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Background: Ventricular fibrillation (VF) waveform analysis has been proposed as a potential non-invasive guide to optimize timing of defibrillation. Methods: The AMplitude Spectrum Area (AMSA) trial is an open-label, multicenter randomized controlled study reporting the first in-human use of AMSA analysis in out-of-hospital cardiac arrest (OHCA). The primary efficacy endpoint was the termination of VF for an AMSA ≥ 15.5 mV-Hz. Adult shockable OHCAs randomly received either an AMSA-guided cardiopulmonary resuscitation (CPR) or a standard-CPR. Randomization and allocation to trial group were carried out centrally. In the AMSA-guided CPR, an initial AMSA ≥ 15.5 mV-Hz prompted for immediate defibrillation, while lower values favored chest compression (CC). After completion of the first 2-min CPR cycle, an AMSA < 6.5 mV-Hz deferred defibrillation in favor of an additional 2-min CPR cycle. AMSA was measured and displayed in real-time during CC pauses for ventilation with a modified defibrillator. Findings: The trial was early discontinued for low recruitment due to the COVID-19 pandemics. A total of 31 patients were recruited in 3 Italian cities, 19 in AMSA-CPR and 12 in standard-CPR, and included in the data analysis. No difference in primary outcome was observed between the two groups. Termination of VF occurred in 74% of patients in the AMSA-CPR compared to 75% in the standard CPR (OR 0.93 [95% CI 0.18–4.90]). No adverse events were reported. Interpretation: AMSA was used prospectively in human patients during ongoing CPR. In this small trial, an AMSA-guided defibrillation provided no evidence of an improvement in termination of VF. Trial registration: NCT03237910. Funding: European Commission - Horizon 2020; ZOLL Medical Corp., Chelmsford, USA (unrestricted grant); Italian Ministry of Health - Current research IRCCS.

Transplacental trafficking of maternal and fetal cells during pregnancy establishes long-term reciprocal microchimerism in both mother and child. Consequently, the maternal immune system may become sensitized to paternal histocompatibility antigens. It has been hypothesized that mother's “exposure” to paternal HLA haplotype antigens during pregnancy may affect the outcome of hematopoietic stem cell transplantation (HSCT) when the mother serves as a donor for the child. In T cell-depleted HLA haploidentical HSCT, maternal donors have been associated with improved transplantation outcomes. The present retrospective multicenter study, conducted on behalf of the Cellular Therapy and Immunobiology Working Party of the European Society of Blood and Marrow Transplantation, involved 409 patients (102 pediatric and 307 adult) with acute leukemia who underwent HLA-haploidentical HSCT. The goal of the study was to evaluate the role of maternal donors in a large cohort of haploidentical transplantation recipients. Transplantation from maternal donors was associated with a lower relapse incidence in T cell-depleted HSCTs (hazard ratio [HR], 2.13; 95% confidence interval [CI], 1.16 to 3.92; P = .018) as well as in a limited series of unmanipulated in vivo T cell-depleted HSCTs (HR, 4.15; 95% CI, 0.94 to 18.35; P = .06), along with better graft-versus-host disease/relapse-free survival (GRFS) in T cell-depleted HSCT (HR, 1.67; 95% CI, 1.02 to 2.73; P = .04). These results indicate that the mother is the preferred donor to provide better GRFS in T cell-depleted HLA-haploidentical HSCT for acute leukemia.

Objective: Extracorporeal cardiopulmonary resuscitation (eCPR) with venoarterial extracorporeal membrane oxygenation (VA-ECMO) is gaining importance as a rescue therapy for refractory cardiac arrest. VA-ECMO, especially in the setting of eCPR, is plagued by hemorrhagic and thromboembolic complications. The authors’ aims were to describe the coagulation profile in refractory cardiac arrest and assess its prognostic role. Design: Single-center retrospective study. Setting: Cardiac surgical intensive care unit of a university hospital. Participants: One hundred eighty-eight patients treated with eCPR for intra-hospital and out-of-hospital refractory cardiac arrest, between 2008 and 2017. Interventions: The authors retrospectively analyzed data from the first blood sample drawn during cannulation for VA-ECMO to understand the association of coagulation parameters with survival to hospital discharge, number of blood components transfused, anticoagulation therapy, serum lactate levels, no-flow time, and low-flow time. Measurements and Main Results: Platelet count was 126 ± 79 × 109/L and in 17% of the population it was lower than 50 × 109/L, prothrombin time was 3.22 ± 4.01, activated partial thromboplastin time was 117 ± 78 seconds, fibrinogen was 186 ± 148 mg/dL, antithrombin was 47 ± 16%, and D-dimer was ≥2-fold the normal upper limit in 95% of patients. Fifty percent of patients had a disseminated intravascular coagulation (DIC) score ≥6 (52% among out-of-hospital cardiac arrest, 33% among in-hospital cardiac arrest), according to the criteria of the Japanese Society on Thrombosis and Hemostasis (2016). The median DIC score was 5.5 points (interquartile range 4-8), significantly different between survivors and nonsurvivors (4 [3-6] v 6 [4-8], p = 0.007). Every DIC score point contributed to the mortality risk (OR 1.34, 95% CI 1.09-1.67, p = 0.006). Patients with overt DIC less frequently received anticoagulants (28.6% v 55.9%, p = 0.002), started anticoagulant therapy

Human leukocyte antigen (HLA) class-I mismatches that trigger donor-versus-recipient natural killer (NK)-cell alloreactivity reduce the incidence of leukemia relapse and improve survival of acute myeloid leukemia patients after T-cell-depleted HLA-haplotype mismatched (“haploidentical”) hematopoietic transplantation. In murine graft-versus-host disease (GvHD) models, alloreactive NK-cells also prevent GvHD. Here we report the results of a non-interventional, prospective study performed on behalf of the Cellular Therapy and Immunobiology Working Party of the European Society for Blood and Marrow Transplantation. The study was aimed at re-assessing the role of NK-cell alloreactivity in a cohort of haploidentical transplants performed in Europe between 2012 and 2015 and composed of unmanipulated, as well as T-cell-depleted transplants. One hundred thirty-eight patients with acute myeloid or lymphoid leukemias were analyzed. Eighty-six patients received ex-vivo T-cell-depleted transplants, 52 patients received unmanipulated transplants. Fifty patients were transplanted from NK alloreactive donors, 88 from non-NK alloreactive donors. NK cell alloreactivity did not impact on GvHD/relapse-free survival (GRFS) in unmanipulated transplants (HR: 1.66 (0.9–3.1), p = 0.1). In contrast, it did impact beneficially on GRFS in T-cell-depleted transplants (HR: 0.6, (0.3–1.2), p = 0.14, interaction p < 0.001). This effect was the consequence of reduced incidences of acute and chronic GvHD and non-relapse mortality.

Objective There is initial evidence that the use of volatile anesthetics can reduce the postoperative release of cardiac troponin I, the need for inotropic support, and the number of patients requiring prolonged hospitalization following coronary artery bypass graft (CABG) surgery. Nevertheless, small randomized controlled trials have failed to demonstrate a survival advantage. Thus, whether volatile anesthetics improve the postoperative outcome of cardiac surgical patients remains uncertain. An adequately powered randomized controlled trial appears desirable. Design Single blinded, international, multicenter randomized controlled trial with 1:1 allocation ratio. Setting Tertiary and University hospitals. Interventions Patients (n = 10,600) undergoing coronary artery bypass graft will be randomized to receive either volatile anesthetic as part of the anesthetic plan, or total intravenous anesthesia. Measurements and main results The primary end point of the study will be one-year mortality (any cause). Secondary endpoints will be 30-day mortality; 30-day death or non-fatal myocardial infarction (composite endpoint); cardiac mortality at 30 day and at one year; incidence of hospital re-admission during the one year follow-up period and duration of intensive care unit, and hospital stay. The sample size is based on the hypothesis that volatile anesthetics will reduce 1-year unadjusted mortality from 3% to 2%, using a two-sided alpha error of 0.05, and a power of 0.9. Conclusions The trial will determine whether the simple intervention of adding a volatile anesthetic, an intervention that can be implemented by all anesthesiologists, can improve one-year survival in patients undergoing coronary artery bypass graft surgery.

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HLA-haploidentical haematopoietic stem cell transplantation (haplo-HSCT) is increasingly offered to patients with high-risk acute leukaemia. Unfortunately, haplo-HSCT is followed by a delayed immunoreconstitution. The aim of this EBMT registry study was to explore the clinical impact of lymphocyte subset counts after haplo-HSCT. We considered 144 leukaemic patients transplanted in the period 2001–2012. Pre-transplantation clinical variables and differential immune-cell counts (CD3, CD4, CD8 T cells, NK and B cells) measured before day 100 were evaluated for their capacity to predict overall survival, relapse mortality or non-relapse mortality (NRM). Negative prognostic factors for overall survival were advanced disease state at transplantation, host age and CMV seropositivity. Higher CD3, CD4 and CD8 counts were associated with a better overall survival and a lower NRM. Strikingly, when tested in multivariable analysis, higher CD3 and CD8 counts were still significantly associated with a lower NRM. These results indicate that an accelerated T-cell reconstitution correlates with less transplantation mortality, likely due to the protective role of T cells against viral infections. This observation suggests that CD8+ T-cell counts should be investigated as surrogate biomarkers of outcome in prospective haplo-HSCT trials.

The noble gas argon (Ar) is a 'biologically' active element and has been extensively studied preclinically for its organ protection properties. This work reviews all preclinical studies employing Ar and describes the clinical uses reported in literature, analyzing 55 pertinent articles found by means of a search on PubMed and Embase. Ventilation with Ar has been tested in different models of acute disease at concentrations ranging from 20% to 80% and for durations between a few minutes up to days. Overall, lesser cell death, smaller infarct size, and better functional recovery after ischemia have been repeatedly observed. Modulation of the molecular pathways involved in cell survival, with resulting anti-apoptotic and pro-survival effects, appeared as the determinant mechanism by which Ar fulfills its protective role. These beneficial effects have been reported regardless of onset and duration of Ar exposure, especially after cardiac arrest. In addition, ventilation with Ar was safe both in animals and humans. Thus, preclinical and clinical data support future clinical studies on the role of inhalatory Ar as an organ protector.

Background: Although the incidence of intracerebral hemorrhage (ICH) has appeared to be increasing over the years, its prognosis remains dismal. No consensus has yet been reached regarding the management of ICH; however, minimally invasive surgery should limit, if not avoid, intraoperative parenchymal damage. Therefore, we have presented a novel, modified “homemade” approach aimed to shorten the operative time and minimize the corticectomy and brain manipulation. Methods: From 2008 to 2017, 53 patients (32 men and 21 women; mean age, 63.8 years) were admitted to our neurosurgery department and surgically treated for a lobar ICH. A modified suction tube, coupled with the endoscope light source, was used. Clot evacuation was performed under loupe magnification without the use of the microscope or endoscope. The light source of the latter was only used to provide light in the working cavity. Results: The mean hematoma volume was 69.2 mL (range, 40–100) preoperatively and 12.1 mL (range, 0–20) postoperatively, with a mean clot evacuation of 84.3% (range, 60%–100%). The mean postoperative Glasgow coma scale score was 11.6, with an improvement of 14% from the admission score (mean, 9.2). Conclusions: The results from our clinical series have shown the effectiveness of endoscopic clot evacuation in surgical ICH. In addition, we have demonstrated an efficient technique that can be used in urgent cases and in less-developed areas owing to its reduced demand on resources and its shorter learning curve. The outcomes were good and comparable to those with the classical endoscopic approach.