A free-standing children's hospital helps a post-partum woman needing VV-ECMO during COVID-19 Pandemic when ECMO resources were limited

Our case is a 21 y/o pregnant female, 26weeks gestation who presented to OB triage with COVID-19. She was admitted to OB/GYN unit in acute hypoxic respiratory failure and started on steroids and remdesivir. On hospital day 6, she underwent an emergent c-section for fetal distress due to increasing hypoxia and severe ARDS. As her arterial blood gas being ph 7.17/81/40/29.6/-0.4, lactate 6.8nmol/L with escalating vasoactive medication and ventilator settings;ECMO was decided. However, all adult ECMO resources were limited, even within other adult facilities in Central Florida. Through multidisciplinary discussions amongst OB/GYN, adult ICU, and our pediatric ECMO activation team, it was decided to transfer the patient to our free-standing pediatric hospital. The patient was successfully transferred and cannulated for VV-ECMO. Total ECMO run was 413 hours. On ECMO day #12 patient underwent a tracheostomy. On ECMO day # 17, patient developed headaches and seizure activity in which CT revealed a subdural hemorrhage. She was taken off ECMO and underwent an emergent decompressive craniectomy with hematoma evacuation by our pediatric neurosurgical team. Once stable enough, she was discharged post ECMO day #15 (PICU day #32) to rehabilitation center. Two weeks later she had her bone flap replaced, trach removed, and she walked out of our unit home. This case exudes two key points for discussion. The first point of understanding ECMO physiology allows a team to treat many different patient populations. Although this patient was unusual to our pediatric bedside providers being post-partum, our team knew we could help. The second key point is excellent multidisciplinary teamwork and that communication is essential. At Orlando Health Arnold Palmer Hospital, our ECMO activation team consists of surgeons, pediatric intensivists, CT surgeons, perfusionists, nursing, and administration. We meet virtually to discuss how to execute initiation and daily ECMO treatment plans. There were some on the virtual call that were hesitant in accepting care of this adult due to variety of reasons, saying no would have been the easier answer, but not the right thing to do. What we learned from this case may seem so obvious and simple but very difficult to execute;multidisciplinary teamwork, humility, and open communication gave this patient the ability to walk out of the hospital with her baby. Other pediatric ECMO teams can learn from this case is they too can help in extraordinary times such as during a pandemic when adult recourses are limited.

SARS-CoV-2 in Pediatric Intensive Care Unit.

In a lesser extent than adults Intensive Care Units (ICUs), Pediatric ICUs (PICUs) had to deal with the SARS-CoV-2 pandemic. Pediatric intensivists managed serious pediatric forms of primary infections and then in a second stage, post-infectious systemic inflammatory attacks. Some of them helped with the management of adults with a severe form of SARS-CoV-2. Therefore, they had to adapt in record time. In this review, we report (i) the literature data on these two severe pediatric forms, the primary infection and the systemic inflammatory manifestations associated with SARS-CoV-2;(ii) the experience of PICUs in the management of critically ill adults with SARS-CoV-2 infection and (iii) and the impact of the pandemic on the place of families of children in critical situation in PICUs.Copyright © SRLF 2021.

Consequences of Social Distancing Measures during the Covid-19 Pandemic First Wave on the Epidemiology of Children Admitted to Pediatric Intensive Care Units: A Systematic Review

BACKGROUND AND AIM: To synthesize knowledge describing the impact of social distancing measures (SDM) during the first wave of the COVID-19 pandemic on acute illness in children by focusing on the admission to pediatric emergency departments (PED) and intensive care units (PICU). METHOD(S): We searched Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, EPOC Register, MEDLINE, Evidence-Based Medicine Reviews, EMBASE, WHO database on COVID-19, Cochrane Resources on COVID-19, Oxford COVID-19 Evidence Service, Google Scholar for literature on COVID-19 in December 2020. We did not apply study design filtering. The primary outcomes of interest were the global incidence of admission to PICU and PED, disease etiologies, and elective/emergency surgeries. RESULT(S): We identified 6,660 records and eighty-seven articles met our inclusion criteria. All the studies were with before and after study design compared with the historical data, with an overall high risk of bias. The median daily PED admissions decreased to 65% in 39 included studies and a 54% reduction in PICU admission in eight studies. There was a significant decline reported in acute respiratory illness and LRTI in five studies with a median decrease of 63%. We did not find a consistent trend in the incidence of poisoning, but there was an increasing trend in burns, DKA, and a downward trend in trauma and unplanned surgeries. CONCLUSION(S): SDMs in the first wave of the COVID-19 pandemic reduced the global incidence of pediatric acute illnesses. Continual effort and research into the subject should be essential for us to protect the well-being of children.

COVID-19 and the risk of CNS demyelinating diseases: a systematic review

Background: Viral infections are thought proposed as a possible cause of central nervous system (CNS) demyelinating diseases, including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). During the past two years, CNS demyelinating events associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported, but causality is unclear. Objective(s): To investigate the relationship between CNS demyelinating disease development with antecedent and/or concurrent COVID-19 infection. Method(s): A systematic literature review of all publications describing either a new disease onset or relapse of CNS demyelinating diseases (MS, NMOSD, MOGAD) in association with SARS-CoV-2 infection was performed utilizing PRISMA guidelines. Descriptive statistics were used for data analysis, using a case analysis approach. Result(s): Fifty articles were meet inclusion criteria for the study. Most of the reported cases ofNMOSD (n=10., 66.7% of reported cases)and MOGAD (n=12, 92% of reported cases) were of new disease onset, presenting with typical clinical and radiographic features of these conditions, respectively. In contrast, reported MS cases varied amongst newly diagnosed cases (n=11, 13% of reported cases), relapses (n=48, 56.5%) and pseudo-relapses (n=26, 30.5%). Median duration between COVID-19 infection and demyelinating event onset was 9 days (range 0-30 days) in NMOSD, 4 days (range-7-+21 days) in MOGAD, and 13.5 days (range-21-+180 days) in MS. Most cases received high-dose corticosteroids with a good clinical outcome. Conclusion(s): Based upon available literature, the rate of CNS demyelinating events occurring in the setting of preceding or concurrent SARS-CoV-2 infection is relatively low given the prevalence of infection. The clinical outcome of new-onset or relapsing MS, NMOSD or MOGAD associated with antecedent or concurrent infection is mostly favorable. Larger prospective epidemiological studies are needed to better delineate the impact of COVID-19 on CNS demyelinating diseases.

Detection of Transmissible Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) in Blood and Biopsies From Deceased Kidney Donors

Background: We recently reported that in United States, 388 organs from SARSCoV- 2 nucleic acid test (NAT) positive 150 donors were procured between Aug 2020 to Sep 2021. Nearly 1 million deaths have been attributed to SARS-CoV-2 pandemic however only selected group of donor organs were assessed for transplantation. Even after procurement, 28% (of 388) organs were discarded. For kidney transplants (KT), commonest reason for relatively high-quality organ discards (35%) was 'exhaustion of wait list', indicating reluctance to accept these organs. Method(s): We investigated potential risk of donor transmission of SARS-CoV-2 by a prospective study including 23 KT recipients with prior SARS-CoV-2 vaccination. Donor serum and pre-implantation kidney biopsy tissue were assessed for detection of SARSCoV- 2 via a validated commercially available real-time reverse transcription polymerase chain reaction (RT-PCR) (threshold 73 copies/mL). All recipients had SARS-CoV-2 RTPCR on plasma and nasopharyngeal swab at Day-7 post-KT. Result(s): A total of 23 KT were performed from 22 SARS-CoV-2 NAT positive donors between Nov 2021 and Feb 2022. All 22-donor serum samples and 23 procurement biopsies were negative for SARS-CoV-2, including those from 8 donors with symptomatic disease. Six (of 22 donors;27%) had death attributable to SARS-CoV-2 complications. Three recipients with asymptomatic donors were diagnosed with clinical SARS-CoV-2 disease at 10, 14, and 23 days post-KT during 4th pandemic surge. Both graft and patient survival rate was 100% at a median 3 month followup. Collation with national 'Organ Procurement and Transplant Network' registry showed that majority of other organs from these donors were not procured [zero pancreata, zero lungs, 11 (50%) livers, 19 (86%) hearts]. Among 42 KT [55% (23/42) performed at our center], 10 transplanted livers, and 3 hearts;no graft loss or death was reported. Conclusion(s): In this single-center study we report an absence of detectable SARSCoV- 2 virus in donor kidney tissue and plasma from SARS-CoV-2 positive donors.and absence of recipient viremia and nasopharyngeal detectable virus immediately after KT indicating a lack of donor transmission. Our results of excellent graft and patient survival favor utilization of SARS-CoV-2 infected donors.

Robotic-Assisted Kidney Transplantation from Living Donors: Single Center Experience

Introduction: Robotic-assisted kidney transplantation (RAKT) is being adopted for renal transplantation in obese patients with ESRD. Method(s): Consecutive RAKT procured via robotic live donor nephrectomy at our center between June 2018 and August 2021 were retrospectively analyzed. Our first 20 cases (Group I) were compared (student's t-test and Fisher's exact test, p < 0.05 significant) to the later 20 cases (Group II). Result(s): There was no difference in donor age (39.6+/-10.51 vs 38.4+/-12.14 years) or BMI (27.46+/-4.64 vs 29.48+/-4.06) between the two groups. 75% of recipients in both groups received a left kidney. A majority (>60%) of recipients in both groups were African Americans. Recipients in Group II were significantly older than in Group I. There was no significant difference in patient or graft survival or serum creatinine (1.67+/-0.99 mg/dL vs 1.93+/-0.55 mg/dL) at 1-year post-RAKT. One patient in group I died from respiratory failure due to COVID-19. The anastomosis times (35.16+/-7.75 vs 32.00+/-7.32 mins) were not significantly different, though the re-warming time was a significantly longer in our early experience (47.75+/-9.59 vs 42.00+/-6.55 mins, p = 0.016). The incidence of post-op washout (10%), ileus (10%), incisional hernia (5%) and delayed graft function (20%) were similar in both groups. Conclusion(s): Our early and more recent experience demonstrates that RAKT from living donors can be safely performed with excellent outcomes in obese, predominantly African American patients with ESRD. Practice paradigms are evolving to offer RAKT to patients with BMI >40 who may otherwise be considered ineligible for kidney transplantation.

Disparate air pollution reductions during California’s COVID-19 economic shutdown

Minority communities in the United States often experience higher-than-average exposures to air pollution. However, the relative contribution of institutional biases to these disparities can be difficult to disentangle from other factors. Here, we use the economic shutdown associated with the 2020 COVID-19 shelter-in-place orders to causally estimate pollution exposure disparities caused by the in-person economy in California. Using public and citizen-science ground-based monitor networks for respirable particulate matter, along with satellite records of nitrogen dioxide, we show that sheltering in place produced disproportionate air pollution reductions for non-White (especially Hispanic and Asian) and low-income communities. We demonstrate that these racial and ethnic effects cannot be explained by weather patterns, geography, income or local economic activity as measured by local changes in mobility. They are instead driven by regional economic activity, which produces local harms for diffuse economic benefits. This study thus provides indirect, yet substantial, evidence of systemic racial and ethnic bias in the generation and control of pollution from the portion of the economy most impacted in the early pandemic period. © 2022, The Author(s), under exclusive licence to Springer Nature Limited.

Experience with IMGN632, a novel CD123-targeting antibody-drug conjugate (ADC), in frontline patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN)

BACKGROUND: BPDCN is a rare, aggressive hematologic malignancy characterized by historically poor overall survival and limited therapeutic options. Despite the recent approval of tagraxofusp-erzs for BPDCN, outcomes remain suboptimal for many patients. Additionally, patients with BPDCN are older and often have co-morbidities at baseline, preventing them from receiving tagraxofusp-erzs. Therefore, novel therapies are needed in the frontline setting for patients with BPDCN. Overexpression of CD123 (IL-3Rα) is present in all BPDCN cases, thereby establishing this surface marker as a target for therapeutic intervention. IMGN632 is a CD123-targeting ADC, comprised of a high-affinity anti-CD123 antibody coupled to a DNA-alkylating payload of the novel IGN (indolinobenzodiazepine pseudodimer) class. IMGN632 has demonstrated favorable safety and promising clinical activity in relapsed/refractory (R/R) BPDCN [Blood (2020) 136 (Supplement 1): 11-13], leading to the FDA granting IMGN632 Breakthrough Therapy Designation (BTD) for R/R BPDCN (Oct 2020). Following BTD and alignment with FDA, a pivotal cohort in frontline (no prior systemic treatment) BPDCN patients was initiated in addition to a continuing cohort of patients with R/R disease, where we have enrolled 33 patients to date. Here we report the initial experience of three frontline patients who are not part of the pivotal cohort. METHODS: IMGN632 was administered IV at a dose of 0.045 mg/kg on day 1 of a 21-day cycle to all patients. Efficacy was assessed using modified Severity Weighted Assessment Tool (for skin lesions), PET/CT, and blast percentage in bone marrow aspirates. The response criteria were adapted from established BPDCN criteria (Pemmaraju NEJM 2019). RESULTS: Three patients with frontline BPDCN (no prior systemic therapy) received IMGN632. All three of these frontline patients achieved a clinical complete remission (CRc). Patient 1 was a 79yo woman who presented with skin, nodal, and extensive bone marrow disease (80% involvement). After one dose of IMGN632, she cleared her bone marrow (0%), and after 3 cycles, her nodal lesions and skin lesions resolved to achieve a CRc. Upon complete response, treatment was held due to patient co-morbidities. With just 3 cycles of IMGN632, this patient achieved duration of response (DOR) of 10.7 months without further therapy. Patient 2 was a 67yo man who had extensive skin disease covering >20% of the body;over several cycles, he achieved a PR then a CRc and bridged to an allogeneic stem cell transplant (SCT). The patient achieved a DOR of 13.5 months, with no evidence of disease relapse when he died from graft versus host disease. Patient 3 was a 66yo woman who presented with extensive skin and nodal lesions. After improvement over 4 cycles, she achieved a CRc with clearing of most of her skin lesions and all nodal lesions. Unfortunately, while still in CRc, the patient died of COVID-19 pneumonia, with a DOR of 3.7 months. CONCLUSION: Administration of IMGN632 to frontline BPDCN patients resulted in clinical complete remission in the initial three patients with durable responses in the two non-COVID impacted patients. None of these patients progressed while on therapy, and one patient successfully bridged to SCT. Enrollment continues in the pivotal frontline and R/R cohorts. (BPDCNtrial.com;NCT03386513).

Zanubrutinib in patients with B-cell malignancies intolerant to ibrutinib and/or acalabrutinib

Introduction: Bruton tyrosine kinase inhibitor (BTKi) therapy is remarkably effective in a number of B-cell malignancies;however, its continuous use is limited by adverse events (AE) leading to discontinuation. Zanubrutinib is a potent and selective BTKi with the potential to be a safe and effective therapy after intolerance to previous BTKi therapy. Here, we report preliminary results of a phase 2 study of zanubrutinib in patients with B-cell malignancies intolerant to ibrutinib and/or acalabrutinib based on a median follow-up of 6 months. Methods: Patients meeting protocol criteria for intolerance to ibrutinib, acalabrutinib, or both (without documented progressive disease on ibrutinib or acalabrutinib) were given zanubrutinib monotherapy (160mg twice daily or 320mg once daily at investigator's discretion). Recurrence of adverse events that led to intolerance to prior BTKi and additional safety measures were assessed based on the Common Terminology Criteria for AEs v5.0. Investigators determined responses using disease status at study entry as baseline and standard established disease response criteria. Results: As of 1 March 2021 (cutoff), 64 patients (n=48 chronic lymphocytic leukemia/small lymphocytic lymphoma, n=10 Waldenström macroglobulinemia, n=3 mantle cell lymphoma, n=3 marginal zone lymphoma) were enrolled, received ≥1 dose of zanubrutinib, and were analyzed for safety. The median age was 71 y (range, 49-91);the median duration of treatment was 5.9 months (range, 0.6-16.6). The median number of prior regimens was 2 (range, 1-12). Regarding prior BTKi, 55 patients had received ibrutinib monotherapy, eight had received ibrutinib combination therapy, and seven had received acalabrutinib monotherapy. The median number of ibrutinib- or acalabrutinib-intolerant adverse events per patient was 2 (range, 1-5). Most ibrutinib- (75%) and acalabrutinib-intolerant events (75%) did not recur with zanubrutinib (Table 1). A majority (90%) of the recurrent ibrutinib-intolerant events were less severe with zanubrutinib than with ibrutinib. Ibrutinib intolerance events present in >1 patient that did not recur on zanubrutinib were alanine aminotransferase increased, aspartate transaminase increased, neutropenia, and pain in extremity. The ibrutinib-intolerant events that recurred were diarrhea, dizziness, insomnia, nausea, constipation, myalgia, stomatitis, arthralgia, headache, muscle spasm, rash, atrial fibrillation, fatigue, hemorrhage, and hypertension. One-third of the recurrent acalabrutinibintolerant events were less severe with zanubrutinib than with acalabrutinib. The acalabrutinib-intolerant events that recurred were myalgia and arthralgia. Two events of arthralgia that induced acalabrutinib intolerance did not recur with zanubrutinib. No ibrutinib- or acalabrutinib-intolerant events recurred at a higher severity while patients were on zanubrutinib. At cutoff, 57 patients remained on treatment;one withdrew consent due to zanubrutinib-unrelated grade 3 syncope. Grade ≥3 adverse events were reported in 14 patients (21.9%), serious adverse events in five patients (7.8%;pain in jaw;COVID-19 pneumonia;anemia;febrile neutropenia and salmonella infection [occurred in the same patient]), adverse events requiring dose interruptions in 15 patients (23.4%), and adverse events leading to dose reduction in three patients (4.7%). Adverse events led to zanubrutinib discontinuation for three patients (4.7%). One death was reported (COVID-19 pneumonia). Among efficacy evaluable patients (n=48), the disease control rate was 89.6% and the overall response rate was 50.0%. Conclusions: In patients with B-cell malignancies intolerant to ibrutinib and/or acalabrutinib, zanubrutinib therapy was effective and controlled patient's disease or induced responses to therapy, and was well-tolerated;most adverse events that led to discontinuation of previous BTKi therapy did not recur while patients were on zanubrutinib.

[Delay in Diagnosis and Treatment in Breast Cancer Patients during the Covid-19 Pandemic - Case Study]

INTRODUCTION: The SARS-CoV-2 pandemic presents a challenge to health systems in general and for cancer patients in particular. The hurdles of receiving ongoing medical treatment starting from diagnosis through continuous medical care is exemplified in this case report. Here, we describe a patient who was diagnosed with advanced breast cancer concurrently with COVID-19. The patient needed urgent medical care for her cancer due to the delay in diagnosis that stemmed from fear of exposure to the COVID-19 virus. We will discuss the extent of the COVID-19 pandemic in cancer patients and specifically in breast cancer patients, the complexity of treating these patients and the influence of the pandemic on delays in diagnosis of cancer.

Phase 2 Study of Zanubrutinib in BTK Inhibitor-Intolerant Patients (Pts) with Relapsed/Refractory B-Cell Malignancies

Background: Bruton tyrosine kinase inhibitors (BTKis) are important tools to treat B-cell malignancies. However, duration of treatment may be limited by adverse events (AEs). Zanubrutinib (zanu) is a BTKi approved for mantle cell lymphoma (MCL) and is in development for other hematologic malignancies. Data from phase 3 head-to-head trials of zanu vs ibrutinib (ibr) in pts with Waldenström macroglobulinemia (WM) or chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) demonstrated that pts treated with zanu showed lower rates of AEs leading to discontinuation (Blood 2020;136(18):2038-50;EHA 2021 LB1900). Preliminary results from BGB-3111-215 (NCT04116437) show that zanu was well-tolerated in pts who discontinued ibr and/or acalabrutinib (acala) treatment due to AEs (EHA 2021 EP642). Here, we report updated results from the BGB-3111-215 study with a median follow-up of 9 months. Methods: This study is an ongoing US, phase 2, multicenter, single-arm, open-label study. The safety and efficacy of zanu monotherapy (160 mg twice daily or 320 mg once daily) were evaluated in pts with B-cell malignancies who met criteria for continued treatment after having become intolerant to prior BTKi therapy. Pts were divided into cohort 1 (pts who were intolerant to ibr only) and cohort 2 (pts who were intolerant to acala alone/and ibr). Pts with documented progressive disease (PD) on prior BTKi therapy were excluded. Efficacy and safety, including recurrence of intolerant AEs to the prior BTKi, were evaluated. AEs were assessed for severity, seriousness, and relation to zanu;as well as dose reductions, holds, or discontinuations. Response was assessed by investigators based on response criteria for their respective indications (Blood 2008;131:2745;J Clin Oncol 2012;30:2820;J Clin Oncol 2014;32:3059;Br J Haemtol 2013;160:171). Disease parameters from study entry were the baseline for response assessment. Mutational analysis was performed on pts who discontinued treatment, and data will be shared once available. To support clinical findings, kinase selectivity was assessed using Kinome profiling at 100X IC50 (against BTK) for zanu, ibr, acala and its major metabolite, M27 (Reaction Biology Corp). Results: As of 7 June 2021 (data cutoff), 57 pts (n=44 CLL/SLL;n=9 WM;n=2 MCL;n=2 marginal zone lymphoma [MZL]) were enrolled in cohort 1, and 7 pts were enrolled in cohort 2 (n=4 CLL;n=1 WM;n=1 MCL;n=1 MZL). All received ≥1 dose of zanu and were analyzed for safety. The median age was 71 years (range, 49-91) in cohort 1 and 71 years (range, 65-76) in cohort 2;median duration of treatment was 8.7 months (range, 0.6-17.9) in cohort 1 and 8.2 months (range, 6.4-11.4) in cohort 2;median number of prior regimens was 1 (range, 1-12) in cohort 1 and 3 (range, 2-5) in cohort 2. Within cohort 2, 5 pts were intolerant to both ibr and acala. Median number of intolerant events per pt for both cohorts 1 and 2 was 2 (range, 1-5). Overall, 73% of pts did not experience recurrence of their ibr or acala intolerant events and 79% of recurrent events recurred at a lower severity (Figure 1). At cutoff, 54 pts remained on treatment. Reasons for treatment discontinuation were AEs (n=4), PD (n=4), physician's decision (n=1), and consent withdrawal (n=1). Grade ≥3 AEs were reported in 18 pts (28%), and serious AEs occurred in 7 pts (11%). AEs requiring dose interruptions occurred in 17 pts (27%), and AEs leading to dose reduction occurred in 3 pts (5%). One death, due to COVID-19, was reported. Pts demonstrated maintained (41%) and improved (53%) response with zanu treatment from their reported best overall response on prior BTKis for a total disease control rate of 94% (including a 42% partial response rate in pts with CLL/SLL, 30% in pts with WM, and a 20% very good partial response rate in pts with WM). Zanu also demonstrated good selectivity by kinase profiling. It showed >50% inhibition on 7/370 kinases, while ibr, acala, and M27 had more off-target binding (17, 15 and 23 kinases, respectively) at their respective 100X IC50 (BTK) c ncentrations (Figure 2). Conclusion: In pts with B-cell malignancies intolerant to ibr and/or acala, zanu treatment resulted in continued disease control or improved response. Zanu was well-tolerated, and most AEs that led to discontinuation of previous BTKi therapy did not recur or recurred at a lower grade. In support of clinical findings, differentiation between BTKi selectivity profiles favor zanu over ibr and acala. [Formula presented] Disclosures: Shadman: Abbvie, Genentech, AstraZeneca, Sound Biologics, Pharmacyclics, Beigene, Bristol Myers Squibb, Morphosys, TG Therapeutics, Innate Pharma, Kite Pharma, Adaptive Biotechnologies, Epizyme, Eli Lilly, and Atara Biotherapeutics, Adaptimmune: Consultancy;Mustang Bio, Celgene, Bristol Myers Squibb, Pharmacyclics, Gilead, Genentech, Abbvie, TG Therapeutics, Beigene, AstraZeneca, Sunesis, Atara Biotherapeutics, GenMab: Research Funding;Abbvie, Genentech, AstraZeneca, Sound Biologics, Pharmacyclics, Beigene, Bristol Myers Squibb, Morphosys, TG Therapeutics, Innate Pharma, Kite Pharma, Adaptive Biotechnologies, Epizyme, Eli Lilly, and Atara Biotherapeutics, Adaptimmune: Membership on an entity's Board of Directors or advisory committees. Flinn: Nurix Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute;Seagen: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding;MorphoSys: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding;Forty Seven: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding;Calithera Biosciences: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding;Verastem: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding;Curis: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding;Takeda: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding;Yingli Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute;IGM Biosciences: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding;AbbVie: Consultancy, Other: All Consultancy and Research Funding payments made to Sarah Cannon Research Institute, Research Funding;Portola Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding;Trillium Therapeutics: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding;Rhizen Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding;Incyte: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding;Acerta Pharma: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding;Agios: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding;Kite, a Gilead Company: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding;Gilead Sciences: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding;Pharmacyclics LLC, an AbbVie Company: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding;Karyopharm Therapeutics: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding;Forma Therapeutics: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding;Genentech: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding;ArQule: Other: All research funding payments mad to Sarah Cannon Research Institute, Research Funding;Triphase Research & Development Corp.: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding;Roche: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding;Pfizer: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding;Teva: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding;Infinity Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding;Unum Therapeutics: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding;Celgene: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding;Constellation Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding;Juno Therapeutics: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding;AstraZeneca: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding;Iksuda Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute;Loxo: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding;Merck: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding;Novartis: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding;Great Point Partners: Consultancy, Other: All consultancy payments made toSarah Cannon Research Institute;BeiGene: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding;Janssen: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding;TG Therapeutics: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding;Century Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute;Hutchison MediPharma: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute;Vincerx Pharma: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute;Sarah Cannon Research Institute: Current Employment;Servier Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute;Yingli Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute;Seagen: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute;Servier Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute;Unum Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute, Research Funding;Johnson & Johnson: Current holder of individual stocks in a privately-held company;Seattle Genetics: Research Funding. Levy: Epizyme: Consultancy, Other: Promotional speaker;Amgen Inc.: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau;Gilead Sciences, Inc.: Consultancy, Honoraria, Speakers Bureau;GSK: Consultancy, Other: Promotional speaker;Morphosys: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau;AbbVie: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau;Beigene: Consultancy, Honoraria, Speakers Bureau;Karyopharm: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau;AstraZeneca: Consultancy, Honoraria, Speakers Bureau;Takeda: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau;Novartis: Consultancy, Other: Promotional speaker;Dova: Consultancy, Other: Promotional speaker;TG Therapeutics: Co sultancy, Honoraria, Speakers Bureau;Bristol Myers Squibb: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau;Seattle Genetics: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau;Jazz Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau;Janssen Pharmaceuticals: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau. Burke: SeaGen: Consultancy, Speakers Bureau;Beigene: Consultancy, Speakers Bureau;MorphoSys: Consultancy;Bristol Myers Squibb: Consultancy;AstraZeneca: Consultancy;Epizyme: Consultancy;Verastem: Consultancy;Kura: Consultancy;Kymera: Consultancy;AbbVie: Consultancy;Adaptive Biotechnologies: Consultancy;Roche/Genentech: Consultancy;X4 Pharmaceuticals: Consultancy. Cultrera: Beigene: Research Funding. Yimer: Astrazeneca: Speakers Bureau;Karyopharm: Current equity holder in publicly-traded company, Speakers Bureau;Janssen: Speakers Bureau;Beigene: Speakers Bureau;GSK: Speakers Bureau;Sanofi: Speakers Bureau;Amgen: Speakers Bureau;Pharmacyclics: Speakers Bureau;Texas Oncology: Current Employment. Chaudhry: Medical Oncology Associates, PS (dba Summit Cancer Centers): Current Employment;Novartis, Immunomedics: Current holder of individual stocks in a privately-held company. Gandhi: TG Therapeutics: Honoraria;Karyopharm Therapeutics: Honoraria;GlaxoSmithKline: Honoraria. Kingsley: Comprehensive Cancer Centers of Nevada: Current Employment. Tumula: Texas Oncology: Current Employment. Manda: Morphosys: Honoraria;Genmab: Current equity holder in publicly-traded company. Chen: BeiGene: Current Employment, Divested equity in a private or publicly-traded company in the past 24 months. Cohen: BeiGene: Current Employment, Current equity holder in publicly-traded company, Other: Travel, Accommodations, Expenses. By: BeiGene, Ltd: Current Employment. Xu: Beigene: Current Employment;AstraZeneca: Ended employment in the past 24 months. Liu: BeiGene Co., Ltd: Current Employment, Current equity holder in publicly-traded company. Sharman: TG Therapeutics: Consultancy;Centessa: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees;Pharmacyclics LLC, an AbbVie Company: Consultancy;BMS: Consultancy;AbbVie: Consultancy;BeiGene: Consultancy;AstraZeneca: Consultancy;Lilly: Consultancy.

Safety of the COVID-19 vaccines in NMOSD and MOGAD: Results from an online survey

Background: The COVID-19 vaccines are currently recommended for people with Neuromyelitis optica spectrum disorders (NMOSD) and MOG-antibody-associated disease (MOGAD). However, the vaccines were not specifically tested in this population, and their safety profile is uncertain. Objective To report safety data of the COVID-19 vaccine in NMOSD and MOGAD. Methods An anonymous survey was distributed to members of the Facebook 'NMO Clinic' page. Participants were asked general demographic and disease-related questions and specific questions regarding the safety profile of the COVID-19 vaccine. Results 438 participants completed the questionnaire. The median age was 51 years (range 18-82 years);366 were females (83.6%);367 (83.8%) reside in the USA;330 (75.3%) were white. 120 participants (27.4%) had associated comorbidities, and 354 participants (80.1%) were treated with immunotherapies. 239 participants (66.2%) were younger than 55 years of age. 251 participants (57.3% of the responders) received the Pfizer vaccine;153 (34.9%) received the Moderna vaccine;32 (7.3%) received the AstraZeneca vaccine, and 2 (0.04%) received the Johnson & Johnson vaccine. 138 participants (31.5%) reported immediate adverse events. Of these, 93 (67.4%) were < 55 years old, and 45 (32.6%) were > 55 years old (p=0.0086). The most common adverse event was pain at the injection site, reported by 102 participants (23.3%). 73 participants (16.7%;47.3 % of those <55 years and 64.4 % of those > 55 years, p=0.3649) reported new or worsening neurological symptoms following the vaccination, the most frequent being sensory disturbances (48 participants, 65.8%). Most symptoms occurred within the first 24 hours after vaccination and resolved within three days. Only 13 participants (17.8 %) reported the need of additional medications to treat their symptoms. Conclusions This survey indicates an overall favorable safety profile of the COVID-19 vaccines in NMOSD and MOGAD. Additional studies are warranted to confirm these data.

COMPARISON OF ICSI WITH FRESH AND FROZEN EJACULATED SPERM IN DONOR OOCYTE RECIPIENT CYCLES UTILIZING SIBLING OOCYTES

Objective: Use of frozen sperm in non-male factor infertility is often needed in donor cycles. Most studies to date examining outcomes of fresh vs frozen sperm are unable to control for oocyte quality. Studies examining sibling oocytes represent a unique model to control for oocyte quality. A recent small study using this model found worse outcomes in the frozen group. We sought to evaluate, in a large cohort, if fresh and frozen ejaculated sperm are associated with similar pregnancy outcomes by analyzing paired donor egg recipient (DER) cycles. Materials and Methods: Retrospective cohort study from 2016-2019 at a large fertility center. Patients who underwent DER cycles where oocytes were split between two couples and one couple used fresh sperm and the other used frozen sperm were included. All patients with uterine factor, male factor or surgically obtained sperm were excluded. Primary outcome was Ongoing pregnancy/Live birth rate (OPR). Secondary outcome included clinical pregnancy rate (CPR) and miscarriage rate. GEE analysis was performed to control for confounding factors and donors providing oocytes to both study cohorts. Results: 1255 donor oocytes cycles were screened. A total of 205 unique oocytes donors were identified with oocytes inseminated with discrepant sperm in different recipient cycles. There were 698 recipient transfer cycles, 405 fresh and 293 frozen. Cohorts were similar in baseline characteristics (table 1). There were no differences in OPR/LBR with fresh vs frozen sperm (53.6% vs 55.6%, p=0.7) or clinical pregnancies (66.4% vs 63.5%, p=0.4). Spontaneous miscarriage (<20 weeks) was significantly higher in the fresh cohort (12.3% vs 6.1%, p=0.01). Conclusions: In this large study uniquely controlling for oocyte quality, there are no differences in live birth rate when fresh or frozen sperm was utilized on the same donor oocytes. This type of comparison is important as it helps control as much as possible the oocyte, thus isolating the discrepant sperm state as a determinant of outcome. There was a significant increase in miscarriage rate when fresh sperm was used. Impact Statement: In this large study comparing paired sibling donor oocytes, no difference in live birth rate was seen when couples utilized fresh or frozen sperm. This is particularly important in large donor or international programs especially during the COVID19 pandemic in which it may be difficult for the partner to be present, and a frozen sample may be needed. [Formula presented]

Patient attitudes towards NMOSD diagnosis and treatment: Final survey results

Objective: To better understand the neuromyelitis optica spectrum disorder (NMOSD) patient experience throughout the course of their illness.Background: NMOSD is a rare autoimmune disorder that causes recurrent inflammatory attacks of the optic nerve, spinal cord, and brain. As a rare disease, knowledge and awareness of NMOSD are often limited, resulting in potential delays in diagnosis and treatment. Design/Methods: We developed a comprehensive survey to understand the patient's perspective on their journey, from initial presentation to present status. After validating the instrument, we shared it with members of the NMO Clinic Facebook group. 151 patients responded to the 85 questions covering basic demographics, symptoms, medical testing to reach a diagnosis, and the patient's psychosocial responses to the process. Consistency between internal responses indicated that the vast majority of patients understood the questions. Results: Patients primarily self-reported as White (76%), Asian (7%), or African American (7%). Time to diagnosis;mean (SD) was 2.2 (3.2) years. Initial reactions were primarily fear/shock and/or frustration. First contact with a medical professional was felt to be "not helpful" or "somewhat helpful" for many patients (71%), in part due to non-specific diagnosis and/or treatment. Once referred to specialists (primarily neurologists), the majority (98%) reported finding a professional who could help. While most patients reported that having a diagnosis and being under the care of a specialist gave them a comprehensive plan with the best hope for their future, 29% still felt challenged for a variety of reasons. Despite the complexities of the ongoing COVID-19 pandemic, 83% of patients reported confidence that their team had done all they can to help manage the current environment. Conclusions: The NMOSD patient journey frequently begins with fear and frustration. Finding the right specialist and identifying appropriate screening tests can lead to earlier diagnosis and progression towards better patient outcomes.

Asthma deaths in Scotland during the first peak of covid-19: Did reduced hospital admission result in excess asthma mortality?

Introduction During the first wave of the COVID-19 pandemic in the UK there was a reduction in A&E attendances and hospital admissions. Monthly excess deaths peaked in April 2020;driven by COVID-19.1 We investigated whether hospital admissions due to asthma were reduced in April 2020 compared to the previous five years and if this was accompanied by an increase in asthma deaths. Methods Five-year data were obtained from Public Health Scotland from the time period January 2015 to June 2020. Hospital admission data was sourced from Public Health Scotland's Scottish Morbidity Records, death certificate data from National Records of Scotland and A&E attendance data from Public Health Scotland. Data were analysed using statistical process control charts. Results A&E presentations in April 2020 reduced to 44% of April 2019. Hospital admissions for all conditions reduced, as did asthma admissions (figure 1a) [218 in April 2020 versus previous 5 year mean of 418]. 7958 deaths occurred in April 2020;an excess of 2731 from previous 5-year mean. In 130 deaths asthma was recorded on the death certificate as either the underlying or the contributory cause, giving rise to around 100 apparent excess deaths versus the previous 5-year mean of 27.5 (figure 1b). Asthma was recorded as the underlying cause of death in 7 cases, comparable with the previous 5 year mean of 9.2 deaths (figure 1c). The age distribution of those with asthma on the death certificate was: 97-65, 27 aged 45-65, 6 aged 18-44 and 0 <18 years. Of the 123 patients with asthma recorded as a contributory cause, 81 had COVID-19 recorded as the underlying cause of death. All 7 patients with asthma recorded as underlying cause of death were elderly and the location of death was: 3 at home, 2 in residential care, 1 in hospital and 1 in a hospice. Conclusions Reduced acute healthcare utilisation by people with asthma during the first peak of COVID-19 did not appear to result in increased mortality where asthma was the primary underlying cause of death.