Initial five and ten-minute regional cerebral oxygen saturation as a predictor of the futility of resuscitation for out-of-hospital cardiac arrest

This study aimed to investigate the usefulness of cerebral regional oxygen saturation (rSO2) during the initial 5 and 10 minutes of cardiopulmonary resuscitation (CPR) compared with an initial rSO2 and mean rSO2 during entire CPR to predict the futility of resuscitation for patients without of-hospital-cardiac arrest (OHCA). This was a prospective study involving 52 adult patients presenting in OHCA and whose cerebral rSO2 values were measured until either CPR was terminated or sustained return of spontaneous circulation (ROSC) was achieved. Receiver operating characteristics analyses were used to evaluate which time and type of measurement is better to predict non-ROSC. The area under the curve (AUC) of each rSO2 value according to measurement time (overall, initial 5 minutes and 10 minutes) were the highest value of 0.743, 0.724, and 0.739, mean values of 0.724, 0.677 and 0.701 and rSO2 (Changes in values of regional cerebral oxygen) value of 0.722, 0.734 and 0.724, respectively, while all of the initial values had a poor AUC (<0.7) and also were not statistically significant. The optimal cut-off value of each rSO2 values during overall, initial 5 minutes and 10 minutes were the highest value of 26% (sensitivity, 53.9% specificity, 92.3%), 24% (sensitivity, 56.4% specificity, 92.3%), and 30% (sensitivity, 61.5% specificity, 84.6%), mean value of 15.2%, 15.3% and 16%, respectively. None of the patients with a persistent rSO2 <=18% during the overall period achieved ROSC. Initial 5 minutes and 10 minutes cerebral rSO2 values an out-of-hospital-cardiac arrest (OHCA) are a better predictor in deciding the futility of CPR, compared to initial and overall measurements.Copyright © 2023 The Author(s). Published by MRE Press.

Efficacy and Safety of Eltrombopag Combined with Cyclosporine As First-Line Therapy in Adults with Severe Acquired Aplastic Anemia: Results of the Interventional Phase 2 Single-Arm Soar Study

Background: Severe aplastic anemia (SAA) is a rare bone marrow failure disorder associated with significant morbidity and mortality. SAA is characterized by severe pancytopenia and a hypocellular (<25%) bone marrow. The standard of care treatment is hemopoietic stem cell transplant or immunosuppressive therapy (IST) for patients (pts) who are ineligible for transplant. IST usually comprises an antithymocyte globulin (ATG) derived from horse or rabbit, and cyclosporine A (CsA). Although IST can be an effective treatment, individual intolerance, insufficient response, relapse, and clonal evolution remain significant limitations. The lack of global availability of the more effective horse ATG also leaves many pts with limited treatment options and poorer outcomes. In addition, pts with SAA often require transfusions which can be burdensome and negatively impact their quality of life. Eltrombopag (ETB) is indicated for use in pts with SAA who have had an insufficient response to IST (FDA PI, 2014) or are refractory to IST (EMA SmPC, 2015). More recently in the USA, ETB may also be used in combination with IST as first-line (1L) treatment (FDA PI, 2018). Aims: To assess the efficacy and safety of ETB + CsA (without ATG) as 1L therapy in adult pts with SAA. Methods: SOAR (NCT02998645) is a Phase 2, single-arm, multicenter, open-label study. Treatment-naive pts with SAA received ETB + CsA for 6 months;responders continued CsA therapy for an additional 24 months (later reduced to 18 months). The primary efficacy endpoint was overall response rate (ORR) by 6 months. ORR was defined as the proportion of pts with complete response ([CR] = absolute neutrophil count [ANC] ≥1000/μL AND platelet count ≥100,000/μL AND hemoglobin ≥10 g/dL) plus the proportion of pts with partial response ([PR] = any 2 of the following counts: ANC ≥500/μL;platelet count ≥20,000/μL;automated reticulocyte count ≥60,000/μL, but not sufficient for a CR). CR and PR were confirmed by 2 assessments ≥7 days apart;transfusion restrictions were also applied. For the primary endpoint to be considered ‘clinically meaningful’ at least 17/54 pts treated were required to have a response. Other endpoints included ORR by 3 months, ORR at 6 months (ie, confirmed response at the 6-month visit), and transfusion independence, which was defined as transfusion not being required in a period of ≥28 days for platelet transfusions and ≥56 days for red blood cell (RBC) transfusions. Results: Pts (N=54) had a median (interquartile range [IQR]) age of 55.0 (40.0-67.0) years and 63.0% were male. The majority of pts were White (40.7%) or Asian (40.7%). The median (IQR) duration of exposure to ETB and CsA was 5.7 (2.5-5.8) months and 5.7 (2.4-8.1) months, respectively, and the median (IQR) daily ETB dose was 150.0 (100.0-150.0) mg/day. In the full analysis set, the primary endpoint was met, with 25/54 pts having a CR or PR by 6 months (ORR 46.3%;95% confidence interval [CI], 32.6-60.4%). Of the 25 responders, 2 (3.7%) achieved a CR by 6 months. ORR by 3 months was 40.7% (95% CI, 27.6-55.0%;n=22/54), and ORR at 6 months was 37.0% (95% CI, 24.3-51.3%;n=20/54). 70.4% of all pts qualified for ≥1 period of RBC and/or platelet transfusion independence by 6 months, including all 25 (100%) responders and 13/29 (44.8%) non-responders (Fig. 1). 40.7% of all pts (responders: 68.0%;non-responders: 17.2%) qualified for ≥1 period of RBC transfusion independence (corresponding percentages for platelet transfusion independence were the same as for the combined RBC and/or platelet endpoint). Adverse events (AEs) occurred in 52/54 (96.3%) pts;45 (83.3%) pts experienced treatment-related AEs (TAEs), 23 (42.6%) of whom had a grade ≥3 TAE. The most common all-grade AEs were increased blood bilirubin (40.7%), nausea (29.6%), increased alanine aminotransferase (22.2%), and diarrhea (22.2%). Seven (13.0%) pts discontinued treatment due to grade ≥3 AEs. There were 8 on-treatment deaths (aplastic anemia [n=3];COVID-19, hemorrhage, multi-organ dysfunction syndrom , pyrexia, and thrombosis [all n=1]);no deaths were considered treatment-related. Conclusion: Data from the SOAR study indicate that ETB + CsA may be beneficial for pts with SAA ineligible for transplant who cannot access or tolerate ATG. All responders and almost half of non-responders qualified for ≥1 period of transfusion independence by 6 months, suggestive of a decreased transfusion burden. No new safety signals were identified. [Formula presented] Disclosures: Vallejo: Novartis: Honoraria;Sanofi: Honoraria;Pfizer: Honoraria. Finelli: Takeda: Consultancy;Celgene BMS: Consultancy, Research Funding, Speakers Bureau;Novartis: Consultancy, Speakers Bureau. Calado: Agios: Membership on an entity's Board of Directors or advisory committees;AA&MDS International Foundation: Research Funding;Alexion Brasil: Consultancy;Instituto Butantan: Consultancy;Novartis Brasil: Honoraria;Team Telomere, Inc.: Membership on an entity's Board of Directors or advisory committees. Peffault De Latour: Novartis: Consultancy, Honoraria, Research Funding;Pfizer: Consultancy, Honoraria, Research Funding;Amgen: Research Funding;Alexion: Consultancy, Honoraria, Research Funding;Apellis Pharmaceuticals Inc: Consultancy, Honoraria;Swedish Orphan Biovitrum AB: Consultancy, Honoraria. Kriemler-Krahn: Novartis: Current Employment. Haenig: Novartis: Current Employment. Maier: Novartis: Current Employment. Scheinberg: Alexion pharmaceuticals: Consultancy, Honoraria, Speakers Bureau;Novartis: Consultancy, Honoraria, Speakers Bureau;BioCryst Pharmaceuticals: Consultancy;Roche: Consultancy;Abbvie: Consultancy. OffLabel Disclosure: In the United States, eltrombopag is a thrombopoietin receptor agonist indicated in combination with standard immunosuppressive therapy (ATG + CsA) for the first-line treatment of adult and pediatric patients aged 2 years and older with severe aplastic anemia (SAA). It is also indicated for the treatment of patients with SAA who have had an insufficient response to immunosuppressive therapy. The SOAR trial aims to assess the efficacy and safety of eltrombopag + CsA (without ATG) as first-line therapy in adult patients with SAA.

Management of allergic patients during severe acute respiratory syndrome coronavirus-2 pandemic

A novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019 in China. The mutated coronavirus spread worldwide, and some patients infected with SARS-CoV-2 developed coronavirus disease 2019 (COVID-19) manifested with upper respiratory infection, pneumonia, or respiratory distress. Since the SARS-CoV-2 pandemic was declared with surging confirmed cases and mortality of COVID-19 worldwide, it has reshaped our way of living and how to manage patients with allergic diseases. The medical staff, including allergy specialists, has been at the forefront of fighting against the SARSCoV-2 pandemic and is struggling to guarantee safety to themselves and their patients. Thanks to vigorous research into the relationship between SARS-CoV-2 and allergic diseases, we have become able to treat allergic patients with the best of evidence to date. The clinician should make a careful decision on each clinical situation with regard to patient characteristics, local and national circumstances as well as the knowledge we have, since it is still limited. We hope further efforts to identify the nature of SARS-CoV-2 and COVID-19 clearer and effective SARS-CoV-2 vaccination will soon remove the grim picture of the worldwide pandemic and bring us back to normal.