The Association of COVID-19 Severity with Laboratory Parameters, Radiologic Findings, Maternal and Neonatal Outcomes in Pregnant Women: A Multicenter Study in Indonesia

Objectives: Severe acute respiratory syndrome-coronavirus 2/COVID-19 infection is still a global concern, with pregnant women are considered as vulnerable population. Until now, the characteristics of pregnant women in Indonesia who are infected with COVID-19, as well as pregnancy and neonatal outcomes, are still unknown. This study aims to obtain national data, which are expected to be useful for the prevention and management of COVID-19 in pregnant women in Indonesia. Method(s): There were 1,427 patients recruited in this retrospective multicenter study. This study involved 11 hospitals in 10 provinces in Indonesia and was carried out using secondary patient data from April 2020 to July 2021. COVID-19 severity was differentiated into asymptomatic-to-mild symptoms and moderate-to-severe symptoms. The collected data include maternal characteristics, laboratory examinations, imaging, pregnancy outcomes, and neonatal outcomes. Result(s): Leukocyte, platelets, basophil, neutrophils segment, lymphocytes, monocytes, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, alanine aminotransferase (ALT), aspartate aminotransferase (AST), C-reactive protein (CRP), urea, and creatinine were found to be significantly associated with severity differences (p < 0.05). Moderate-severe symptoms of COVID-19 also shown to have suggestive pneumonia findings on chest X-ray findings. Patients with asymptomatic-to-mild symptoms had significantly (p < 0.001) higher recovery rate, shorter hospital stay, less intensive care unit (ICU) admission, and had more vaginal delivery. Neonates from mother with mild symptoms also had significantly (p < 0.001) higher survival rate, higher birth weight, and higher APGAR score. Conclusion(s): Several laboratory and radiology components, as well as maternal and neonatal outcomes are related to the severity of COVID-19 in pregnant women in Indonesia.Copyright © The Author(s). 2023.

Prevention of COVID-19 coronavirus infection with aminodihydrophthalazinedione sodium (Galavit) in medical staff of the "red zone": results of the multicenter observational study

COVID-hospital healthcare workers belong to a high-risk SARS-CoV-2 infection. The aminodihydrophthalazinedione sodium (Galavit) belongs to the group of immunomodulatory and anti-inflammatory drugs. It has been shown that aminodihydrophthalazinedione sodium is effective in the prevention of acute respiratory infections, respiratory tract diseases and ENT-organs of bacterial and viral etiology. The purpose of the study. To evaluate the effectiveness and safety of immunoprophylaxis of new coronavirus infection (COVID-19) with aminodihydrophthalazinedione sodium in healthcare workers providing medical care in the "red zone". Material and methods. A multicenter prospective-retrospective observational comparative non-randomized study in healthcare workers providing medical care in the "red zone" was conducted. 428 participants were included in the study: the observation group - healthcare workers who administered aminodihydrophthalazinedione sodium (Galavit) for prophylactic purposes (n=214), and control group (n=214). The observation period of the participants or the period of collecting retrospective data in the study was 30 days. The results of PCR tests and tests for antibodies to the SARS-CoV-2 were analyzed, clinical status (COVID-19 in any form) was assessed. Descriptive statistic methods and Pearson chi2 test were used. The risk ratios, odds ratios and 95% confidence intervals were calculated with them. The influence of potential confounding factors (age, gender, work place in clinical site, the presence or absence of concomitant disease) on the clinical status were analyzed using logistic regression. The analysis of propensity score matching was carried out. The Stata/IC 14.2 for Windows software used for statistical analysis. Results and discussion. Observational study results describe the risk ratios and odds ratios of infection with a new coronavirus (COVID-19) in healthcare workers providing medical care in the "red zone" considering prophylactic administration of aminodihydrophthalazinedione sodium (Galavit). 205 (95.8%) participants in the group of healthcare workers who took aminodihydrophthalazinedione sodium (Galavit) for prophylactic purposes and 194 (90.7%) participants in control group had a negative PCR test during the observation period, chi2=4.48, p=0.034. The risk of a positive status according to the PCR test for 30 days in the preventive group was 0,04, and in the control group 0.09. The risk difference was -0.05 [95% confidence interval (CI) -0.099;-0.004]. The adjusted odds ratio using multiple logistic regression was - 0.41 (95% CI 0.18-0.93). No adverse events were observed during the prophylactic administration of aminodihydrophthalazinedione sodium over 30 days. Conclusion. Galavit preventive administration in a tablet form at a dose of 50-100 mg per day by employees of medical institutions providing medical care to patients with CIVID-19 significantly reduces the risk of SARS-CoV-2 infection and more than 2 times increases the chances not ill of new coronavirus infection. Galavit administration up to 30 days at a dose of 50-100 mg was well tolerated, no adverse events were registered.Copyright © 2022 by the authors.

Conference Proceedings 33rd AAAP Annual Meeting and Scientific Symposium

The proceedings contain 20 papers. The topics discussed include: the effect of specialty addiction consultation on prescribing medication for opioid use disorder (MOUD) during general hospital admission;mindfulness-based interventions for adolescent drug and alcohol use: a systematic review and meta-analysis;early changes in irritability predict longer-term abstinence from drug use in adults with stimulant use disorder: findings from the stride study;carfentanil, a highly potent opioid responding to high doses of naloxone, what can help?;an inpatient protocol for managing methamphetamine withdrawal;COVID-19 treatment outcome in a cohort of methamphetamine and cannabis users;the impact of COVID-19 on overdose risk and healthcare-seeking behaviors among hospitalized patients with opioid use disorder;and inpatient low dose transitions from full agonist opioids including methadone onto long-acting depot buprenorphine: case series from a multicenter clinical trial.

Updated efficacy and safety of taletrectinib in patients (pts) with ROS1+ non-small cell lung cancer (NSCLC)

Background Taletrectinib is a potent, next-generation, CNS-active, ROS1 tyrosine kinase inhibitor (TKI) with selectivity over TRKB. In previous reports from TRUST-I, taletrectinib showed meaningful clinical efficacy and was well tolerated in pts with ROS1+ NSCLC (n = 109) regardless of crizotinib (CRZ) pretreatment status. We report updated efficacy and safety data with ~1.5 yr follow-up. Methods TRUST-I is a multicenter, open-label, single-arm study with two cohorts: ROS1 TKI-naive and CRZ-pretreated. Pts in both cohorts received taletrectinib 600 mg QD. Key study endpoints included IRC-confirmed ORR (cORR), DoR, disease control rate (DCR), PFS, and safety. A pooled analysis of ORR, PFS, and safety including pts from additional clinical trials was also conducted. Results In the 109 pts from TRUST-I (enrolled prior to Feb 2022) the median follow-up was 18.0 mo in TKI-naive (n = 67) and 16.9 mo in CRZ-pretreated pts (n = 42). cORR was 92.5% in TKI-naive and 52.6% in CRZ-pretreated pts (table). Median DoR (mDoR) and mPFS were not reached. Intracranial-ORR was 91.6%;ORR in pts with G2032R was 80.0%. In a pooled analysis with phase I studies, ORR was 89.5% and 50.0% for TKI-naive and CRZ-pretreated pts, respectively;mPFS was 33.2 mo and 9.8 mo. In 178 pts treated at 600 mg QD, treatment-emergent adverse events (TEAEs) were 92.7%;most (64.0%) were grade 1-2. The most common TEAEs were increased AST (60.7%), increased ALT (55.6%), and diarrhea (55.6%). Neurological TEAEs (dizziness, 18.5%;dysgeusia, 12.4%) and discontinuations due to TEAEs (3.4%) were low. Further updated results will be presented. [Formula presented] Conclusions With additional follow-up, taletrectinib continued to demonstrate meaningful efficacy outcomes including high response rates, prolonged PFS, robust intracranial activity, activity against G2032R, and tolerable safety with low incidence of neurological AEs. Clinical trial identification NCT04395677. Editorial acknowledgement Medical writing and editorial assistance were provided by Arpita Kulshrestha of Peloton Advantage, LLC, an OPEN Health company, and funded by AnHeart Therapeutics, Inc Legal entity responsible for the study AnHeart Therapeutics, Inc. Funding AnHeart Therapeutics, Inc. Disclosure S. He: Financial Interests, Personal, Other, Employment: AnHeart Therapeutics. T. Seto: Financial Interests, Institutional, Research Grant: AbbVie, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly Japan, Kissei Pharmaceutical, MSD, Novartis Pharma, Pfizer Japan, Takeda Pharmaceutical;Financial Interests, Personal, Other, Employment: Precision Medicine Asia;Financial Interests, Personal, Speaker's Bureau, Honoraria for lectures: AstraZeneca, Bristol-Myers Squibb, Chugai Pharmaceutical, Covidien Japan, Daiichi Sankyo, Eli Lilly Japan, Kyowa Hakko Kirin, MSD, Mochida Pharmaceutical, Nippon Boehringer Ingelheim, Novartis Pharma, Ono Pharmaceutical, Pfizer Japan, Taiho Pharmaceutical, Takeda Pharmaceutical, Towa Pharmaceutical. C. Zhou: Financial Interests, Personal, Other, Consulting fees: Innovent Biologics Qilu, Hengrui, TopAlliance Biosciences Inc;Financial Interests, Personal, Speaker's Bureau, Payment or honoraria: Eli Lilly China, Sanofi, BI, Roche, MSD, Qilu, Hengrui, Innovent Biologics, C-Stone LUYE Pharma, TopAlliance Biosciences Inc, Amoy Diagnositics, AnHeart. All other authors have declared no conflicts of interest.Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc.

Satisfaction of patients after implant-based subpectoral reconstruction with a titanized polypropylene mesh (TiLOOP Bra) compared to prepectoral reconstruction with a titanzied polypropylene pocket (TiLOOP Bra Pocket)

Introduction Patients' satisfaction after breast reconstruction can be evaluated with validated questionnaires as the Breast-Q questionnaire. The Breast-Q questionnaire includes different domains;one of them is "satisfaction with the result". Material(s) and Method(s): In the multicentre, prospective studies PRO (patient related outcome)-BRA (clinicaltrials.gov: NCT01885572) and PRO-Pocket (clinicaltrials.gov: NCT03868514), patient satisfaction was assessed using the Breast-Q questionnaire. In the PRO-Bra study, 269 patients underwent subpectoral surgery using the TiLOOP Bra polypropylene mesh (pfm medical ag, Germany). In the 'PRO-Pocket' study, 311 patients underwent prepectoral surgery using the TiLOOP Bra Pocket polypropylene mesh. For the evaluation, those patients from the PRO-Bra and PRO-Pocket studies who completed a Breast-Q questionnaire 6 and/or 12 months after surgery were included. The BreastQ score is measured from 0 to 100, with a score of 100 corresponding to 'very satisfied'. Satisfaction with the result of the breast reconstruction was evaluated. Result(s): In the PRO-Bra study, a total of 221 and 203 patients completed a Breast-Q at 6 months and/or 12 months FU, respectively. The mean age and BMI of the patients with completed Breast-Q were comparable between the two studies (PRO-Bra: 49.3 [+/-11.6] years, 22.9 kg/m2 [+/-3.5];PRO-Pocket: 47.7 [+/-11.7] years, 24.5 kg/m2 [+/-4.3]). In the PRO-Pocket study, a total of 258 and 266 patients completed a Breast-Q at 6 months and/or 12 months FU, respectively. In the PRO-Bra study the mean score of satisfaction with the result at 6 months follow-up (FU) was 74.5 (+/-19.9), in the PRO-Pocket 79.1 (+/-19.1), at 12 months FU the mean scores were 76.3 (+/-18.9) for PRO-Bra and 78.2 (+/-20.4) for PRO-Pocket. Furthermore, stratification according to age (cutoff 50 years) or BMI (cutoff 25 kg/m2) did not reveal any differences between the subgroups or the two studies (see Table). PRO-Bra PRO-Pocket mean score (+/-SD) 6 months 12 months 6 months 12 months BMI <= 25 75.1 (+/-19.7) 76.4 (+/-17.8) 77.7 (+/-19.9) 78.9 (+/-19.8) BMI > 25 72.1 (+/-20.7) 76.1 (+/-22.9) 82.1 (+/-16.9) 76.8 (+/-21.8) age <= 50 76.4 (+/-18.7) 77.0 (+/-18.9) 80.1 (+/-18.7) 78.1 (+/-19.6) age > 50 71.5 (+/-21.5) 75.3 (+/-19.0) 77.5 (+/-19.5) 78.4 (+/-21.8) Conclusion(s): Our data so far show high patient satisfaction with overall outcome of the surgery. In addition, patients' satisfaction with the result was comparable after subpectoral as well as prepectoral implant placement. This is particularly important in the PRO-Pocket study, as approximately 60% of the operations and the follow-up period took place during the COVID-19 pandemic.

Off Label Medication to Combat COVID-19: Review Results to Date

Background: Severe viral pneumonia cases were observed in the people of Wuhan, China in December 2019. It has already affected almost every country around the globe and was declared a pandemic by the World Health Organization. We aim to evaluate the therapeutics and safety of various off label COVID-19 drugs. Method(s): PubMed, Research Gate, Science Direct, Google Scholar, Centre for Disease control and prevention (CDC) portal, Chinese Centre for Disease Control and prevention (CCDC) portal, World Health Organization (WHO) portal were searched for obtaining reliable data. Result(s): COVID-19 is creating a storm of deaths and active cases globally, which is forcing the pharmaceutical companies and scientists to work day and night to find an effective and safer anti-COVID-19 medication. Various in vitro and clinical trials had been performed as well as are currently ongoing to analyze the mechanisms and therapeutics of off label medications like Chloroquine, Hydroxychloro-quine, Amodiaquine, Azithromycin, Remdesivir, Favipiravir, Ritonavir/Lopinavir, Umifenovir, Osel-tamivir, Ribavirin, Nafamostat, Camostat, Tocilizumab, Ivermectin, Nitazoxanide, Famotidine, Vitamin D, Corticosteroids and Dexamethasone. In vitro studies were performed by utilizing Vero E6 cells and hSLAM cells while open/closed, randomized/non-randomized, single-centered/multi-centered and retrospective clinical trials and case studies were organized to determine their safety and efficacy. Conclusion(s): Although these drugs have shown promising results against COVID-19 patients, it cannot be concluded that these drugs are truly safe and effective because there are no conclusive evidence to support the facts since only limited researches and studies had been investigated.Copyright © 2021 Bentham Science Publishers.

Lack of seroconversion following COVID-19 vaccination, but not treatment, is an independent risk factor for breakthrough SARS-CoV-2 infection in patients with inflammatory bowel disease: Data from ESCAPE -an IG-IBD Study

Background: As patients with immune conditions were excluded from COVID-19 vaccine clinical trials, it is important to accumulate realworld data in this setting, particularly to identify those who would benefit from repeated doses. Method(s): Effectiveness and Safety of COVID-19 Vaccine in Patients with Inflammatory Bowel Disease (IBD) Treated with Immunomodulatory or Biological Drugs (ESCAPE) is a prospective, multicentre, observational study assessing effectiveness and safety of COVID-19 vaccines in patients with IBD (ClinicalTrials.gov ID: NCT04769258). Here we present data on the rate of breakthrough SARS-CoV-2 infections in the timeframe between 14 days after the second dose and the third dose of COVID-19 vaccine (or a maximum of 9 months from the second dose). The risk factors for SARS-CoV-2 infection, including lack of seroconversion (cut-off for IgG anti-SARS-CoV-2: OD 0.28) and IgG anti-SARS-CoV-2 levels after 8 weeks from the second dose, and treatment for IBD, were assessed. Result(s): Out of the 1076 patients with IBD enrolled in the ESCAPE study, data on breakthrough SARS-CoV-2 infection were available in 953 cases. Most of the patients received homologous, doubledose mRNA-based vaccines (BNT162b2 or mRNA-1273: 99.2%). Seroconversion was reported in 92.7% of cases (median OD 1.60 [IQR 0.8-3.6]), while SARS-CoV-2 infection was documented in 95 patients (10.0%), of whom 9 died. At multivariable regression analyses, age (OR 0.97, 95% CI 0.96-0.99;p<0.001) being former smoker (OR 2.23, 95% CI 1.26-3.88;p=0.005), and lack of seroconversion (OR 0.42, 95% CI 0.20-0.99;p=0.034) were independent predictors of SARS-CoV-2 infection. Conversely, none of the treatments for IBD was associated with breakthrough SARS-CoV-2 infection. Notably, all 9 patients who died had reported seroconversion after the second dose. Conclusion(s): IBD patients without seroconversion after COVID-19 vaccines are at increased risk for SARS-CoV-2 infection, while medications for IBD had no impac.

Improving Data Quality in Multicenter Trials: Innovative Approaches Utilized within the Wake Forest Nci Community Oncology Research Program Research Base (Wf Ncorp Rb)

Introduction: Efficient and comprehensive trial oversight and data management ensures valid, robust outcomes necessary to inform health policy and improve patient outcomes. This is particularly challenging in the context of multicenter trials. The format of this session will include four introductory presentations (15 min each), followed by 30-min panel discussion/Q&A focusing on recent experiences and innovative approaches utilized within the Wake Forest NCI Community Oncology Research Program Research Base (WF NCORP RB). Since 2017, WF has managed 15 studies with approximately 3000 patient and 1000 provider/stakeholder accruals across 1000 potential participating community oncology practices within the United States and Puerto Rico. These practices often operate differently from academic medical centers, with varying patient capacity, provider number and level of engagement, use of advanced practice providers, and services offered. In addition, practices within this network have heterogeneous utility of electronic health records (EHRs) and display a wide range of clinical research staffing models. The COVID-19 pandemic has highlighted the need for streamlining research visits and maximizing telehealth technologies when applicable, particularly for intervention non-therapeutic clinical trials. As such, research expectations must be standardized to ensure quality trial conduct and data collection across diverse practices. Recently, the WF NCORP RB has taken many steps to improve efficiency and data quality across our studies. This session will discuss a comprehensive approach to data quality and management across the lifespan of a trial. This starts with consent/ recruitment strategies and general oversight/ monitoring of our portfolio of trials. WF RB now utilizes REDCap for all data capture, as this allows direct data entry for site personnel and participant entered patient-reported outcomes using surveys. In addition, REDCap facilitates data monitoring, query, and auditing strategies. We will also introduce a team-based approach to adjudicate complex outcomes. Talk 1 (15 min): Specifically, Karen Craver, our RB administrator, will discuss approaches to obtain robust data as a result of strong screening and recruitment. She will provide an overview on how we survey practice research staff within the Landscape assessment and brief, pre-trial interest surveys to identify optimal target populations during the planning stage. We utilize our internal EHR to create custom screening reports to identify potential participants and generalize these for other practices to customize and use as a screening tool within their clinic. The RB has integrated remote consenting in part due to the pandemic, but we realize the need to continue offering flexibility in consent modality moving forward. Talk 2 (15 min): Emily Dressler, lead Biostatistician, will discuss oversight of the RB portfolio using dynamic reports within Tableau. These reports update daily and provide a comprehensive assessment of all ongoing and completed studies. RB personnel can filter reports to create custom results subset by timeframe, practice or set of practices, trial type, and/or other demographic characteristics. This has greatly reduced the request for study-specific accrual reports and has standardized our reporting across studies. She will also discuss the rationale for transitioning to REDCap, including strengths and weaknesses for integrating in multicenter studies. Talk 3 (15 min): Bill Stanfield, lead data manager, will demonstrate our utilization of the REDCap Data Resolution Workflow and Data Quality modules to efficiently manage data collection, data quality, and audits. He will show how REDCap can be used to seamlessly communicate with research staff to obtain missing or late data, verify out of range values, and then validate and lock responses for analysis. Talk 4 (15 min): Glenn Lesser, WF NCORP multiple principal investigator (mPI), will discuss a team approach to adjudicating cancer treatment information that often consists of combination of surgery, radiation, chemotherapy, or immunotherapy/targeted agents. This remains a particularly challenging problem in large trials enrolling patients with multiple types of cancer who may be treated with a wide spectrum of standard therapeutic regimens. This diversity limits both the effectiveness of automated reviews of remote data entries and the study-specific training of data management staff at sites. Data are pulled in real time from multiple forms within REDCap and collated into participant-level summaries of treatment, starting with the time of baseline assessment and sorted sequentially for each drug administration or event. A multidisciplinary team of data managers, biostatisticians, and clinicians meet to adjudicate each participant as data collection completes. Particularly for trials with multiple cancer types or treatment regimens, our experience with this approach has shown it identifies significant data gaps in treatment, with at least 75% of entries requiring clarification from research staff prior to finalizing and locking data. This process highlighted the challenge of real-time adjudication of treatment data in patients receiving multiple anti-cancer agents, given at varying doses and schedules, and in multiple combinations and/or phases over an individual patient's course of therapy. Panel (30 min): We will conclude with a panel discussion and Q&A. The panel will contribute additional perspective on implications of these strategies in the conduct of multilevel cancer care delivery research studies. We will also incorporate perspectives from NCORP community sites implementing these strategies. Panelists will discuss the broad applicability of these strategies for diverse trials, with attention to size/ complexity, database vendor, and patient population.

Fifteen-year experience with natalizumab in the treatment of multiple sclerosis - a description of 15 clinical cases.

Natalizumab, a humanized anti-alpha4-integrin antibody, is a valuable therapeutic option for relapsing-remitting multiple sclerosis and has been widely used in this indication since 2006. The growing body of data on its high efficacy and safety profile, both from randomised trials and clinical practice, has allowed to identify risk factors for progressive multifocal leukoencephalopathy and to develop a preventive algorithm, which increased the therapeutic safety. Natalizumab also seems relatively safe in pregnant women as there is no indication in the available literature suggesting that exposure to this drug has a significant impact on pregnancy outcomes. However, adequate and well-controlled studies are still lacking and natalizumab should only be used in pregnancy if clearly needed. The mechanism of action of natalizumab also proved successful during the COVID-19 pandemic. Most patients receiving this therapy experienced only mild infection and developed normal vaccine-induced immunity after immunisation. We present a description of 15 patients with relapsing-remitting multiple sclerosis treated with natalizumab in 15 different centres throughout Poland. The drug was included both due to first-line treatment failure and in cases of rapidly progressing, severe form of multiple sclerosis. The patients differed in terms of disease duration, the length of natalizumab therapy, and JCV serological status. The described cases include patients from the natalizumab registration trial, women who became pregnant while on the therapy, and patients who developed COVID-19. The presented case reports summarise the experience to date with the use of natalizumab in the treatment of relapsing-remitting multiple sclerosis in PolandCopyright © 2022 Buchajewicz et al.

Methylprednisolone in the treatment of post-COVID-19 Interstitial Lung Disease (STERCOV-ILD)

Introduction: Post-COVID-19 Interstitial Lung Disease (ILD) is controversial and need for treatment is unclear. Aim(s): To investigate the efficacy of methylprednisolone in the treatment of post-COVID-19 ILD. Method(s): This multicentre, prospective, randomized controlled clinical trial, included post-COVID ILD patients (ClinicalTrials.gov, NCT:04988282). Post-COVID ILD was defined as the presence of respiratory symptoms, hypoxemia, restrictive lung functions and parenchymal infiltrates on thorax HRCT. 262 post-COVID-19 patients were randomly assigned to one of two arms: the steroid group (n:135) or control group (n:127). For 4 weeks, the steroid group received oral methylprednisolone at a dose of 0.5 mg/kg/day (maximum dose: 48 mg/day). At the end of the study, thorax HRCT, 6-minute walking test and lung function tests were re-evaluated. A good response was defined as a mMRC score of 0, a FVC percentage greater than 80% and absence of hypoxemia at rest or during exercise, greater than 90% resolution of lesions on CT. Result(s): Good clinical and functional response rates were higher in steroid group compared to the control group (62.9% vs 33.3%;54.1% vs 33.7%, p<0.001, respectively). Patients with a radiological response in steroid group tend to be higher than control group, but not statistically significant (61.1 % vs 51.1 %, p=0.159). The increase in oxygen saturation, FVC, and 6-minute walking distance were significantly higher in the steroid group compared to the control. Discussion(s): Systemic corticosteroids improves clinical and functional characteristics and increases oxygen saturation, FVC, and exercise capacity in post-COVID ILD patients compared to the natural course of the disease.

The golden patient initiative: A systematic review

Introduction: Operating theatres and surgical resource consumption comprise a significant proportion of all healthcare costs. Inefficiencies in theatre lists remain an important focus for cost management. During COVID-19 pandemic, The number of patients On theatre waiting lists has surged. Hence there is a pressing need to utilise already limited theatre time and fraught resources with innovative methods. In this systematic review we consider The Golden Patient Initiative (GPI), in which The first patient On The operating list is pre-assessed The day prior to surgery, and we aimed to assess its overall efficacy. Method(s): A literature search using four databases: MEDLINE, CINAHL, EMBASE, and The Cochrane library identified all clinical research concerning The GPI. Two independent authors screened articles against eligibility criteria, using a process adapted from PRISMA guidelines. Data extracted included outcomes measured, follow-uP period and study design. The result displayed significant heterogeneity;therefore a narrative review was conducted. Result(s): 13 of 73 eligible articles were included for analysis. Outcomes included delay in theatre start time, number of surgical case cancellations and changes to total case numbers. Across The studies, a 19-30 minute improvement of theatre start time was reported (P<0.05), as was a statistically significant decrease in case cancellations. Conclusion(s): Our analysis gives encouraging conclusions for theatre efficiency with The GPI, a low cost solution which can easily be implemented to helP improve patient safety lead to cost savings. However, at present it is largely implemented amongst local trusts, hence larger multicentre studies are required to provide conclusive evidence. Take-home message: Our analysis gives encouraging conclusions for greater theatre efficiency with The GPI, a low cost solution which can easily be implementedtohelP improve patient safety leadto cost savings.

COVID-19 vaccination from 6 to 17 years carries a similar risk for fatal or life-threatening myocarditis than being struck by lightning

Background and Aim: There are some concerns about the cost/ben-efit ratio of Covid-19 vaccination in the pediatric age due to the greater response to immune stimulation in children and young adolescents. Myocarditis is a feared adverse event (AE). Method(s): On January 4, 2022 we searched the Pubmed and EMBASE datasets for population studies assessing myocarditis events in pediatric subjects, and the US nationwide data about COVID-19 vaccinations and AEs. Result(s): The studies selected (n = 10) were highly heterogeneous, and did not include subjects lt;12 years. In a nationwide study the incidence of myocarditis was 1.34 over 100,000 in males and 7 over 1,000,000 in females aged 16-19 years after the first dose, and 1.51 over 10,000 in males and 4.6 over 1,000,000 in females after the second dose. All studies with available data reported a higher risk in males and after the second dose. Based on US data, the estimated incidence of myocarditis was 2.80 over 100,000 in fully vaccinated individuals (i.e., receiving two doses of mRNA vaccines or received one dose of a single-dose vaccine) aged 6-17 years. No events were reported in subjects lt;5 years (n = 9,985). The incidence of myocarditis was 1.05 over 100,000 in those aged 18-64 years, and 2.75 over 1,000,000 >=65 years. The incidence of fatal or life-threatening myocarditis was 3.78 over 1,000,000 6-17 years, 1.78 over 1,000,000 18-64 years, and 8.54 over 10,000,000 >=65 years, with the same order of mag-nitude than the odds of being struck by lightning (around 2 over 1,000,000). The incidence of COVID-19 myocarditis is 1.33 in 1000 lt;16 years, i.e., 47.5-fold higher than fully vaccinated individuals. Conclusion(s): The reported incidence of myocarditis in subjects aged >=12 years is slightly higher in males and after the second dose, but extremely low. No case of myocarditis lt;5 years were reported in the US. In fully vaccinated individuals aged 6-17 years, the esti-mated incidence of myocarditis was 2.80 over 100,000, and of fatal or life-threatening myocarditis 3.78 over 1,000,000, with the same order of magnitude than being struck by lightning, and far lower than the risk of COVID-19 myocarditis.

THAT BLOODY CLOT DOES NOT ALWAYS NEED A TUNNEL TO MIGRATE: A CASE OF MULTIPLE ARTERIAL AND VENOUS THROMBOSIS IN A COVID-19 PATIENT

SESSION TITLE: Rare Cases of Nervous System and Thrombotic Complication Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Covid 19 virus has impacted nearly 450 million people across the globe;ranging from an asymptomatic carrier state to respiratory symptoms, cardiovascular symptoms, hematologic manifestations and multiorgan failure to death. Thrombotic events are one of its devastating complications. CASE PRESENTATION: A 66 year old man with a history of diabetes mellitus, hypertension and 30 pack years smoking history presented to the emergency room with hypoxia and altered mental status. On exam, his GCS was 8/15 and oxygen saturation was 85% on room air. He was subsequently intubated. CTA chest demonstrated bilateral diffuse ground glass opacities and left pulmonary embolism (PE). CT abdomen and pelvis showed multifocal infarcts in the right kidney with findings suggestive of renal artery thrombosis. Initial platelet count was 80,000/ul with creatinine of 3.9 mg/dl and creatine kinase (CK) of 3977 u/l. His INR was 1.4. Patient was not a candidate for thrombolysis given his thrombocytopenia. He was started on intravenous (IV) heparin and given IV hydration. On day 3 of his admission, he developed dry gangrene of the toes. Ankle brachial index of the right lower extremity (LE) was 1.16 and left LE was 0. Duplex ultrasonography of left LE showed mid to distal popliteal artery thrombus occluding below knee popliteal and tibial arteries. Echocardiogram showed ejection fraction of 55% and bubble study was negative for any intra atrial or pulmonary shunting. On day 4 of his admission, he developed oliguria and his gangrene got worse. His platelet counts decreased to 36,000/ul. Other pertinent labs showed INR 1.2, PT 15.3, PTT 34, D dimer 14.82, fibrinogen 498, CK 6434 mg/dl, hemoglobin 13.2 g/dl, haptoglobin 243 mg/dl and LDH 1041 U/l. Given his poor prognosis in the setting of ventilator dependent respiratory failure, multiple thrombosis and kidney failure requiring hemodialysis, the family decided to withdraw care. DISCUSSION: There are multiple hypotheses of thrombus formation in Covid 19 infection such as interleukin 6 and other cytokines induced endothelial injury, angiogenesis and elevated prothrombotic factors such as factor VIII and fibrinogen. Our patient had PE, renal artery thrombosis and popliteal artery thrombosis. Despite being on full dose anticoagulation, he developed gangrene of the toes. His lab results were not consistent with disseminated intravascular coagulation, thrombotic thrombocytopenic purpura and he was not known to have any baseline hypercoagulable disorder. He did not have any intra cardiac shunts. Hence, it is most likely Covid 19 induced multiple arterial and venous thrombosis. CONCLUSIONS: The treatment of Covid 19 related thrombosis has become very challenging especially in the setting of multiple clots. It is crucial to have large multicenter studies to investigate vascular complications of Covid-19 and to formulate management strategies to ensure good patient outcomes. Reference #1: https://www.nejm.org/doi/full/10.1056/nejmoa2015432 Reference #2: https://journal.chestnet.org/article/S0012-3692(21)01126-0/fulltext DISCLOSURES: No relevant relationships by Devashish Desai No relevant relationships by Swe Swe Hlaing no disclosure on file for Jean Marie Koka;No relevant relationships by Hui Chong Lau No relevant relationships by Subha Saeed No relevant relationships by Anupam Sharma No relevant relationships by Muhammad Moiz Tahir

ADJUNCTIVE USE OF DISPOSABLE 1.1-MM CRYOPROBE WITH ROBOTIC-ASSISTED BRONCHOSCOPY

SESSION TITLE: Tales in Bronchoscopy SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: Peripheral pulmonary nodule biopsy can be challenging based on its location and size. Robotic bronchoscopy is augmenting peripheral navigation, allowing for approximation of peripheral nodules. The diagnostic yield is variable and is primarily dependent upon operator experience, selection of biopsy equipment and nodule texture. Hard pulmonary nodules are difficult to biopsy with a needle, brush and forceps. We report a case of utilizing combined disposable 1.1 mm cryoprobe and robotic bronchoscopy to diagnose a right lower lobe nodule. CASE PRESENTATION: A 83-year-old woman with a remote history of non-Hodgkin's lymphoma presented with dyspnea and fatigue. 18F-FDG PET/CT revealed a 2.7 cm hypermetabolic nodule with central photopenia in the right lower lobe (RLL) along with patchy bilateral ground-glass opacities related to COVID-19 infection. After a few weeks, robotic navigation was used for approximation of the RLL superior segment nodule. Under fluoroscopic and radial guidance with circumferential signal, 6 forcep biopsies and 5 fine needle aspirations with 21-gauge needle yielded a non-diagnostic sample. A decision was made to utilize a 1.1 mm disposable cryoprobe, which was inserted through the opening made by the forceps into the target lesion. Six cryo biopsies were obtained with 4-6 seconds freeze time. Minimal bleeding was encountered and no pneumothorax occurred. Histopathological examination revealed necrotizing granulomatous inflammation. DISCUSSION: To the best of our knowledge, this is the first reported case of combination 1.1 mm disposable cryoprobe biopsy with robotic bronchoscopy. Interventional pulmonologists are primarily using cryo probe for mechanical tumor debulking and peripheral lung biopsy for diagnosis of interstitial lung disease. The use of a 1.1 mm cryoprobe under robotic guidance allows for well-preserved tissue samples and possibly boosting diagnostic yield. The advantage of the 1.1 mm cryoprobe lies with its size and excellent flexibility. The robotic platform also corrects for any unwanted deflection. One limitation of using a flexible cryoprobe is its blunt tip, requiring an additional step in gaining access to nodules located outside the airway with either the biopsy needle or forceps. Future improvements in cryoprobe design with a sharp tip may address this limitation. CONCLUSIONS: Combining 1.1 mm disposable cryoprobe with robotic bronchoscopy is safe and can be considered as an adjunct to conventional biopsy, allowing for well-preserved tissue. Further prospective studies to evaluate its performance and safety is warranted. Reference #1: Kho SS, Chai CS, Nyanti LE, et al. Combination of 1.1 mm flexible cryoprobe with conventional guide sheath and therapeutic bronchoscope in biopsy of apical upper lobe solitary pulmonary nodule. BMC Pulm Med. 2020. 158(20). doi.org/10.1186/s12890-020-01199-3 Reference #2: Chen AC, Pastis NJ Jr, Mahajan AK, et al. Robotic Bronchoscopy for Peripheral Pulmonary Lesions: A Multicenter Pilot and Feasibility Study (BENEFIT). Chest. 2021;159(2):845-852. doi:10.1016/j.chest.2020.08.2047 Reference #3: Sahajal Dhooria, Inderpaul Singh Sehgal, Ashutosh NA Digambar Behera, Ritesh Agarwal. Diagnostic Yield and Safety of Cryoprobe Transbronchial Lung Biopsy in Diffuse Parenchymal Lung Diseases: Systematic Review and Meta-Analysis. Respiratory Care. 2016. 61(5):700-712. doi.org/10.4187/respcare.04488 DISCLOSURES: No relevant relationships by Sailendra Chundu No relevant relationships by Moiz Javed No relevant relationships by Abid Khokar No relevant relationships by Ali Saeed No relevant relationships by Andrew Talon No relevant relationships by Melinda Wang

SUPERIOR SAGITTAL SINUS THROMBOSIS PRESENTING AS DETERIORATING RESIDUAL WEAKNESS

SESSION TITLE: Imaging, ECMO, and other Procedures in the ICU Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Superior sagittal sinus (SSS) thrombosis is a rare cause of stroke that is difficult to identify due to various clinical presentations. It is the most common form of dural sinus thrombosis, and common risk factors include hypercoagulable state, traumatic head injury, pregnancy/postpartum, and malignancy. More than 85 percent of adult patients have at least one risk factor for cerebral venous thrombosis. Some patients with SSS thrombosis do not have clearly identifiable risk factors, and this case highlights one such patient. CASE PRESENTATION: A 60-year-old Caucasian male with hypertension, hyperlipidemia, and a recent intracranial hemorrhage with residual left-sided weakness, presented to the emergency department with worsening left-sided weakness. Upon admission, his physical exam was notable for 4/5 strength in the left upper extremity and 2/5 strength in the left lower extremity. This was a reduction in strength from a baseline of 4/5 in the left upper and lower extremities. Labs on admission were normal except for high-sensitivity troponin of 86 and WBC of 14.5. UA with a small amount of blood. An initial CT brain without contrast showed no acute changes, evolutionary changes in the right frontal temporal lobe, and subtle curvilinear hyperdensity near a site of the intracranial hemorrhage identified in the prior month. This curvilinear hyperdensity was thought to reflect early parenchymal calcification. MRI brain without contrast showed new and evolving areas of abnormal signaling and an evolving hematoma with surrounding vasogenic edema, all of which are in the right lobe. There was no apparent diffusion coefficient correlate. Thus, MRI with contrast and MRV was recommended. EEG showed no evidence of epileptiform activity. Additionally, transthoracic echo demonstrated new non-ischemic cardiomyopathy with an EF of 35-40%. The diagnosis was ultimately made after the patient had a Magnetic Resonance Venography (MRV) which showed evidence of the SSS thrombosis and an indication that the previously visualized curvilinear hyperdensity is suspected to represent slowed flow within a surface vein. Heparin was started to recanalize the sinus and prevent thrombus propagation. After the appropriate treatment was started, the patient's weakness improved dramatically. DISCUSSION: Typically, patients with SSS thrombosis have identifiable risk factors like hypercoagulable states, traumatic head injuries, pregnancy/postpartum, malignancy, and more recently association with COVID-19 infection. In this case, since the patient lacked identifiable risk factors, the MRV played a key role in the diagnosis. CONCLUSIONS: Like our patient, 30-40 percent of patients present with an intracerebral hemorrhage. Differentials of SSS thrombosis should be considered in etiologies for intracerebral hemorrhage, especially when an identifiable cause is lacking, in order to avoid delays in treatment and resolution. Reference #1: Abdalkader M, Shaikh SP, Siegler JE, Cervantes-Arslanian AM, Tiu C, Radu RA, Tiu VE, Jillella DV, Mansour OY, Vera V, Chamorro Á, Blasco J, López A, Farooqui M, Thau L, Smith A, Gutierrez SO, Nguyen TN, Jovin TG. Cerebral Venous Sinus Thrombosis in COVID-19 Patients: A Multicenter Study and Review of Literature. J Stroke Cerebrovasc Dis. 2021 Jun;30(6):105733. doi: 10.1016/j.jstrokecerebrovasdis.2021.105733. Epub 2021 Mar 4. PMID: 33743411;PMCID: PMC7931726. Reference #2: Rehman A, Husnain MG, Mushtaq K, Eledrisi MS. Cerebral venous sinus thrombosis precipitated by Graves’ disease. BMJ Case Rep. 2018 Jun 4;2018:bcr2017224143. doi: 10.1136/bcr-2017-224143. PMID: 29866676;PMCID: PMC5990097. Reference #3: Nakase H, Takeshima T, Sakaki T, Heimann A, Kempski O. Superior sagittal sinus thrombosis: a clinical and experimental study. Skull Base Surg. 1998;8(4):169-74. doi: 10.1055/s-2008-1058178. PMID: 17171061;PMCID: PMC1656696. DISCLOSURES: No relevant rel tionships by Ken Johnson No relevant relationships by Nina Le No relevant relationships by Riaz Mahmood No relevant relationships by Ngoc Phan

CASE REPORT: USE OF THE SERAPH-100 BLOOD FILTER IN LINE WITH EXTRACORPOREAL MEMBRANE OXYGENATION CIRCUIT FOR TREATMENT OF SEPTIC SHOCK FROM ENTEROCOCCUS FAECALIS BACTEREMIA

SESSION TITLE: Close Critical Care Calls SESSION TYPE: Case Reports PRESENTED ON: 10/18/2022 11:15 am - 12:15 pm INTRODUCTION: With the development of resistant organisms, additional therapies are needed to effectively treat patients with severe infections. The Seraph®-100 Microbind Affinity Blood Filter utilizes immobilized heparinized microbeads, acting similar as the human glycocalyx, to bind and remove these substrates. In vitro and pre-clinical studies have shown up to 99% clearance of Enterococcus faecalis exposed to the Seraph®-100 blood filter. This novel extracorporeal blood purification system could assist with infection source control and reduction of vasopressor requirements. CASE PRESENTATION: A 30-year-old male with no significant past medical history was admitted due to severe ARDS secondary to COVID-19 infection and required extracorporeal membrane oxygenation (ECMO) after an unsuccessful trial of conventional supportive therapies. The patient's hospital course was complicated by multiple infections, including bacteremia from methicillin susceptible Staphylococcus aureus, candidemia and Enterobacter ventilator associated pneumonia. These infections initially improved with use of appropriate intravenous antimicrobials. However, the patient experienced an acute hemodynamic decompensation requiring multiple vasoactive medications. He was empirically started on broad spectrum anti-microbials including meropenem, vancomycin, and isavuconazole. Blood cultures revealed Enterococcus faecalis, susceptible to broad-spectrum antibiotics. After 24 hours of broad-spectrum antimicrobials without improvements in vasopressor requirements, the Seraph-100® blood filter was used in-parallel with the ECMO circuit. Immediate improvement in vasopressors was noted with discontinuation of vasopressin and decrease in norepinephrine by 75%. The patient finished a 2-week course of intravenous ampicillin/sulbactam. His respiratory status subsequently improved and he was able to be removed from ECMO 24 days later. DISCUSSION: Initial studies have shown the Seraph-100 is capable of clearing the SARS-Cov-2 virus and use has been associated with decreased mortality in patients with SARS-Cov-2. The ability to remove additional pathogens including bacteria, fungi and viruses would aid in obtaining source control and augment the effects of intravenous antibiotics. This case not only illustrates the benefits with the use of the Seraph ®-100 blood filter along with broad spectrum antibiotics, but also the ability to use this extracorporeal blood purification system in-line with ECMO. CONCLUSIONS: With the emergence of multi-drug resistant pathogens, additional treatment options are urgently needed. The Seraph®-100 may be a useful adjunct to broad spectrum antimicrobials and may improve hemodynamics in patients with vasopressor-dependent septic shock. Further prospective studies are needed to assess clinical improvements with the use of the Seraph-100 Microbind blood filter in patients with bacteremia and those requiring ECMO. Reference #1: Olson SW, Oliver JD, Collen J, et al. Treatment for Severe Coronavirus Disease 2019 With the Seraph 100 Microbind Affinity Blood Filter. Critical Care Explor. 2020;2(8):e0180. Reference #2: Chitty, Stephen, Mobbs, Sarah, Chung, Kevin et al., for the PURIFY INVESTIGATORS. A Multicenter Evaluation of Blood Purification with Seraph 100 Microbind Affinity Blood Filter for the Treatment of Severe COVID-19: A Preliminary Report. medRxiv 2021.04.20.21255810;doi: https://doi.org/10.1101/2021.04.20.21255810 Reference #3: Seffer, Malin-Theres, et al. "Heparin 2.0: a new approach to the infection crisis.” Blood Purification 50.1 (2021): 28-34. DISCLOSURES: No relevant relationships by Joshua Boster No relevant relationships by Henry Danchi Speaker/Speaker's Bureau relationship with Janssen Please note: $1001 - $5000 by Michael Morris, value=Honoraria Speaker/Speaker's Bureau relationship with GSK Please note: $1001 - $5000 by Michael Morris, value=Honoraria Removed 03/29/2022 by Michael Morris No releva t relationships by Mai Nguyen No relevant relationships by Melissa Rosas No relevant relationships by Steven Stoffel No relevant relationships by Robert Walter

A RARE PRESENTATION OF COVID-19-ASSOCIATED CENTRAL VENOUS THROMBOSIS

SESSION TITLE: COVID-19 Case Report Posters 3 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Due to a wide range of clinical presentations, central venous thrombosis (CVT) is a rare neurologic condition that can be difficult to diagnose. Since the COVID-19 pandemic, more cases of venous thromboembolic events have emerged and been found associated with COVID-19. We detail a potential case of COVID-19 associated CVT. CASE PRESENTATION: A 28-year-old female with past medical history of obesity, polycystic ovary syndrome, recurrent sinusitis, and presumed history of COVID-19 infection with anosmia, ageusia, and sinusitis symptoms three- months prior presented to the hospital with 1-month history of worsening, right-sided pain behind her ear, eye, head, posterior neck and shoulder, nausea, and photophobia, which had worsened in the last 5 days. She initially tried over-the-counter medications with no improvement. Vital signs were unremarkable. Examination was notable for frontal sinus and right postauricular tenderness to palpation. C- reactive protein was elevated at 26.2 mg/L. Non- contrasted brain computed tomography (CT) was concerning for right transverse sinus and superior sagittal sinus thrombosis. Brain magnetic resonance imaging (MRI) showed early signs of cortical edema and venous infarction and findings concerning for right mastoiditis. Intracranial venous MRI showed complete thrombosis of the right transverse and sigmoid sinus, superior sagittal sinus, and most of the superior draining cortical veins. Heparin drip was started. Initial empiric antibiotics for mastoiditis were stopped. Hyper-coagulopathy work-up with beta- 2 glycoprotein 1 antibodies and phospholipid antibodies were negative. As there were no other inciting factors for CVT found and no history of positive COVID-19 test, a COVID-19 antibody immunoassay was obtained and returned positive. The patient did not have a history of COVID vaccination. She was discharged on warfarin and enoxaparin. Anticoagulation was stopped after 6 months with repeat imaging showing resolution of clot burden. DISCUSSION: Usual risk factors associated with CVT are morbid obesity, hormone replacement therapy, oral contraceptive use, hereditary thrombophilia, and pregnancy. Literature on CVT related to COVID-19 is limited. In 41 documented cases, the average age of incidence is 50 years old and median onset of neurological symptoms from initial COVID-19 diagnosis is 7 days [0 to 21 days]. Our patient's neurological symptoms began about 3 months after her initial diagnosis, potentially making it the first known case of COVID-19 associated CVT with symptom onset past 21 days. Anticoagulation is the mainstay treatment for CVT, and duration depends on the presence of provoking factor. CONCLUSIONS: In patients with new neurologic symptoms and recent diagnosis of COVID-19, CVT should be considered in the differential diagnosis as it can initially present in a subtle manner. Early recognition could improve patient morbidity and mortality. Reference #1: Abdalkader, M., Shaikh, S. P., Siegler, J. E., Cervantes-Arslanian, A. M., Tiu, C., Radu, R. A., Tiu, V. E., Jillella, D. v., Mansour, O. Y., Vera, V., Chamorro, Á., Blasco, J., López, A., Farooqui, M., Thau, L., Smith, A., Gutierrez, S. O., Nguyen, T. N., Jovin, T. G. (2021). Cerebral Venous Sinus Thrombosis in COVID-19 Patients: A Multicenter Study and Review of Literature. Journal of Stroke and Cerebrovascular Diseases. https://doi.org/10.1016/j.jstrokecerebrovasdis.2021.105733 Reference #2: Idiculla, P. S., Gurala, D., Palanisamy, M., Vijayakumar, R., Dhandapani, S., Nagarajan, E. (2020). Cerebral Venous Thrombosis: A Comprehensive Review. European Neurology (Vol. 83, Issue 4). https://doi.org/10.1159/000509802 Reference #3: Ostovan VR, Foroughi R, Rostami M, et al. Cerebral venous sinus thrombosis associated with COVID-19: a case series and literature review. Journal of Neurology. 2021 Oct;268(10):3549-3560. DOI: 10.1007/s00415-021-10450-8. PMID: 33616740;PMCID: PMC7897893. DI CLOSURES: No relevant relationships by Shu Xian Lee No relevant relationships by Arif Sarwari No relevant relationships by Benita Wu

Mental, physical, and cognitive impairments of COVID-19 patients admitted to intensive care during the pandemic in Chile: An observational, multicentre study

Introduction: Mental, physical, and cognitive impairments are common after an intensive care unit (ICU) stay. It remains unknown to what extent the extraordinary increase in bed occupancy during the pandemic could be linked to the severity and frequency of patient's impairments. Objective: To determine the frequency, severity, and risk factors for mental, physical, and cognitive impairments at ICU discharge during high and low bed occupancy periods. Methods: Prospective cohort study in seven Chilean ICUs (ClinicalTrials.gov Identifier: NCT04979897). We included adults, mechanically ventilated >48 hours in the ICU who could walk independently prior to admission. Trained physiotherapists assessed the Medical Research Council Sum-Score (MRC-SS), Montreal Cognitive Assessment (MOCA-blind), Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale-Revised (IES-R), and the World Health Organization Disability Assessment Schedule (WHODAS 2.0) at ICU discharge. Pre-admission employment status, educational level, and Clinical Frailty Scale (CFS) were also collected. We compared periods of low and high bed-occupancy, defined as less or more than 90% of staffed ICU beds occupied. We used t-test for normally distributed, Mann-Whitney for those not normally distributed, and chi-square for categorical variables. We explored risk factors for mental, physical, and cognitive impairments using logistic regression adjusted for age, sex, educational level, and bed occupancy. Analyses were performed in Stata/SE 16.0. Results: We included 192 patients with COVID-19 of which 126 [66%] were admitted during a high bedoccupancy period (January to April 2021). Majority were male (137 [71%]) and worked full-time (127 [66%]). Median [P25-P75] age was 57 [47-67], length of ICU stay was 15[ 11-27] days, and duration of mechanical ventilation (MV) was 9 [6-16.5] days. Seven (4%) patients were clinically frail, 65 (34%) had ICUacquired weakness (ICU-AW), 134(70%) had cognitive impairment, 122 (64%) had post-traumatic stress symptoms (PTSS), 53 (28%) had depressive symptoms, 106 (55%) had anxiety symptoms, and 148 (77%) had severe disability. Table 1 shows the combined prevalence of physical and mental health problems. Patients admitted during the high-occupancy period were younger (mean 54, 95% confidence interval [47, 61] vs 61 [58, 64]), more likely to have a higher education qualification(HEQ) (OR 1.67 [0.9, 3.06]), and had a shorter duration of MV (8 [6-13] vs 13 [8-34];p<0.001) and ICU stay (13 [10-19] vs 21.5 [13-42];p<0.001). Mental, physical, and cognitive impairments were similar in low and high occupancy periods. Patients with a HEQ were less likely to have ICU-AW (OR 0.23 [0.11, 0.46]), cognitive impairments (OR 0.26 [0.11, 0.6]), symptoms of depression (OR 0.45 [0.22, 0.9]) or anxiety (OR 0.26 [0.13, 0.5]), and severe disability (OR 0.4 [0.18, 0.94]). Females were more likely to have ICU-AW (OR 2.4 [1.13, 4.93]). Older patients were less likely to suffer PTSS (OR 0.97 [0.94, 0.99] per year old). Conclusions: Majority of patients had at least one mental, physical or cognitive impairment being similar by bed occupancy. Having a higher education qualification was the main protective factor for impairments at ICU discharge. Preventative treatments programmes should target patients with <12 years of education.

Defendor: Real-world evidence of primary prolonged G-CSF prophylaxis by empegfilgrastim for relative dose intensity compliance in patients with solid tumors- The primary analysis

Background: Maintaining relative dose intensity (RDI) of chemotherapy is important to ensure optimal patient outcomes in a variety of solid cancers. RDI < 85% significantly decrease therapy efficiency (including overall survival) in almost solid tumors (ST). Chemotherapy-induced neutropenia (CIN) is the most common adverse event (AE) leading to low RDI. Proper administration of primary G-CSF prophylaxis (PP) allows to achieve optimal therapy efficiency. There are several trials and meta-analyses have shown a superior efficiency prolonged G-CSF vs short G-CSF. This multicenter prospective observational post-registration study of prolonged G-CSF empegfilgrastim (Extimia) was designed to evaluate the RDI of the cytotoxic therapy course under PP by empegfilgrastim in patients (pts) with ST receiving myelosuppressive therapy in the routine clinical practice. Methods: 2000 pts with ST receiving cytotoxic therapy (4-8 cycles per course are allowed) under PP with empegfilgrastim by investigator choice in the routine clinical practice. RDI of therapy course was primary endpoint and presented here for pts who completed the planned regimen. For each agent, both the planned and actual dose intensity were calculated by dividing the total cumulative dose by treatment duration in days. RDI was calculated for each single agent in chemotherapy-based (CTb) regimen and for CTb regimen in total. These descriptive analyses and RDI calculations were performed for the whole CT based regimen (chemotherapeutic agents, molecular target agents, monoclonal antibodies). Funded by JSC Biocad;Defendor Clinical-Trials.gov No NCT04811443. Results: At the data cut-off 1074 pts from 31 Russian sites underwent ≥ one cycle of CTb regimens combined with empegfilgrastim. Distribution of all-cancer types was in line with epidemiology data in Russia. 526 pts completed the planned CT course. 352 (66,9%) of them have at least one of FN risk factor. RDI≥85% were achieved in 492 (93,5%) pts. RDI by key nosology is presented in Tab.1. 118 (22,4%) cases of interval prolongation and/or dose reduction was registered. The main reasons of RDI decrease were personal pts's issues 69 (13,1%), COVID-19 pandemic 26 (4,9%), holidays 9 (1,7%) and others. Neutropenia was in 6 (1,1%) cases as a reason of RDI decrease. Treatment-related AEs of grade 1-2 occurred 12 (2,3%) pts (back pain, ossalgia, myalgia). Conclusions: Thus, PP with prolonged G-CSF empefilgrastim allows effectively maintain RDI in different nosology and treatment groups in pts with ST in the routine clinical practice.