ABSTRACT
Background & Aim: The pro-angiogenic, immunoregulatory and anti- inflammatory properties of MSCs are being exploited for the development of cellular therapies, including the treatment of graft versus host disease (GvHD), inflammatory bowel disease and COVID-19. SNBTS have developed a GMP process to bank umbilical cord MSCs (UC-MSCs) whereby we can reliably bank 100 vials of 10 million P2 UC-MSCs per cord. Each of these vials can be extensively expanded and stored for specific applications. The ultimate aim of the bank is for off-the-shelf clinical use, e.g., in GvHD or as an adjuvant therapy in Islet transplantations. Methods, Results & Conclusion(s): During process development, different basal media and supplements were screened for proliferation and MSC marker expression. Cells grown in promising media combinations were then tested for tri-lineage differentiation (identity), their chemokine/cytokine expression and T-cell inhibition (function) assessed. Medium selected for further GMP development and scale up was ultimately determined by all round performance and regulatory compliance. GMP-like UC-MSCs were shown to have immune-modulatory activity in T-cell proliferation assays at 4:1 or 16:1 ratios. Co-culture of UC-MSCs and freshly isolated leukocytes, +/- the immune activating agent LPS, show a dose dependent survival effect on leukocytes. In particular, neutrophils, which are normally very short lived in vitro demonstrated increased viability when co-cultured with UCMSCs. The survival effect was partially reproduced when UC-MSC were replaced with conditioned medium or cell lysate indicating the involvement of soluble factors. This improved neutrophil survival also correlates with results from leukocyte migration studies that demonstrate neutrophils to be the main cell type attracted to MSCs in in vitro and in vivo. Genetic modification of UC-MSC may improve their therapeutic potential. We have tested gene editing by CRISPR/Cas9 technology in primary UC-MSCS. The CXCL8 gene, highly expressed in UC-MSC, was targeted in isolates from several different donors with editing efficiencies of 78-96% observed. This translated to significant knockdown of CXCL8 protein levels in resting cells, however after stimulation levels of CXCL8 were found to be very similar in edited and non-edited UC-MSCs. This observation requires further study, but overall the results show the potential to generate future banks of primary UC-MSCS with genetically enhanced pro-angiogenic, immunoregulatory and/or anti-inflammatory activities.Copyright © 2023 International Society for Cell & Gene Therapy
ABSTRACT
Background: The CoV-2 envelope (E) protein plays an important role in virus assembly, budding, immunopathogenesis and disease severity. E protein has ion channel activity, is located in Golgi and ER membranes of infected cells and is associated with inflammasome activation and immune dysregulation. Here we report that BIT225, an investigational HIV clinical compound, inhibits E ion channel activity and prevents body weight loss and mortality and reduces inflammation in lethally infected K18-hACE2 transgenic mice. BIT225 efficacy was observed when dosing was initiated before or 24 h or 48 h after infection. Method(s): SARS-CoV-2 E protein ion channel activity and Xenopus TMEM16A were measured in Xenopus oocytes. K18-hACE2 transgenic mice were infected intranasally with 104 pfu SARS CoV 2 (US-WA1/2020) and dosed orally twice daily with BIT225 for up to 12 Days. Dosing was initiated 12 h pre-infection or 24 h or 48 h post-infection. Disease parameters measured were survival, body weight, viral RNA by qPCR and infectious virus titre (plaque assay) in lung tissue homogenates and serum. In addition, levels of pro-inflammatory cytokines (IL-6, IL-1alpha, IL-1beta, TNFalpha & TGFbeta, MCP-1) were measured in lung and serum samples. Result(s): BIT225 inhibited ion channel activity of E-protein, but not that of TMEM16A in Xenopus oocytes. BIT225 dosed at 300mg/kg BID for 12 days starting 12 h pre-infection completely prevented body weight loss and mortality in SARS-CoV-2 infected K18 mice (n=12), while all vehicle-dosed animals reached a mortality endpoint by day 9 across two studies (n=12). Figure 1 shows results from a time of addition study: When treatment with BIT225 started at 24 h post-infection, body weight loss and mortality was also prevented (100% survival, n=5). In the group of mice where treatment started at 48 h after infection, body weight loss and mortality were prevented in 4 of 5 mice. Treatment efficacy was associated with significant reduction in lung viral load (3.5 log10), virus titer (4000 pfu/ml) and lung and serum cytokine levels. Conclusion(s): BIT225 is an inhibitor of SARS-CoV-2 E-protein viroporin activity. In the K18 model BIT225 protected mice from weight loss and death, inhibited virus replication and reduced inflammation. These effects were noted when treatment with BIT225 was initiated before or 24-48 hours after infection and validate viroporin E as a viable antiviral target and support the clinical study of BIT225 in treatment of SARS-CoV-2.
ABSTRACT
This chapter is focused on sport events hosted at a national level. In meeting this aim, the chapter explores the impact of COVID-19 on a national sport event held in Australia as the major case study. The authors conducted a detailed analysis on a national road cycling event held in Ballarat in the state of Victoria. The city of Ballarat hosted the 2021 Australian Road Nationals Cycling Championships, with this national event providing a series of COVID-19-related logistical and event management challenges that are documented and dissected in the chapter. © 2023 selection and editorial matter, Stephen Frawley and Nico Schulenkorf;individual chapters, the contributors.
ABSTRACT
Purpose : Microincision vitrectomy surgery (MIVS) studies have shown low complication rates. In the setting of the COVID-19 pandemic and rural satellite clinics, we investigated the role of telemedicine as an alternative to postoperative visit (POV) regimens after uncomplicated MIVS. Methods : This IRB approved, prospective single-site, and single-surgeon study included patients without any history of glaucoma, ocular trauma, or severe systemic or ocular disease who underwent uncomplicated MIVS for any indication between January-August 2021. Prophylactic topical pressure-lowering drops were prescribed if POV intraocular pressure (IOP) was ≥22 mmHg. POVs included the same day after surgery, week(s) 1, 2, 8, and 12. Patients were randomly assigned (1:1) into two arms: telemedicine (TM) or In-person (IP). Weeks 1 and 8 POV utilized protocol-based and questionnaire guided undilated exams performed by an ophthalmology fellow that were conducted either TM or IP, according to arm assignment. Any patients with concerning symptoms identified at these visits were scheduled for dilated exams with the surgeon. All patients underwent dilated exams performed by the surgeon on the same day after surgery, weeks 2 and 12. Primary endpoint was mean best corrected visual acuity (BCVA). Secondary endpoints included changes in intraocular pressure (IOP), retinal nerve fiber layer thickness, and number of additional visits. Statistical analysis included Mann Whitney U and chi-square tests. Results : Fifty-two eyes from 50 patients (33 female, 17 male;p-value=0.02) with mean ages of 68.4±6.8 years underwent 55 total surgeries with 25 or 27G MIVS platforms. Forty-seven patients have completed all POVs. Mean preop BCVA logMAR was 0.53±0.55 and 0.40±0.45, and at 12 weeks, they were 0.39±0.45 and 0.26±0.33 for the TM and IP groups, respectively. No significant between-group differences were found for primary or secondary outcomes. All cases of abnormal IOP resolved by the following POV with pressure lowering drops. Concerning symptoms were identified in five patients requiring additional visits, revealing two cases of worsening macular edema (1 TM and 1 IP) and one case each of cataract progression (TM), vitreous hemorrhage (IP), and macular hole recurrence (TM). No complications presented at the TM or IP visits. Conclusions : Telemedicine-assisted POV regimens may be a safe and convenient alternative for patients undergoing uncomplicated MIVS.
ABSTRACT
Aim: The Enhanced Recovery After Surgery (ERAS) protocol for total laryngectomies was first implemented in our tertiary head and neck centre from November 2019. It includes pre-operative carbohydrate loading and an early swallow test which facilitates recommencement of oral intake to improve outcomes. Protocol adherence rate and patient outcomes were measured to determine the effectiveness and benefits of ERAS in laryngectomy patients. Method: 22 total laryngectomy patients from November 2019 to September 2021 were enrolled onto the ERAS protocol, 18 primary and 3 salvage cases. An analysis of the respective patient cohorts was performed to determine adherence to the ERAS protocol and outcomes such as complications and length of inpatient stay were measured. Results: 19 patients (86%) received pre-operative carbohydrate loading successfully, while 3 patients were contraindicated due to background of diabetes. Early swallow test was performed in 59% of patients. Potential reasons for delay were stoma dehiscence or clinical suspicion of neo-pharyngeal leak. 59% of primary cases were deemed medically fit for discharge within the target timeframe of 12-14 days whereas no target was set for salvage cases due to expected poor healing. Main complication in primary cases was neo-pharyngeal leak followed by stoma dehiscence with 28% and 11% respectively. Conclusion: Limitations of our study include small sample size due to the COVID-19 pandemic. Despite its infancy, the ERAS protocol has achieved good outcomes in early recommencement of oral intake post-laryngectomy and encouraging early safe discharge from hospital. Future plans include establishment of Prehab Clinic and application of ERAS to neck dissection patients.
ABSTRACT
Introduction: The incorporation of telemedicine into the post-COVID-19 pandemic spine practice remains unclear. The objective of this study is to compare the likelihood of missing an appointment between scheduled telemedicine visits and in-person appointments for spine patients of varying socioeconomic status. Materials and Methods: Patients with scheduled outpatient appointments with the orthopaedic spine division between 2019 and 2021 were retrospectively evaluated. Patients were divided into the two cohorts by appointment type: telemedicine visit (N = 4,387) and in-person appointment (N = 3,810). Home addresses were used to calculate the Area Deprivation Index (ADI), a validated measure of socioeconomic status reported as a percentile with 100 representing the most disadvantaged neighborhood. ADI was also stratified into low (<25), medium (25-75), and high (>75) levels of deprivation. The primary outcome measure was missed clinic appointments, which was defined as having at least one appointment that was cancelled or labeled as 'no show'. Statistical analysis included Student's T-test or Wilcoxon's rank-sum test for continuous variables and Chi-square analysis for categorical variables. Results: Patients with in-person appointments were significantly more likely to miss an appointment compared with patients with telemedicine visits (51% versus 25%, p < 0.001). Patients with high ADI were also more likely to miss in-person appointments than patients with medium and low ADI (60% versus 52% and 48%, p < 0.001). However, there was no significant difference in the likelihood of missing a telemedicine visit between patients with high, medium, and low ADI (28% versus 25% versus 24%, p = 0.294). Patients who missed an appointment were 42% more likely to be high ADI (OR 1.42, 95% CI 1.20-1.68, p < 0.001) and 13% more likely to be medium ADI (OR 1.13, 95% CI 1.03-1.26, p = 0.015) and compared with patients with low ADI. Conclusion: Patients with low socioeconomic status were more likely to miss in-person appointments than patients of higher socioeconomic status. However, there was no difference in the likelihood of missing a telemedicine appointment among patients of different socioeconomic status, suggesting that telemedicine may aid in reducing the barriers to healthcare access. Spine surgeons should consider offering telemedicine as an option to patients, particularly those with low socioeconomic status.
ABSTRACT
Objective: To compare professional burnout and depression in medical residents of our health institution before and after the pandemic. Background: Medical residencies are one of the most affected sectors within the health system by the COVID-19 pandemic, generating a negative impact on both clinical practice and professional exhaustion, as well as on the emotional aspect. Design/Methods: Observational analytical study conducted through anonymous self-administered questionnaires in two groups of medical residents, differed by 3 years (2018/2021). Demographic data and medical history were collected. In addition to Maslach Burnout Inventory (MBI, for professional exhaustion) and Beck Depression Inventory (BDI-II, for depression). Results: 68 residents participated (2018: 31;2021: 37), female (2018: 48%;2021: 62%), with an average age of 27.2 +-2.4 SD (2018);30.2 +-3.3 SD (2021). In 2021 there was a reduction in elderly residents' participation (2018/2021: PGY1 22.6%/18.9%, PGY2 22.6%/10.8%, PY3 35.5%/24.3%, PGY4 19.4%/45.9%). In 2018 no one reported insomnia neither chronic drug and/or alcohol abuse, in 2021 27% reported insomnia (p=0.02) and 8.1% abuse. Slept hours in the last 72 hours were 13.6 +- 4.1 SD in 2018 and 16.5 +-5.4 SD in 2021. Severe and extreme depression scored by BDI-II were a new finding this year (2018/2021: Normal 51.6%/16.2%, mild mood disturbance 25.8%/29.7%, mild depression 12.9%/21.6%, moderate depression 9.7%/10.8%, severe depression 0%/13.5% and extreme depression 0%/8.1%). In 2021 greater emotional exhaustion and lack of personal fulfillment were observed compared to 2018, but no depersonalization or burnout criteria were made when answered BDI-II (2018/2021: Normal 51.6%/16.2%, mild mood disturbance 25.8%/29.7%, mild depression 12.9%/21.6%, moderate depression 9.7%/10.8%, severe depression 0%/13.5% and extreme depression 0%/8.1%). Conclusions: In our medical residents an increased level of depression was observed in 2021 compared to 2018. The pandemic working overload probably exacerbated bad working conditions. It is important to improve the quality of life and work of doctors in training.
ABSTRACT
Objective To compare and contrast methodology used for the Royal College of Obstetricians and Gynaecologist's (RCOG) COVID-19 guidance with established standards, as well as the RCOG's Green-top Guidelines. Case report The RCOG has developed guidance for over 20 years and currently publishes different formats including Green-top Guidelines (GTG), which achieved NICE accreditation renewal in 2020. In March 2020, the RCOG started developing guidance to support women and healthcare professionals working in maternity and/or gynaecology services during the COVID- 19 pandemic. In this case study we describe the development of the RCOG/RCM Coronavirus Infection and Pregnancy guidance (https://www.rcog.org.uk/en/guidelines-research-se rvices/guidelines/coronavirus-pregnancy/). We compare and contrast the methods used, both with internationally agreed principles for developing guidance during the COVID-19 pandemic and those used by Green-top Guidelines, in order to understand what can be learned for future guideline development. To meet the need for timely guidance, Green-top Guideline methodology was not suitable for the COVID-19 Infection and Pregnancy guidance co-developed by the RCOG and RCM. Instead, the development team initially published emergency guidance using pragmatic methods. They later adopted methods to align with principles on guidelines development processes during the pandemic, as outlined by the Guidelines International Network, adapting these where appropriate. These principles include: Convening a multi-disciplinary group;Defining the scope of the guidance;Describing the methods used, including how the evidence was identified and reviewed, how the recommendations were agreed and how they link to the evidence. Undertaking external review;and Specifying when the guidance will be reviewed and updated. Discussion Through establishing and refining methods in accordance with the principles of the Guidelines International Network, whilst striving to review evidence and implement policy changes on a weekly basis, important differences between the methods and purpose of the COVID- 19 Infection and Pregnancy guidance and the Green-top Guidelines emerge. The most significant of these differences relate to the emergent and low quality nature of the evidence base, the uncertain trajectory of the pandemic, the lack of a formal critical appraisal tool used and the associated grading of evidence and recommendations. Conclusion The pandemic created an unprecedented need to rapidly develop guidance for maternity healthcare professionals in the UK and around the world, as well as information for women themselves. Those developing this guidance are required to continuously balance the need for up-to-date guidance with the time and resource required to follow a high quality development process.
ABSTRACT
Background: Neoadjuvant endocrine therapy has traditionally been considered a treatment option for locallyadvanced and/or surgically high-risk women with hormone positive disease. Early stage hormone-positive breast cancer, on the other hand, is usually managed with upfront surgery, with post-operative hormone therapy as a risk-reducing adjunct. During the COVID-19 pandemic, however, widespread closures of operating rooms throughout thecountry resulted in many breast cancer patients being offered presurgical endocrine therapy as a bridge to surgery.We explored the demographic and clinicopathologic characteristics of these patients and quantified their rate of uptake. Methods: The Institutional Breast Cancer Database was queried for all patients who were diagnosed withER+ stage 0, I, or II breast cancer and were offered presurgical endocrine therapy (tamoxifen or aromatase inhibitor)by a medical oncologist from 3/12/2020 to 4/30/2020. Variables of interest included demographics, tumorcharacteristics, and rate of medication uptake and compliance. Results: Of 192 newly diagnosed breast cancerpatients seen at NYU Perlmutter Cancer Center during this time period, 136 patients had early stage ER+ breast cancer. Forty-five patients had not yet undergone surgery, and were recommended to receive presurgical hormonaltherapy as a bridge given the COVID-19 pandemic (Table 1). The average age was 60.5 years old (SD=13.8 years, range 31-89), and all were female. Thirty-four of 44 patients were post-menopausal (75.6%), while 10 were premenopausal (22.2%), and one was perimenopausal (2.2%). Twenty-six patients were white (57.8%), 12 were black (26.7%) 3 were Asian (6.7%), and 4 were other (8.9%). Thirty-four patients (75.6%) had invasive disease, while 8 had ductal carcinoma in situ (DCIS, 17.8%), and 3 had DCIS with microinvasion (6.7%). Nine patients (20%)did not take the medication for various reasons: 1 contracted COVID-19, 1 refused any treatment, 1 decided totransfer care out of state, 1 preferred to take a homeopathic remedy instead of endocrine therapy, 1 preferred towait for surgery without medication, and 4 were scheduled for surgery sooner than anticipated and did not start themedication. The remaining 36 patients (80%) took medication for an average of 43.6 days (SD=27.3 days, range 9-101 days) prior to surgery. Twenty-eight patients (77.8%) took an aromatase inhibitor, and 8 (22.2%) took tamoxifen.Forty-two patients have now undergone surgery (93.3%);the remainder include the patient who is refusing alltreatment, the patient who transferred out of state, and one patient who has not yet scheduled surgery, but isreportedly still taking an aromatase inhibitor. Conclusion: Improving adherence to long-term adjuvant endocrinetherapy is an urgent need as patient acceptance is low. Reported completion rates range around 50%, and have notbeen improved by educational or technology-based interventions. The unique situation posed by the current COVID-19 pandemic has temporarily changed the management of early-stage breast cancer, and resulted in a high initialacceptance of endocrine therapy (80%), although duration is shorter in this presurgical setting. Furtherinvestigations will evaluate length of use, the psychosocial and behavioral factors that influence willingness to takeendocrine therapy, and apply these lessons to management of early-stage hormone-positive breast cancer.
ABSTRACT
SESSION TITLE: Late-breaking Abstract Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: A characteristic feature of COVID-19 infection is the speed with which patients can deteriorate, leaving little time to determine an appropriate ceiling of care. The usage of a novel COVID-19 specific treatment escalation plan (TEP) aims to improve care by clarifying early treatment goals with the patient and family. In the event of deterioration, a TEP quickly identifies a patient who will require intensive care review. In addition, a TEP will also prevent unnecessary harm if resuscitation is likely to be futile or against the patient’s wishes. Review of whether TEPs are utilized, at this unprecedented time, is required. Our objective was to audit the use of a COVID-19 TEP document on admission to Glasgow Royal Infirmary for patients with suspected COVID-19 infection. METHODS: Pre-intervention fifty patient notes were retrospectively reviewed if they were triaged as possible COVID-19 by nursing staff on admission. Documentation was reviewed once scanned onto clinical portal. This determined whether a TEP was placed, discussion with family occurred, capacity assessed, ceiling of care established and if the TEP was countersigned by a consultant. Five patients were excluded after review as COVID-19 infection symptoms were not evident. The intervention included verbal reminders to departmental staff alongside posters in key clinical areas. Thirty-six patient notes were reviewed post intervention and four excluded due to non COVID-19 presentation. Two spot data collections were used due to lower case numbers. RESULTS: Pre-intervention data collection showed 37/45 (82.2%) of admitted patients with possible COVID-19 infection had a COVID-19 TEP in place. Of these 54% were countersigned by a consultant (n=20), 100% had ceiling of care and CPR decision documented, and 54% had communication/ capacity section completed (n=20). Post-intervention 37.5% (12/32) had a TEP in place, with 5 being a new generic TEP that had been introduced on site. Seven were COVID-19 TEPs, of these 2 were countersigned by a consultant (28.5%), 100% had a ceiling of care and CPR decision documented, 85.7% had communication/ capacity section completed (n=6). CONCLUSIONS: This audit demonstrated an excellent initial uptake of TEP practice in response to COVID-19. However, there was a clear reduction in the number of TEPs in the subsequent months regardless of the educational intervention and rolling out of a generic TEP. We conclude that despite good adherence at the start of the pandemic, this reduced rapidly possibly due to falling infection rates, clinician fatigue or lack of awareness. Formal TEP education and further interventions are required to maintain high levels of TEP completion on admission. CLINICAL IMPLICATIONS: It was clear that despite initial excellent uptake of TEPs on admission for patients with possible COVID-19 infection, which is a priority for good care, adherence reduced significantly over a short time period. DISCLOSURES: no disclosure on file for Ava Acharya;No relevant relationships by Mark Cotton, source=Web Response No relevant relationships by Rebecca Jameson, source=Web Response No relevant relationships by Christopher McAlpine, source=Web Response No relevant relationships by Andrea Thomson, source=Web Response