Long-term support of COVID-19 patients with veno-venous extracorporeal membrane oxygenation: Complications, predictors of mortality and long-term outcome

Objectives: Treatment of severe respiratory distress syndrome (ARDS) due to COVID-19 by veno-venous extracorporeal membrane oxygenation (VV-ECMO) had a mortality of up to 70% in Germany. Many patients with COVID-19 need VV-ECMO support longer than 28 days (long-term VV-ECMO). Evidence on mortality, complications during intensive care, functional status after discharge and mortality-predictors for patients supported with long-term VV-ECMO is lacking. Method(s): Retrospective study of 137 consecutive patients treated with VV-ECMO for ARDS due to COVID-19 at University Hospital Regensburg from March 2020 to March 2022. Result(s): 38% (n=52;87% male) of patients needed longterm VV-ECMO support. In these, SOFA score (median [IQR]) at ECMO initiation was 9 [8-11], age 58.2 [50.6- 62.5] years, PaO2/FiO2-ratio 67 [52-88] mmHg, pCO262 [52-74] mmHg, Murray-Score 3.3 [3.0-3.6] and PEEP 15 [13 - 16] cmH2O. Duration of long-term support was 45 [35-65] days. 26 (50%) patients were discharged from the ICU. Only one patient died after hospital discharge. At VVECMO initiation, baseline characteristics did not differ between deceased and survivors. Complications were frequent (acute kidney injury: 31/52, renal replacement therapy: 14/52, pulmonary embolism: 21/52, intracranial hemorrhage 8/52, major bleeding 34/52 and secondary sclerosing cholangitis: 5/52) and more frequent in the deceased. Karnofsky index (normal 100) after rehabilitation was 70 [57.5-82.5]. Twelve of the 18 patients discharged from rehabilitation had a satisfactory quality of life according to their own subjective assessment. Four patients required nursing support. Mortality-predictors within the first 30 days on VV-ECMO only observed in those who deceased later, were: Bilirubin >5mg/dl for > 7 days, pulmonary compliance <10ml/mbar for >14 days, and repeated serum concentrations of interleukin 8 >150ng/L. Conclusion(s): Long-term extracorporeal lung support in patients with COVID-19 resulted in 50 % survival and subsequently lead to a satisfactory quality of life and functionality in the majority of patients. It should preferably be performed in experienced centers because of a high incidence of complications. Several findings during the early course were associated with late mortality but need validation in large prospective studies.

Differences in nosocomial infections in patients on VV-ECMO for COVID-19 and influenza

Objectives: In COVID-19 associated acute respiratory distress syndrome (ARDS) requiring VV-ECMO, ventilator-associated-pneumonia (VAP), pulmonary aspergillosis and viral reactivations are observed frequently, but there is only little knowledge on incidence, onset and causative pathogens. This study analyzes frequency of VAP, pulmonary aspergillus infections, and viral reactivations in a large cohort of patients with ARDS treated with VV-ECMO due to either COVID-19 or Influenza. Method(s): Retrospective analysis of all consecutively patients at the University Hospital Regensburg requiring VVECMO due to COVID-19 (March 2020 and May 2022) or Influenza (May 2012 and December 2022). VAP was diagnosed according to current guidelines. Pulmonary Aspergillosis met criteria of probable COVID-associated Aspergillosis according to current guidelines. Result(s): 147 patients (age (median [IQR]) 55.3 [48.7 - 61.7], SOFA at VV-ECMO initiation 9 [8 - 12], 23 [14 - 38] days on VV-ECMO) suffering from COVID-19 and 72 influenza patients (age 55.3 [46 - 61.3], SOFA at VV-ECMO initiation 13 [10 - 15], 16 [10 - 23] days on VV-ECMO) were included in the analysis. Pulmonary superinfections were more frequent in COVID-19 than in influenza (VAP: 61% vs. 39%, pulmonary Aspergillosis: 33% vs. 22%, CMV reactivation: 19% vs. 4%, HSV reactivation: 49% vs. 26%.) The first episode of VAP in COVID-19 and Influenza was detected 2 days [1 - 15] after and 1 day (-3 - 22) before ECMO initiation, respectively. First VAP-episode in COVID-19 were mainly caused by Klebsiella spp. (29%,), Staphylococcus aureus (27%) and E. coli (11%). Further VAP-episodes (30% in COVID-19) and relapses of VAP were mainly caused by Klebsiella spp. (53%, 64%, respectively). In Influenza, VAP was mainly caused by Staphylococcus aureus (28%) and Streptococcus pneumoniae(28%), further VAP episodes were not observed. Conclusion(s): Superinfections were common in patients treated with VV-ECMO and occur more frequently in COVID-19 ARDS compared to Influenza. VAP occurs early and may significantly contribute to the need of VV-ECMO. Therefore, a meticulous routine microbiologic workup is advisable. The observed differences in the spectrum of secondary infectious agents in COVID19 compared to Influenza are not understood yet.

SARS-CoV-2 Vaccine Against Virus: Mission Accomplished!?

Since the beginning of the COVID-19 pandemic in late 2019, SARS-CoV-2 has started to optimize itself. After crossing the species barrier between bats and humans, it has developed mutations in the viral spike protein, in particular at positions 69/70, 452, 501, 614, and 681, that enhance binding to the ACE-2 receptor and entry into host cells, thereby promoting viral transmissibility and pathogenesis. Mutations at positions 417 and 484 have begun to undermine the effectiveness of convalescent plasma, monoclonal antibodies, and currently available vaccines. The targeted and convergent evolution of SARS-CoV-2, which occurred despite the proofreading activity of the exonuclease, has resulted so far in five variants of concern, which have replaced previous strains. This calls for a worldwide surveillance of viral evolution including animal transmission and the development of vaccines responding to escape variants and inducing mucosal immunity. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

Efficacy of a Mouthwash Containing CHX and CPC in SARS-CoV-2-Positive Patients: A Randomized Controlled Clinical Trial.

Soon after the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, preprocedural mouthwashes were recommended for temporarily reducing intraoral viral load and infectivity of individuals potentially infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in order to protect medical personnel. Particularly, the antiseptic cetylpyridinium chloride (CPC) has shown virucidal effects against SARS-CoV-2 in vitro. Therefore, the aim of this randomized controlled clinical trial was to investigate the efficacy of a commercially available mouthwash containing CPC and chlorhexidine digluconate (CHX) at 0.05% each in SARS-CoV-2-positive patients as compared to a placebo mouthwash. Sixty-one patients who tested positive for SARS-CoV-2 with onset of symptoms within the last 72 h were included in this study. Oropharyngeal specimens were taken at baseline, whereupon patients had to gargle mouth and throat with 20 mL test or placebo (0.9% NaCl) mouthwash for 60 s. After 30 min, further oropharyngeal specimens were collected. Viral load was analyzed by quantitative reverse transcriptase polymerase chain reaction, and infectivity of oropharyngeal specimens was analyzed by virus rescue in cell culture and quantified via determination of tissue culture infectious doses 50% (TCID50). Data were analyzed nonparametrically (α = 0.05). Viral load slightly but significantly decreased upon gargling in the test group (P = 0.0435) but not in the placebo group. Viral infectivity as measured by TCID50 also significantly decreased in the test group (P = 0.0313), whereas there was no significant effect but a trend in the placebo group. Furthermore, it was found that the specimens from patients with a vaccine booster exhibited significantly lower infectivity at baseline as compared to those without vaccine booster (P = 0.0231). This study indicates that a preprocedural mouthwash containing CPC and CHX could slightly but significantly reduce the viral load and infectivity in SARS-CoV-2-positive patients. Further studies are needed to corroborate these results and investigate whether the observed reductions in viral load and infectivity could translate into clinically useful effects in reducing COVID-19 transmission (German Clinical Trials Register DRKS00027812).

Coronavirus disease 2019 is associated with multi-lineage, morphologic changes in peripheral blood cells

Introduction: The clinical course of coronavirus disease 2019 (COVID-19) varies from mild symptoms to acute respiratory distress syndrome, hyper-infammation and coagulation disorder. The hematopoietic system plays a critical role in the observed hyperinfammation, particularly in severely ill patients. Method(s): We conducted a prospective diagnostic study performing a blood differential analyzing morphologic changes in peripheral blood of COVID-19 patients. COVID-19 associated morphologic changes were defned in a training cohort and subsequently validated in a second cohort (n=45). Morphologic aberrations were further analyzed by electron microscopy (EM) and fow cytometry of lymphocytes was performed. Result(s): We included 45 COVID-19 patients in our study (median age 58 years;82% on intensive care unit). The blood differential showed a specific pattern of pronounced multi-lineage aberrations in lymphocytes (80% of patients) and monocytes (91%). 84%, 98%, and 98% of patients exhibited aberrations in granulopoiesis, erythropoiesis and thrombopoiesis, respectively. Electron microscopy revealed the ultrastructural equivalents of the observed changes and confrmed the multi-lineage aberrations already seen by light microscopy. Conclusion(s): The morphologic pattern caused by COVID-19 is characteristic and underlines the serious perturbation of the hematopoietic system. We defned a hematologic COVID-19 pattern to facilitate further independent diagnostic analysis and to investigate the impact on the he-matologic system during the clinical course of COVID-19 patients.

Reduction in Health Care Facility Onset Catheter-Associated Urinary Tract Infections: A Resident-Led Quality Improvement Initiative

Background. Hospital-acquired catheter-associated urinary tract infection (CAUTI) was estimated to cause 19,700 cases in 2020 across the United States per the Centers for Disease Control and Prevention (CDC). While this is a 25% decrease in reported incidence rates since 2015, ad-hoc changes in care practices and limitations of surveillance definitions brought on by the giant burden of COVID-19 on the healthcare system possibly resulted in underreporting of CAUTIs. In a 290-bed tertiary, community hospital in the Detroit metropolitan area, there was a 200% increase CAUTIs from 2020 (5 CAUTIs) to 2021(16 CAUTIs). A multidisciplinary, resident-led team was assembled to reduce hospital-acquired CAUTIs. Methods. A multi-pronged quality improvement initiative was conducted from January 1, 2021, through March 31, 2022. CAUTIs were identified and reviewed via electronic health records using predefined criteria related to CDC surveillance definitions, urinary catheter insertion indications, laboratory data, and antibiotic use. Plan-Do-Study-Act (PDSA) Cycle model was used to guide the initiative. Thus far one PDSA cycle has been completed. The initial intervention bundle was designed by the multidisciplinary team and led by internal medicine and transitional year residents. The intervention bundle included 1. Provider (including physician and RN) education, 2. Design and implementation of an appropriate urinary catheter practice algorithm, and 3. Expert review of positive urine cultures and CAUTI cases. Results. Baseline data collected from January to December 2021 showed 16 CAUTIs. Post-implementation of the intervention bundle from January to March 2022 resulted in a 75% reduction in CAUTI incidence (1 CAUTI flagged). Conclusion. A targeted intervention bundle improved CAUTI incidence by reducing inappropriate urinary catheter insertion and prolonged removal. Ongoing local initiatives focused on hospital-acquired infections, such as this one, are paramount to the persistent optimization of infection prevention despite national trends.

Effect of Cytokine Adsorption on Mortality: A Meta-Analysis

Background: Cytokine adsorption using the CytoSorb device had been proposed to be beneficial in various clinical settings including sepsis, ARDS, hyperinflammatory syndromes, cardiac surgery or recovery after cardiac arrest. The aim of this analysis was to provide evidence for the efficacy of the CytoSorb device with regard to mortality in these settings. Method(s): We searched Medline, Cochrane Library database and used the database provided by CytosorbentsTM. Central Register of Controlled Trials and clinicaltrials. gov for randomized, controlled studies (01.1.2010-28.2.22). We considered randomized controlled trials and observational studies with a control group. The longest reported mortality (30 days-, hospital- or ICU-mortality) was defined as primary endpoint. For analyzing the data we computed risk ratios and 95%-confidence intervals and used DerSimonian and Lairds random effects model (R 4.1). We analysed all studies together and separated in the subgroups sepsis, cardiac surgery, SARS-CoV-2 infection, recovery from cardiac arrest, other severe illness. The meta-analysis was registered in advance (PROSPERO: CRD42022290334). Result(s): Of initial 1249 publications, 37 trials were found eligible, in total including 1256 patients treated with CytoSorb and 1230 controls. Concerning the primary endpoint mortality Cytosorb did not show a positive effect in all studies together 1.10 [0.92;1.33] RR [95%-CI], in sepsis 1.03 [0.81;1.31], CPB surgery 0.85 [0.51;1.44], severe illness 1.05 [0.79;1.39], SARS-CoV-2 1.58 [0.50;4.94], and recovery from cardiac arrest 1.22 [1.02;1.46] (figure). Likewise we did not find significant difference in ICU length of stay, lactate levels, or norepinephrine after treatment. Conclusion(s): To date there is no evidence for a positive effect of the CytoSorb adsorber on mortality across a bunch of indications that justifies its widespread use in intensive care medicine. (Table Presented).

Increase in Mental Disorders During the COVID-19 Pandemic - Role of Occupational & Financial Strains : Nico Dragano

Background Numerous studies reported an increase in mental disorders during the COVID-19 pandemic, but the specific causes for this increase are unclear. We therefore investigate whether pandemic-related occupational and financial changes (e.g., reduced working hours, working from home, financial losses) were associated with increased symptoms of depression and anxiety compared with the situation before the pandemic. Methods We analyzed data from the German National Cohort Study (NAKO). Between May and November 2020, 161,849 participants answered questions on their mental state and social circumstances. Responses were compared with data from the baseline survey before the pandemic (2014-2019). Linear fixed-effects models were used to determine whether individual changes in the symptoms of depression (PHQ-9) or anxiety (GAD-7) were associated with occupational/financial changes (controlling for covariates). Results A pronounced increase in symptoms was observed among those who became unemployed during the pandemic (+ 1.16 points on the depression scale, 95% confidence interval [0.91;1.41], range 0-27). Increases were also seen for reduced working hours without short-term working allowance, increased working hours, working from home, insecurity regarding employment, and financial strain. The deterioration in mental health was largely statistically explained by the occupational and financial changes investigated in the model. Conclusions Depressive symptoms and anxiety disorders increased in the study population during the first year of the COVID-19 pandemic and occupational and financial difficulties were an essential contributory factor. These strains should be taken into account both in the care of individual patients and in the planning of targeted prevention measures. Results suggest that welfare state benefits such as short-time allowance in times of crises may reduce mental load in affected populations.

Working from Home (WFH) 2022-Best Practices Implementation and Case Study of Company Agreement

While four per cent of employees in Germany worked from home before the covid crisis, this figure was around 30 per cent in the first lockdown in April 2020. Now working from home and mobile working are part of the everyday life of many employees. Experience has shown that many activities can also be carried out from other locations than the classic office in the company. Location-flexible work will also still be standard in some sectors after the crisis. This article shows employees' experiences with working from home in corona times, with serious advantages and disadvantages being reported. Best practices as implementation of company agreements are presented based on an Original Equipment Manufacturer (OEM) example: Example of working from home (WFH) / office work, life-phase oriented working time instruments as a personnel management success factor, promotion of cross-border cooperation, efficient use of resources, questions on learning from the pandemic, working through the corona period with employees, recommendations for surviving this crisis and culture of trust versus control

Willingness to participate in a COVID-19 follow-up study and symptoms 1.5 years after infection : Sara Schramm

Introduction Data on willingness to participate in population-based long-COVID studies are sparse. We invited all citizens of Essen aged 18-74 years with a positive SARS-CoV-2 PCR test between Mar-Aug 2020 and assessed COVID-related symptoms in responders ∼1.5 years after infection. Methods The invited population included 1282 infected citizens (48% women). At the time of testing 64% reported symptoms. We asked responders about past and current symptoms, hospitalization, smoking, sport, pre-existing conditions (heart attack, stroke, diabetes), subjective health status as compared to before infection, assessed BMI, and performed descriptive statistics. Results We investigated 255 participants (50% women, 19-73 years, response rate 20%) ∼20 month (median) after the PCR test. 95% reported symptoms at the time of testing: 67% fatigue, 58% taste disorders, 56% limb pain, 55% odor disorders, 54% headache, 50% cough, 43% fever;10% needed hospitalization, 3% intensive care, 1.6% artificial ventilation. Compared to the non-hospitalized the formerly inpatients were more often male (62% vs 49%), older (56±13 vs 49±14 years), less often never smokers (42% vs 53%), had a higher BMI (31±7 vs 28±5 kg/m2), and more pre-existing conditions (23% vs 10%). Compared to before infection, 53% rated their current health worse, with a higher rate among inpatients (81%). After ∼1.5 years, 55% still reported symptoms: 25% fatigue, 20% concentration disorder, 18% breathing problems, 13% odor and 11% taste disorders. Persistent symptoms were more common in inpatients than in non-hospitalized (69% vs 53%). Conclusions Symptomatic individuals are more likely to participate in a COVID19 follow-up study than asymptomatic ones. This may overestimate the number of individuals with long-term symptoms in population-based long-COVID study populations. However, persistent symptoms seem to be more likely in formerly inpatients compared to non-hospitalized individuals with former SARS-CoV-2 infection. Key messages • Symptomatic individuals are more likely to participate in a COVID19 follow-up study than asymptomatic ones. • Persistent symptoms seem to be more likely in formerly inpatients compared to non-hospitalized individuals with former SARS-CoV-2 infection.

ROLE OF VENOVENOUS EXTRACORPOREAL MEMBRANE OXYGENATION IN SALVAGE THERAPY FOR CENTRAL AIRWAY OBSTRUCTION: A CASE REPORT

SESSION TITLE: Pulmonary Procedures: Creativity and Complications SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 10:15 am - 11:10 am INTRODUCTION: Recent advances in the management of airway disorders have provided additional therapeutic options for pathology, such as central airway obstruction (CAO). Symptomatic CAO has been managed by bronchoscopic interventions with a high risk of airway compromise and respiratory failure. Other alternatives such as mechanical and jet ventilation may not ensure adequate respiratory support during the procedure and cause delays in life-saving treatments. Venovenous extracorporeal membrane oxygenation (VV ECMO) has been used as an adjunct to preserve safety during these airway interventions [1,2]. We present a case of complete tracheal occlusion successfully intervened using VV ECMO support. CASE PRESENTATION: The patient is a 55-year-old male with a history of ventilator-dependent respiratory failure s/p tracheostomy, secondary to post COVID-19 fibrosis, who presented from a long-term acute care facility with worsening hypoxemia. The patient was transferred to the intensive care unit, where he underwent flexible bronchoscopy via the tracheostomy lumen, which did not reveal a patent airway. Orotracheal intubation was unsuccessful as there was complete occlusion of the airway below the vocal cords with abundant granulation tissue. Interventional pulmonology was consulted, and emergent recanalization of the airway with rigid bronchoscopy-mediated debulking was performed. Due to the severity of hypoxemia, cardiothoracic surgery was consulted, and the patient was placed on VV ECMO to support further intervention. The patient was intubated with EFER-DUMON 13 mm rigid bronchoscope. Complete recanalization was achieved using a rigid barrel and forceps with patency of both mainstems and all segmental bronchi. There were no postprocedural complications, and the patient returned to his baseline ventilator settings. DISCUSSION: VV ECMO has been used as an adjunct to preserve safety during high-risk bronchoscopic interventions, primarily in CAO. Acute respiratory decompensation remains a feared complication during these interventions in cases of CAO. Initiating ECMO before these interventions may reduce the incidence of respiratory failure and airway compromise. In a case series, ECMO has been described by Stokes et al. as a supportive measure facilitating such interventions [3]. Further guidelines are required to standardize ECMO initiation as procedural support during airway interventions. CONCLUSIONS: Planned preprocedural ECMO initiation can prevent respiratory emergencies and allow therapeutic high-risk airway interventions. The choices for this patient were stark- either airway recanalization without ECMO bridge with a risk of hypoxic brain injury vs. VV ECMO support and curative airway intervention. In the absence of large-scale data and based on local availability of excellent ECMO support and Interventional Pulmonology, the latter approach was used, leading to successful and safe airway recanalization. Reference #1: Zapol WM, Wilson R, Hales C, Fish D, Castorena G, Hilgenberg A et al.Venovenous bypass with a membrane lung to support bilateral lung lavage. JAMA 1984;251:3269–71. Reference #2: Fung R, Stellios J, Bannon PG, Ananda A, Forrest P. Elective use of venovenous extracorporeal membrane oxygenation and high-flow nasal oxygen for resection of subtotal malignant distal airway obstruction. Anaesth Intensive Care 2017;45:88–91. Reference #3: Stokes JW, Katsis JM, Gannon WD, Rice TW, Lentz RJ, Rickman OB, Avasarala SK, Benson C, Bacchetta M, Maldonado F. Venovenous extracorporeal membrane oxygenation during high-risk airway interventions. Interact Cardiovasc Thorac Surg. 2021 Nov 22;33(6):913-920. doi: 10.1093/icvts/ivab195. PMID: 34293146;PMCID: PMC8632782 DISCLOSURES: No relevant relationships by Vatsal Khanna No relevant relationships by Anurag Mehrotra No relevant relationships by Trishya Reddy No relevant relationships by Bernadette Schmidt

[Epidemiology of SARS-CoV-2/COVID-19]. / Epidemiologie von SARS-CoV-2/COVID 19: Aktueller Stand.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a beta coronavirus, which first appeared in 2019 and rapidly spread causing a worldwide pandemic. Here we present a nonsystematic review of the current knowledge on its epidemiological features. The SARS-CoV­2 replicates mainly in the upper and lower respiratory tract and is mainly transmitted by droplets and aerosols from asymptomatic and symptomatic infected subjects. The estimate for the basic reproduction number (R0) is between 2 and 3 and the median incubation period is 6 days (range 2-14 days). Similar to the related coronaviruses SARS and Middle East respiratory syndrome (MERS), superspreading events play an important role in spreading the disease. The majority of infections run an uncomplicated course but 5-10% of those infected develop pneumonia or a systemic inflammation leading to hospitalization, respiratory and potentially multiorgan failure. The most important risk factors for a complicated disease course are age, hypertension, diabetes, chronic cardiovascular and pulmonary diseases and immunodeficiency. The current infection fatality rate over all age groups is between 0.5% and 1% and the rate rises after the sixth decade of life. Nosocomial transmission and infections in medical personnel have been reported. A drastic reduction of social contacts has been implemented in many countries with outbreaks of SARS-CoV­2, leading to rapid reductions in R0. Most interventions have used bundles and which of the measures have been more effective is still unknown. Using mathematical models an incidence of 0.4%-1.8% can be estimated for the first wave in Germany.

Health, competence and trust

Health literacy is important for health, but there is a social gradient in health literacy. If considering the willingness to vaccinate against Covid-19 as an expression of applied health literacy, the social gradient becomes apparent. Because the willingness to vaccinate depends on trust in the vaccine and the responsible institutions, and because trust is socially unequally distributed, social measures to promote trust are necessary.

History and Memory of Dissident Sexualities from Latin America: An Analysis of the Foundation, Current Activities, and Projects of AMAI LGBTQIA+

This article focuses on Red Latinoamericana de Archivos, Museos, Acervos y Investigadores LGBTQIA+ (AMAI LGBTQIA+), a network composed of researchers and institutions related to LGBTQIA+ memory in Latin America, founded in 2019. First, the authors analyse the network's creation arising from the discontent of some participants of the June 2019 Archives, Libraries, Museums and Special Collections (ALMS) Conference, in Berlin, who felt bothered by the lack of attention given to subaltern perspectives on LGBTQIA+ history and memory. Next, the authors describe and analyse the network's first year of activities communicated through its Facebook group. Multiple challenges arose from creating a network with members from different national origins, languages, and identities, especially considering the conservative political contexts of several Latin American countries and the social distancing measures imposed by the COVID-19 pandemic. Next, the authors present a general profile of the network's members and a map of partner institutions. Finally, the article points out some challenges to the network's continuity and its desire to render Latin America more visible in the broader panorama of global LGBTQIA+ history. The authors conclude by highlighting the importance of AMAI LGBTQIA+ in stimulating further discussions about the participation of global-south researchers and perspectives on global queer history initiatives. © 2021. All Rights Reserved.

Durvalumab in frail and older patients with stage iv non-small cell lung cancer: The randomized phase ii duration trial

Introduction: Checkpoint inhibitors have recently been established as first-line treatment for metastatic NSCLC. Notably, a phenomenon known as immunosenescence, i.e. the progressive remodeling of the immune system with aging, as well as the inflammatory status, may interfere with the activity of PD-1/PD-L1 inhibitors. Although frail and older patients represent a major fraction of non-small cell lung cancer (NSCLC) patients in routine clinical practice, this population is still underrepresented in most clinical trials. Thus, clinical evidence about tolerability and efficacy of these novel agents in the elder and frail population is urgently required. Methods/Design: DURATION (NCT03345810) is a prospective, open label, treatment stratified, randomized, multicenter phase II study. The protocol foresaw the enrollment of 200 patients diagnosed with stage IV NSCLC ≥70 years old and/or with Charlson-Comorbidity Index > 1 and/ or with a performance status ECOG > 1. Patients were stratified according to Cancer and Age Research Group (CARG) score in 'fit' and 'less fit'. Patients were then randomized 1:1 to receive either CT or two cycles of CT followed by two cycles of durvalumab and durvalumab maintenance. Details are shown in figure 1. The primary endpoint is the rate of treatment-related grade III/IV adverse events. Secondary endpoints are progression-free survival, response rate and overall survival and quality of life assessment. The trial is accompanied by a biomaterial repository to explore potential biomarkers. Results: The last patient was enrolled in January 2021. Forty-nine, 48, 51, and 52 patients were allocated to arm A, arm B, arm C, and arm D, respectively. Currently, 145 patients have completed the study, 13 patients are under treatment (12 in total in durvalumab-maintenance arms and 1 in the CT arm), while 42 are in follow-up. Conclusions: Inspite of the COVID-19 pandemic, the DURATION trial successfully completed the planned enrollment of 200 patients, underlying the urgent need for evidence of efficacy and tolerability of immunotherapy in the challenging population of frail and elderly patients.

Background-oriented schlieren imaging during Jet ventilation models aersolization during COVID-19

Introduction: During the COVID-19 pandemic, minimizing the surgeon's exposure to aerosol-generating procedures is critical, and to our knowledge, the airflow dynamics and subsequent risk to the surgical team due to a back-flow or plume during jet ventilation has not been studied. Backgroundoriented Schlieren (BOS) imaging detects distortions in airflow to see the invisible: a density gradient creates a refractive index change in the air, which uses small shifts to the recording of a visually textured background that are revealed using imaging-processing techniques. We aimed to use the BOS technique to illustrate the airflow patterns of jet ventilation. Method: A manikin model of jet ventilation was created to mimic lung compliance in an open system. A laryngoscope was used to expose the model and was suspended. The Monsoon III high-frequency jet ventilation system (Vyaire, Chicago, Illinois, USA) was used in either a supraglottic (delivered via laryngoscope port) or infraglottic technique (Hunsaker Mon-Jet ventilation theter, Medtronic, Minneapolis, USA). Various delivery settings were tested including driving pressure, ventilation frequency, and use of a variety of suction types/position. Images were obtained with a high-speed camera, and BOS processing was performed. Plume size was measured with ImageJ software (National Institutes of Health, Bethesda, Maryland, USA). Results: We successfully used BOS imaging to demonstrate variations in plume volume during supraglottic and infraglottic techniques. Low-frequency jet ventilation (12 cycles/min) and lower driving pressures had a smaller plume than highfrequency jet ventilation (120 cycles/min) or higher driving pressures with all other settings stable. There appeared to be a higher transnasal plume during supraglottic jet ventilation. Suction position significantly affected the plume size. Conclusion: High-frequency, low-volume, infraglottic jet ventilation with dual suction appears to have a lower risk of aerosolization compared with other modes of ventilation. Higher driving pressures were correlated to plume size.