A Case of Myositis in Patient with Atypical Bacterial Pneumonia

Case report - Introduction: Bacterial community-acquired atypical pneumonia is sometimes complicated by myositis or by renal parenchymal disease. They can present with myositis and present with muscle weakness, pain or swelling, and elevated muscle enzymes. We present the case of a patient with lower limb weakness and raised creatinine kinase with atypical pneumonia caused by Legionella pneumophila. Case report - Case description: A 76-year-old Caucasian man, who was previously fit and independent and walked 3 miles every day presented with a 1-week history of progressive leg weakness, and inability to mobilize. He had a fall and was on the floor for 2 hours. He had a background history of hypercholesterolemia and was on atorvastatin for 15 years. On his vital observation, he was found tachypnoeic, tachycardic, and hypoxic. He had a right upper lobe crackle but he didn't have respiratory symptoms. His muscle power in his leg was 3/5 with carpet burns on knees and elbow. Initial investigation showed raised inflammatory marker CRP 412mg/L, AKI stage 1, and CK 43400 IU/L. His CXR showed dense right upper lobe consolidation. Legionella urinary antigen was positive. Myositis myoblot, ANA, ANCA negative. COVID-19 swab negative. Treated with IV antibiotic, supplemental oxygen, and IV fluid. Transferred to ITU due to worsening of hypoxia and kidney function. Interestingly, the CK level had improved significantly within 48 hours along with clinical improvement in his symptoms. There was no role of steroid or immunosuppressant due to his significant clinical improvement. On day 7 he was off oxygen, kidney function improved, had physiotherapy, and transferred to ward and on day 10 he was ambulant and discharged home. Case report - Discussion: To date, very few case reports of myositis in a patient with atypical pneumonia have been reported. The mechanism underlying acute myositis in atypical pneumonia is still unknown. The present analysis points out that the organism underlying atypical bacterial pneumonia may occasionally invade the muscle tissue thereby inducing both myositis and secondary kidney damage. Case report - Key learning points: We should be aware of this rare complication of atypical pneumonia and the resolution of symptoms that occur with the treatment of pneumonia. This would avoid unnecessary investigation and use of steroid.

Reducing the carbon footprint from general anaesthesia throughout the North East of England and North Cumbria

In 2019, the North East Anaesthesia Sustainable Healthcare (NEASH) Network was formed. Its aim is to encourage coordinated sustainability efforts. We comprise over 80 anaesthetists with representatives in every Trust in our region. The NHS accounts for 4% of UK carbon emissions. Two per cent of NHS emissions come solely from anaesthetic gases. In late 2020, we began a region-wide project to raise awareness of the environmental impact of general anaesthesia (GA) with the aim of reducing emissions throughout our geographical area. Methods NEASH performed a snapshot audit of 1 full week's GA data in early 2021. Consumed volatile agent, nitrous oxide (N2O) and total intravenous anaesthesia (TIVA) were converted into kilograms of carbon dioxide equivalents (kg CO2e) [1, 2]. Each Trust's emissions were divided by total GA time giving kg CO2e per hour (kg CO2e.h-1), allowing efficiency comparison between sites. We presented our results and the following messages to each Trust. Firstly, stop using desflurane and use N2O only when essential as these agents have the highest global warming potential (GWP). Secondly, we encouraged sevoflurane use as it has the lowest GWP of volatiles (followed by isoflurane);low fresh gas flows are essential. Thirdly, consider TIVA, as its GWP is lower than volatile GA. Although outside the scope of our audit, we reminded colleagues that local or regional anaesthesia have a lower CO2e than GA. In early 2022, we re-audited to assess the impact of our messages. Results The results of 5340 h of GA data are displayed in the table below. Discussion Due to increased operating post-COVID-19 and the inclusion of a hospital that was unable to participate in round 1, round 2 contained 787 more hours of data. Despite this, emissions of CO2e were 12.83 t lower, demonstrating an average hourly emission reduction of 61.1%. This was mainly driven by reduced desflurane and N2O use. Two hospitals in our region have since decommissioned N2O manifolds and two others are undertaking this process. Region-wide procurement data obtained by NEASH showed that three hospitals have ceased ordering desflurane. TIVA use remained broadly the same, which may be due to a lack of availability of equipment. This region-wide project is easily reproducible nationwide and could make significant contributions towards NHS net zero. (Table Presented).

A Case of Myositis in Patient with Atypical Bacterial Pneumonia

Case report - Introduction: Bacterial community-acquired atypical pneumonia is sometimes complicated by myositis or by renal parenchymal disease. They can present with myositis and present with muscle weakness, pain or swelling, and elevated muscle enzymes. We present the case of a patient with lower limb weakness and raised creatinine kinase with atypical pneumonia caused by Legionella pneumophila. Case report - Case description: A 76-year-old Caucasian man, who was previously fit and independent and walked 3 miles every day presented with a 1-week history of progressive leg weakness, and inability to mobilize. He had a fall and was on the floor for 2 hours. He had a background history of hypercholesterolemia and was on atorvastatin for 15 years. On his vital observation, he was found tachypnoeic, tachycardic, and hypoxic. He had a right upper lobe crackle but he didn't have respiratory symptoms. His muscle power in his leg was 3/5 with carpet burns on knees and elbow. Initial investigation showed raised inflammatory marker CRP 412mg/L, AKI stage 1, and CK 43400 IU/L. His CXR showed dense right upper lobe consolidation. Legionella urinary antigen was positive. Myositis myoblot, ANA, ANCA negative. COVID-19 swab negative. Treated with IV antibiotic, supplemental oxygen, and IV fluid. Transferred to ITU due to worsening of hypoxia and kidney function. Interestingly, the CK level had improved significantly within 48 hours along with clinical improvement in his symptoms. There was no role of steroid or immunosuppressant due to his significant clinical improvement. On day 7 he was off oxygen, kidney function improved, had physiotherapy, and transferred to ward and on day 10 he was ambulant and discharged home. Case report - Discussion: To date, very few case reports of myositis in a patient with atypical pneumonia have been reported. The mechanism underlying acute myositis in atypical pneumonia is still unknown. The present analysis points out that the organism underlying atypical bacterial pneumonia may occasionally invade the muscle tissue thereby inducing both myositis and secondary kidney damage. Case report - Key learning points: We should be aware of this rare complication of atypical pneumonia and the resolution of symptoms that occur with the treatment of pneumonia. This would avoid unnecessary investigation and use of steroid.

Implications of Pre-Transplant (tx) COVID-19 on SOT or HCT: A Multicenter Study

Purpose: Describe outcomes of patients (pt) with pre-tx COVID-19. Method(s): Multicenter study of SOT/HCT candidates who had a positive (pos) SARS-CoV-2 PCR pre-tx. Result(s): Pre-tx: Of 208 pt, median age was 56 (range 3-76). 87.8% were SOT candidates (40.5% kidney, 40.5% liver, 9.8% lung, 6.9% heart, 2.3% pancreas) and 13.9% were HCT candidates (54.2% allo, 45.8% auto). Pt underwent a median of 2 tests (range 1 - 14). In 41% of pt, > 1 neg PCR was required by the tx center before reactivation. Neg PCR was documented in 67.4% of pt at a median of 41 days (18-68) after pos PCR. Waitlist mortality was 11.0%;deaths were due to COVID-19 in 60% (12/20). Post-tx (all pt): 78 pt underwent tx at a median of 65.5 days (range 17-324) from COVID-19;71/78 have completed 4-weeks of follow-up. 24/78 (30.7%) pt were still PCR pos at time of tx (details below). 54/78 (69.2%) pt underwent routine PCR testing post-tx;62% were tested regularly for 8 weeks. Only 1 pt, who remained asymptomatic, developed recurrent pos PCR on surveillance testing 18 days post-tx. 1 pt had graft loss. There were no deaths at 4 weeks post-tx. Pt transplanted without a negative PCR: 24 pt with COVID-19 did not have neg PCR at time of tx: 9 (37.5%) kidney, 9 (37.5%) liver, 2 (8.3%) SLK, 1 (4.2%) lung, 1 heart (4.2%), 2 auto-HSCT (8.3%), 2 allo-HSCT (8.3%). Of 24 pt who were reactivated at a median of 21 days (range 8 - 38) from COVID-19 diagnosis, 7 underwent tx emergently (5 liver, 1 lung, 1 heart). 20/24 completed 4-weeks of follow-up;all were alive. PCR Cycle thresholds (Ct) increased over time, suggesting a reduction in SARS-CoV-2 viral loads with time elapsed since COVID-19 diagnosis. Conclusion(s): Short-term outcomes of transplantation in SOT/HCT candidates with prior COVID-19 were promising in this small cohort, even with a positive PCR going into transplant. Whether documentation of a negative PCR should be required for all tx candidates with a history of COVID-19 prior to transplantation should be investigated further, particularly among lung tx candidates. For certain tx candidates with COVID-19, relying time-based strategy instead of a test-based strategy may be safe.

A SPECTRUM OF CAUSES OF MOLECULAR INJURY IS DETECTED BY DONOR-DERIVED CELL-FREE DNA AFTER LUNG TRANSPLANT: PRELIMINARY EXPERIENCE

SESSION TITLE: Lung Transplantation: New Issues in 2022 SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm PURPOSE: Donor-derived cell-free DNA (dd-cfDNA) is a promising plasma analyte for surveillance of rejection and lung transplant (LT) injury. Herein we report our preliminary real-world experiences in concert with standard of practice (SOP) assessments. METHODS: We performed a prospective, cross-sectional, cohort study of a clinically available dd-cfDNA test (the Prospera™ test, Natera, Inc.) combined with SOP clinical assessments − spirometry, fiberoptic bronchoscopy (FOB), donor-specific HLA antibodies (DSA). Single LT dd-cfDNA results were corrected (2X) for lung mass before analysis. Clinical-pathologic cohorts were assigned based on ISHLT guidelines for acute cellular rejection (ACR), uncomplicated chronic lung allograft dysfunction (U-CLAD), and either CoVid-19 or Non-CoVid-19 allograft infection. We also compared median dd-cfDNA fractions between patients experiencing allograft dysfunction (AD) (defined by ΔFEV1≥ -10%) vs stability (STA) and stratified by DSA status. Groups were analyzed by Mann-Whitney (p<0.05) and data expressed as median with 25-75% interquartile range (IQR). RESULTS: A total of 54 plasma samples from 42 unique LT recipients (Single=6, Double=36) were collected at Spectrum Health between November 2021 and February 2022. Primary diagnoses included chronic obstructive pulmonary disease (n=7), interstitial lung disease (n=31), CoVid-19 related ARDS (n=2), CF (n=1) and PAH (n=1). Matching histopathology was available for 68% of dd-cfDNA samples. dd-cfDNA fraction trended 2-fold higher in patient with ACR (1.59%, IQR: 0.09-3.57;n=3) and U-CLAD (1.88%, IQR: 0.88-3.32;n=4) than STA (0.86%, IQR: 0.21-1.62;n=14) patients. Patients with CoVid-19 had significantly higher dd-cfDNA fraction (6.91%, IQR: 2.41-9.77;n=4) than both STA (p=0.035) and NON-CoVid-19 infection cohorts (p=0.049). Although no antibody-mediated rejection (AMR) events were observed, dd-cfDNA fraction was significantly elevated in DSA(+) patients (2.75%, IQR: 1.72-6.25;n=8, class I (4) and II (4)) vs DSA(-) (1.035%, 0.04-1.64;n=46) cohorts (p=0.011). A trend was noted with elevated dd-cfDNA with AD (1.58%, IQR: 0.74-3.62;n=17) vs AS (1.05%, 0.66-1.79;n=37) (p=0.29). CONCLUSIONS: Our preliminary experience is consistent with prior studies, suggesting elevated dd-cfDNA fraction during LT allograft rejection and specific types of infection, in particular, CoVid-19. Of interest, dd-cfDNA detected potential occult molecular injury associated with anti-HLA DSA. CLINICAL IMPLICATIONS: dd-cfDNA fraction assessment after LT represents a valuable clinical tool for clinical surveillance of organ transplant health. DISCLOSURES: Employee relationship with Veracyte, Inc Please note: 2 years by Sangeeta Bhorade, value=Salary Removed 04/03/2022 by Sangeeta Bhorade Employee relationship with Natera Inc Please note: 2/22/22- present Added 04/03/2022 by Sangeeta Bhorade, value=Salary Employee relationship with Natera Please note: 05/2021-present Added 04/04/2022 by Kathryn Crabtree, value=Salary research relationship with United Therapeutics Please note: 2016- ongoing by Reda Girgis, value=Grant/Research research relationship with Pfizer Please note: 2014-2020 by Reda Girgis, value=Grant/Research Speaker/Speaker's Bureau relationship with Boehringher Ingelheim Please note: 2016-ongoing by Reda Girgis, value=Honoraria Speaker/Speaker's Bureau relationship with Genentech Please note: 2016-ongoing by Reda Girgis, value=Honoraria no disclosure on file for Cameron Lawson;No relevant relationships by Edward Murphy Employee relationship with Natera, Inc. Please note: 2020- present by David Ross, value=Salary

COVID-19 Tests the Limits of Biodiversity Laws in a Health Crisis: Rethinking "Country of Origin" for Virus Access and Benefit-sharing

The COVID-19 pandemic raises serious questions about the operation of international agreements for accessing and sharing viruses potentially delaying emergency responses. The access and benefit-sharing (ABS) frameworks under the United Nations' Convention on Biological Diversity and its Nagoya Protocol apply to the collection and use of the COVID-19 pathogen SARS-CoV-2. These frameworks aim to ensure countries of origin reap some of the benefits from the use of their resources. Using real-world examples, we demonstrate conceptual and definitional ambiguities relating to "country of origin" that make not only operationalising the ABS scheme for biodiversity conservation and sustainable use objectives difficult but may also undermine public health emergency responses. Understanding how COVID-19 fits (or does not fit) within ABS laws is a valuable exercise for international policy-makers trying to determine how best to operationalise pathogen ABS, an issue currently under examination at the World Health Organization and critical to responding to pandemics.

Association of working shifts, inside and outside of healthcare, with severe COVID-19: an observational study.

BACKGROUND: Health and key workers have elevated odds of developing severe COVID-19; it is not known, however, if this is exacerbated in those with irregular work patterns. We aimed to investigate the odds of developing severe COVID-19 in health and shift workers. METHODS: We included UK Biobank participants in employment or self-employed at baseline (2006-2010) and with linked COVID-19 data to 31st August 2020. Participants were grouped as neither a health worker nor shift worker (reference category) at baseline, health worker only, shift worker only, or both, and associations with severe COVID-19 investigated in logistic regressions. RESULTS: Of 235,685 participants (81·5% neither health nor shift worker, 1·4% health worker only, 16·9% shift worker only, and 0·3% both), there were 580 (0·25%) cases of severe COVID-19. The odds of severe COVID-19 was higher in health workers (adjusted odds ratio: 2·32 [95% CI: 1·33, 4·05]; shift workers (2·06 [1·72, 2·47]); and in health workers who worked shifts (7·56 [3·86, 14·79]). Being both a health worker and a shift worker had a possible greater impact on the odds of severe COVID-19 in South Asian and Black and African Caribbean ethnicities compared to White individuals. CONCLUSIONS: Both health and shift work (measured at baseline, 2006-2010) were independently associated with over twice the odds of severe COVID-19 in 2020; the odds were over seven times higher in health workers who work shifts. Vaccinations, therapeutic and preventative options should take into consideration not only health and key worker status but also shift worker status.

COVID-19 and Fieldwork: Challenges and Solutions

This reflection article presents insights on conducting fieldwork during and after COVID-19 from a diverse collection of political scientists-from department heads to graduate students based at public and private universities in the United States and abroad. Many of them contributed to a newly published volume, Stories from the Field: A Guide to Navigating Fieldwork in Political Science (Krause and Szekely 2020). As in the book, these contributors draw on their years of experience in the field to identify the unique ethical and logistical challenges posed by COVID-19 and offer suggestions for how to adjust and continue research in the face of the pandemic's disruptions. Key themes include how contingency planning must now be a central part of our research designs;how cyberspace has increasingly become "the field"for the time being;and how scholars can build lasting, mutually beneficial partnerships with "field citizens,"now and in the future. © The Author(s), 2021. Published by Cambridge University Press on behalf of the American Political Science Association.

ALEMTUZUMAB FOR CHRONIC LUNG ALLOGRAFT DYSFUNCTION

SESSION TITLE: Transplantation Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Chronic lung allograft dysfunction (CLAD) remains the leading cause of long-term mortality after lung transplantation (LTX) with no proven therapeutic strategies except re-transplantation. Anecdotal reports suggest a role for the lymphocyte depleting agent, Alemtuzumab (AL), an anti-CD52 monoclonal antibody. We reviewed our experience with AL for the treatment of refractory CLAD. METHODS: Eight consecutive LTX recipients were identified. AL was given as a single subcutaneous dose of 30 mg. Cell-cycle inhibitor therapy was held and valganciclovir and azole prophylaxis were given for at least 6 months after AL treatment. The slope of FEV1 3 months before and after AL were compared. Complications of AL therapy including infections and survival were assessed. RESULTS: The cohort consisted of 5 males and 3 females with a median age at time of AL administration of 66 y (range: 50-72). Time post-transplant was 2.43 y (range: 1.4-5.4). Pre-transplant diagnoses were COPD (n=3), and 1 each of CF, bronchiectasis (immotile cilia syndrome), IPF, PVOD and IPAH. All subjects were bilateral recipients and 1 was post-left pneumonectomy early after transplant. All had a predominantly obstructive CLAD phenotype, stages 4 (N=2), 3 (N=4), 2 (N=1) and 1 (N=1) with rapid loss of lung function. The median slope of decline in FEV1 in the 3 months prior to AL was -336ml/m (range: -39 to -552) compared with +24 ml/m (range: -171 to +48) during the 3 months post AL administration (P = 0.016). No acute reactions to AL treatment were observed. Clinically symptomatic infections occurred in 4 patients following AL. Community acquired respiratory viral infections were observed in 2 (parainfluenza and coronavirus on 2 separate occasions in 1 patient and rhinovirus in another). Pseudomonas tracheobronchitis developed in 1. These infections were considered mild-moderate. One subject developed new parenchymal opacities with isolation of Rasamsonia argillacea and Mycobacterium fortuitum. Two patients died due to progressive CLAD 3 and 6 months after AL. The other six are alive at a median follow-up time of 12 months (range: 7 – 20). Kaplan-Meier survival estimate at one year was 75%. At last follow-up, CLAD stages among survivors was 4 (N=1), 3 (N=4) and 2 (N=1). CONCLUSIONS: AL therapy was associated with a significant attenuation in lung function decline in lung transplant recipients with rapidly progressive CLAD. Treatment was generally well tolerated with few serious infection complications. CLINICAL IMPLICATIONS: AL should be considered for rapidly progressive CLAD. Randomized controlled trials are required to establish efficacy and safety. DISCLOSURES: No relevant relationships by Reda Girgis, source=Web Response No relevant relationships by Ryan Hadley, source=Web Response no disclosure submitted for Anupam Kumar;No relevant relationships by Cameron Lawson, source=Web Response no disclosure on file for Marzia Leacche;No relevant relationships by Jennifer McDermott, source=Web Response no disclosure on file for Edward Murphy;No relevant relationships by Gayathri Sathiyamoorthy, source=Web Response