Impact of extra-corporeal life support (ECLS) cannulation strategy on outcome after durable mechanical circulation support system implantation on behalf of durable MCS after ECLS Study Group

Background: The literature on outcomes of patients requiring durable mechanical circulatory support (MCS) after extra-corporeal life support (ECLS) is limited. The aim of this study was to investigate the impact of preoperative ECLS cannulation on postoperative outcome after durable MCS implantation. Methods: The durable MCS after ECLS registry is a multicenter retrospective study that gathered data on consecutive patients who underwent durable MCS implantation after ECLS between January 2010 and August 2018 in eleven high volume European centers. Patients who underwent the implantation of total artificial heart, pulsatile pumps, or first-generation pumps after ECLS were excluded from the analysis. The remaining patients were divided into two groups; central ECLS group (cECLS) and peripheral ECLS group (pECLS). A 1:1 propensity score analysis was performed to identify two matched groups. The outcome of these two groups was compared. Results: A total of 531 durable MCS after ECLS were implanted during this period. The ECLS cannulation site was peripheral in 87% (n=462) and central in 13% (n=69) of the patients. After excluding pulsatile pumps and total artificial heart patients, a total of 494 patients remained (pECLS =434 patients, cECLS =60 patients). A 1:1 propensity score analysis resulted in 2 matched groups (each 55 patients) with median age of 54 years (48-60 years) in cECLS group and 54 years (43-60 years) in pECLS group. HeartWare HVAD (Medtronic, Minneapolis, MN) was implanted in the majority of the patients (cECLS =71% vs. pECLS =76%, P=0.67). All postoperative morbidities were comparable between the groups. The thirty-day, one year and long-term survival was comparable between the groups (P=0.73). Conclusions: The cannulation strategy of ECLS appears to have no impact on the post-operative outcome after durable MCS implantation

Dacarbazine (DTIC) versus vaccination with autologous peptide-pulsed dendritic cells (DC) in first-line treatment of patients with metastatic melanoma: a randomized phase III trial of the DC study group of the DeCOG

Background: This randomized phase III trial was designed to demonstrate the superiority of autologous peptide-loaded dendritic cell (DC) vaccination over standard dacarbazine (DTIC) chemotherapy in stage IV melanoma patients. Patients and methods: DTIC 850 mg/m2 intravenously was applied in 4-week intervals. DC vaccines loaded with MHC class I and II-restricted peptides were applied subcutaneously at 2-week intervals for the first five vaccinations and every 4 weeks thereafter. The primary study end point was objective response (OR); secondary end points were toxicity, overall (OS) and progression-free survival (PFS). Results: At the time of the first interim analysis 55 patients had been enrolled into the DTIC and 53 into the DC-arm (ITT). OR was low (DTIC: 5.5%, DC: 3.8%), but not significantly different in the two arms. The Data Safety & Monitoring Board recommended closure of the study. Unscheduled subset analyses revealed that patients with normal serum LDH and/or stage M1a/b survived longer in both arms than those with elevated serum LDH and/or stage M1c. Only in the DC-arm did those patients with (i) an initial unimpaired general health status (Karnofsky = 100) or (ii) an HLA-A2+/HLA-B44− haplotype survive significantly longer than patients with a Karnofsky index <100 (P = 0.007 versus P = 0.057 in the DTIC-arm) or other HLA haplotypes (P = 0.04 versus P = 0.57 in DTIC-treated patients). Conclusions: DC vaccination could not be demonstrated to be more effective than DTIC chemotherapy in stage IV melanoma patients. The observed association of overall performance status and HLA haplotype with overall survival for patients treated by DC vaccination should be tested in future trials employing DC vaccine

The European Registry for Patients with Mechanical Circulatory Support (EUROMACS)

OBJECTIVES: A second paediatric report has been generated from the European Registry for Patients with Mechanical Circulatory Support (EUROMACS). The purpose of EUROMACS, which is operated by the European Association for Cardio-Thoracic Surgery, is to gather data related to durable mechanical circulatory support for scientific purposes and to publish reports with respect to the course of mechanical circulatory support therapy. Since the first report issued, efforts to increase compliance and participation have been extended. Additionally, the data provided the opportunity to analyse patients of younger age and lower weight. METHODS: Participating hospitals contributed pre-, peri- and long-term postoperative data on mechanical circulatory support implants to the registry. Data for all implants in paediatric patients (≤19 years of age) performed from 1 January 2000 to 1 July 2019 were analysed. This report includes updates of patient characteristics, implant frequency, outcome (including mortality rates, transplants and recovery rates) as well as adverse events including neurological dysfunction, device malfunction, major infection and bleeding. RESULTS: Twenty-nine hospitals contributed 398 registered implants in 353 patients (150 female, 203 male) to the registry. The most frequent aetiology of heart failure was any form of cardiomyopathy (61%), followed by congenital heart disease and myocarditis (16.4% and 16.1%, respectively). Competing outcomes analysis revealed that a total of 80% survived to transplant or recovery or are ongoing; at the 2-year follow-up examination, 20% died while on support. At 12 months, 46.7% received transplants, 8.7% were weaned from their device and 18.5% died. The 3-month adverse events rate was 1.69 per patient-year for device malfunction including pump exchange, 0.48 for major bleeding, 0.64 for major infection and 0.78 for neurological events. CONCLUSIONS: The overall survival rate was 81.5% at 12 months following ventricular assist device implant. The comparison of survival rates of the early and later eras shows no significant difference. A focus on specific subgroups showed that survival was less in patients of younger age (<1 year of age) (P = 0.01) and lower weight (<20 kg) (P = 0.015). Transplant rates at 6 months contin

Remote sensing of biological soil crust under simulated climate change manipulations in the Mojave Desert

Earth\u27s arid and semiarid ecosystems are subject to novel combinations of disruptive factors and unprecedented rates of change. Biotic soil crust is believed to be sensitive to impacts caused by land use and climate changes. This study examined the potential for spectral detection of different biological soil crusts (BSC: cyanobacteria, moss and lichen) and bare soil components at a long-term manipulative experiment at the Mojave Global Change Facility (MGCF) in southwestern Nevada. We evaluated the potential for spectral detection of experimental treatments using laboratory and field measured reflectance spectra in the second and third year of the experiment, and airborne hyperspectral data obtained in the third year of the manipulations for soil disturbance, increased summer rainfall, and dry nitrogen deposition. Laboratory spectra of individual components of biological soil crust and bare soil measured under controlled laboratory conditions were spectrally different over much of the spectrum and exhibited features at 0.42, 0.50, and 0.68 μm, which could differentiate these materials. Field measured spectra were more similar in overall shape in each of the MGCF treatments and individual BSC could not be distinguished. The field spectra most closely resemble cyanobacteria from laboratory measurements, which are known to cover up to 60% of the inter-shrub spaces. There were significant treatment differences between control, soil disturbance, and irrigation treatments in field spectral measurements and a spectral feature in the 2.00–2.08 μm region could distinguish these treatments. The treatments were also apparent in high spatial resolution (~ 4 m ground IFOV) airborne hyperspectral imagery using a minimum noise fraction (MNF) analysis, although treatments were not distinct in terms of laboratory or field-based specific features. Disturbance treatments were easily apparent in color-infrared imagery although other treatments were not distinguished. Three-band composites from a MNF analysis and classification images of the six most significant MNF bands for treatment differences, revealed disturbed and irrigation treatments and combinations of these with nitrogen treatments can be observed but control treatments were not separated from the untreated background. Nitrogen treatments were generally not significantly different from controls unless combined with irrigation or disturbance treatments. These data suggest that hyperspectral imagery could be used to monitor local and perhaps regional changes in biological soil crust in the southwestern deserts of the United States, even if crust components are not individually detected

Adenosine triphosphate-induced oxygen radical production and CD11b up-regulation: Ca++ mobilization and actin reorganization in human eosinophils.

Eosinophils are major effector cells in cellular inflammatory conditions such as parasitic infections, atopic diseases, bullous dermatoses, and vasculitis. Biological activities of adenosine triphosphate (ATP) were characterized in human eosinophils and compared with those of other eosinophil activators such as complement fragment product C5a, platelet-activating factor (PAF), and eotaxin. ATP initiated production of reactive oxygen metabolites, as demonstrated by lucigenin-dependent chemiluminescence. Furthermore, ATP caused up-regulation of the integrin CD11b. In addition, fluorescence microscope measurements labeled with fura-2 (1-[2-(5-carboxy-oxazol-2-yl)-6-aminobenzofuran-5-oxy]-2-(2' -amino-5' -methyl-phenoxy)-ethane-N, N, N, N'-tetraacetic acid, pentaacetoxymethyl ester) eosinophils in the presence or absence of ethyleneglycotetraacetic acid (EGTA) indicated that there was Ca(++) mobilization from intracellular stores by ATP. Flow cytometric studies showed transient actin polymerization upon stimulation with ATP and its stable analogues adenosine 5'-0-(3-thiotriphosphate) and 2-methylthioadenosine triphosphate tetrasodium (met-ATP). The reactions induced by ATP were comparable to those obtained by C5a, PAF, and eotaxin. Production of reactive oxygen metabolites and actin polymerization after stimulation with ATP was inhibited by pertussis toxin, which indicated involvement of receptor-coupled guanine nucleotide-binding proteins (G(i) proteins). In addition, experiments with oxidized ATP also suggest involvement of P2X receptors in this activation process. The results show that ATP is a strong activator of eosinophils and has biological activity comparable to those of the eosinophil chemotaxins C5a, PAF, and eotaxin. The findings strongly suggest a role of ATP in the pathogenesis of eosinophilic inflammation as an activator of proinflammatory effector functions