Nebulized Recombinant Tissue Plasminogen Activator (rt-PA) for Acute COVID-19-Induced Respiratory Failure: An Exploratory Proof-of-Concept Trial

Acute lung injury in COVID-19 results in diffuse alveolar damage with disruption of the alveolar-capillary barrier, coagulation activation, alveolar fibrin deposition and pulmonary capillary thrombi. Nebulized recombinant tissue plasminogen activator (rt-PA) has the potential to facilitate localized thrombolysis in the alveolar compartment and improve oxygenation. In this proof-of-concept safety study, adults with COVID-19-induced respiratory failure and a <300 mmHg PaO2/FiO2 (P/F) ratio requiring invasive mechanical ventilation (IMV) or non-invasive respiratory support (NIRS) received nebulized rt-PA in two cohorts (C1 and C2), alongside standard of care, between 23 April–30 July 2020 and 21 January–19 February 2021, respectively. Matched historical controls (MHC; n = 18) were used in C1 to explore efficacy. Safety co-primary endpoints were treatment-related bleeds and <1.0–1.5 g/L fibrinogen reduction. A variable dosing strategy with clinical efficacy endpoint and minimal safety concerns was determined in C1 for use in C2; patients were stratified by ventilation type to receive 40–60 mg rt-PA daily for ≤14 days. Nine patients in C1 (IMV, 6/9; NIRS, 3/9) and 26 in C2 (IMV, 12/26; NIRS, 14/26) received nebulized rt-PA for a mean (SD) of 6.7 (4.6) and 9.1(4.6) days, respectively. Four bleeds (one severe, three mild) in three patients were considered treatment related. There were no significant fibrinogen reductions. Greater improvements in mean P/F ratio from baseline to study end were observed in C1 compared with MHC (C1; 154 to 299 vs. MHC; 154 to 212). In C2, there was no difference in the baseline P/F ratio of NIRS and IMV patients. However, a larger improvement in the P/F ratio occurred in NIRS patients (NIRS; 126 to 240 vs. IMV; 120 to 188) and fewer treatment days were required (NIRS; 7.86 vs. IMV; 10.5). Nebulized rt-PA appears to be well-tolerated, with a trend towards improved oxygenation, particularly in the NIRS group. Randomized clinical trials are required to demonstrate the clinical effect significance and magnitude

Nebulized Recombinant Tissue Plasminogen Activator (rt-PA) for Acute COVID-19-Induced Respiratory Failure : An Exploratory Proof-of-Concept Trial

Acknowledgments We would like to extend our sincerest gratitude to all the colleagues and hospital staff who worked tirelessly throughout the pandemic and without whom this work would not have been possible. Firstly, we would like to thank our colleagues in the intensive care unit (ICU), in particular the matrons, Sean Carroll and Sinead Hanton, and research nurses, Filipe Helder and Amitaa Maharajh for their support, and bedside nurses who bore the responsibility of drug administration. We would also like to extend our thanks to ICU consultants who acted as professional legal consultees on behalf of critical care patients. Equally, we would like to thank colleagues within the respiratory team. Their expertise was instrumental to our role in treating patients on 8N and 8E wards. A special mention to lead Nurse Mary Emerson; we were grateful for her knowledge, support and for facilitating the training for the nebulizer and drug administration on the wards. We would like to thank Aarti Nandani and all the staff in the Royal Free clinical trials pharmacy for their immense support throughout the whole pandemic, especially considering their ever-increasing workload at the time. Thanks also to the HSL coagulation laboratory, the Trust R&D department and all the staff working to cover during a very challenging time. We are also very grateful to the Royal Free charity for funding this study. Finally, we would like to thank all the clinical nurses, physiotherapists, research data managers and healthcare professionals within the Haemophilia department (and wider hospital) for all their many efforts in supporting this study. This trial was overseen by an independent data monitoring committee, chaired by Najib Rahman, Director of the Oxford Respiratory Trials Unit, University of Oxford and comprises the following committee members: Mike Makris, Jonathan Silversides and Henry Watson. Funding Royal Free Charity Trust Fund 35 provided funding for this study. The study drug was provided by Boehringer Ingelheim (BI). BI had no role in the design, analysis, or interpretation of the results. They were given the opportunity to review the manuscript for medical and scientific accuracy since it relates to BI substances and intellectual property considerations.Peer reviewedPublisher PD

Nebulized Recombinant Tissue Plasminogen Activator (rt-PA) for Acute COVID-19-Induced Respiratory Failure: An Exploratory Proof-of-Concept Trial

Acute lung injury in COVID-19 results in diffuse alveolar damage with disruption of the alveolar-capillary barrier, coagulation activation, alveolar fibrin deposition and pulmonary capillary thrombi. Nebulized recombinant tissue plasminogen activator (rt-PA) has the potential to facilitate localized thrombolysis in the alveolar compartment and improve oxygenation. In this proof-of-concept safety study, adults with COVID-19-induced respiratory failure and a <300 mmHg PaO2/FiO2 (P/F) ratio requiring invasive mechanical ventilation (IMV) or non-invasive respiratory support (NIRS) received nebulized rt-PA in two cohorts (C1 and C2), alongside standard of care, between 23 April–30 July 2020 and 21 January–19 February 2021, respectively. Matched historical controls (MHC; n = 18) were used in C1 to explore efficacy. Safety co-primary endpoints were treatment-related bleeds and <1.0–1.5 g/L fibrinogen reduction. A variable dosing strategy with clinical efficacy endpoint and minimal safety concerns was determined in C1 for use in C2; patients were stratified by ventilation type to receive 40–60 mg rt-PA daily for ≤14 days. Nine patients in C1 (IMV, 6/9; NIRS, 3/9) and 26 in C2 (IMV, 12/26; NIRS, 14/26) received nebulized rt-PA for a mean (SD) of 6.7 (4.6) and 9.1(4.6) days, respectively. Four bleeds (one severe, three mild) in three patients were considered treatment related. There were no significant fibrinogen reductions. Greater improvements in mean P/F ratio from baseline to study end were observed in C1 compared with MHC (C1; 154 to 299 vs. MHC; 154 to 212). In C2, there was no difference in the baseline P/F ratio of NIRS and IMV patients. However, a larger improvement in the P/F ratio occurred in NIRS patients (NIRS; 126 to 240 vs. IMV; 120 to 188) and fewer treatment days were required (NIRS; 7.86 vs. IMV; 10.5). Nebulized rt-PA appears to be well-tolerated, with a trend towards improved oxygenation, particularly in the NIRS group. Randomized clinical trials are required to demonstrate the clinical effect significance and magnitude

Étude comparative de l’oxydation de SO

L'analyse des spectres infrarouge des espèces sulfate formées par oxydation de SO2 montre une plus grande hétérogénéité dans le cas du rutile. Suivant la quantité de sulfate formée, au moins trois types d'espèces sulfate superficielles sont mis en évidence sur rutile; ils sont caractérisés par une bande à 1325 cm-1 (spécifique à cette variété cristalline), 1375 ou 1390-1400 cm-1. Cette dernière bande peut correspondre à des espèces S2O72-peu stables. Le déplacement observé pour les autres bandes par suite d'échanges isotopiques utilisant H218O montre que les espèces sulfate superficielles, présentent, à l'état anhydre, une structure avec un seul groupement S=O. Sur rutile, pour des teneurs importantes en sulfate, il apparaît aussi une bande à 1160cm-1, insensible à l'échange isotopique par H218O, ce qui montre qu'elle correspond à la formation d'une quantité limitée de sulfates dits de "cœur", ne se formant pas dans le cas de l'anatase. Les résultats gravimétriques montrent que les quantités de SO2 adsorbées et oxydées sont identiques pour les deux variétés. Cependant, lors du chauffage sous vide ou en présence d'hydrogène, les espèces sulfate formées par oxydation de SO2, sont moins stables thermiquement et plus réactives vis-à-vis de l'hydrogène dans le cas de la variété rutile

Cordierite containing ceramic membranes from smectetic clay using natural organic wastes as pore-forming agents

International audienceCordierite ceramic membranes were manufactured from natural clay, oxides and organic wastes as pore forming agents. Mixtures aforementioned materials with the pore-forming agents (up to 10 wt.%) were investigated in the range 1000-1200 degrees C using thermal analysis, X-ray diffraction, scanning electron microscopy, mercury porosimetry and filtration tests. Physical properties (density, water absorption and bending strength) were correlated to the processing factors (pore-forming agent addition, firing temperature and soaking time). The results showed that cordierite together with spinel, diopside and clinoenstatite neoformed. SEM analysis revealed heterogeneous aspects. The results of the response surface methodology showed that the variations of physical properties versus processing parameters were well described by the used polynomial model. The addition of pore forming agent and temperature were the most influential factors. Filtration tests were performed on the best performing sample. The results allowed to testify that these membranes could be used in waste water treatment. (C) 2017 The Ceramic Society of Japan and the Korean Ceramic Society. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license

Sulfate species in MgO-supported LaMn0.5Mg0.5O3 perovskites: an insigh into the chemistry of MgO

The structure, thermal stability, and reducibility in H2 of sulfate species formed in MgO-promoted perovskites, LaMn0.5Mg0.5O3·17 MgO, have been studied by infrared spectroscopy, temperature-programmed desorption, and temperature-programmed reduction−mass spectrometry. Sulfation at 1073 K generates on the MgO phase both bulk and subsurface sulfates, whereas the latter species are the major product of sulfation at room temperature. In contrast with high-surface MgO samples (where sulfate species of covalent nature are found), the surface species closely resemble those in the bulk. Bulk sulfates are more resistant to thermal treatments than surface sulfates. A transformation of bulk sulfates at higher temperature into sulfides is suggested by IR spectroscopy and proved by chemical analysis. SO2, SO, and H2S are the products of sulfate reduction

Experimental investigation on the use of alfa fibers as reinforcement of cementitious materials

ACTIInternational audienc

Effect of Alfa fibers on the mechanical and thermal properties of compacted earth bricks

International audienc

Fast Removal of Citalopram Drug from Waste Water Using Magnetic Nanoparticles Modified with Sodium Dodecyl Sulfate Followed by UV-Spectrometry

A simple and sensitive, solid-phase extraction method for the removal of Citalopram drug from waste water has been developed by using magnetic nanoparticles modified with surfactant sodium dodecyl sulfate. These magnetic nanoparticles have shown great adsorptive tendency towards Citalopram drug. The effect of different parameters influencing the extraction efficiency of this drug were investigated and optimized including the pH, amount of the surfactant, contact time and temperature. The extracts were analyzed by ultraviolet spectrophotometry at 239nm. Under these conditions, the related standard deviation (RSD %) of the method at two concentrations (5 and 50µg.mL-1) was in the range of (3.14–3.75) % (n = 8). The calibration curve was linear in the range of 2-100 µg.mL-1 of Citalopram drug with a correlation coefficient of >0.99