Direct costs of hospital care according to coinfection in adult COVID-19 patients

Objective: To estimate the direct costs of hospital care according to coinfection in adult COVID-19 patients. Material(s) and Method(s): A retrospective follow-up study of adult patients hospitalized for COVID-19 between March and August 2020 at the San Vicente Foundation Hospitals (Medellin and Rionegro, Colombia). Patients whose diagnosis of SARS-Cov2 pneumonia was confirmed by RT-PCR test were included. Death from any cause and length of stay were considered outcome variables. Costs were estimated in 20 20 US dollars. Result(s): 365 patients with an average age of 60 years (IQR: 46-71), 40% female, were analyzed. 60.5% required an Intensive Care Unit (ICU). All-cause mortality was 2.87 per 100 patient-days. Patients admitted to the ICU who developed coinfection had an average length of stay of 27.8 days (SD:17.1) and an average cost of $23,935.7 (SD: $16,808.2);patients admitted to the ICU who did not develop a coinfection had an average length of stay of 14.7 days (SD:8.6) and an average cost of $9,968.5 (SD: $8,054.0). Conclusion(s): A high percentage of patients required intensive care, and there was a high mortality due to COVID-19. In addition, a higher cost of care was observed for those patients who developed coinfection and were admitted to ICU.Copyright © 2023 Asociacion Colombiana de Infectologia. All rights reserved.

Reproduction of the Control Group in REMDACTA Trial Using the Millennial Medical Record, an Electric Health Record Database, in Japan

Objectives: Developing a control group of a clinical trial using real world data is desirable and ethically sound despite challenges pertaining to internal validity. To examine the internal validity, we reproduced the control group in a Randomized Controlled Trial (RCT) using Electric Health Record (EHR) data and evaluated the difference between the outcome of the original trial and that of the reproduced analysis. Method(s): We selected an RCT, REMDACTA trial, that was performed to evaluate the efficacy of tocilizumab plus remdesivir against placebo plus remdesivir in patients with severe COVID-19 pneumonia. We reproduced its control group (patients with severe COVID-19 pneumonia taking only remdesivir), using Japanese EHR data, Millennial Medical Record provided by Life Data Initiative. Target patients for the main analysis were those prescribed remdesivir within 2 days after admission and diagnosed with COVID-19 (defined by ICD-10 code, U07.1) and/or with COVID-19 pneumonia (defined by diagnosis name). Patients in the sub analysis included only those with COVID-19 pneumonia diagnosis. Among the target patients, those undergoing image inspection, oxygen administration, and not taking any medicines for pneumonia before the first remdesivir prescription were eligible for the analyses. Median length of stay was compared in the reproduced group and in REMDACTA trial. Result(s): The database included 676 and 110 target patients for the main and sub analyses, respectively. However, only 57 and 14 patients met the eligibility criteria for the main and sub analyses, respectively. The reduction in the number of patients is attributed to the criteria of image inspection and oxygen administration. Median length of stay in the reproduced group were 13 and 11 days in the main and sub analyses, respectively. In REMDACTA trial, 95% CI of median time was 11.0-16.0. Conclusion(s): We successfully reproduced the median time of the control group by EHR data.Copyright © 2023

Medical intensivist directed VV ECMO cannulation for the facilitation of tracheostomy in a patient with severe tracheal stenosis: A case report

Objectives: We present a case report of medical intensivist driven ECMO program using ECMO as a pre-procedural tool to maintain oxygenation in a patient with critical tracheal stenosis during tracheostomy placement. Method(s): VV ECMO is primarily used to support patients when mechanical ventilation is unable to provide adequate gas exchange. Alternatively, it has been used pre-procedurally when intubation is required in anticipation of a difficult airway. Described here is the first intensivist preformed awake VV ECMO cannulation to facilitate tracheostomy in a patient with severe tracheal stenosis. Result(s): The patient is a 41-year-old female with the relevant background of COVID19 pneumonia status post tracheostomy and subsequently decannulated after prolonged intubation and ICU stay. As a result, the patient developed symptomatic tracheal stenosis and presented two years after her ICU stay for scheduled bronchoscopy and balloon dilation. However, the patient developed worsening stridor and shortness of breath requiring heliox and BPAP. After multidisciplinary discussion between the critical care team ENT teams, the decision was made to cannulate for VV ECMO as a pre-procedural maneuver to allow for oxygenation during open tracheostomy in the OR. Dexmedetomidine and local anesthesia were used for the procedure with the patient sitting at 30 degrees on non-invasive ventilation and heliox. The patient was cannulated with a 21F right internal jugular return cannula and 25F right common femoral drainage cannula by medical intensivists in the intensive care unit using ultrasound guidance. The patient went for operative tracheostomy the next day and was subsequently decannulated from ECMO the following day without complication. She was discharged home on trach collar. Conclusion(s): Intensivist performed ECMO cannulation has been shown to be safe and effective. We anticipate the indications and use will continue to expand. This case is an example that intensivist driven preprocedural ECMO is a viable extension of that practice.

A New Registry for Genetic Diagnosis of Inborn Errors of Immunity within the Military Health System

Genotypic definition of monogenic inborn errors of immunity (IEIs) continues to accelerate with broader access to next generation sequencing, underscoring this aggregated group of disorders as a major health burden impacting both civilian and military populations. At an estimated prevalence of 1 in 1200 individuals, IEIs affect ~8,000 patients within the Military Health System (MHS). Despite access to targeted gene/exome panels at military treatment facilities, most affected patients never receive a definitive genetic diagnosis that would significantly improve clinical care. To address this gap, we established the first registry of IEI patients within the MHS with the goal of identifying known and novel pathogenic genetic defects to increase diagnosis rates and enhance clinical care. Using the registry, a research protocol was opened in July 2022. Since July we have enrolled 75 IEI patients encompassing a breadth of phenotypes including severe and recurrent infections, bone marrow failure, autoimmunity/autoinflammation, atopic disease, and malignancy. Enrolled patients provide blood and bone marrow samples for whole genome, ultra-deep targeted panel and comprehensive transcriptome sequencing, plus cryopreservation of peripheral blood mononuclear cells for future functional studies. We are also implementing and developing analytical methods for identifying and interrogating non-coding and structural variants. Suspected pathogenic variants are adjudicated by a clinical molecular geneticist using state-of-the-art analysis pipelines. These analyses subsequently inform in vitro experiments to validate causative mutations using cell reporter systems and primary patient cells. Clinical variant validation and return of genetic results are planned with genetic counseling provided. As a proof of principle, this integrated genetic evaluation pipeline revealed a novel, candidate TLR7 nonsense variant in two adolescent brothers who both endured critical COVID-19 pneumonia, requiring mechanical ventilation and extracorporeal membrane oxygenation. Our protocol is therefore poised to greatly enrich clinical genetics resources available in the MHS for IEI patients, contributing to better diagnosis rates, informed family counseling, and targeted treatments that collectively improve the health and readiness of the military community. Moreover, our efforts should yield new mechanistic insights on immune pathogenesis for a broad variety of known and novel IEIs.Copyright © 2023 Elsevier Inc.

COVID-19 pneumonia - increased incidence of pneumothorax/mediastinal emphysema after invasive mechanical and non-invasive ventilation.

Introduction: COVID pneumonia can lead to pneumomediastinum or pneumothorax during non-invasive or invasive mechanical ventilation. This affects the prognosis. Methodology: During the study period, 121 patients with SARS-CoV-2 infections and invasive or non-invasive ventilation therapy were recorded in our hospital. All patients with a pneumothorax or pneumomediastinum were analyzed in more detail. Result(s): Pneumothorax and pneumomediastinum occurred in 12 patients and resulted in 7 deaths. Discussion(s): The incidence of pneumothorax with COVID infection ranges from 0.56 to 1%, reaching 3.5% in our own studies and 4.2% under invasive mechanical ventilation. The incidence of pneumomediastinum was 10% and 9.2% in our own patients. Overall mortality was 58.3% and similar to that reported in the literature, up to 60%.Copyright © 2023 Dustri-Verlag Dr. K. Feistle.

Teclistamab in combination with daratumumab and lenalidomide in multiple myeloma (MajesTEC-2 study)

Introduction: Combination of daratumumab (Dara) and lenalidomide (Len) may enhance the function of teclistamab (Tec), potentially resulting in improved antimyeloma activity in a broader population. We present initial safety and efficacy data of Tec-Dara- Len combination in patients with multiple myeloma (MM) in a phase 1b study (MajesTEC-2;NCT04722146). Method(s): Eligible patients who received 1-3 prior lines of therapy (LOT), including a proteasome inhibitor and immune-modulatory drug, were given weekly doses of Tec (0.72-or- 1.5 mg/kg with step-up dosing) + Dara 1800 mg + Len 25 mg. Responses per International Myeloma Working Group criteria, adverse events (Aes) per CTCAE v5.0, and for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) per ASTCT guidelines, were assessed. Result(s): 32 patients received Tec-Dara- Len (0.72 mg/kg, n = 13;1.5 mg/kg, n = 19). At data cut-off (11 July 2022), median follow-up (range) was 5.78 months (1.0-10.4) and median treatment duration was 4.98 months (0.10-10.35). Median age was 62 years (38-75);87.5% were male. Median prior LOT was 2 (1-3), 18.8% were refractory to Dara and 28.1% refractory to Len. CRS was most frequent AE (81.3% [n = 26], all grade 1/2), 95% occurred during cycle1. Median time to onset was 2 days (1-8), median duration was 2 days (1-22). No ICANS were reported. Frequent Aes (>=25.0% across both dose levels) were neutropenia (75.0% [n = 24];grade 3/4: 68.8% [n = 22]), fatigue (43.8% [n = 14];grade 3/4: 6.3% [n = 2]), diarrhoea (37.5% [n = 12];all grade 1/2), insomnia (31.3% [n = 10];grade 3/4: 3.1% [n = 1]), cough (28.1% [n = 9];all grade 1/2), hypophosphatemia (25.0% [n = 8];all grade 1/2), and pyrexia (25% [n = 8];grade 3/4: 6.3% [n = 2]). Febrile neutropenia frequency was 12.5% (n = 4). Infections occurred in 24 patients (75.0%;grade 3/4: 28.1% [n = 9]). Most common were upper respiratory infection (21.9% [n = 7]), COVID-19 (21.9% [n = 7]), and pneumonia (21.9% [n = 7]). Three (9.4%) had COVID-19 pneumonia. One (3.1%) discontinued due to COVID-19 infection and this patient subsequently died of this infection. Overall response rate (ORR, median follow-up) was 13/13 (8.61 months) at 0.72 mg/kg and 13/16 evaluable patients (less mature at 4.17 months) at 1.5 mg/kg. 12 patients attained very good/better partial response at 0.72 mg/kg dose, and response was not mature for 1.5 mg/kg group. Median time to first response was 1.0 month (0.7-2.0). Preliminary pharmacokinetic concentrations of Tec-Dara- Len were similar as seen with Tec monotherapy. Tec-Dara- Len- treatment led to proinflammatory cytokine production and T-cell activation. Conclusion(s): The combination of Tec-Dara- Len has no new safety signals beyond those seen with Tec or Dara-Len individually. Promising ORR supports the potential for this combination to have enhanced early disease control through the addition of Tec. These data warrant further investigation.

Pregnancy Outcomes in Women with Sickle Cell Disease in Ireland: A Retrospective Review

Background: Sickle cell disease (SCD) is one of the most common single gene disorders worldwide and is characterised by significant morbidity and early mortality.[1] Pregnancy in SCD is associated with an increased risk of maternal and foetal complications.[2,3] The 2011 RCOG and the 2021 BSH guidelines[5,6] on the management of pregnancy in SCD have provided the basis for best practice care in the UK over the past decade and is the guidance which we follow in Ireland. To date, there is no published data on outcomes for pregnant women with SCD in Ireland. The number of Irish patients with SCD has risen over the past 20 years. Without a national database, the exact prevalence is not known but currently there are at least 600 adults and children with SCD in Ireland, whose population is just over 5 million.[4] Aims: Our study assesses outcomes of pregnant patients with SCD from 2015 to 2022. Our aims were to: * Assess adherence to current guidelines * Assess pregnancy outcomes and maternal complications * Assess transfusion rates amongst our patient cohort. Method(s): This is a retrospective cohort study. We do not have a directly matched cohort, but have compared our findings to published data on Irish pregnancy outcomes from the Irish Maternity Indicator System National Report and have correlated our findings with studies of women with SCD who were managed in UK centres.[8,9,10] Results: We reviewed outcomes of 29 pregnancies in 19 women over a 7-year period. The median age was 29 (range 20-41) and the predominant maternal sickle genotype was HbSS (65.5%). Before conception, 55.2% of cases had pre-existing complications of SCD, including acute chest syndrome (ACS), pulmonary hypertension (PHTN) and prior stroke. In accordance with current guidelines, 100% of women (n=29) were prescribed folic acid, penicillin, and aspirin prophylaxis. 51.7% (n=15) of women had documented maternal complications during pregnancy, including ACS (34%), vaso-occlusive crisis (34%), gestational diabetes (10%), VTE (3%) and UTI (3%). Two women (7%) developed Covid-19 pneumonitis despite vaccination. There was one case of maternal bacteraemia (3%). 65.5% of cases (n=19) required blood transfusion during pregnancy. One woman was already on a blood transfusion programme for disease modification prior to pregnancy. In 6 cases (20.6%), a transfusion programme was commenced during pregnancy due to prior pregnancy complications or intrauterine growth restriction. During pregnancy, 27.6% (n=8) of women required emergency red cell exchange for ACS. Prior studies have suggested that between 30% and 70% of pregnant women with SCD require at least one blood transfusion during pregnancy.[8,9,10] By comparison, only 2.6% of the Irish general obstetric population required transfusion during pregnancy.[7] 20.6% (n=6) of births were preterm at <37 weeks' gestation. There was one live preterm birth (3%) at <34 weeks and one intrauterine death (3%) at 23 weeks' gestation. Similar to UK data[9], 31% of women required critical care stay (n=9) during pregnancy, in comparison with 1.44% nationwide in 2020.[7] Conclusion(s): It is well established that pregnancy in SCD is high risk, and despite adherence to current guidelines, we have shown very high rates of critical care admission, significant transfusion requirement and hospital admissions. Our findings are comparable to published UK outcomes and they further support the need for a comprehensive specialist care setting for this patient cohort.

Long-term functional outcome of severe COVID19 pneumonia treated with venovenous extracorporeal membrane oxygenation support - learnings from a single centre

Objectives: Implementation of venovenous extracorporeal membrane oxygenation (VVECMO) allowed survival of patients with severe respiratory failure associated with SARS-CoV-2 infection. However, VVECMO treatment is usually associated with long ICU stays, prolonged sedation, and neuromuscular blockage days. Functional disability, due to delirium and acquired muscle weakness, is frequently an inevitable burden causing long term disability. This study aims to analyse main characteristics of patients under ECMO due to COVID-19 pneumonia, their outcomes and functional status six months after ICU discharge. Method(s): Retrospective review of a prospectively collected database in an ECMO referral centre. All patients receiving VVECMO for SARS-CoV-2 infection were included. Epidemiological and clinical data were reviewed. Functional status at 6 months after ICU discharge was assessed with modified Rankin Scale (mRS). Result(s): Ninety-three patients were included (29% female). Median age was 54+/-12 years, mean SOFA was 5.7+/-2.9, mean SAPS II was 35.6+/-13.6. Mean time from intubation to cannulation was 5+/-5.6 days in 91 patients;awake-ECMO was performed in 2 patients. Mean ECMO run duration was 33.1+/-30 days (longest ECMO run was 194 days). A period of awake-ECMO was performed on 36.5% of patients, during 16.4+/-21.2 days. ICU-acquired weakness was diagnosed on 64.5% of patients and delirium on 63.4%. Mortality was 24.7% (23 patients) with only 1 patient deceased in hospital after ICU discharge. At 6 months follow-up, all patients were still alive and most of them (65.1%) were independent on all daily activities (mRS <= 2). Conclusion(s): Patients with severe COVID-19 treated with VVECMO support had very good functional outcomes at six-month follow-up. Despite long ICU length-of-stay, high incidence of delirium and acquired muscle weakness, full recovery at six-month post-ICU discharge was achievable in most patients.

Hemoperfusion with CytoSorb as Adjuvant Therapy in Critically Ill Patients with SARS-CoV2 Pneumonia

Background: Several pro- and anti-inflammatory cytokines involved in COVID-19 and it is reasonable to speculate that their removal from blood might limit organ damage. Hemoperfusion with CytoSorb is a technique developed to adsorb molecules in the middle molecular weight range (up to 55 kDa). Studies in vitro and in vivo have shown that HP is highly effective in clearing blood from a number of cytokines. Method(s): We report a case series of 9 consecutive COVID-patients admitted to our COVID Intensive Care Unit (ICU). Five of them were treated with HP using CytoSorb (T), due to the heavy emergency overload it was impossible to deliver blood purification in the other 4 patients (C), who were also considered as potential candidates by the attending medical team. All patients had pneumonia and respiratory failure requiring continuous positive airway pressure. Different antibacterial prophylaxes, antiviral, and anti-inflammatory therapies including steroids were delivered. Result(s): Our results show a better clinical course of T compared to control patients (C), in fact all T except 1 survived, and only 2 of them were intubated, while all C required intubation and died. CRP decreased in both groups, but to a greater extent after HP. Lymphocytopenia worsened in control patient but not in treated patient after HP. Procalcitonin increased in 2 of the not treated patients. In all survived patients (n = 4) HP reduced pro-inflammatory cytokines, as IL-6, TNF-alpha, and IL-8. Notably, a striking effect was observed on IL-6 levels that at the end of the second session were decreased by a 40% than before the first treatment. Serum levels of IL-8 and TNF-alpha were lowered within normal range. In all patients the treatment was safe and there were no complications. Conclusion(s): Our study suggests a potential efficacy of HP in an early phase of viral infection not only for improving survival in the treated patients but also by the remodeling treatment-associated cytokine levels.

The effectiveness of Tocilizumab in severe covid 19 pneumonia among critically ill patients

Background: Tocilizumab, an interleukin-6 (IL-6) antagonist, is being evaluated for the management of covid-19 pneumonia. The objective of this study was to assess the effectiveness of Tocilizumab in severe covid-19 pneumonia. Method(s): This was a retrospective, observational, single centre study performed in 121 patients diagnosed with severe covid-19 pneumonia. 83 patients received standard of care treatment whereas 38 patients received tocilizumab along with standard of care. Tocilizumab was administered intravenously at 8mg/kg (upto a maximum of 800mg). The second dose of Tocilizumab was given 12 to 24 hours apart. The primary outcome measure was ICU related and hospital related mortality. The secondary outcome measures were change in clinical status of patients measured by WHO (World Health Organisation) 7 category ordinary scale, changes in interleukin-6 (IL-6) levels, secondary infections and duration of ICU stay. Result(s): Tocilizumab was administered between 3-27 days after the patient reported symptoms ( a median of 10.9 days ) and between the 1st to 3rd day of ICU admission (median of 2.1 days) . In Tocilizumab group, 16(42.1%) of 38 patients died in ICU whereas in standard of care group, 27(32.53%) of 83 patients died. The difference in clinical status assessed using WHO (World Health Organisation) 7 category ordinary scale at 28 days between Tocilizumab group and standard of care group was not statistically significant (odds ratio 1.35, 95% confidence interval 0.61 to 2.97, p = 0.44). Conclusion(s): Tocilizumab plus standard care was not superior to standard care alone in reducing mortality and improving clinical outcomes at day 28.Copyright © RJPT All right reserved.

Anaesthetic Management for A Patient Presenting for Caesarean Delivery with A giant Thymoma - A Case Report

Presentation of a thymoma during pregnancy means that safe delivery becomes more challenging. We present a 33-year-old pregnant woman who was diagnosed with a large thymoma causing marked compression of the tracheobronchial tree and right atrium. After various multidisciplinary meetings she presented for elective caesarean section delivery at 31 weeks of gestation. A combined spinal-epidural anaesthesia was performed, along with colloid pre-and co-loading, and vasopressor support. The delivery was uneventful. The possibility of catastrophic complications was foreseen. Therefore, all requirements for the possibility of airway or haemodynamic collapse were planned carefully, including the possibility of emergent cardiopulmonary bypass.Copyright © 2023, College of Anaesthesiologists of Sri Lanka. All rights reserved.

Evaluation of Lung Ultrasound in Assessment of Critically Ill patients in Respiratory Intensive Care Unit

Reaching a proper diagnosis for critically ill patients is like collecting pieces of puzzle and bed side lung ultrasound (LUS) becomes a crucial piece complementary to clinical and laboratory pieces. It is a bed side, real time tool for diagnosis of patients in ICU who are critical to be transferred to radiology unit especially in Covid-19 pandemic with risk of infection transmission. The aim was to evaluate the accuracy of lung ultrasound in assessment of critically ill patients admitted to Respiratory Intensive Care Unit (RICU), moreover to assess its diagnostic performance in different pulmonary diseases as compared to the gold standard approach accordingly. This observational prospective (cross sectional) study with a total 183 patients who met the inclusion criteria,were selected from patients admitted at the RICU;Chest Department, Zagazig University Hospitals, during the period from September 2019 to September 2021. LUS examination was performed to diagnose the different pulmonary diseases causing RF. All cases were examined by LUS on admission. From a total 183 patients, 111 patients 60.7% were males and 72 patients 39.3% were females, with a mean age of 56+/-12.77 years, 130 patients were breathing spontaneously received conservative management with O2 therapy, 32 patients needed NIV while 21 patients needed IMV with ETT. Exacerbated COPD was the most common disease finally diagnosed followed by bacterial pneumonia, exacerbated ILD, post Covid-19 fibrosis and pulmonary embolism in32, 29,27, 19 and 11 patients respectively with corresponding diagnostic accuracy of LUS 97.3%, AUC=0.943, 93.9% (AUC=0.922), 96.7%(AUC=0.920), 97.8%, AUC=0.895, and 97.8% respectively, while Covid-19 pneumonia was the final diagnosis in 8 patients with LUS diagnostic accuracy of 97.8% (AUC=0.869) with no statistical significant difference p-value=0.818 with bacterial pneumonia in distribution of US profiles. A profile was the commonest detected US profile among the studied patients followed by B profile, C profile, A/B profile and A' profile in 37.2%, 24.6%, 15.8% 4.9%, and 3.8% of cases respectively. Bed side LUS has a reliable, valuable diagnostic performance when integrated with clinical and laboratory data for the diagnosis of most pulmonary diseases in RICU.Copyright © 2023, Colegio de Farmaceuticos de la Provincia de Buenos Aires. All rights reserved.

Procalcitonin and NLR Measurements in COVID-19 Patients

The disease COVID-19 is brought on by SARS-CoV-2, a brand-new coronavirus. Following its detection by the WHO, this novel virus was found on December 31, 2019, in a number of individuals in Wuhan, People's Republic of China, who had viral pneumonia. This study was carried out in Al-Amal Hospital in Najaf Governorate on a group of 50 patients who had been infected with Coronavirus. The results revealed substantial disparities among the infected, as the average rates of PCT in the serum were practically identical. Those in critical condition had a three-fold higher fatality risk than patients in moderate condition, according to our data. That there is a substantial difference in NLR between the groups of moderate and severe COVID-19 patients, as they have considerably greater NLR in all patients. Statistical analysis revealed that in the severe group, NLR and PCT were strongly linked infected with COVID-19 pneumonia (P 0.05).In the severe group, NLR and PCT were positively associated. Furthermore, in the severe group, multifactorial logistic regression analysis for NLR, PCT, and NLR was found to be an independent risk factor for severe COVID-19 pneumonia and severe COVID-19 pneumonia.Copyright © 2023, Colegio de Farmaceuticos de la Provincia de Buenos Aires. All rights reserved.

Current status and hotspot of Lonicera Japonica Flos research based on bibliometrics.

In order to comprehensively understand the research hotspots and development trends of Lonicera Japonica Flos in the past 20 years, and to provide intuitive data reference and objective opinions and suggestions for subsequent related research in this field, this study collected 8 871 Chinese literature and 311 English literature related to Lonicera Japonica Flos research in the core collection databases of Wanfang Data), CNKI and Web of Science (WOS) from 2002 to 2021, and conducted bibliometric and visual analysis using vosviewer. The results showed that the research on the active components of Lonicera Japonica Flos based on phenolic acid components, the research on the mechanism of novel coronavirus pneumonia based on data mining and molecular docking technology, and the pharmacological research on the anti-inflammatory and antiviral properties of Lonicera Japonica Flos are the three hot research directions in the may become the future research direction. In this paper, we analyze the research on Lonicera Japonica Flos from five aspects: active ingredients, research methods, formulation and preparation, pharmacological effects and clinical applications, aiming to reveal the research hotspots, frontiers and development trends in this field and provide predictions and references for future research.Copyright © Drug Evaluation Research 2022.

Use of novel oxygenated right ventricular assist device hybrid ECLS for adolescents with refractory hypoxemic respiratory dailure due to Covid-19 pneumonia

Objectives: To describe institutional experience using Oxygenated Right Ventricular Assist Device (OxyRVAD) Hybrid ECLS for adolescents with respiratory failure due to SARS-CoV-2 pneumonia. Method(s): Between September and December 2021, 44 Covid-19+ patients were admitted to our regional Pediatric Intensive Care Unit (PICU), including 4 adolescents who required Extracorporeal life support (ECLS) due to refractory hypoxemia. Two patients were initially cannulated onto Veno-Venous (VV) ECLS and converted to Oxy-RVAD ECLS due to refractory hypoxemia;the others were cannulated directly onto Oxy-RVAD ECLS. Two patients had observed right ventricular (RV) dysfunction or failure on echocardiography. Cannulations were performed in the cardiac catheterization suite by an interventional cardiologist using percutaneous technique under fluoroscopy. Circuit construction was varied and included the use of a dedicated RVAD cannula or standard cannula used for VA/VV ECLS. All patients were connected to Cardiohelp systems with built in centrifugal pumps and oxygenators. Result(s): Two patients were initially placed on VV-ECLS and converted to Oxy-RVAD ECLS days into their course due to severe, refractory hypoxemia with one having improvement in hypoxemia after the conversion. Two patients received renal replacement therapy (RRT) without complications, the others did not have indications for renal support. Two patients underwent tracheostomy on ECMO though none were able to separate from mechanical ventilation. Three patients survived to discharge. No incidents of circuit air or clotting were noted. The patient with the longest ECLS run required one circuit change and was the only patient to develop a superinfection: a successfully-treated fungal infection. All patients were mobilized on ECLS to sitting in a chair;one was able to ambulate. Conclusion(s): Oxy-RVAD hybrid ECLS can be used to effectively support adolescents with severe respiratory disease from conditions associated with RV dysfunction. Pediatric providers can collaborate with adult critical care colleagues to use novel methods to support these patients. RRT can also be used with this circuit. While more experience and data on this modality is needed, Oxy-RVAD ECLS should be considered in patients with severe RV dysfunction and associated refractory hypoxemia. (Figure Presented).

Immunosuppression and Covid-19: Risk factor or treatment?

Introduction: During the Covid-19 pandemic, 540,895 people were identified as immunosuppressed and believed to be at increased risk of severe disease.1 As the pandemic evolved, biologic immunosuppression became a treatment of severe Covid-19.2 The true impact of immunosuppression on disease severity remains unclear. Objective(s): 1. Identify the incidence of immunosuppressed patients admitted to the ICU. 2. Analyse the mortality of those who are immunocompetent and immunosuppressed. 3. Examine the differences in mortality and level of care required between sub groups of patients on immunosuppression;those on biologics, non-biologics, and a combination of both. Method(s): A retrospective search of all Covid-19 positive admissions from March 2020 to November 2021 across two adult ICUs at Chelsea & Westminster NHS Trust was performed, using the EPR system. We identified those on immunosuppressive drugs, the level of care they required, and 28 day mortality. We categorised different types of immunosuppression, vaccination status, if applicable and co-morbidities. The exclusion criteria were primarily those with false positive swabs or incomplete data. Result(s): Baseline characteristics were median age (56 vs 56), and APCHE II score (20.08 in the immunosuppressed group vs 14.0 in immunocompetent). Thirteen immunosuppressed patients were identified. Reasons for drug immunosuppression in this group included solid organ transplant (6/13), and autoimmune conditions (7/13). Two patients were on biologic drugs alone, 8 were on non-biologics, and 3 were on a combination. Four of this group had received at least 2 doses of a Covid-19 vaccine. Mortality was 61.54% (8/13) in the immunosuppressed group vs 36.65% (199/543) in the immunocompetent group. Conclusion(s): Despite similar demographics, patients on immunosuppression had a significantly higher mortality than the immunocompetent group. Interestingly, those on targeted biological immunosuppression had the lowest incidence of requiring level 3 care, and no deaths. It is a possibility that biologics dampen the hyper-inflammation seen in severe Covid-19 pneumonitis, raising the question of a possible protective benefit from severe disease. This reflects the findings of the REMAP-CAP investigators,3 who showed that the IL-6 inhibiting biologics Tocilizumab and Sarilumab are efficacious against the most severe disease following admission to ICU with Covid-19 pneumonitis. The single centre and retrospective observational design, combined with small numbers on immunosuppression, despite a large inclusion criterion, mean it is not possible to make statistical conclusions. Confounding factors include the effects of vaccination, shielding and the change in SARS-CoV-2 variant prevalent during different times during the pandemic.

Membrane dysfunction in patients with severe COVID-19 treated with venovenous extracorporeal membrane oxygenation - analysis from a pooled data from a single centre

Objectives: It is well known that severe COVID-19 is associated with complex immunological and inflammatory dysregulation. Both these physiopathological events translate to a high risk of major thrombotic or hemorrhagic events. In patients treated with venovenous extracorporeal membrane oxygenation (VVECMO), membrane dysfunction might affect systemic oxygenation and limit its duration-expectancy. This study aimed to assess the possible causes of extracorporeal membrane failure in COVID-19 patients and its impact on outcome. Method(s): Retrospective, single-center, observational case-control study involving adult COVID-19 patients admitted to an ECMO referral centre in a tertiary university hospital. All patients required VVECMO for acute respiratory failure, including 48 cases who needed one or more extracorporeal membrane exchanges and 45 controls (no membrane exchange). These two groups were compared for demographic characteristics, severity of the disease using validated scores (SAPS II and SOFA), duration of ECMO run, coagulation assessment, cumulative anticoagulation dose, associated complications, and outcomes (ICU and hospital mortality). Result(s): Most patients were males (71.0%) and younger than 50 years (79.5%). Median ECMO run duration was significantly longer in the case group (35.0 vs 14.0 days, p <0.001), as well as ICU length-of-stay (45.5 vs 28 days, p <0.001). Membrane exchange tended to be associated with sepsis (56% vs 33%, p=0.037), major hemorrhage (58% vs 43%, p=0.022), heparin-induced thrombocytopenia (25% vs 9%, p=0.054), higher D-dimer title (17.36 ng/dL vs 7.5 ng/dL, p=0.07) and lower platelet counts (133.000/muL vs 154.000/muL). Median SAPS II (32.0 vs 33.0, p=0.20) and the mortality (27% vs 24%, p >0.99) were similar between these groups. Conclusion(s): In patients with SARS-CoV-2 pneumonia and severe hypoxemia treated with VVECMO support the emergence of infection, coagulopathy and inflammation were associated with high risk of membrane dysfunction. No impact on mortality could be confirmed from these data. Anticoagulation monitoring and dosing strategies should be reinforced to promote membrane protection.

Successful ECMO course in an Acquired Immune Deficiency Syndrome (AIDS) patient with ARDS complicated by pneumocystis jirovecii pneumonia and COVID-19: A unique case

Objectives: Reviewing current literature and case reports of patients placed on Venous-Venous ECMO support for HIV and AIDS, with confection with Pneumocystis pneumonia and covid-19 pneumonia. The use of extracorporeal membrane oxygenation (ECMO) in patients who have acute respiratory distress syndrome has been shown to have very good outcomes. However, there is limited data to support the initiation of ECMO in patients who have human immunodeficiency virus infection with or without acquired immune deficiency syndrome. Method(s): We present a unique and challenging case of a 30 year old male, with no known past medical history, unvaccinated against covid-19, who presented with one week of progressive shortness of breath. On admission he was found with moderate bilateral infiltrates and was diagnosed with covid-19 pneumonia. Despite appropriate medical therapy, patient developed worsening hypoxic respiratory failure. Found to have elevated (1- 3)-7beta;-d-glucan and tested positive for HIV. CD4 count 11, HIV viral load 70,000. The patient remained severely hypoxemic despite mechanical ventilation, sedation, paralytics and proning. Venous venous extracorporeal membrane oxygenation was initiated. Considering his non improvement with variety of antivirals and antibiotics and with elevated (1-3)-7beta;-d-glucan in the setting of AIDS he was treated for presumed Pneumocystis pneumonia. The patient tolerated proning while on VV ECMO and his course was complicated with bilateral pneumothorax necessitating chest tube placement. Result(s): The patient successfully completed 64 days on VV ECMO, where he was treated for PCP pneumonia, covid pneumonia, CMV viremia and tolerated initiation of anti-retroviral therapy. Patient was successfully decannulated, and ultimately discharged from the hospital. Conclusion(s): VV-ECMO can be a beneficial intervention with successful outcomes in severely immunocomprimised patients with AIDS. This case highlights the importance of minimizing sedation and early mobilization on ECMO support. (Figure Presented).

NR3C1 rs41423247: genetic predictor of complications in pneumonia caused by SARS-CoV-2

Background/Objectives: Runaway inflammation is a key feature of COVID-19. NR3C1 gene encodes for glucocorticoid receptor which plays an important role in inflammation reaction. The variant rs41423247 cause increased glucocorticoid receptors sensitivity. This study aimed to investigate the impact of variants of NR3C1 gene on the course of COVID-19 pneumonia in patients with necessarily artificial lung ventilation. Method(s): The study group included 20 patients (9 women and 11 men) with diagnosis viral COVID-19 pneumonia on artificial lung ventilation at the intensive care unit. All patients underwent daily standard examinations according clinical protocols. Determination of NR3C1 gene variants was carried out by using PCRRFLP. Result(s): There were found the significant negative correlations between NR3C1 gene variants and level of SpO2 (rS = -0.601, p = 0.008), Glasgow Coma Scale score (rS = -0.523, p = 0.026). Also, it was defined a protective effect of genotype CC at risk of development acute respiratory distress syndrome in this patients (chi2 = 4.38, p = 0.037, OR = 0.05 (CI:0.01-0.66)). Conclusion(s): The investigated variant rs41423247 of the NR3C1 gene may be the genetic predictor of complicated course of COVID-19 pneumonia. .