ABSTRACT
Background: The use of veno-venous extracorporeal membrane oxygenation (vv-ECMO) in acute lung failure has witnessed a notable increase. The PiCCO system is frequently used for advanced hemodynamic monitoring in this cohort. Our study aimed to investigate whether the choice of indicator injection site (jugular vs. femoral) in patients undergoing vv-ECMO therapy affects transpulmonary thermodilution (TPTD) measurements using the PiCCO® device (Pulsion Medical Systems SE, Munich, Germany). Methods: In a retrospective single-center analysis, we compared thermodilution-derived hemodynamic parameters after simultaneous jugular and femoral injections in 28 measurements obtained in two patients with respiratory failure who were undergoing vv-ECMO therapy. Results: Elevated values of the extravascular lung water index (EVLWI), intrathoracic blood volume index (ITBVI) and global end-diastolic volume index (GEDVI) were observed following femoral indicator injection compared to jugular indicator injection (EVLWI: 29.3 ± 10.9 mL/kg vs. 18.3 ± 6.71 mL/kg, p = 0.0003; ITBVI: 2163 ± 631 mL/m2 vs. 806 ± 125 mL/m2, p < 0.0001; GEDVI: 1731 ± 505 mL/m2 vs. 687 ± 141 mL/m2, p < 0.0001). The discrepancy between femoral and jugular measurements exhibited a linear correlation with extracorporeal blood flow (ECBF). Conclusions: In a PiCCO®-derived hemodynamic assessment of patients on vv-ECMO, the femoral indicator injection, as opposed to the jugular injection, resulted in an overestimation of all index parameters. This discrepancy can be attributed to mean transit time (MTt) and downslope time-dependent (DSt) variations in GEDVI and cardiac function index and is correlated with ECBF.
ABSTRACT
Key Clinical Message: In near-fatal asthma, the combination of ECMO therapy and isoflurane application via an intensive care ventilator with an anesthetic conservation device represents a therapeutic combination in seemingly hopeless clinical situations. Abstract: We report a case of an adult patient with near-fatal asthma, who was implanted venovenous extracorporeal membrane oxygenation in an extern hospital before transfer to our tertiary center. After 13 days and various therapeutic approaches, including inhaled isoflurane therapy via an anesthetic-conserving device, the patient was decannulated and extubated 3 days later.
ABSTRACT
Myeloid cell arginase-mediated arginine depletion with consecutive inhibition of T cell functions is a key component of tumor immune escape. Both, granulocytic myeloid-derived suppressor cells (G-MDSC) and conventional mature human polymorphonuclear neutrophil granulocytes (PMN) express high levels of arginase 1 and can act as suppressor cells of adaptive anti-cancer immunity. Here we demonstrate that pharmacological inhibition of PMN-derived arginase 1 not only prevents the suppression of T cell functions but rather leads to a strong hyperactivation of T cells. Human PMN were incubated in cell culture medium in the absence or presence of an arginase inhibitor. T cells from healthy donors were then activated either polyclonally or in an antigen-specific manner in the supernatants of the PMN cultures at different PMN-T cell ratios. T cell proliferation was completely suppressed in these supernatants in the absence of an arginase inhibitor. Arginase inhibition led to a strong hyperinduction of T cell proliferation, which exceeded control activation conditions up to 25-fold. The hyperinduction was correlated with higher PMN-T cell ratios and was only apparent when PMN arginase activity was blocked sufficiently. The T cell stimulatory factor was liberated very early by PMN and was present in the < 3 kDa fraction of the PMN supernatants. Increased T cell production of specific proinflammatory cytokines by PMN supernatant in the presence of arginase inhibitor was apparent. Upon arginase inhibition, downregulation of important T cell membrane activation and costimulation proteins was completely prevented or de novo induction accelerated. Antigen-specific T cell cytotoxicity against tumor cells was enhanced by PMN supernatant itself and could be further increased by PMN arginase blockade. Finally, we analyzed anergic T cells from multiple myeloma patients and noticed a complete reversal of anergy and the induction of strong proliferation upon T cell activation in PMN supernatants by arginase inhibition. In summary, we discovered a potent PMN-mediated hyperactivation of human T cells, which is apparent only when PMN arginase-mediated arginine depletion is concurrently inhibited. Our findings are clearly relevant for the analysis and prevention of human tumor immune escape in conjunction with the application of arginase inhibitors already being developed clinically.
Subject(s)
Arginase/metabolism , Lymphocyte Activation/immunology , Neutrophils/enzymology , T-Lymphocytes/immunology , Cell Proliferation/physiology , Cells, Cultured , Humans , Multiple Myeloma/immunology , Neutrophils/immunology , Tumor Escape/immunologyABSTRACT
Low-frequency magnetic fields (LF-MF) generated by power lines represent a potential environmental health risk and are classified as possibly carcinogenic by the World Health Organization. Epidemiological studies indicate that LF-MF might propagate neurodegenerative diseases like Alzheimer's disease (AD) or amyotrophic lateral sclerosis (ALS). We conducted a comprehensive analysis to determine whether long-term exposure to LF-MF (50 Hz, 1 mT) interferes with disease development in established mouse models for AD and ALS, namely APP23 mice and mice expressing mutant Cu/Zn-superoxide dismutase (SOD1), respectively. Exposure for 16 months did not aggravate learning deficit of APP23 mice. Likewise, disease onset and survival of SOD1(G85R) or SOD1(G93A) mice were not altered upon LF-MF exposure for ten or eight months, respectively. These results and an extended biochemical analysis of protein aggregation, glial activation and levels of toxic protein species suggests that LF-MF do not affect cellular processes involved in the pathogenesis of AD or ALS.
