Length of Pre-Ecmo Mechanical Ventilation Is Not Associated with Mortality in Patients with Covid-19

INTRODUCTION: Previous studies suggest that delayed initiation of extracorporeal membrane oxygenation (ECMO) is associated with higher patient mortality. Hence, we hypothesized that prolonged invasive mechanical ventilation (IMV) prior to ECMO was associated with higher mortality in patients with COVID-19. METHOD(S): The COVID-19 Critical Care Consortium, a prospective international multicenter registry, was queried for all patients with COVID-19 infection who received IMV and ECMO. Patients who were intubated prior to transfer to a study site were excluded. The primary variable was number of days on IMV prior to ECMO initiation and study endpoint was death or discharge from the study site. Cox proportional hazards model for the time between ECMO initiation and death was built using covariates including age, gender, selected comorbidities, and time intervals from ICU admission to IMV and IMV to ECMO initiation. RESULT(S): Between 1/1/2020 and 6/6/2022, A total of 593 patients from 107 study sites and 25 countries were included in the analysis. In this cohort, the median age was 50 (Interquartile range [IQR]: 40-58) years. Obesity and hypertension were prevalent among 220 (38.4%) and 223 (38.8%) of the patients, respectively. Twenty-four (4.2%) patients had chronic pulmonary disease. Prior to ECMO initiation, patients spent a median of 3.68 (IQR: 1.36-8.07) days in the ICU and a median of 2.49 (IQR: 0.88-5.65) days on IMV. Overall mortality was 47.2% with 3.9% patients' status not finalized or unknown. According to the final survival model, the number of days on IMV prior to ECMO initiation was not associated with mortality. The hazard ratios for 0, 3, 7, and 14 days of pre-ECMO IMV were 0.94 (95% confidence interval [CI]: 0.83 to 1.07), 1.02 (95% CI: 0.97 to 1.08), 1.09 (95% CI: 0.92 to 1.3) and 1.09 (95% CI: 0.83 to 1.42), respectively. Other noticeable contributory factors in the model included age and gender. CONCLUSION(S): Among patients with COVID-19 who received ECMO, the length of pre-ECMO IMV was not associated with hospital mortality. Further studies evaluating the ventilator settings before and after ECMO initiation are needed.

Early Clinical Experience with ALVR109, a Partially HLA-Matched SARS-CoV-2 Specific T-Cell Therapy, in Immunocompromised Patients with COVID-19

Purpose: Therapies for COVID-19 in immunocompromised (IC) patients (pts), including transplant (tx) pts, are limited. We describe our experience with ALVR109, an allogeneic, partially HLA-matched T-cell product, given through emergency investigational new drug (eIND) application to 4 consecutive IC pts with protracted COVID-19. Method(s): To measure SARS-CoV-2 viral loads, SARS-2 RNA was quantified by RT-PCR (N gene) in plasma and saliva. ALVR109 was manufactured for Allovir at Baylor College of Medicine. Result(s): Between May and October 2021, ALVR109 was given to 4 IC pts with COVID-19 (details in Table 1). 2 pts had lymphoma (1 post auto-tx) and 2 had lung tx. All pts had SARS-CoV-2 RNA detected in plasma (viremia) in the weeks leading up to ALVR109 administration. Infusions (20-40 million cells (MC) per dose) were well-tolerated with no adverse events. Prior to ALVR109, pts 1 and 3 had progressive COVID-19 and ongoing SARS-CoV-2 viremia despite monoclonal antibodies (mABs) and remdesivir. Following ALVR109 administration both patients had a decrease in viremia with marked clinical improvement in pt 1, but both eventually died from their underlying disease. Viral loads (plasma/saliva) and functional scores for pt 1 are shown in the figure. Autopsy of pt 3 showed no evidence of SARS-CoV-2 infection by lung in-situ hybridization (ISH). Pts 2 and 4 received ALVR109 as adjunctive therapy to mABs and remdesivir;viremia continued to decline following ALVR109 and both pts survived and were discharged home. Conclusion(s): This initial experience suggests a potential role of ALVR109 in the treatment of IC and tx pts with COVID-19. SARS-CoV-2-specific T-cells appear to be safe and may control viremia in IC pts. Larger studies are needed to confirm this observation, define the best candidates for ALVR109, and determine optimal timing of administration. (Table Presented).

The Impact of Morbid Obesity on Patients with COVID-19 who Develop Respiratory Failure requiring Extracorporeal Membrane Oxygenation

Background: In patients with COVID-19 and respiratory failure, class 3 obesity (body mass index > 40 kg/m2) has been associated with worse survival. Obese patients on mechanical ventilation with progressively more severe acute respiratory syndrome (ARDS) may be offered venovenous (VV) extracorporeal membrane oxygenation (ECMO) therapy. The impact of morbid obesity on the outcome of COVID-19 patients supported with VV ECMO has been underexplored. Methods: This is a multicenter, retrospective observational cohort analysis of critically ill adults with COVID-19 ARDS requiring advanced mechanical ventilation with or without VV ECMO. Data was collected from 236 international institutions forming the COVID-19 Critical Care Consortium international registry. Patients were admitted between January 2020 to December 2021. Included patients were stratified by ECMO status and a BMI threshold at 40 kg/m2. Median values with interquartile range (IQR) were used to summarize continuous variables and multi-state analysis was used to explore the effect of Class 3 obesity on the study endpoints of patient survival to discharge or death. Results: Complete data was available on 8851 of 9059 patients on mechanical ventilation, of which 767 patients required VV ECMO. For the entire study group, older age and male gender were associated with an increased risk of death. The demographics and comorbidities of the higher BMI (H >40 kg/m2) and lower BMI (L ≤40 kg/m2) cohorts were similar with the exception of age and weight. Patients with a higher BMI were younger. The median age of the H, non-ECMO cohort was 56 years (46-64), and the H, ECMO cohort was 41 years (35-51) versus the L, non-ECMO cohort of 64 years(55-71), and the L, ECMO cohort of 53years (45-60). Patients requiring VV ECMO had higher SOFA scores, experienced longer ICU and hospital lengths of stay, and a longer duration of total mechanical ventilation. Table The median time to intubation was longer in the mechanical ventilation only group (2 versus 0 days). Predictors for requiring ECMO included younger age, higher BMI and male gender. Risk factors for death included advancing age (every 10 years), male gender and increasing BMI (every 5kg/m2). The association between BMI and a higher rate of death was reduced in the mechanical ventilation only group (HR 0.92, 95% confidence interval 0.85 to 0.99). Conclusion: In patients with severe ARDS due to COVID-19 requiring mechanical ventilation, the likelihood of progressing to VV ECMO therapy or experiencing death is impacted by age, gender and higher BMI. The cohort of COVID-19 patients that ultimately required ECMO appear to be sicker at time hospital admission owing to the shorter time until mechanical ventilation. It appears the association between increasing BMI and death differs among the ECMO and mechanical ventilation alone cohorts. We would advocate for a prospective study to determine the benefit of VVECMO for the obese patient requiring VV-ECMO for COVID-19 ARDS. (Figure Presented).

Using Social Media to Foster Engagement and Connection in Sport Psychology Classrooms

Sport and exercise psychology (SEP) educators are tasked with fostering innovation in the classroom. Given the current generation of students' heightened attraction to technology along with an increase in social isolation due to the COVID-19 pandemic, social media may be useful in the classroom. The purpose of this article is to explain the process of implementing social media as a tool to foster engagement and connection in two sections of an online SEP university course. Feedback from students indicated using social media for assignments fostered a connected learning environment and provided a refreshing way to engage with peers. Lessons learned are provided for instructors considering using social media.

SARS-CoV-2 RNAEMIA AS A BIOMARKER of LOWER RESPIRATORY VIRAL LOAD in COVID-19

Background: SARS-CoV-2 plasma RNAemia correlates strongly with COVID-19 severity and predicts clinical outcome, but how RNAemia levels relate to viral load in the lower respiratory tract has not been well-defined. Delineating the relationship of viral load in the lung and blood compartments in COVID-19 may help guide therapeutic interventions and could provide insight into the viral dynamics of these two compartments. Here we compared SARS-CoV-2 RNA levels in plasma to those in lower respiratory secretions. Methods: We used an internally-controlled, ultrasensitive (1 copy/extraction) qRT-PCR assay for SARS-CoV-2 N gene RNA to test plasma and endotracheal aspirate (ETA) samples collected on the same day from mechanically-ventilated patients with COVID-19 prospectively enrolled from three hospitals in Pittsburgh. Samples were collected at enrollment on day 1 (D1), D5, and D10. Results: SARS-CoV-2 RNA was detected in 22/33 (67%) plasma (median 32 cps/mL, IQR [<3-2608 cps/mL]) and 28/33 (85%) ETA samples (median 66,300 cps/mL, IQR [2395-1,028,500 cps/mL]) collected on D1. Of the 28 ETA samples with detectable SARS-CoV-2 RNA, 22 (79%) had detectable RNAemia. Viral RNA levels were more than 2,000-fold higher in ETA than plasma, but plasma and ETA viral RNA levels were strongly correlated (Spearman r=0.83, p<0.0001, Fig 1A). Viral RNA levels generally decreased concordantly over time in both plasma and ETA samples (Fig 1B and C). Conclusion: SARS-CoV-2 viral RNA levels in plasma and lower respiratory tract secretions are strongly correlated in patients with severe COVID-19. This finding provides support for plasma viral RNA as a biomarker of lung infection, which could prove to be useful in guiding therapeutic interventions and monitoring response to therapies.

Acute to Chronic Pain Signatures Program (a2CPS): Implementation of Remote Training for a Multisite Observation Study During COVID-19

Chronic pain produces the largest non-fatal burden of disease, yet our understanding of factors that contribute to the transition from acute chronic pain are poorly understood. The Acute to Chronic Pain Signatures Program (A2CPS) is a longitudinal, multi-site observational study to identify biomarkers (individual or biosignature combinations) that predict susceptibility or resilience to the development of chronic pain after surgery (knee replacement or thoracotomy). Due to the COVID-19 pandemic, however, travel between sites was restricted just as the study was preparing to begin enrollment. Here, we present multiple training protocol adaptations that were successfully implemented to facilitate remote research-related training. The A2CPS consortium includes 2 Multisite Clinical Centers (MCCs, 10 recruitment sites), a Clinical Coordinating Center (CCC), a Data Integration and Resource Center (DIRC), 3 Omics Data Generation Centers, and representation from the NIH Pain Consortium, Common Fund, and National Institute of Drug Abuse. The A2CPS is collecting candidate and exploratory biomarkers including pain, fatigue, function, sleep, psychosocial factors, quantitative sensory testing (QST), genomics, proteomics, metabolomics, lipidomics, and brain imaging. The CCC adapted the A2CPS training and evaluation techniques for certifying the MCCs to ensure competency with recruitment, assessments (surveys, QST, function), and data entry across clinical sites using a combination of virtual training sessions, standardized quantitative measurements, video demonstrations, and reliability assessments. Staff at data collection sites have been successfully certified in all psychophysical assessments (QST, function). This included use of stop watches and metronomes to ensure standard application rates, completion of application-rate and inter-rater-reliability worksheets at each clinical site, designation of site-specific master examiners, training rubrics and video demonstration to verify competency was harmonized across sites. Adaptation of training protocols to a remote format enabled initiation of subject enrollment while maintaining documented standards with high data completion rates for surveys and assessments. The A2CPS Consortium is supported by the National Institutes of Health Common Fund, which is managed by the OD/Office of Strategic Coordination (OSC). Consortium components include: Clinical Coordinating Center (UO1NS077179), Data Integration and Resource Center (UO1NS077352), Omics Data Generation Centers (U54DA049116, U54DA049115, U54DA09113), and Multisite Clinical Centers: MCC 1 (UM1NS112874) and MCC 2 (UM1NS118922). Postdoctoral support for GB provided by the National Institutes of Neurological Disease and Stroke (NINDS) of the NIH under Award Number U24NS112873-03S2.

Safety and Efficacy of Cusatuzumab in Combination with Venetoclax and Azacitidine (CVA) in Patients with Previously Untreated Acute Myeloid Leukemia (AML) Who Are Not Eligible for Intensive Chemotherapy;An Open-Label, Multicenter, Phase 1b Study

Background: Acute myeloid leukemia (AML) is driven by aberrant leukemic stem cells (LSCs) that initiate and sustain malignancy. To circumvent resistance to therapy, combination therapies with additive mechanisms of action are needed. CD70, a tumor necrosis factor receptor ligand, and its receptor CD27 are expressed on LSCs and AML blasts, but not on hematopoietic stem cells. Cusatuzumab, a high-affinity humanized monoclonal anti-CD70 antibody, kills CD70-expressing cells by Fc domain-mediated effector functions and is a potent inhibitor of CD70-CD27 signaling. Here we report initial results of a study of cusatuzumab in combination with the current standard of care therapy, venetoclax plus azacitidine (CVA), in patients with untreated AML (de novo or secondary) ineligible for intensive chemotherapy due to age ≥75 years or medical comorbidities. Methods: The primary objective of this open label, multicenter, phase 1b study was to assess safety and tolerability of CVA. Key secondary objectives included response rate per ELN 2017 criteria and time to response. Patients received cusatuzumab 10 or 20 mg/kg IV on Day 3 and Day 17, a 3-day ramp-up of venetoclax (100, 200, and 400 mg PO) followed by 400 mg daily dosing, and azacitidine 75 mg/m 2 SC or IV on Days 1-7 of each 28-day cycle. Results: Based on data through Jul 9, 2021, 44 patients enrolled with median age 75 years (range 32-89), 36.4% had secondary AML, 40.9% had an ECOG performance status of 2, and ELN risk was favorable, intermediate and adverse in 18.2%, 20.5% and 61.4%, respectively. All patients received 20 mg/kg cusatuzumab except for 3 patients who received a starting dose of 10 mg/kg with the option to escalate to 20 mg/kg. Of these 3 patients, 1 escalated to 20 mg/kg. At a median follow-up of 29.1 weeks, the median number of treatment cycles was 4.0 (range 1.0-11.0). Grade 3 or above TEAEs were reported in 97.7% of patients;the most common (reported in ≥10%) were neutropenia (68.2%), thrombocytopenia (65.9%), febrile neutropenia (36.4%), anemia (34.1%), leukopenia (29.5%), sepsis (27.3%), and lymphopenia (15.9%). Treatment-emergent serious adverse events (SAEs) were reported in 75% of patients;the most common (reported in at least ≥5%) were febrile neutropenia (27.3%), sepsis (22.7%), COVID-19 (6.8%), and thrombocytopenia (6.8%). Treatment-emergent SAEs of grade ≥3 were reported in 72.7% of the patients. Infusion-related reactions (IRRs) were reported for 11.4% of patients with 2.3% at grade ≥3. Six (13.6%) patients discontinued treatment due to AEs, and 5 (11.4%) TEAEs resulted in death. The mortality rate within 30 days from start of treatment was 4.5%. Table 1 summarizes best response to study treatment. In the intent-to-treat analysis set (n=44) complete remission (CR) rate was 45.5%, while CR + CR with partial hematologic recovery (CRh) + CR with incomplete hematologic recovery (CRi) was 77.3%;MLFS was observed in 11.4% of patients. Of 34 responders (defined as CR, CRi or CRh), 47% were MRD negative by flow cytometry at or after achievement of response. Median time to first response for patients who achieved CR, CRh or CRi was 4.21 (3.0-25.0) weeks. Best response rates in the post-hoc response evaluable analysis set (n=42) that excluded two patients who died before the first disease evaluation were: CR in 47.6%, CR + CRh + CRi in 81.0% and MLFS in 11.9% of patients (Table 1). The majority (97.1%) of responders experienced at least one cycle delay in administration of CVA post response. Conclusions: Cusatuzumab administered in combination with venetoclax and azacitidine to elderly patients with untreated AML was generally well tolerated and demonstrated a safety profile consistent with that previously reported with venetoclax-azacitidine, with the addition of generally manageable IRRs. Response rates support an additive effect of cusatuzumab to the standard of care with potential for improved clinical outcomes. However, further clinical trials are needed for validation of these initial results. HK and GB contributed equally to this publ cation. [Formula presented] Disclosures: Roboz: AstraZeneca: Consultancy;Janssen: Research Funding;Bristol Myers Squibb: Consultancy;Jasper Therapeutics: Consultancy;Agios: Consultancy;Novartis: Consultancy;Amgen: Consultancy;Blueprint Medicines: Consultancy;Janssen: Consultancy;Helsinn: Consultancy;Daiichi Sankyo: Consultancy;Glaxo SmithKline: Consultancy;Celgene: Consultancy;Jazz: Consultancy;MEI Pharma - IDMC Chair: Consultancy;Mesoblast: Consultancy;Actinium: Consultancy;AbbVie: Consultancy;Astex: Consultancy;Bayer: Consultancy;Astellas: Consultancy;Roche/Genentech: Consultancy;Pfizer: Consultancy;Otsuka: Consultancy. Aribi: Seagen: Consultancy. Brandwein: Astellas: Honoraria;Jazz: Honoraria;Amgen: Honoraria;Taiho: Honoraria;BMS/Celgene: Honoraria;Pfizer: Honoraria;Abbvie: Honoraria;University of Alberta: Current Employment. Döhner: Astellas: Consultancy, Honoraria, Research Funding;AstraZeneca: Consultancy, Honoraria;Berlin-Chemie: Consultancy, Honoraria;Amgen: Consultancy, Honoraria, Research Funding;Abbvie: Consultancy, Honoraria, Research Funding;Agios: Consultancy, Honoraria, Research Funding;Celgene: Consultancy, Honoraria, Research Funding;GEMoaB: Consultancy, Honoraria;Helsinn: Consultancy, Honoraria;Janssen: Consultancy, Honoraria;Jazz: Consultancy, Honoraria, Research Funding;Novartis: Consultancy, Honoraria, Research Funding;Oxford Biomedicals: Consultancy, Honoraria;Pfizer: Research Funding;Roche: Consultancy, Honoraria;Gilead: Consultancy, Honoraria;Bristol Myers Squibb: Consultancy, Honoraria, Research Funding;Astex: Consultancy, Honoraria;Ulm University Hospital: Current Employment. Fiedler: Jazz Pharmaceuticals: Consultancy, Other: support for meeting attendance;Abbvie: Consultancy, Honoraria;Morphosys: Consultancy;Celgene: Consultancy;Pfizer: Consultancy, Research Funding;Novartis: Consultancy;ARIAD/Incyte: Consultancy;Amgen: Consultancy, Other: support for meeting attendance, Patents & Royalties, Research Funding;Servier: Consultancy, Other: support for meeting attendance;Daiichi Sankyo: Consultancy, Other: support for meeting attendance;Stemline: Consultancy. Gandini: argenx: Current Employment, Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months. Geddes: University of Calgary: Current Employment;Taiho: Consultancy, Membership on an entity's Board of Directors or advisory committees;Jazz: Consultancy, Membership on an entity's Board of Directors or advisory committees;Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees;Novartis: Consultancy;BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau;Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees;Amgen: Consultancy;Paladin: Consultancy;Janssen: Research Funding;Geron: Research Funding;Abbvie: Membership on an entity's Board of Directors or advisory committees, Research Funding. Hou: University of Pittsburgh Medical Center Hillman Cancer Centers: Current Employment;AbbVie: Honoraria;AstraZeneca: Honoraria;Karyopharm: Honoraria;Chinese American Hematology Oncology Network: Membership on an entity's Board of Directors or advisory committees. Howes: Janssen R&D, part of Johnson & Johnson: Current Employment;Johnson & Johnson: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Hultberg: argenx: Current Employment, Patents & Royalties. Huselton: University of Rochester: Current Employment. Jacobs: Argenx BV: Current Employment, Current equity holder in publicly-traded company;University of Antwerp: Ended employment in the past 24 months. Kane: Janssen R&D, part of Johnson & Johnson: Current Employment, Current equity holder in publicly-traded company. Lech-Marańda: Takeda: Membership on an entity's Board of Directors or advisory committees;AbbVie: Membership on an entity's Board of Directors r advisory committees;Novartis: Membership on an entity's Board of Directors or advisory committees;Roche: Membership on an entity's Board of Directors or advisory committees;Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees;Amgen: Membership on an entity's Board of Directors or advisory committees;Sanofi: Membership on an entity's Board of Directors or advisory committees;Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding. Louwers: argenx: Current Employment, Patents & Royalties: Patents (no royalties). Nottage: Janssen R&D, part of Johnson & Johnson: Current Employment;Johnson & Johnson: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Platzbecker: Novartis: Honoraria;AbbVie: Honoraria;Janssen: Honoraria;Celgene/BMS: Honoraria;Geron: Honoraria;Takeda: Honoraria. Rampal: Pharmaessentia: Consultancy;BMS/Celgene: Consultancy;Abbvie: Consultancy;Sierra Oncology: Consultancy;Incyte: Consultancy, Research Funding;Blueprint: Consultancy;Disc Medicine: Consultancy;Jazz Pharmaceuticals: Consultancy;Constellation: Research Funding;Kartos: Consultancy;Stemline: Consultancy, Research Funding;CTI: Consultancy;Novartis: Consultancy;Memorial Sloan Kettering: Current Employment. Salman: Janssen: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Shah: Janssen R&D, part of Johnson & Johnson: Current Employment. Stuart: Clinical Drug Development Consultants LLC: Current Employment;Argenx: Consultancy;Cleave Therapeutics: Consultancy;Triphase Accelerator Corp: Consultancy;IgM Biosciences: Consultancy;Revolution Medicines: Consultancy;Jiya Corp:Consultancy;Geron Corp: Current holder of individual stocks in a privately-held company. Subklewe: Janssen: Consultancy;Pfizer: Consultancy, Speakers Bureau;Takeda: Speakers Bureau;Klinikum der Universität München: Current Employment;MorphoSys: Research Funding;Novartis: Consultancy, Research Funding, Speakers Bureau;Roche: Research Funding;Seattle Genetics: Consultancy, Research Funding;Miltenyi: Research Funding;Gilead: Consultancy, Research Funding, Speakers Bureau;Amgen: Consultancy, Research Funding, Speakers Bureau;BMS/Celgene: Consultancy, Research Funding, Speakers Bureau. Sumbul: argenx: Current Employment. Wang: Takeda: Consultancy, Honoraria, Other: Advisory board;Jazz Pharmaceuticals: Consultancy, Honoraria, Other: Advisory Board;Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees;Stemline Therapeutics: Consultancy, Honoraria, Other: Advisory board, Speakers Bureau;AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees;Kite Pharmaceuticals: Consultancy, Honoraria, Other: Advisory Board;GlaxoSmithKline: Consultancy, Honoraria, Other: Advisory Board;Genentech: Membership on an entity's Board of Directors or advisory committees;BMS/Celgene: Membership on an entity's Board of Directors or advisory committees;DAVA Oncology: Consultancy, Speakers Bureau;Kura Oncology: Consultancy, Honoraria, Other: Advisory board, steering committee, Speakers Bureau;Novartis: Consultancy, Honoraria, Other: Advisory Board;Mana Therapeutics: Consultancy, Honoraria;Pfizer: Consultancy, Honoraria, Other: Advisory Board, Speakers Bureau;Rafael Pharmaceuticals: Other: Data safety monitoring committee;Gilead: Consultancy, Honoraria, Other: Advisory board;Daiichi Sankyo: Consultancy, Honoraria, Other: Advisory board;PTC Therapeutics: Consultancy, Honoraria, Other: Advisory board;Genentech: Consultancy;MacroGenics: Consultancy. Wierzbowska: Jazz: Research Funding;Pfizer: Honoraria;Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees;Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees;Astellas: Honoraria, Membership on an entity's Board of Directors or advisory comm ttees;Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees;BMS: Honoraria. Yao: Statagize LLC: Current Employment;Puma Biotechnology, Inc.: Ended employment in the past 24 months;Argenx: Consultancy. Yee: Astex: Membership on an entity's Board of Directors or advisory committees, Research Funding;Janssen: Research Funding;TaiHo: Membership on an entity's Board of Directors or advisory committees;Otsuka: Membership on an entity's Board of Directors or advisory committees;Onconova: Research Funding;Pfizer: Membership on an entity's Board of Directors or advisory committees;Tolero: Research Funding;Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;Paladin: Membership on an entity's Board of Directors or advisory committees;MedImmune: Research Funding;AbbVie: Honoraria;Bristol-Myers Squibb/Celgene: Membership on an entity's Board of Directors or advisory committees;Shattuck Labs: Membership on an entity's Board of Directors or advisory committees;Forma Therapeutics: Research Funding;Takeda: Membership on an entity's Board of Directors or advisory committees;Geron: Research Funding;Genentech: Research Funding;F. Hoffmann La Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding;Jazz: Research Funding. Kantarjian: Immunogen: Research Funding;Astra Zeneca: Honoraria;KAHR Medical Ltd: Honoraria;Astellas Health: Honoraria;Pfizer: Honoraria, Research Funding;NOVA Research: Honoraria;Ascentage: Research Funding;Precision Biosciences: Honoraria;Novartis: Honoraria, Research Funding;Aptitude Health: Honoraria;Ipsen Pharmaceuticals: Honoraria;Jazz: Research Funding;Daiichi-Sankyo: Research Funding;BMS: Research Funding;Amgen: Honoraria, Research Funding;AbbVie: Honoraria, Research Funding;Taiho Pharmaceutical Canada: Honoraria. Borthakur: Protagonist: Consultancy;Ryvu: Research Funding;Astex: Research Funding;GSK: Consultancy;Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees;Takeda: Membership on an entity's Board of Directors or advisory committees;University of Texas MD Anderson Cancer Center: Current Employment;ArgenX: Membership on an entity's Board of Directors or advisory committees.

Challenges and Unexpected Affordances of Physical Computing Going Remote

Engaging in physical computing activities involving both hardware and software provides a hands-on introduction to computer science. The move to remote learning for primary and secondary schools during the 2020-2021 school year due to COVID-19 made implementing physical computing activities especially challenging. However, it is important that these activities are not simply eliminated from the curriculum. This paper explores how a unit centered around students investigating how programmable sensors that can support data-driven scientific inquiry was collaboratively adapted for remote instruction. A case study of one teacher's experience implementing the unit with a group of middle school students (ages 11 to 14) in her STEM elective class examines how her students could still engage in computational thinking practices around data and programming. The discussion includes both the challenges and unexpected affordances of engaging in physical computing activities remotely that emerged from her implementation. © 2021 ACM.

Prone position during veno-venous extracorporeal membrane oxygenation for COVID-19

Objective: Prone positioning for severe acute respiratory distress syndrome (ARDS) is associated with improved outcome. It is unclear whether prone positioning during Venovenous extracorporeal membrane oxygenation (VV ECMO) has survival benefit. The study investigated the impact of prone positioning on survival during VV ECMO support for COVID-19 acute respiratory failure. Methods: An observational analysis of VV ECMO patients using the COVID-19 Critical Care Consortium (COVID Critical) international registry. We used a multi-state survival model to compare the outcomes of patients treated with or without prone positioning during ECMO. Results: There were 213 COVID-19 patients at 67 participating institutions who were supported with VV ECMO from February 19, 2020, to October 31, 2020. Proning was used in 160 patients (75%) before initiation of ECMO and in 67 patients (31%) during ECMO. Prone positioning during ECMO support was associated with reduced mortality (hazard ratio 0.33, 95% CI, 0.15 to 0.73). Conclusions: Our study highlights that prone-positioning during VV ECMO support for refractory COVID- 19-related ARDS is associated with reduced mortality. Given our observational study design, a randomized controlled trial of prone positioning on VV ECMO is needed to confirm these findings.

COVID-19 outcome: Insights from quantification of viremia and neutralizing antibody

Background: Although SARS-CoV-2 “RNAemia” (viral RNA in blood) has been detected in patients with COVID-19, more often in severe disease, important questions remain: 1) Is the viral RNA in blood in cell-free virions? 2) Is the level of viremia prognostic? 3) Are viremia and neutralizing antibody titer related? We investigated these questions using multiple complementary approaches. Methods: We developed an internally-controlled, ultrasensitive (1 copy/ extraction) qRT-PCR assay for SARS-CoV-2 N gene RNA and applied this assay to plasma samples (0.5 - 1.0 ml) from COVID-19 outpatients and inpatients with variable severity of illness by WHO scale. For a subset of samples, we centrifuged plasma at 21,000xg for 2 hours, assayed viral RNA in both pelleted and supernatant fractions, and performed electron tomography on the pelleted fraction. SARS-CoV-2-specific antibody titers were determined using S1 and N EIAs and neutralizing antibody titers by infectious virus plaque reduction assay. Results: SARS-CoV-2 RNA was detected in plasma of 22/22 (100%) ICU patients, 9/18 (50%) non-ICU patients and 1/9 outpatients. Plasma viral RNA levels were significantly higher in ICU > non-ICU > outpatients (Fig 1A;p<0.0001 by Kruskal Wallis test), and among inpatients were strongly correlated with WHO score at admission (Spearman r=0.5338, p=0.0006), maximum WHO score during hospitalization (Fig 1B;Spearman r=0.6978, p<0.0001) and clinical outcomes of death, discharge to hospital-level care, discharge to home or discharge asymptomatic (p=0.0035 by Kruskal Wallis test). 80% of viral RNA was recovered in the pelleted fraction after centrifugation, and characteristic virions were observed in the pelleted fraction by electron tomography (Fig 1C). Neutralizing antibody titers showed no overall correlation with plasma viral RNA (Fig 1D) but revealed distinct subgroups with higher level viremia (>1000 copies/ml) and either low titer (<100) or higher titer (>100) neutralizing antibody. Conclusion: SARS-CoV-2 viremia quantified by ultrasensitive RT-PCR was detected in 100% of ICU patients and 50% of non-ICU inpatients. The level of viremia correlated with disease severity and outcome, which may prove useful for clinical decision making. A subgroup of hospitalized patients with high-level viremia and low neutralizing antibody may be the best candidates for antibody therapy.

Making at a Distance: Teaching Hands-on Courses during the Pandemic

Classes involving physical making were severely disrupted by COVID-19. As workshops, makerspaces, and fab labs shut down in Spring 2020, instructors developed new models for teaching physical prototyping, electronics production, and digital fabrication at a distance. Instructors shipped materials and equipment directly to students, converted makerspaces to job-shops, and substituted low-tech construction methods and hobbyist equipment for industrial tools. The experiences of students and instructors during the pandemic highlighted new learning opportunities when making outside the makerspace. Simultaneously, the shutdown raised new questions on the limits of remote learning for digital fabrication, electronics, and manual craft. This panel brings together experts in making to discuss their experiences teaching physical production in art, design, and engineering during the pandemic. Panelists will discuss their teaching strategies, describe what worked and what did not, and argue for how we can best support students learning hands-on skills going forward. © 2021 Owner/Author.

Nurse navigation in the ambulatoryoncology clinic: Patient-centered findings from a survey of50 breast cancer patients

Introduction A nurse navigator is a registered nurse who serves as a patient advocate, educator, and coordinatorfor newly referred cancer patients. Nurse navigators assist with the coordination of care before a patient's firstappointment with their provider. In some healthcare centers, they are also the point-person throughout a patient'sentire treatment process. The nurse navigator role is designed to promote cancer patient empowerment throughadvocacy, educational support, resource navigation, and psychosocial care. Our study attempted to assess theimpact of a newly implemented nurse navigator program, in an academic setting, and measure the effect on patientknowledge, care coordination, and emotional well-being before their breast oncology appointment. Methods A mixed-methods approach was implemented. We provided an Institutional Review Board-approved 9-question survey created from items adapted from Patient Satisfaction with Interpersonal Relationship withNavigators (PSN-I) to UCSF Breast Care Center patients before their first appointments with a breast oncologyprovider. After survey completion, patients were asked to participate in an open-ended interview about their patientexperience with a member of the study team. Results 50 patients were surveyed. 22 (44%) patients surveyed had nurse contact and 28 (56%) did not have priornurse contact before their appointment. With regards to patient knowledge prior to the oncology appointment, 16 out of 22 (73%) of patients with nurse contact felt informed compared to 16 out of 28 (57%) of patients without nurse contact. With regards to having initial questions ans wered before their visit, 11 out of 22 (50%) of patients with nursecontact strongly agreed compared to 4 out of 28 (14.3%) of patients without nurse contact. In response to thestatement, “my care is coordinated effectively in the Breast Care Center,” 15 out of 22 (68%) of patients with nursecontact strongly agreed compared to 12 out of 28 (43%) of patients without nurse contact. Patients with nurse contact were asked whether speaking with a nurse did 1) improve their patient experience and2) better deal with stressful emotions. Among 22 patients with nurse contact, 16 (73%) of patients with nurse contactstrongly agreed to statement 1, and 20 (91%) agreed with statement 2. Patients without nurse contact were asked topredict whether nurse contact would 1) improve their patient experience and 2) better deal with stressful emotions.Out of 28 patients, 14 (50%) strongly agreed to both statements. From our open-ended interviews, we found the following themes: appreciation for preliminary knowledge,identification of knowledge gaps, appointment scheduling, and insurance coverage barriers, and humanistic carefrom nurse navigators. Patients reported that they appreciate not only a nurse navigator's facilitation in coordinationand education but also their companionship during their cancer journey. Conclusions Nurse navigators can play a vital role in improving patient knowledge, workflow/care coordination, andemotional well-being at cancer centers. A greater proportion of patients with initial nurse contact felt informed beforetheir appointment and believed their care was effectively coordinated than those without nurse contact. The majority of patients with nurse contact believed their nurses improved their patient experience and relieved anxiety andstress. Based on this study, we will fully implement initial contact with patients to provide information and coordinateservices for in-person visits. Given the changes brought by COVID, that first contact could also be with a nurse orphysician via video consult prior to an in-person appointment. Future studies should investigate the impact of alongitudinal nurse navigator in providing continuity of care beyond the first referral.