The MASSIVE Survey. VI. The spatial sistribution and kinematics of warm ionized gas in the most massive local early-type galaxies

We present the first systematic investigation of the existence, spatial distribution, and kinematics of warm ionized gas as traced by the [O ii] 3727 Å emission line in 74 of the most massive galaxies in the local universe. All of our galaxies have deep integral-field spectroscopy from the volume- and magnitude-limited MASSIVE survey of early-type galaxies with stellar mass $\mathrm{log}({M}_{* }/{M}_{\odot })\gt 11.5$ (M K < −25.3 mag) and distance D < 108 Mpc. Of the 74 galaxies in our sample, we detect warm ionized gas in 28, which yields a global detection fraction of 38 ± 6% down to a typical [O ii] equivalent width limit of 2 Å. MASSIVE fast rotators are more likely to have gas than MASSIVE slow rotators with detection fractions of 80 ± 10% and 28 ± 6%, respectively. The spatial extents span a wide range of radii (0.6–18.2 kpc; 0.1–4R e ), and the gas morphologies are diverse, with 17/28 ≈ 61 ± 9% being centrally concentrated, 8/28 ≈ 29 ± 9% exhibiting clear rotation out to several kiloparsecs, and 3/28 ≈ 11 ± 6% being extended but patchy. Three out of four fast rotators show kinematic alignment between the stars and gas, whereas the two slow rotators with robust kinematic measurements available exhibit kinematic misalignment. Our inferred warm ionized gas masses are roughly ~105 M ⊙. The emission line ratios and radial equivalent width profiles are generally consistent with excitation of the gas by the old underlying stellar population. We explore different gas origin scenarios for MASSIVE galaxies and find that a variety of physical processes are likely at play, including internal gas recycling, cooling out of the hot gaseous halo, and gas acquired via mergers

A randomised phase 2a study to investigate the effects of blocking interleukin-33 with tozorakimab in patients hospitalised with COVID-19:Accord-2

BACKGROUND: Increased serum interleukin (IL)-33 predicts poor outcomes in patients hospitalised with coronavirus disease 2019 (COVID-19). We examined the efficacy and safety of tozorakimab, a monoclonal antibody that neutralises IL-33, in improving outcomes in ACCORD-2 (EudraCT: 2020-001736-95).METHODS: ACCORD-2 was an open-label, phase 2a study in adults hospitalised with COVID-19. Patients were randomised 1:1 to tozorakimab 300 mg plus standard of care (SoC) or SoC alone. The primary end-point was time to clinical response (sustained clinical improvement of ≥2 points on the World Health Organization ordinal scale, discharge from hospital or fit for discharge) by day 29. Other end-points included death or respiratory failure, mortality and intensive care unit admission by day 29, and safety. Serum IL-33/soluble stimulated-2 (sST2) complex levels were measured by high-sensitivity immunoassay.RESULTS: Efficacy analyses included 97 patients (tozorakimab+SoC, n=53; SoC, n=44). Median time to clinical response did not differ between the tozorakimab and SoC arms (8.0 and 9.5 days, respectively; HR 0.96, 80% CI 0.70-1.31; one-sided p=0.33). Tozorakimab was well tolerated and the OR for risk of death or respiratory failure with treatment versus SoC was 0.55 (80% CI 0.27-1.12; p=0.26), while the OR was 0.31 (80% CI 0.09-1.06) in patents with high baseline serum IL-33/sST2 complex levels.CONCLUSIONS: Overall, ACCORD-2 results suggest that tozorakimab could be a novel therapy for patients hospitalised with COVID-19, warranting further investigation in confirmatory phase 3 studies.</p

The Grizzly, October 1, 1991

Whittaker Relates Gulf Experience • Sorority Pledging Underway • U.S.E.A.C. Conference a Success • Ursinus Students Feel the Excitement of Habitat • College Tutorial Project Thrives • U.C. Welcomes New Instructors • Leadershop 1991 • U.S.G.A. Finds a Home • A Plea for Help • GN\u27R: Illusion ... of Good Music • State Museum Exhibits Berman Sculptures • Jane Ira Bloom Jazzes It Up • Sky Sands Strikes Ursinus • Aerobics Attack • The Tempting Temple • Field Hockey Faces Tough Times • Bears Terrorized by Western Maryland • Lady Bears Finish 4th • Bears Tee Off • Runners Get Recognition • Soccer Splits Two • Cross Country Cruises to 3rd Place • Gift to Give • Alcohol Policy Enforcement Tightens • Intellect Over Image • Wismer Whine • Healing the Wounds of the Gulf War • The Search For the Chemical Promisehttps://digitalcommons.ursinus.edu/grizzlynews/1278/thumbnail.jp

Abstracts from the NIHR INVOLVE Conference 2017

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A randomised phase 2a study to investigate the effects of blocking interleukin-33 with tozorakimab in patients hospitalised with COVID-19: ACCORD-2

Background Increased serum interleukin (IL)-33 predicts poor outcomes in patients hospitalised with coronavirus disease 2019 (COVID-19). We examined the efficacy and safety of tozorakimab, a monoclonal antibody that neutralises IL-33, in improving outcomes in ACCORD-2 (EudraCT: 2020-001736-95). Methods ACCORD-2 was an open-label, phase 2a study in adults hospitalised with COVID-19. Patients were randomised 1:1 to tozorakimab 300 mg plus standard of care (SoC) or SoC alone. The primary end-point was time to clinical response (sustained clinical improvement of ⩾2 points on the World Health Organization ordinal scale, discharge from hospital or fit for discharge) by day 29. Other end-points included death or respiratory failure, mortality and intensive care unit admission by day 29, and safety. Serum IL-33/soluble stimulated-2 (sST2) complex levels were measured by high-sensitivity immunoassay. Results Efficacy analyses included 97 patients (tozorakimab+SoC, n=53; SoC, n=44). Median time to clinical response did not differ between the tozorakimab and SoC arms (8.0 and 9.5 days, respectively; HR 0.96, 80% CI 0.70–1.31; one-sided p=0.33). Tozorakimab was well tolerated and the OR for risk of death or respiratory failure with treatment versus SoC was 0.55 (80% CI 0.27–1.12; p=0.26), while the OR was 0.31 (80% CI 0.09–1.06) in patents with high baseline serum IL-33/sST2 complex levels. Conclusions Overall, ACCORD-2 results suggest that tozorakimab could be a novel therapy for patients hospitalised with COVID-19, warranting further investigation in confirmatory phase 3 studies

Cost-Effectiveness Analysis of Gilteritinib Versus Best Supportive Care (BSC) for the Treatment of Relapsed or Refractory (R/R) FLT3 Mutation-Positive (FLT3mut+) Acute Myeloid Leukemia (AML)

Introduction: AML is an aggressive hematopoietic malignancy, and ~30% of patients have mutations in the FLT3 gene. Historically, patients with R/R FLT3mut+ AML experienced dismal survival outcomes. The approval of FLT3-targeted agents has resulted in a paradigm change in the management of these patients. In 2018, gilteritinib was approved as the first targeted agent for R/R FLT3mut+ AML based on results of the phase 3 ADMIRAL trial, showing significantly improved median overall survival (OS) of 9.3 months. Historically, due to limited effective options and tolerability concerns, 11-40% of patients with R/R FLT3mut+ AML received BSC (defined as no active leukemia-directed therapy). Patients managed by BSC still incur substantial resource use and have poor outcomes. The estimated median OS was 2-3 months, with the majority of patients (&gt; 90%) dying within one year. To quantify the incremental benefit and economic value of gilteritinib over BSC, a cost-effectiveness analysis (CEA) model was constructed to model disease trajectory, quality of life impact, and economic impact. Methods: A CEA was developed to compare the costs and effectiveness of gilteritinib and BSC from a US third-party payer's perspective over a lifetime horizon. The model used a 1-month cycle and 3% discount rate and comprised a decision tree followed by a three-stage partitioned survival model. In the decision tree stage, patients were first classified based on whether they received allogeneic hematopoietic stem cell transplantation (HSCT). Following stratification, patients were distributed among three health states: event-free survival (EFS), alive and post-event, and death. Due to the palliative nature of BSC, all patients in the BSC arm were assumed to start in the alive and post-event state and were not eligible to receive subsequent HSCT based on clinical inputs. For patients in the gilteritinib arm, the efficacy inputs were based on the ADMIRAL trial for patients without HSCT or literature (Evers 2018) for those with HSCT. For patients in the BSC arm, the efficacy inputs were based on available literature (Sarkozy 2013). Parametric survival models or hazard ratios were used to predict probabilities in different health states until year 3. After year 3, all patients who remained alive were considered cured with a two-fold increase in mortality risk compared to the general population. Treatment costs (drug, administration, and hospitalization), adverse event (AE) costs, subsequent HSCT costs, medical costs for health states, FLT3 testing, post-progression treatment, and terminal care costs were obtained from public databases and literature. Patients managed by BSC were assumed not to incur any costs related to treatment, AEs, or HSCT. All costs were inflated to 2018 US dollar (USD). Utilities for each health state were derived from the ADMIRAL trial and disutilities for AEs were derived from the literature. The model calculated total costs, and total effectiveness measured by life years (LYs) and quality-adjusted life years (QALYs) for gilteritinib and BSC, respectively. Incremental cost-effectiveness ratios (ICERs), defined as the incremental cost per additional gain in health effect (i.e., LY and QALY), were estimated comparing gilteritinib to BSC. To test the robustness of the results, deterministic sensitivity analyses (DSA) and probabilistic sensitivity analyses (PSA) were performed. Results: Over a lifetime horizon, treatment with gilteritinib, compared to BSC, was associated with an incremental LY gain of 2.82 and QALY gain of 2.32, respectively. With an additional cost of $239,623 relative to BSC, the ICER per one LY gained was$84,922, and ICER per one QALY gained was $103,110. The results were most sensitive to discount rate, cure assumptions, and gilteritinib cost. PSA showed 100$150,000/QALY in the US. Conclusions: Gilteritinib led to substantial clinical benefit compared to BSC for treatment of R/R FLT3mut+ AML. Despite the large cost difference, the ICER is still within a reasonable range of less than $150,000/QALY, as established by the US Institute for Clinical and Economic Review. Gilteritinib fulfills an important unmet need in the treatment landscape and represents a potential paradigm shift in the current management of R/R FLT3mut+ AML for patients who otherwise would not have received active therapy. Disclosures Zeidan: BeyondSpring: Honoraria; Acceleron Pharma: Consultancy, Honoraria, Research Funding; Celgene Corporation: Consultancy, Honoraria, Research Funding; Boehringer-Ingelheim: Consultancy, Honoraria, Research Funding; Trovagene: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; ADC Therapeutics: Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; Cardinal Health: Honoraria; Otsuka: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Jazz: Honoraria; Ariad: Honoraria; Agios: Honoraria; Novartis: Honoraria; Astellas: Honoraria; Daiichi Sankyo: Honoraria; Medimmune/AstraZeneca: Research Funding; Seattle Genetics: Honoraria. Pandya:Astellas Pharmaceuticals: Employment. Qi:Astellas: Other: I am an employee of Analysis Group, Inc., which provided paid consulting services to Astellas for the conduct of this study; Analysis Group, Inc.: Employment. Garnham:Astellas: Employment. Yang:Analysis Group, Inc.: Employment; Astellas: Other: I am an employee of Analysis Group, Inc., which provided paid consulting services to Astellas for the conduct of this study. Shah:Astellas: Employment. </jats:sec