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INTRODUCTION: To examine the patient-centered outcomes and the occurrence of lung fibrotic changes on Chest computed tomography (CT) imaging following pneumonia-related acute respiratory distress syndrome (ARDS). We sought to investigate outpatient clinic chest CT imaging in survivors of COVID19-related ARDS and non-COVID-related ARDS, to determine group differences and explore relationships between lung fibrotic changes and functional outcomes. METHOD(S): Retrospective practice analysis of electronic health records at an ICU Recovery Clinic in tertiary academic medical center. RESULT(S): One-hundred four patients with mean age 54 +/- 13 and 52% male were included (n=74 COVID-19 and n=30 non-COVID groups). There were no differences for age, sex, mechanical ventilation duration, tracheotomy, or sequential organ failure assessment (SOFA) scores between two groups. Six-weeks after hospital discharge, fibrotic changes visualized on CT imaging occurred in a higher proportion of COVID-19 survivors (69%) compared to non-COVID (43%, chi2 = 5.6, p = 0.018). In general, across both groups, patients with fibrotic changes (n=64) were older, had a lower BMI, and had longer duration of mechanical ventilation. Overall, patients performed poorly on six-minute walk test (44 +/- 27% of predictive distance), had poor respiratory function (FEV1% = 66 +/- 27% and FVC% = 65 +/- 20%), and had high occurrences of anxiety, depression, emotional distress, and mild cognitive impairment regardless of presence of fibrotic changes. CONCLUSION(S): Patients surviving pneumonia-ARDS are at high risk of impairments in physical, emotional, and cognitive health related to Post-Intensive Care Syndrome. Of clinical importance, pulmonary fibrotic changes on chest CT occurred in a higher proportion in COVID-ARDS group;however, no differences were measured in spirometry or functional assessments at six weeks post hospital discharge. Whether COVID infection imparts a unique recovery is not evident from these data but suggest that long-term follow up is necessary for all survivors of ARDS.
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SESSION TITLE: ECMO and ARDS in COVID-19 Infections SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/17/2022 12:15 pm - 1:15 pm PURPOSE: The SARS-CoV-2 virus preferentially attacks alveolar Type 2 cells that have the membrane ACE2 receptors. Type 2 cells are the surfactant producing cells in the lung. Damage to Type 2 cells can result in decreased/abnormal surfactant production leading to ARDS and respiratory failure. Surfactant is further inactivated by inflammatory proteins during ARDS. We sought to evaluate the feasibility, safety and tolerability of surfactant therapy in COVID-19 associated ARDS using a synthetic surfactant, lucinactant. METHODS: Open-label, single arm, multicenter study (NCT04389671) in adults with COVID-19 associated ARDS, who have been intubated and on mechanical ventilation (MV) with a P/F ratio <= 300. COVID-19 infection was confirmed by PCR. Lucinactant at a dose of 160 ml (∼80 mg TPL/kg lean body weight) was delivered intratracheally within 7 days of intubation. Retreatment was allowed at >= 6-hour intervals if subjects remained on MV. Assessments included time to deliver the dose, physiologic parameters of oxygenation (P/F, OI, PaO2), FiO2, PaCO2, lung compliance (CL) from baseline (pre-dosing) through day 5 post-dosing. Safety parameters included peri-dosing (PD) events (bradycardia, desaturation, hypotension, regurgitation) and adverse events through 30 days post dosing. RESULTS: 20 subjects were enrolled and 19 received at least one dose. Five subjects received 2 doses of lucinactant. The mean age of subjects was 49 years, 80% were male, 60% were white. The mean time to administer the dose was 31 minutes. FiO2 requirements, PaO2 and PCO2 remained stable throughout the 5-day period post dosing. Baseline mean P/F ratio and standard deviation (SD) was 196 (68), 179 (57) at 12 hours and 193 (61) at day 1 post-dosing, followed by a gradual increase to 223 (105) at day 5. Mean CL increased from 40.5 (16) at baseline to 49.8 (23) at day 5. Seven subjects (37%) died, 6 due to secondary infection and sepsis > 13 days after dosing. Two subjects experienced transient PD events (desaturation, regurgitation). Lucinactant administration in severe ARDS due to COVID-19 was safe and generally well tolerated. The incidence of PD events was low. Stable to improved physiologic parameters of oxygenation were observed post dosing. Increasing the dose and number of administrations may provide additional benefit. CLINICAL IMPLICATIONS: The data support continued study of lucinactant in ARDS patients. DISCLOSURES: Consultant relationship with Windtree Therapeutics Please note: August 2000 Added 03/31/2022 by Carlos Guardia, value=Consulting fee Consultant relationship with Windtree Therapeutics Inc. Please note: August 2000 Added 03/31/2022 by Carlos Guardia, value=Consulting fee Removed 03/31/2022 by Carlos Guardia Advisory Committee Member relationship with Windtree, inc Please note: 4/2021-2/2022 Added 04/04/2022 by Yuh-Chin Huang, value=Grant/Research No relevant relationships Added 04/04/2022 by Peter Morris, value=Consulting fee Removed 04/04/2022 by Peter Morris Employee relationship with Windtree Therapeutics, Inc. Please note: 2008-2022 Added 04/04/2022 by Phillip Simmons, value=Salary Employee relationship with Windtree Therapeutics Please note: 2014 to present Added 04/14/2022 by Steven Simonson, value=Salary
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Background: The University of Hawaii Cancer Center (UHCC) Minority/Underserved NCI Community Oncology Research Program (Hawaii MU NCORP) provides access to NCI-sponsored clinical trials in Hawaii. The Hawaii MU NCORP is dedicated to increasing minority and underserved accruals to clinical trials. Native Hawaiian women have the highest breast cancer incidence and mortality;only 26% of Micronesian women in Hawaii over the age of 40 have ever had a mammogram. In 2018, the Hawaii MU NCORP became a recruitment site for the ECOG-ACRIN Tomosynthesis Mammographic Imaging Screening Trial (TMIST). A pilot study was launched in 2019, to support our NCORP recruitment of underrepresented Native Hawaiian and other Pacific Islander (NHPI) women to the TMIST study. Subsequently, specific funding was provided by the NCI's Center to Reduce Cancer Health Disparities that enabled the UHCC's Office of Community Outreach and Engagement (COE) to develop an effective multilevel recruitment strategy together with the Hawaii MIU NCORP. Methods: To foster community awareness of the TMIST study among NHPI women, the UHCC COE hired a Community Health Educator (CHE). The CHE, a Pacific Islander woman, utilized small group educational sessions to provide culturally and linguistically appropriate cancer prevention information and promote the TMIST study to NHPI women in Hawaii. The CHE worked in partnership with Hawaii MU NCORP clinical research associates (CRAs) in these efforts. In 2020, statewide COVID-19 health and safety protocols were enacted, limiting public group interactions in Hawaii. Despite this challenge, the CHE successfully adapted the in-person educational sessions on clinical trials and TMIST to conduct sessions using Zoom and Facebook Messenger. Results: Before the hire of the CHE in 2019, only one Pacific Islander (Micronesian) woman was recruited to the TMIST in Hawaii. The CHE conducted 21 community health events with 426 attendees from 2019 to 2021. The Hawaii MU NCORP NHPI TMIST enrollment went from the 9.9% in 2018 to 2019, to 20.1% in 2019 to 2020 and to 33% in 2020 to 2021. To date, 18 Micronesian, 52 Native Hawaiian and 6 Other Pacific Islander women out of 353 participants ware enrolled. Conclusions: The multilevel intervention of our CHE, in collaboration with NCORP staff providing clinical trial awareness training and community outreach, resulted in increasing the enrollment of NHPI women to the TMIST Trial. CHE-led community health education sessions on cancer prevention can be delivered using emergent technologies and social media. The use of culturally and gender concordant CHEs working with CRAs have the potential to increase awareness and accruals to cancer clinical trials.
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RATIONALE: Long-term quality of life is a significant concern for survivors of sepsis and acute respiratory failure (ARF). Financial burdens await as many patients never return to work. Notably, the duration of the ICU stay significantly correlates with the severity of physical impairment and up to 25% of skeletal muscle is lost within one week in the ICU. The recent pandemic due to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) is likely to exacerbate these issues. We have previously reported that metabolites related to mitochondrial bioenergetics status can predict acute patient outcomes. Here, we propose that these same metabolomic and mitochondrial biomarkers of mortality also predict physical function in survivors. METHODS: To test this hypothesis, we performed a retrospective analysis of metabolomic changes in ARF survivors using ultrahigh performance liquid chromatography mass spectrometry. Six months after ICU admission, physical function was determined by the short physical performance battery (SPPB), an objective physical function measurement assessing gait speed, balance and lower extremity strength. A total of 70 consecutively enrolled patients were selected, of which 35 had good physical function (SPPB ≥ 7) and 35 had poor physical function (SPPB ≤6). The patients were matched for age, race and sex. Metabolomic analysis of patient's serum was measured at ICU admittance (n=70), 5d-post admittance (n=20) and discharge (n=20). RESULTS: More than 1250 named compounds were identified. There were only 19 metabolites that were significantly different at admittance (ANOVA;p < 0.05), of which seven were bile acids. However at discharge, despite less patient samples tested, 151 metabolites were significantly different (ANOVA;p < 0.05). Specifically, we found that 10 lysophospholipids, eight bile acids, three TCA cycle metabolites, eight kynurenine-related metabolites and nine urea cycle metabolites were significantly different. Many of these pathways have previously been shown to be altered in nonsurvivors of sepsis and ARF. CONCLUSIONS: Findings suggest that bioenergetic abnormalities arising during the acute phase of recovery may be persistent and predict longer-term decrements of physical function in survivors of ARF. Larger retrospective and prospective studies are needed to confirm these preliminary findings;however, predicting poor physical function in survivors as well as identifying the affected metabolic pathways may lead to improved therapies and long-term patient outcomes.
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Background: Early data suggested a higher risk of COVID-19 in oncology patients, in particular those with co-morbidities or on systemic anticancer therapy (SACT). Immunisation strategies are likely to be critical in risk-reduction patient management. We examined patients' attitudes towards COVID-19 vaccines, studying factors affecting uptake such as demographics, socioeconomics, cancer diagnoses and treatments, and previous influenza vaccination. Methods: An anonymised questionnaire was distributed among oncology patients attending for SACT from November to December 2020. Statistical analyses were performed using SPSS v23 (IBM, Armonk, NY, USA). Results: In total 115 patients completed the survey. Of these, 30 (26%) were aged > 65, 65 (56%) were female and 54 (47%) were treated for metastatic disease. Overall 68 (59%) were receiving cytotoxic chemotherapy, and 15 (13%) were receiving immunotherapy. The most common cancer was breast (29%), followed by colorectal (18%) and lung (10%). Most patients (72%) had received or were intending to receive the influenza vaccine. Of patients surveyed 19 (17%) had friends or family who had been diagnosed with COVID-19, while only 3 (2.6%) had had COVID-19. The majority (81%) were in favour of receiving a COVID-19 vaccine if it was recommended for them. A small number however (5.2%) were against receiving a vaccine. Similar numbers of patients worried (30%) and did not worry (33%) that a COVID-19 vaccine could be unsafe. Interestingly 42% stated they if a COVID-19 vaccine were to be made available they would prefer to wait rather than to get it immediately. Patients who had received or intended to receive the influenza vaccine were less likely to want to delay receiving a COVID-19 vaccine (p=0.018). Age group, education level and palliative treatment was not associated with a significant difference in vaccine acceptance. Conclusions: The majority of patients surveyed were agreeable to COVID-19 vaccination, particularly those with prior influenza vaccination. An interesting finding was that though 42% of patients would prefer not to be first to receive the vaccine the majority welcomed vaccination. This finding, especially within a cohort regarded as being "highly vulnerable” to COVID, may have implications for the vaccine program in the general population. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
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The COVID-19 pandemic has affected all individuals across the globe in some way. Despite large numbers of reported seroprevalence studies, there remains a limited understanding of how the magnitude and epitope utilization of the humoral immune response to SARS-CoV-2 viral anti-gens varies within populations following natural infection. Here, we designed a quantitative, multi-epitope protein microarray comprising various nucleocapsid protein structural motifs, including two structural domains and three intrinsically disordered regions. Quantitative data from the microarray provided complete differentiation between cases and pre-pandemic controls (100% sensitivity and specificity) in a case-control cohort (n = 100). We then assessed the influence of disease severity, age, and ethnicity on the strength and breadth of the humoral response in a multi-ethnic cohort (n = 138). As expected, patients with severe disease showed significantly higher antibody titers and interestingly also had significantly broader epitope coverage. A significant increase in antibody titer and epitope coverage was observed with increasing age, in both mild and severe disease, which is promising for vaccine efficacy in older individuals. Additionally, we observed significant differences in the breadth and strength of the humoral immune response in relation to ethnicity, which may reflect differences in genetic and lifestyle factors. Furthermore, our data enabled localization of the immuno-dominant epitope to the C-terminal structural domain of the viral nucleocapsid protein in two independent cohorts. Overall, we have designed, validated, and tested an advanced serological assay that enables accurate quantitation of the humoral response post natural infection and that has revealed unexpected differences in the magnitude and epitope utilization within a population.
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Background: Hepatitis C virus (HCV) remains a major public health crisis in rural communities across Northern California Successful detection and linkage-to-care continues to face significant challenges especially with the lack of 'treaters' in these communities A targeted approach to primary care provider (PCP) education in rural communities utilizing telementoring was developed as part of a multifaceted initiative to increase provider capacity within Northern California (called ECHO-PLUS) The primary intent was to cultivate local HCV treatment champions, providing patients access to timely care Methods: Tele-mentoring using a telemedicine-based approach with provider and patient both in the exam room at the PCP 'mentee' site, and an HCV specialist and specialty pharmacist at the mentor site. Prior to the first patient encounter, mentees received 1-hour CME-certified HCVfocused education Subsequently, patients were scheduled for clinic times with new visits lasting 30 minutes and follow-ups lasting 15 minutes There was additional 5-10 minutes pre/ post visit discussion between mentor and mentee related to management of the patient's hepatitis C A provider readiness survey was done independently by the specialist and pharmacist on a Likert-type scale with three questions (scored 1-5, total score 15) following each patient visit Results: A total of 19 providers from 14 discrete clinics located in 14 counties spread over Northern California and Central Valley participated 11 of the 19 providers saw at least one HCV patient with a mentor;the other 8 providers only attended the CME-based HCV education Of the 11 participating providers, 5 classified themselves as 'experienced' having treated previously with PEG-interferon and 6 as 'inexperienced' or never-treated HCV A total of 60 hours of tele-mentoring sessions were completed with 31 patients treated jointly, all of whom successfully underwent HCV treatment Inexperienced treaters saw at least 3 patients and a maximum of 6 patients, while experienced treaters saw 1-2 patients Experienced treaters had 1 5-3 hours of tele-mentoring compared to 3-7 hours for inexperienced treaters Provider readiness surveys showed a median improvement by 7-points with a final score of 13 5 versus starting score of 6 5, with inexperienced treaters showing the greatest change Within a month of tele-mentoring completion defined by their readiness survey, the prior inexperienced treaters noted treating 2-5 patients independently Conclusion: Individualized tele-mentoring led to early adoption of HCV therapy ECHO programs combining various modalities of telemedicine can help successfully create 'champion' providers in rural and underserved communities providing essential care that becomes especially relevant with the surge of SARS-CoV-2.
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Background: The coronavirus disease-2019 pandemic has restricted availability of intensive care unit resources. Symptomatic patients with coronary artery disease considered surgical candidates have therefore needed revascularization with percutaneous coronary intervention (PCI). We describe demographics/in-hospital clinical outcomes of this novel cohort. Methods: From March 1, 2020, to May 31, 2020, anonymized data of 171 patients in 38 U.K. centers were enrolled in a prospective registry. All were considered surgical candidates. Results: Tables 1-3 show demographics, procedural characteristics, and outcomes. A comparison with routine PCI (British Cardiovascular Intervention Society data) and U.K. coronary bypass surgical data are listed if available and appropriate. There was significantly more prior myocardial infarction, PCI, and coronary artery bypass graft in the routine PCI database than in ReVasc Registry patients, suggesting more acute presentation in latter group. However, these were complex patients — mean SYNTAX score of 27.8 (range 9 to 65);and >20 times the number of LMS plus multivessel disease compared to the routine PCI group, with high use of adjunctive imaging. Radial use was high at 94.1%. PCI success was 97.0%. Complete revascularization was 52% and residual SYNTAX score 1.42 (0 to 20). The 2 deaths were acute, and mortality rate comparable to published surgical data. A 50% reduction in in-patient stay was observed. [Formula presented] Conclusion: In this multicenter U.K. registry, in-hospital outcomes with PCI for patients with complex coronary disease, normally treated with coronary artery bypass graft, compared well with surgical data suggesting the role of PCI could be extended. Future long-term follow-up is planned. Categories: CORONARY: Complex and Higher Risk Procedures for Indicated Patients (CHIP)
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Background: The COVID-19 pandemic has impacted significantly on health systems across the globe. It has been reported to have higher incidence and to be associated with worse outcomes in patients with cancer. Beaumont Hospital is a large Dublin-based teaching hospital which was at the centre of the Irish outbreak of COVID-19. Methods: During the period 11th March to 15th May 2020, patients diagnosed with COVID-19 infection who were attending Beaumont Hospital for systemic anti-cancer therapy were included. Data were collected by chart review. Statistical analyses were performed using SPSS. Cancer-related prognosis was estimated using the Palliative Prognostic Score (PAP) with a score ≥11 associated with a 30-day survival of <30%. Results: In total, 717 patients attended oncology services for cancer directed treatment during the study period. 27 of these patients were diagnosed with COVID-19 based on RT-PCR. A further 4 patients were diagnosed clinically due to characteristic symptoms and radiology. The median age was 60 (38-84). 12 (39%) were female. The most common cancer type was lung n=9 (29%). 21 (67%) had metastatic disease;4 (13%) locally advanced disease and 6 (19%) were being treated with curative intent. Of the 31 patients diagnosed with COVID-19, 25 (80%) were hospitalised and none were admitted to intensive care. In total, 12/31 (41%) died, of which 5 (41%) had lung cancer, 10 (83%) had an PS of ≥3 and 3 (25%) had received systemic anti-cancer treatment in the last 30 days of life. The median age was 66 (38-84). 4 (33%) were female. All had incurable, locally advanced or metastatic disease. The mean time from diagnosis to death was 9.5 days. Those with an ECOG performance status (PS) ≥3 were more likely to die than those with PS ≤2 (p<0.001).Compared to those who recovered, patients who died from COVID-19 had higher mean number of organs affected by cancer (3.7 vs. 1.8, p=0.015) and higher mean PAP score (9.6 vs. 1.5, p<0.001). Conclusions: Patients with cancer who contracted COVID-19 and died had more sites of metastatic disease, a poorer performance status, and a higher Palliative Prognostic Score. The presence of multi-organ involvement appears to predict for poorer outcomes in COVID-19 positive cancer patients. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
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Background: The COVID-19 pandemic poses significant challenges for the management of patients with cancer. In our institution we adapted our delivery of outpatient systemic anti-cancer therapy (SACT) by introducing a number of ‘risk-reducing’ measures including pre-assessment screening. We sought to evaluate our patients’ experiences of this and to gain an insight into their perception of the risks associated with COVID-19. This is a cohort of patients who are at risk of increased morbidity and mortality and often have complex care needs. Methods: Patients on active SACT attending the oncology day ward during the COVID-19 pandemic were eligible for participation. Data were collected over a one week period during the most intensive phase of Government restrictions, from 11/May/20-18/May/20. Personal demographics including information on social supports were recorded. In order to assess how patients perceived their care during COVID-19 they were asked questions under three headings: risk of infection exposure, changes to treatment plan and psychological impact of COVID-19. Results: 100 patients were assessed, of these 60 (60%) were male, 41 (41%) were >65 years of age and 67 (67%) had advanced cancer. 11 (11%) patients were living alone. 95 (95%) had family/friends available to help with daily activities such as shopping and transport to medical appointments. 57 (57%) reported feeling at increased risk in general of contracting COVID-19, with 95 (95%) practising social isolation. 68 (68%) patients reported that they were not worried about contracting COVID-19 in the hospital. 96 (96%) patients stated that they wanted to continue on their treatment as originally planned, reporting feeling safer on therapy. 58 (58%) felt isolated and 40 (40%) reported increased anxiety. 10 (10%) opted to delay medical attention if unwell at home. Conclusions: Though patients on active treatment for cancer during the COVID-19 pandemic reported increased anxiety and feelings of isolation due to COVID-19, the majority of patients wanted to continue SACT as originally planned. Patients may benefit from enhanced psycho-oncological supports in the event of a 2nd peak or prolonged COVID pandemic. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
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Background: The delivery of systemic anticancer therapy during the COVID-19 pandemic is extremely challenging. Increased hospital visits and active anticancer therapy have been described as risk factors for developing more severe infection. In order to balance the benefits of continuing anticancer therapy with these risks, we undertook a series of system changes in the delivery of cancer care. We examined the rate of COVID-19 infection in patients attending for systemic anticancer treatments and the impact of COVID-19 on therapy delivered at our oncology dayward. Methods: Patients who attended our dayward over a 4 month period were included. Data were obtained from electronic patient records and chemotherapy prescribing records. Patients were screened for symptoms of COVID-19 infection at two separate timepoints: the day prior to their visit via telephone, and using a symptom questionnaire given in a preassessment area on arrival at the hospital. This area was established so that patients didn't have to transit through the main hospital. If patients displayed COVID-19 symptoms, they were isolated and a viral swab was arranged. Results: A total of 456 patients attended from January 1st to April 30th. During this time there were 2369 patient visits to the oncology dayward and 1953 intravenous therapies administered. 416 (18%) visits did not lead to treatments, 114 (27%) of which were scheduled non-treatment visits. 194 (47%) treatments were held due to disease-related illness and 108 (26%) treatments were held due to treatment-related complications. 19 patients were identified as having COVID-19 symptoms via telephone screening. 34 patients were symptomatic on arrival at our pre-assessment area and referred for swabs, of which 4 were positive. Those with a negative swab were rescheduled for chemotherapy the following week. Overall, 53 treatments were held due to the screening process. Conclusions: With the introduction of a new patient screening pathway, there have been few treatment disruptions due to the COVID-19 pandemic. The overall rate of symptomatic COVID-19 infection appears low in those who continue on active treatments with regular hospital visits. With careful systematic changes, it is feasible to continue to safely deliver systemic anticancer therapy during the COVID-19 pandemic. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.