeutic targeting antithrombin as a means to improve thrombin generation and promote hemostasis in people with hemophilia A or B, with or without inhibitors. A completed Phase I study demonstrated that monthly subcutaneous administration of fitusiran was generally well tolerated and lowered antithrombin in a dose-dependent manner, resulting in increased thrombin generation and decreased bleeding frequency (Pasi et al. New Engl J Med. 2017). The aim of this abstract is to describe long-term durability, safety and efficacy of monthly fitusiran treatment for patients with hemophilia A or B, with or without inhibitors, in the Phase II open-label extension study. Methods: The fitusiran Phase I study (NCT02035605) followed by the Phase II open-label extension study (NCT02554773) included male patients, >18 years of age, with moderate or severe hemophilia A and B, with or without inhibitors. Patients received monthly fixed doses of fitusiran 50 mg or 80 mg subcutaneously. Exploratory post-hoc analysis of bleed events was used to calculate median annualized bleed rate in patients with hemophilia A and B, with or without inhibitors. Results: Thirty-four patients (hemophilia A, n=27 [13 with inhibitors and 14 without inhibitors]; hemophilia B, n=7 [2 with inhibitors and 5 without inhibitors) were enrolled in the Phase 2 open-label extension study, and were treated for up to 4.7 years with a median exposure of approximately 2.6 years (as of March 10, 2020). Once-monthly subcutaneous dosing of fitusiran prophylaxis lowered antithrombin (a reduction of between 85% to 72% from baseline) across patients over a sustained period of time. An exploratory analysis of bleeding events showed an overall median annualized bleed rate of 0.84 during the observation period (see figure). Breakthrough bleeds were managed successfully in accordance with the revised bleed management guidelines for reduced doses of bypassing agents and replacement factors. As of March 10, 2020, fitusiran was generally well tolerated and no anti-drug antibody formation was detected. Conclusions: Monthly fitusiran prophylaxis provided sustained antithrombin lowering in people with hemophilia A and B, with or without inhibitors, resulting in a low annualized bleeding rate over a median of 2.6 years in an open-label extension study. Disclosures Pipe: Medical and Scientific Advisory Council to the National Hemophilia Foundation; Medical Advisory Board to World Federation of Hemophilia: Membership on an entity's Board of Directors or advisory committees; Apcintex, Bayer, BioMarin, Catalyst Biosciences, CSL Behring, HEMA Biologics, Freeline, Novo Nordisk, Pfizer, F. Hoffmann-La Roche Ltd/Genentech, Inc., Sangamo Therapeutics, Sanofi, Takeda, Spark Therapeutics, uniQure: Consultancy; Siemens: Research Funding. Pasi:Catalyst Biosciences: Consultancy, Other: Personal fees and nonfinancial support; honoraria as member of scientific advisory boards and symposia; Biotest: Consultancy, Honoraria, Other: Personal fees and nonfinancial support; honoraria as member of scientific advisory boards and symposia; Alnylam (Sanofi): Other: Personal fees and nonfinancial support ; Octapharma: Honoraria, Other: Personal fees and nonfinancial support; honoraria as member of scientific advisory boards and symposia , Speakers Bureau; Pfizer: Other; Novo Nordisk: Honoraria, Other: Personal fees and nonfinancial support; honoraria as member of scientific advisory boards and symposia ; Roche: Honoraria, Other; Sobi: Consultancy, Honoraria, Other; Tremeau: Research Funding; Sigilon: Research Funding; ApcinteX: Consultancy, Other: Personal fees ; uniQure: Other: Grants and nonfinancial support , Research Funding; BioMarin: Consultancy, Honoraria, Other: Grants, personal fees, and nonfinancial support; honoraria as member of scientific advisory boards and symposia; Sanofi: Honoraria, Other: Personal fees and nonfinancial support; honoraria as member of scientific advisory boards and symposia, Research Funding; Takeda: Consultancy, Honoraria, Other: Personal fees; honoraria as member of scientific advisory boards and symposia . Lissitchkov:CSL Behring: Other: Principal investigator of clinical trials ; Bayer: Other: Principal investigator of clinical trials ; Novo Nordisk: Other: Principal investigator of clinical trials ; Octapharma: Other: Principal investigator of clinical trials ; Sanofi: Other: Principal investigator of clinical trials ; Roche: Membership on an entity's Board of Directors or advisory committees, Other: lecturer; Shire: Other: lecturer; Sobi: Membership on an entity's Board of Directors or advisory committees, Other: lecturer; Catalyst Biosciences: Other: Principal investigator of clinical trials . Ragni:Alnylam Pharmaceuticals Inc., Baxalta/Takeda, BioMarin, Bioverativ, and Spark Therapeutics: Membership on an entity's Board of Directors or advisory committees; Sangamo: Consultancy, Research Funding; Takeda: Research Funding; Bioverativ: Consultancy, Research Funding; Spark: Consultancy, Research Funding; BioMarin: Consultancy, Research Funding; Alnylam/Sanofi, ATHN, BioMarin, Bioverativ, Sangamo, Spark: Research Funding; Alnylam/Sanofi, BioMarin, Bioverativ, Spark: Consultancy; American Thrombosis Hemostasis Network: Other: Committee work; Baxalta/Takeda, CSL Behring, Genentech, a member of the Roche Group, OPKO Biologics, and Vascular Medicine Institute: Research Funding. Négrier:CSL, F. Hoffmann-La Roche Ltd, Sobi: Other: Travel support; CSL Behring, Octapharma, Shire/Takeda, Sobi: Research Funding; Bayer, Biomarin, CSL Behring, Freeline, LFB, Novo Nordisk, Octapharma, Pfizer, F. Hoffmann-La Roche Ltd, Sanofi, Shire/Takeda, Sobi, Spark: Consultancy. Yu:Sanofi: Other: was an employee and stockholder of Sanofi, at the time of study; Albireo Pharmaceuticals, Inc: Current Employment. Poloskey:Sanofi: Current Employment. Mei:Sanofi: Current Employment, Current equity holder in publicly-traded company. Andersson:Sanofi: Current Employment, Current equity holder in publicly-traded company.

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CARROLL, BERNARD J. "Psychoneuroendocrinology: The Scientific Basis of Clinical Practice. Edited by O. M. Wolkowitz and A. J. Rothschild. (Pp. 606; $73.95; ISBN 0-88048-857-3 pb.) American Psychiatric Publishing, Inc.: Arlington, Virginia, 2003." Psychological Medicine 34, no. 7 (October 2004): 1359–60. http://dx.doi.org/10.1017/s0033291704213678.

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24

Wang, Eunice S., Elizabeth A. Griffiths, Roland B. Walter, Martin S. Tallman, Aaron D. Goldberg, Boo Messahel, and Richard M. Stone. "Tolerability and Efficacy of Crenolanib and Cytarabine/Anthracycline Chemotherapy in Older Patients (Aged 61 to 75) with Newly Diagnosed FLT3-Mutated Acute Myeloid Leukemia (AML)." Blood 134, Supplement_1 (November 13, 2019): 3829. http://dx.doi.org/10.1182/blood-2019-130536.

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Background: Older AML patients often present with comorbidities and may have a compromised ability to tolerate intensive chemotherapy. These patients are more likely to have AML secondary to MDS/MPN and are considered to have a biologically distinct disease compared to their younger counterparts, with more frequent occurrence of adverse-risk cytogenetic abnormalities and mutations in genes regulating epigenetic modifications. In addition, the heterogeneity of driver mutations within a single patient contributes to limited responses to standard induction chemotherapy. While FLT3 mutations occur in this population, they are often subclonal, adding to the challenge of eradicating AML in older adult patients. Studies combining sorafenib or midostaurin with standard induction chemotherapy have shown relatively modest improvements in response rates and survival, and relapses, both early and late, remain a major concern. There is a major unmet need for optimizing chemotherapy and TKI treatment in this medically fragile population. We here report the safety and efficacy results in newly diagnosed older patients with FLT3 mutant AML treated with crenolanib, a type I FLT3 inhibitor, in combination with intensive induction and consolidation chemotherapy (NCT02283177). Methods: Fifteen consecutively treated patients, aged 61-75 (median age: 68), at four academic cancer centers were included in this analysis. Patients received 7+3 induction with cytarabine 100 mg/m2 for 7 days and either daunorubicin 60 mg/m2 or idarubicin 12 mg/m2 for 3 days. Crenolanib 100 mg TID was administered continuously starting 24 hours after chemotherapy until 72 hours prior to the next chemotherapy cycle. Consolidation consisted of up to 4 cycles of high-dose cytarabine (HiDAC: 1 g/m2) q12h on days 1, 3, and 5 with crenolanib starting 24 hours after the final HiDAC dose. Eligible patients proceeded to allogeneic hematopoietic stem cell transplant (HSCT). Maintenance with crenolanib at 100mg TID was started after HiDAC or 30-90 days after HSCT for up to 12 cycles. Results: Fourteen patients completed induction chemotherapy (one patient withdrew consent at day 19). Crenolanib could be safely combined with either daunorubicin or idarubicin based induction chemotherapy. The most common adverse events (grade ≥3) were diarrhea, nausea, and febrile neutropenia. Ten of 14 patients were able to receive full doses of crenolanib during induction. The major reason for dose reduction was edema in 3 patients and GI bleeding in 1 patient. There was one treatment-related death, with 93% survival at 30 and 60 days and 87% survival at 100 days. Complete remissions with full count recovery (CR) were achieved in 10 of 15 patients after just one cycle of induction chemotherapy. Two patients achieved a complete remission after reinduction for an overall CR rate of 86%. Of the 12 patients who achieved CR, 10 patients received HiDAC consolidation, with two patients unable to receive consolidation therapy on study. Three patients received crenolanib maintenance after multiple cycles of HiDAC consolidation. Six patients underwent HSCT and 3 received crenolanib maintenance. As of July 2019, median OS for the intent to treat population is 20.2 months. One-year survival was 67% and 5 patients remain alive and in remission. All 5 long term survivors were ≤70 years old. All surviving patients received either multiple cycles of HiDAC or HiDAC plus transplant, and 4/5 underwent crenolanib maintenance. The patient who did not receive transplant completed 3 cycles of HiDAC consolidation and a full year of crenolanib maintenance. Summary/Conclusion: This safety study shows that crenolanib can be combined at full doses (100mg TID) for the duration of 7+3 induction, consolidation, and maintenance in older patients with FLT3 mutant AML. Therapy was relatively well tolerated, with less than one third of patients requiring dose reductions. Long-term survival rates are encouraging in this high-risk population, but additional studies are needed to confirm the efficacy of this combination older adults. Figure 1 Disclosures Wang: Pfizer: Other: Advisory role, Speakers Bureau; Stemline: Other: Advisory role, Speakers Bureau; Abbvie: Other: Advisory role; Kite: Other: Advisory role; Jazz: Other: Advisory role; Astellas: Other: Advisory role, Speakers Bureau; celyad: Other: Advisory role; Daiichi: Other: Advisory role; Amgen: Other: Advisory role; Agios: Other: Advisory role. Griffiths:Abbvie, Inc.: Consultancy; Genentech, Inc.: Research Funding; Celgene, Inc: Consultancy, Research Funding; Onconova Therapeutics: Other: PI on a clinical trial; Novartis Inc.: Consultancy; Appelis Pharmaceuticals: Other: PI on a clinical trial; Onconova Therapeutics: Other: PI on a clinical trial; Appelis Pharmaceuticals: Other: PI on a clinical trial; New Link Genetics: Consultancy; Partner Therapeutics: Consultancy; Genentech, Inc.: Research Funding; Astex Phramaceuticals/Otsuka Pharmaceuticals: Consultancy, Research Funding; Astex Phramaceuticals/Otsuka Pharmaceuticals: Consultancy, Research Funding; Abbvie, Inc.: Consultancy, PI on a clinical trial; Celgene, Inc: Consultancy, Research Funding; Boston Scientific: Consultancy; Boston Scientific: Consultancy; Persimmune: Consultancy; Persimmune: Consultancy; New Link Genetics: Consultancy; Partner Therapeutics: Consultancy; Novartis Inc.: Consultancy. Walter:Jazz Pharmaceuticals: Consultancy; Agios: Consultancy; Amgen: Consultancy; Amphivena Therapeutics: Consultancy, Equity Ownership; Aptevo Therapeutics: Consultancy, Research Funding; Argenx BVBA: Consultancy; Astellas: Consultancy; BioLineRx: Consultancy; Kite Pharma: Consultancy; New Link Genetics: Consultancy; Pfizer: Consultancy, Research Funding; Race Oncology: Consultancy; Seattle Genetics: Research Funding; Boston Biomedical: Consultancy; Covagen: Consultancy; BiVictriX: Consultancy; Daiichi Sankyo: Consultancy; Boehringer Ingelheim: Consultancy. Tallman:Hematology Oncology of Indiana: Honoraria; Salzberg Weill Cornall MSKCC Seminar in Hematologic Malignancies: Honoraria; University of Oklahoma Medical Center: Honoraria; Bioline: Membership on an entity's Board of Directors or advisory committees, Research Funding; BioSight: Membership on an entity's Board of Directors or advisory committees, Research Funding; Daiichi-Sankyo: Membership on an entity's Board of Directors or advisory committees; KAHR: Membership on an entity's Board of Directors or advisory committees; Nohla: Membership on an entity's Board of Directors or advisory committees, Research Funding; Rigel: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; ADC Therapeutics: Research Funding; Arog Pharmaceuticals: Research Funding; Cellerant Therapeutics: Research Funding; Orsenix: Membership on an entity's Board of Directors or advisory committees, Research Funding; UpToDate: Patents & Royalties; Mayo Clinic: Honoraria; New Orleans Summer Cancer Conference: Honoraria; Indy Hematology Review: Honoraria; Amgen: Consultancy; 14th Annual Miami Cancer Meeting: Honoraria; Danbury Hospital Tumor Board: Honoraria; International Conference in Leukemia: Honoraria. Goldberg:ADC Therapeutics: Research Funding; Arog Pharmaceuticals: Research Funding; American Society of Clinical Oncology: Research Funding; American Society of Hematology: Research Funding; Celgene: Consultancy; Abbvie: Research Funding; Pfizer: Research Funding; Abbvie: Consultancy; Daiichi-Sankyo: Consultancy, Research Funding; DAVA Oncology: Honoraria. Messahel:Arog Pharmaceuticals: Employment. Stone:Pfizer: Consultancy; Stemline: Consultancy; Astra-Zeneca: Consultancy; Argenix: Other: DSMB; Otsuka: Consultancy; Astellas: Consultancy; Argenix: Other: DSMB; Celgene: Consultancy, Other: DSMB; Stemline: Consultancy; Actinium: Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy; Biolinerx: Consultancy; Biosight: Consultancy; Trovagene: Consultancy; Arog: Consultancy, Research Funding; Takeda: Other: DSMB; Novartis: Consultancy, Research Funding; Daiichi-Sankyo: Consultancy; Celgene: Consultancy, Other: DSMB; Abbvie: Consultancy, Research Funding; Agios: Consultancy, Research Funding; Takeda: Other: DSMB; Biolinerx: Consultancy; Daiichi-Sankyo: Consultancy; Actinium: Membership on an entity's Board of Directors or advisory committees; Otsuka: Consultancy; Jazz: Consultancy; Trovagene: Consultancy; Astra-Zeneca: Consultancy; Novartis: Consultancy, Research Funding; Roche: Consultancy; Macrogenics: Consultancy; Agios: Consultancy, Research Funding; Biosight: Consultancy; Abbvie: Consultancy, Research Funding; Arog: Consultancy, Research Funding; Pfizer: Consultancy; Trovagene: Consultancy; Novartis: Consultancy, Research Funding; Agios: Consultancy, Research Funding; Arog: Consultancy, Research Funding; Macrogenics: Consultancy; Otsuka: Consultancy; Argenix: Other: DSMB; Astellas: Consultancy; Amgen: Membership on an entity's Board of Directors or advisory committees; Jazz: Consultancy; Biolinerx: Consultancy.

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Ragni, Margaret V., Frederico Xavier, Craig D. Seaman, Suchitra Acharya, Catherine E. McGuinn, Eric J. Werner, Courtney Elizabeth Lawrence, et al. "Inhibit Clinical Trials Platform to Prevent and Eradicate Inhibitors: Feasibility Survey of Current Prophylaxis and Immune Tolerance Practices." Blood 136, Supplement 1 (November 5, 2020): 14–15. http://dx.doi.org/10.1182/blood-2020-136814.

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Introduction: Among the most challenging complications of hemophilia A is inhibitor formation. A T-cell dependent B-cell response to exogenous factor VIII (FVIII), inhibitors result in a high burden of disease, with poorly controlled bleeding, twice the hospitalizations, 10-fold the cost, and 3.5-fold the mortality of non-inhibitor patients. Thus, a major goal of hemophilia management is to prevent and eradicate inhibitors. With the availability of novel therapies, including eloctate, a recombinant Fc-fusion protein (rFVIII-Fc) which induces regulatory T cells to promote FVIII tolerance, and emicizumab, a bispecific monoclonal FVIII mimetic, we designed the INHIBIT Clinical Trials Platform (X01HL143024), Fig.1. The platform is composed of two linked randomized phase III trials, the Inhibitor Prevention Trial (NCT04303559), comparing rFVIII-Fc vs emicizumab prophylaxis to prevent inhibitors, and the Inhibitor Eradication Trial (NCT04303572), comparing rFVIII-Fc immune tolerance induction (ITI) plus emicizumab vs rFVIII-Fc ITI alone to eradicate inhibitors. The platform uses adaptive design to incorporate historical data (Bayesian priors) on inhibitor formation to increase power and promote efficient use of rare data. Yet, there is equipoise regarding the optimal approach to inhibitor prevention and eradication, and, as clinical practice is changing, we aimed to test the feasibility of the INHIBIT trial design. Methods: To establish design feasibility, we conducted interviews with 30 hemophilia treatment center (HTC) physicians participating in the INHIBIT trials, to determine prophylaxis and tolerance regimens they prescribe and perceived barriers to the INHIBIT trials design. A 4-question survey was subsequently emailed to these physicians to ascertain the initial prophylaxis regimens they prescribe in previously untreated patients (PUPs) with severe hemophilia A, and the initial immune tolerance induction (ITI) they prescribe in high-responding inhibitor patients with severe hemophilia A; if new inhibitors had been observed during emicizumab prophylaxis, and willingness to participate in post-trial surveillance. Results: In interviews, HTC physicians indicated the issues that influenced choice of prophylaxis/ ITI regimen were patient preference, family history of inhibitors, infusion frequency, IV access, port requirement, and family fatigue. In the absence of clinical trials data in PUPs, there was general agreement that emicizumab prophylaxis, with it simpler subcutaneous (SQ) administration, might delay or potentially prevent inhibitors. Survey findings in Table 1 indicated 75% of physicians prescribe extended half-life (EHL) FVIII in a once-weekly prophylaxis regimen, as planned in the Prevention Trial, despite the persistent 27% inhibitor rate (ALong PUPs Trial, Königs et al, ISTH 2020) and potential risks with port use. There was support for the 1:3 preferential randomization to emicizumab in the Prevention Trial due to the simpler SQ route, despite concern it might delay rather than prevent inhibitor formation, although no inhibitors were reported by physician survey with emicizumab use alone. There was also concern that breakthrough bleeds requiring FVIII during emicizumab prophylaxis, might lead to immune activation and inhibitor formation. There was strong agreement, however, in 29 (97%) of physicians to participate in post-trial surveillance for long-term inhibitor outcomes. FVIII ITI was considered essential to eradicate inhibitors, despite the intensity of the infusion regimen. Notably, 60% prescribe emicizumab with FVIII ITI, as planned in the Eradicate Trial, although the every-other-day infusion was considered a potential barrier to participation. Omitting FVIII ITI was not favored due to the risk of inhibitor anamnesis if FVIII treatment was subsequently required for surgery or acute hemorrhages. Despite these concerns, there was agreement to participate in the trials. Discussion: Physician interviews and surveys confirm there is heterogeneity in current hemophilia clinical practice, specifically in initial prophylaxis regimens and in initial immune tolerance regimens, including agent choice and duration. However, there is physician consensus with the INHIBIT trial aims and with the proposed INHIBIT trial regimens to prevent and eradicate inhibitors. Disclosures Ragni: Bioverativ: Membership on an entity's Board of Directors or advisory committees, Research Funding; Alnylam/Sanofi: Membership on an entity's Board of Directors or advisory committees, Research Funding; BioMarin: Membership on an entity's Board of Directors or advisory committees, Research Funding; ATHN: Research Funding; Sangamo: Research Funding. Seaman:Bayer: Consultancy; Genentech: Consultancy; Spark Therapeutics: Consultancy; Takeda: Consultancy. Acharya:Novonordisk: Membership on an entity's Board of Directors or advisory committees; BPL: Membership on an entity's Board of Directors or advisory committees; Bayer Pharma Inc.: Research Funding. Wheeler:Novo Nordisk: Membership on an entity's Board of Directors or advisory committees; Biomarin: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; UniQure: Membership on an entity's Board of Directors or advisory committees. Tarango:Takeda/Shire: Honoraria, Other; Bayer: Consultancy, Other; Sanofi: Honoraria, Other. Dunn:ATHN: Research Funding; Spire: Honoraria; Medscape: Honoraria; World Federation of Hemophilia USA: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; BioMarin: Research Funding; uniQure: Consultancy; Genentech, Inc.: Consultancy; Nationwide Children's Hospital: Current Employment. Kulkarni:Sanofi/ Bioverativ, Bayer, Biomarin, Shire/Takeda, Novo Nordisk, Freeline: Other: clinical trial research grants ; Bioverativ/Sanofi, BPL, Genentech, Kedrion, Novo Nordisk, Octapharma, Pfizer, Takeda, Catalyst Bioscience Bayer: Membership on an entity's Board of Directors or advisory committees. Ahuja:Genentech: Consultancy, Honoraria; Sanofi Genzyme: Consultancy, Honoraria; XaTek, Inc.: Consultancy, Patents & Royalties, Research Funding. Chitlur:Takeda: Honoraria; Biovertiv: Honoraria; Agios Pharmaceuticals: Research Funding; Pfizer: Honoraria; Novo Nordisk: Consultancy, Honoraria. Pipe:Apcintex, Bayer, BioMarin, Catalyst Biosciences, CSL Behring, HEMA Biologics, Freeline, Novo Nordisk, Pfizer, F. Hoffmann-La Roche Ltd/Genentech, Inc., Sangamo Therapeutics, Sanofi, Takeda, Spark Therapeutics, uniQure: Consultancy; Siemens: Research Funding; Medical and Scientific Advisory Council to the National Hemophilia Foundation; Medical Advisory Board to World Federation of Hemophilia: Membership on an entity's Board of Directors or advisory committees. Malec:Sanofi Genzyme: Consultancy, Research Funding, Speakers Bureau; CSL: Consultancy; Takeda: Consultancy; Bayer: Consultancy; SOBI: Consultancy. Leissinger:Bayer: Consultancy; Kedrion: Consultancy; CSL Behring: Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy; HEMA Biologics: Consultancy; Takeda: Consultancy; Uniqure: Consultancy; Spark: Consultancy. Carpenter:Hemostasis & Thrombosis Research Society: Membership on an entity's Board of Directors or advisory committees; American Academy of Pediatrics: Other: PREP Heme/Onc editorial board; Kedrion: Honoraria; Novo Nordisk: Honoraria; Genentech, Inc.: Honoraria; American Thrombosis and Hemostasis Network: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Research Funding; Shire: Research Funding. Knoll:NovoNordisk: Membership on an entity's Board of Directors or advisory committees. Wang:Bioverativ Inc: Honoraria; Bayer: Honoraria; CSL Behring: Honoraria; Biomarin: Honoraria; Genentech: Honoraria; Takeda: Honoraria. Young:Genentech/Roche, Grifols, and Takeda: Research Funding; Bayer, CSL Behring, Freeline, UniQure: Consultancy; BioMarin, Freeline, Genentech/Roche, Grifols, Kedrion, Novo Nordisk, Sanofi Genzyme, Spark, Takeda, and UniQure: Honoraria. Thornburg:Genentech: Speakers Bureau; Spark Therapeutics: Consultancy; Bluebird Bio: Consultancy; Ironwood Pharmaceuticals: Consultancy, Other: Data Safety Monitoring Board; American Thrombosis and Hemostasis Network: Research Funding; Sanofi Genzyme: Consultancy, Other: Data Safety Monitoring Board, Research Funding; NovoNordisk: Research Funding; Biomarin: Consultancy, Speakers Bureau; Bayer Pharmaceuticals: Research Funding; National Hemophilia Foundation: Membership on an entity's Board of Directors or advisory committees, Research Funding. Lucas:CRISPR Therapeutics: Membership on an entity's Board of Directors or advisory committees. Hwang:Shire: Honoraria; Takeda: Honoraria.

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Pransky, Joanne. "The Pransky interview: Dr Yulun Wang, Founder and CEO of InTouch Health." Industrial Robot: An International Journal 42, no. 5 (August 17, 2015): 381–85. http://dx.doi.org/10.1108/ir-05-2015-0111.

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Purpose – The following paper is a “Q & A interview” conducted by Joanne Pransky of Industrial Robot Journal as a method to impart the combined technological, business and personal experience of a prominent, robotic industry engineer-turned entrepreneur regarding the evolution, commercialization and challenges of bringing a technological invention to market. Design/methodology/approach – The interviewee is Dr Yulun Wang, an inventor, self-taught entrepreneur, business leader and world-renowned authority on robotics and health care. Dr Wang shares his successful three-decade journey that began with researching the market needs and aligning himself with medical experts, followed by pioneering robotic solutions specifically for the health care industry. In the process, Dr Wang founded and spearheaded both a public and private robotics company. Findings – Dr Yulun Wang received a BSc and an MSc in Computer Science, and a PhD in Electrical Engineering, from the University of California, Santa Barbara (UCSB). After teaching at UCSB for a few years, with a grant he won from NASA, Dr Wang founded Computer Motion, Inc. in 1989 and conducted research on endoscopic robots. Computer Motion went public in 1997 and later merged with its competitor, Intuitive Surgical (NASDAQ:IRSG) in 2003 to forge the multi-billion dollar surgical robotics industry. Dr Wang founded InTouch Technologies (d.b.a. InTouch Health), in 2002, named one of the fastest-growing biomedical companies in the USA by INC Magazine. Originality/value – Dr Wang launched his career at the intersection of health care and technology with his invention of the voice-controlled robotic arm AESOP, the first US Food and Drug Administration (FDA)-cleared surgical robot. His next generation ZEUS robotic surgical system (ZRSS), was cleared by the FDA in 2001. Also in 2001, ZRSS was used in the world’s first telesurgery, as surgeons in New York controlled the arms of the Zeus to perform a cholecystectomy on a patient in Strasbourg, France, via a high-speed fiber optic supplied by France Telecom. This led Dr Wang to found InTouch Health, a company that pioneers remote presence robot systems that enable health care professionals to provide more effective and efficient health care. Dr Wang has received multiple other entrepreneurship and leadership awards, including being elected to the prestigious ranks of the National Academy of Engineering in 2011. He is the author of over 50 scientific publications, and holds over 100 patents registered in his name. Dr Wang serves on several boards, including the American Telemedicine Association (ATA) Board of Directors, where he also serves as an officer.

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Kranzler, Elissa C., Erica E. Fortune, Melissa F. Miller, Kelly Clark, Jemeille Ackourey, Linda Bohannon, Heather Badt, et al. "Treatment Decision-Making and Decisional Support Experiences Among Acute Myeloid Leukemia Survivors." Blood 136, Supplement 1 (November 5, 2020): 20. http://dx.doi.org/10.1182/blood-2020-136747.

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Background: With the availability of newer acute myeloid leukemia (AML) treatment combinations and targeted therapies, it is important for patients to understand all available treatment options, including their associated benefits, risks and side effects, before treatment decisions are made. Open communication between patients and clinicians about such options is a critical step toward collaborative treatment decision-making. The purpose of this study is to characterize AML patient experiences regarding treatment decision-making (TDM) and satisfaction with health care team (HCT) communication. Methods: Fifty-six (56) AML patients and survivors enrolled in the Cancer Support Community's online survey, the Cancer Experience Registry®. Forty (40) participants completed survey items pertinent to TDM and satisfaction with HCT communication. Items assessed participants' knowledge about treatment options prior to making a treatment decision, involvement in the TDM process, perceived preparation to discuss treatment options with their doctor, satisfaction with their doctor's explanation of the benefits of each treatment option, satisfaction with their doctor's explanation of the risks and side effects of each treatment option (response options for these five items: 0-4, where 0=Not at all and 4=Very much), and desire for additional support prior to making a treatment decision (response options: Yes/No). Frequencies for these items and socio-demographic and clinical history measures were examined. Results: Among the 40 participants who completed TDM measures, 55% were female and 95% were White, with a mean (SD) age of 52.7 (12.9) years (range: 20-77). Mean time since diagnosis was 5.6 years. Forty-three (43%) percent of participants reported that they were receiving treatment at the time of survey completion, and 28% indicated having ever experienced a recurrence of their cancer. While 65% of participants reported that they were quite a bit or very much involved in their TDM process, only 43% indicated that they were quite a bit or very much knowledgeable about their treatment options prior to making their treatment decision, and 40% of participants reported that they would have liked more support prior to making their treatment decision. More than half of respondents indicated that they were quite a bit or very much satisfied with their doctor's explanation of the benefits of each treatment option (55%), and the risks and side effects of each treatment option (58%); however, only 38% of participants indicated that they felt quite a bit or very much prepared to discuss treatment options with their doctor. Conclusions: Findings demonstrate that substantial proportions of AML patients and survivors express considerable involvement in their treatment decision-making process, and satisfaction with their doctor's explanation of the benefits and the risks and side effects of each treatment option. However, fewer individuals diagnosed with AML reported high levels of knowledge about their treatment options prior to making their treatment decision, and relatively few felt prepared to discuss treatment options with their doctor. Furthermore, many AML patients and survivors indicated a desire for additional support prior to making a treatment decision. Together, results highlight a need for resources, such as TDM guides or in-person counseling, to enhance HCT communication surrounding TDM for individuals with AML. Such efforts may provide AML patients with sufficient knowledge about treatment options to ensure that they feel adequately prepared to discuss these options and select the appropriate treatment pathway. Disclosures Kranzler: Astellas Pharma US, Inc.: Research Funding; Pharmacyclics, Inc.: Research Funding; Janssen Oncology: Research Funding; Takeda Oncology: Research Funding; Jazz Pharmaceuticals: Research Funding. Fortune:Genentech: Research Funding; Boston Scientific Foundation: Research Funding. Leblanc:UpToDate: Patents & Royalties: Royalties; Agios, AbbVie, and Bristol Myers Squibb/Celgene: Speakers Bureau; AstraZeneca: Research Funding; AbbVie, Agios, Amgen, AstraZeneca, CareVive, BMS/Celgene, Daiichi-Sankyo, Flatiron, Helsinn, Heron, Otsuka, Medtronic, Pfizer, Seattle Genetics, Welvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; American Cancer Society, BMS, Duke University, NINR/NIH, Jazz Pharmaceuticals, Seattle Genetics: Research Funding. Liesveld:Abbvie: Honoraria; Onconova: Other: data safety monitoring board. Zaleta:Pfizer, Inc.: Research Funding; Athenex Oncology: Research Funding; Gilead Sciences, Inc: Research Funding.

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Gómez Chávez, Lino Francisco Jacobo, Paola Cortés Almanzar, Vilma Zoraida del Carmen Rodríguez Melchor, Javier Iván Salazar Pérez, and Miriam Yunuen Gómez Chávez. "Actividad física y cáncer: una revisión bibliométrica 2016-2021 (Physical activity and cancer: a bibliographic review 2016-2021)." Retos 45 (May 6, 2022): 622–27. http://dx.doi.org/10.47197/retos.v45i0.92728.

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Los análisis bibliométricos relacionados con el cáncer son comunes, sin embargo, los asociados a la actividad física y el cáncer no lo son en la misma medida. Objetivo: analizar la producción científica relacionada con la actividad física y el cáncer de 2016 a 2021. Método: se trata de un análisis bibliométrico realizado a través de EBSCO Discovery Service, se utilizó para la búsqueda el concepto en inglés Physical activity and cancer dispuesto exclusivamente en el título de las publicaciones, solo se consideraron las publicaciones realizadas de 2016 a 2021 y los textos con acceso total a través del buscador. Resultados: se localizaron 2.316 recursos bibliográficos, 97,4% son artículos. Las principales temáticas son ejercicio físico (15,3%), actividad física (13,7%) y sobrevivientes de cáncer (5,6%). Los principales editores de las publicaciones Elsevier 17,0%, Springer 13,8% y Biomed Central 8,76%. Casi la totalidad de las publicaciones son en inglés 97,4%. Los países de origen de las publicaciones son Estados Unidos 31,6%, Reino Unido 18,3% y Australia 14,7%. Las organizaciones que realizan en mayor medida publicaciones son la Sociedad Americana del Cáncer, Estudios sobre la salud de las enfermeras y la Organización Mundial de la Salud (en todos los casos con 17,7%), Conclusiones: los resultados del estudio proporcionan información que puede ayudar a entender el presente en la investigación de la actividad física como un factor determinante en la prevención y la supervivencia al cáncer, así como contribuir en la generación de conocimiento desde Iberoamérica y en castellano. Abstract. Bibliometric analyses related to cancer are common, but those associated with physical activity and cancer are not. Objective: to analyze the scientific production related to physical activity and cancer from 2016 to 2021. Method: this is a bibliometric analysis carried out through EBSCO Discovery Service, the Physical activity and cancer concept was used for the search, which was exclusively provided in the titles of the publications, only publications made from 2016 to 2021 and texts with full access through the search engine were considered. Results: 2,316 bibliographic resources were located, 97.4% are articles. The main topics are physical exercise (15.3%), physical activity (13.7%) and cancer survivors (5.6%). The main publishers of the publications Elsevier 17.0%, Springer 13.8% and Biomed Central 8.76%. Almost all publications are in English 97.4%. The countries of origin of the publications are the United States 31.6%, the United Kingdom 18.3% and Australia 14.7%. The organizations that make the most publications are American Cancer Society Inc., Nurses' Health Study and the World Health Organization (in all cases with 17.7%), Conclusions: the results of the study provide information that can help understand the present in the research of physical activity as a determining factor in the prevention and survival of cancer, as well as contributing to the generation of knowledge from Spain and Latin America and written in Spanish.

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Borzova, Alla Yu, Olga V. Volosyuk, and Nino D. Nikolashvili. "Spanish Humanitarian Policy in Latin America: Peculiarities and Priorities." Vestnik RUDN. International Relations 22, no. 3 (December 15, 2022): 586–99. http://dx.doi.org/10.22363/2313-0660-2022-22-3-586-599.

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The article deals with the establishment and formation of the humanitarian policy of Spain, the evolution of the concept of “Hispanidad” in relation to Latin America, when Spain, along with the expansion of investment and economic cooperation, was building up educational, scientific, cultural interaction based on a common historical past, and intended positioning itself as a “bridge” between the EU and this region. The authors apply the theory of constructivism, based on the position that “historical and cultural paradigms,” norms and beliefs, and not only economic power influences the rapprochement of states. The chronological order makes possible to trace the evolution of the features and priorities of the country’s humanitarian policy, starting from the second half of the 2010s, when it was reduced to the dominance of the educational and scientific factor in Spanish public diplomacy towards Latin America. The Spanish state has achieved significant results in improving the system of higher education, making it attractive to foreign students. The activities of public and private structures (Ministry of Foreign Affairs, AECID, Carolina Foundation, Casa America) are focused not only at creating a positive image of Spain (the Program “Spain Global”), but also at forming a common Ibero-American scientific and educational space. In the Ibero-American Community of Nations (ICN), which unites countries on the basis of language and culture, an important place is given to youth problems related to the availability of quality education and employment, as well as issues of digitalization, economic modernization, renewable energy. Within the framework of the ICN, the Tordesillas Group, the Association of Ibero-American Universities, the La Rabida Group, etc., are intended to implement the 2021 Goals in the field of education. The use of professional research networks, the introduction of new skills and competencies for students and teachers, the creation of the Ibero-American Institute for Education and Productivity (IIEYP), focusing on the relationship between education and economic growth, became a real basis for strengthening a common Ibero-American educational and scientific space as a main priority in the actual humanitarian policy of Spain.

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Choi, Seong-Ho, Felicia Ruffin, Lawrence Park, Batu K. Sharma-Kuinkel, Maria Souli, Bobby Warren, Brenda Hansen, Felix Mba Medie, and Vance G. Fowler. "1060. Risk Factors for Recurrent Staphylococcus aureus Bacteremia." Open Forum Infectious Diseases 5, suppl_1 (November 2018): S317. http://dx.doi.org/10.1093/ofid/ofy210.897.

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Abstract Background Recurrent Staphylococcus aureus bacteremia (Re-SAB) occurs in 2–17% of patients with SAB within 3–12 months after resolution of the first episode. The risk factors for Re-SAB are incompletely understood. Methods Re-SAB was defined as a second episode of SAB after the resolution of the first episode occurring at least 14 days from the date of the last positive blood culture of the first episode. Using the SAB Group Prospective Cohort Study (SABG-PCS) data between January 2008 and May 2015, patients with Re-SAB were selected and compared with those without it. Pulsed-field gel electrophoresis (PFGE) was done for the clinical isolates from the Re-SAB group, and spa typing was for those from both groups. Baseline sera from patients with Re-SAB and age/race/gender matched (1:1) control subjects with SAB but without Recurrence underwent Luminex multiplex cytokine array. Results Seventy patients experienced Re-SAB (9.3%) and 686 SAB patients did not. In the Re-SAB group, 156 episodes of SAB were observed. Median time to Re-SAB was 147.5d (IQR, 76–358). Among 65 PFGE-analyzed pairs of isolates from the first and the subsequent episodes, the time to Re-SAB of <300 days was more commonly found in the PFGE-identical pairs than in the PFGE-different pairs (75.6% vs. 33.8%, P = 0.001). In the comparison of clinical factors between 56 Re-SAB patients with available data and 686 without Re-SAB, African American race, dialysis dependence, the presence of foreign body, persistent bacteremia, metastatic abscess formation, and methicillin-resistant S. aureus (MRSA) were more frequently observed in patients with Re-SAB. In a multivariate analysis to identify risk factors for Re-SAB, African American race, dialysis dependence, metastatic abscess formation, and MRSA were independent risk factors. The distribution of spa types between the two group was presented in Figure 1. Conclusion Re-SAB involves a combination of multiple factors of host, microbe, and treatment. Further laboratory investigation for any determinants in host and microbe is required. Disclosures V. G. Fowler Jr., Merck, Cerexa/Actavis, Pfizer, Advanced Liquid Logis, NIH, MedImmune, Basilea, Karius, Contrafect, Regneron, Genentech, Affinergy, Locus, Medical Surface, Inc., Achaogen, Astellas, Arsanis, Bayer, Cubist, Debiopharm, Durata, Grifols, Medicines Co, Novartis: Collaborator, Consultant and Scientific Advisor, Consulting fee, Research grant and Research support.

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Kim, Joseph, Kellie Beumer, and Melissa Kelly. "Abstract P6-04-19: Engaging pathologists in a social peer-to-peer learning collaborative to discuss the emergence of HER2-low breast cancer." Cancer Research 83, no. 5_Supplement (March 1, 2023): P6–04–19—P6–04–19. http://dx.doi.org/10.1158/1538-7445.sabcs22-p6-04-19.

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Abstract Introduction: Recent advances in research have shown clinical effectiveness when targeting the lower range of HER2 expression (ie, HER2-low) in patients with metastatic breast cancer. American Society for Clinical Pathology worked in collaboration with Q Synthesis to develop a peer-to-peer learning collaborative to proactively prepare pathologists for HER2-low and to discuss the clinical implications around this emerging classification. This CME project was supported by an educational grant from AstraZeneca Pharmaceuticals LP and Daiichi Sankyo Inc. Methods: ASCP launched a peer-to-peer (P2P) learning collaborative (HER2 Breast Trailblazers) where small groups of pathologists met to discuss some of the practical implications associated with HER2-low. 38 pathologists from a mix of academic and community settings participated in this CME program. For foundational knowledge, learners completed online modules covering scientific updates on HER2-low. Through small-group, case-based discussions, learners reviewed operational challenges and opportunities to prepare for HER2-low. They applied this knowledge to lead projects at their own institutions focusing on the anticipated changes around HER2-low. ASCP also launched a series of peer-led Twitter Chats that were designed to reach a broad audience and foster open dialogue about the emerging science of HER2-low breast cancer. This approach engaged Twitter users who were eager to share and disseminate the education to their colleagues. Twitter Chats provided peer-to-peer feedback regarding ways to navigate obstacles, barriers, and other challenges affecting HER2 testing in breast cancer. Results: The learners identified the following challenges and opportunities: Defining HER2-low: Several learners had heard misconceptions around the definition of HER2-low. Recent studies have defined HER2-low as IHC 1+ or IHC 2+ with ISH-negative. Interobserver concordance with IHC 0 vs 1+: Several learners discussed the challenges around interpreting IHC 0 vs 1+. They felt that some pathologists may need guided feedback to improve their diagnostic skills. Use of IHC vs. ISH: Several learners only performed ISH for HER2 testing on all breast cancer samples. If HER2-low emerges as a third category, they would need to return to IHC. Implications for non-metastatic breast cancer: Recent HER2-low studies have focused on patients with metastatic breast cancer. If HER2-low emerges as a third category, it is unclear whether this designation will also be used in patients who have early-stage breast cancer. Leadership: As pathologists prepare for HER2-low, they have opportunities to lead projects to assess and improve IHC interobserver concordance, coach others on IHC interpretation, increase operational efficiency, strength communication skills, and build up the team by proactively anticipating challenges around HER2-low. Conclusions: HER2-low breast cancer appears to be emerging as a new classification and pathologists need to be prepared to ensure accurate testing and interpretation. Through a peer-to-peer learning collaborative, pathologists identified ways to proactively prepare and demonstrate leadership so that cancer centers and laboratories may be ready to embrace a new paradigm of HER2 classification in breast cancer. A series of public Twitter Chats broadened this discussion and increased awareness among pathologists. Citation Format: Joseph Kim, Kellie Beumer, Melissa Kelly. Engaging pathologists in a social peer-to-peer learning collaborative to discuss the emergence of HER2-low breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-04-19.

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Patel, Yesha, Anjali Doshi, Anna Levesque, Shelsie Lindor, Robert Moranville, Sheila Okere, Danielle Robinson, Lauren Taylor, Mark Lustberg, and Carlos Malvestutto. "835. Improvement in Diet Attenuates Antiretroviral Therapy (ART) Associated Weight Gain in Persons with Human Immunodeficiency Virus (PWH)." Open Forum Infectious Diseases 8, Supplement_1 (November 1, 2021): S509—S510. http://dx.doi.org/10.1093/ofid/ofab466.1031.

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Abstract Background Weight gain among PWH on ART is a growing clinical concern. We explore factors associated with weight gain at The Ohio State University Wexner Medical Center Infectious Diseases Clinic. Methods This was a single-center, retrospective, cohort study of adult PWH on ART for at least 3 months seen at our clinic from 1/1/2015 to 1/1/2019. Patients with CD4+ T cell count < 200 cells/mm3, viral load >200 copies/mL, history of malignancy, or pregnancy were excluded. 870 patients met criteria. Patient demographics, lifestyle factors, medical co-morbidities, concurrent medications, and ART regimens were documented during the study period. The primary outcome was percent weight change over the follow up period. Secondary outcome was the odds of > 5kg weight gain over the study period. The effects of concurrent medications, medical comorbidities, ART combinations, and self-reported lifestyle behaviors on these outcomes were modeled using mixed effect linear and logistic regression analysis. Results At baseline, 83.6% were male, 29.2% were African American, and 65.6% had a body mass index ≥ 25 kg/m. Over a mean follow up of 1.86 years, the study population gained a mean percent weight of 2.12 ± 0.21% (p< 0.001) with an odds of weight gain >5kg of 0.293 (p< 0.001). Male sex and increasing age were significantly associated with a decrease in percent weight over the study period as reflected in the table below. Diet was also significantly associated with a decrease in percent weight change over the study period of -1.99 ± 0.47 %, p= < 0.001 and a lower odds of > 5kg of weight gain (OR= 0.70, 95% CI= 0.50 – 0.97, p=0.03). In regression models, combination therapy with tenofovir alafenamide (TAF) and integrase strand transfer inhibitor (INSTI) containing regimens were significantly associated with an increase in percent weight over the study period. Other significant factors including demographics and ART regimens are noted in Table 1. Table 1. Multivariable Regression Models* Conclusion Weight gain in PWH is multifactorial. Key factors associated with weight gain include combination therapy with TAF, particularly when combined with an INSTI. This data highlights the influential role of diet in PWH at risk of ART-associated weight gain. Disclosures Carlos Malvestutto, M.D., Lilly (Scientific Research Study Investigator)Regeneron Inc. (Scientific Research Study Investigator)ViiV Healthcare (Advisor or Review Panel member)

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Rech, Andrew, Yury Goltsev, Nikolay Samusik, and Anna Kaznadzey. "Abstract 3509: Using generative AI for filtering and comprehension of drug target discovery screen results." Cancer Research 84, no. 6_Supplement (March 22, 2024): 3509. http://dx.doi.org/10.1158/1538-7445.am2024-3509.

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Abstract Recent advancements in generative AI, including models such as GPT-4 and LLAMA2, have been rapidly integrated into cancer research. Cellformatica, Inc. has developed a pipeline designed to enhance the accuracy of functional and genomic drug target discovery screens by reducing the incidence of false positives and refining the interpretation process. This pipeline is capable of conducting comprehensive investigations, including genome-wide analyses, and is accessible via web and API interfaces. At the core of the pipeline is the use of the extensive global corpus of scientific literature to assess the relevance of each gene within the context defined by the experimental design of the screen. To address the issue of AI-generated inaccuracies, often referred to as 'hallucinations,' the pipeline incorporates a custom-tuned language model (LLM) component within the generative AI framework. This fine-tuning process is specifically tailored to the gene set under investigation. The pipeline's multi-agent architecture is a distinctive feature. It scores candidates based on three orthogonally-tuned criteria: effectiveness, confidence, and novelty. In benchmarking tests, this multi-agent scoring system has outperformed GPT-4 and has proven particularly adept at identifying candidate targets that may have been overlooked in previous research. These candidates are recognized for their significant therapeutic potential and are corroborated by existing scientific findings. The versatility of the Cellformatica pipeline is demonstrated through its application in three distinct areas of cancer research. First, it has been employed to optimize chimeric antigen receptor (CAR) T-cell therapies, a form of immunotherapy for cancer treatment. Second, the pipeline has been used to elucidate the network of chemotactic molecules that orchestrate immune cell infiltration and tissue remodeling in the lungs of patients with COVID-19. Third, it has been used to spatially define signaling pathways in humanized xenograft murine tumor experiments, for which existing cross-species database knowledge is limited. These applications underscore the pipeline's potential to contribute to the understanding and treatment of complex diseases. Citation Format: Andrew Rech, Yury Goltsev, Nikolay Samusik, Anna Kaznadzey. Using generative AI for filtering and comprehension of drug target discovery screen results [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3509.

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Négrier, Claude, Margaret V. Ragni, John Pasi, Steven W. Pipe, Gili Kenet, Savita Rangarajan, Salim Kichou, Baisong Mei, and Shauna R. Andersson. "Longitudinal Assessment of Thrombin Generation in Patients with Hemophilia Receiving Fitusiran Prophylaxis: Phase II Study Results." Blood 136, Supplement 1 (November 5, 2020): 36–37. http://dx.doi.org/10.1182/blood-2020-136536.

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Introduction: Thrombin plays a central role in hemostasis: in the initiation, amplification, and propagation phases of coagulation and in the formation of a stable fibrin clot. Normal hemostatic function requires a balance between procoagulant and anticoagulant proteins that regulate thrombin generation (Negrier et al. Blood Reviews. 2019). Co-inheritance of antithrombin deficiency in people with hemophilia is associated with a milder bleeding phenotype (Shetty et al. Br J Haematol. 2007; Bolliger et al. Thromb Haemost. 2010), supporting the hypothesis that a reduction in antithrombin levels will increase thrombin generation and thus normalize hemostasis in people with hemophilia. Fitusiran is a subcutaneously administered investigational RNA interference therapeutic targeting antithrombin for prophylactic treatment of patients with hemophilia A and B, with or without inhibitors. In a completed Phase I study, monthly subcutaneous administration of fitusiran was found to lower antithrombin levels, increase thrombin generation, and was generally well tolerated (Pasi et al. Blood. 2016; Pasi et al. New Engl J Med. 2017). The aim of this abstract is to describe the longitudinal assessment of thrombin generation with fitusiran in the Phase I/II open-label extension study (NCT02554773). Methods: The fitusiran Phase I dose-escalation study (NCT02035605) was followed by the Phase II open-label extension study (NCT02554773), which included male patients, >18 years of age, with moderate or severe hemophilia A and B, with or without inhibitors, who were eligible to continue dosing with monthly subcutaneous fixed doses of fitusiran 50 mg or 80 mg. Thrombin generation was assessed monthly for the first 2 years and every 6 months thereafter using the calibrated automated thrombogram (CAT) assay. Results: Thirty-four patients aged 19-61 with hemophilia A (n=27; 13 with inhibitors and 14 without inhibitors) or hemophilia B (n=7; 2 with inhibitors and 5 without inhibitors) were treated for up to 4.7 years with a median exposure of approximately 2.6 years at the time of the data cut (March 10, 2020). Peak thrombin generation was assessed over the length of the study for each patient. Once-monthly subcutaneous dosing of 50 mg or 80 mg fitusiran prophylaxis over a period of 48 months resulted in sustained antithrombin lowering (a reduction of between 85% to 72% from baseline), which led to peak thrombin levels and an endogenous thrombin potential approaching the normal range seen in healthy volunteers (see figure). Additional subgroup analyses (hemophilia A and B, with or without inhibitor) will be conducted for presentation at the congress. Conclusions: Monthly fitusiran prophylaxis resulted in consistent peak thrombin generation levels in patients with hemophilia A and B, with or without inhibitors over an extended period of time. With the thrombin generation levels in people with hemophilia on fitusiran approaching that of normal healthy adults, this sustained lowering of thrombin has the potential to provide consistent bleed protection in patients over time. Disclosures Négrier: CSL, F. Hoffmann-La Roche Ltd, Sobi: Other: Travel support; CSL Behring, Octapharma, Shire/Takeda, Sobi: Research Funding; Bayer, Biomarin, CSL Behring, Freeline, LFB, Novo Nordisk, Octapharma, Pfizer, F. Hoffmann-La Roche Ltd, Sanofi, Shire/Takeda, Sobi, Spark: Consultancy. Ragni:Alnylam Pharmaceuticals Inc., Baxalta/Takeda, BioMarin, Bioverativ, and Spark Therapeutics: Membership on an entity's Board of Directors or advisory committees; Sangamo: Consultancy, Research Funding; Takeda: Research Funding; Bioverativ: Consultancy, Research Funding; Spark: Consultancy, Research Funding; BioMarin: Consultancy, Research Funding; Alnylam/Sanofi, ATHN, BioMarin, Bioverativ, Sangamo, Spark: Research Funding; Alnylam/Sanofi, BioMarin, Bioverativ, Spark: Consultancy; American Thrombosis Hemostasis Network: Other: Committee work; Baxalta/Takeda, CSL Behring, Genentech, a member of the Roche Group, OPKO Biologics, and Vascular Medicine Institute: Research Funding. Pasi:BioMarin: Consultancy, Honoraria, Other: Grants, personal fees, and nonfinancial support; honoraria as member of scientific advisory boards and symposia; Sanofi: Honoraria, Other: Personal fees and nonfinancial support; honoraria as member of scientific advisory boards and symposia, Research Funding; Roche: Honoraria, Other; Pfizer: Other; Octapharma: Honoraria, Other: Personal fees and nonfinancial support; honoraria as member of scientific advisory boards and symposia , Speakers Bureau; Novo Nordisk: Honoraria, Other: Personal fees and nonfinancial support; honoraria as member of scientific advisory boards and symposia ; Catalyst Biosciences: Consultancy, Other: Personal fees and nonfinancial support; honoraria as member of scientific advisory boards and symposia; Biotest: Consultancy, Honoraria, Other: Personal fees and nonfinancial support; honoraria as member of scientific advisory boards and symposia; Alnylam (Sanofi): Other: Personal fees and nonfinancial support ; Takeda: Consultancy, Honoraria, Other: Personal fees; honoraria as member of scientific advisory boards and symposia ; ApcinteX: Consultancy, Other: Personal fees ; uniQure: Other: Grants and nonfinancial support , Research Funding; Sigilon: Research Funding; Tremeau: Research Funding; Sobi: Consultancy, Honoraria, Other. Pipe:Apcintex, Bayer, BioMarin, Catalyst Biosciences, CSL Behring, HEMA Biologics, Freeline, Novo Nordisk, Pfizer, F. Hoffmann-La Roche Ltd/Genentech, Inc., Sangamo Therapeutics, Sanofi, Takeda, Spark Therapeutics, uniQure: Consultancy; Siemens: Research Funding; Medical and Scientific Advisory Council to the National Hemophilia Foundation; Medical Advisory Board to World Federation of Hemophilia: Membership on an entity's Board of Directors or advisory committees. Kenet:PI Healthcare, CSL Behring: Honoraria; Bayer, Pfizer, Takeda, BioMarin, Novo Nordisk: Speakers Bureau; Bayer, Pfizer, Roche, Alnylam (Sanofi), Shire: Research Funding; Bayer, Pfizer, BioMarin, Takeda, Roche, Novo Nordisk, Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Rangarajan:Sangamo: Research Funding; Takeda, Grifols, Roche, Reliance Life Sciences: Other: Conference support, Speakers Bureau. Kichou:Sanofi: Current Employment. Mei:Sanofi: Current Employment, Current equity holder in publicly-traded company. Andersson:Sanofi: Current Employment, Current equity holder in publicly-traded company.

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Zilberberg, Marya D., Brian Nathanson, Rachel Harrington, James Spalding, and Andrew F. Shorr. "Epidemiology and Outcomes of Hospitalizations with Invasive Aspergillosis in the United States, 2010–2013." Open Forum Infectious Diseases 4, suppl_1 (2017): S88—S89. http://dx.doi.org/10.1093/ofid/ofx163.047.

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Abstract Background Invasive aspergillosis (IA) complicates the care of up to 13% of patients with varying forms of immune compromise. The accompanying morbidity and mortality associated with IA remains high. We sought to describe the epidemiology and outcomes for all hospitalizations associated with IA in the United States. Methods We analyzed the National Inpatient Sample (NIS) from the Agency for Healthcare Research and Quality (AHRQ) for 2010–2013. We identified subjects with high-risk conditions for IA (stem cell or solid organ transplant, critical illness, major surgery, mild-to-moderate immune compromise, severe immune compromise, and other [human immunodeficiency virus, pneumonia, chronic obstructive pulmonary disease]). IA was identified via ICD-9-CM codes 117.3, 117.9, and 484.6. We compared characteristics and outcomes between those with (IA) and without IA (non-IA). We calculated the IA-associated excess mortality, length of stay (LOS) and costs using propensity-score (PS) matching. Results Of the 66,634,683 discharges who met the study inclusion criteria, 154,888 (0.2%) had a diagnosis of IA. Patients with IA were more likely to be male (50.9% IA vs. 46.7% non-IA, P < 0.001), and African American (15.3% IA vs. 12.5% non-IA, P < 0.001). The most common high-risk condition among those not classified as IA was major surgery (50.1%). In the IA group critical illness was noted most frequently (41.0%). The burden of both chronic (median [interquartile range, IQR] number of Elixhauser comorbidities 3 [1, 5] non-IA vs. 4 [3, 6] IA, P < 0.001) and acute (median [IQR] number of procedures during the hospitalization 2 [1, 3] non-IA vs. 3 [1, 6] IA, P < 0.001) illnesses was higher in the IA group than the non-IA. After PS-matching, mortality in IA (14.1%) was 37% higher than in non-IA (10.3%, P < 0.001), translating to an odds ratio = 1.43; 95% CI (1.36, 1.51). IA was associated with 6.0 (95% CI 5.7, 6.4) excess days in the hospital and excess $15,542 (95% CI $13,869, $17,215) in costs/hospitalization. Conclusion Although rare even among high-risk groups, IA is associated with high hospital mortality, excess duration of hospitalization, and costs. Given nearly 40,000 annual IA admissions in the United States, we estimate that the aggregate IA-attributable excess costs may reach $600 million annually. Disclosures M. D. Zilberberg, Astellas: Grant Investigator, Research support. B. Nathanson, EviMed, LLC: Consultant, Consulting fee. R. Harrington, Astellas Pharma Global Development, Inc.: Employee, Salary. J. Spalding, Astellas Pharma Global Development, Inc.: Employee, Salary. A. F. Shorr, Astellas: Consultant and Speaker’s Bureau, Consulting fee, Research support and Speaker honorarium. Cidara: Consultant, Consulting fee. Merck: Consultant, Scientific Advisor and Speaker’s Bureau, Research support and Speaker honorarium

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Huang, Jiajie, Haigang Gu, Janet Orton, Marina Sedova, Amir Marcovitz, Jennifer Burke, Sarah Brozio, et al. "Abstract 7657: Detection of KMT2A-PTDs and KMT2A fusions using next generation sequencing." Cancer Research 84, no. 6_Supplement (March 22, 2024): 7657. http://dx.doi.org/10.1158/1538-7445.am2024-7657.

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Abstract Introduction: KMT2A (MLL) rearrangements (fusions) is a therapeutic biomarker for Menin inhibitors. KMT2A-PTDs (partial tandem duplications) are considered a prognostic biomarker in myeloid malignancies. KMT2A fusions and PTDs are traditionally detected by RT-qPCR (quantitative real-time PCR). This study investigates KMT2A PTDs levels in healthy donors and myeloid malignancy samples to establish a threshold to report samples with high PTDs, using next generation sequencing (NGS) with OncomineTM Myeloid Assay GX v2. We also report KMT2A fusions in myeloid malignancies. Methods: We sequenced 8483 research samples with known myeloid malignancies at Sonora Quest LaboratoriesTM and at Thermo Fisher ScientificTM. We acquired 20 healthy donor whole blood samples (total 127 replicates) from StanfordTM Blood Center and Discovery Life SciencesTM and sequenced them at 3 different sites of Thermo Fisher ScientificTM. Samples were sequenced with the Ion TorrentTM GenexusTM 6.6 or Ion GeneStudioTM S5 System. They were profiled for 6 different KMT2A-PTD variants and 199 KMT2A fusion isoforms. Results: The mean read length of this data set is 90 - 120 bp and the mean mapped fusion reads is 20,000 - 30,000. KMT2A-PTDs were detected in both healthy donors and myeloid samples. Healthy donor PTD read counts were consistently <2000 and averaged 1/3 of myeloid sample PTD read counts. About 33% of myeloid samples had higher PTD read counts than any healthy donor sample. BLAT (BLAST-Like Alignment Tool) analysis confirmed specific exon matching on the KMT2A gene in both cohorts. Among the 8483 myeloid samples, 162 samples contained a total of 5 unique KMT2A PTDs, and 105 samples contained a total of 30 unique KMT2A fusion isoforms with KMT2A-MLLT1 and KMT2A-MLLT3 being the most prevalent KMT2A fusion gene pairs. Conclusions: We characterize the KMT2A fusions present in myeloid malignant samples. We also describe the abundance of KMT2A PTDs in both healthy donor and myeloid samples, with myeloid cases showing significantly higher PTD read counts. KMT2A PTD read count >2000 is present only in malignant samples but not in healthy donors. This intriguing finding opens opportunities for prospective studies to monitor individuals with elevated PTD levels for myeloid malignancy development and retrospective studies to explore whether healthy donors identified with this alteration years ago after blood donation were subsequently recorded in the national health system with myeloid malignancies. (For research use only. Not for use in diagnostic procedures. © 2023 Thermo Fisher Scientific Inc. All rights reserved. All trademarks are the property of Thermo Fisher Scientific and its subsidiaries unless otherwise specified. Stanford is a trademark of the Board of Trustees of the Leland Stanford Junior University. Discovery Life Sciences is a trademark of Discovery Life Sciences. Sonora Quest Laboratories is a trademark of Sonora Quest Laboratories.) Citation Format: Jiajie Huang, Haigang Gu, Janet Orton, Marina Sedova, Amir Marcovitz, Jennifer Burke, Sarah Brozio, Paul Williams, Scott Myrand, Nate Olowo, Adam Broomer, Brendan Deal, Collyn Seeger, Seth Sadis, Sophie Rozenzhak, Fiona Hyland, Guang Liu. Detection of KMT2A-PTDs and KMT2A fusions using next generation sequencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7657.

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Varava, Liudmila, and Yelyzaveta Dekaliuk. "Psychological Factors Of Intragroup Process Efficiency Within Modern Organizations." 73, no. 73 (December 30, 2022): 42–51. http://dx.doi.org/10.26565/2225-7756-2022-73-05.

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The article is devoted to consideration of the problematic issue of improving productivity and increasing the efficiency of management, which is faced by the managers of Ukrainian enterprises and organizations providing social services in the competitive market of goods supply in conditions of full-scale war. Since the organization’s high performance indicators may provide an advantage over competitors and boost financial success, each organization, in turn, strives to become a leader and even a monopolist in a competitive market by its own means. Depending on the productivity of such actions, the organization may gain a significant competitive advantage, which is an integral component of business economic opportunities that can be employed to achieve strategic goals and objectives. Given the current economic behavior of business entities, the need to isolate the psychological factors of corporate culture directly affecting the organizational management efficiency is undeniable, since highly professional psychologists and business consultants in this field may contribute to solving problems of organizational interaction. The article analyzes the theoretical background of the corporate culture phenomenon, value orientations and organization in psychological science. The authors’ interpretations of scientific terms from the standpoint of economic, managerial, sociological and psychological approaches are considered. It is noted that corporate culture is driving force of dynamics in organizational changes and collective behavior, which determines the core of activity of the company's functional divisions. Corporate values are a fundamental psychological factor, being in dyadic interaction with each employee’s personal values. Therefore, the employees’ system of career value orientations should be consistent with the company’s system of professional values, for in synergy these are capable of helping the organization improve its efficiency and achieve the desired goal. A comparative analysis of organizational cultures, career and personal value orientations between the representatives of the Ukrainian metallurgical company "Metinvest" and the American telecommunications company "Koscom Cable Inc" was performed. It has been established that internal integration, mutual exchange of knowledge and management experience, and also improvement of the enterprises’ organizational structure should increase the performance of Ukrainian businesses in wartime.

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Sharma, Anupma, Guobin Luo, Na Li, Giorgio Pea, and Fiona Hyland. "Abstract 331: Ion TorrentTM NGS sequencing of the TERT promoter hotspots with Ion AmpliSeqTM HD technology." Cancer Research 84, no. 6_Supplement (March 22, 2024): 331. http://dx.doi.org/10.1158/1538-7445.am2024-331.

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Abstract Introduction: Recurrent mutations C228T and C250T in the TERT gene promoter are prevalent in cancer and serve as important biomarkers for aggressive disease. Ion Torrent™ NGS sequencing, combined with Ion AmpliSeqTM HD technology, enables comprehensive genomic profiling with ultra-high sensitivity for low-frequency variants in cell-free DNA (cf-DNA) and highly heterogeneous solid tumor samples. However, the high GC content (>80%) and the presence of G repeats that are known to adopt a compact stacked three-G-quadruplex conformation in the TERT gene promoter region pose sequencing challenges such as low read depth and strand-bias, i.e. prematurely truncated reads on one strand. Methods: We designed nine AmpliSeqTM HD panels with amplicon sizes of 70 to 104 bp, ideal for cf-DNA and FFPE samples, to target the recurrent TERT promoter hotspots. The designs were tested alone and combined with a larger Ion AmpliSeqTM HD DNA research panel resulting in highly multiplexed libraries. The libraries were used for Ion 540TM chip template preparation on the Ion ChefTM instrument and subsequently sequenced using the Ion GeneStudioTM S5 System. Sequencing data was used to evaluate coverage of the target hotspots by each design for each condition, and additional panels were designed to test single amplicons covering both TERT promoter hotspots. Results: Through performance evaluation, we selected two overlapping amplicons, each effectively amplifying one of the two hotspots. Individually tested, these amplicons yielded approximately 3000 families each from a 10ng gDNA input and when combined into the larger Ion AmpliSeqTM HD DNA research panel, they produced several thousand reads across various libraries, providing molecular coverage of around 200 functional molecules. While capture efficiency was lower compared to TERT amplicon-only libraries, these improved amplicons allow downstream analysis of variants. A single-pool solution (single amplicon/s covering both hotspots) will be explored further using the second batch of amplicons/primers. Conclusions: The optimized amplicons in two pools developed in this study enable the detection of challenging yet clinically significant TERT promoter hotspot mutations using the ultra-sensitive Ion AmpliSeqTM HD technology. For Research Use Only. Not for use in diagnostic procedures. © 2023 Thermo Fisher Scientific Inc. All rights reserved. All trademarks are the property of Thermo Fisher Scientific and its subsidiaries unless otherwise specified. Citation Format: Anupma Sharma, Guobin Luo, Na Li, Giorgio Pea, Fiona Hyland. Ion TorrentTM NGS sequencing of the TERT promoter hotspots with Ion AmpliSeqTM HD technology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 331.

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Weller, Toni. "The History and Heritage of Scientific and Technological Information Systems20061Edited by W.B. Rayward and M.E. Bowden. The History and Heritage of Scientific and Technological Information Systems. Medford NJ, on behalf of the American Society for Information Science and the Chemical Heritage Foundation: Information Today Inc. 2004. 440 pp., ISBN: 1‐57387‐229‐6." Journal of Documentation 62, no. 2 (March 2006): 291–93. http://dx.doi.org/10.1108/00220410610653343.

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Wetzman, A., T. Barnetche, C. Lukas, C. Gaujoux-Viala, B. Combe, J. Morel, and P. Szafors. "OP0214 INCIDENCE OF CANCER (RELAPSE OR NEW ONE) FOLLOWING BDMARDS INITIATION IN PATIENT WITH RHEUMATOID ARTHRITIS AND HISTORY OF CANCER: A SYSTEMATIC REVIEW WITH META-ANALYSIS OF OBSERVATIONAL STUDIES." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 133.2–133. http://dx.doi.org/10.1136/annrheumdis-2020-eular.4963.

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Background:The tolerance of targeted biologic therapies (bDMARDs) used in rheumatoid arthritis (RA) has been studied in patients with no history of cancer. A 5-year cancer remission is recommended to initiate treatment with bDMARDs. However, in the context of the aging of the population and the increase in screening for neoplasia, the question of targeted treatment in a patient with RA with a history of cancer is usual.Objectives:To determine the risk of recurrence or a new malignancy when exposed to a b-DMARDs in adults with RA and a history of cancer.Methods:A systematic literature search of EMBASE, MEDLINE, Cochrane Library, and electronic abstract databases of the annual scientific meetings of both the European League Against Rheumatism and the American College of Rheumatology was conducted through June 2019 and selected all cohort follow-up studies including adults with RA with a history of cancer and treated with b-DMARDs (TNF inhibitors, rituximab, abatacept and tocilizumab). We compared the risk of relapse or new cancer onset between the groups treated with and without b-DMARDs. The RevMan 5.3 software was used to calculate the cumulative risks from each group’s Hazard Ratio (HR), with their 95% confidence intervals. The heterogeneity of the studies was evaluated by the Cochran Q test and expressed with the I2value.Results:26 observational cohort studies were selected, of which 12 were included in the meta-analysis. The overall risk of new cancer or recurrence of neoplasia in RA patients with a history of cancer, compared to control subjects, for all b-DMARDs combined was 1.09 (p=0.29, 95%CI [0.92-1.32], I2=16%). The risk of relapse or new cancer onset in patients exposed to TNF inhibitors was 1.11 (p=0.45, 95%CI [0.85-1.46], I2=48%) and 0.79 (p=0.49, 95%CI [0.41-1.53], I2=10%) for rituximab. The rate of recurrence was 1.32 (p=0.04, 95%CI [1.02-1.72], I2=0%) for skin cancer, 1.28 (p=0.07, 95%CI [0.98-1.67], I2=0%) for skin cancers excluding melanoma and 1.21 (p=0.31, 95%CI [0.84-1.72], I2=0%) for breast neoplasia.Conclusion:This is the first meta-analysis evaluating the risk of recurrence or new cancers in a RA population with a history of neoplasia exposed to b-DMARD. For patients with a history of cancer, for whom the benefit / risk balance has been found to be favorable, the initiation of b-DMARD treatment for RA does not seem to significantly increase the risk of recurrence or new cancer compared to patients naïve to biological treatments, apart from skin cancers including melanoma.Disclosure of Interests:Amélie Wetzman: None declared, Thomas Barnetche: None declared, Cédric Lukas: None declared, Cecile Gaujoux-Viala: None declared, Bernard Combe Grant/research support from: Novartis, Pfizer, Roche-Chugai, Consultant of: AbbVie; Gilead Sciences, Inc.; Janssen; Eli Lilly and Company; Pfizer; Roche-Chugai; Sanofi, Speakers bureau: Bristol-Myers Squibb; Gilead Sciences, Inc.; Eli Lilly and Company; Merck Sharp & Dohme; Pfizer; Roche-Chugai; UCB, Jacques Morel: None declared, Paulina Szafors: None declared

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Young, Guy, Miguel Escobar, Steven Pipe, and David L. Cooper. "Safety and Efficacy of Recombinant Factor VIIa (rFVIIa) in Congenital Hemophilia with Inhibitors (CHwI) in the Home Treatment Setting: Systematic Review of Clinical Studies and Registries." Blood 126, no. 23 (December 3, 2015): 2302. http://dx.doi.org/10.1182/blood.v126.23.2302.2302.

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Abstract Background: The FDA approved rFVIIa (NovoSeven®RT) in 1999 for treatment of CHwI patients (pts) and it has been studied in compassionate/emergency use programs, clinical trials, and registries for nearly 30 years in this indication. US prescribing information directs that initially, treatment should be instituted under supervision of a physician. While home treatment is common in hemophilia including patients with inhibitors in clinical studies, scientific publications often omit the treatment location. Recent information requests in relation to policy decisions by payers around home use of rFVIIa prompted systematic analysis of clinical studies and registries where predominant use was in the home setting. Aim: To analyze rFVIIa safety and efficacy data in home treatment in clinical trials and registries. Methods: A systematic review focusing on the efficacy and safety of rFVIIa for the management of congenital hemophilia A and B patients with inhibitors in the home setting was performed. Studies included in the review consisted of clinical trials (phase I-IV) and prospective and retrospective registries evaluating bleed management and prophylaxis. Results: A detailed review identified 14 studies for treatment of bleeding (3 phase II, 2 phase III, 9 phase IV) in the home setting including studies reporting on standard doses (90 mcg/kg), high single doses (270 mcg/kg), and observational studies (dosing per physician direction). These studies captured 865 patients treated for 9,024 bleeding episodes (see Table 1), including 640 patients with 6,999 episodes in studies where efficacy was evaluable. Efficacy was consistently high across studies. The 10-year Japanese post-marketing study (F7HAEM-1947) required all adverse events to be reported irrespective of causality; one patient had visual field defect and suspected cerebral infarction, one central venous occlusion, and two others had events that are not clearly thrombotic (hemolytic uremic syndrome, acute renal failure). The only thromboembolic event (TE) reported in phase II-III studies was in 1 patient in the phase II adept™2 trial, which compared vatreptacog alpha with rFVIIa. Apart from the Japanese study, thrombotic rate was 1/7306 bleeds (0.014%). Table 1. On demand treatment of bleeding with rFVIIa Trial ID Phase Number of Patients Number of Bleeds Efficacy Safety F7HAEM-1510 II 22 42 88% No TE F7HAEM-2068 II 24 45 91-92% No TE NN7128-1907 (Pioneer 1) II 23 359 84% No TE F7HT/USA/1/USA (US Home Trx) III 56 877 92% No TE NN1731-3562 (adept™2) III 57 227 93% 1 TE HRS/HTRS Registry (2000-2003) IV 42 793 87% No TE HTRS Registry (2004-2008) IV 129 2,041 89-93% No TE F7HAEM-1965 (DOSE) IV 35 158 Not assessed (diary) No TE F7HAEM-3507 (ONE) IV 102 496 85-96% No TE NN7025-3601 (SMART-7) IV 51 511 Not reported (interim) No TE F7HAEM-3537 (UKHCDO Registry) IV 139 1,356 Not reported (diaries) No TE F7HAEM-1947 IV 144* 1,718* 88% 2TE† F7AHEM-1921 (WIRK Registry) IV 14 269 90% No TE F7HAEM-3850 IV 27 132 81%-92% No TE Total 865 9,024 * Patients with evaluable efficacy. † One visual field defect with suspected cerebral infarction, one central venous occlusion. Two studies evaluated rFVIIa for secondary prophylaxis (1 phase II, 1 phase IV) (see Table 2). The phase II study captured 22 patients treated with 90 or 270 mcg/kg daily. The phase IV retrospective study captured 86 patients with varied rFVIIa doses that often changed over time. Effective reduction in bleeding was seen in both studies. Across 108 patients treated with prophylaxis at home over 42,861 days, there were no thrombotic events reported. Table 2. Secondary Prophylaxis with rFVIIa Trial ID Phase Number of Patients Number of Prophylaxis Days Efficacy Safety F7HAEM-1505 II 22 1,885 45-59% reduction No TE F7HAEM-3695 (PRO-PACT) IV 86 40,976 46-52% No TE Total 108 42,861 Conclusions: Analysis of data from clinical studies of rFVIIa in home treatment of bleeding and secondary prophylaxis of bleeding demonstrates consistent efficacy for treatment and prevention of bleeding. Thrombotic events were uncommon across ~9,000 bleeding episodes and not reported in ~43,000 prophylaxis days. These data support the safety and efficacy of rFVIIa in the home treatment setting and sufficient evidence for payers to continue its approval in the home management of hemophilia patients. Disclosures Young: Kedrion: Consultancy; Bayer: Consultancy; Baxter: Consultancy; Biogen Idec: Consultancy, Honoraria; Novo Nordisk: Consultancy, Honoraria. Escobar:Novo Nordisk Inc.: Consultancy; Baxter: Consultancy; Bayer: Consultancy; Pfizer: Consultancy; Biogen: Consultancy; CSL Behring: Consultancy. Pipe:Biogen Idec Inc: Consultancy; CSL Behring: Consultancy; Bayer: Consultancy; American Thrombosis and Hemostasis Network: Other: Chair of the Board of Directors; National Hemophilia Foundation: Other: member of the Medical and Scientific Advisory Committee; Novo Nordisk: Consultancy; Baxter: Consultancy. Cooper:Novo Nordisk Inc.: Employment.

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Boschee, Pam. "Comments: New Year Marks JPT’s 75th Anniversary." Journal of Petroleum Technology 76, no. 01 (January 1, 2024): 10–11. http://dx.doi.org/10.2118/0124-0010-jpt.

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We’re excited to begin the year with the commemoration of JPT’s 75th anniversary. This issue launches our special features dedicated to JPT’s reporting of technology and practices over the past 7½ decades. Emerging Technology Senior Editor Stephen Rassenfoss and Senior Technology Editor Trent Jacobs penned this month’s articles highlighting innovations in drilling, completions, and reservoir engineering. Each month, our editors will dive into the archives to round up milestones of industry advancements and achievements as reported in JPT. Since its inaugural issue in January 1949, JPT has remained true to its mission of reporting the technological and scientific learnings and advancements in the global oil and gas industry. Built upon a strong technical foundation, it continues to draw upon the expertise and knowledge of industry experts to disseminate up-to-date, relevant information to SPE members from all disciplines. JPT’s evolution began with The American Institute of Mining, Metallurgical, and Petroleum Engineers (AIME), founded in 1871 in Wilkes-Barre, Pennsylvania. It was one of the first national engineering societies established in the US. In subsequent years, AIME was joined by four other engineering founder societies—The American Society of Mechanical Engineers (ASME), the American Institute of Electrical Engineers (now the Institute of Electrical and Electronics Engineers [IEEE]), the American Society of Civil Engineers (ASCE), and the American Institute of Chemical Engineers (AIChE)—and formed the United Engineering Foundation. (US President Herbert Hoover, a mining engineer, served as AIME’s president in 1920.) As AIME itself continued to grow, it decentralized and formed four independently operated member societies: SME (Society for Mining, Metallurgy, and Exploration); TMS (The Minerals, Metals, and Materials Society); AIST (Association for Iron & Steel Technology); and SPE (Society of Petroleum Engineers). AIME had as part of its membership a small, but growing, number of petroleum engineers. These members had specific technological issues far removed from their peers in the older, more-established engineering disciplines. The AIME Petroleum Branch Executive Committee (whose members represented companies such as The Pure Oil Co., Dowell Inc., Humble Oil and Refining Co., and the Texas Co.) determined that the best way to meet this group’s needs was to develop a “publication so dominantly petroleum as to secure wide reader interest,” one that would “rapidly gain the respect of the industry.” Over the years, that goal was achieved. JPT came to be recognized worldwide as the source for authoritative technical information in the petroleum industry. JPT’s first issue included four technical papers, one of which was “A Hydraulic Process for Increasing the Productivity of Wells.” The paper’s author, J.B. Clark, noted, “To date the process has been used in 32 jobs on 23 wells in 7 fields, resulting in a sustained increase in production in 11 wells.” The hydraulic fracturing techniques for well stimulation that he discussed have been responsible for the subsequent recovery of billions of barrels of oil. Also, bear in mind that the world’s total crude oil production in 1949 was about 3.8 billion bbl, less than the projected total US annual production in 2023—4.7 billion bbl. Other articles related to the oil and gas business were “Private Financing of Oil-Producing Properties” and “Middle Eastern Oil and Its Importance to the World.” Interestingly, although the content is outdated, both topics remain relevant today, 75 years later. Join us each month to explore our rich history and follow us on LinkedIn. All issues of JPT from 1949 to date are available in OnePetro. Even a cursory glance at the titles of the papers will show the remarkable evolution of technology over the years. We wish you the best in 2024, both in your professional and personal lives.

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Mack, Andrew R., Christopher Bethel, Steven Marshall, Robin Patel, Robin Patel, David van Duin, Vance G. Fowler, et al. "133. ARGONAUT-III: Susceptibility of Carbapenem-resistant Klebsiellae to Cefepime-Taniborbactam." Open Forum Infectious Diseases 8, Supplement_1 (November 1, 2021): S81—S82. http://dx.doi.org/10.1093/ofid/ofab466.133.

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Abstract Background Klebsiellae are Gram-negative pathogens responsible for serious nosocomial and community-acquired infections. Carbapenem resistance, both intrinsic and acquired, complicates therapy. Taniborbactam (formerly VNRX-5133; Fig 1) is a bicyclic boronate β-lactamase inhibitor (BLI) that inhibits all four Ambler classes of β-lactamase enzymes, both serine- and metallo-, with the notable exception of class B IMP β-lactamases. Taniborbactam is currently undergoing phase 3 clinical trials in combination with cefepime (FEP; Fig 1) as part of the β-lactam-BLI (BL-BLI) combination FEP-taniborbactam (FTB). Figure 1. Structures of taniborbactam and cefepime. The β-lactamase inhibitor is in red and the β-lactam antibiotic is in black. Methods We determined the activity of FTB against 200 carbapenem-resistant Klebsiellae (CRK) strains collected as part of the Antibiotic Resistance Leadership Group (ARLG) Consortium on Resistance against Carbapenems in Klebsiella (CRACKLE) study. Among these strains, 193 expressed class A KPCs, one expressed a class B NDM, and six expressed class D OXA-48 or variants. Broth microdilution minimum inhibitory concentrations (MIC)s were determined using the ThermoFisher Sensititre system with custom assay panels. American Type Culture Collection strains were used for quality control. The susceptible-dose-dependent breakpoint for FEP was provisionally used for FTB, where taniborbactam was fixed at 4 µg/mL. Results Among the 200 Klebsiella strains tested, susceptibility for β-lactams alone ranged from 1% for ceftazidime (CAZ), 2.5% for meropenem, and 13.5% for FEP (Table 1). The addition of BLIs increased % susceptibility compared to BL alone to: 98% for CAZ-avibactam (CZA); 95.5% for MEM-vaborbactam (MVB); and 99.0% for FTB. MIC50 and MIC90 were in the susceptible and provisionally susceptible range for CZA and MVB, and in the provisionally susceptible range for FTB. Analyzing the CZA and MVB non-susceptible strains, 7 of 9 MVB non-susceptible strains and 2 of 4 CZA-resistant strains were provisionally susceptible to FTB. Table 1. MIC50 and MIC90 values (μg/mL) and percent susceptibility for Klebsiella pneumoniae strains (n=200). AMK, amikacin; CST, colistin; CAZ, ceftazidime; CZA, ceftazidime-avibactam; FEP, cefepime; FTB, cefepime-taniborbactam; MEM, meropenem; MVB, meropenem-vaborbactam; TGC, tigecycline. * The breakpoint for CST is intermediate, as no susceptible breakpoint is available. ** The susceptible-dose-dependent breakpoint for FEP alone was provisionally applied to FTB, where taniborbactam was fixed at 4 μg/mL. Breakpoints from CLSI M100, 31st ed, 2021. Conclusion The addition of taniborbactam restored susceptibility to FEP in 99.0% of CRACKLE isolates studied, comparable to CZA and MVB. Taniborbactam also restored FEP activity against some MVB- and CZA-resistant strains. FTB may provide a promising therapy for CRK infections. Disclosures Robin Patel, MD, 1928 Diagnostics (Consultant)BioFire Diagnostics (Grant/Research Support)ContraFect Corporation (Grant/Research Support)Curetis (Consultant)Hylomorph AG (Grant/Research Support)IDSA (Other Financial or Material Support, Editor’s Stipend)Infectious Diseases Board Review Course (Other Financial or Material Support, Honoraria)Mammoth Biosciences (Consultant)NBME (Other Financial or Material Support, Honoraria)Netflix (Consultant)Next Gen Diagnostics (Consultant)PathoQuest (Consultant)PhAST (Consultant)Qvella (Consultant)Samsung (Other Financial or Material Support, Patent Royalties)Selux Diagnostics (Consultant)Shionogi & Co., Ltd. (Grant/Research Support)Specific Technologies (Consultant)TenNor Therapeutics Limited (Grant/Research Support)Torus Biosystems (Consultant)Up-to-Date (Other Financial or Material Support, Honoraria) Robin Patel, MD, BioFire (Individual(s) Involved: Self): Grant/Research Support; Contrafect (Individual(s) Involved: Self): Grant/Research Support; IDSA (Individual(s) Involved: Self): Editor’s stipend; NBME, Up-to-Date and the Infectious Diseases Board Review Course (Individual(s) Involved: Self): Honoraria; Netflix (Individual(s) Involved: Self): Consultant; TenNor Therapeutics Limited (Individual(s) Involved: Self): Grant/Research Support; to Curetis, Specific Technologies, Next Gen Diagnostics, PathoQuest, Selux Diagnostics, 1928 Diagnostics, PhAST, Torus Biosystems, Mammoth Biosciences and Qvella (Individual(s) Involved: Self): Consultant David van Duin, MD, PhD, Entasis (Advisor or Review Panel member)genentech (Advisor or Review Panel member)Karius (Advisor or Review Panel member)Merck (Grant/Research Support, Advisor or Review Panel member)Pfizer (Consultant, Advisor or Review Panel member)Qpex (Advisor or Review Panel member)Shionogi (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member)Utility (Advisor or Review Panel member) Vance G. Fowler, Jr., MD, MHS, Achaogen (Consultant)Advanced Liquid Logics (Grant/Research Support)Affinergy (Consultant, Grant/Research Support)Affinium (Consultant)Akagera (Consultant)Allergan (Grant/Research Support)Amphliphi Biosciences (Consultant)Aridis (Consultant)Armata (Consultant)Basilea (Consultant, Grant/Research Support)Bayer (Consultant)C3J (Consultant)Cerexa (Consultant, Other Financial or Material Support, Educational fees)Contrafect (Consultant, Grant/Research Support)Debiopharm (Consultant, Other Financial or Material Support, Educational fees)Destiny (Consultant)Durata (Consultant, Other Financial or Material Support, educational fees)Genentech (Consultant, Grant/Research Support)Green Cross (Other Financial or Material Support, Educational fees)Integrated Biotherapeutics (Consultant)Janssen (Consultant, Grant/Research Support)Karius (Grant/Research Support)Locus (Grant/Research Support)Medical Biosurfaces (Grant/Research Support)Medicines Co. (Consultant)MedImmune (Consultant, Grant/Research Support)Merck (Grant/Research Support)NIH (Grant/Research Support)Novadigm (Consultant)Novartis (Consultant, Grant/Research Support)Pfizer (Grant/Research Support)Regeneron (Consultant, Grant/Research Support)sepsis diagnostics (Other Financial or Material Support, Pending patent for host gene expression signature diagnostic for sepsis.)Tetraphase (Consultant)Theravance (Consultant, Grant/Research Support, Other Financial or Material Support, Educational fees)Trius (Consultant)UpToDate (Other Financial or Material Support, Royalties)Valanbio (Consultant, Other Financial or Material Support, Stock options)xBiotech (Consultant) Daniel D. Rhoads, MD, Becton, Dickinson and Company (Grant/Research Support) Michael Jacobs, MBBS, Venatorx Pharmaceuticals, Inc. (Grant/Research Support) Focco van den Akker, PhD, Venatorx Pharmaceuticals, Inc. (Grant/Research Support) David A. Six, PhD, Venatorx Pharmaceuticals, Inc. (Employee) Greg Moeck, PhD, Venatorx Pharmaceuticals, Inc. (Employee) Krisztina M. Papp-Wallace, Ph.D., Merck & Co., Inc. (Grant/Research Support)Spero Therapeutics, Inc. (Grant/Research Support)Venatorx Pharmaceuticals, Inc. (Grant/Research Support)Wockhardt Ltd. (Other Financial or Material Support, Research Collaborator) Robert A. Bonomo, MD, entasis (Research Grant or Support)Merck (Grant/Research Support)NIH (Grant/Research Support)VA Merit Award (Grant/Research Support)VenatoRx (Grant/Research Support)

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Mack, Andrew R., Christopher Bethel, Steven Marshall, Robin Patel, Robin Patel, David van Duin, Vance G. Fowler, et al. "1055. ARGONAUT-IV: Susceptibility of Carbapenem-resistant Klebsiellae to Ceftibuten/VNRX-5236." Open Forum Infectious Diseases 8, Supplement_1 (November 1, 2021): S619—S620. http://dx.doi.org/10.1093/ofid/ofab466.1249.

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Abstract Background Carbapenem resistance in Klebsiellae spp. arises through mutational and acquired mechanisms and is considered an “urgent threat” by the CDC. VNRX-5236 is a bicyclic boronate β-lactamase inhibitor (BLI) that combines oral bioavailability (via etzadroxil prodrug VNRX-7145; Figure 1) and activity against all three Ambler classes of serine β-lactamases. VNRX-7145 is currently in development with the oral cephalosporin, ceftibuten (CTB) (Figure 1). Figure 1. Structures of VNRX-7145, VNRX-5236, and ceftibuten. The β-lactamase inhibitors are in red and the β-lactam antibiotic is in black. Methods The activity of CTB/VNRX-5236 against 200 carbapenem-resistant Klebsiellae from the Consortium on Resistance against Carbapenems in Klebsiella (CRACKLE) was assessed in this study. Among these, 193 expressed class A KPC enzymes, one expressed a class B NDM enzyme, and six expressed a class D OXA-48 or variant enzyme. Minimum inhibitory concentrations (MIC) were determined by broth microdilution (CLSI M07 Ed. 11) using the ThermoFisher Sensititre system with custom assay panels. MICs were interpreted using CLSI M100 Ed. 30, except the EUCAST breakpoint for CTB (S≤1 µg/mL) was used for CTB and was applied for comparative purposes to CTB/VNRX-5236 MICs where VNRX-5236 was fixed at 4 µg/mL. American Type Culture Collection strains were used for quality control. Results 92.5% of stains studied in this CRACKLE collection were provisionally susceptible to CTB/VNRX-5236. In comparison, strains were 95.5% and 98% susceptible to meropenem-vaborbactam (MVB) and ceftazidime-avibactam (CZA), respectively. MIC50s were in the susceptible range for CZA, MVB, and CTB/VNRX-5236; and resistant for CTB, ceftazidime (CAZ) and meropenem (MEM). MIC90s were in the susceptible range for CZA, MVB, and CTB/VNRX-5236 and resistant range for CAZ, MEM, and CTB (Table 1). One of four CZA-resistant and three of nine MVB non-susceptible strains were provisionally susceptible to CTB/VNRX-5236. MIC50 and MIC90 values (µg/mL) and percent susceptibility for Klebsiella pneumoniae strains (n=200). AMK, amikacin; CST, colistin; CAZ, ceftazidime; CZA, ceftazidime-avibactam; FEP, cefepime; MEM, meropenem; MVB, meropenem-vaborbactam; CTB, ceftibuten; TGC, tigecycline. * The breakpoint for CST is intermediate, as no susceptible breakpoint is available. ** The CTB breakpoint is valid only for urinary tract isolates. *** The breakpoint for CTB was provisionally used for CTB/VNRX-5236, where VNRX-5236 was fixed at 4 µg/mL. Conclusion The addition of VNRX-5236 enhanced the activity of CTB against the 200 Klebsiella isolates tested, reaching a total of 92.5% susceptibility. The prodrug (VNRX-7145) allows for oral administration, making it a potential option for step-down therapy. Importantly, VNRX-5236 has a broader spectrum of activity than existing oral BLIs, opening new treatment options for resistant infections as a key addition to the existing antibiotic arsenal. Disclosures Robin Patel, MD, 1928 Diagnostics (Consultant)BioFire Diagnostics (Grant/Research Support)ContraFect Corporation (Grant/Research Support)Curetis (Consultant)Hylomorph AG (Grant/Research Support)IDSA (Other Financial or Material Support, Editor’s Stipend)Infectious Diseases Board Review Course (Other Financial or Material Support, Honoraria)Mammoth Biosciences (Consultant)NBME (Other Financial or Material Support, Honoraria)Netflix (Consultant)Next Gen Diagnostics (Consultant)PathoQuest (Consultant)PhAST (Consultant)Qvella (Consultant)Samsung (Other Financial or Material Support, Patent Royalties)Selux Diagnostics (Consultant)Shionogi & Co., Ltd. (Grant/Research Support)Specific Technologies (Consultant)TenNor Therapeutics Limited (Grant/Research Support)Torus Biosystems (Consultant)Up-to-Date (Other Financial or Material Support, Honoraria) Robin Patel, MD, BioFire (Individual(s) Involved: Self): Grant/Research Support; Contrafect (Individual(s) Involved: Self): Grant/Research Support; IDSA (Individual(s) Involved: Self): Editor’s stipend; NBME, Up-to-Date and the Infectious Diseases Board Review Course (Individual(s) Involved: Self): Honoraria; Netflix (Individual(s) Involved: Self): Consultant; TenNor Therapeutics Limited (Individual(s) Involved: Self): Grant/Research Support; to Curetis, Specific Technologies, Next Gen Diagnostics, PathoQuest, Selux Diagnostics, 1928 Diagnostics, PhAST, Torus Biosystems, Mammoth Biosciences and Qvella (Individual(s) Involved: Self): Consultant David van Duin, MD, PhD, Entasis (Advisor or Review Panel member)genentech (Advisor or Review Panel member)Karius (Advisor or Review Panel member)Merck (Grant/Research Support, Advisor or Review Panel member)Pfizer (Consultant, Advisor or Review Panel member)Qpex (Advisor or Review Panel member)Shionogi (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member)Utility (Advisor or Review Panel member) Vance G. Fowler, Jr., MD, MHS, Achaogen (Consultant)Advanced Liquid Logics (Grant/Research Support)Affinergy (Consultant, Grant/Research Support)Affinium (Consultant)Akagera (Consultant)Allergan (Grant/Research Support)Amphliphi Biosciences (Consultant)Aridis (Consultant)Armata (Consultant)Basilea (Consultant, Grant/Research Support)Bayer (Consultant)C3J (Consultant)Cerexa (Consultant, Other Financial or Material Support, Educational fees)Contrafect (Consultant, Grant/Research Support)Debiopharm (Consultant, Other Financial or Material Support, Educational fees)Destiny (Consultant)Durata (Consultant, Other Financial or Material Support, educational fees)Genentech (Consultant, Grant/Research Support)Green Cross (Other Financial or Material Support, Educational fees)Integrated Biotherapeutics (Consultant)Janssen (Consultant, Grant/Research Support)Karius (Grant/Research Support)Locus (Grant/Research Support)Medical Biosurfaces (Grant/Research Support)Medicines Co. (Consultant)MedImmune (Consultant, Grant/Research Support)Merck (Grant/Research Support)NIH (Grant/Research Support)Novadigm (Consultant)Novartis (Consultant, Grant/Research Support)Pfizer (Grant/Research Support)Regeneron (Consultant, Grant/Research Support)sepsis diagnostics (Other Financial or Material Support, Pending patent for host gene expression signature diagnostic for sepsis.)Tetraphase (Consultant)Theravance (Consultant, Grant/Research Support, Other Financial or Material Support, Educational fees)Trius (Consultant)UpToDate (Other Financial or Material Support, Royalties)Valanbio (Consultant, Other Financial or Material Support, Stock options)xBiotech (Consultant) Daniel D. Rhoads, MD, Becton, Dickinson and Company (Grant/Research Support) Michael Jacobs, MBBS, Venatorx Pharmaceuticals, Inc. (Grant/Research Support) Focco van den Akker, PhD, Venatorx Pharmaceuticals, Inc. (Grant/Research Support) David A. Six, PhD, Venatorx Pharmaceuticals, Inc. (Employee) Greg Moeck, PhD, Venatorx Pharmaceuticals, Inc. (Employee) Krisztina M. Papp-Wallace, Ph.D., Merck & Co., Inc. (Grant/Research Support)Spero Therapeutics, Inc. (Grant/Research Support)Venatorx Pharmaceuticals, Inc. (Grant/Research Support)Wockhardt Ltd. (Other Financial or Material Support, Research Collaborator) Robert A. Bonomo, MD, entasis (Research Grant or Support)Merck (Grant/Research Support)NIH (Grant/Research Support)VA Merit Award (Grant/Research Support)VenatoRx (Grant/Research Support)

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Fortune, Erica E., Melissa F. Miller, Elissa C. Kranzler, Jemeille Ackourey, Kelly Clark, Heather Badt, Linda Bohannon, Craig E. Cole, Thomas W. Leblanc, and Alexandra K. Zaleta. "Financial Burden Is Associated with Postponing Care and Decreasing Physical and Emotional Quality of Life Among Patients with Multiple Myeloma and Chronic Lymphocytic Leukemia." Blood 136, Supplement 1 (November 5, 2020): 45. http://dx.doi.org/10.1182/blood-2020-137050.

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Background: Numerous factors contribute to the financial burden experienced by the cancer population, including medical expenses and possible job disruption or loss. The financial burdens that accompany a cancer diagnosis can influence cancer-care decisions, including the delay of essential treatment or appointments, with deleterious effects on physical and mental quality of life (QOL). Further, certain sociodemographic groups face increased risk of financial burden. The aim of this study was to examine the relationships between financial burden, postponing care, and physical and emotional quality of life among patients with multiple myeloma (MM) and chronic lymphocytic leukemia (CLL). Methods: 435 patients (72% MM; 28% CLL) enrolled in the Cancer Support Community's online survey, the Cancer Experience Registry, answered questions related to financial burden (8 items; yes/no response), postponing care (6 items; 5-point Likert scale), and QOL assessed using Patient-Reported Outcomes Measurement Information System (PROMIS-29v2.0) subscales (Anxiety, Depression, Physical Function, and Fatigue) with transformed T scores. We applied Structural Equation Modeling (SEM) to understand the direct and indirect relationship of financial burden (tally of "yes" responses to the 8 financial cost variables) with latent constructs comprising postponing care, physical QOL, and emotional QOL, and sociodemographic and clinical predictor variables. Results: Sample characteristics: mean age=62 yrs (9.2); 88% non-Hispanic White; 6% non-Hispanic Black; mean time since diagnosis=5.2 yrs (4.3); 28% ISS Stage 3 for MM or Rai Stage 3-4 for CLL. Regarding financial status, 21% have an annual income <$40k; 22% spent >$500 in monthly out-of-pocket (OOP) costs to cover cancer care and an additional 23% spent over $250. Due to the financial costs of cancer care, 29% of participants depleted their savings, 19% borrowed against or used money from a retirement plan, 13% liquidated assets, 7% collected unemployment insurance, 4% took an extra job, 4% chose a less effective treatment, 4% cashed in a life insurance policy early, and 2% had their house foreclosed. While 41% were moderately to very seriously concerned about health insurance or money, 66% reported that no one from their health care team talked to them about costs. Based on the percent reporting sometimes, often, or always engaging in behaviors related to postponing care: 12% postponed doctor's appointments, 5% postponed follow-up screening or bloodwork, 6% postponed filling prescriptions, 5% skipped dosages of prescribed drugs, 12% delayed complementary treatment including therapy, and 16% postponed psychological counseling or support. SEM analyses demonstrate that age (standardized path coefficient β=-0.17), low income (β=0.24), OOP costs (β=0.18), time since diagnosis (β=0.11), and advanced stage (β=0.17) had a significant (p<.05) effect on financial burden and financial burden, in turn, had a significant effect on postponing care (β=0.40)Further, financial burden had both a direct (β=-0.17) and indirect (β=-0.10) effect through postponing care on physical QOL, and both a direct (β=0.15) and indirect (β=0.12) effect through postponing care on emotional QOL. The χ2 of the final model was 454.2 (df=129, p<.001) and was a reasonably good fit to the data (RMSEA=0.076). Conclusions: Findings highlight the significant effect of financial burden on postponing care and poorer QOL among MM and CLL patients. Financial burden was associated with patients' treatment decisions for both cancer and psychological care, and while many patients reported distress about money and health insurance, the majority did not discuss cost of care with their health care team. Thus, MM and CLL patients may benefit from access to no- or low-cost preventative and supportive psychosocial care, as well as financial counseling and assistance with health care team communication. Patient-focused organizations help address this need through no-cost resources, including distress screening tools, access to a financial counselor on a toll-free helpline, and information about treatment decision-making. Future research that incorporates cost of care into physician-patient communication is warranted. Disclosures Fortune: Boston Scientific Foundation: Research Funding; Genentech: Research Funding. Kranzler:Astellas Pharma US, Inc.: Research Funding; Pharmacyclics, Inc.: Research Funding; Jazz Pharmaceuticals: Research Funding; Takeda Oncology: Research Funding; Janssen Oncology: Research Funding. Leblanc:Agios, AbbVie, and Bristol Myers Squibb/Celgene: Speakers Bureau; AstraZeneca: Research Funding; AbbVie, Agios, Amgen, AstraZeneca, CareVive, BMS/Celgene, Daiichi-Sankyo, Flatiron, Helsinn, Heron, Otsuka, Medtronic, Pfizer, Seattle Genetics, Welvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; American Cancer Society, BMS, Duke University, NINR/NIH, Jazz Pharmaceuticals, Seattle Genetics: Research Funding; UpToDate: Patents & Royalties: Royalties. Zaleta:Athenex Oncology: Research Funding; Gilead Sciences, Inc: Research Funding; Pfizer, Inc.: Research Funding.

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Pickle, Loni, Andrew Hatch, Gokhan Yavas, Melanie Spears, Louis Gasparini, Vida Talebian, Anna Ying-Wah Lee, et al. "Abstract 4416: Rapid, low-input, targeted NGS workflow for DNA methylation." Cancer Research 84, no. 6_Supplement (March 22, 2024): 4416. http://dx.doi.org/10.1158/1538-7445.am2024-4416.

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Abstract DNA methylation is a fundamental epigenetic process that regulates human gene expression. In cancer, methylation changes promote proliferation networks and metastasis. Development of biomarkers for methylation will be enabled by flexible, fast, low-input next generation sequencing workflows. We describe the first Ion AmpliSeq™ Methylation targeted panel and protocol on the turn-key Genexus™ Integrated Sequencer as part an ongoing collaboration with Ontario Institute for Cancer Research (OICR) to detect and predict response in early stage breast cancer and improve diagnostics for Black and Asian women. A 2-pool Ion AmpliSeq™ Methylation Panel for Breast Cancer Research was developed as a demonstration of design, workflow, and reporting for targeted, low-input methylation assessment in a multiplex setting across a variety of samples sources including FFPE. The panel contains 327 amplicons and was designed to target both strands and 10ng DNA input into bisulfite conversion was used for controls. A complete workflow begins at bisulfite conversion and progresses through the Genexus™ Integrated Sequencer which combines library construction, template preparation, and sequencing into a single run. The bioinformatics pipeline provides DNA methylation calls on both Watson and Crick strands at single base resolution and methylated:unmethylated ratios for each CpG. The entire end-to-end workflow was completed in 2 days, including a full analysis software solution. The panel was evaluated using 2 control gDNA samples. The first had an expected average methylation state across all CpGs of >98% and the second <5%. An equal mixture of these two samples was also tested. The Methylation Panel for Cancer Research performed well on control samples. The single lane Loading, Total Bases, Final Reads, and Raw Read Accuracy were >92%, >1G, >14 Million, and >90% respectively. The workflow was also demonstrated on research FFPE cancer samples. This Methylation Panel protocol offers a 2-day, end-to-end workflow with high resolution, targeted and quantitative methylation analysis from DNA input as low as 10ng into bisulfite conversion. The option to design custom methylation panels for interrogation of targets of interest without the need for whole genome methylation is now available. <For Research Use Only. Not for use in diagnostic procedures. Early access materials were provided by Thermo Fisher Scientific™ to OICR in support of this abstract, but no other financial support. This study was conducted with the support of the Ontario Institute for Cancer Research through funding provided by the Government of Ontario. © 2023 Thermo Fisher Scientific Inc. All rights reserved. All trademarks are the property of Thermo Fisher Scientific and its subsidiaries unless otherwise specified.> Citation Format: Loni Pickle, Andrew Hatch, Gokhan Yavas, Melanie Spears, Louis Gasparini, Vida Talebian, Anna Ying-Wah Lee, Mathieu Lariviere, Jane Bayani, Seth Sadis, Jeffrey M. Smith. Rapid, low-input, targeted NGS workflow for DNA methylation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4416.

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Guerino-Cunha, Renato L., Diego Clé, Leonardo Carvalho Palma, Camila Dermínio Donadel, Lucas Oliveira, Patricia Oliveira da Cunha Terra, Thalita Cristina de Mello Costa, et al. "Viability of Chimeric Antigen Receptor T Cell Therapy in Latin America." Blood 138, Supplement 1 (November 5, 2021): 4843. http://dx.doi.org/10.1182/blood-2021-154217.

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Abstract Introduction: Treatment of diffuse large B cell lymphoma (DLBCL) may be a challenge for Latin American countries. Thus, novel strategies to reduce the economic burden of oncological care are necessary. In Brazil, the DLBCL annual incidence is approximately 6.000 cases, among which 30% will relapse or become refractory (R/R). In this scenario, the limited access to the new therapies reinforce the need to develop new local technologies and improve research initiatives. Here we report the development and clinical application of a Brazilian platform to manufacture genetically modified T-cells to treat patients with R/R leukemia and lymphomas, which may also help reverse the poor prognosis of these patients in low and middle-income countries. Patients and Methods: All patients were referred to our center to consider compassionate use of anti-CD19 CAR-T cell therapy. The treatment was authorized by the local medical ethical committee. Once patients were deemed to be eligible for CAR-T, they were scheduled for lymphopheresis and the cells were processed and cryopreserved. During the manufacturing process and after completion of lymphophersis, all three patients received bridging therapy. Prior to infusion of CAR-T, patients were given lymphodepletion chemotherapy with cyclophosphamide and fludarabine for 3 days. Patients were monitored daily for the occurrence of cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS), which were graduated according to the criteria of the American Society for Transplantation and Cellular Therapy. These treatments were only available because we developed a Brazilian platform to manufacture genetically modified T-cells. Firstly, we developed and validated in vitro and in vivo anti-CD19 CAR T cell expression, expansion, and cytotoxicity. Secondly, in-house lentiviral good-manufacturing practice (GMP) protocols were established for clinical purposes. Thirdly, we upscaled the manufacturing process into the GMP facility originally developed for MSCs and adapted it to genetically modified T-cells. Finally, in-house procedures to deliver anti-CD19 CAR T cells for clinical use were established according to the Brazilian Health Regulatory Agency (ANVISA) policies. Once these steps were implemented, we were able to treat the first three patients of a patient with CAR-T cells produced in Latin America. Results: Two patients presented CAR-T cell expansion after the procedure (Figure 1). Within thirty days after the infusion one patient achieved complete response, one had partial response and one was not evaluated (Table 1). All patients had CRS and only one had ICANS. Two patients died, one from infection and other from intracranial hemorrhage due to domestic accident, --- and --- days after CAR-T cell infusion, respectively. Discussion: At least two of the reported patients presented improvement of their disease. The other one died before the expected response could have been evaluated. None of the patients died from complications related to manufacturing or infusion procedures, highlighting an acceptable safety profile of the platform. Although these are preliminary results, the CAR-T cell expansion profile, presence of systemic inflammatory response and lack of early disease progression suggest the treatment effectiveness. Conclusion: Apart from all the scientific challenges, this experience highlights the feasibility to implement a viable and efficient CAR-T platform in middle-income countries. Besides, implementation of advanced cellular therapy can also contribute to enhancing the quality of other cellular therapies. Figure 1 Figure 1. Disclosures Guerino-Cunha: Novartis: Other: Speaker; BMS: Other: Speaker; Janssen: Other: Speaker. Calado: Instituto Butantan: Consultancy; Alexion Brasil: Consultancy; Team Telomere, Inc.: Membership on an entity's Board of Directors or advisory committees; Novartis Brasil: Honoraria; Agios: Membership on an entity's Board of Directors or advisory committees; AA&MDS International Foundation: Research Funding.

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Mack, Andrew R., Christopher Bethel, Steven Marshall, Robin Patel, Robin Patel, David van Duin, Vance G. Fowler, et al. "1063. ARGONAUT-V: Susceptibility of Multidrug-Resistant (MDR) Pseudomonas aeruginosa to Cefepime-Taniborbactam." Open Forum Infectious Diseases 8, Supplement_1 (November 1, 2021): S623—S624. http://dx.doi.org/10.1093/ofid/ofab466.1257.

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Abstract Background P. aeruginosa is a Gram-negative pathogen responsible for many serious infections. MDR, both intrinsic and acquired, presents major clinical challenges. Taniborbactam (formerly VNRX-5133; Fig 1) is a β-lactamase inhibitor (BLI) characterized as a bicyclic boronate, uniquely possessing activity toward all four Ambler classes of β-lactamases, both serine and metallo, with the exception of class B IMP β-lactamases. The β-lactam-BLI (BL-BLI) combination cefepime-taniborbactam (FTB; Fig 1) is currently in phase 3 clinical trials. Structures of taniborbactam and cefepime. The β-lactamase inhibitor is in red and the β-lactam antibiotic is in black. Methods The activity of FTB was tested against 197 well-characterized clinical P. aeruginosa isolates that were part of PRIMERS (Platforms for Rapid Identification of MDR-Gram-negative bacteria and Evaluation of Resistance Studies). Nearly 58% of these strains were reported as carbapenem-non-susceptible. Porin changes, efflux pumps, and/or the presence of acquired class A or class B carbapenemases were previously reported. Broth microdilution minimum inhibitory concentrations (MICs) were determined by CLSI M07 Ed. 11 methods with custom Sensititre frozen panels and interpreted using CLSI M100 Ed. 30 breakpoints. American Type Culture Collection strains were used for quality control. FEP breakpoints were provisionally used for FTB, where taniborbactam was fixed at 4 µg/mL. Results Percent susceptibility to BL agents alone was 45.2% for imipenem (IPM), 55.8% for meropenem (MEM), 60.9% for ceftazidime (CAZ), and 67.0% for FEP. The addition of BLI to BL increased % susceptibility for MEM-vaborbactam (MVB), 56.9%; ceftolozane-tazobactam (C/T), 77.7%, CAZ-avibactam (CZA), 79.7%, and FTB, 82.7%. MIC50s were in the susceptible range for all drugs except IPM, which was intermediate, and all MIC90s were in the resistant range (Table 1). Taniborbactam reduced FEP MIC by 2-fold in 32% of isolates and ≥ 4-fold in 13% of isolates. Against carbapenem-non-susceptible strains, % susceptibilities were: FTB, 68.5%, CZA, 63.0%, C/T, 59.3%; and MVB, 21.3% (Table 2). MIC50 and MIC90 values (µg/mL) and percent susceptibility (%S) for all P. aeruginosa strains (n=197). AMK, amikacin; ATM, aztreonam; C/T, ceftolozane-tazobactam; CAZ, ceftazidime; CZA, ceftazidime-avibactam; FEP, cefepime; FTB, cefepime-taniborbactam; IPM, imipenem; MEM, meropenem; MVB, meropenem-vaborbactam; TZP, piperacillin-tazobactam; TOB, tobramycin. *The breakpoints for FEP and MEM alone were provisionally applied to FTB and MVB, respectively. Tazobactam, avibactam, and taniborbactam were fixed at 4 µg/mL, while vaborbactam was fixed at 8 µg/mL. Breakpoints from CLSI M100, 31st ed, 2021. MIC50 and MIC90 values (µg/mL) and percent susceptibility (%S) for the subset of carbapenem-non-susceptible P. aeruginosa strains (n=108). AMK, amikacin; ATM, aztreonam; C/T, ceftolozane-tazobactam; CAZ, ceftazidime; CZA, ceftazidime-avibactam; FEP, cefepime; FTB, cefepime-taniborbactam; IPM, imipenem; MEM, meropenem; MVB, meropenem-vaborbactam; TZP, piperacillin-tazobactam; TOB, tobramycin. *The breakpoints for FEP and MEM alone were provisionally applied to FTB and MVB, respectively. Tazobactam, avibactam, and taniborbactam were fixed at 4 µg/mL, while vaborbactam was fixed at 8 µg/mL. Breakpoints from CLSI M100, 31st ed, 2021. Conclusion Compared to MVB, CZA, and C/T, FTB demonstrated the greatest activity against the 197 P. aeruginosa strains tested, including many carbapenem-non-susceptible strains. Pending completion of clinical development, FTB may be a promising therapeutic option for MDR P. aeruginosa infections. Disclosures Robin Patel, MD, 1928 Diagnostics (Consultant)BioFire Diagnostics (Grant/Research Support)ContraFect Corporation (Grant/Research Support)Curetis (Consultant)Hylomorph AG (Grant/Research Support)IDSA (Other Financial or Material Support, Editor’s Stipend)Infectious Diseases Board Review Course (Other Financial or Material Support, Honoraria)Mammoth Biosciences (Consultant)NBME (Other Financial or Material Support, Honoraria)Netflix (Consultant)Next Gen Diagnostics (Consultant)PathoQuest (Consultant)PhAST (Consultant)Qvella (Consultant)Samsung (Other Financial or Material Support, Patent Royalties)Selux Diagnostics (Consultant)Shionogi & Co., Ltd. (Grant/Research Support)Specific Technologies (Consultant)TenNor Therapeutics Limited (Grant/Research Support)Torus Biosystems (Consultant)Up-to-Date (Other Financial or Material Support, Honoraria) Robin Patel, MD, BioFire (Individual(s) Involved: Self): Grant/Research Support; Contrafect (Individual(s) Involved: Self): Grant/Research Support; IDSA (Individual(s) Involved: Self): Editor’s stipend; NBME, Up-to-Date and the Infectious Diseases Board Review Course (Individual(s) Involved: Self): Honoraria; Netflix (Individual(s) Involved: Self): Consultant; TenNor Therapeutics Limited (Individual(s) Involved: Self): Grant/Research Support; to Curetis, Specific Technologies, Next Gen Diagnostics, PathoQuest, Selux Diagnostics, 1928 Diagnostics, PhAST, Torus Biosystems, Mammoth Biosciences and Qvella (Individual(s) Involved: Self): Consultant David van Duin, MD, PhD, Entasis (Advisor or Review Panel member)genentech (Advisor or Review Panel member)Karius (Advisor or Review Panel member)Merck (Grant/Research Support, Advisor or Review Panel member)Pfizer (Consultant, Advisor or Review Panel member)Qpex (Advisor or Review Panel member)Shionogi (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member)Utility (Advisor or Review Panel member) Vance G. Fowler, Jr., MD, MHS, Achaogen (Consultant)Advanced Liquid Logics (Grant/Research Support)Affinergy (Consultant, Grant/Research Support)Affinium (Consultant)Akagera (Consultant)Allergan (Grant/Research Support)Amphliphi Biosciences (Consultant)Aridis (Consultant)Armata (Consultant)Basilea (Consultant, Grant/Research Support)Bayer (Consultant)C3J (Consultant)Cerexa (Consultant, Other Financial or Material Support, Educational fees)Contrafect (Consultant, Grant/Research Support)Debiopharm (Consultant, Other Financial or Material Support, Educational fees)Destiny (Consultant)Durata (Consultant, Other Financial or Material Support, educational fees)Genentech (Consultant, Grant/Research Support)Green Cross (Other Financial or Material Support, Educational fees)Integrated Biotherapeutics (Consultant)Janssen (Consultant, Grant/Research Support)Karius (Grant/Research Support)Locus (Grant/Research Support)Medical Biosurfaces (Grant/Research Support)Medicines Co. (Consultant)MedImmune (Consultant, Grant/Research Support)Merck (Grant/Research Support)NIH (Grant/Research Support)Novadigm (Consultant)Novartis (Consultant, Grant/Research Support)Pfizer (Grant/Research Support)Regeneron (Consultant, Grant/Research Support)sepsis diagnostics (Other Financial or Material Support, Pending patent for host gene expression signature diagnostic for sepsis.)Tetraphase (Consultant)Theravance (Consultant, Grant/Research Support, Other Financial or Material Support, Educational fees)Trius (Consultant)UpToDate (Other Financial or Material Support, Royalties)Valanbio (Consultant, Other Financial or Material Support, Stock options)xBiotech (Consultant) Daniel D. Rhoads, MD, Becton, Dickinson and Company (Grant/Research Support) Michael Jacobs, MBBS, Venatorx Pharmaceuticals, Inc. (Grant/Research Support) Focco van den Akker, PhD, Venatorx Pharmaceuticals, Inc. (Grant/Research Support) David A. Six, PhD, Venatorx Pharmaceuticals, Inc. (Employee) Greg Moeck, PhD, Venatorx Pharmaceuticals, Inc. (Employee) Krisztina M. Papp-Wallace, Ph.D., Merck & Co., Inc. (Grant/Research Support)Spero Therapeutics, Inc. (Grant/Research Support)Venatorx Pharmaceuticals, Inc. (Grant/Research Support)Wockhardt Ltd. (Other Financial or Material Support, Research Collaborator) Robert A. Bonomo, MD, entasis (Research Grant or Support)Merck (Grant/Research Support)NIH (Grant/Research Support)VA Merit Award (Grant/Research Support)VenatoRx (Grant/Research Support)

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Bagot, Martine, Stéphane Dalle, Lubomir Sokol, Athanasios Tsianakas, Amy Musiek, Pablo Ortiz-Romero, Brian Poligone, et al. "Long-Term Clinical Benefit to Anti-CCR4 Mogamulizumab: Results from the Phase 3 Mavoric Study in Previously Treated Cutaneous T-Cell Lymphoma (CTCL)." Blood 132, Supplement 1 (November 29, 2018): 2901. http://dx.doi.org/10.1182/blood-2018-99-118473.

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Abstract Background: CTCL represents a rare group of non-Hodgkin lymphomas with substantial negative impact on patient (pt) quality of life and mortality in advanced-stage disease. Mycosis fungoides (MF), the most common subtype of CTCL, and the rarer leukemic variant Sézary syndrome (SS) are distinct subtypes of CTCL. Mogamulizumab is a first-in-class, defucosylated monoclonal antibody directed against C-C chemokine receptor 4 (CCR4), which is highly expressed on malignant T-cells in CTCL. Primary results from the MAVORIC study (data cut-off December 2016), a phase 3 trial comparing mogamulizumab to FDA-approved vorinostat in adults with relapsed/refractory MF/SS, showed mogamulizumab significantly prolonged median progression-free survival compared with vorinostat (7.7 vs 3.1 months, P<0.0001), with a confirmed overall global response rate (comprised of all disease compartments) of 28% and an expected and generally manageable safety profile. This follow-up analysis assessed the safety and efficacy of mogamulizumab based on treatment exposure in order to characterize pts with MF/SS who were able to achieve long-term clinical benefit with mogamulizumab. Methods: This was an open-label, randomized, international, phase 3 study (NCT01728805). Pts with MF/SS who were treated with ≥1 prior systemic therapy were randomized 1:1 to receive mogamulizumab (1.0 mg/kg, administered once weekly for the first 28-day cycle, then on Days 1 and 15 of subsequent cycles) or oral vorinostat (400 mg daily). In this follow-up analysis (data cut-off September 2017), exposure quartiles were determined, and baseline demographics, confirmed global response rate, and safety were analyzed by exposure group. To detect linear trends across exposure quartiles, frequencies were analyzed using Chi-square test and continuous data were assessed by analysis of variance. Results: A total of 184 pts randomized to mogamulizumab were included in this analysis. Mean time of mogamulizumab exposure was 275 days (d; standard deviation [SD]: 292 d; range: 1-1617). Based on quartile assessment, >351 d was defined as cut-off for long-term exposure. Baseline characteristics across exposure groups are shown in the Table. Significant trends were observed for baseline Eastern Cooperative Oncology Group performance status (ECOG PS; P=0.04), disease type (P=0.03), and blood involvement (defined as ≥B1 per Olsen et al J Clin Oncol 2011; P<0.001), with long-term pts more likely to have an ECOG PS grade of 0, SS, and/or blood involvement. Confirmed global response rates increased with increasing exposure to mogamulizumab in pts with MF and SS (Figure; trend P<0.001 for MF, SS, or MF+SS). Of all randomized pts exposed to mogamulizumab for >351 d, 76% had a confirmed global response (ie, either complete or partial response). The percentage of pts reporting a treatment-emergent adverse event (AE) or serious AE did not vary with increasing exposure to mogamulizumab (<72 d exposure: 26% of pts with TEAEs and 6% with SAEs; 72-170 d: 18% and 3%, respectively; 171-350 d: 23% and 6%, respectively; >351 d: 21% and 4%, respectively). The most common treatment-related AEs reported by pts after >351 d of exposure to mogamulizumab were drug eruption (9/45 [20%]), thrombocytopenia (5/45 [11%]), stomatitis (4/45 [9%]), and anemia (4/45 [9%]). Conclusions: This follow-up analysis of the phase 3 MAVORIC study demonstrated mogamulizumab treatment of pts with MF/SS for approximately 1 year was not associated with an increased safety risk. Significant long-term clinical benefit was observed in pts with blood involvement at baseline, regardless of CCR4 expression status. A higher proportion of pts who had long-term (>351 days) exposure attained confirmed global response versus those who had less exposure. Disclosures Bagot: Takeda: Membership on an entity's Board of Directors or advisory committees; Innate Pharma: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Kyowa Kirin: Membership on an entity's Board of Directors or advisory committees; Actelion: Membership on an entity's Board of Directors or advisory committees. Dalle:Kyowa Hakko Kirin Pharmaceutical: Research Funding. Sokol:Mallinckrodt Pharmaceuticals: Consultancy; Seattle Genetics: Consultancy; Spectrum Pharmaceuticals: Consultancy. Tsianakas:Kyowa Kirin: Research Funding. Musiek:Seattle Genetics: Honoraria; Kyowa Kirin: Honoraria; Actelion: Other: Scientific Advisory Committee . Ortiz-Romero:Innate Pharma: Consultancy; Takeda: Consultancy; MEDA: Research Funding; Actelion: Consultancy; 4SC: Consultancy. Poligone:Johnson and Johnson: Research Funding; Kyowa Hakko Kirin: Research Funding; Soligenix: Research Funding; Mallinckrodt: Speakers Bureau; Stemline Therapeutics: Honoraria; Seattle Genetics: Honoraria. Duvic:Clinical Care Options: Consultancy; Soligenix, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Mallinckrddt Pharmaceuticals (formerly Therakos): Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Huron Consulting Group: Consultancy; Taiwan Liposome Company LTD: Consultancy; Rhizen Pharma: Research Funding; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kyowa Hakko Kirin, Co: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Precision Oncology, LLC: Membership on an entity's Board of Directors or advisory committees; Eisai: Research Funding; UT MD Anderson Cancer Center: Employment; Dr. Reddy's Laboratories (A.K.A. Promius Pharma): Consultancy; Defined Health: Consultancy; Medivir AB: Membership on an entity's Board of Directors or advisory committees; Medscape: Other: Speaker/Preceptor; Guidepoint Global: Consultancy; Jonathan Wood & Associates: Other: Speaker; Celgene Corp: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Evidera, Inc.: Consultancy; Kiniksa Pharmaceuticals: Consultancy; MEDACorp: Consultancy; The Lynx Group: Consultancy; Spatz Foundation: Research Funding; Forty Seven, Inc.: Membership on an entity's Board of Directors or advisory committees; Shape: Research Funding; Aclaris Therapeutics Int'l Ltd.: Honoraria, Membership on an entity's Board of Directors or advisory committees; Cell Medica Inc.: Consultancy, Honoraria; Allos: Research Funding; American Council on Extracorporeal Photopheresis (ACE): Membership on an entity's Board of Directors or advisory committees; Concert Pharmaceuticals, Inc.: Consultancy; Millennium Pharmaceuticals, Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; MiRagen Therapeutics: Consultancy; Huya Bioscience Int'l: Consultancy; Array Biopharma: Consultancy, Honoraria; Oncoceuticals: Research Funding; Tetralogics: Research Funding. Elmets:NCI: Research Funding; Veterans Administration: Research Funding; California Wine Grape Association: Research Funding; Soligenix: Research Funding; Elorac: Research Funding; Leo Pharma: Other: Data and Safety Monitoring Board. Leoni:Kyowa Kirin: Employment. Dwyer:Kyowa Kirin: Employment. Sun:Kyowa Kirin: Employment. Nikonova:Kyowa Kirin: Employment. Kim:miRagen: Research Funding; Forty Seven Inc: Research Funding; Kyowa-Kirin-Pharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Innate Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Horizon Pharma: Consultancy, Research Funding; Merck: Research Funding; Soligenix: Research Funding; Eisai: Membership on an entity's Board of Directors or advisory committees, Research Funding; Medivir: Membership on an entity's Board of Directors or advisory committees; Neumedicine: Consultancy, Research Funding; Portola: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Galderma: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Tetralogic: Research Funding.

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Brokars, John, Arianna Kee, Ali McBride, Sheila R. Reddy, Eunice Chang, Marian H. Tarbox, and Thomas W. LeBlanc. "Dasatinib Treatment Patterns after Pleural Effusion Among Patients with Chronic Myeloid Leukemia." Blood 138, Supplement 1 (November 5, 2021): 3607. http://dx.doi.org/10.1182/blood-2021-145456.

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Abstract Introduction Decision-making in the treatment (Tx) of chronic myeloid leukemia (CML) is complex and dependent on many factors, including disease phase and drug tolerability. The tyrosine kinase inhibitor (TKI) dasatinib is an effective long-term Tx option for most patients (pts) with newly diagnosed CML, based on the deep and durable responses reported in the DASISION trial (Cortes JE, et al. J Clin Oncol 2016); however, dasatinib was associated with the development of pleural effusion, an adverse event caused by the build-up of excess fluid in the pleural space outside of the lungs (Jany and Welte Dtsch Arztebl Int 2019). Data regarding the optimal strategy for managing pleural effusion among pts treated with dasatinib are limited. Dose reductions, interruptions or switching to another TKI are commonly used strategies but in the SIMPLICITY trial, pts who remained on first-line Tx had better clinical outcomes than pts who switched Tx (Gambacorti-Passerini C, et al. Eur J Haematol 2020). Here we present results of a study examining Tx patterns, including duration of dasatinib use after pleural effusion, and healthcare resource utilization (HCRU) and costs among pts with CML treated with dasatinib who experienced a subsequent pleural effusion. Methods Data from the IBM MarketScan ® Commercial and Medicare Supplemental Databases were used to identify pts diagnosed with CML (ICD-9-CM code 205.1x, 205.8x; ICD-10-CM code C92.1x, C92.Zx) during the study period (Jan 1, 2014 - Sep 30, 2019). Eligible pts were ≥ 18 y, had ≥ 1 pharmacy claim for dasatinib, and experienced a pleural effusion after dasatinib Tx (ICD-9-CM: 511.1, 511.89; ICD-10-CM: J90) during the identification (ID) period (Jan 1, 2015 - Sep 30, 2018). All pts had ≥ 1 filled prescription for dasatinib before the index date (defined as date of first pleural effusion during ID period), with dasatinib available on the index date, and no code for pleural effusion recorded during the baseline period (1-y pre-index); pts were also required to be continuously enrolled (baseline to follow-up at 1-y post-index). Demographic and clinical characteristics were described, and endpoints evaluated included Tx patterns (dose modification, switching to another TKI, duration of dasatinib Tx), HCRU, and cost. Results In total, 123 pts met the study criteria. The mean (standard deviation [SD]) age was 62.2 (10.9) y, 23.6% were female, and the mean (SD) Charlson Comorbidity Index was 3.8 (2.1). Overall, 38.2% of pts had a dose modification and 61.8% a stable dose after pleural effusion. At the 1-y follow-up, most pts (72.3%) with a dose modification did not switch Tx, and, of those, 70.6% continued Tx whereas the majority (57.9%) of pts with a stable dose switched to another TKI (Figure A). The mean (SD) number of days from first pleural effusion to end of dasatinib Tx (duration of dasatinib Tx) was significantly greater in pts with a dose modification compared with those with a stable dose (262.0 [124.0] vs 149.1 [155.2]; P < 0.001). In pts with a dose modification, the mean (SD) number of days from pleural effusion to dose modification was 73.7 (77.1) days, and from dose modification to end of Tx was 188.3 (128.7) days. Pts with a dose modification took a significantly longer time to switch from dasatinib to another TKI compared with pts with a stable dose (mean [SD]: 164.7 [105.8] vs 74.8 [76.0] days; P < 0.001; Figure B). Overall, 48.0% of pts had an inpatient hospitalization, with a mean (SD) total stay of 11.3 (14.3) days, and 37.4% had a visit to an emergency department. The mean (SD) number of physician office visits was 24.3 (16.7). Total mean (SD) costs were $196,797 (143,848). There were no statistically significant differences in HCRU and costs between pts with dose modification and stable dose. Conclusions These findings demonstrate that dasatinib discontinuation may not be necessary after development of pleural effusion. Pts who had a dose modification of dasatinib after development of pleural effusion were able to continue on dasatinib for a longer duration and had a lower rate of switching to another TKI but with similar HCRU and costs compared with pts who maintained a stable dose. Although not all pts required a dose modification to continue dasatinib Tx after pleural effusion, these findings suggest that in some pts, dose modification of dasatinib may allow for continued Tx with the potential to sustain outcomes. Study support Funded by Bristol Myers Squibb Figure 1 Figure 1. Disclosures Brokars: Bristol Myers Squibb: Current Employment. Kee: Bristol Myers Squibb: Current Employment. McBride: Bristol Myers Squibb: Current Employment. Reddy: Amgen: Other: I am an employee of PHAR, LLC, which was paid by this company to conduct research in the last 24 months; Partnership for Health Analytic Research (PHAR), LLC: Current Employment; Greenwich Biosciences: Other: I am an employee of PHAR, LLC, which was paid by this company to conduct research in the last 24 months; GRAIL: Other: I am an employee of PHAR, LLC, which was paid by this company to conduct research in the last 24 months; Prothena: Other: I am an employee of PHAR, LLC, which was paid by this company to conduct research in the last 24 months; Jazz: Other: I am an employee of PHAR, LLC, which was paid by this company to conduct research in the last 24 months; Kite: Other: I am an employee of PHAR, LLC, which was paid by this company to conduct research in the last 24 months; Genentech: Other: I am an employee of PHAR, LLC, which was paid by this company to conduct research in the last 24 months; Verde Technologies: Other: I am an employee of PHAR, LLC, which was paid by this company to conduct research in the last 24 months; Exact Sciences Corporation: Other: I am an employee of PHAR, LLC, which was paid by this company to conduct research in the last 24 months; Eisai: Other: I am an employee of PHAR, LLC, which was paid by this company to conduct research in the last 24 months; Dompe: Other: I am an employee of PHAR, LLC, which was paid by this company to conduct research in the last 24 months; Celgene: Other: I am an employee of PHAR, LLC, which was paid by this company to conduct research in the last 24 months; Sage: Other: I am an employee of PHAR, LLC, which was paid by this company to conduct research in the last 24 months; Otsuka: Other: I am an employee of PHAR, LLC, which was paid by this company to conduct research in the last 24 months; Novartis: Other: I am an employee of PHAR, LLC, which was paid by this company to conduct research in the last 24 months; Mirum Pharmaceuticals: Other: I am an employee of PHAR, LLC, which was paid by this company to conduct research in the last 24 months; Boston Scientific Corporation: Other: I am an employee of PHAR, LLC, which was paid by this company to conduct research in the last 24 months; Bristol Myers Squibb: Other: I am an employee of PHAR, LLC, which was paid by this company to conduct research in the last 24 months; Sanofi US Services: Other: I am an employee of PHAR, LLC, which was paid by this company to conduct research in the last 24 months; Takeda Pharmaceuticals: Other: I am an employee of PHAR, LLC, which was paid by this company to conduct research in the last 24 months; Akcea: Other: I am an employee of PHAR, LLC, which was paid by this company to conduct research in the last 24 months; BioMarin Pharmaceutical: Other: I am an employee of PHAR, LLC, which was paid by this company to conduct research in the last 24 months. Chang: AstraZeneca: Other: I am an employee of PHAR, LLC, which was paid by AstraZeneca to conduct research; Bristol Myers Squibb: Other: I am an employee of PHAR, LLC, which was paid by BMS to conduct research; Boston Scientific Corporation: Other: I am an employee of PHAR, LLC, which was paid by Boston Scientific Corporation to conduct research; Celgene: Other: I am an employee of PHAR, LLC, which was paid by Celgene to conduct research; Eisai: Other: I am an employee of PHAR, LLC, which was paid by Eisai to conduct research; Ethicon: Other: I am an employee of PHAR, LLC, which was paid by Ethicon to conduct research; GRAIL: Other: I am an employee of PHAR, LLC, which was paid by GRAIL to conduct research; Helsinn: Other: I am an employee of PHAR, LLC, which was paid by Helsinn to conduct research; Illumina: Other: I am an employee of PHAR, LLC, which was paid by Illumina to conduct research; Ionis: Other: I am an employee of PHAR, LLC, which was paid by Ionis to conduct research; Jazz: Other: I am an employee of PHAR, LLC, which was paid by Jazz to conduct research; Kite: Other: I am an employee of PHAR, LLC, which was paid by Kite to conduct research; Novartis: Other: I am an employee of PHAR, LLC, which was paid by Novartis to conduct research; Otsuka: Other: I am an employee of PHAR, LLC, which was paid by Otsuka to conduct research; Pathnostics: Other: I am an employee of PHAR, LLC, which was paid by Pathnostics to conduct research; Prothena: Other: I am an employee of PHAR, LLC, which was paid by Prothena to conduct research; Sage: Other: I am an employee of PHAR, LLC, which was paid by Sage to conduct research; Verde Technologies: Other: I am an employee of PHAR, LLC, which was paid by Verde Technologies to conduct research; Genentech, Inc.: Other: I am an employee of PHAR, LLC, which was paid by Genentech to conduct research; Greenwich Biosciences, Inc.: Other: I am an employee of PHAR, LLC, which was paid by Greenwich Biosciences to conduct research; Mirum Pharmaceuticals, Inc.: Other: I am an employee of PHAR, LLC, which was paid by Mirum Pharmaceuticals, Inc. to conduct research; Dompe US, Inc.: Other: I am an employee of PHAR, LLC, which was paid by Dompe US, Inc. to conduct research; Sanofi US Services, Inc.: Other: I am an employee of PHAR, LLC, which was paid by Sanofi US Services Inc. to conduct research; Sunovion Pharmaceuticals, Inc.: Other: I am an employee of PHAR, LLC which was paid by Sunovion Pharmaceuticals, Inc. to conduct research. ; BioMarin Pharmaceuticals Inc.: Other: I am an employee of PHAR, LLC which was paid by BioMarin Pharmaceuticals, Inc. to conduct research. ; Takeda Pharmaceuticals U.S.A., Inc.: Other: I am an employee of PHAR, LLC which was paid by Takeda Pharmaceuticals U.S.A., Inc., to conduct research. ; Exact Sciences Corporation: Other: I am an employee of PHAR, LLC which was paid by Exact Sciences Corporation to conduct research. ; Amgen: Other: I am an employee of PHAR, LLC, which was paid by Amgen to conduct research; Akcea: Other: I am an employee of PHAR, LLC, which was paid by Akcea to conduct research; AbbVie: Other: I am an employee of PHAR, LLC, which was paid by AbbVie to conduct research; Partnership for Health Analytic Research (PHAR), LLC: Current Employment, Other. Tarbox: Partnership for Health Analytic Research (PHAR), LLC: Current Employment, Other: I am an employee of PHAR, LLC, which was paid by Celgene/BMS to conduct this research.; AbbVie: Other: I am an employee of PHAR, LLC, which was paid by this company to conduct research in the last 24 months; Akcea: Other: I am an employee of PHAR, LLC, which was paid by this company to conduct research in the last 24 months; Amgen: Other: I am an employee of PHAR, LLC, which was paid by this company to conduct research in the last 24 months; BioMarin Pharmaceuticals: Other: I am an employee of PHAR, LLC, which was paid by this company to conduct research in the last 24 months; Bristol Myers Squibb: Other: I am an employee of PHAR, LLC, which was paid by this company to conduct research in the last 24 months; Boston Scientific Corporation: Other: I am an employee of PHAR, LLC, which was paid by this company to conduct research in the last 24 months; Celgene: Other: I am an employee of PHAR, LLC, which was paid by this company to conduct research in the last 24 months; Dompe: Other: I am an employee of PHAR, LLC, which was paid by this company to conduct research in the last 24 months; Eisai: Other: I am an employee of PHAR, LLC, which was paid by this company to conduct research in the last 24 months; Exact Sciences Corporation: Other: I am an employee of PHAR, LLC, which was paid by this company to conduct research in the last 24 months; Genentech: Other: I am an employee of PHAR, LLC, which was paid by this company to conduct research in the last 24 months; GRAIL: Other: I am an employee of PHAR, LLC, which was paid by this company to conduct research in the last 24 months; Greenwich Biosciences: Other: I am an employee of PHAR, LLC, which was paid by this company to conduct research in the last 24 months; Jazz: Other: I am an employee of PHAR, LLC, which was paid by this company to conduct research in the last 24 months; Kite: Other: I am an employee of PHAR, LLC, which was paid by this company to conduct research in the last 24 months; Mirum Pharmaceuticals: Other: I am an employee of PHAR, LLC, which was paid by this company to conduct research in the last 24 months; Novartis: Other: I am an employee of PHAR, LLC, which was paid by this company to conduct research in the last 24 months; Otsuka: Other: I am an employee of PHAR, LLC, which was paid by this company to conduct research in the last 24 months; Prothena: Other: I am an employee of PHAR, LLC, which was paid by this company to conduct research in the last 24 months; Sage: Other: I am an employee of PHAR, LLC, which was paid by this company to conduct research in the last 24 months; Sanofi US Services: Other: I am an employee of PHAR, LLC, which was paid by this company to conduct research in the last 24 months; Takeda Pharmaceuticals USA: Other: I am an employee of PHAR, LLC, which was paid by this company to conduct research in the last 24 months; Verde Technologies: Other: I am an employee of PHAR, LLC, which was paid by this company to conduct research in the last 24 months. LeBlanc: Jazz Pharmaceuticals: Research Funding; Daiichi-Sankyo: Consultancy, Honoraria, Other: Advisory board; Astellas: Consultancy, Honoraria, Other: Advisory board; AstraZeneca: Consultancy, Honoraria, Other: Advisory board, Research Funding; Amgen: Consultancy, Other: travel; American Cancer Society: Research Funding; CareVive: Consultancy, Other, Research Funding; Flatiron: Consultancy, Other: Advisory board; Pfizer: Consultancy, Other: Advisory Board; Helsinn: Consultancy, Research Funding; BMS/Celgene: Consultancy, Honoraria, Other: Travel fees, Research Funding, Speakers Bureau; Seattle Genetics: Consultancy, Other: Advisory board, Research Funding; Otsuka: Consultancy, Honoraria, Other; Duke University: Research Funding; UpToDate: Patents & Royalties; NINR/NIH: Research Funding; Agios: Consultancy, Honoraria, Other: Advisory board; Travel fees, Speakers Bureau; AbbVie: Consultancy, Honoraria, Other: Advisory board; Travel fees, Speakers Bureau; Heron: Consultancy, Honoraria, Other: advisory board.

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